Sample records for significant inter-individual variability

  1. Linking Inter-Individual Variability in Functional Brain Connectivity to Cognitive Ability in Elderly Individuals

    PubMed Central

    Li, Rui; Yin, Shufei; Zhu, Xinyi; Ren, Weicong; Yu, Jing; Wang, Pengyun; Zheng, Zhiwei; Niu, Ya-Nan; Huang, Xin; Li, Juan

    2017-01-01

    Increasing evidence suggests that functional brain connectivity is an important determinant of cognitive aging. However, the fundamental concept of inter-individual variations in functional connectivity in older individuals is not yet completely understood. It is essential to evaluate the extent to which inter-individual variability in connectivity impacts cognitive performance at an older age. In the current study, we aimed to characterize individual variability of functional connectivity in the elderly and to examine its significance to individual cognition. We mapped inter-individual variability of functional connectivity by analyzing whole-brain functional connectivity magnetic resonance imaging data obtained from a large sample of cognitively normal older adults. Our results demonstrated a gradual increase in variability in primary regions of the visual, sensorimotor, and auditory networks to specific subcortical structures, particularly the hippocampal formation, and the prefrontal and parietal cortices, which largely constitute the default mode and fronto-parietal networks, to the cerebellum. Further, the inter-individual variability of the functional connectivity correlated significantly with the degree of cognitive relevance. Regions with greater connectivity variability demonstrated more connections that correlated with cognitive performance. These results also underscored the crucial function of the long-range and inter-network connections in individual cognition. Thus, individual connectivity–cognition variability mapping findings may provide important information for future research on cognitive aging and neurocognitive diseases. PMID:29209203

  2. Intra- and Inter-Individual Variation in Self-Reported Code-Switching Patterns of Adult Multilinguals

    ERIC Educational Resources Information Center

    Dewaele, Jean-Marc; Li, Wei

    2014-01-01

    The present study is a large-scale quantitative analysis of intra-individual variation (linked to type of interlocutor) and inter-individual variation (linked to multilingualism, sociobiographical variables and three personality traits) in self-reported frequency of code-switching (CS) among 2116 multilinguals. We found a significant effect of…

  3. Inter- and Intra-individual Variability in Response to Transcranial Direct Current Stimulation (tDCS) at Varying Current Intensities.

    PubMed

    Chew, Taariq; Ho, Kerrie-Anne; Loo, Colleen K

    2015-01-01

    Translation of transcranial direct current stimulation (tDCS) from research to clinical practice is hindered by a lack of consensus on optimal stimulation parameters, significant inter-individual variability in response, and in sufficient intra-individual reliability data. Inter-individual differences in response to anodal tDCS at a range of current intensities were explored. Intra-individual reliability in response to anodal tDCS across two identical sessions was also investigated. Twenty-nine subjects participated in a crossover study. Anodal-tDCS using four different current intensities (0.2, 0.5, 1 and 2 mA), with an anode size of 16 cm2, was tested. The 0.5 mA condition was repeated to assess intra-individual variability. TMS was used to elicit 40 motor-evoked potentials (MEPs) before 10 min of tDCS, and 20 MEPs at four time-points over 30 min following tDCS. ANOVA revealed no main effect of TIME for all conditions except the first 0.5 mA condition, and no differences in response between the four current intensities. Cluster analysis identified two clusters for the 0.2 and 2 mA conditions only. Frequency distributions based on individual subject responses (excitatory, inhibitory or no response) to each condition indicate possible differential responses between individuals to different current intensities. Test-retest reliability was negligible (ICC(2,1) = -0.50). Significant inter-individual variability in response to tDCS across a range of current intensities was found. 2 mA and 0.2 mA tDCS were most effective at inducing a distinct response. Significant intra-individual variability in response to tDCS was also found. This has implications for interpreting results of single-session tDCS experiments. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  4. Inter-individual cognitive variability in children with Asperger's syndrome

    PubMed Central

    Gonzalez-Gadea, Maria Luz; Tripicchio, Paula; Rattazzi, Alexia; Baez, Sandra; Marino, Julian; Roca, Maria; Manes, Facundo; Ibanez, Agustin

    2014-01-01

    Multiple studies have tried to establish the distinctive profile of individuals with Asperger's syndrome (AS). However, recent reports suggest that adults with AS feature heterogeneous cognitive profiles. The present study explores inter-individual variability in children with AS through group comparison and multiple case series analysis. All participants completed an extended battery including measures of fluid and crystallized intelligence, executive functions, theory of mind, and classical neuropsychological tests. Significant group differences were found in theory of mind and other domains related to global information processing. However, the AS group showed high inter-individual variability (both sub- and supra-normal performance) on most cognitive tasks. Furthermore, high fluid intelligence correlated with less general cognitive impairment, high cognitive flexibility, and speed of motor processing. In light of these findings, we propose that children with AS are characterized by a distinct, uneven pattern of cognitive strengths and weaknesses. PMID:25132817

  5. Evaluation of inter-day and inter-individual variability of tear peptide/protein profiles by MALDI-TOF MS analyses

    PubMed Central

    González, Nerea; Iloro, Ibon; Durán, Juan A.; Elortza, Félix

    2012-01-01

    Purpose To characterize the tear film peptidome and low molecular weight protein profiles of healthy control individuals, and to evaluate changes due to day-to-day and individual variation and tear collection methods, by using solid phase extraction coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling. Methods The tear protein profiles of six healthy volunteers were analyzed over seven days and inter-day and inter-individual variability was evaluated. The bilaterality of tear film and the effect of tear collection methods on protein profiles were also analyzed in some of these patients. MALDI-TOF MS analyses were performed on tear samples purified by using a solid phase extraction (SPE) method based on C18 functionalized magnetic beads for peptide and low molecular weight protein enrichment, focusing spectra acquisition on the 1 to 20 kDa range. Spectra were analyzed using principal component analysis (PCA) with MultiExperiment Viewer (TMeV) software. Volunteers were examined in terms of tear production status (Schirmer I test), clinical assessment of palpebral lids and meibomian glands, and a subjective OSD questionnaire before tear collection by a glass micro-capillary. Results Analysis of peptides and proteins in the 1–20 kDa range showed no significant inter-day differences in tear samples collected from six healthy individuals during seven days of monitoring, but revealed subtle intrinsic inter-individual differences. Profile analyses of tears collected from the right and left eyes confirmed tear bilaterality in four healthy patients. The addition of physiologic serum for tear sample collection did not affect the peptide and small protein profiles with respect to the number of resolved peaks, but it did reduce the signal intensity of the peaks, and increased variability. Magnetic beads were found to be a suitable method for tear film purification for the profiling study. Conclusions No significant variability in tear peptide and protein profiles below 20 kDa was found in healthy controls over a seven day period, nor in right versus left eye profiles from the same individual. Subtle inter-individual differences can be observed upon tear profiling analysis and confirm intrinsic variability between control subjects. Addition of physiologic serum for tear collection affects the proteome and peptidome in terms of peak intensities, but not in the composition of the profiles themselves. This work shows that MALDI-TOF MS coupled with C18 magnetic beads is an effective and reproducible methodology for tear profiling studies in the clinical monitoring of patients. PMID:22736947

  6. Inter-individual Differences in Heart Rate Variability Are Associated with Inter-individual Differences in Empathy and Alexithymia.

    PubMed

    Lischke, Alexander; Pahnke, Rike; Mau-Moeller, Anett; Behrens, Martin; Grabe, Hans J; Freyberger, Harald J; Hamm, Alfons O; Weippert, Matthias

    2018-01-01

    In the present study, we investigated whether inter-individual differences in vagally mediated heart rate variability (vmHRV) would be associated with inter-individual differences in empathy and alexithymia. To this end, we determined resting state HF-HRV in 90 individuals that also completed questionnaires assessing inter-individual differences in empathy and alexithymia. Our categorical and dimensional analyses revealed that inter-individual differences in HF-HRV were differently associated with inter-individual differences in empathy and alexithymia. We found that individuals with high HF-HRV reported more empathy and less alexithymia than individuals with low HF-HRV. Moreover, we even found that an increase in HF-HRV was associated with an increase in empathy and a decrease in alexithymia across all participants. Taken together, these findings indicate that individuals with high HF-HRV are more empathetic and less alexithymic than individuals with low HF-HRV. These differences in empathy and alexithymia may explain why individuals with high HF-HRV are more successful in sharing and understanding the mental and emotional states of others than individuals with low HF-HRV.

  7. Trunk-pelvis coordination during turning: A cross sectional study of young adults with and without a history of low back pain.

    PubMed

    Smith, Jo Armour; Kulig, Kornelia

    2016-07-01

    During steady-state locomotion, symptomatic individuals with low back pain demonstrate reduced ability to modulate coordination between the trunk and the pelvis in the axial plane. It is unclear if this is also true during functional locomotor perturbations such as changing direction, or if this change in coordination adaptability persists between symptomatic episodes. The purpose of this study was to compare trunk-pelvis coordination during walking turns in healthy individuals and asymptomatic individuals with a history of low back pain. Participants performed multiple ipsilateral turns. Axial plane inter-segmental coordination and stride-to-stride coordination variability were quantified using the vector coding technique. Frequency of coordination mode and amplitude of coordination variability was compared between groups using Wilcoxon signed-rank tests and paired t-tests respectively. During stance phase of the turn, there was no significant difference in either inter-segmental coordination or coordination variability between groups. Inter-segmental coordination between the trunk and the pelvis was predominantly inphase during this part of the turn. During swing phase, patterns of coordination were more diversified, and individuals with a history of low back pain had significantly greater trunk phase coordination than healthy controls. Coordination variability was the same in both groups. Changes in trunk-pelvis coordination are evident between symptomatic episodes in individuals with a history of low back pain. However, previously demonstrated decreases in coordination variability were not found between symptomatic episodes in individuals with recurrent low back pain and therefore may represent a response to concurrent pain rather than a persistent change in motor control. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Inter-individual variability in response to non-invasive brain stimulation paradigms.

    PubMed

    López-Alonso, Virginia; Cheeran, Binith; Río-Rodríguez, Dan; Fernández-Del-Olmo, Miguel

    2014-01-01

    Non-invasive Brain Stimulation (NIBS) paradigms are unique in their ability to safely modulate cortical plasticity for experimental or therapeutic applications. However, increasingly, there is concern regarding inter-individual variability in the efficacy and reliability of these paradigms. Inter-individual variability in response to NIBS paradigms would be better explained if a multimodal distribution was assumed. In three different sessions for each subject (n = 56), we studied the Paired Associative Stimulation (PAS25), Anodal transcranial DC stimulation (AtDCS) and intermittent theta burst stimulation (iTBS) protocols. We applied cluster analysis to detect distinct patterns of response between individuals. Furthermore, we tested whether baseline TMS measures (such as short intracortical inhibition (SICI), resting motor threshold (RMT)) or factors such as time of day could predict each individual's response pattern. All three paradigms show similar efficacy over the first hour post stimulation--there is no significant effect on excitatory or inhibitory circuits for the whole sample, and AtDCS fares no better than iTBS or PAS25. Cluster analysis reveals a bimodal response pattern--but only 39%, 45% and 43% of subjects responded as expected to PAS25, AtDCS, and iTBS respectively. Pre-stimulation SICI accounted for 10% of the variability in response to PAS25, but no other baseline measures were predictive of response. Finally, we report implications for sample size calculation and the remarkable effect of sample enrichment. The implications of the high rate of 'dose-failure' for experimental and therapeutic applications of NIBS lead us to conclude that addressing inter-individual variability is a key area of concern for the field. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Neuroanatomical correlates of biological motion detection.

    PubMed

    Gilaie-Dotan, Sharon; Kanai, Ryota; Bahrami, Bahador; Rees, Geraint; Saygin, Ayse P

    2013-02-01

    Biological motion detection is both commonplace and important, but there is great inter-individual variability in this ability, the neural basis of which is currently unknown. Here we examined whether the behavioral variability in biological motion detection is reflected in brain anatomy. Perceptual thresholds for detection of biological motion and control conditions (non-biological object motion detection and motion coherence) were determined in a group of healthy human adults (n=31) together with structural magnetic resonance images of the brain. Voxel based morphometry analyzes revealed that gray matter volumes of left posterior superior temporal sulcus (pSTS) and left ventral premotor cortex (vPMC) significantly predicted individual differences in biological motion detection, but showed no significant relationship with performance on the control tasks. Our study reveals a neural basis associated with the inter-individual variability in biological motion detection, reliably linking the neuroanatomical structure of left pSTS and vPMC with biological motion detection performance. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Excessive motor overflow reveals abnormal inter-hemispheric connectivity in Friedreich ataxia.

    PubMed

    Low, Sze-Cheen; Corben, Louise A; Delatycki, Martin B; Ternes, Anne-Marie; Addamo, Patricia K; Georgiou-Karistianis, Nellie

    2013-07-01

    This study sought to characterise force variability and motor overflow in 12 individuals with Friedreich ataxia (FRDA) and 12 age- and gender-matched controls. Participants performed a finger-pressing task by exerting 30 and 70 % of their maximum finger force using the index finger of the right and left hand. Control of force production was measured as force variability, while any involuntary movements occurring on the finger of the other, passive hand, was measured as motor overflow. Significantly greater force variability in individuals with FRDA compared with controls is indicative of cortico-cerebellar disruption affecting motor control. Meanwhile, significantly greater motor overflow in this group provides the first evidence of possible abnormal inter-hemispheric activity that may be attributable to asymmetrical neuronal loss in the dentate nucleus. Overall, this study demonstrated a differential engagement in the underlying default processes of the motor system in FRDA.

  11. Genome-wide DNA methylation map of human neutrophils reveals widespread inter-individual epigenetic variation

    PubMed Central

    Chatterjee, Aniruddha; Stockwell, Peter A.; Rodger, Euan J.; Duncan, Elizabeth J.; Parry, Matthew F.; Weeks, Robert J.; Morison, Ian M.

    2015-01-01

    The extent of variation in DNA methylation patterns in healthy individuals is not yet well documented. Identification of inter-individual epigenetic variation is important for understanding phenotypic variation and disease susceptibility. Using neutrophils from a cohort of healthy individuals, we generated base-resolution DNA methylation maps to document inter-individual epigenetic variation. We identified 12851 autosomal inter-individual variably methylated fragments (iVMFs). Gene promoters were the least variable, whereas gene body and upstream regions showed higher variation in DNA methylation. The iVMFs were relatively enriched in repetitive elements compared to non-iVMFs, and were associated with genome regulation and chromatin function elements. Further, variably methylated genes were disproportionately associated with regulation of transcription, responsive function and signal transduction pathways. Transcriptome analysis indicates that iVMF methylation at differentially expressed exons has a positive correlation and local effect on the inclusion of that exon in the mRNA transcript. PMID:26612583

  12. Statistically Characterizing Intra- and Inter-Individual Variability in Children with Developmental Coordination Disorder

    ERIC Educational Resources Information Center

    King, Bradley R.; Harring, Jeffrey R.; Oliveira, Marcio A.; Clark, Jane E.

    2011-01-01

    Previous research investigating children with Developmental Coordination Disorder (DCD) has consistently reported increased intra- and inter-individual variability during motor skill performance. Statistically characterizing this variability is not only critical for the analysis and interpretation of behavioral data, but also may facilitate our…

  13. QIVIVE Approaches to Evaluate Inter-individual Toxicokinetic Variability

    EPA Science Inventory

    Manifestation of inter-individual variability in toxicokinetics (TK) will result in identical external exposure concentrations yielding differing blood or tissue concentrations. As efforts to incorporate in vitro testing strategies into human health assessment continue to grow, a...

  14. Toward human resource management in inter-professional health practice: linking organizational culture, group identity and individual autonomy.

    PubMed

    Tataw, David

    2012-01-01

    The literature on team and inter-professional care practice describes numerous barriers to the institutionalization of inter-professional healthcare. Responses to slow institutionalization of inter-professional healthcare practice have failed to describe change variables and to identify change agents relevant to inter-professional healthcare practice. The purpose of this paper is to (1) describe individual and organizational level barriers to collaborative practice in healthcare; (2) identify change variables relevant to the institutionalization of inter-professional practice at individual and organizational levels of analysis; and (3) identify human resource professionals as change agents and describe how the strategic use of the human resource function could transform individual and organizational level change variables and therefore facilitate the healthcare system's shift toward inter-professional practice. A proposed program of institutionalization includes the following components: a strategic plan to align human resource functions with organizational level inter-professional healthcare strategies, activities to enhance professional competencies and the organizational position of human resource personnel, activities to integrate inter-professional healthcare practices into the daily routines of institutional and individual providers, activities to stand up health provider champions as permanent leaders of inter-professional teams with human resource professionals as consultants and activities to bring all key players to the table including health providers. Copyright © 2012 John Wiley & Sons, Ltd.

  15. Intra- and inter-individual variation of BIS-index and Entropy during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study.

    PubMed

    Haenggi, Matthias; Ypparila-Wolters, Heidi; Hauser, Kathrin; Caviezel, Claudio; Takala, Jukka; Korhonen, Ilkka; Jakob, Stephan M

    2009-01-01

    We studied intra-individual and inter-individual variability of two online sedation monitors, BIS and Entropy, in volunteers under sedation. Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS and Entropy (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered. Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy values showed greater variability than BIS(R) values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation. The large intra-individual and inter-individual variability of BIS and Entropy values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability. clinicaltrials.gov Nr. NCT00641563.

  16. Population pharmacokinetic study of memantine: effects of clinical and genetic factors.

    PubMed

    Noetzli, Muriel; Guidi, Monia; Ebbing, Karsten; Eyer, Stephan; Wilhelm, Laurence; Michon, Agnès; Thomazic, Valérie; Alnawaqil, Abdel-Messieh; Maurer, Sophie; Zumbach, Serge; Giannakopoulos, Panteleimon; von Gunten, Armin; Csajka, Chantal; Eap, Chin B

    2013-03-01

    Memantine, a frequently prescribed anti-dementia drug, is mainly eliminated unchanged by the kidneys, partly via tubular secretion. Considerable inter-individual variability in plasma concentrations has been reported. We aimed to investigate clinical and genetic factors influencing memantine disposition. A population pharmacokinetic study was performed including data from 108 patients recruited in a naturalistic setting. Patients were genotyped for common polymorphisms in renal cation transporters (SLC22A1/2/5, SLC47A1, ABCB1) and nuclear receptors (NR1I2, NR1I3, RXR, PPAR) involved in transporter expression. The average clearance was 5.2 L/h with a 27 % inter-individual variability (percentage coefficient of variation). Glomerular filtration rate (p = 0.007) and sex (p = 0.001) markedly influenced memantine clearance. NR1I2 rs1523130 was identified as the unique significant genetic covariate for memantine clearance (p = 0.006), with carriers of the NR1I2 rs1523130 CT/TT genotypes presenting a 16 % slower memantine elimination than carriers of the CC genotype. The better understanding of inter-individual variability of memantine disposition might be beneficial in the context of individual dose optimization.

  17. Antecedents of the attitude towards inter-group reconciliation in a setting of armed conflict.

    PubMed

    Alzate, Mónica; Sabucedo, José-Manuel; Durán, Mar

    2013-02-01

    The concept of Reconciliation as applied to inter-group conflict has come into use only recently. Throughout the history of Psychology, Reconciliation was mostly understood at the individual and inter-personal level. In the present study we shall analyse the roles played by trust, negotiating attitude, legitimacy and ethnocentric attitude over the attitude towards social reconciliation. To this end we studied a group of 188 Colombian civilians living under conditions of real socio-political conflict. A path analysis was performed using the statistical program AMOS whose fit indexes indicate a good fit of the model and a variance of .36. The results show that the variables of trust, negotiating attitude and legitimacy have a significant and positive effect on the reconciliation variable, and significant negative effect on the ethnocentric attitude variable. This study contributes to the integration of a number of variables that facilitate process of social reconciliation, as it explicitly deals with some of the perceptions, attitudes and beliefs which could change the course of a confrontation.

  18. Inter-individual variability in high-throughput risk prioritization of environmental chemicals (IVIVE)

    EPA Science Inventory

    We incorporate inter-individual variability into an open-source high-throughput (HT) toxicokinetics (TK) modeling framework for use in a next-generation risk prioritization approach. Risk prioritization involves rapid triage of thousands of environmental chemicals, most which hav...

  19. Prediction of Biological Motion Perception Performance from Intrinsic Brain Network Regional Efficiency

    PubMed Central

    Wang, Zengjian; Zhang, Delong; Liang, Bishan; Chang, Song; Pan, Jinghua; Huang, Ruiwang; Liu, Ming

    2016-01-01

    Biological motion perception (BMP) refers to the ability to perceive the moving form of a human figure from a limited amount of stimuli, such as from a few point lights located on the joints of a moving body. BMP is commonplace and important, but there is great inter-individual variability in this ability. This study used multiple regression model analysis to explore the association between BMP performance and intrinsic brain activity, in order to investigate the neural substrates underlying inter-individual variability of BMP performance. The resting-state functional magnetic resonance imaging (rs-fMRI) and BMP performance data were collected from 24 healthy participants, for whom intrinsic brain networks were constructed, and a graph-based network efficiency metric was measured. Then, a multiple linear regression model was used to explore the association between network regional efficiency and BMP performance. We found that the local and global network efficiency of many regions was significantly correlated with BMP performance. Further analysis showed that the local efficiency rather than global efficiency could be used to explain most of the BMP inter-individual variability, and the regions involved were predominately located in the Default Mode Network (DMN). Additionally, discrimination analysis showed that the local efficiency of certain regions such as the thalamus could be used to classify BMP performance across participants. Notably, the association pattern between network nodal efficiency and BMP was different from the association pattern of static directional/gender information perception. Overall, these findings show that intrinsic brain network efficiency may be considered a neural factor that explains BMP inter-individual variability. PMID:27853427

  20. Investigating the state-of-the-art in whole-body MR-based attenuation correction: an intra-individual, inter-system, inventory study on three clinical PET/MR systems.

    PubMed

    Beyer, Thomas; Lassen, Martin L; Boellaard, Ronald; Delso, Gaspar; Yaqub, Maqsood; Sattler, Bernhard; Quick, Harald H

    2016-02-01

    We assess inter- and intra-subject variability of magnetic resonance (MR)-based attenuation maps (MRμMaps) of human subjects for state-of-the-art positron emission tomography (PET)/MR imaging systems. Four healthy male subjects underwent repeated MR imaging with a Siemens Biograph mMR, Philips Ingenuity TF and GE SIGNA PET/MR system using product-specific MR sequences and image processing algorithms for generating MRμMaps. Total lung volumes and mean attenuation values in nine thoracic reference regions were calculated. Linear regression was used for comparing lung volumes on MRμMaps. Intra- and inter-system variability was investigated using a mixed effects model. Intra-system variability was seen for the lung volume of some subjects, (p = 0.29). Mean attenuation values across subjects were significantly different (p < 0.001) due to different segmentations of the trachea. Differences in the attenuation values caused noticeable intra-individual and inter-system differences that translated into a subsequent bias of the corrected PET activity values, as verified by independent simulations. Significant differences of MRμMaps generated for the same subjects but different PET/MR systems resulted in differences in attenuation correction factors, particularly in the thorax. These differences currently limit the quantitative use of PET/MR in multi-center imaging studies.

  1. Population Pharmacokinetic-Pharmacodynamic Modeling of 5-Fluorouracil for Toxicities in Rats.

    PubMed

    Kobuchi, Shinji; Ito, Yukako; Sakaeda, Toshiyuki

    2017-08-01

    Myelosuppression is a dose-limiting toxicity of 5-fluorouracil (5-FU). Predicting the inter- and intra-patient variability in pharmacokinetics and toxicities of 5-FU may contribute to the individualized medicine. This study aimed to establish a population pharmacokinetic-pharmacodynamic model that could evaluate the inter- and intra-individual variability in the plasma 5-FU concentration, 5-FU-induced body weight loss and myelosuppression in rats. Plasma 5-FU concentrations, body weight loss, and blood cell counts in rats following the intravenous administration of various doses of 5-FU for 4 days were used to develop the population pharmacokinetic-pharmacodynamic model. The population pharmacokinetic model consisting of a two-compartment model with Michaelis-Menten elimination kinetics successfully characterized the individual and population predictions of the plasma concentration of 5-FU and provided credible parameter estimates. The estimates of inter-individual variability in maximal rate of saturable metabolism and residual variability were 8.1 and 22.0%, respectively. The population pharmacokinetic-pharmacodynamic model adequately described the individual complete time-course of alterations in body weight loss, erythrocyte, leukocyte, and lymphocyte counts in rats treated with various doses of 5-FU. The inter-individual variability of the drug effects in the pharmacodynamic model for body weight loss was 82.6%, which was relatively high. The results of the present study suggest that not only individual fluctuations in the 5-FU concentration but also the cell sensitivity would affect the onset and degree of 5-FU-induced toxicity. This population pharmacokinetic-pharmacodynamic model could evaluate the inter- and intra-individual variability in drug-induced toxicity and guide the assessments of novel anticancer agents in drug development.

  2. Spontaneous individual differences in cognitive performances of young adult rats predict locomotor response to amphetamine.

    PubMed

    Dellu-Hagedorn, F

    2005-01-01

    Inter-individual differences in cognitive capacities of young adult rats have largely been ignored. To explore this variability and its neurobiological bases, the relationships between individual differences in working memory and locomotor responses to novelty and to amphetamine were investigated in SD rats. Groups of good and poor learners were isolated, the latter demonstrating a markedly slower learning of the task compared to performant rats, with more perseverations independently to motivational state. They also presented a much higher increase in amphetamine-induced locomotion that remained significant for more than 1h after the injection. These results provide evidence that variability in cognitive capacities can be used to reveal their neurobiological substrates. They open new perspectives to study a possible cognitive origin of addictive behaviors and to investigate the involvement of these inter-individual differences on those observed later in life.

  3. Response variability of different anodal transcranial direct current stimulation intensities across multiple sessions.

    PubMed

    Ammann, Claudia; Lindquist, Martin A; Celnik, Pablo A

    It is well known that transcranial direct current stimulation (tDCS) is capable of modulating corticomotor excitability. However, a source of growing concern has been the observed inter- and intra-individual variability of tDCS-responses. Recent studies have assessed whether individuals respond in a predictable manner across repeated sessions of anodal tDCS (atDCS). The findings of these investigations have been inconsistent, and their methods have some limitations (i.e. lack of sham condition or testing only one tDCS intensity). To study inter- and intra-individual variability of atDCS effects at two different intensities on primary motor cortex (M1) excitability. Twelve subjects participated in a crossover study testing 7-min atDCS over M1 in three separate conditions (2 mA, 1 mA, sham) each repeated three times separated by 48 h. Motor evoked potentials were recorded before and after stimulation (up to 30min). Time of testing was maintained consistent within participants. To estimate the reliability of tDCS effects across sessions, we calculated the Intra-class Correlation Coefficient (ICC). AtDCS at 2 mA, but not 1 mA, significantly increased cortical excitability at the group level in all sessions. The overall ICC revealed fair to high reliability of tDCS effects for multiple sessions. Given that the distribution of responses showed important variability in the sham condition, we established a Sham Variability-Based Threshold to classify responses and to track individual changes across sessions. Using this threshold an intra-individual consistent response pattern was then observed only for the 2 mA condition. 2 mA anodal tDCS results in consistent intra- and inter-individual increases of M1 excitability. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Inter-birth interval in zebras is longer following the birth of male foals than after female foals

    NASA Astrophysics Data System (ADS)

    Barnier, Florian; Grange, Sophie; Ganswindt, Andre; Ncube, Hlengisizwe; Duncan, Patrick

    2012-07-01

    Mammalian reproductive rates vary among individuals for physiological and environmental reasons. This study aims to determine reproductive rates from an individually monitored population of wild Plains zebras Equus quagga, and to assess the sources of variability in inter-birth intervals. The animals were monitored, where possible, every six months from 2004 to 2011. Thirty nine intervals corresponding to 65 births in 26 mares were identified, using direct observations and faecal steroid monitoring. Mean foaling rate of the population is 0.74 foal/year, and comparable with the literature. There was no significant effect of mother's age, nor of the season of previous birth on the length of inter-birth intervals. Inter-birth interval was significantly longer when the first foal was a male. This finding indicates that additional costs of having a son may delay future reproduction and thus reduce the total number of offspring a mare can have during her lifetime. Individually-based data provide critical information on the determinants of reproductive rates, and are therefore a key to understanding the causes of variations in life-history traits.

  5. Impact of Reconstruction Algorithms on CT Radiomic Features of Pulmonary Tumors: Analysis of Intra- and Inter-Reader Variability and Inter-Reconstruction Algorithm Variability.

    PubMed

    Kim, Hyungjin; Park, Chang Min; Lee, Myunghee; Park, Sang Joon; Song, Yong Sub; Lee, Jong Hyuk; Hwang, Eui Jin; Goo, Jin Mo

    2016-01-01

    To identify the impact of reconstruction algorithms on CT radiomic features of pulmonary tumors and to reveal and compare the intra- and inter-reader and inter-reconstruction algorithm variability of each feature. Forty-two patients (M:F = 19:23; mean age, 60.43±10.56 years) with 42 pulmonary tumors (22.56±8.51mm) underwent contrast-enhanced CT scans, which were reconstructed with filtered back projection and commercial iterative reconstruction algorithm (level 3 and 5). Two readers independently segmented the whole tumor volume. Fifteen radiomic features were extracted and compared among reconstruction algorithms. Intra- and inter-reader variability and inter-reconstruction algorithm variability were calculated using coefficients of variation (CVs) and then compared. Among the 15 features, 5 first-order tumor intensity features and 4 gray level co-occurrence matrix (GLCM)-based features showed significant differences (p<0.05) among reconstruction algorithms. As for the variability, effective diameter, sphericity, entropy, and GLCM entropy were the most robust features (CV≤5%). Inter-reader variability was larger than intra-reader or inter-reconstruction algorithm variability in 9 features. However, for entropy, homogeneity, and 4 GLCM-based features, inter-reconstruction algorithm variability was significantly greater than inter-reader variability (p<0.013). Most of the radiomic features were significantly affected by the reconstruction algorithms. Inter-reconstruction algorithm variability was greater than inter-reader variability for entropy, homogeneity, and GLCM-based features.

  6. Inter-individual Variability in Soccer Players of Different Age Groups Playing Different Positions

    PubMed Central

    Nikolaidis, Pantelis; Ziv, Gal; Lidor, Ronnie; Arnon, Michal

    2014-01-01

    The purpose of this study was twofold: (a) to profile physical characteristics and motor abilities of three age groups of soccer players – under 14 years, 14–17, and over 17, playing different positions – goalkeepers, defenders, midfielders, and forwards; and (b) to examine the inter-individual variability among the players in each age group in all physical and physiological measurements performed in the study. In addition, anthropometric, power, strength, and flexibility tests were administered. Findings showed large inter-individual variability in all three age groups and in all playing positions. Differences between playing positions were found only in the 14–17 group (body mass) and in the over-17 group (body height, body mass, fat-free mass, and mean power in the Wingate Anaerobic Test). Due to the observed large inter-individual variability, it was concluded that the findings obtained in the physical and physiological tests should be interpreted with caution when attempting to differentiate between successful and unsuccessful soccer players, as well as when trying to predict future success in soccer. PMID:25031689

  7. Inter-individual variability and pattern recognition of surface electromyography in front crawl swimming.

    PubMed

    Martens, Jonas; Daly, Daniel; Deschamps, Kevin; Staes, Filip; Fernandes, Ricardo J

    2016-12-01

    Variability of electromyographic (EMG) recordings is a complex phenomenon rarely examined in swimming. Our purposes were to investigate inter-individual variability in muscle activation patterns during front crawl swimming and assess if there were clusters of sub patterns present. Bilateral muscle activity of rectus abdominis (RA) and deltoideus medialis (DM) was recorded using wireless surface EMG in 15 adult male competitive swimmers. The amplitude of the median EMG trial of six upper arm movement cycles was used for the inter-individual variability assessment, quantified with the coefficient of variation, coefficient of quartile variation, the variance ratio and mean deviation. Key features were selected based on qualitative and quantitative classification strategies to enter in a k-means cluster analysis to examine the presence of strong sub patterns. Such strong sub patterns were found when clustering in two, three and four clusters. Inter-individual variability in a group of highly skilled swimmers was higher compared to other cyclic movements which is in contrast to what has been reported in the previous 50years of EMG research in swimming. This leads to the conclusion that coaches should be careful in using overall reference EMG information to enhance the individual swimming technique of their athletes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Population pharmacokinetics of Rilpivirine in HIV-1-infected patients treated with the single-tablet regimen rilpivirine/tenofovir/emtricitabine.

    PubMed

    Néant, Nadège; Gattacceca, Florence; Lê, Minh Patrick; Yazdanpanah, Yazdan; Dhiver, Catherine; Bregigeon, Sylvie; Mokhtari, Saadia; Peytavin, Gilles; Tamalet, Catherine; Descamps, Diane; Lacarelle, Bruno; Solas, Caroline

    2018-04-01

    Rilpivirine, prescribed for the treatment of HIV infection, presents an important inter-individual pharmacokinetic variability. We aimed to determine population pharmacokinetic parameters of rilpivirine in adult HIV-infected patients and quantify their inter-individual variability. We conducted a multicenter, retrospective, and observational study in patients treated with the once-daily rilpivirine/tenofovir disoproxil fumarate/emtricitabine regimen. As part of routine therapeutic drug monitoring, rilpivirine concentrations were measured by UPLC-MS/MS. Population pharmacokinetic analysis was performed using NONMEM software. Once the compartmental and random effects models were selected, covariates were tested to explain the inter-individual variability in pharmacokinetic parameters. The final model qualification was performed by both statistical and graphical methods. We included 379 patients, resulting in the analysis of 779 rilpivirine plasma concentrations. Of the observed trough individual plasma concentrations, 24.4% were below the 50 ng/ml minimal effective concentration. A one-compartment model with first-order absorption best described the data. The estimated fixed effect for plasma apparent clearance and distribution volume were 9 L/h and 321 L, respectively, resulting in a half-life of 25.2 h. The common inter-individual variability for both parameters was 34.1% at both the first and the second occasions. The inter-individual variability of clearance was 30.3%. Our results showed a terminal half-life lower than reported and a high proportion of patients with suboptimal rilpivirine concentrations, which highlights the interest of using therapeutic drug monitoring in clinical practice. The population analysis performed with data from "real-life" conditions resulted in reliable post hoc estimates of pharmacokinetic parameters, suitable for individualization of dosing regimen.

  9. Age and CD161 Expression Contribute to Inter-Individual Variation in Interleukin-23 Response in CD8+ Memory Human T Cells

    PubMed Central

    Abraham, Clara; Cho, Judy H.

    2013-01-01

    The interleukin-23 (IL-23) pathway plays a critical role in the pathogenesis of multiple chronic inflammatory disorders, however, inter-individual variability in IL-23-induced signal transduction in circulating human lymphocytes has not been well-defined. In this study, we observed marked, reproducible inter-individual differences in IL-23 responsiveness (measured by STAT3 phosphorylation) in peripheral blood CD8+CD45RO+ memory T and CD3+CD56+ NKT cells. Age, but not gender, was a significant (Pearson’s correlation coefficient, r = −0.37, p = 0.001) source of variability observed in CD8+CD45RO+ memory T cells, with IL-23 responsiveness gradually decreasing with increasing age. Relative to cells from individuals demonstrating low responsiveness to IL-23 stimulation, CD8+CD45RO+ memory T cells from individuals demonstrating high responsiveness to IL-23 stimulation showed increased gene expression for IL-23 receptor (IL-23R), RORC (RORγt) and CD161 (KLRB1), whereas RORA (RORα) and STAT3 expression were equivalent. Similar to CD4+ memory T cells, IL-23 responsiveness is confined to the CD161+ subset in CD8+CD45RO+ memory T cells, suggesting a similar CD161+ precursor as has been reported for CD4+ Th17 cells. We observed a very strong positive correlation between IL-23 responsiveness and the fraction of CD161+, CD8+CD45RO+ memory T cells (r = 0.80, p<0.001). Moreover, the fraction of CD161+, CD8+CD45RO+ memory T cells gradually decreases with aging (r = −0.34, p = 0.05). Our data define the inter-individual differences in IL-23 responsiveness in peripheral blood lymphocytes from the general population. Variable expression of CD161, IL-23R and RORC affects IL-23 responsiveness and contributes to the inter-individual susceptibility to IL-23-mediated defenses and inflammatory processes. PMID:23469228

  10. Investigating Inter-Individual Differences in Short-Term Intra-Individual Variability

    ERIC Educational Resources Information Center

    Wang, Lijuan; Hamaker, Ellen; Bergeman, C. S.

    2012-01-01

    Intra-individual variability over a short period of time may contain important information about how individuals differ from each other. In this article we begin by discussing diverse indicators for quantifying intra-individual variability and indicate their advantages and disadvantages. Then we propose an alternative method that models…

  11. Pharmacogenetics of drug response in Parkinson's disease.

    PubMed

    Džoljić, Eleonora; Novaković, Ivana; Krajinovic, Maja; Grbatinić, Ivan; Kostić, Vladimir

    2015-01-01

    Parkinson's disease (PD) is a debilitating, demoralizing and financially devastating condition affecting 1% of population at the age of 60 years. Thus, very important issue to address is individual therapy optimization. Recent results have shown evidence that variable efficacy of treatment and risk of motor and mental complications could have genetic origin. Significant roles in that process play (pharmaco)genomic/genetic studies of PD. Variability in genes coding for drug-metabolizing enzymes, drug receptors and proteins involved in drug pathway signaling is an important factor determining inter-individual variability in drug responses. Interpersonal differences in drug responses are clearly documented although individualized treatment of PD is not widely known. Treatment with antiparkinsonian drugs is associated with the development of complications, such as L-DOPA-induced dyskinesia (LID), hallucinations and excessive daytime sleepiness. Carriers of specific genetic polymorphisms are particularly susceptible to development of some of these drug adverse effects. Pharmacogenomics aims to understand the relationship between genetic factors and inter-individual variations in drug responses, and to translate this information in therapy tailored to individual patient genetics. Relatively few efforts have been made to investigate the role of pharmacogenetics in the individual response to anti-PD drugs. Thus, many genetic variations and polymorphisms in myriad of different proteins can influence individual response to anti-PD drugs.

  12. Costs and Benefits of Orthographic Inconsistency in Reading: Evidence from a Cross-Linguistic Comparison

    PubMed Central

    Marinelli, Chiara Valeria; Romani, Cristina; Burani, Cristina; McGowan, Victoria A.; Zoccolotti, Pierluigi

    2016-01-01

    We compared reading acquisition in English and Italian children up to late primary school analyzing RTs and errors as a function of various psycholinguistic variables and changes due to experience. Our results show that reading becomes progressively more reliant on larger processing units with age, but that this is modulated by consistency of the language. In English, an inconsistent orthography, reliance on larger units occurs earlier on and it is demonstrated by faster RTs, a stronger effect of lexical variables and lack of length effect (by fifth grade). However, not all English children are able to master this mode of processing yielding larger inter-individual variability. In Italian, a consistent orthography, reliance on larger units occurs later and it is less pronounced. This is demonstrated by larger length effects which remain significant even in older children and by larger effects of a global factor (related to speed of orthographic decoding) explaining changes of performance across ages. Our results show the importance of considering not only overall performance, but inter-individual variability and variability between conditions when interpreting cross-linguistic differences. PMID:27355364

  13. Costs and Benefits of Orthographic Inconsistency in Reading: Evidence from a Cross-Linguistic Comparison.

    PubMed

    Marinelli, Chiara Valeria; Romani, Cristina; Burani, Cristina; McGowan, Victoria A; Zoccolotti, Pierluigi

    2016-01-01

    We compared reading acquisition in English and Italian children up to late primary school analyzing RTs and errors as a function of various psycholinguistic variables and changes due to experience. Our results show that reading becomes progressively more reliant on larger processing units with age, but that this is modulated by consistency of the language. In English, an inconsistent orthography, reliance on larger units occurs earlier on and it is demonstrated by faster RTs, a stronger effect of lexical variables and lack of length effect (by fifth grade). However, not all English children are able to master this mode of processing yielding larger inter-individual variability. In Italian, a consistent orthography, reliance on larger units occurs later and it is less pronounced. This is demonstrated by larger length effects which remain significant even in older children and by larger effects of a global factor (related to speed of orthographic decoding) explaining changes of performance across ages. Our results show the importance of considering not only overall performance, but inter-individual variability and variability between conditions when interpreting cross-linguistic differences.

  14. Decision making in healthy participants on the Iowa Gambling Task: new insights from an operant approach.

    PubMed

    Bull, Peter N; Tippett, Lynette J; Addis, Donna Rose

    2015-01-01

    The Iowa Gambling Task (IGT) has contributed greatly to the study of affective decision making. However, researchers have observed high inter-study and inter-individual variability in IGT performance in healthy participants, and many are classified as impaired using standard criteria. Additionally, while decision-making deficits are often attributed to atypical sensitivity to reward and/or punishment, the IGT lacks an integrated sensitivity measure. Adopting an operant perspective, two experiments were conducted to explore these issues. In Experiment 1, 50 healthy participants completed a 200-trial version of the IGT which otherwise closely emulated Bechara et al.'s (1999) original computer task. Group data for Trials 1-100 closely replicated Bechara et al.'s original findings of high net scores and preferences for advantageous decks, suggesting that implementations that depart significantly from Bechara's standard IGT contribute to inter-study variability. During Trials 101-200, mean net scores improved significantly and the percentage of participants meeting the "impaired" criterion was halved. An operant-style stability criterion applied to individual data revealed this was likely related to individual differences in learning rate. Experiment 2 used a novel operant card task-the Auckland Card Task (ACT)-to derive quantitative estimates of sensitivity using the generalized matching law. Relative to individuals who mastered the IGT, persistent poor performers on the IGT exhibited significantly lower sensitivity to magnitudes (but not frequencies) of rewards and punishers on the ACT. Overall, our findings demonstrate the utility of operant-style analysis of IGT data and the potential of applying operant concurrent-schedule procedures to the study of human decision making.

  15. Inter-worker variability in lower body postures during assembly line work: implications for exposure assessment.

    PubMed

    Keyserling, W Monroe; Wiggermann, Neal; Werner, Robert A; Gell, Nancy

    2010-05-01

    This study evaluated inter-worker variability in lower body posture and work activity during highly-structured assembly line work. Data were collected from 79 unique assembly line workstations in an engine manufacturing plant. Because the plant utilized work teams, 4-8 workers rotated through each workstation. At least 30 min of videotape was collected from at least three workers at each workstation. A computer-assisted work sampling procedure randomly selected 200 video "freeze-frames" for each worker. Lower body posture/movement (e.g., sit, stand, walk, etc.) was determined for each frame and used to estimate the percentage of time the worker spent in various postures and activities. Chi-square analyses were performed for each workstation to assess the significance of inter-worker differences. Due to variations in individual work methods, significant differences (p <.05) were found at 57 out of 79 workstations (72%). The greatest differences occurred when workers had the option to choose between standing and sitting (significant in 8 of 8 cases; in extreme examples, sit time ranged between 0-100% on one job, and 6.5-98% on another). Studying a single worker (or "proxy") can contribute to substantial error when estimating exposures in workplace studies of ergonomic stressors, since the proxy may not be representative of all workers who perform the job. Individual measurements are preferable, particularly for jobs where workers have substantial latitude to develop individualized work methods.

  16. Neurobiological degeneracy and affordance perception support functional intra-individual variability of inter-limb coordination during ice climbing.

    PubMed

    Seifert, Ludovic; Wattebled, Léo; Herault, Romain; Poizat, Germain; Adé, David; Gal-Petitfaux, Nathalie; Davids, Keith

    2014-01-01

    This study investigated the functional intra-individual movement variability of ice climbers differing in skill level to understand how icefall properties were used by participants as affordances to adapt inter-limb coordination patterns during performance. Seven expert climbers and seven beginners were observed as they climbed a 30 m icefall. Movement and positioning of the left and right hand ice tools, crampons and the climber's pelvis over the first 20 m of the climb were recorded and digitized using video footage from a camera (25 Hz) located perpendicular to the plane of the icefall. Inter-limb coordination, frequency and types of action and vertical axis pelvis displacement exhibited by each climber were analysed for the first five minutes of ascent. Participant perception of climbing affordances was assessed through: (i) calculating the ratio between exploratory movements and performed actions, and (ii), identifying, by self-confrontation interviews, the perceptual variables of environmental properties, which were significant to climbers for their actions. Data revealed that experts used a wider range of upper and lower limb coordination patterns, resulting in the emergence of different types of action and fewer exploratory movements, suggesting that effective holes in the icefall provided affordances to regulate performance. In contrast, beginners displayed lower levels of functional intra-individual variability of motor organization, due to repetitive swinging of ice tools and kicking of crampons to achieve and maintain a deep anchorage, suggesting lack of perceptual attunement and calibration to environmental properties to support climbing performance.

  17. Spontaneous Fluctuations in Sensory Processing Predict Within-Subject Reaction Time Variability.

    PubMed

    Ribeiro, Maria J; Paiva, Joana S; Castelo-Branco, Miguel

    2016-01-01

    When engaged in a repetitive task our performance fluctuates from trial-to-trial. In particular, inter-trial reaction time variability has been the subject of considerable research. It has been claimed to be a strong biomarker of attention deficits, increases with frontal dysfunction, and predicts age-related cognitive decline. Thus, rather than being just a consequence of noise in the system, it appears to be under the control of a mechanism that breaks down under certain pathological conditions. Although the underlying mechanism is still an open question, consensual hypotheses are emerging regarding the neural correlates of reaction time inter-trial intra-individual variability. Sensory processing, in particular, has been shown to covary with reaction time, yet the spatio-temporal profile of the moment-to-moment variability in sensory processing is still poorly characterized. The goal of this study was to characterize the intra-individual variability in the time course of single-trial visual evoked potentials and its relationship with inter-trial reaction time variability. For this, we chose to take advantage of the high temporal resolution of the electroencephalogram (EEG) acquired while participants were engaged in a 2-choice reaction time task. We studied the link between single trial event-related potentials (ERPs) and reaction time using two different analyses: (1) time point by time point correlation analyses thereby identifying time windows of interest; and (2) correlation analyses between single trial measures of peak latency and amplitude and reaction time. To improve extraction of single trial ERP measures related with activation of the visual cortex, we used an independent component analysis (ICA) procedure. Our ERP analysis revealed a relationship between the N1 visual evoked potential and reaction time. The earliest time point presenting a significant correlation of its respective amplitude with reaction time occurred 175 ms after stimulus onset, just after the onset of the N1 peak. Interestingly, single trial N1 latency correlated significantly with reaction time, while N1 amplitude did not. In conclusion, our findings suggest that inter-trial variability in the timing of extrastriate visual processing contributes to reaction time variability.

  18. Spontaneous Fluctuations in Sensory Processing Predict Within-Subject Reaction Time Variability

    PubMed Central

    Ribeiro, Maria J.; Paiva, Joana S.; Castelo-Branco, Miguel

    2016-01-01

    When engaged in a repetitive task our performance fluctuates from trial-to-trial. In particular, inter-trial reaction time variability has been the subject of considerable research. It has been claimed to be a strong biomarker of attention deficits, increases with frontal dysfunction, and predicts age-related cognitive decline. Thus, rather than being just a consequence of noise in the system, it appears to be under the control of a mechanism that breaks down under certain pathological conditions. Although the underlying mechanism is still an open question, consensual hypotheses are emerging regarding the neural correlates of reaction time inter-trial intra-individual variability. Sensory processing, in particular, has been shown to covary with reaction time, yet the spatio-temporal profile of the moment-to-moment variability in sensory processing is still poorly characterized. The goal of this study was to characterize the intra-individual variability in the time course of single-trial visual evoked potentials and its relationship with inter-trial reaction time variability. For this, we chose to take advantage of the high temporal resolution of the electroencephalogram (EEG) acquired while participants were engaged in a 2-choice reaction time task. We studied the link between single trial event-related potentials (ERPs) and reaction time using two different analyses: (1) time point by time point correlation analyses thereby identifying time windows of interest; and (2) correlation analyses between single trial measures of peak latency and amplitude and reaction time. To improve extraction of single trial ERP measures related with activation of the visual cortex, we used an independent component analysis (ICA) procedure. Our ERP analysis revealed a relationship between the N1 visual evoked potential and reaction time. The earliest time point presenting a significant correlation of its respective amplitude with reaction time occurred 175 ms after stimulus onset, just after the onset of the N1 peak. Interestingly, single trial N1 latency correlated significantly with reaction time, while N1 amplitude did not. In conclusion, our findings suggest that inter-trial variability in the timing of extrastriate visual processing contributes to reaction time variability. PMID:27242470

  19. Heart rate variability is associated with social value orientation in males but not females.

    PubMed

    Lischke, Alexander; Mau-Moeller, Anett; Jacksteit, Robert; Pahnke, Rike; Hamm, Alfons O; Weippert, Matthias

    2018-05-09

    Phylogenetic and neurobiological theories suggest that inter-individual differences in high frequency heart rate variability (HF-HRV) are associated with inter-individual differences in social behavior and social cognition. To test these theories, we investigated whether individuals with high and low HF-HRV would show different preferences for cooperative behavior in social contexts. We recorded resting state HF-HRV in 84 healthy individuals before they completed the Social Value Orientation task, a well-established measure of cooperative preferences. HF-HRV was derived from short-term (300 s) and ultra-short-term (60 s, 120 s) recordings of participants' heart rate to determine the robustness of possible findings. Irrespective of recording length, we found a sex-dependent association between inter-individual differences in HF-HRV and inter-individual differences in social value orientation: The preference for cooperation was more pronounced among individuals with high as compared low HF-HRV, albeit only in male and not in female participants. These findings suggest that males with high HF-HRV are more inclined to engage in cooperative behavior than males with low HF-HRV.

  20. Heart rate variability is associated with psychosocial stress in distinct social domains.

    PubMed

    Lischke, Alexander; Jacksteit, Robert; Mau-Moeller, Anett; Pahnke, Rike; Hamm, Alfons O; Weippert, Matthias

    2018-03-01

    Psychosocial stress is associated with substantial morbidity and mortality. Accordingly, there is a growing interest in biomarkers that indicate whether individuals show adaptive (i.e., stress-buffering and health-promoting) or maladaptive (i.e., stress-escalating and health-impairing) stress reactions in social contexts. As heart rate variability (HRV) has been suggested to be a biomarker of adaptive behavior during social encounters, it may be possible that inter-individual differences in HRV are associated with inter-individual differences regarding stress in distinct social domains. To test this hypothesis, resting state HRV and psychosocial stress was assessed in 83 healthy community-dwelling individuals (age: 18-35years). HRV was derived from heart rate recordings during spontaneous and instructed breathing to assess the robustness of possible associations between inter-individual differences in HRV and inter-individual differences in psychosocial stress. Psychosocial stress was determined with a self-report questionnaire assessing stress in distinct social domains. A series of categorical and dimensional analyses revealed an association between inter-individual differences in HRV and inter-individual differences in psychosocial stress: Individuals with high HRV reported less stress in social life, but not in family life, work life or everyday life, than individuals with low HRV. On basis of these findings, it may be assumed that individuals with high HRV experience less psychosocial stress than individuals with low HRV. Although such an assumption needs to be corroborated by further findings, it seems to be consistent with previous findings showing that individuals with high HRV suffer less from stress and stress-related disorders than individuals with low HRV. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Decision making in healthy participants on the Iowa Gambling Task: new insights from an operant approach

    PubMed Central

    Bull, Peter N.; Tippett, Lynette J.; Addis, Donna Rose

    2015-01-01

    The Iowa Gambling Task (IGT) has contributed greatly to the study of affective decision making. However, researchers have observed high inter-study and inter-individual variability in IGT performance in healthy participants, and many are classified as impaired using standard criteria. Additionally, while decision-making deficits are often attributed to atypical sensitivity to reward and/or punishment, the IGT lacks an integrated sensitivity measure. Adopting an operant perspective, two experiments were conducted to explore these issues. In Experiment 1, 50 healthy participants completed a 200-trial version of the IGT which otherwise closely emulated Bechara et al.'s (1999) original computer task. Group data for Trials 1–100 closely replicated Bechara et al.'s original findings of high net scores and preferences for advantageous decks, suggesting that implementations that depart significantly from Bechara's standard IGT contribute to inter-study variability. During Trials 101–200, mean net scores improved significantly and the percentage of participants meeting the “impaired” criterion was halved. An operant-style stability criterion applied to individual data revealed this was likely related to individual differences in learning rate. Experiment 2 used a novel operant card task—the Auckland Card Task (ACT)—to derive quantitative estimates of sensitivity using the generalized matching law. Relative to individuals who mastered the IGT, persistent poor performers on the IGT exhibited significantly lower sensitivity to magnitudes (but not frequencies) of rewards and punishers on the ACT. Overall, our findings demonstrate the utility of operant-style analysis of IGT data and the potential of applying operant concurrent-schedule procedures to the study of human decision making. PMID:25904884

  2. Analysis of variance to assess statistical significance of Laplacian estimation accuracy improvement due to novel variable inter-ring distances concentric ring electrodes.

    PubMed

    Makeyev, Oleksandr; Joe, Cody; Lee, Colin; Besio, Walter G

    2017-07-01

    Concentric ring electrodes have shown promise in non-invasive electrophysiological measurement demonstrating their superiority to conventional disc electrodes, in particular, in accuracy of Laplacian estimation. Recently, we have proposed novel variable inter-ring distances concentric ring electrodes. Analytic and finite element method modeling results for linearly increasing distances electrode configurations suggested they may decrease the truncation error resulting in more accurate Laplacian estimates compared to currently used constant inter-ring distances configurations. This study assesses statistical significance of Laplacian estimation accuracy improvement due to novel variable inter-ring distances concentric ring electrodes. Full factorial design of analysis of variance was used with one categorical and two numerical factors: the inter-ring distances, the electrode diameter, and the number of concentric rings in the electrode. The response variables were the Relative Error and the Maximum Error of Laplacian estimation computed using a finite element method model for each of the combinations of levels of three factors. Effects of the main factors and their interactions on Relative Error and Maximum Error were assessed and the obtained results suggest that all three factors have statistically significant effects in the model confirming the potential of using inter-ring distances as a means of improving accuracy of Laplacian estimation.

  3. Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish.

    PubMed

    Román, Angel-Carlos; Vicente-Page, Julián; Pérez-Escudero, Alfonso; Carvajal-González, Jose M; Fernández-Salguero, Pedro M; de Polavieja, Gonzalo G

    2018-04-25

    Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive. We use the zebrafish (Danio rerio) as a model to test the influence of histone modifications on behavior. We find that laboratory and isogenic zebrafish larvae show consistent individual behaviors when swimming freely in identical wells or in reaction to stimuli. This behavioral inter-individual variability is reduced when we impair the histone deacetylation pathway. Individuals with high levels of histone H4 acetylation, and specifically H4K12, behave similarly to the average of the population, but those with low levels deviate from it. More precisely, we find a set of genomic regions whose histone H4 acetylation is reduced with the distance between the individual and the average population behavior. We find evidence that this modulation depends on a complex of Yin-yang 1 (YY1) and histone deacetylase 1 (HDAC1) that binds to and deacetylates these regions. These changes are not only maintained at the transcriptional level but also amplified, as most target regions are located near genes encoding transcription factors. We suggest that stochasticity in the histone deacetylation pathway participates in the generation of genetic-independent behavioral inter-individual variability.

  4. Development from childhood to adulthood increases morphological and functional inter-individual variability in the right superior temporal cortex.

    PubMed

    Bonte, Milene; Frost, Martin A; Rutten, Sanne; Ley, Anke; Formisano, Elia; Goebel, Rainer

    2013-12-01

    We study the developmental trajectory of morphology and function of the superior temporal cortex (STC) in children (8-9 years), adolescents (14-15 years) and young adults. We analyze cortical surface landmarks and functional MRI (fMRI) responses to voices, other natural categories and tones and examine how hemispheric asymmetry and inter-subject variability change across age. Our results show stable morphological asymmetries across age groups, including a larger left planum temporale and a deeper right superior temporal sulcus. fMRI analyses show that a rightward lateralization for voice-selective responses is present in all groups but decreases with age. Furthermore, STC responses to voices change from being less selective and more spatially diffuse in children to highly selective and focal in adults. Interestingly, the analysis of morphological landmarks reveals that inter-subject variability increases during development in the right--but not in the left--STC. Similarly, inter-subject variability of cortically-realigned functional responses to voices, other categories and tones increases with age in the right STC. Our findings reveal asymmetric developmental changes in brain regions crucial for auditory and voice perception. The age-related increase of inter-subject variability in right STC suggests that anatomy and function of this region are shaped by unique individual developmental experiences. © 2013.

  5. Reduced variability and execution time to reach a target with a needle GPS system: Comparison between physicians, residents and nurse anaesthetists.

    PubMed

    Fevre, Marie-Cécile; Vincent, Caroline; Picard, Julien; Vighetti, Arnaud; Chapuis, Claire; Detavernier, Maxime; Allenet, Benoît; Payen, Jean-François; Bosson, Jean-Luc; Albaladejo, Pierre

    2018-02-01

    Ultrasound (US) guided needle positioning is safer than anatomical landmark techniques for central venous access. Hand-eye coordination and execution time depend on the professional's ability, previous training and personal skills. Needle guidance positioning systems (GPS) may theoretically reduce execution time and facilitate needle positioning in specific targets, thus improving patient comfort and safety. Three groups of healthcare professionals (41 anaesthesiologists and intensivists, 41 residents in anaesthesiology and intensive care, 39 nurse anaesthetists) were included and required to perform 3 tasks (positioning the tip of a needle in three different targets in a silicon phantom) by using successively a conventional US-guided needle positioning and a needle GPS. We measured execution times to perform the tasks, hand-eye coordination and the number of repositioning occurrences or errors in handling the needle or the probe. Without the GPS system, we observed a significant inter-individual difference for execution time (P<0.05), hand-eye coordination and the number of errors/needle repositioning between physicians, residents and nurse anaesthetists. US training and video gaming were found to be independent factors associated with a shorter execution time. Use of GPS attenuated the inter-individual and group variability. We observed a reduced execution time and improved hand-eye coordination in all groups as compared to US without GPS. Neither US training, video gaming nor demographic personal or professional factors were found to be significantly associated with reduced execution time when GPS was used. US associated with GPS systems may improve safety and decrease execution time by reducing inter-individual variability between professionals for needle-handling procedures. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  6. Elevated Outcome-Anticipation and Outcome-Evaluation ERPs Associated with a Greater Preference for Larger-But-Delayed Rewards

    PubMed Central

    Pornpattananangkul, Narun; Nadig, Ajay; Heidinger, Storm; Walden, Keegan; Nusslock, Robin

    2017-01-01

    Although waiting for a reward reduces or discounts its value, some people have a stronger tendency to wait for larger rewards and forgo smaller-but-immediate rewards. This ability to delay gratification is captured by individual differences in so-called inter-temporal choices in which individuals are asked to choose between larger-but-delayed versus smaller-but-immediate rewards. The current study used event-related potentials (ERPs) to examine whether enhancement in two neuro-cognitive processes, outcome-anticipation and outcome-evaluation, modulate individual variability in inter-temporal responses. After completing a behavioral inter-temporal choice task, 34 participants performed an ERP gambling task. From this ERP task, we separately examined individual differences in outcome-anticipation (Stimulus-Preceding Negativity, SPN), early outcome-evaluation (Feedback-Related Negativity; FRN) and late outcome-evaluation (P3). We observed that both elevated outcome-anticipation (SPN) and late outcome-evaluation (P3) neural processes predicted a stronger preference toward larger-but-delayed rewards. No relationship was observed between inter-temporal responses and early outcome-evaluation (FRN), indicating that the relationship between outcome-evaluation and inter-temporal responses was specific to the late outcome-evaluation processing stream. Moreover, multiple regression analyses indicated that the SPN and P3 independently modulate individual differences in inter-temporal responses, suggesting separate mechanisms underlie the relationship between these two neuro-cognitive processes and inter-temporal responses. Accordingly, we identify two potential neural-cognitive modulators of individual variability in inter-temporal responses. We discuss the mechanisms underlying these modulators in terms of anticipation-related processing (SPN) and a saliency-bias toward gain (compared to loss) outcomes (P3). PMID:28224457

  7. Language-independent talker-specificity in first-language and second-language speech production by bilingual talkers: L1 speaking rate predicts L2 speaking rate

    PubMed Central

    Bradlow, Ann R.; Kim, Midam; Blasingame, Michael

    2017-01-01

    Second-language (L2) speech is consistently slower than first-language (L1) speech, and L1 speaking rate varies within- and across-talkers depending on many individual, situational, linguistic, and sociolinguistic factors. It is asked whether speaking rate is also determined by a language-independent talker-specific trait such that, across a group of bilinguals, L1 speaking rate significantly predicts L2 speaking rate. Two measurements of speaking rate were automatically extracted from recordings of read and spontaneous speech by English monolinguals (n = 27) and bilinguals from ten L1 backgrounds (n = 86): speech rate (syllables/second), and articulation rate (syllables/second excluding silent pauses). Replicating prior work, L2 speaking rates were significantly slower than L1 speaking rates both across-groups (monolinguals' L1 English vs bilinguals' L2 English), and across L1 and L2 within bilinguals. Critically, within the bilingual group, L1 speaking rate significantly predicted L2 speaking rate, suggesting that a significant portion of inter-talker variation in L2 speech is derived from inter-talker variation in L1 speech, and that individual variability in L2 spoken language production may be best understood within the context of individual variability in L1 spoken language production. PMID:28253679

  8. Individual diet variation in a marine fish assemblage: Optimal Foraging Theory, Niche Variation Hypothesis and functional identity

    NASA Astrophysics Data System (ADS)

    Cachera, M.; Ernande, B.; Villanueva, M. C.; Lefebvre, S.

    2017-02-01

    Individual diet variation (i.e. diet variation among individuals) impacts intra- and inter-specific interactions. Investigating its sources and relationship with species trophic niche organization is important for understanding community structure and dynamics. Individual diet variation may increase with intra-specific phenotypic (or "individual state") variation and habitat variability, according to Optimal Foraging Theory (OFT), and with species trophic niche width, according to the Niche Variation Hypothesis (NVH). OFT proposes "proximate sources" of individual diet variation such as variations in habitat or size whereas NVH relies on "ultimate sources" related to the competitive balance between intra- and inter-specific competitions. The latter implies as a corollary that species trophic niche overlap, taken as inter-specific competition measure, decreases as species niche width and individual niche variation increase. We tested the complementary predictions of OFT and NVH in a marine fish assemblage using stomach content data and associated trophic niche metrics. The NVH predictions were tested between species of the assemblage and decomposed into a between- and a within-functional group component to assess the potential influence of species' ecological function. For most species, individual diet variation and niche overlap were consistently larger than expected. Individual diet variation increased with intra-specific variability in individual state and habitat, as expected from OFT. It also increased with species niche width but in compliance with the null expectation, thus not supporting the NVH. In contrast, species niche overlap increased significantly less than null expectation with both species niche width and individual diet variation, supporting NVH corollary. The between- and within-functional group components of the NVH relationships were consistent with those between species at the assemblage level. Changing the number of prey categories used to describe diet (from 16 to 41) did not change the results qualitatively. These results suggest that, besides proximate sources, intra-specific competition favors higher individual diet variation than expected while inter-specific competition limits the increase of individual diet variation and of species niche overlap with species niche expansion. This reveals partial trophic resource partitioning between species. Various niche metrics used in combination allow inferring competition effects on trophic niches' organization within communities.

  9. Assessment of metabolic phenotypic variability in children’s urine using 1H NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Maitre, Léa; Lau, Chung-Ho E.; Vizcaino, Esther; Robinson, Oliver; Casas, Maribel; Siskos, Alexandros P.; Want, Elizabeth J.; Athersuch, Toby; Slama, Remy; Vrijheid, Martine; Keun, Hector C.; Coen, Muireann

    2017-04-01

    The application of metabolic phenotyping in clinical and epidemiological studies is limited by a poor understanding of inter-individual, intra-individual and temporal variability in metabolic phenotypes. Using 1H NMR spectroscopy we characterised short-term variability in urinary metabolites measured from 20 children aged 8-9 years old. Daily spot morning, night-time and pooled (50:50 morning and night-time) urine samples across six days (18 samples per child) were analysed, and 44 metabolites quantified. Intraclass correlation coefficients (ICC) and mixed effect models were applied to assess the reproducibility and biological variance of metabolic phenotypes. Excellent analytical reproducibility and precision was demonstrated for the 1H NMR spectroscopic platform (median CV 7.2%). Pooled samples captured the best inter-individual variability with an ICC of 0.40 (median). Trimethylamine, N-acetyl neuraminic acid, 3-hydroxyisobutyrate, 3-hydroxybutyrate/3-aminoisobutyrate, tyrosine, valine and 3-hydroxyisovalerate exhibited the highest stability with over 50% of variance specific to the child. The pooled sample was shown to capture the most inter-individual variance in the metabolic phenotype, which is of importance for molecular epidemiology study design. A substantial proportion of the variation in the urinary metabolome of children is specific to the individual, underlining the potential of such data to inform clinical and exposome studies conducted early in life.

  10. Intra-individual variability in tinnitus patients : current thoughts and perspectives.

    PubMed

    Dauman, N; Erlandsson, S; Lundlin, L; Dauman, R

    2015-04-01

    Most tinnitus studies have attempted to compare groups of individuals, thus revealing inter-individuals differences, i.e., variations between compared subjects. For methodological reasons, inter-individual studies cannot take into account the variability of tinnitus experience, which has been known for decades to be relevant in daily practice with tinnitus patients. The concept of intra-individual variability has been promoted in the research literature, in order to shed light on this aspect of individual perception. In previous studies, unrelated to hearing, the concept of intra-individual variability implied inclusion of the environment (i.e., physical and social interactions) as a factor of individual performance. In tinnitus research, we believe that the concept of variability (within a person) could find a place beside the concept of variation (between groups of subjects). In this paper, four perspectives of tinnitus experiences from the clinical and research fields are described: (1) ENT consultation; (2) short-term group psychotherapy; (3) psychodynamic psychotherapy; and (4) clinical psychological research. Intra-individual variability stresses the importance of defining tinnitus in a dynamic way, contrary to the current definition of tinnitus as the perception of sound(s). In clinical practice, it is useful to embrace the perspective of the perceiver of tinnitus, and to include social and cultural circumstances as well as audiological/physical changes.

  11. Between-session intra-individual variability in sustained, selective, and integrational non-linguistic attention in aphasia.

    PubMed

    Villard, Sarah; Kiran, Swathi

    2015-01-01

    A number of studies have identified impairments in one or more types/aspects of attention processing in patients with aphasia (PWA) relative to healthy controls; person-to-person variability in performance on attention tasks within the PWA group has also been noted. Studies using non-linguistic stimuli have found evidence that attention is impaired in this population even in the absence of language processing demands. An underlying impairment in non-linguistic, or domain-general, attention processing could have implications for the ability of PWA to attend during therapy sessions, which in turn could impact long-term treatment outcomes. With this in mind, this study aimed to systematically examine the effect of task complexity on reaction time (RT) during a non-linguistic attention task, in both PWA and controls. Additional goals were to assess the effect of task complexity on between-session intra-individual variability (BS-IIV) in RT and to examine inter-individual differences in BS-IIV. Eighteen PWA and five age-matched neurologically healthy controls each completed a novel computerized non-linguistic attention task measuring five types of attention on each of four different non-consecutive days. A significant effect of task complexity on both RT and BS-IIV in RT was found for the PWA group, whereas the control group showed a significant effect of task complexity on RT but not on BS-IIV in RT. Finally, in addition to these group-level findings, it was noted that different patients exhibited different patterns of BS-IIV, indicating the existence of inter-individual variability in BS-IIV within the PWA group. Results may have implications for session-to-session fluctuations in attention during language testing and therapy for PWA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. How Plantar Exteroceptive Efficiency Modulates Postural and Oculomotor Control: Inter-Individual Variability.

    PubMed

    Foisy, Arnaud; Kapoula, Zoï

    2016-01-01

    In a previous experiment, we showed that among young and healthy subjects, thin plantar inserts improve postural control and modify vergence amplitudes. In this experiment, however, significant inter-individual variability was observed. We hypothesize that its origin could be attributed to a different reliance upon feet cutaneous afferents. In order to test this hypothesis, we re-analyzed the data relative to 31 young (age 25.7 ± 3.8) and healthy subjects who participated in the first experiment after having classified them into two groups depending on their Plantar Quotient (PQ = Surface area of CoPfoam/Surface area of CoPfirm ground × 100). Foam decreases the information arising from the feet, normally resulting in a PQ > 100. Hence, the PQ provides information on the weight of plantar cutaneous afferents used in postural control. Twelve people were Plantar-Independent Subjects, as indicated by a PQ < 100. These individuals did not behave like the Normal Plantar Quotient Subjects: they were almost insensitive to the plantar stimulations in terms of postural control and totally insensitive in terms of oculomotor control. We conclude that the inter-individual variability observed in our first experiment is explained by the subjects' degree of plantar reliance. We propose that plantar independence is a dysfunctional situation revealing inefficiency in plantar cutaneous afferents. The latter could be due to a latent somatosensory dysfunction generating a noise which prevents the CNS from correctly processing and using feet somatosensory afferents both for balance and vergence control: Plantar Irritating Stimulus. Considering the non-noxious nature and prevalence of this phenomenon, these results can be of great interest to researchers and clinicians who attempt to trigger postural or oculomotor responses through mechanical stimulation of the foot sole.

  13. Temporal dynamics of circadian phase shifting response to consecutive night shifts in healthcare workers: role of light-dark exposure.

    PubMed

    Stone, Julia E; Sletten, Tracey L; Magee, Michelle; Ganesan, Saranea; Mulhall, Megan D; Collins, Allison; Howard, Mark; Lockley, Steven W; Rajaratnam, Shantha M W

    2018-06-01

    Shift work is highly prevalent and is associated with significant adverse health impacts. There is substantial inter-individual variability in the way the circadian clock responds to changing shift cycles. The mechanisms underlying this variability are not well understood. We tested the hypothesis that light-dark exposure is a significant contributor to this variability; when combined with diurnal preference, the relative timing of light exposure accounted for 71% of individual variability in circadian phase response to night shift work. These results will drive development of personalised approaches to manage circadian disruption among shift workers and other vulnerable populations to potentially reduce the increased risk of disease in these populations. Night shift workers show highly variable rates of circadian adaptation. This study examined the relationship between light exposure patterns and the magnitude of circadian phase resetting in response to night shift work. In 21 participants (nursing and medical staff in an intensive care unit) circadian phase was measured using 6-sulphatoxymelatonin at baseline (day/evening shifts or days off) and after 3-4 consecutive night shifts. Daily light exposure was examined relative to individual circadian phase to quantify light intensity in the phase delay and phase advance portions of the light phase response curve (PRC). There was substantial inter-individual variability in the direction and magnitude of phase shift after three or four consecutive night shifts (mean phase delay -1:08 ± 1:31 h; range -3:43 h delay to +3:07 h phase advance). The relative difference in the distribution of light relative to the PRC combined with diurnal preference accounted for 71% of the variability in phase shift. Regression analysis incorporating these factors estimated phase shift to within ±60 min in 85% of participants. No participants met criteria for partial adaptation to night work after three or four consecutive night shifts. Our findings provide evidence that the phase resetting that does occur is based on individual light exposure patterns relative to an individual's baseline circadian phase. Thus, a 'one size fits all' approach to promoting adaptation to shift work using light therapy, implemented without knowledge of circadian phase, may not be efficacious for all individuals. © 2018 Monash University. The Journal of Physiology © 2018 The Physiological Society.

  14. Nonsense-mediated mRNA decay: inter-individual variability and human disease

    PubMed Central

    Nguyen, Lam Son; Wilkinson, Miles; Gecz, Jozef

    2013-01-01

    Nonsense-Mediated mRNA Decay (NMD) is a regulatory pathway that functions to degrade transcripts containing premature termination codons (PTCs) and to maintain normal transcriptome homeostasis. Nonsense and frameshift mutations that generate PTCs cause approximately one-third of all known human genetic diseases and thus NMD has a potentially important role in human disease. In genetic disorders in which the affected genes carry PTC-generating mutations, NMD acts as a double-edge sword. While it can benefit the patient by degrading PTC-containing mRNAs that encode detrimental, dominant-negative truncated proteins, it can also make the disease worse when a PTC-containing mRNA is degraded that encodes a mutant but still functional protein. There is evidence that the magnitude of NMD varies between individuals, which, in turn, has been shown to correlate with both clinical presentations and the patients’ responses to drugs that promote read-through of PTCs. In this review, we examine the evidence supporting the existence of inter-individual variability in NMD efficiency and discuss the genetic factors that underlie this variability. We propose that inter-individual variability in NMD efficiency is a common phenomenon in human populations and that an individual’s NMD efficiency should be taken into consideration when testing, developing, and making therapeutic decisions for diseases caused by genes harboring PTCs. PMID:24239855

  15. To Each Their Own: Molecular Mechanisms of Inter-Individual Variability in Toxic Exposure Effects

    EPA Science Inventory

    Traditional approaches to identifying susceptible populations have relied on factors such as age, genotype, and disease status to explain variability in exposure outcomes; however, these are neither sufficient to faithfully identify differentially responsive individuals nor are t...

  16. Engagement with the auditory processing system during targeted auditory cognitive training mediates changes in cognitive outcomes in individuals with schizophrenia

    PubMed Central

    Biagianti, Bruno; Fisher, Melissa; Neilands, Torsten B.; Loewy, Rachel; Vinogradov, Sophia

    2016-01-01

    BACKGROUND Individuals with schizophrenia who engage in targeted cognitive training (TCT) of the auditory system show generalized cognitive improvements. The high degree of variability in cognitive gains maybe due to individual differences in the level of engagement of the underlying neural system target. METHODS 131 individuals with schizophrenia underwent 40 hours of TCT. We identified target engagement of auditory system processing efficiency by modeling subject-specific trajectories of auditory processing speed (APS) over time. Lowess analysis, mixed models repeated measures analysis, and latent growth curve modeling were used to examine whether APS trajectories were moderated by age and illness duration, and mediated improvements in cognitive outcome measures. RESULTS We observed signifcant improvements in APS from baseline to 20 hours of training (initial change), followed by a flat APS trajectory (plateau) at subsequent time-points. Participants showed inter-individual variability in the steepness of the initial APS change and in the APS plateau achieved and sustained between 20–40 hours. We found that participants who achieved the fastest APS plateau, showed the greatest transfer effects to untrained cognitive domains. CONCLUSIONS There is a significant association between an individual's ability to generate and sustain auditory processing efficiency and their degree of cognitive improvement after TCT, independent of baseline neurocognition. APS plateau may therefore represent a behavioral measure of target engagement mediating treatment response. Future studies should examine the optimal plateau of auditory processing efficiency required to induce significant cognitive improvements, in the context of inter-individual differences in neural plasticity and sensory system efficiency that characterize schizophrenia. PMID:27617637

  17. High inter-specimen variability of baseline data for the tibio-talar contact area.

    PubMed

    Matricali, Giovanni A; Bartels, Ward; Labey, Luc; Dereymaeker, Greta Ph E; Luyten, Frank P; Vander Sloten, Jos

    2009-01-01

    The tibio-talar contact area has been widely investigated to monitor biomechanical changes due to articular incongruities or an altered loading. This study aims to investigate for the first time in a systematic way the extent of the inter-specimen variability of the tibio-talar contact area, and its repercussions when analyzing data concerning this parameter. Ten specimens were loaded to record the tibio-talar contact characteristics by use of pressure sensitive film. The size of the talar dome area, the size of the (normalized) tibio-talar contact area, the position of the tibio-talar contact area, and the shape of the latter were determined and analyzed. Inter-specimen variability was expressed as the coefficient of variation and was calculated for the datasets of previous studies as well. The size of the tibio-talar contact area showed a very high inter-specimen variability, as is the case in previous studies. This high variability persisted when a normalized tibio-talar contact area was calculated. The shape of the tibio-talar contact area showed some basic characteristics, but a high variation in details could be observed. Every specimen can be considered to have its own "ankle print". By this variability, articular incongruities are expected to have a different effect on local biomechanical characteristics in every single individual. Therefore, every single case has to be evaluated and reported for significant changes. In case of modeling, this also underscores the need to use subject specific models fed by sets of parameters derived from a series of single specimens.

  18. Analytical and biological variability in biomarker measurement in the Hispanic Community Health Study/Study of Latinos.

    PubMed

    Thyagarajan, Bharat; Howard, Annie Green; Durazo-Arvizu, Ramon; Eckfeldt, John H; Gellman, Marc D; Kim, Ryung S; Liu, Kiang; Mendez, Armando J; Penedo, Frank J; Talavera, Gregory A; Youngblood, Marston E; Zhao, Lihui; Sotres-Alvarez, Daniela

    2016-12-01

    Biomarker variability, which includes within-individual variability (CV I ), between-individual variability (CV G ) and methodological variability (CV P + A ) is an important determinant of our ability to detect biomarker-disease associations. Estimates of CV I and CV G may be population specific and little data exists on biomarker variability in diverse Hispanic populations. Hence, we evaluated all 3 components of biomarker variability in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) using repeat blood collections (n=58) and duplicate blood measurements (n=761-929 depending on the biomarker). We estimated the index of individuality (II) ((CV I +CV P + A )/CV G ) for 41 analytes and evaluated differences in the II across sexes and age groups. Biomarkers such as fasting glucose, triglycerides and ferritin had substantially higher inter-individual variability and lower II in HCHS/SOL as compared to the published literature. We also found significant sex-specific differences in the II for neutrophil count, platelet count, hemoglobin, % eosinophils and fasting glucose. The II for fasting insulin, post oral glucose tolerance test glucose and cystatin C was significantly higher among the 18-44y age group as compared to the 45+y age group. The implications of these findings for determining biomarker-disease associations in Hispanic populations need to be evaluated in future studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Clinical Pharmacokinetics and Pharmacodynamics of Clopidogrel

    PubMed Central

    Jiang, Xi-Ling; Samant, Snehal; Lesko, Lawrence J.; Schmidt, Stephan

    2017-01-01

    Acute coronary syndromes (ACS) remain life-threatening disorders that are associated with high morbidity and mortality. Dual-antiplatelet therapy with aspirin and clopidogrel has shown to reduce cardiovascular events in patients with ACS. However, there is substantial inter-individual variability in response to clopidogrel treatment in addition to prolonged recovery of platelet reactivity as a result of irreversible binding to P2Y12 receptors. This high inter-individual variability in treatment response has primarily been associated with genetic polymorphisms in the genes encoding for cytochrome (CYP) 2C19 that affect clopidogrel’s pharmacokinetics. While FDA has issued a boxed warning for CYP2C19 poor metabolizers due to a potentially reduced efficacy in these patients, results from multivariate analyses suggest that additional factors, including age, sex, obesity, concurrent diseases and drug-drug interactions, may all contribute to the overall between-subject variability in treatment response. However, the extent to which each of these factors contributes to the overall variability and how they are interrelated is currently unclear. The objective of this review article is to provide a comprehensive update on the different factors that influence clopidogrel’s pharmacokinetics and pharmacodynamics and how they mechanistically contribute to inter-individual differences in response to clopidogrel treatment. PMID:25559342

  20. Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes.

    PubMed

    Mena, Pedro; Ludwig, Iziar A; Tomatis, Virginia B; Acharjee, Animesh; Calani, Luca; Rosi, Alice; Brighenti, Furio; Ray, Sumantra; Griffin, Julian L; Bluck, Les J; Del Rio, Daniele

    2018-04-03

    There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated. Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites. (Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids. The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet.

  1. Rethinking "normal": The role of stochasticity in the phenology of a synchronously breeding seabird.

    PubMed

    Youngflesh, Casey; Jenouvrier, Stephanie; Hinke, Jefferson T; DuBois, Lauren; St Leger, Judy; Trivelpiece, Wayne Z; Trivelpiece, Susan G; Lynch, Heather J

    2018-05-01

    Phenological changes have been observed in a variety of systems over the past century. There is concern that, as a consequence, ecological interactions are becoming increasingly mismatched in time, with negative consequences for ecological function. Significant spatial heterogeneity (inter-site) and temporal variability (inter-annual) can make it difficult to separate intrinsic, extrinsic and stochastic drivers of phenological variability. The goal of this study was to understand the timing and variability in breeding phenology of Adélie penguins under fixed environmental conditions and to use those data to identify a "null model" appropriate for disentangling the sources of variation in wild populations. Data on clutch initiation were collected from both wild and captive populations of Adélie penguins. Clutch initiation in the captive population was modelled as a function of year, individual and age to better understand phenological patterns observed in the wild population. Captive populations displayed as much inter-annual variability in breeding phenology as wild populations, suggesting that variability in breeding phenology is the norm and thus may be an unreliable indicator of environmental forcing. The distribution of clutch initiation dates was found to be moderately asymmetric (right skewed) both in the wild and in captivity, consistent with the pattern expected under social facilitation. The role of stochasticity in phenological processes has heretofore been largely ignored. However, these results suggest that inter-annual variability in breeding phenology can arise independent of any environmental or demographic drivers and that synchronous breeding can enhance inherent stochasticity. This complicates efforts to relate phenological variation to environmental variability in the wild. Accordingly, we must be careful to consider random forcing in phenological processes, lest we fit models to data dominated by random noise. This is particularly true for colonial species where breeding synchrony may outweigh each individual's effort to time breeding with optimal environmental conditions. Our study highlights the importance of identifying appropriate null models for studying phenology. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

  2. Comparison of propranolol and metoprolol in the management of hyperthyroidism.

    PubMed

    Murchison, L E; How, J; Bewsher, P D

    1979-12-01

    1 Propranolol and metoprolol were both effective in controlling the symptoms and signs of hyperthyroidism. 2 Propranolol caused a highly significant increase in serum reverse T3 concentrations with lesser changes in other serum thyroid hormone levels, whereas metoprolol did not have this effect. 3 Steady-state plasma propranolol and metoprolol levels showed marked inter-individual variation. Metoprolol concentrations showed relatively little intra-individual variability, and could be related to the clinical efficacy of the drug, whereas no such relationship was demonstrated for propranolol.

  3. Molecular Targets in Advanced Therapeutics of Cancers: The Role of Pharmacogenetics.

    PubMed

    Abubakar, Murtala B; Gan, Siew Hua

    2016-01-01

    The advent of advanced molecular targeted therapy has resulted in improved prognoses for patients with advanced malignancies. However, despite the significant success and specificity of this advocated targeted therapy, significant on- and off-target adverse effects and inter-individual variability in treatment responses have been reported. The interpatient variability in drug response has been suggested to be partly due to variations in patient genomes. Therefore, the identification of genetic biomarkers by conducting pharmacogenetics studies can help predict patient responses to targeted therapy and may serve as a basis for individualized treatment. In this review, both clinically established and potential molecular targets are highlighted. Overall, current literature suggests that individualization of targeted therapy is promising; however, integrating the clinical benefits of identified biomarkers into clinical practice for personalized medicine remains a major challenge, and further studies to validate these markers and identify novel therapeutic approaches are needed. © 2016 S. Karger AG, Basel.

  4. Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase

    PubMed Central

    Sletten, Tracey L.; Segal, Ahuva Y.; Flynn-Evans, Erin E.; Lockley, Steven W.; Rajaratnam, Shantha M. W.

    2015-01-01

    Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01), greater sleepiness (r = 0.510, p < 0.0001), and more slow eye movements (r = 0.375, p = 0.022) were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual’s circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation. PMID:26043207

  5. Intra-tumoral heterogeneity of gemcitabine delivery and mass transport in human pancreatic cancer

    NASA Astrophysics Data System (ADS)

    Koay, Eugene J.; Baio, Flavio E.; Ondari, Alexander; Truty, Mark J.; Cristini, Vittorio; Thomas, Ryan M.; Chen, Rong; Chatterjee, Deyali; Kang, Ya'an; Zhang, Joy; Court, Laurence; Bhosale, Priya R.; Tamm, Eric P.; Qayyum, Aliya; Crane, Christopher H.; Javle, Milind; Katz, Matthew H.; Gottumukkala, Vijaya N.; Rozner, Marc A.; Shen, Haifa; Lee, Jeffrey E.; Wang, Huamin; Chen, Yuling; Plunkett, William; Abbruzzese, James L.; Wolff, Robert A.; Maitra, Anirban; Ferrari, Mauro; Varadhachary, Gauri R.; Fleming, Jason B.

    2014-12-01

    There is substantial heterogeneity in the clinical behavior of pancreatic cancer and in its response to therapy. Some of this variation may be due to differences in delivery of cytotoxic therapies between patients and within individual tumors. Indeed, in 12 patients with resectable pancreatic cancer, we previously demonstrated wide inter-patient variability in the delivery of gemcitabine as well as in the mass transport properties of tumors as measured by computed tomography (CT) scans. However, the variability of drug delivery and transport properties within pancreatic tumors is currently unknown. Here, we analyzed regional measurements of gemcitabine DNA incorporation in the tumors of the same 12 patients to understand the degree of intra-tumoral heterogeneity of drug delivery. We also developed a volumetric segmentation approach to measure mass transport properties from the CT scans of these patients and tested inter-observer agreement with this new methodology. Our results demonstrate significant heterogeneity of gemcitabine delivery within individual pancreatic tumors and across the patient cohort, with gemcitabine DNA incorporation in the inner portion of the tumors ranging from 38 to 74% of the total. Similarly, the CT-derived mass transport properties of the tumors had a high degree of heterogeneity, ranging from minimal difference to almost 200% difference between inner and outer portions of the tumor. Our quantitative method to derive transport properties from CT scans demonstrated less than 5% difference in gemcitabine prediction at the average CT-derived transport value across observers. These data illustrate significant inter-patient and intra-tumoral heterogeneity in the delivery of gemcitabine, and highlight how this variability can be reproducibly accounted for using principles of mass transport. With further validation as a biophysical marker, transport properties of tumors may be useful in patient selection for therapy and prediction of therapeutic outcome.

  6. Inter- and Intra-individual variability following intermittent theta burst stimulation: implications for rehabilitation and recovery.

    PubMed

    Hinder, Mark R; Goss, Emily L; Fujiyama, Hakuei; Canty, Alison J; Garry, Michael I; Rodger, Jennifer; Summers, Jeffery J

    2014-01-01

    The continued refinement of non-invasive brain stimulation (NBS) techniques is indicative of promising clinical and rehabilitative interventions that are able to modulate cortical excitability. Intermittent theta burst stimulation (iTBS) is one such technique that can increase cortical excitability, purportedly via LTP-like mechanisms. While iTBS may have the capacity to promote recovery after neurological injury, and to combat cognitive and motor decline, recent reports observed highly variable effects across individuals, questioning the efficacy of iTBS as a clinical tool. The aim of this study was to examine intra-individual reliability and inter-individual variability in responses to iTBS. Thirty healthy participants completed two experimental sessions of the iTBS protocol 1-3 weeks apart. Motor evoked potentials in response to single pulse TMS were used to assess corticospinal excitability prior to, and up to 36 min following, iTBS. At the group level, iTBS evoked statistically significant increases in motor cortical excitability across both sessions (P < 0.001), with 22 out of 30 participants exhibiting increases in excitability in both sessions. A strong intraclass correlation demonstrated that both the direction, and magnitude of the plastic changes were reliable at the individual level. Overall, our results suggest that iTBS is capable of inducing relatively robust and consistent effects within and between young individuals. As such, the capacity for iTBS to be exploited in clinical and rehabilitative interventions should continue to be explored. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. A review on therapeutic drug monitoring of immunosuppressant drugs.

    PubMed

    Mohammadpour, Niloufar; Elyasi, Sepideh; Vahdati, Naser; Mohammadpour, Amir Hooshang; Shamsara, Jamal

    2011-11-01

    : Immunosuppressants require therapeutic drug monitoring because of their narrow therapeutic index and significant inter-individual variability in blood concentrations. This variability can be because of factors like drug-nutrient interactions, drug-disease interactions, renal-insufficiency, inflammation and infection, gender, age, polymorphism and liver mass. Drug monitoring is widely practiced especially for cyclosporine, tacrolimus, sirolimus and mycophenolic acid. CYCLOSPORINE: Therapeutic monitoring of immunosuppressive therapy with cyclosporine is a critical requirement because of intra- and inter-patient variability of drug absorption, narrow therapeutic window and drug induced nephrotoxicity. MYCOPHENOLIC ACID MPA: Some reasons for therapeutic drug monitoring of MPA during post-transplant period include: relationship between MPA pharmacokinetic parameters and clinical outcomes, Inter-patient pharmacokinetic variability for MPA despite fixed MMF doses, alternations of MPA pharmacokinetics during the first months after transplantation, drug- drug interaction and influence of kidney function on MPA pharmacokinetic. SIROLIMUS: A recent review of the pharmacokinetics of sirolimus suggested a therapeutic range of 5 to 10 μg l(-1) in whole blood. However, the only consensus guidelines published on the therapeutic monitoring of sirolimus concluded that there was not enough information available about the clinical use of the drug to make recommendations. TACROLIMUS: Sudies have shown, in kidney and liver transplant patients, significant associations of low tacrolimus concentrations with rejection and of high concentrations with nephrotoxicity. Although the feasibility of a limited sampling scheme to predict AUC has been demonstrated, as yet, trough, or pre-dose, whole blood concentration monitoring is still the method of choice.

  8. Inter-Individual Variability in Human Response to Low-Dose Ionizing Radiation, Final Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rocke, David

    2016-08-01

    In order to investigate inter-individual variability in response to low-dose ionizing radiation, we are working with three models, 1) in-vivo irradiated human skin, for which we have a realistic model, but with few subjects, all from a previous project, 2) ex-vivo irradiated human skin, for which we also have a realistic model, though with the limitations involved in keeping skin pieces alive in media, and 3) MatTek EpiDermFT skin plugs, which provides a more realistic model than cell lines, which is more controllable than human samples.

  9. Language, motor and cognitive development of extremely preterm children: modeling individual growth trajectories over the first three years of life.

    PubMed

    Sansavini, Alessandra; Pentimonti, Jill; Justice, Laura; Guarini, Annalisa; Savini, Silvia; Alessandroni, Rosina; Faldella, Giacomo

    2014-01-01

    Survival rate of extremely low gestational age (ELGA) newborns has increased over 80% in the last 15 years, but its consequences on the short- and longer-term developmental competencies may be severe. The aim of this study was to describe growth trajectories of linguistic, motor and cognitive skills among ELGA children, compared to full-term (FT) peers, from the first to the third year of life, a crucial period for development. Growth curve analysis was used to examine individual and group differences in terms of initial status at 12 months and rate of growth through the second and the third year of life with five points of assessment. Twenty-eight monolingual Italian children, of whom 17 were ELGA (mean GA 25.7 weeks) and 11 were FT children, were assessed through the BSID-III at 12, 18, 24, 30 and 36 months for language skills and at 12, 24 and 30 months for motor and cognitive skills. ELGA children presented significantly lower scores than FT peers in language, motor and cognitive skills and they did not overcome their disadvantage by 3 years, even if their corrected age was taken into account. Concerning growth curves, in motor development a significant increasing divergence was found showing a Matthew effect with the preterm sample falling further behind the FT sample. In linguistic and cognitive development, instead, a stable gap between the two samples was found. In addition, great inter-individual differences in rate of change were observed for language development in both samples. Our findings highlight the theoretical and clinical relevance of analyzing, through growth curve analyses, the developmental trajectories of ELGA children in language skills taking into account their inter-individual variability also across motor and cognitive domains. After reading this article, the reader will interpret: (a) characteristics and growth trajectories of ELGA children from the first to the third year of life with respect to FT children in language, motor and cognitive development; (b) the method of growth curve analyses to describe group as well as inter-individual trajectories; (c) the rate of inter-individual variability in language as well as motor and cognitive skills, which gives useful indications for early interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability

    EPA Science Inventory

    We incorporate inter-individual variability, including variability across demographic subgroups, into an open-source high-throughput (HT) toxicokinetics (TK) modeling framework for use in a next-generation risk prioritization approach. Risk prioritization involves rapid triage of...

  11. Systematic assessment of duration and intensity of anodal transcranial direct current stimulation on primary motor cortex excitability.

    PubMed

    Tremblay, Sara; Larochelle-Brunet, Félix; Lafleur, Louis-Philippe; El Mouderrib, Sofia; Lepage, Jean-François; Théoret, Hugo

    2016-09-01

    Since the initial demonstration of linear effects of stimulation duration and intensity on the strength of after-effects associated with transcranial direct current stimulation (tDCS), few studies have systematically assessed how varying these parameters modulates corticospinal excitability. Therefore, the objective of this study was to systematically evaluate the effects of anodal tDCS on corticospinal excitability at two stimulation intensities (1 mA, 2 mA) and durations (10 min, 20 min), and determine the value of several variables in predicting response. Two groups of 20 individuals received, in two separate sessions, 1 and 2 mA anodal tDCS (left primary motor cortex (M1)-right supra-orbital montage) for either 10- or 20-min. Transcranial magnetic stimulation was delivered over left M1 and motor evoked potentials (MEPs) of the contralateral hand were recorded prior to tDCS and every 5 min for 20-min post-tDCS. The following predictive variables were evaluated: I-wave recruitment, stimulation intensity, baseline M1 excitability and inter-trial MEP variability. Results show that anodal tDCS failed to significantly modulate corticospinal excitability in all conditions. Furthermore, low response rates were identified across all parameter combinations. No baseline measure was significantly correlated with increases in MEP amplitude. However, a decrease in inter-trial MEP variability was linked to response to anodal tDCS. In conclusion, the present findings are consistent with recent reports showing high levels of inter-subject variability in the neurophysiological response to tDCS, which may partly explain inconsistent group results. Furthermore, the level of variability in the neurophysiological outcome measure, i.e. MEPs, appears to be related to response. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Influence of Pacing by Periodic Auditory Stimuli on Movement Continuation: Comparison with Self-regulated Periodic Movement

    PubMed Central

    Ito, Masanori; Kado, Naoki; Suzuki, Toshiaki; Ando, Hiroshi

    2013-01-01

    [Purpose] The purpose of this study was to investigate the influence of external pacing with periodic auditory stimuli on the control of periodic movement. [Subjects and Methods] Eighteen healthy subjects performed self-paced, synchronization-continuation, and syncopation-continuation tapping. Inter-onset intervals were 1,000, 2,000 and 5,000 ms. The variability of inter-tap intervals was compared between the different pacing conditions and between self-paced tapping and each continuation phase. [Results] There were no significant differences in the mean and standard deviation of the inter-tap interval between pacing conditions. For the 1,000 and 5,000 ms tasks, there were significant differences in the mean inter-tap interval following auditory pacing compared with self-pacing. For the 2,000 ms syncopation condition and 5,000 ms task, there were significant differences from self-pacing in the standard deviation of the inter-tap interval following auditory pacing. [Conclusion] These results suggest that the accuracy of periodic movement with intervals of 1,000 and 5,000 ms can be improved by the use of auditory pacing. However, the consistency of periodic movement is mainly dependent on the inherent skill of the individual; thus, improvement of consistency based on pacing is unlikely. PMID:24259932

  13. AVHRR channel selection for land cover classification

    USGS Publications Warehouse

    Maxwell, S.K.; Hoffer, R.M.; Chapman, P.L.

    2002-01-01

    Mapping land cover of large regions often requires processing of satellite images collected from several time periods at many spectral wavelength channels. However, manipulating and processing large amounts of image data increases the complexity and time, and hence the cost, that it takes to produce a land cover map. Very few studies have evaluated the importance of individual Advanced Very High Resolution Radiometer (AVHRR) channels for discriminating cover types, especially the thermal channels (channels 3, 4 and 5). Studies rarely perform a multi-year analysis to determine the impact of inter-annual variability on the classification results. We evaluated 5 years of AVHRR data using combinations of the original AVHRR spectral channels (1-5) to determine which channels are most important for cover type discrimination, yet stabilize inter-annual variability. Particular attention was placed on the channels in the thermal portion of the spectrum. Fourteen cover types over the entire state of Colorado were evaluated using a supervised classification approach on all two-, three-, four- and five-channel combinations for seven AVHRR biweekly composite datasets covering the entire growing season for each of 5 years. Results show that all three of the major portions of the electromagnetic spectrum represented by the AVHRR sensor are required to discriminate cover types effectively and stabilize inter-annual variability. Of the two-channel combinations, channels 1 (red visible) and 2 (near-infrared) had, by far, the highest average overall accuracy (72.2%), yet the inter-annual classification accuracies were highly variable. Including a thermal channel (channel 4) significantly increased the average overall classification accuracy by 5.5% and stabilized interannual variability. Each of the thermal channels gave similar classification accuracies; however, because of the problems in consistently interpreting channel 3 data, either channel 4 or 5 was found to be a more appropriate choice. Substituting the thermal channel with a single elevation layer resulted in equivalent classification accuracies and inter-annual variability.

  14. Variability of cholesterol accessibility in human red blood cells measured using a bacterial cholesterol-binding toxin

    PubMed Central

    Chakrabarti, Rima S; Ingham, Sally A; Kozlitina, Julia; Gay, Austin; Cohen, Jonathan C; Radhakrishnan, Arun; Hobbs, Helen H

    2017-01-01

    Cholesterol partitions into accessible and sequestered pools in cell membranes. Here, we describe a new assay using fluorescently-tagged anthrolysin O, a cholesterol-binding bacterial toxin, to measure accessible cholesterol in human red blood cells (RBCs). Accessible cholesterol levels were stable within individuals, but varied >10 fold among individuals. Significant variation was observed among ethnic groups (Blacks>Hispanics>Whites). Variation in accessibility of RBC cholesterol was unrelated to the cholesterol content of RBCs or plasma, but was associated with the phospholipid composition of the RBC membranes and with plasma triglyceride levels. Pronase treatment of RBCs only modestly altered cholesterol accessibility. Individuals on hemodialysis, who have an unexplained increase in atherosclerotic risk, had significantly higher RBC cholesterol accessibility. Our data indicate that RBC accessible cholesterol is a stable phenotype with significant inter-individual variability. Factors both intrinsic and extrinsic to the RBC contribute to variation in its accessibility. This assay provides a new tool to assess cholesterol homeostasis among tissues in humans. DOI: http://dx.doi.org/10.7554/eLife.23355.001 PMID:28169829

  15. Cluster analysis and subgrouping to investigate inter-individual variability to non-invasive brain stimulation: a systematic review.

    PubMed

    Pellegrini, Michael; Zoghi, Maryam; Jaberzadeh, Shapour

    2018-01-12

    Cluster analysis and other subgrouping techniques have risen in popularity in recent years in non-invasive brain stimulation research in the attempt to investigate the issue of inter-individual variability - the issue of why some individuals respond, as traditionally expected, to non-invasive brain stimulation protocols and others do not. Cluster analysis and subgrouping techniques have been used to categorise individuals, based on their response patterns, as responder or non-responders. There is, however, a lack of consensus and consistency on the most appropriate technique to use. This systematic review aimed to provide a systematic summary of the cluster analysis and subgrouping techniques used to date and suggest recommendations moving forward. Twenty studies were included that utilised subgrouping techniques, while seven of these additionally utilised cluster analysis techniques. The results of this systematic review appear to indicate that statistical cluster analysis techniques are effective in identifying subgroups of individuals based on response patterns to non-invasive brain stimulation. This systematic review also reports a lack of consensus amongst researchers on the most effective subgrouping technique and the criteria used to determine whether an individual is categorised as a responder or a non-responder. This systematic review provides a step-by-step guide to carrying out statistical cluster analyses and subgrouping techniques to provide a framework for analysis when developing further insights into the contributing factors of inter-individual variability in response to non-invasive brain stimulation.

  16. Cognitive inconsistency in bipolar patients is determined by increased intra-individual variability in initial phase of task performance.

    PubMed

    Krukow, Paweł; Szaniawska, Ola; Harciarek, Michał; Plechawska-Wójcik, Małgorzata; Jonak, Kamil

    2017-03-01

    Bipolar patients show high intra-individual variability during cognitive processing. However, it is not known whether there are a specific fluctuations of variability contributing to the overall high cognitive inconsistency. The objective was to compare dynamic profiles of patients and healthy controls to identify hypothetical differences and their associations with overall variability and processing speed. Changes of reaction times iSD during processing speed test performance over time was measured by dividing the iSD for whole task into four consecutive parts. Motor speed and cognitive effort were controlled. Patients with BD exhibited significantly lower results regarding processing speed and higher intra-individual variability comparing with HC. The profile of intra-individual variability changes over time of performance was significantly different in BD versus HC groups: F(3, 207)=8.60, p<0.0001, η p 2 =0.11. iSD of BD patients in the initial phase of performance was three times higher than in the last. There was no significant differences between four intervals in HC group. Inter-group difference in the initial part of the profiles was significant also after controlling for several cognitive and clinical variables. Applied computer version of Cognitive Speed Test was relatively new and, thus, replication studies are needed. Effect seen in the present study is driven mainly by the BD type I. Patients with BD exhibits problems with setting a stimulus-response association in starting phase of cognitive processing. This deficit may negatively interfere with the other cognitive functions, decreasing level of psychosocial functioning, therefore should be explored in future studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. The inter and intra rater reliability of the Netball Movement Screening Tool.

    PubMed

    Reid, Duncan A; Vanweerd, Rebecca J; Larmer, Peter J; Kingstone, Rachel

    2015-05-01

    To establish the inter- and intra-rater reliability of the Netball Movement Screening Tool, for screening adolescent female netball players. Inter- and intra-rater reliability study. Forty secondary school netball players were recruited to take part in the study. Twenty subjects were screened simultaneously and independently by two raters to ascertain inter-rater agreement. Twenty subjects were scored by rater one on two occasions, separated by a week, to ascertain intra-rater agreement. Inter and intra-rater agreement was assessed utilising the two-way mixed inter class correlation coefficient and weighted kappa statistics. No significant demographic differences were found between the inter and intra-rater groups of subjects. Inter class correlation coefficients' demonstrated excellent inter-rater (two-way mixed inter class correlation coefficients 0.84, standard error of measurement 0.25) and intra-rater (two-way mixed inter class correlation coefficients 0.96, standard error of measurement 0.13) reliability for the overall Netball Movement Screening Tool score and substantial-excellent (two-way mixed inter class correlation coefficients 1.0-0.65) inter-rater and substantial-excellent intra-rater (two-way mixed inter class correlation coefficients 0.96-0.79) reliability for the component scores of the Netball Movement Screening Tool. Kappa statistic showed substantial to poor inter-rater (k=0.75-0.32) and intra-rater (k=0.77-0.27) agreement for individual tests of the NMST. The Netball Movement Screening Tool may be a reliable screening tool for adolescent netball players; however the individual test scores have low reliability. The screening tool can be administered reliably by raters with similar levels of training in the tool but variable clinical experience. On-going research needs to be undertaken to ascertain whether the Netball Movement Screening Tool is a valid tool in ascertaining increased injury risk for netball players. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  18. Variations of Histone Modification Patterns: Contributions of Inter-plant Variability and Technical Factors

    PubMed Central

    Brabencová, Sylva; Ihnatová, Ivana; Potěšil, David; Fojtová, Miloslava; Fajkus, Jiří; Zdráhal, Zbyněk; Lochmanová, Gabriela

    2017-01-01

    Inter-individual variability of conspecific plants is governed by differences in their genetically determined growth and development traits, environmental conditions, and adaptive responses under epigenetic control involving histone post-translational modifications. The apparent variability in histone modifications among plants might be increased by technical variation introduced in sample processing during epigenetic analyses. Thus, to detect true variations in epigenetic histone patterns associated with given factors, the basal variability among samples that is not associated with them must be estimated. To improve knowledge of relative contribution of biological and technical variation, mass spectrometry was used to examine histone modification patterns (acetylation and methylation) among Arabidopsis thaliana plants of ecotypes Columbia 0 (Col-0) and Wassilewskija (Ws) homogenized by two techniques (grinding in a cryomill or with a mortar and pestle). We found little difference in histone modification profiles between the ecotypes. However, in comparison of the biological and technical components of variability, we found consistently higher inter-individual variability in histone mark levels among Ws plants than among Col-0 plants (grown from seeds collected either from single plants or sets of plants). Thus, more replicates of Ws would be needed for rigorous analysis of epigenetic marks. Regarding technical variability, the cryomill introduced detectably more heterogeneity in the data than the mortar and pestle treatment, but mass spectrometric analyses had minor apparent effects. Our study shows that it is essential to consider inter-sample variance and estimate suitable numbers of biological replicates for statistical analysis for each studied organism when investigating changes in epigenetic histone profiles. PMID:29270186

  19. Variations of Histone Modification Patterns: Contributions of Inter-plant Variability and Technical Factors.

    PubMed

    Brabencová, Sylva; Ihnatová, Ivana; Potěšil, David; Fojtová, Miloslava; Fajkus, Jiří; Zdráhal, Zbyněk; Lochmanová, Gabriela

    2017-01-01

    Inter-individual variability of conspecific plants is governed by differences in their genetically determined growth and development traits, environmental conditions, and adaptive responses under epigenetic control involving histone post-translational modifications. The apparent variability in histone modifications among plants might be increased by technical variation introduced in sample processing during epigenetic analyses. Thus, to detect true variations in epigenetic histone patterns associated with given factors, the basal variability among samples that is not associated with them must be estimated. To improve knowledge of relative contribution of biological and technical variation, mass spectrometry was used to examine histone modification patterns (acetylation and methylation) among Arabidopsis thaliana plants of ecotypes Columbia 0 (Col-0) and Wassilewskija (Ws) homogenized by two techniques (grinding in a cryomill or with a mortar and pestle). We found little difference in histone modification profiles between the ecotypes. However, in comparison of the biological and technical components of variability, we found consistently higher inter-individual variability in histone mark levels among Ws plants than among Col-0 plants (grown from seeds collected either from single plants or sets of plants). Thus, more replicates of Ws would be needed for rigorous analysis of epigenetic marks. Regarding technical variability, the cryomill introduced detectably more heterogeneity in the data than the mortar and pestle treatment, but mass spectrometric analyses had minor apparent effects. Our study shows that it is essential to consider inter-sample variance and estimate suitable numbers of biological replicates for statistical analysis for each studied organism when investigating changes in epigenetic histone profiles.

  20. The influence of divided attention on walking turns: Effects on gait control in young adults with and without a history of low back pain.

    PubMed

    Smith, Jo Armour; Gordon, James; Kulig, Kornelia

    2017-10-01

    The cognitive control of gait is altered in individuals with low back pain, but it is unclear if this alteration persists between painful episodes. Locomotor perturbations such as walking turns may provide a sensitive measure of gait adaptation during divided attention in young adults. The purpose of this study was to investigate changes in gait during turns performed with divided attention, and to compare healthy young adults with asymptomatic individuals who have a history of recurrent low back pain (rLBP). Twenty-eight participants performed 90° ipsilateral walking turns at a controlled speed of 1.5m/s. During the divided attention condition they concurrently performed a verbal 2-back task. Step length and width, trunk-pelvis and hip excursion, inter-segmental coordination and stride-to-stride variability were quantified using motion capture. Mixed-model ANOVA were used to examine the effect of divided attention and group, and interaction effects on the selected variables. Step length variability decreased significantly with divided attention in the healthy group but not in the rLBP group (post-hoc p=0.024). Inter-segmental coordination variability was significantly decreased during divided attention (main effect of condition p <0.000). There were small but significant reductions in hip axial and sagittal motion across groups (main effect of condition p=0.044 and p=0.040 respectively), and a trend toward increased frontal motion in the rLBP group only (post-hoc p=0.048). These findings suggest that the ability to switch attentional resources during gait is altered in young adults with a history of rLBP, even between symptomatic episodes. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Comparison of propranolol and metoprolol in the management of hyperthyroidism.

    PubMed Central

    Murchison, L E; How, J; Bewsher, P D

    1979-01-01

    1 Propranolol and metoprolol were both effective in controlling the symptoms and signs of hyperthyroidism. 2 Propranolol caused a highly significant increase in serum reverse T3 concentrations with lesser changes in other serum thyroid hormone levels, whereas metoprolol did not have this effect. 3 Steady-state plasma propranolol and metoprolol levels showed marked inter-individual variation. Metoprolol concentrations showed relatively little intra-individual variability, and could be related to the clinical efficacy of the drug, whereas no such relationship was demonstrated for propranolol. PMID:391258

  2. Addressing the inter-individual variation in response to consumption of plant food bioactives: Towards a better understanding of their role in healthy aging and cardiometabolic risk reduction.

    PubMed

    Manach, Claudine; Milenkovic, Dragan; Van de Wiele, Tom; Rodriguez-Mateos, Ana; de Roos, Baukje; Garcia-Conesa, Maria Teresa; Landberg, Rikard; Gibney, Eileen R; Heinonen, Marina; Tomás-Barberán, Francisco; Morand, Christine

    2017-06-01

    Bioactive compounds in plant-based foods have health properties that contribute to the prevention of age-related chronic diseases, particularly cardiometabolic disorders. Conclusive proof and understanding of these benefits in humans is essential in order to provide effective dietary recommendations but, so far, the evidence obtained from human intervention trials is limited and contradictory. This is partly due to differences between individuals in the absorption, distribution, metabolism and excretion of bioactive compounds, as well as to heterogeneity in their biological response regarding cardiometabolic health outcomes. Identifying the main factors underlying inter-individual differences, as well as developing new and innovative methodologies to account for such variability constitute an overarching goal to ultimately optimize the beneficial health effects of plant food bioactives for each and every one of us. In this respect, this position paper from the COST Action FA1403-POSITIVe examines the main factors likely to affect the individual responses to consumption of plant food bioactives and presents perspectives for assessment and consideration of inter-individual variability. © 2016 The Authors. Molecular Nutrition & Food Research published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Why is seed production so variable among individuals? A ten-year study with oaks reveals the importance of soil environment.

    PubMed

    Pérez-Ramos, Ignacio M; Aponte, Cristina; García, Luis V; Padilla-Díaz, Carmen M; Marañón, Teodoro

    2014-01-01

    Mast-seeding species exhibit not only a large inter-annual variability in seed production but also considerable variability among individuals within the same year. However, very little is known about the causes and consequences for population dynamics of this potentially large between-individual variability. Here, we quantified seed production over ten consecutive years in two Mediterranean oak species - the deciduous Quercus canariensis and the evergreen Q. suber - that coexist in forests of southern Spain. First, we calibrated likelihood models to identify which abiotic and biotic variables best explain the magnitude (hereafter seed productivity) and temporal variation of seed production at the individual level (hereafter CVi), and infer whether reproductive effort results from the available soil resources for the plant or is primarily determined by selectively favoured strategies. Second, we explored the contribution of between-individual variability in seed production as a potential mechanism of satiation for predispersal seed predators. We found that Q. canariensis trees inhabiting moister and more fertile soils were more productive than those growing in more resource-limited sites. Regarding temporal variation, individuals of the two studied oak species inhabiting these resource-rich environments also exhibited larger values of CVi. Interestingly, we detected a satiating effect on granivorous insects at the tree level in Q. suber, which was evident in those years where between-individual variability in acorn production was higher. These findings suggest that individual seed production (both in terms of seed productivity and inter-annual variability) is strongly dependent on soil resource heterogeneity (at least for one of the two studied oak species) with potential repercussions for recruitment and population dynamics. However, other external factors (such as soil heterogeneity in pathogen abundance) or certain inherent characteristics of the tree might be also involved in this process.

  4. Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 1: metals.

    PubMed

    Smolders, Roel; Koch, Holger M; Moos, Rebecca K; Cocker, John; Jones, Kate; Warren, Nick; Levy, Len; Bevan, Ruth; Hays, Sean M; Aylward, Lesa L

    2014-12-01

    The aim of the current HBM-study is to further the understanding of the impact of inter- and intra-individual variability in HBM surveys as it may have implications for the design and interpretation of the study outcomes. As spot samples only provide a snapshot in time of the concentrations of chemicals in an individual, it remains unclear to what extent intra-individual variability plays a role in the overall variability of population-wide HBM surveys. The current paper describes the results of an intensive biomonitoring study, in which all individual urine samples of 8 individuals were collected over a 6-day sampling period (a total of 352 unique samples). By analyzing different metals (As, Cd, Mn, Ni) in each individual sample, inter- and intra-individual variability for these four metals could be determined, and the relationships between exposure, internal dose, and sampling protocol assessed. Although the range of biomarker values for different metals was well within the normal range reported in large-scale population surveys, large intra-individual differences over a 6-day period could also be observed. Typically, measured biomarker values span at least an order of magnitude within an individual, and more if specific exposure episodes could be identified. Fish consumption for example caused a twenty- to thirty-fold increase in urinary As-levels over a period of 2-6h. Intra-class correlation coefficients (ICC) were typically low for uncorrected biomarker values (between 0.104 and 0.460 for the 4 metals), but improved when corrected for creatinine or specific gravity (SG). The results show that even though urine is a preferred matrix for HBM studies, there are certain methodological issues that need to be taken into account in the interpretation of urinary biomarker data, related to the intrinsic variability of the urination process itself, the relationship between exposure events and biomarker quantification, and the timing of sampling. When setting up HBM-projects, this expected relationship between individual exposure episode and urinary biomarker concentration needs to be taken into account. Copyright © 2014. Published by Elsevier Ireland Ltd.

  5. Variability and epistemic uncertainty in water ingestion rates and pharmacokinetic parameters, and impact on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population.

    PubMed

    Avanasi, Raghavendhran; Shin, Hyeong-Moo; Vieira, Veronica M; Bartell, Scott M

    2016-04-01

    We recently utilized a suite of environmental fate and transport models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations, and also assessed the association of those concentrations with preeclampsia for participants in the C8 Health Project (a cross-sectional study of over 69,000 people who were environmentally exposed to PFOA near a major U.S. fluoropolymer production facility located in West Virginia). However, the exposure estimates from this integrated model relied on default values for key independent exposure parameters including water ingestion rates, the serum PFOA half-life, and the volume of distribution for PFOA. The aim of the present study is to assess the impact of inter-individual variability and epistemic uncertainty in these parameters on the exposure estimates and subsequently, the epidemiological association between PFOA exposure and preeclampsia. We used Monte Carlo simulation to propagate inter-individual variability/epistemic uncertainty in the exposure assessment and reanalyzed the epidemiological association. Inter-individual variability in these parameters mildly impacted the serum PFOA concentration predictions (the lowest mean rank correlation between the estimated serum concentrations in our study and the original predicted serum concentrations was 0.95) and there was a negligible impact on the epidemiological association with preeclampsia (no change in the mean adjusted odds ratio (AOR) and the contribution of exposure uncertainty to the total uncertainty including sampling variability was 7%). However, when epistemic uncertainty was added along with the inter-individual variability, serum PFOA concentration predictions and their association with preeclampsia were moderately impacted (the mean AOR of preeclampsia occurrence was reduced from 1.12 to 1.09, and the contribution of exposure uncertainty to the total uncertainty was increased up to 33%). In conclusion, our study shows that the change of the rank exposure among the study participants due to variability and epistemic uncertainty in the independent exposure parameters was large enough to cause a 25% bias towards the null. This suggests that the true AOR of the association between PFOA and preeclampsia in this population might be higher than the originally reported AOR and has more uncertainty than indicated by the originally reported confidence interval. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Individual differences and time-varying features of modular brain architecture.

    PubMed

    Liao, Xuhong; Cao, Miao; Xia, Mingrui; He, Yong

    2017-05-15

    Recent studies have suggested that human brain functional networks are topologically organized into functionally specialized but inter-connected modules to facilitate efficient information processing and highly flexible cognitive function. However, these studies have mainly focused on group-level network modularity analyses using "static" functional connectivity approaches. How these extraordinary modular brain structures vary across individuals and spontaneously reconfigure over time remain largely unknown. Here, we employed multiband resting-state functional MRI data (N=105) from the Human Connectome Project and a graph-based modularity analysis to systematically investigate individual variability and dynamic properties in modular brain networks. We showed that the modular structures of brain networks dramatically vary across individuals, with higher modular variability primarily in the association cortex (e.g., fronto-parietal and attention systems) and lower variability in the primary systems. Moreover, brain regions spontaneously changed their module affiliations on a temporal scale of seconds, which cannot be simply attributable to head motion and sampling error. Interestingly, the spatial pattern of intra-subject dynamic modular variability largely overlapped with that of inter-subject modular variability, both of which were highly reproducible across repeated scanning sessions. Finally, the regions with remarkable individual/temporal modular variability were closely associated with network connectors and the number of cognitive components, suggesting a potential contribution to information integration and flexible cognitive function. Collectively, our findings highlight individual modular variability and the notable dynamic characteristics in large-scale brain networks, which enhance our understanding of the neural substrates underlying individual differences in a variety of cognition and behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. [Inter-and intra-operator variability in the analysis of semen parameters: results from a quality control program].

    PubMed

    Daoud, Salima; Chakroun-Feki, Nozha; Sellami, Afifa; Ammar-Keskes, Leila; Rebai, Tarek

    2016-01-01

    Semen analysis is a key part of male infertility investigation. The necessity of quality management implementation in the andrology laboratory has been recognized in order to ensure the reliability of its results. The aim of this study was to evaluate intra- and inter-individual variability in the assessment of semen parameters in our laboratory through a quality control programme. Four participants from the laboratory with different experience levels have participated in this study. Semen samples of varying quality were assessed for sperm motility, concentration and morphology and the results were used to evaluate inter-participant variability. In addition, replicates of each semen sample were analyzed to determine intra-individual variability for semen parameters analysis. The average values of inter-participant coefficients of variation for sperm motility, concentration and morphology were 12.8%, 19.8% and 48.9% respectively. The mean intra-participant coefficients of variation were, respectively, 6.9%, 12.3% and 42.7% for sperm motility, concentration and morphology. Despite some random errors of under- or overestimation, the overall results remained within the limits of acceptability for all participants. Sperm morphology assessment was particularly influenced by the participant's level of experience. The present data emphasize the need for appropriate training of the laboratory staff and for regular participation in internal quality control programmes in order to improve the reliability of laboratory results.

  8. Performance of Encounternet Tags: Field Tests of Miniaturized Proximity Loggers for Use on Small Birds

    PubMed Central

    Levin, Iris I.; Zonana, David M.; Burt, John M.; Safran, Rebecca J.

    2015-01-01

    Proximity logging is a new tool for understanding social behavior as it allows for accurate quantification of social networks. We report results from field calibration and deployment tests of miniaturized proximity tags (Encounternet), digital transceivers that log encounters between tagged individuals. We examined radio signal behavior in relation to tag attachment (tag, tag on bird, tag on saline-filled balloon) to understand how radio signal strength is affected by the tag mounting technique used for calibration tests. We investigated inter-tag and inter-receiver station variability, and in each calibration test we accounted for the effects of antennae orientation. Additionally, we used data from a live deployment on breeding barn swallows (Hirundo rustica erythrogaster) to analyze the quality of the logs, including reciprocal agreement in dyadic logs. We evaluated the impact (in terms of mass changes) of tag attachment on the birds. We were able to statistically distinguish between RSSI values associated with different close-proximity (<5m) tag-tag distances regardless of antennae orientation. Inter-tag variability was low, but we did find significant inter-receiver station variability. Reciprocal agreement of dyadic logs was high and social networks were constructed from proximity tag logs based on two different RSSI thresholds. There was no evidence of significant mass loss in the time birds were wearing tags. We conclude that proximity loggers are accurate and effective for quantifying social behavior. However, because RSSI and distance cannot be perfectly resolved, data from proximity loggers are most appropriate for comparing networks based on specific RSSI thresholds. The Encounternet system is flexible and customizable, and tags are now light enough for use on small animals (<50g). PMID:26348329

  9. Inter-Population Variability of Endosymbiont Densities in the Asian Citrus Psyllid (Diaphorina citri Kuwayama).

    PubMed

    Chu, Chia-Ching; Gill, Torrence A; Hoffmann, Mark; Pelz-Stelinski, Kirsten S

    2016-05-01

    The Asian citrus psyllid (Diaphorina citri Kuwayama) is an insect pest capable of transmitting Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus greening in North America. D. citri also harbors three endosymbionts, Wolbachia, Candidatus Carsonella ruddii, and Candidatus Profftella armatura, which may influence D. citri physiology and fitness. Although genomic researches on these bacteria have been conducted, much remains unclear regarding their ecology and inter-population variability in D. citri. The present work examined the densities of each endosymbiont in adult D. citri sampled from different populations using quantitative PCR. Under field conditions, the densities of all three endosymbionts positively correlated with each other, and they are associated with D. citri gender and locality. In addition, the infection density of CLas also varied across populations. Although an analysis pooling D. citri from different populations showed that CLas-infected individuals tended to have lower endosymbiont densities compared to uninfected individuals, the difference was not significant when the population was included as a factor in the analysis, suggesting that other population-specific factors may have stronger effects on endosymbiont densities. To determine whether there is a genetic basis to the density differences, endosymbiont densities between aged CLas-negative females of two D. citri populations reared under standardized laboratory conditions were compared. Results suggested that inter-population variability in Wolbachia infection density is associated with the genotypes of the endosymbiont or the host. Findings from this work could facilitate understanding of D. citri-bacterial associations that may benefit the development of approaches for managing citrus greening, such as prevention of CLas transmission.

  10. Reliability of fMRI for Studies of Language in Post-Stroke Aphasia Subjects

    PubMed Central

    Eaton, Kenneth P.; Szaflarski, Jerzy P.; Altaye, Mekibib; Ball, Angel L.; Kissela, Brett M.; Banks, Christi; Holland, Scott K.

    2008-01-01

    Quantifying change in brain activation patterns associated with post-stroke recovery and reorganization of language function over time requires accurate understanding of inter-scan and inter-subject variability. Here we report inter-scan variability measures for fMRI activation patterns associated with verb generation (VG) and semantic decision/tone decision (SDTD) tasks in 4 healthy controls and 4 aphasic left middle cerebral artery (LMCA) stroke subjects. A series of 10 fMRI scans was completed on a 4T Varian scanner for each task for each subject, except for one stroke subject who completed 5 and 6 scans for SDTD and VG, thus yielding 35 and 36 total stroke subject scans for SDTD and VG, respectively. Group composite and intraclass correlation coefficient (ICC) maps were computed across all subjects and trials for each task. The patterns of reliable activation for the VG and SDTD tasks correspond well to those regions typically activated by these tasks in healthy and aphasic subjects. ICCs for activation were consistently high (R0.05 ≈ 0.8) for individual tasks among both control and aphasic subjects. These voxel-wise measures of reliability highlight regions of low inter-scan variability within language circuitry for control and post-recovery stroke subjects. ICCs computed from the combination of the SDTD/VG data were markedly reduced for both control and aphasic subjects as compared with the ICCs for the individual tasks. These quantitative measures of inter-scan variability support the proposed use of these fMRI paradigms for longitudinal mapping of neural reorganization of language processing following left hemispheric insult. PMID:18411061

  11. Inter-relationships between objective and subjective measures of the residential environment among urban African American women

    PubMed Central

    Sealy-Jefferson, Shawnita; Messer, Lynne; Slaughter-Acey, Jaime; Misra, Dawn P.

    2016-01-01

    Background The inter-relationships between objective (census-based) and subjective (resident reported) measures of the residential environment is understudied in African American (AA) populations. Methods Using data from the Life Influences on Fetal Environments Study (2009–2011) (n=1,387) of AA women, we quantified the area-level variation in subjective reports of residential healthy food availability, walkability, safety and disorder that can be accounted for with an objective neighborhood disadvantage index (NDI). Two-level generalized linear models estimated associations between objective and subjective measures of the residential environment, accounting for individual-level covariates. Results In unconditional models, intraclass correlation coefficients for block-group variance in subjective reports ranged from 11% (healthy food availability) to 30% (safety). Models accounting for the NDI (versus both NDI and individual level covariates) accounted for more variance in healthy food availability (23% versus 8%) and social disorder (40% versus 38%). The NDI and individual level variables accounted for 39% and 51% of the area-level variation in walkability and safety. Associations between subjective and objective measures of the residential environment were significant and in the expected direction. Conclusions Future studies on neighborhood effects on health, especially among AAs, should include a wide range of residential environment measures, including subjective, objective and spatial contextual variables. PMID:28160971

  12. Inter-relationships between objective and subjective measures of the residential environment among urban African American women.

    PubMed

    Sealy-Jefferson, Shawnita; Messer, Lynne; Slaughter-Acey, Jaime; Misra, Dawn P

    2017-03-01

    The inter-relationships between objective (census based) and subjective (resident reported) measures of the residential environment is understudied in African American (AA) populations. Using data from the Life Influences on Fetal Environments Study (2009-2011; n = 1387) of AA women, we quantified the area-level variation in subjective reports of residential healthy food availability, walkability, safety, and disorder that can be accounted for with an objective neighborhood disadvantage index (NDI). Two-level generalized linear models estimated associations between objective and subjective measures of the residential environment, accounting for individual-level covariates. In unconditional models, intraclass correlation coefficients for block-group variance in subjective reports ranged from 11% (healthy food availability) to 30% (safety). Models accounting for the NDI (vs. both NDI and individual-level covariates) accounted for more variance in healthy food availability (23% vs. 8%) and social disorder (40% vs. 38%). The NDI and individual-level variables accounted for 39% and 51% of the area-level variation in walkability and safety, respectively. Associations between subjective and objective measures of the residential environment were significant and in the expected direction. Future studies on neighborhood effects on health, especially among AAs, should include a wide range of residential environment measures, including subjective, objective, and spatial contextual variables. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Reversed Priming Effects May Be Driven by Misperception Rather than Subliminal Processing.

    PubMed

    Sand, Anders

    2016-01-01

    A new paradigm for investigating whether a cognitive process is independent of perception was recently suggested. In the paradigm, primes are shown at an intermediate signal strength that leads to trial-to-trial and inter-individual variability in prime perception. Here, I used this paradigm and an objective measure of perception to assess the influence of prime identification responses on Stroop priming. I found that sensory states producing correct and incorrect prime identification responses were also associated with qualitatively different priming effects. Incorrect prime identification responses were associated with reversed priming effects but in contrast to previous studies, I interpret this to result from the (mis-)perception of primes rather than from a subliminal process. Furthermore, the intermediate signal strength also produced inter-individual variability in prime perception that strongly influenced priming effects: only participants who on average perceived the primes were Stroop primed. I discuss how this new paradigm, with a wide range of d' values, is more appropriate when regression analysis on inter-individual identification performance is used to investigate perception-dependent processing. The results of this study, in line with previous results, suggest that drawing conclusions about subliminal processes based on data averaged over individuals may be unwarranted.

  14. Reversed Priming Effects May Be Driven by Misperception Rather than Subliminal Processing

    PubMed Central

    Sand, Anders

    2016-01-01

    A new paradigm for investigating whether a cognitive process is independent of perception was recently suggested. In the paradigm, primes are shown at an intermediate signal strength that leads to trial-to-trial and inter-individual variability in prime perception. Here, I used this paradigm and an objective measure of perception to assess the influence of prime identification responses on Stroop priming. I found that sensory states producing correct and incorrect prime identification responses were also associated with qualitatively different priming effects. Incorrect prime identification responses were associated with reversed priming effects but in contrast to previous studies, I interpret this to result from the (mis-)perception of primes rather than from a subliminal process. Furthermore, the intermediate signal strength also produced inter-individual variability in prime perception that strongly influenced priming effects: only participants who on average perceived the primes were Stroop primed. I discuss how this new paradigm, with a wide range of d′ values, is more appropriate when regression analysis on inter-individual identification performance is used to investigate perception-dependent processing. The results of this study, in line with previous results, suggest that drawing conclusions about subliminal processes based on data averaged over individuals may be unwarranted. PMID:26925016

  15. Bioavailability and pharmacokinetic profile of grape pomace phenolic compounds in humans.

    PubMed

    Castello, Fabio; Costabile, Giuseppina; Bresciani, Letizia; Tassotti, Michele; Naviglio, Daniele; Luongo, Delia; Ciciola, Paola; Vitale, Marilena; Vetrani, Claudia; Galaverna, Gianni; Brighenti, Furio; Giacco, Rosalba; Del Rio, Daniele; Mena, Pedro

    2018-05-15

    Grape pomace, the major byproduct of the wine and juice industry, is a relevant source of bioactive phenolic compounds. However, polyphenol bioavailability in humans is not well understood, and the inter-individual variability in the production of phenolic metabolites has not been comprehensively assessed to date. The pharmacokinetic and excretive profiles of phenolic metabolites after the acute administration of a drink made from red grape pomace was here investigated in ten volunteers. A total of 35 and 28 phenolic metabolites were quantified in urine and plasma, respectively. The main circulating metabolites included phenyl-γ-valerolactones, hydroxybenzoic acids, simple phenols, hydroxyphenylpropionic acids, hydroxycinnamates, and (epi)catechin phase II conjugates. A high inter-individual variability was shown both in urine and plasma samples, and different patterns of circulating metabolites were unravelled by applying unsupervised multivariate analysis. Besides the huge variability in the production of microbial metabolites of colonic origin, an important variability was observed due to phase II conjugates. These results are of interest to further understand the potential health benefits of phenolic metabolites on individual basis. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Inter-individual variability in the patterns of responses for electromyography and mechanomyography during cycle ergometry using an RPE-clamp model.

    PubMed

    Cochrane-Snyman, Kristen C; Housh, Terry J; Smith, Cory M; Hill, Ethan C; Jenkins, Nathaniel D M; Schmidt, Richard J; Johnson, Glen O

    2016-09-01

    To examine inter-individual variability versus composite models for the patterns of responses for electromyography (EMG) and mechanomyography (MMG) versus time relationships during moderate and heavy cycle ergometry using a rating of perceived exertion (RPE) clamp model. EMG amplitude (amplitude root-mean-square, RMS), EMG mean power frequency (MPF), MMG-RMS, and MMG-MPF were collected during two, 60-min rides at a moderate (RPE at the gas exchange threshold; RPEGET) and heavy (RPE at 15 % above the GET; RPEGET+15 %) intensity when RPE was held constant (clamped). Composite (mean) and individual responses for EMG and MMG parameters were compared during each 60-min ride. There was great inter-individual variability for each EMG and MMG parameters at RPEGET and RPEGET+15 %. Composite models showed decreases in EMG-RMS (r (2) = -0.92 and R (2) = 0.96), increases in EMG-MPF (R (2) = 0.90), increases in MMG-RMS (r (2) = 0.81 and 0.55), and either no change or a decrease (r (2) = 0.34) in MMG-MPF at RPEGET and RPEGET+15 %, respectively. The results of the present study indicated that there were differences between composite and individual patterns of responses for EMG and MMG parameters during moderate and heavy cycle ergometry at a constant RPE. Thus, composite models did not represent the unique muscle activation strategies exhibited by individual responses when cycling in the moderate and heavy intensity domains when using an RPE-clamp model.

  17. Genetic basis of inter-individual variability in the effects of exercise on the alleviation of lifestyle-related diseases

    PubMed Central

    Mori, Masayuki; Higuchi, Keiichi; Sakurai, Akihiro; Tabara, Yasuharu; Miki, Tetsuro; Nose, Hiroshi

    2009-01-01

    Habitual exercise training, including a high-intensity interval walking programme, improves cardiorespiratory fitness and alleviates lifestyle-related diseases, such as obesity, hypertension and dyslipidaemia. However, the extent of improvement has been shown to differ substantially among individuals for various exercise regimens. A body of literature has demonstrated that gene polymorphisms could account for the inter-individual variability in the improvement of risk factors for lifestyle-related diseases following exercise training. However, the fractions of the variability explained by the polymorphisms are small (∼5%). Also, it is likely that the effects of gene polymorphisms differ with exercise regimens and subject characteristics. These observations suggest the necessity for further studies to exhaustively identify such gene polymorphisms. More importantly, the physiological and molecular genetic mechanisms by which gene polymorphisms interact with exercise to influence the improvements of risk factors for lifestyle-related diseases differentially remain to be clarified. A better understanding of these issues should lead to more effective integration of exercise to optimize the treatment and management of individuals with lifestyle-related diseases. PMID:19736300

  18. Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

    PubMed Central

    Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

    2013-01-01

    Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

  19. The contribution of wine-derived monoterpene glycosides to retronasal odour during tasting.

    PubMed

    Parker, Mango; Black, Cory A; Barker, Alice; Pearson, Wes; Hayasaka, Yoji; Francis, I Leigh

    2017-10-01

    This study investigated the sensory significance of monoterpene glycosides during tasting, by retronasal perception of odorant aglycones released in-mouth. Monoterpene glycosides were isolated from Gewürztraminer and Riesling juices and wines, chemically characterised and studied using sensory time-intensity methodology, together with a synthesised monoterpene glucoside. When assessed in model wine at five times wine-like concentration, Gewürztraminer glycosides and geranyl glucoside gave significant fruity flavour, although at wine-like concentrations, or in the presence of wine volatiles, the effect was not significant. Gewürztraminer glycosides, geranyl glucoside and guaiacyl glucoside were investigated using a sensory panel (n=39), revealing large inter-individual variability, with 77% of panellists responding to at least one glycoside. The study showed for the first time that grape-derived glycosides can contribute perceptible fruity flavour, providing a means of enhancing flavour in wines, and confirms the results of previous studies that the effect is highly variable across individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients.

    PubMed

    Hor, S Y; Lee, S C; Wong, C I; Lim, Y W; Lim, R C; Wang, L Z; Fan, L; Guo, J Y; Lee, H S; Goh, B C; Tan, T

    2008-04-01

    Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.

  1. Morphometric variability of Arctodiaptomus salinus (Copepoda) in the Mediterranean-Black Sea region.

    PubMed

    Anufriieva, Elena V; Shadrin, Nickolai V

    2015-11-18

    Inter-species variability in morphological traits creates a need to know the range of variability of characteristics in the species for taxonomic and ecological tasks. Copepoda Arctodiaptomus salinus, which inhabits water bodies across Eurasia and North Africa, plays a dominant role in plankton of different water bodies-from fresh to hypersaline. This work assesses the intra- and inter-population morphometric variability of A. salinus in the Mediterranean-Black Sea region and discusses some observed regularities. The variability of linear body parameters and proportions was studied. The impacts of salinity, temperature, and population density on morphological characteristics and their variability can manifest themselves in different ways at the intra- and inter-population levels. A significant effect of salinity, pH and temperature on the body proportions was not found. Their intra-population variability is dependent on temperature and salinity. Sexual dimorphism of A. salinus manifests in different linear parameters, proportions, and their variability. There were no effects of temperature, pH and salinity on the female/male parameter ratio. There were significant differences in the body proportions of males and females in different populations. The influence of temperature, salinity, and population density can be attributed to 80%-90% of intra-population variability of A. salinus. However, these factors can explain less than 40% of inter-population differences. Significant differences in the body proportions of males and females from different populations may suggest that some local populations of A. salinus in the Mediterranean-Black Sea region are in the initial stages of differentiation.

  2. Interpersonal Coordination and Individual Organization Combined with Shared Phenomenological Experience in Rowing Performance: Two Case Studies

    PubMed Central

    Seifert, Ludovic; Lardy, Julien; Bourbousson, Jérôme; Adé, David; Nordez, Antoine; Thouvarecq, Régis; Saury, Jacques

    2017-01-01

    The principal aim of this study was to examine the impact of variability in interpersonal coordination and individual organization on rowing performance. The second aim was to analyze crew phenomenology in order to understand how rowers experience their joint actions when coping with constraints emerging from the race. We conducted a descriptive and exploratory study of two coxless pair crews during a 3000-m rowing race against the clock. As the investigation was performed in an ecological context, we postulated that our understanding of the behavioral dynamics of interpersonal coordination and individual organization and the variability in performance would be enriched through the analysis of crew phenomenology. The behavioral dynamics of individual organization were assessed at kinematic and kinetic levels, and interpersonal coordination was examined by computing the relative phase between oar angles and oar forces and the difference in the oar force impulse of the two rowers. The inter-cycle variability of the behavioral dynamics of one international and one national crew was evaluated by computing the root mean square and the Cauchy index. Inter-cycle variability was considered significantly high when the behavioral and performance data for each cycle were outside of the confidence interval. Crew phenomenology was characterized on the basis of self-confrontation interviews and the rowers' concerns were then analyzed according to course-of-action methodology to identify the shared experiences. Our findings showed that greater behavioral variability could be either “perturbing” or “functional” depending on its impact on performance (boat velocity); the rowers experienced it as sometimes meaningful and sometimes meaningless; and their experiences were similar or diverging. By combining phenomenological and behavioral data, we explain how constraints not manipulated by an experimenter but emerging from the ecological context of a race can be associated with functional adaptations or perturbations of the interpersonal coordination. PMID:28194127

  3. Individuality embedded in the isolation calls of captive beluga whales (Delphinapterus leucas).

    PubMed

    Mishima, Yuka; Morisaka, Tadamichi; Itoh, Miho; Matsuo, Ikuo; Sakaguchi, Aiko; Miyamoto, Yoshinori

    2015-01-01

    Species with fission-fusion social systems tend to exchange individualized contact calls to maintain group cohesion. Signature whistles by bottlenose dolphins are unique compared to the contact calls of other non-human animals in that they include identity information independent of voice cues. Further, dolphins copy the signatures of conspecifics and use them to label specific individuals. Increasing our knowledge of the contact calls of other cetaceans that have a fluid social structure may thus help us better understand the evolutionary and adaptive significance of all forms of individually distinctive calls. It was recently reported that one type of broadband pulsed sounds (PS1), rather than whistles, may function as individualized contact calls in captive belugas. The objective of this study was to assess the function and individual distinctiveness of PS1 calls in an isolation context. Recordings were made from five captive belugas, including both sexes and various ages. PS1 was the predominant call type (38 % in total) out of five broader sound categories. One sub-adult and three adults had individually distinctive and stereotyped pulse repetition pattern in PS1; one calf showed no clear stereotyped pulse repetition pattern. While visual inspection of the PS1 power spectra uncovered no apparent individual specificity, statistical analyses revealed that both temporal and spectral parameters had inter-individual differences and that there was greater inter-individual than intra-individual variability. Discriminant function analysis based on five temporal and spectral parameters classified PS1 calls into individuals with an overall correct classification rate of 80.5 %, and the most informative parameter was the average Inter-pulse interval, followed by peak frequency. These results suggest that belugas use individually distinctive contact calls in an isolation context. If belugas encode signature information in PS1 calls, as seen in bottlenose dolphins, the pulse repetition pattern may be the carrier, as it is individually stereotyped and appears to require vocal development. This idea is supported by the finding that the average inter-pulse interval is the most powerful discriminator in discriminant analysis. Playback experiments will elucidate which parameters are perceived as individual characteristics, and whether one of the parameters functions as a signature.

  4. Intra- and inter-population variability and evaluation of the physical development of a young generation.

    PubMed

    Yampolskaya, Yulia A

    2005-07-01

    This study is concerned with long-term anthropometric examinations of children and adolescents aged 3-17 years in Moscow (over 10,500 persons, longitudinal and cross-sectional). Population variability of physical development was analyzed by means of regional estimation tables, which were developed on the basis of a regression analysis (scale of the regression of body mass to body length within a range from M - 1sigmaR to M + 2 sigmaR) and used for individual and group diagnostics taking into account age and sex. Such an approach allowed for the determination of the dynamics of the variability of Moscow schoolchildren from decade to decade (inter-population variability) and variations due to social differences (intra-population variability).

  5. Ilaprazole for the treatment of gastro-esophageal reflux.

    PubMed

    Savarino, Edoardo; Ottonello, Andrea; Martinucci, Irene; Dulbecco, Pietro; Savarino, Vincenzo

    2016-10-01

    Despite the undoubted benefit of proton pump inhibitors (PPIs), they have several shortcomings, such as a slow onset of action and a remarkable inter-individual variability, that limit the complete success of these drugs. Recently, a new PPI, ilaprazole, has been developed and used in GERD patients. The present review provides an update on the following points: current knowledge of GERD mechanisms; limitations of actual therapies; pharmacokinetic profile and metabolism of ilaprazole; initial studies on the therapeutic efficacy of ilaprazole in GERD. Compared with all other approved PPIs, ilaprazole has shown an extended plasma half-life, a metabolism not significantly influenced by CYP2C19 genetic polymorphism and similar safety. This characteristics account for a low inter-individual variability, particularly in Asian populations, a higher suppression of gastric acid secretion, a more rapid acid control and consequent quicker symptom relief and a better effect on nocturnal acidity. However, clinical investigations assessing the efficacy of ilaprazole in the management of GERD are lacking and therefore the potential improvements achievable with ilaprazole in the current standard of care for acid-suppressing treatment must be confirmed in large and randomly controlled clinical trials enrolling patients with both erosive and non-erosive reflux disease.

  6. Intra- and Inter-Individual Variability in Location Data for Two U.S. Health-Compromised Elderly Cohorts

    EPA Science Inventory

    This study provides descriptive statistical data on daily time spent in three locations of exposure assessment interest for two panel studies of health-compromised elderly individuals > 65 y old having multi-days of human activity data. The panel studies include individuals livi...

  7. The circadian body temperature rhythm in the elderly: effect of single daily melatonin dosing.

    PubMed

    Gubin, D G; Gubin, G D; Waterhouse, J; Weinert, D

    2006-01-01

    The present study is part of a more extensive investigation dedicated to the study and treatment of age-dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self-chosen sleep-wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age-dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra- and inter-individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38+/-0.19 degrees C vs. 36.17+/-0.21 degrees C) and circadian amplitude (0.33+/-0.01 degrees C vs. 0.26+/-0.01 degrees C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19+/-1.66 vs. 16.93+/-3.08 h). However, the inter-individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter-daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1 degrees C and the amplitude increased to 0.34+/-0.01 degrees C, a similar value to that found in young adults. This was probably due to the increase of the inter-daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter-individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age-dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep-improving effects.

  8. Physiologically Based Pharmacokinetic (PBPK) Modeling of Interstrain Variability in Trichloroethylene Metabolism in the Mouse

    EPA Science Inventory

    Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, inter-individual differences in the population are accounted for by default assumptions or, in rare cas...

  9. Inter-Individual Variability in High-Throughput Risk Prioritization of Environmental Chemicals (Sot)

    EPA Science Inventory

    We incorporate realistic human variability into an open-source high-throughput (HT) toxicokinetics (TK) modeling framework for use in a next-generation risk prioritization approach. Risk prioritization involves rapid triage of thousands of environmental chemicals, most which have...

  10. Impact of Flavonols on Cardiometabolic Biomarkers: A Meta-Analysis of Randomized Controlled Human Trials to Explore the Role of Inter-Individual Variability

    PubMed Central

    Menezes, Regina; Rodriguez-Mateos, Ana; Kaltsatou, Antonia; González-Sarrías, Antonio; Greyling, Arno; Giannaki, Christoforos; Andres-Lacueva, Cristina; Milenkovic, Dragan; Gibney, Eileen R.; Dumont, Julie; Schär, Manuel; Garcia-Aloy, Mar; Palma-Duran, Susana Alejandra; Ruskovska, Tatjana; Maksimova, Viktorija; Combet, Emilie; Pinto, Paula

    2017-01-01

    Several epidemiological studies have linked flavonols with decreased risk of cardiovascular disease (CVD). However, some heterogeneity in the individual physiological responses to the consumption of these compounds has been identified. This meta-analysis aimed to study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood pressure and plasma glucose, as well as factors affecting their inter-individual variability. Data from 18 human randomized controlled trials were pooled and the effect was estimated using fixed or random effects meta-analysis model and reported as difference in means (DM). Variability in the response of blood lipids to supplementation with flavonols was assessed by stratifying various population subgroups: age, sex, country, and health status. Results showed significant reductions in total cholesterol (DM = −0.10 mmol/L; 95% CI: −0.20, −0.01), LDL cholesterol (DM = −0.14 mmol/L; 95% CI: −0.21, 0.07), and triacylglycerol (DM = −0.10 mmol/L; 95% CI: −0.18, 0.03), and a significant increase in HDL cholesterol (DM = 0.05 mmol/L; 95% CI: 0.02, 0.07). A significant reduction was also observed in fasting plasma glucose (DM = −0.18 mmol/L; 95% CI: −0.29, −0.08), and in blood pressure (SBP: DM = −4.84 mmHg; 95% CI: −5.64, −4.04; DBP: DM = −3.32 mmHg; 95% CI: −4.09, −2.55). Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and normal baseline values. In conclusion, flavonol consumption improved biomarkers of CVD risk, however, country of origin and health status may influence the effect of flavonol intake on blood lipid levels. PMID:28208791

  11. Inter-decadal change in potential predictability of the East Asian summer monsoon

    NASA Astrophysics Data System (ADS)

    Li, Jiao; Ding, Ruiqiang; Wu, Zhiwei; Zhong, Quanjia; Li, Baosheng; Li, Jianping

    2018-05-01

    The significant inter-decadal change in potential predictability of the East Asian summer monsoon (EASM) has been investigated using the signal-to-noise ratio method. The relatively low potential predictability appears from the early 1950s through the late 1970s and during the early 2000s, whereas the potential predictability is relatively high from the early 1980s through the late 1990s. The inter-decadal change in potential predictability of the EASM can be attributed mainly to variations in the external signal of the EASM. The latter is mostly caused by the El Niño-Southern Oscillation (ENSO) inter-decadal variability. As a major external signal of the EASM, the ENSO inter-decadal variability experiences phase transitions from negative to positive phases in the late 1970s, and to negative phases in the late 1990s. Additionally, ENSO is generally strong (weak) during a positive (negative) phase of the ENSO inter-decadal variability. The strong ENSO is expected to have a greater influence on the EASM, and vice versa. As a result, the potential predictability of the EASM tends to be high (low) during a positive (negative) phase of the ENSO inter-decadal variability. Furthermore, a suite of Pacific Pacemaker experiments suggests that the ENSO inter-decadal variability may be a key pacemaker of the inter-decadal change in potential predictability of the EASM.

  12. Population pharmacokinetics of intravenous Erwinia asparaginase in pediatric acute lymphoblastic leukemia patients.

    PubMed

    Sassen, Sebastiaan D T; Mathôt, Ron A A; Pieters, Rob; Kloos, Robin Q H; de Haas, Valérie; Kaspers, Gertjan J L; van den Bos, Cor; Tissing, Wim J E; Te Loo, Maroeska; Bierings, Marc B; Kollen, Wouter J W; Zwaan, Christian M; van der Sluis, Inge M

    2017-03-01

    Erwinia asparaginase is an important component in the treatment of pediatric acute lymphoblastic leukemia. A large variability in serum concentrations has been observed after intravenous Erwinia asparaginase. Currently, Dutch Childhood Oncology Group protocols dose alterations are based on trough concentrations to ensure adequate asparaginase activity (≥100 IU/L). The aim of this study was to describe the population pharmacokinetics of intravenous Erwinia asparaginase to quantify and gather insight into inter-individual and inter-occasion variability. The starting dose was evaluated on the basis of the derived population pharmacokinetic parameters. In a multicenter prospective observational study, a total of 714 blood samples were collected from 51 children (age 1-17 years) with acute lymphoblastic leukemia. The starting dose was 20,000 IU/m 2 three times a week and adjusted according to trough levels from week three onwards. A population pharmacokinetic model was developed using NONMEM ® A 2-compartment linear model with allometric scaling best described the data. Inter-individual and inter-occasion variability of clearance were 33% and 13%, respectively. Clearance in the first month of treatment was 14% higher ( P <0.01). Monte Carlo simulations with our pharmacokinetic model demonstrated that patients with a low weight might require higher doses to achieve similar concentrations compared to patients with high weight. The current starting dose of 20,000 IU/m 2 might result in inadequate concentrations, especially for smaller, lower weight patients, hence dose adjustments based on individual clearance are recommended. The protocols were approved by the institutional review boards. (Registered at NTR 3379 Dutch Trial Register; www.trialregister.nl). Copyright© Ferrata Storti Foundation.

  13. Universality of human microbial dynamics

    NASA Astrophysics Data System (ADS)

    Bashan, Amir; Gibson, Travis E.; Friedman, Jonathan; Carey, Vincent J.; Weiss, Scott T.; Hohmann, Elizabeth L.; Liu, Yang-Yu

    2016-06-01

    Human-associated microbial communities have a crucial role in determining our health and well-being, and this has led to the continuing development of microbiome-based therapies such as faecal microbiota transplantation. These microbial communities are very complex, dynamic and highly personalized ecosystems, exhibiting a high degree of inter-individual variability in both species assemblages and abundance profiles. It is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra- and inter-species interactions in population dynamics models, are largely host-independent (that is, universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle, physiology or genetics, then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species. Here we develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studies—the Human Microbiome Project and the Student Microbiome Project—we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection but is observed in the same set of subjects after faecal microbiota transplantation. These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiome-based therapies.

  14. Human variability in high-throughput risk prioritization of environmental chemicals (Texas AM U. webinar)

    EPA Science Inventory

    We incorporate inter-individual variability into an open-source high-throughput (HT) toxicokinetics (TK) modeling framework for use in a next-generation risk prioritization approach. Risk prioritization involves rapid triage of thousands of environmental chemicals, most which hav...

  15. Emerging Approaches and Opportunities to inform Internal Dosimetry and Inter-individual Variability

    EPA Science Inventory

    This talk provided an update to EPA ORD scientists and program officers about planned research within the Chemical Safety for Sustainability program to address chemical toxicokinetics and strategies to understand better the range of variability across different populations and li...

  16. Personality Traits and Behavioral Syndromes in Differently Urbanized Populations of House Sparrows (Passer domesticus)

    PubMed Central

    Bókony, Veronika; Kulcsár, Anna; Tóth, Zoltán; Liker, András

    2012-01-01

    Urbanization creates novel environments for wild animals where selection pressures may differ drastically from those in natural habitats. Adaptation to urban life involves changes in various traits, including behavior. Behavioral traits often vary consistently among individuals, and these so-called personality traits can be correlated with each other, forming behavioral syndromes. Despite their adaptive significance and potential to act as constraints, little is known about the role of animal personality and behavioral syndromes in animals' adaptation to urban habitats. In this study we tested whether differently urbanized habitats select for different personalities and behavioral syndromes by altering the population mean, inter-individual variability, and correlations of personality traits. We captured house sparrows (Passer domesticus) from four different populations along the gradient of urbanization and assessed their behavior in standardized test situations. We found individual consistency in neophobia, risk taking, and activity, constituting three personality axes. On the one hand, urbanization did not consistently affect the mean and variance of these traits, although there were significant differences between some of the populations in food neophobia and risk taking (both in means and variances). On the other hand, both urban and rural birds exhibited a behavioral syndrome including object neophobia, risk taking and activity, whereas food neophobia was part of the syndrome only in rural birds. These results indicate that there are population differences in certain aspects of personality in house sparrows, some of which may be related to habitat urbanization. Our findings suggest that urbanization and/or other population-level habitat differences may not only influence the expression of personality traits but also alter their inter-individual variability and the relationships among them, changing the structure of behavioral syndromes. PMID:22574204

  17. Inter-Investigator Reliability of Anthropometric Prediction of 1RM Bench Press in College Football Players

    PubMed Central

    SCHUMACHER, RICHARD M.; ARABAS, JANA L.; MAYHEW, JERRY L.; BRECHUE, WILLIAM F.

    2016-01-01

    The purpose of this study was to determine the effect of inter-investigator differences in anthropometric assessments on the prediction of one-repetition maximum (1RM) bench press in college football players. Division-II players (n = 34, age = 20.4 ± 1.2 y, 182.3 ± 6.6 cm, 99.1 ± 18.4 kg) were measured for selected anthropometric variables and 1RM bench press at the conclusion of a heavy resistance training program. Triceps, subscapular, and abdominal skinfolds were measured in triplicate by three investigators and used to estimate %fat. Arm circumference was measured around a flexed biceps muscle and was corrected for triceps skinfold to estimate muscle cross-sectional area (CSA). Chest circumference was measured at mid-expiration. Significant differences among the testers were evident in six of the nine anthropometric variables, with the least experienced tester being significantly different from the other testers on seven variables, although average differences among investigators ranged from 1–2% for circumferences to 4–9% for skinfolds. The two more experienced testers were significantly different on only one variable. Overall agreement among testers was high (ICC>0.895) for each variable, with low coefficients of variation (CV<10.7%). Predicted 1RMs for testers (126.9 ± 20.6, 123.4 ± 22.0, and 132.1 ± 28.4 kg, respectively) were not significantly different from actual 1RM (129.2 ± 20.6 kg). Individuals with varying levels of experience appear to have an acceptable level of ability to estimate 1RM bench press using a non-performance anthropometric equation. Minimal experience in anthropometry may not impede strength and conditioning specialists from accurately estimating 1RM bench press. PMID:27766130

  18. Inter-Investigator Reliability of Anthropometric Prediction of 1RM Bench Press in College Football Players.

    PubMed

    Schumacher, Richard M; Arabas, Jana L; Mayhew, Jerry L; Brechue, William F

    2016-01-01

    The purpose of this study was to determine the effect of inter-investigator differences in anthropometric assessments on the prediction of one-repetition maximum (1RM) bench press in college football players. Division-II players (n = 34, age = 20.4 ± 1.2 y, 182.3 ± 6.6 cm, 99.1 ± 18.4 kg) were measured for selected anthropometric variables and 1RM bench press at the conclusion of a heavy resistance training program. Triceps, subscapular, and abdominal skinfolds were measured in triplicate by three investigators and used to estimate %fat. Arm circumference was measured around a flexed biceps muscle and was corrected for triceps skinfold to estimate muscle cross-sectional area (CSA). Chest circumference was measured at mid-expiration. Significant differences among the testers were evident in six of the nine anthropometric variables, with the least experienced tester being significantly different from the other testers on seven variables, although average differences among investigators ranged from 1-2% for circumferences to 4-9% for skinfolds. The two more experienced testers were significantly different on only one variable. Overall agreement among testers was high (ICC>0.895) for each variable, with low coefficients of variation (CV<10.7%). Predicted 1RMs for testers (126.9 ± 20.6, 123.4 ± 22.0, and 132.1 ± 28.4 kg, respectively) were not significantly different from actual 1RM (129.2 ± 20.6 kg). Individuals with varying levels of experience appear to have an acceptable level of ability to estimate 1RM bench press using a non-performance anthropometric equation. Minimal experience in anthropometry may not impede strength and conditioning specialists from accurately estimating 1RM bench press.

  19. Morphometric variability of Arctodiaptomus salinus (Copepoda) in the Mediterranean-Black Sea region

    PubMed Central

    ANUFRIIEVA, Elena V.; SHADRIN, Nickolai V.

    2015-01-01

    Inter-species variability in morphological traits creates a need to know the range of variability of characteristics in the species for taxonomic and ecological tasks. Copepoda Arctodiaptomus salinus, which inhabits water bodies across Eurasia and North Africa, plays a dominant role in plankton of different water bodies-from fresh to hypersaline. This work assesses the intra- and inter-population morphometric variability of A. salinus in the Mediterranean-Black Sea region and discusses some observed regularities. The variability of linear body parameters and proportions was studied. The impacts of salinity, temperature, and population density on morphological characteristics and their variability can manifest themselves in different ways at the intra- and inter-population levels. A significant effect of salinity, pH and temperature on the body proportions was not found. Their intra-population variability is dependent on temperature and salinity. Sexual dimorphism of A. salinus manifests in different linear parameters, proportions, and their variability. There were no effects of temperature, pH and salinity on the female/male parameter ratio. There were significant differences in the body proportions of males and females in different populations. The influence of temperature, salinity, and population density can be attributed to 80%-90% of intra-population variability of A. salinus. However, these factors can explain less than 40% of inter-population differences. Significant differences in the body proportions of males and females from different populations may suggest that some local populations of A. salinus in the Mediterranean-Black Sea region are in the initial stages of differentiation. PMID:26646569

  20. Individual Variability in Reproductive Success Determines Winners and Losers under Ocean Acidification: A Case Study with Sea Urchins

    PubMed Central

    Schlegel, Peter; Havenhand, Jon N.; Gillings, Michael R.; Williamson, Jane E.

    2012-01-01

    Background Climate change will lead to intense selection on many organisms, particularly during susceptible early life stages. To date, most studies on the likely biotic effects of climate change have focused on the mean responses of pooled groups of animals. Consequently, the extent to which inter-individual variation mediates different selection responses has not been tested. Investigating this variation is important, since some individuals may be preadapted to future climate scenarios. Methodology/Principal Findings We examined the effect of CO2-induced pH changes (“ocean acidification”) in sperm swimming behaviour on the fertilization success of the Australasian sea urchin Heliocidaris erythrogramma, focusing on the responses of separate individuals and pairs. Acidification significantly decreased the proportion of motile sperm but had no effect on sperm swimming speed. Subsequent fertilization experiments showed strong inter-individual variation in responses to ocean acidification, ranging from a 44% decrease to a 14% increase in fertilization success. This was partly explained by the significant relationship between decreases in percent sperm motility and fertilization success at ΔpH = 0.3, but not at ΔpH = 0.5. Conclusions and Significance The effects of ocean acidification on reproductive success varied markedly between individuals. Our results suggest that some individuals will exhibit enhanced fertilization success in acidified oceans, supporting the concept of ‘winners’ and ‘losers’ of climate change at an individual level. If these differences are heritable it is likely that ocean acidification will lead to selection against susceptible phenotypes as well as to rapid fixation of alleles that allow reproduction under more acidic conditions. This selection may ameliorate the biotic effects of climate change if taxa have sufficient extant genetic variation upon which selection can act. PMID:23300876

  1. Using a respiratory navigator significantly reduces variability when quantifying left ventricular torsion with cardiovascular magnetic resonance.

    PubMed

    Hamlet, Sean M; Haggerty, Christopher M; Suever, Jonathan D; Wehner, Gregory J; Andres, Kristin N; Powell, David K; Charnigo, Richard J; Fornwalt, Brandon K

    2017-03-01

    Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion. We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure and then enforce variability in end-expiratory position between all LV basal and apical acquisitions. From these data, we quantified the inter-test variability of torsion in the absence and presence of enforced end-expiratory position variability, which established an upper bound for the expected torsion variability. For the second experiment (in 20 new, healthy volunteers), 10 pairs of cine DENSE basal and apical images were each acquired from consecutive breath-holds and consecutive navigator-gated scans (with a single acceptance position). Inter-test variability of torsion was compared between the breath-hold and navigator-gated scans to quantify the variability due to natural breath-hold variation. To demonstrate the importance of these variability reductions, we quantified the reduction in sample size required to detect a clinically meaningful change in LV torsion with the use of a respiratory navigator. The mean torsion was 3.4 ± 0.2°/cm. From the first experiment, enforced variability in end-expiratory position translated to considerable variability in measured torsion (0.56 ± 0.34°/cm), whereas inter-test variability with consistent end-expiratory position was 57% lower (0.24 ± 0.16°/cm, p < 0.001). From the second experiment, natural respiratory variability from consecutive breath-holds translated to a variability in torsion of 0.24 ± 0.10°/cm, which was significantly higher than the variability from navigator-gated scans (0.18 ± 0.06°/cm, p = 0.02). By using a respiratory navigator with DENSE, theoretical sample sizes were reduced from 66 to 16 and 26 to 15 as calculated from the two experiments. A substantial portion (22-57%) of the inter-test variability of LV torsion can be reduced by using a respiratory navigator to ensure a consistent breath-hold position between image acquisitions.

  2. Characterizing Individual Differences in Functional Connectivity Using Dual-Regression and Seed-Based Approaches

    PubMed Central

    Smith, David V.; Utevsky, Amanda V.; Bland, Amy R.; Clement, Nathan; Clithero, John A.; Harsch, Anne E. W.; Carter, R. McKell; Huettel, Scott A.

    2014-01-01

    A central challenge for neuroscience lies in relating inter-individual variability to the functional properties of specific brain regions. Yet, considerable variability exists in the connectivity patterns between different brain areas, potentially producing reliable group differences. Using sex differences as a motivating example, we examined two separate resting-state datasets comprising a total of 188 human participants. Both datasets were decomposed into resting-state networks (RSNs) using a probabilistic spatial independent components analysis (ICA). We estimated voxelwise functional connectivity with these networks using a dual-regression analysis, which characterizes the participant-level spatiotemporal dynamics of each network while controlling for (via multiple regression) the influence of other networks and sources of variability. We found that males and females exhibit distinct patterns of connectivity with multiple RSNs, including both visual and auditory networks and the right frontal-parietal network. These results replicated across both datasets and were not explained by differences in head motion, data quality, brain volume, cortisol levels, or testosterone levels. Importantly, we also demonstrate that dual-regression functional connectivity is better at detecting inter-individual variability than traditional seed-based functional connectivity approaches. Our findings characterize robust—yet frequently ignored—neural differences between males and females, pointing to the necessity of controlling for sex in neuroscience studies of individual differences. Moreover, our results highlight the importance of employing network-based models to study variability in functional connectivity. PMID:24662574

  3. Large inter-individual and intra-individual variability in the effect of perceptual load

    PubMed Central

    Yeshurun, Yaffa

    2017-01-01

    This study examined whether the recurrent difficulty to replicate results obtained with paradigms measuring distractor processing as a function of perceptual load is due to individual differences. We first reanalyzed, at the individual level, the data of eight previously reported experiments. These reanalyses revealed substantial inter-individual differences, with particularly low percentage of participants whose performance matched the load theory’s predictions (i.e., larger distractor interference with low than high levels of load). Moreover, frequently the results were opposite to the theory's predictions–larger interference in the high than low load condition; and often a reversed compatibility effect emerged–better performance in the incompatible than neutral condition. Subsequently, seven observers participated in five identical experimental sessions. If the observed inter-individual differences are due to some stable trait or perceptual capacity, similar results should have emerged in all sessions of a given participant. However, all seven participants showed large between-sessions variations with similar patterns to those found between participants. These findings question the theoretical foundation implemented with these paradigms, as none of the theories suggested thus far can account for such inter- and intra-individual differences. Thus, these paradigms should be used with caution until further research will provide better understanding of what they actually measure. PMID:28406997

  4. Motor imagery-induced EEG patterns in individuals with spinal cord injury and their impact on brain-computer interface accuracy

    NASA Astrophysics Data System (ADS)

    Müller-Putz, G. R.; Daly, I.; Kaiser, V.

    2014-06-01

    Objective. Assimilating the diagnosis complete spinal cord injury (SCI) takes time and is not easy, as patients know that there is no ‘cure' at the present time. Brain-computer interfaces (BCIs) can facilitate daily living. However, inter-subject variability demands measurements with potential user groups and an understanding of how they differ to healthy users BCIs are more commonly tested with. Thus, a three-class motor imagery (MI) screening (left hand, right hand, feet) was performed with a group of 10 able-bodied and 16 complete spinal-cord-injured people (paraplegics, tetraplegics) with the objective of determining what differences were present between the user groups and how they would impact upon the ability of these user groups to interact with a BCI. Approach. Electrophysiological differences between patient groups and healthy users are measured in terms of sensorimotor rhythm deflections from baseline during MI, electroencephalogram microstate scalp maps and strengths of inter-channel phase synchronization. Additionally, using a common spatial pattern algorithm and a linear discriminant analysis classifier, the classification accuracy was calculated and compared between groups. Main results. It is seen that both patient groups (tetraplegic and paraplegic) have some significant differences in event-related desynchronization strengths, exhibit significant increases in synchronization and reach significantly lower accuracies (mean (M) = 66.1%) than the group of healthy subjects (M = 85.1%). Significance. The results demonstrate significant differences in electrophysiological correlates of motor control between healthy individuals and those individuals who stand to benefit most from BCI technology (individuals with SCI). They highlight the difficulty in directly translating results from healthy subjects to participants with SCI and the challenges that, therefore, arise in providing BCIs to such individuals.

  5. Inter- and intra-specific variability in δ13C and δ18O values of freshwater gastropod shells from Lake Lednica, western Poland

    NASA Astrophysics Data System (ADS)

    Apolinarska, Karina; Pełechaty, Mariusz

    2017-09-01

    This study focuses on the inter- and intra-specific variability in δ13C and δ18O values of shells and opercula of gastropods sampled live from the littoral zone of Lake Lednica, western Poland. The δ13C and δ18O values were measured in individual opercula of Bithynia tentaculata and in shells of Bithynia tentaculata, Gyraulus albus, Gyraulus crista, Lymnaea sp., Physa fontinalis, Radix auricularia, Theodoxus fluviatilis and Valvata cristata. The gastropods selected for the study are among the species most commonly found in European Quaternary lacustrine sediments. The carbon isotope composition of the gastropod shells was species-specific and the same order of species from the most to the least 13C-depleted was observed at all sites sampled. Differences in shell δ13C values between species were similar at all sampling sites, thus the factors influencing shell isotopic composition were interpreted as species-specific. The δ18O values of shells were similar in all the species investigated. Significant intra-specific variability in shell δ13C and δ18O values was observed not only within the populations of Lake Lednica, which can be explained by heterogeneity of δ13C DIC, δ18O water and water temperature between the sites where macrophytes with snails attached were sampled, but also between individuals sampled from restricted areas of the lake's bottom. The latter points to the importance of factors related to the ontogeny of individual gastropods.

  6. Operator Variability in Scan Positioning is a Major Component of HR-pQCT Precision Error and is Reduced by Standardized Training

    PubMed Central

    Bonaretti, Serena; Vilayphiou, Nicolas; Chan, Caroline Mai; Yu, Andrew; Nishiyama, Kyle; Liu, Danmei; Boutroy, Stephanie; Ghasem-Zadeh, Ali; Boyd, Steven K.; Chapurlat, Roland; McKay, Heather; Shane, Elizabeth; Bouxsein, Mary L.; Black, Dennis M.; Majumdar, Sharmila; Orwoll, Eric S.; Lang, Thomas F.; Khosla, Sundeep; Burghardt, Andrew J.

    2017-01-01

    Introduction HR-pQCT is increasingly used to assess bone quality, fracture risk and anti-fracture interventions. The contribution of the operator has not been adequately accounted in measurement precision. Operators acquire a 2D projection (“scout view image”) and define the region to be scanned by positioning a “reference line” on a standard anatomical landmark. In this study, we (i) evaluated the contribution of positioning variability to in vivo measurement precision, (ii) measured intra- and inter-operator positioning variability, and (iii) tested if custom training software led to superior reproducibility in new operators compared to experienced operators. Methods To evaluate the operator in vivo measurement precision we compared precision errors calculated in 64 co-registered and non-co-registered scan-rescan images. To quantify operator variability, we developed software that simulates the positioning process of the scanner’s software. Eight experienced operators positioned reference lines on scout view images designed to test intra- and inter-operator reproducibility. Finally, we developed modules for training and evaluation of reference line positioning. We enrolled 6 new operators to participate in a common training, followed by the same reproducibility experiments performed by the experienced group. Results In vivo precision errors were up to three-fold greater (Tt.BMD and Ct.Th) when variability in scan positioning was included. Inter-operator precision errors were significantly greater than short-term intra-operator precision (p<0.001). New trained operators achieved comparable intra-operator reproducibility to experienced operators, and lower inter-operator reproducibility (p<0.001). Precision errors were significantly greater for the radius than for the tibia. Conclusion Operator reference line positioning contributes significantly to in vivo measurement precision and is significantly greater for multi-operator datasets. Inter-operator variability can be significantly reduced using a systematic training platform, now available online (http://webapps.radiology.ucsf.edu/refline/). PMID:27475931

  7. A multi-segment foot model based on anatomically registered technical coordinate systems: method repeatability in pediatric feet.

    PubMed

    Saraswat, Prabhav; MacWilliams, Bruce A; Davis, Roy B

    2012-04-01

    Several multi-segment foot models to measure the motion of intrinsic joints of the foot have been reported. Use of these models in clinical decision making is limited due to lack of rigorous validation including inter-clinician, and inter-lab variability measures. A model with thoroughly quantified variability may significantly improve the confidence in the results of such foot models. This study proposes a new clinical foot model with the underlying strategy of using separate anatomic and technical marker configurations and coordinate systems. Anatomical landmark and coordinate system identification is determined during a static subject calibration. Technical markers are located at optimal sites for dynamic motion tracking. The model is comprised of the tibia and three foot segments (hindfoot, forefoot and hallux) and inter-segmental joint angles are computed in three planes. Data collection was carried out on pediatric subjects at two sites (Site 1: n=10 subjects by two clinicians and Site 2: five subjects by one clinician). A plaster mold method was used to quantify static intra-clinician and inter-clinician marker placement variability by allowing direct comparisons of marker data between sessions for each subject. Intra-clinician and inter-clinician joint angle variability were less than 4°. For dynamic walking kinematics, intra-clinician, inter-clinician and inter-laboratory variability were less than 6° for the ankle and forefoot, but slightly higher for the hallux. Inter-trial variability accounted for 2-4° of the total dynamic variability. Results indicate the proposed foot model reduces the effects of marker placement variability on computed foot kinematics during walking compared to similar measures in previous models. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Predator personality and prey behavioural predictability jointly determine foraging performance.

    PubMed

    Chang, Chia-Chen; Teo, Huey Yee; Norma-Rashid, Y; Li, Daiqin

    2017-01-17

    Predator-prey interactions play important roles in ecological communities. Personality, consistent inter-individual differences in behaviour, of predators, prey or both are known to influence inter-specific interactions. An individual may also behave differently under the same situation and the level of such variability may differ between individuals. Such intra-individual variability (IIV) or predictability may be a trait on which selection can also act. A few studies have revealed the joint effect of personality types of both predators and prey on predator foraging performance. However, how personality type and IIV of both predators and prey jointly influence predator foraging performance remains untested empirically. Here, we addressed this using a specialized spider-eating jumping spider, Portia labiata (Salticidae), as the predator, and a jumping spider, Cosmophasis umbratica, as the prey. We examined personality types and IIVs of both P. labiata and C. umbratica and used their inter- and intra-individual behavioural variation as predictors of foraging performance (i.e., number of attempts to capture prey). Personality type and predictability had a joint effect on predator foraging performance. Aggressive predators performed better in capturing unpredictable (high IIV) prey than predictable (low IIV) prey, while docile predators demonstrated better performance when encountering predictable prey. This study highlights the importance of the joint effect of both predator and prey personality types and IIVs on predator-prey interactions.

  9. Predator personality and prey behavioural predictability jointly determine foraging performance

    PubMed Central

    Chang, Chia-chen; Teo, Huey Yee; Norma-Rashid, Y.; Li, Daiqin

    2017-01-01

    Predator-prey interactions play important roles in ecological communities. Personality, consistent inter-individual differences in behaviour, of predators, prey or both are known to influence inter-specific interactions. An individual may also behave differently under the same situation and the level of such variability may differ between individuals. Such intra-individual variability (IIV) or predictability may be a trait on which selection can also act. A few studies have revealed the joint effect of personality types of both predators and prey on predator foraging performance. However, how personality type and IIV of both predators and prey jointly influence predator foraging performance remains untested empirically. Here, we addressed this using a specialized spider-eating jumping spider, Portia labiata (Salticidae), as the predator, and a jumping spider, Cosmophasis umbratica, as the prey. We examined personality types and IIVs of both P. labiata and C. umbratica and used their inter- and intra-individual behavioural variation as predictors of foraging performance (i.e., number of attempts to capture prey). Personality type and predictability had a joint effect on predator foraging performance. Aggressive predators performed better in capturing unpredictable (high IIV) prey than predictable (low IIV) prey, while docile predators demonstrated better performance when encountering predictable prey. This study highlights the importance of the joint effect of both predator and prey personality types and IIVs on predator-prey interactions. PMID:28094288

  10. Auditory Multi-Stability: Idiosyncratic Perceptual Switching Patterns, Executive Functions and Personality Traits

    PubMed Central

    Farkas, Dávid; Denham, Susan L.; Bendixen, Alexandra; Tóth, Dénes; Kondo, Hirohito M.; Winkler, István

    2016-01-01

    Multi-stability refers to the phenomenon of perception stochastically switching between possible interpretations of an unchanging stimulus. Despite considerable variability, individuals show stable idiosyncratic patterns of switching between alternative perceptions in the auditory streaming paradigm. We explored correlates of the individual switching patterns with executive functions, personality traits, and creativity. The main dimensions on which individual switching patterns differed from each other were identified using multidimensional scaling. Individuals with high scores on the dimension explaining the largest portion of the inter-individual variance switched more often between the alternative perceptions than those with low scores. They also perceived the most unusual interpretation more often, and experienced all perceptual alternatives with a shorter delay from stimulus onset. The ego-resiliency personality trait, which reflects a tendency for adaptive flexibility and experience seeking, was significantly positively related to this dimension. Taking these results together we suggest that this dimension may reflect the individual’s tendency for exploring the auditory environment. Executive functions were significantly related to some of the variables describing global properties of the switching patterns, such as the average number of switches. Thus individual patterns of perceptual switching in the auditory streaming paradigm are related to some personality traits and executive functions. PMID:27135945

  11. Genome-wide interactions with dairy intake for body mass index in adults of European descent

    USDA-ARS?s Scientific Manuscript database

    Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. Methods and results: We conducted a genome-wide interaction study to discover genetic variants that account f...

  12. Spatial Topography of Individual-Specific Cortical Networks Predicts Human Cognition, Personality, and Emotion.

    PubMed

    Kong, Ru; Li, Jingwei; Orban, Csaba; Sabuncu, Mert R; Liu, Hesheng; Schaefer, Alexander; Sun, Nanbo; Zuo, Xi-Nian; Holmes, Avram J; Eickhoff, Simon B; Yeo, B T Thomas

    2018-06-06

    Resting-state functional magnetic resonance imaging (rs-fMRI) offers the opportunity to delineate individual-specific brain networks. A major question is whether individual-specific network topography (i.e., location and spatial arrangement) is behaviorally relevant. Here, we propose a multi-session hierarchical Bayesian model (MS-HBM) for estimating individual-specific cortical networks and investigate whether individual-specific network topography can predict human behavior. The multiple layers of the MS-HBM explicitly differentiate intra-subject (within-subject) from inter-subject (between-subject) network variability. By ignoring intra-subject variability, previous network mappings might confuse intra-subject variability for inter-subject differences. Compared with other approaches, MS-HBM parcellations generalized better to new rs-fMRI and task-fMRI data from the same subjects. More specifically, MS-HBM parcellations estimated from a single rs-fMRI session (10 min) showed comparable generalizability as parcellations estimated by 2 state-of-the-art methods using 5 sessions (50 min). We also showed that behavioral phenotypes across cognition, personality, and emotion could be predicted by individual-specific network topography with modest accuracy, comparable to previous reports predicting phenotypes based on connectivity strength. Network topography estimated by MS-HBM was more effective for behavioral prediction than network size, as well as network topography estimated by other parcellation approaches. Thus, similar to connectivity strength, individual-specific network topography might also serve as a fingerprint of human behavior.

  13. Differing Roles of Functional Movement Variability as Experience Increases in Gymnastics

    PubMed Central

    Busquets, Albert; Marina, Michel; Davids, Keith; Angulo-Barroso, Rosa

    2016-01-01

    Current theories, like Ecological Dynamics, propose that inter-trial movement variability is functional when acquiring or refining movement coordination. Here, we examined how age-based experience levels of gymnasts constrained differences in emergent movement pattern variability during task performance. Specifically, we investigated different roles of movement pattern variability when gymnasts in different age groups performed longswings on a high bar, capturing the range of experience from beginner to advanced status. We also investigated the functionality of the relationships between levels of inter-trial variability and longswing amplitude during performance. One-hundred and thirteen male gymnasts in five age groups were observed performing longswings (with three different experience levels: beginners, intermediates and advanced performers). Performance was evaluated by analysis of key events in coordination of longswing focused on the arm-trunk and trunk-thigh segmental relations. Results revealed that 10 of 18 inter-trial variability measures changed significantly as a function of increasing task experience. Four of ten variability measures conformed to a U-shaped function with age implying exploratory strategies amongst beginners and functional adaptive variability amongst advanced performers. Inter-trial variability of arm-trunk coordination variables (6 of 10) conformed to a \\-shaped curve, as values were reduced to complete the longswings. Changes in coordination variability from beginner to intermediate status were largely restrictive, with only one variability measure related to exploration. Data revealed how inter-trial movement variability in gymnastics, relative to performance outcomes, needs careful interpretation, implying different roles as task experience changes. Key points Inter-trial variability while performing longswings on a high bar was assessed in a large sample (113 participants) divided into five age groups (form beginners to advanced gymnasts). Longswing assessment allowed us to evaluate inter-trial variability in representative performance context. Coordination variability presented two different configurations across experience levels depending on the variable of interest: either a U-shaped or a L- or \\-shaped graph. Increased inter-trial variability of the functional phase events offered flexibility to adapt the longswing performance in the advanced gymnasts, while decreasing variability in arm-trunk coordination modes was critical to improve longswing and to achieve the most advanced level. In addition, the relationship between variability measures and the global performance outcome (i.e. the swing amplitude) revealed different functional roles of movement variability (exploratory or restrictive) as a function of changes in experience levels. PMID:27274664

  14. Analysis of the contribution of experimental bias, experimental noise, and inter-subject biological variability on the assessment of developmental trajectories in diffusion MRI studies of the brain.

    PubMed

    Sadeghi, Neda; Nayak, Amritha; Walker, Lindsay; Okan Irfanoglu, M; Albert, Paul S; Pierpaoli, Carlo

    2015-04-01

    Metrics derived from the diffusion tensor, such as fractional anisotropy (FA) and mean diffusivity (MD) have been used in many studies of postnatal brain development. A common finding of previous studies is that these tensor-derived measures vary widely even in healthy populations. This variability can be due to inherent inter-individual biological differences as well as experimental noise. Moreover, when comparing different studies, additional variability can be introduced by different acquisition protocols. In this study we examined scans of 61 individuals (aged 4-22 years) from the NIH MRI study of normal brain development. Two scans were collected with different protocols (low and high resolution). Our goal was to separate the contributions of biological variability and experimental noise to the overall measured variance, as well as to assess potential systematic effects related to the use of different protocols. We analyzed FA and MD in seventeen regions of interest. We found that biological variability for both FA and MD varies widely across brain regions; biological variability is highest for FA in the lateral part of the splenium and body of the corpus callosum along with the cingulum and the superior longitudinal fasciculus, and for MD in the optic radiations and the lateral part of the splenium. These regions with high inter-individual biological variability are the most likely candidates for assessing genetic and environmental effects in the developing brain. With respect to protocol-related effects, the lower resolution acquisition resulted in higher MD and lower FA values for the majority of regions compared with the higher resolution protocol. However, the majority of the regions did not show any age-protocol interaction, indicating similar trajectories were obtained irrespective of the protocol used. Published by Elsevier Inc.

  15. Seasonal Trends and Inter-Individual Heterogeneity: A multi-species record of Mg, Sr, Ba, & Mn in Planktic Foraminifera from the Modern Cariaco Basin

    NASA Astrophysics Data System (ADS)

    Davis, C. V.; Thunell, R.; Astor, Y. M.

    2017-12-01

    The trace element to calcium ratios (TE/Ca) of planktic foraminifera shells are a valuable tool for paleoceanographic reconstructions, and represent a combination of environmental, ecological and biological signals. We present here a three-year record (2010-2013) of TE/Ca (Mg, Sr, Ba, Mn) from four species of foraminifera (Orbulina universa, Globigerina ruber, Globigerinella siphonifera, and Globorotalia menardii) collected by plankton tow in the modern Cariaco basin. Each tow is paired with in situ measurements of water column properties, allowing a direct comparison between shell geochemistry and calcification environment. A combination of Laser Ablation and solution ICP-MS analyses are used to document seasonality, primarily due to the alternating influence of wind-driven coastal upwelling and riverine inputs, in shell TE/Ca. Individual shell data further allows for the quantification of trace element heterogeneity among individual shells within single tows. All TE/Ca ratios vary temporally and show inter-individual variability within single tows. The spread in TE/Ca differs between element and species, with Mg/Ca ratios being the most variable. Despite this, Mg/Ca still tracks temperature changes in G. ruber, O. universa, and G. menardii, with G. ruber most closely reproducing sea surface temperature. Some species show chamber-to-chamber differences in trace element ratios, with G. ruber Mg/Ca and Ba/Ca decreasing in younger chambers (but not other elements) and Mg/Ca, Mn/Ca and Ba/Ca decreasing in younger chambers in G. siphonifera. We find the original Mn/Ca to be variable both temporally and between species, with G. menardii in some samples having extremely high ratios (100 μmol/mol). Assessing seasonal trends and environmental drivers of TE/Ca variability and quantifying the extent of inter-individual heterogeneity in these species will inform the use of their shells as geochemical proxies.

  16. Population structure and genotypic variation of Crataegus pontica inferred by molecular markers.

    PubMed

    Rahmani, Mohammad-Shafie; Shabanian, Naghi; Khadivi-Khub, Abdollah; Woeste, Keith E; Badakhshan, Hedieh; Alikhani, Leila

    2015-11-01

    Information about the natural patterns of genetic variability and their evolutionary bases are of fundamental practical importance for sustainable forest management and conservation. In the present study, the genetic diversity of 164 individuals from fourteen natural populations of Crataegus pontica K.Koch was assessed for the first time using three genome-based molecular techniques; inter-retrotransposon amplified polymorphism (IRAP); inter-simple sequence repeats (ISSR) and start codon targeted (SCoT) polymorphism. IRAP, ISSR and SCoT analyses yielded 126, 254 and 199 scorable amplified bands, respectively, of which 90.48, 93.37 and 83.78% were polymorphic. ISSR revealed efficiency over IRAP and SCoT due to high effective multiplex ratio, marker index and resolving power. The dendrograms based on the markers used and combined data divided individuals into three major clusters. The correlation between the coefficient matrices for the IRAP, ISSR and SCoT data was significant. A higher level of genetic variation was observed within populations than among populations based on the markers used. The lower divergence levels depicted among the studied populations could be seen as evidence of gene flow. The promotion of gene exchange will be very beneficial to conserve and utilize the enormous genetic variability. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Inter-subject Functional Correlation Reveal a Hierarchical Organization of Extrinsic and Intrinsic Systems in the Brain.

    PubMed

    Ren, Yudan; Nguyen, Vinh Thai; Guo, Lei; Guo, Christine Cong

    2017-09-07

    The brain is constantly monitoring and integrating both cues from the external world and signals generated intrinsically. These extrinsically and intrinsically-driven neural processes are thought to engage anatomically distinct regions, which are thought to constitute the extrinsic and intrinsic systems of the brain. While the specialization of extrinsic and intrinsic system is evident in primary and secondary sensory cortices, a systematic mapping of the whole brain remains elusive. Here, we characterized the extrinsic and intrinsic functional activities in the brain during naturalistic movie-viewing. Using a novel inter-subject functional correlation (ISFC) analysis, we found that the strength of ISFC shifts along the hierarchical organization of the brain. Primary sensory cortices appear to have strong inter-subject functional correlation, consistent with their role in processing exogenous information, while heteromodal regions that attend to endogenous processes have low inter-subject functional correlation. Those brain systems with higher intrinsic tendency show greater inter-individual variability, likely reflecting the aspects of brain connectivity architecture unique to individuals. Our study presents a novel framework for dissecting extrinsically- and intrinsically-driven processes, as well as examining individual differences in brain function during naturalistic stimulation.

  18. An analysis of the financial crisis in the KOSPI market using Hurst exponents

    NASA Astrophysics Data System (ADS)

    Yim, Kyubin; Oh, Gabjin; Kim, Seunghwan

    2014-09-01

    Recently, the study of the financial crisis has progressed to include the concept of the complex system, thereby improving the understanding of this extreme event from a neoclassical economic perspective. To determine which variables are related to the financial event caused by the 2008 US subprime crisis using temporal correlations, we investigate the diverse variables that may explain the financial system. These variables include return, volatility, trading volume and inter-trade duration data sets within the TAQ data for 27 highly capitalized individual companies listed on the KOSPI stock market. During 2008 and 2009, the Hurst exponent for the return time series over the whole period was less than 0.5, and the Hurst exponents for other variables, such as the volatility, trading volume and inter-trade duration, were greater than 0.5. Additionally, we analyze the relationships between the variation of temporal correlation and market instability based on these Hurst exponents and the degree of multifractality. We find that for the data related to trading volume, the Hurst exponents do not allow us to detect changes in market status, such as changes from normal to abnormal status, whereas other variables, including the return, volatility and weekly inter-trade duration, indicate a significant change in market status after the Lehman Brothers' bankruptcy. In addition, the multifractality and the measurement defined by subtracting the Hurst exponent of the return time series from that of the volatility time series decrease sharply after the US subprime event and recover approximately 50 days after the Lehman Brothers' collapse. Our findings suggest that the temporal features of financial quantities in the TAQ data set and the market complexity perform very well at diagnosing financial market stability.

  19. Variability in EIT Images of Lung Ventilation as a Function of Electrode Planes and Body Positions

    PubMed Central

    Zhang, Jie; Patterson, Robert

    2014-01-01

    This study is aimed at investigating the variability in resistivity changes in the lung region as a function of air volume, electrode plane and body position. Six normal subjects (33.8 ± 4.7 years, range from 26 to 37 years) were studied using the Sheffield Electrical Impedance Tomography (EIT) portable system. Three transverse planes at the level of second intercostal space, the level of the xiphisternal joint, and midway between upper and lower locations were chosen for measurements. For each plane, sixteen electrodes were uniformly positioned around the thorax. Data were collected with the breath held at end expiration and after inspiring 0.5, 1.0, or 1.5 liters of air from end expiration, with the subject in both the supine and sitting position. The average resistivity change in five regions, two 8x8 pixel local regions in the right lung, entire right, entire left and total lung regions, were calculated. The results show the resistivity change averaged over electrode positions and subject positions was 7-9% per liter of air, with a slightly larger resistivity change of 10 % per liter air in the lower electrode plane. There was no significant difference (p>0.05) between supine and sitting. The two 8x8 regions show a larger inter individual variability (coefficient of variation, CV, is from 30% to 382%) compared to the entire left, entire right and total lung (CV is from 11% to 51%). The results for the global regions are more consistent. The large inter individual variability appears to be a problem for clinical applications of EIT, such as regional ventilation. The variability may be mitigated by choosing appropriate electrode plane, body position and region of interest for the analysis. PMID:25110529

  20. Smoking and Female Sex: Independent Predictors of Human Vascular Smooth Muscle Cells Stiffening

    PubMed Central

    Dinardo, Carla Luana; Santos, Hadassa Campos; Vaquero, André Ramos; Martelini, André Ricardo; Dallan, Luis Alberto Oliveira; Alencar, Adriano Mesquita; Krieger, José Eduardo; Pereira, Alexandre Costa

    2015-01-01

    Aims Recent evidence shows the rigidity of vascular smooth muscle cells (VSMC) contributes to vascular mechanics. Arterial rigidity is an independent cardiovascular risk factor whose associated modifications in VSMC viscoelasticity have never been investigated. This study’s objective was to evaluate if the arterial rigidity risk factors aging, African ancestry, female sex, smoking and diabetes mellitus are associated with VMSC stiffening in an experimental model using a human derived vascular smooth muscle primary cell line repository. Methods Eighty patients subjected to coronary artery bypass surgery were enrolled. VSMCs were extracted from internal thoracic artery fragments and mechanically evaluated using Optical Magnetic Twisting Cytometry assay. The obtained mechanical variables were correlated with the clinical variables: age, gender, African ancestry, smoking and diabetes mellitus. Results The mechanical variables Gr, G’r and G”r had a normal distribution, demonstrating an inter-individual variability of VSMC viscoelasticity, which has never been reported before. Female sex and smoking were independently associated with VSMC stiffening: Gr (apparent cell stiffness) p = 0.022 and p = 0.018, R2 0.164; G’r (elastic modulus) p = 0.019 and p = 0.009, R2 0.184 and G”r (dissipative modulus) p = 0.011 and p = 0.66, R2 0.141. Conclusion Female sex and smoking are independent predictors of VSMC stiffening. This pro-rigidity effect represents an important element for understanding the vascular rigidity observed in post-menopausal females and smokers, as well as a potential therapeutic target to be explored in the future. There is a significant inter-individual variation of VSMC viscoelasticity, which is slightly modulated by clinical variables and probably relies on molecular factors. PMID:26661469

  1. Variability in EIT Images of Lung Ventilation as a Function of Electrode Planes and Body Positions.

    PubMed

    Zhang, Jie; Patterson, Robert

    2014-01-01

    This study is aimed at investigating the variability in resistivity changes in the lung region as a function of air volume, electrode plane and body position. Six normal subjects (33.8 ± 4.7 years, range from 26 to 37 years) were studied using the Sheffield Electrical Impedance Tomography (EIT) portable system. Three transverse planes at the level of second intercostal space, the level of the xiphisternal joint, and midway between upper and lower locations were chosen for measurements. For each plane, sixteen electrodes were uniformly positioned around the thorax. Data were collected with the breath held at end expiration and after inspiring 0.5, 1.0, or 1.5 liters of air from end expiration, with the subject in both the supine and sitting position. The average resistivity change in five regions, two 8x8 pixel local regions in the right lung, entire right, entire left and total lung regions, were calculated. The results show the resistivity change averaged over electrode positions and subject positions was 7-9% per liter of air, with a slightly larger resistivity change of 10 % per liter air in the lower electrode plane. There was no significant difference (p>0.05) between supine and sitting. The two 8x8 regions show a larger inter individual variability (coefficient of variation, CV, is from 30% to 382%) compared to the entire left, entire right and total lung (CV is from 11% to 51%). The results for the global regions are more consistent. The large inter individual variability appears to be a problem for clinical applications of EIT, such as regional ventilation. The variability may be mitigated by choosing appropriate electrode plane, body position and region of interest for the analysis.

  2. Impacts of correcting the inter-variable correlation of climate model outputs on hydrological modeling

    NASA Astrophysics Data System (ADS)

    Chen, Jie; Li, Chao; Brissette, François P.; Chen, Hua; Wang, Mingna; Essou, Gilles R. C.

    2018-05-01

    Bias correction is usually implemented prior to using climate model outputs for impact studies. However, bias correction methods that are commonly used treat climate variables independently and often ignore inter-variable dependencies. The effects of ignoring such dependencies on impact studies need to be investigated. This study aims to assess the impacts of correcting the inter-variable correlation of climate model outputs on hydrological modeling. To this end, a joint bias correction (JBC) method which corrects the joint distribution of two variables as a whole is compared with an independent bias correction (IBC) method; this is considered in terms of correcting simulations of precipitation and temperature from 26 climate models for hydrological modeling over 12 watersheds located in various climate regimes. The results show that the simulated precipitation and temperature are considerably biased not only in the individual distributions, but also in their correlations, which in turn result in biased hydrological simulations. In addition to reducing the biases of the individual characteristics of precipitation and temperature, the JBC method can also reduce the bias in precipitation-temperature (P-T) correlations. In terms of hydrological modeling, the JBC method performs significantly better than the IBC method for 11 out of the 12 watersheds over the calibration period. For the validation period, the advantages of the JBC method are greatly reduced as the performance becomes dependent on the watershed, GCM and hydrological metric considered. For arid/tropical and snowfall-rainfall-mixed watersheds, JBC performs better than IBC. For snowfall- or rainfall-dominated watersheds, however, the two methods behave similarly, with IBC performing somewhat better than JBC. Overall, the results emphasize the advantages of correcting the P-T correlation when using climate model-simulated precipitation and temperature to assess the impact of climate change on watershed hydrology. However, a thorough validation and a comparison with other methods are recommended before using the JBC method, since it may perform worse than the IBC method for some cases due to bias nonstationarity of climate model outputs.

  3. Global Genetic Variations Predict Brain Response to Faces

    PubMed Central

    Dickie, Erin W.; Tahmasebi, Amir; French, Leon; Kovacevic, Natasa; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun; Büchel, Christian; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Gallinat, Juergen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Nichols, Thomas; Lathrop, Mark; Loth, Eva; Pausova, Zdenka; Rietschel, Marcela; Smolka, Michal N.; Ströhle, Andreas; Toro, Roberto; Schumann, Gunter; Paus, Tomáš

    2014-01-01

    Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40–50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R2 = 0.38, p<0.001). Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R2 = 0.32, p<0.001). Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co-opting these regions into the face network. PMID:25122193

  4. SU-E-J-275: Impact of the Intra and Inter Observer Variability in the Delineation of Parotid Glands On the Dose Calculation During Head and Neck Helical Tomotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jodda, A; Piotrowski, T

    2014-06-01

    Purpose: The intra- and inter-observer variability in delineation of the parotids on the kilo-voltage computed tomography (kVCT) and mega-voltage computed tomography (MVCT) were examined to establish their impact on the dose calculation during adaptive head and neck helical tomotherapy (HT). Methods: Three observers delineated left and right parotids for ten randomly selected patients with oropharynx cancer treated on HT. The pre-treatment kVCT and the MVCT from the first fraction of irradiation were selected to delineation. The delineation procedure was repeated three times by each observer. The parotids were delineated according to the institutional protocol. The analyses included intra-observer reproducibility andmore » inter-structure, -observer and -modality variability of the volume and dose. Results: The differences between the left and right parotid outlines were not statistically significant (p>0.3). The reproducibility of the delineation was confirmed for each observer on the kVCT (p>0.2) and on the MVCT (p>0.1). The inter-observer variability of the outlines was significant (p<0.001) as well as the inter-modality variability (p<0.006). The parotids delineated on the MVCT were 10% smaller than on the kVCT. The inter-observer variability of the parotids delineation did not affect the average dose (p=0.096 on the kVCT and p=0.176 on the MVCT). The dose calculated on the MVCT was higher by 3.3% than dose from the kVCT (p=0.009). Conclusion: Usage of the institutional protocols for the parotids delineation reduces intra-observer variability and increases reproducibility of the outlines. These protocols do not eliminate delineation differences between the observers, but these differences are not clinically significant and do not affect average doses in the parotids. The volumes of the parotids delineated on the MVCT are smaller than on the kVCT, which affects the differences in the calculated doses.« less

  5. Characterizing individual differences in functional connectivity using dual-regression and seed-based approaches.

    PubMed

    Smith, David V; Utevsky, Amanda V; Bland, Amy R; Clement, Nathan; Clithero, John A; Harsch, Anne E W; McKell Carter, R; Huettel, Scott A

    2014-07-15

    A central challenge for neuroscience lies in relating inter-individual variability to the functional properties of specific brain regions. Yet, considerable variability exists in the connectivity patterns between different brain areas, potentially producing reliable group differences. Using sex differences as a motivating example, we examined two separate resting-state datasets comprising a total of 188 human participants. Both datasets were decomposed into resting-state networks (RSNs) using a probabilistic spatial independent component analysis (ICA). We estimated voxel-wise functional connectivity with these networks using a dual-regression analysis, which characterizes the participant-level spatiotemporal dynamics of each network while controlling for (via multiple regression) the influence of other networks and sources of variability. We found that males and females exhibit distinct patterns of connectivity with multiple RSNs, including both visual and auditory networks and the right frontal-parietal network. These results replicated across both datasets and were not explained by differences in head motion, data quality, brain volume, cortisol levels, or testosterone levels. Importantly, we also demonstrate that dual-regression functional connectivity is better at detecting inter-individual variability than traditional seed-based functional connectivity approaches. Our findings characterize robust-yet frequently ignored-neural differences between males and females, pointing to the necessity of controlling for sex in neuroscience studies of individual differences. Moreover, our results highlight the importance of employing network-based models to study variability in functional connectivity. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. An IRT Model with a Parameter-Driven Process for Change

    ERIC Educational Resources Information Center

    Rijmen, Frank; De Boeck, Paul; van der Maas, Han L. J.

    2005-01-01

    An IRT model with a parameter-driven process for change is proposed. Quantitative differences between persons are taken into account by a continuous latent variable, as in common IRT models. In addition, qualitative inter-individual differences and auto-dependencies are accounted for by assuming within-subject variability with respect to the…

  7. Genome-wide interactions with dairy intake for body mass index in adults of European descent

    USDA-ARS?s Scientific Manuscript database

    Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. We conducted a genome-wide interaction study to discover genetic variants that account for variation in BMI in the c...

  8. Single-Cell Memory Regulates a Neural Circuit for Sensory Behavior.

    PubMed

    Kobayashi, Kyogo; Nakano, Shunji; Amano, Mutsuki; Tsuboi, Daisuke; Nishioka, Tomoki; Ikeda, Shingo; Yokoyama, Genta; Kaibuchi, Kozo; Mori, Ikue

    2016-01-05

    Unveiling the molecular and cellular mechanisms underlying memory has been a challenge for the past few decades. Although synaptic plasticity is proven to be essential for memory formation, the significance of "single-cell memory" still remains elusive. Here, we exploited a primary culture system for the analysis of C. elegans neurons and show that a single thermosensory neuron has an ability to form, retain, and reset a temperature memory. Genetic and proteomic analyses found that the expression of the single-cell memory exhibits inter-individual variability, which is controlled by the evolutionarily conserved CaMKI/IV and Raf pathway. The variable responses of a sensory neuron influenced the neural activity of downstream interneurons, suggesting that modulation of the sensory neurons ultimately determines the behavioral output in C. elegans. Our results provide proof of single-cell memory and suggest that the individual differences in neural responses at the single-cell level can confer individuality. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Variability in emotional responsiveness and coping style during active avoidance as a window onto psychological vulnerability to stress.

    PubMed

    Gorka, Adam X; LaBar, Kevin S; Hariri, Ahmad R

    2016-05-01

    Individual differences in coping styles are associated with psychological vulnerability to stress. Recent animal research suggests that coping styles reflect trade-offs between proactive and reactive threat responses during active avoidance paradigms, with proactive responses associated with better stress tolerance. Based on these preclinical findings, we developed a novel instructed active avoidance paradigm to characterize patterns of proactive and reactive responses using behavioral, motoric, and autonomic measures in humans. Analyses revealed significant inter-individual variability not only in the magnitude of general emotional responsiveness but also the likelihood to specifically express proactive or reactive responses. In men but not women, individual differences in general emotional responsiveness were linked to increased trait anxiety while proactive coping style was linked to increased trait aggression. These patterns are consistent with preclinical findings and suggest that instructed active avoidance paradigms may be useful in assessing psychological vulnerability to stress using objective behavioral measures. Copyright © 2016. Published by Elsevier Inc.

  10. Inter-individual differences in sleep response to shift work in novice police officers - A prospective study.

    PubMed

    Lammers-van der Holst, Heidi M; Van Dongen, Hans P A; Drosopoulos, Spyridon; Kerkhof, Gerard A

    2016-01-01

    The aim of this longitudinal study on novice police officers was to investigate inter-individual differences in sleep response to shift work, and to identify potential baseline predictors thereof. A total of 42 subjects were assessed at baseline, prior to commencing shift work. They were re-assessed during three follow-up sessions within the first 2 years of shift work exposure after approximately 4, 12, and 20 months of rotating shift work. Wrist actigraphy and sleep logs were used to investigate nocturnal sleep at baseline and daytime sleep after night shifts during the follow-up sessions. Actigraphically estimated total sleep time and subjective sleep quality were analyzed as outcome variables, using mixed-effects analysis of variance. Systematic inter-individual differences were observed in the overall response of these outcome variables to shift work. In this sample, flexibility of sleeping habits and gender were found to be predictors of daytime total sleep time in the first 2 years of shift work exposure. Flexibility of sleeping habits and subjective quality of nighttime sleep prior to shift work were found to be predictors of subjective quality of daytime sleep. These results suggest that it may be possible to detect and even predict sleep deficiencies in response to shift work early on, which could be a basis for the development of individualized interventions to improve shift work tolerance.

  11. Lumbar facet anatomy changes in spondylolysis: a comparative skeletal study.

    PubMed

    Masharawi, Youssef; Dar, Gali; Peleg, Smadar; Steinberg, Nili; Alperovitch-Najenson, Dvora; Salame, Khalil; Hershkovitz, Israel

    2007-07-01

    Opinions differ as to the exact mechanism responsible for spondylolysis (SP) and whether individuals with specific morphological characteristics of the lumbar vertebral neural arch are predisposed to SP. The aim of our study was to reveal the association between SP and the architecture of lumbar articular facets and the inter-facet region. Using a Microscribe three-dimensional apparatus (Immersion Co., San Jose, CA, USA), length, width and depth of all articular facets and all inter-facet distances in the lumbar spine (L1-L5) were measured. From the Hamann-Todd Human Osteological Collection (Cleveland Museum of Natural History, OH, USA) 120 normal male skeletons with lumbar spines in the control group and 115 with bilateral SP at L5 were selected. Analysis of variance was employed to examine the differences between spondylolytic and normal spines. Three profound differences between SP and the norm appeared: (1) in individuals with SP, the size and shape of L4's neural arch had significantly greater inter-facet widths, significantly shorter inter-facet heights and significantly shorter and narrower articular facets; (2) only in the L4 vertebra in individuals with SP was the inferior inter-facet width greater in size than the superior inter-facet width of the vertebra below (L5) (38.7 mm versus 40 mm); (3) in all lumbar vertebrae, the right inferior articular facets in individuals with SP were flatter compared to the control group. Individuals with L4 "SP" characteristics are at a greater risk of developing fatigue fractures in the form of spondylolysis at L5.

  12. Systolic time interval v heart rate regression equations using atropine: reproducibility studies.

    PubMed Central

    Kelman, A W; Sumner, D J; Whiting, B

    1981-01-01

    1. Systolic time intervals (STI) were recorded in six normal male subjects over a period of 3 weeks. On one day per week, each subject received incremental doses of atropine intravenously to increase heart rate, allowing the determination of individual STI v HR regression equations. On the other days STI were recorded with the subjects resting, in the supine position. 2. There were highly significant regression relationships between heart rate and both LVET and QS2, but not between heart rate and PEP. 3. The regression relationships showed little intra-subject variability, but a large degree of inter-subject variability: they proved adequate to correct the STI for the daily fluctuations in heart rate. 4. Administration of small doses of atropine intravenously provides a satisfactory and convenient method of deriving individual STI v HR regression equations which can be applied over a period of weeks. PMID:7248136

  13. Systolic time interval v heart rate regression equations using atropine: reproducibility studies.

    PubMed

    Kelman, A W; Sumner, D J; Whiting, B

    1981-07-01

    1. Systolic time intervals (STI) were recorded in six normal male subjects over a period of 3 weeks. On one day per week, each subject received incremental doses of atropine intravenously to increase heart rate, allowing the determination of individual STI v HR regression equations. On the other days STI were recorded with the subjects resting, in the supine position. 2. There were highly significant regression relationships between heart rate and both LVET and QS2, but not between heart rate and PEP. 3. The regression relationships showed little intra-subject variability, but a large degree of inter-subject variability: they proved adequate to correct the STI for the daily fluctuations in heart rate. 4. Administration of small doses of atropine intravenously provides a satisfactory and convenient method of deriving individual STI v HR regression equations which can be applied over a period of weeks.

  14. Reliability and Concurrent Validity of Dynamic Rotator Stability Test-A Cross Sectional study.

    PubMed

    Binoy Mathew, K V; Eapen, Charu; Kumar, P Senthil

    2012-01-01

    To find intra rater and inter rater reliability of Dynamic Rotator Stability Test (DRST) and to find concurrent validity of Dynamic Rotator Stability Test (DRST) with University of Pennsylvania Shoulder Score (PENN) Scale. 40 subjects of either gender between the age group of 18-70 with painful shoulder conditions of musculoskeletal origin was selected through convenient sampling. Tester 1 and tester 2 administered DRST and PENN scale randomly. In a subgroup of 20 subjects DRST was administered by both the testers to find the inter rater reliability. 180° Standard Universal Goniometer was used to take measurements. For intra-rater reliability, all the test variables were showing highly significant correlation (p=.94 - 1). For inter -rater, with tester 2, test variables like position, ROM, force, direction of abnormal translation, pain during the test, compensatory movement during test were found to be significant (p=.71-1).only some variables of DRST showed significant correlation with PENN scale (P=.320-.450). Dynamic Rotator Stability Test has good intra rater and moderate inter rater reliability. Concurrent validity of Dynamic Rotator Stability Test was found to be poor when compared to PENN Shoulder Score.

  15. Correlations of Handgrip Strength with Selected Hand-Arm-Anthropometric Variables in Indian Inter-university Female Volleyball Players

    PubMed Central

    Koley, Shyamal; Pal Kaur, Satinder

    2011-01-01

    Purpose The purpose of this study was to estimate the dominant handgrip strength and its correlations with some hand and arm anthropometric variables in 101 randomly selected Indian inter-university female volleyball players aged 18-25 years (mean age 20.52±1.40) from six Indian universities. Methods Three anthropometric variables, i.e. height, weight, BMI, two hand anthropometric variables, viz. right and left hand width and length, four arm anthropometric variables, i.e. upper arm length, lower arm length, upper extremity length, upper arm circumference and dominant right and non-dominant handgrip strength were measured among Indian inter-university female volleyball players by standard anthropometric techniques. Results The findings of the present study indicated that Indian female volleyball players had higher mean values in eleven variables and lesser mean values in two variables than their control counterparts, showing significant differences (P<0.032-0.001) in height (t=2.63), weight (t=8.66), left hand width (t=2.10), left and right hand length (t=9.99 and 10.40 respectively), right upper arm length (t=8.48), right forearm length (t=5.41), dominant (right) and non-dominant (left) handgrip strength (t=9.37 and 6.76 respectively). In female volleyball players, dominant handgrip strength had significantly positive correlations (P=0.01) with all the variables studied. Conclusion It may be concluded that dominant handgrip strength had strong positive correlations with all the variables studied in Indian inter-university female volleyball players. PMID:22375242

  16. Individual variability in reproductive success determines winners and losers under ocean acidification: a case study with sea urchins.

    PubMed

    Schlegel, Peter; Havenhand, Jon N; Gillings, Michael R; Williamson, Jane E

    2012-01-01

    Climate change will lead to intense selection on many organisms, particularly during susceptible early life stages. To date, most studies on the likely biotic effects of climate change have focused on the mean responses of pooled groups of animals. Consequently, the extent to which inter-individual variation mediates different selection responses has not been tested. Investigating this variation is important, since some individuals may be preadapted to future climate scenarios. We examined the effect of CO(2)-induced pH changes ("ocean acidification") in sperm swimming behaviour on the fertilization success of the Australasian sea urchin Heliocidaris erythrogramma, focusing on the responses of separate individuals and pairs. Acidification significantly decreased the proportion of motile sperm but had no effect on sperm swimming speed. Subsequent fertilization experiments showed strong inter-individual variation in responses to ocean acidification, ranging from a 44% decrease to a 14% increase in fertilization success. This was partly explained by the significant relationship between decreases in percent sperm motility and fertilization success at ΔpH = 0.3, but not at ΔpH = 0.5. The effects of ocean acidification on reproductive success varied markedly between individuals. Our results suggest that some individuals will exhibit enhanced fertilization success in acidified oceans, supporting the concept of 'winners' and 'losers' of climate change at an individual level. If these differences are heritable it is likely that ocean acidification will lead to selection against susceptible phenotypes as well as to rapid fixation of alleles that allow reproduction under more acidic conditions. This selection may ameliorate the biotic effects of climate change if taxa have sufficient extant genetic variation upon which selection can act.

  17. Quantitative image feature variability amongst CT scanners with a controlled scan protocol

    NASA Astrophysics Data System (ADS)

    Ger, Rachel B.; Zhou, Shouhao; Chi, Pai-Chun Melinda; Goff, David L.; Zhang, Lifei; Lee, Hannah J.; Fuller, Clifton D.; Howell, Rebecca M.; Li, Heng; Stafford, R. Jason; Court, Laurence E.; Mackin, Dennis S.

    2018-02-01

    Radiomics studies often analyze patient computed tomography (CT) images acquired from different CT scanners. This may result in differences in imaging parameters, e.g. different manufacturers, different acquisition protocols, etc. However, quantifiable differences in radiomics features can occur based on acquisition parameters. A controlled protocol may allow for minimization of these effects, thus allowing for larger patient cohorts from many different CT scanners. In order to test radiomics feature variability across different CT scanners a radiomics phantom was developed with six different cartridges encased in high density polystyrene. A harmonized protocol was developed to control for tube voltage, tube current, scan type, pitch, CTDIvol, convolution kernel, display field of view, and slice thickness across different manufacturers. The radiomics phantom was imaged on 18 scanners using the control protocol. A linear mixed effects model was created to assess the impact of inter-scanner variability with decomposition of feature variation between scanners and cartridge materials. The inter-scanner variability was compared to the residual variability (the unexplained variability) and to the inter-patient variability using two different patient cohorts. The patient cohorts consisted of 20 non-small cell lung cancer (NSCLC) and 30 head and neck squamous cell carcinoma (HNSCC) patients. The inter-scanner standard deviation was at least half of the residual standard deviation for 36 of 49 quantitative image features. The ratio of inter-scanner to patient coefficient of variation was above 0.2 for 22 and 28 of the 49 features for NSCLC and HNSCC patients, respectively. Inter-scanner variability was a significant factor compared to patient variation in this small study for many of the features. Further analysis with a larger cohort will allow more thorough analysis with additional variables in the model to truly isolate the interscanner difference.

  18. Isogenic blood-brain barrier models based on patient-derived stem cells display inter-individual differences in cell maturation and functionality.

    PubMed

    Patel, Ronak; Page, Shyanne; Al-Ahmad, Abraham Jacob

    2017-07-01

    The blood-brain barrier (BBB) constitutes an important component of the neurovascular unit formed by specialized brain microvascular endothelial cells (BMECs) surrounded by astrocytes, pericytes, and neurons. Recently, isogenic in vitro models of the BBB based on human pluripotent stem cells have been documented, yet the impact of inter-individual variability on the yield and phenotype of such models remains to be documented. In this study, we investigated the impact of inter-individual variability on the yield and phenotype of isogenic models of the BBB, using patient-derived induced pluripotent stem cells (iPSCs). Astrocytes, BMECs, and neurons were differentiated from four asymptomatic patient-derived iPSCs (two males, two females). We differentiated such cells using existing differentiation protocols and quantified expression of cell lineage markers, as well as BBB phenotype, barrier induction, and formation of neurite processes. iPSC-derived BMECs showed barrier properties better than hCMEC/D3 monolayers; however, we noted differences in the expression and activity among iPSC lines. In addition, we noted differences in the differentiation efficiency of these cells into neural stem cells and progenitor cells (as noted by differences in expression of cell lineage markers). Such differences were reflected later in the terminal differentiation, as seen as ability to induce barrier function and to form neurite processes. Although we demonstrated our ability to obtain an isogenic model of the BBB with different patients' iPSCs, we also noted subtle differences in the expression of cell lineage markers and cell maturation processes, suggesting the presence of inter-individual polymorphisms. © 2017 International Society for Neurochemistry.

  19. Strength of baseline inter-trial correlations forecasts adaptive capacity in the vestibulo-ocular reflex

    PubMed Central

    Beaton, Kara H.; Wong, Aaron L.; Lowen, Steven B.

    2017-01-01

    Individual differences in sensorimotor adaptability may permit customized training protocols for optimum learning. Here, we sought to forecast individual adaptive capabilities in the vestibulo-ocular reflex (VOR). Subjects performed 400 head-rotation steps (400 trials) during a baseline test, followed by 20 min of VOR gain adaptation. All subjects exhibited mean baseline VOR gain of approximately 1.0, variable from trial to trial, and showed desired reductions in gain following adaptation with variation in extent across individuals. The extent to which a given subject adapted was inversely proportional to a measure of the strength and duration of baseline inter-trial correlations (β). β is derived from the decay of the autocorrelation of the sequence of VOR gains, and describes how strongly correlated are past gain values; it thus indicates how much the VOR gain on any given trial is informed by performance on previous trials. To maximize the time that images are stabilized on the retina, the VOR should maintain a gain close to 1.0 that is adjusted predominantly according to the most recent error; hence, it is not surprising that individuals who exhibit smaller β (weaker inter-trial correlations) also exhibited the best adaptation. Our finding suggests that the temporal structure of baseline behavioral data contains important information that may aid in forecasting adaptive capacities. This has significant implications for the development of personalized physical therapy protocols for patients, and for other cases when it is necessary to adjust motor programs to maintain movement accuracy in response to pathological and environmental changes. PMID:28380076

  20. Ecological bridges and barriers in pelagic ecosystems

    NASA Astrophysics Data System (ADS)

    Briscoe, Dana K.; Hobday, Alistair J.; Carlisle, Aaron; Scales, Kylie; Eveson, J. Paige; Arrizabalaga, Haritz; Druon, Jean Noel; Fromentin, Jean-Marc

    2017-06-01

    Many highly mobile species are known to use persistent pathways or corridors to move between habitat patches in which conditions are favorable for particular activities, such as breeding or foraging. In the marine realm, environmental variability can lead to the development of temporary periods of anomalous oceanographic conditions that can connect individuals to areas of habitat outside a population's usual range, or alternatively, restrict individuals from areas usually within their range, thus acting as ecological bridges or ecological barriers. These temporary features can result in novel or irregular trophic interactions and changes in population spatial dynamics, and, therefore, may have significant implications for management of marine ecosystems. Here, we provide evidence of ecological bridges and barriers in different ocean regions, drawing upon five case studies in which particular oceanographic conditions have facilitated or restricted the movements of individuals from highly migratory species. We discuss the potential population-level significance of ecological bridges and barriers, with respect to the life history characteristics of different species, and inter- and intra-population variability in habitat use. Finally, we summarize the persistence of bridge dynamics with time, our ability to monitor bridges and barriers in a changing climate, and implications for forecasting future climate-mediated ecosystem change.

  1. Genetics of human body size and shape: body proportions and indices.

    PubMed

    Livshits, Gregory; Roset, A; Yakovenko, K; Trofimov, S; Kobyliansky, E

    2002-01-01

    The study of the genetic component in morphological variables such as body height and weight, head and chest circumference, etc. has a rather long history. However, only a few studies investigated body proportions and configuration. The major aim of the present study was to evaluate the extent of the possible genetic effects on the inter-individual variation of a number of body configuration indices amenable to clear functional interpretation. Two ethnically different pedigree samples were used in the study: (1) Turkmenians (805 individuals) from Central Asia, and (2) Chuvasha (732 individuals) from the Volga riverside, Russian Federation. To achieve the aim of the present study we proposed three new indices, which were subjected to a statistical-genetic analysis using modified version of "FISHER" software. The proposed indices were: (1) an integral index of torso volume (IND#1), an index reflecting a predisposition of body proportions to maintain a balance in a vertical position (IND#2), and an index of skeletal extremities volume (IND#3). Additionally, the first two principal factors (PF1 and PF2) obtained on 19 measurements of body length and breadth were subjected to genetic analysis. Variance decomposition analysis that simultaneously assess the contribution of gender, age, additive genetic effects and effects of environment shared by the nuclear family members, was applied to fit variation of the above three indices, and PF1 and PF2. The raw familial correlation of all study traits and in both samples showed: (1) all marital correlations did not differ significantly from zero; (2) parent-offspring and sibling correlations were all positive and statistically significant. The parameter estimates obtained in variance analyses showed that from 40% to 75% of inter-individual variation of the studied traits (adjusted for age and sex) were attributable to genetic effects. For PF1 and PF2 in both samples, and for IND#2 (in Chuvasha pedigrees), significant common sib environmental effects were also detectable. Genetic factors substantially influence inter-individual differences in body shape and configuration in two studied samples. However, further studies are needed to clarify the extent of pleiotropy and epigenetic effects on various facets of the human physique.

  2. Atlantic Leatherback Migratory Paths and Temporary Residence Areas

    PubMed Central

    López-Mendilaharsu, Milagros; Miller, Philip; Domingo, Andrés; Evans, Daniel; Kelle, Laurent; Plot, Virginie; Prosdocimi, Laura; Verhage, Sebastian; Gaspar, Philippe; Georges, Jean-Yves

    2010-01-01

    Background Sea turtles are long-distance migrants with considerable behavioural plasticity in terms of migratory patterns, habitat use and foraging sites within and among populations. However, for the most widely migrating turtle, the leatherback turtle Dermochelys coriacea, studies combining data from individuals of different populations are uncommon. Such studies are however critical to better understand intra- and inter-population variability and take it into account in the implementation of conservation strategies of this critically endangered species. Here, we investigated the movements and diving behaviour of 16 Atlantic leatherback turtles from three different nesting sites and one foraging site during their post-breeding migration to assess the potential determinants of intra- and inter-population variability in migratory patterns. Methodology/Principal Findings Using satellite-derived behavioural and oceanographic data, we show that turtles used Temporary Residence Areas (TRAs) distributed all around the Atlantic Ocean: 9 in the neritic domain and 13 in the oceanic domain. These TRAs did not share a common oceanographic determinant but on the contrary were associated with mesoscale surface oceanographic features of different types (i.e., altimetric features and/or surface chlorophyll a concentration). Conversely, turtles exhibited relatively similar horizontal and vertical behaviours when in TRAs (i.e., slow swimming velocity/sinuous path/shallow dives) suggesting foraging activity in these productive regions. Migratory paths and TRAs distribution showed interesting similarities with the trajectories of passive satellite-tracked drifters, suggesting that the general dispersion pattern of adults from the nesting sites may reflect the extent of passive dispersion initially experienced by hatchlings. Conclusions/Significance Intra- and inter-population behavioural variability may therefore be linked with initial hatchling drift scenarios and be highly influenced by environmental conditions. This high degree of behavioural plasticity in Atlantic leatherback turtles makes species-targeted conservation strategies challenging and stresses the need for a larger dataset (>100 individuals) for providing general recommendations in terms of conservation. PMID:21085472

  3. Lumbar facet anatomy changes in spondylolysis: a comparative skeletal study

    PubMed Central

    Dar, Gali; Peleg, Smadar; Steinberg, Nili; Alperovitch-Najenson, Dvora; Salame, Khalil; Hershkovitz, Israel

    2007-01-01

    Opinions differ as to the exact mechanism responsible for spondylolysis (SP) and whether individuals with specific morphological characteristics of the lumbar vertebral neural arch are predisposed to SP. The aim of our study was to reveal the association between SP and the architecture of lumbar articular facets and the inter-facet region. Methods: Using a Microscribe three-dimensional apparatus (Immersion Co., San Jose, CA, USA), length, width and depth of all articular facets and all inter-facet distances in the lumbar spine (L1–L5) were measured. From the Hamann-Todd Human Osteological Collection (Cleveland Museum of Natural History, OH, USA) 120 normal male skeletons with lumbar spines in the control group and 115 with bilateral SP at L5 were selected. Analysis of variance was employed to examine the differences between spondylolytic and normal spines. Results: Three profound differences between SP and the norm appeared: (1) in individuals with SP, the size and shape of L4’s neural arch had significantly greater inter-facet widths, significantly shorter inter-facet heights and significantly shorter and narrower articular facets; (2) only in the L4 vertebra in individuals with SP was the inferior inter-facet width greater in size than the superior inter-facet width of the vertebra below (L5) (38.7 mm versus 40 mm); (3) in all lumbar vertebrae, the right inferior articular facets in individuals with SP were flatter compared to the control group. Conclusions: Individuals with L4 “SP” characteristics are at a greater risk of developing fatigue fractures in the form of spondylolysis at L5. PMID:17440753

  4. Genetic polymorphisms in the amino acid transporters LAT1 and LAT2 in relation to the pharmacokinetics and side effects of melphalan.

    PubMed

    Kühne, Annett; Kaiser, Rolf; Schirmer, Markus; Heider, Ulrike; Muhlke, Sabine; Niere, Wiebke; Overbeck, Tobias; Hohloch, Karin; Trümper, Lorenz; Sezer, Orhan; Brockmöller, Jürgen

    2007-07-01

    Melphalan is widely used in the treatment of multiple myeloma. Pharmacokinetics of this alkylating drug shows high inter-individual variability. As melphalan is a phenylalanine derivative, the pharmacokinetic variability may be determined by genetic polymorphisms in the L-type amino acid transporters LAT1 (SLC7A5) and LAT2 (SLC7A8). Pharmacokinetics were analysed in 64 patients after first administration of intravenous melphalan. Severity of side effects was documented according to WHO criteria. Genomic DNA was analysed for polymorphisms in LAT1 and LAT2 by sequencing of the entire coding region, intron-exon boundaries and 2 kb upstream promoter region. Selected polymorphisms in the common heavy chain of both transporters, the protein 4F2hc (SLC3A2), were analysed by single nucleotide primer extension. Melphalan pharmacokinetics was highly variable with up to 6.2-fold differences in total clearance. A total of 44 polymorphisms were identified in LAT1 and 21 polymorphisms in LAT2. From all variants, only five were in the coding region and only one heterozygous non-synonymous polymorphism (Ala94Thr) was found in LAT2. Numerous polymorphisms were found in the LAT1 and LAT2 5'-flanking regions but did not correlate with expression of the respective genes. No significant correlations could be observed between the polymorphisms in 4F2hc, LAT1, and LAT2 with melphalan pharmacokinetics or with melphalan side effects. The study confirmed that these transporter genes are highly conserved, particularly in the coding sequences. Genetic variation in 4F2hc, LAT1, and LAT2 does not appear to be a major cause of inter-individual variability in pharmacokinetics and of adverse reactions to melphalan.

  5. Weight-correction of carbon dioxide diffusion coefficient (DCO2 ) reduces its inter-individual variability and improves its correlation with blood carbon dioxide levels in neonates receiving high-frequency oscillatory ventilation.

    PubMed

    Belteki, Gusztav; Lin, Benjamin; Morley, Colin J

    2017-10-01

    Carbon-dioxide elimination during high-frequency oscillatory ventilation (HFOV) is thought to be proportional to the carbon dioxide diffusion coefficient (DCO 2 ) which is calculated as frequency x (tidal volume) 2 . DCO 2 can be used to as an indicator of CO 2 elimination but values obtained in different patients cannot be directly compared. To analyze the relationship between DCO 2 , the weight-corrected DCO 2 (DCO 2 corr) and blood gas PCO 2 values obtained from infants receiving HFOV. DCO 2 data were obtained from 14 infants at 1/s sampling rate and the mean DCO 2 was determined over 10 min periods preceding the time of the blood gas. DCO 2 corr was calculated by dividing the DCO 2 by the square of the body weight in kg. Weight-correction significantly reduced the inter-individual variability of DCO 2 . When data from all the babies were combined, standard DCO 2 showed no correlation with PCO 2 but DCO 2 corr showed a weak but statistically significant inverse correlation. The correlation was better when the endotracheal leak was <10%. There was significant inverse but weaker correlation between the HFOV tidal volume (VThf) and the PCO 2 . In any baby, DCO 2 corr >50 mL 2 /sec/kg 2 or VThf > 2.5 mL/kg was rarely needed to avoid hypercapnia. Weight-correction of DCO 2 values improved its comparability between patients. Weight-corrected DCO 2 correlated better with PCO 2 than uncorrected DCO 2 but the correlation was weak. © 2017 Wiley Periodicals, Inc.

  6. Modeling spatial competition for light in plant populations with the porous medium equation.

    PubMed

    Beyer, Robert; Etard, Octave; Cournède, Paul-Henry; Laurent-Gengoux, Pascal

    2015-02-01

    We consider a plant's local leaf area index as a spatially continuous variable, subject to particular reaction-diffusion dynamics of allocation, senescence and spatial propagation. The latter notably incorporates the plant's tendency to form new leaves in bright rather than shaded locations. Applying a generalized Beer-Lambert law allows to link existing foliage to production dynamics. The approach allows for inter-individual variability and competition for light while maintaining robustness-a key weakness of comparable existing models. The analysis of the single plant case leads to a significant simplification of the system's key equation when transforming it into the well studied porous medium equation. Confronting the theoretical model to experimental data of sugar beet populations, differing in configuration density, demonstrates its accuracy.

  7. Missing Oral Health-Related Data in the interRAI-HC - Associations with Selected Variables of General Health and the Effect of Multiple Imputation on the Relationship between Oral and General Health.

    PubMed

    Krausch-Hofmann, Stefanie; Bogaerts, Kris; Hofmann, Michael; de Almeida Mello, Johanna; Fávaro Moreira, Nádia Cristina; Lesaffre, Emmanuel; Declerck, Dominique; Declercq, Anja; Duyck, Joke

    2015-01-01

    Missing data within the comprehensive geriatric assessment of the interRAI suite of assessment instruments potentially imply the under-detection of conditions that require care as well as the risk of biased statistical results. Impaired oral health in older individuals has to be registered accurately as it causes pain and discomfort and is related to the general health status. This study was based on interRAI-Home Care (HC) baseline data from 7590 subjects (mean age 81.2 years, SD 6.9) in Belgium. It was investigated if missingness of the oral health-related items was associated with selected variables of general health. It was also determined if multiple imputation of missing data affected the associations between oral and general health. Multivariable logistic regression was used to determine if the prevalence of missingness in the oral health-related variables was associated with activities of daily life (ADLH), cognitive performance (CPS2) and depression (DRS). Associations between oral health and ADLH, CPS2 and DRS were determined, with missing data treated by 1. the complete-case technique and 2. by multiple imputation, and results were compared. The individual oral health-related variables had a similar proportion of missing values, ranging from 16.3% to 17.2%. The prevalence of missing data in all oral health-related variables was significantly associated with symptoms of depression (dental prosthesis use OR 1.66, CI 1.41-1.95; damaged teeth OR 1.74, CI 1.48-2.04; chewing problems OR 1.74, CI 1.47-2.05; dry mouth OR 1.65, CI 1.40-1.94). Missingness in damaged teeth (OR 1.27, CI 1.08-1.48), chewing problems (OR 1.22, CI 1.04-1.44) and dry mouth (OR 1.23, CI 1.05-1.44) occurred more frequently in cognitively impaired subjects. ADLH was not associated with the prevalence of missing data. When comparing the complete-case technique with the multiple imputation approach, nearly identical odds ratios characterized the associations between oral and general health. Cognitively impaired and depressive individuals had a higher risk of missing oral health-related information. Associations between oral health and ADLH, CPS2 and DRS were not influenced by multiple imputation of missing data. Further research should concentrate on the mechanisms that mediate the occurrence of missingness to develop preventative strategies.

  8. A Novel Group-Fused Sparse Partial Correlation Method for Simultaneous Estimation of Functional Networks in Group Comparison Studies.

    PubMed

    Liang, Xiaoyun; Vaughan, David N; Connelly, Alan; Calamante, Fernando

    2018-05-01

    The conventional way to estimate functional networks is primarily based on Pearson correlation along with classic Fisher Z test. In general, networks are usually calculated at the individual-level and subsequently aggregated to obtain group-level networks. However, such estimated networks are inevitably affected by the inherent large inter-subject variability. A joint graphical model with Stability Selection (JGMSS) method was recently shown to effectively reduce inter-subject variability, mainly caused by confounding variations, by simultaneously estimating individual-level networks from a group. However, its benefits might be compromised when two groups are being compared, given that JGMSS is blinded to other groups when it is applied to estimate networks from a given group. We propose a novel method for robustly estimating networks from two groups by using group-fused multiple graphical-lasso combined with stability selection, named GMGLASS. Specifically, by simultaneously estimating similar within-group networks and between-group difference, it is possible to address inter-subject variability of estimated individual networks inherently related with existing methods such as Fisher Z test, and issues related to JGMSS ignoring between-group information in group comparisons. To evaluate the performance of GMGLASS in terms of a few key network metrics, as well as to compare with JGMSS and Fisher Z test, they are applied to both simulated and in vivo data. As a method aiming for group comparison studies, our study involves two groups for each case, i.e., normal control and patient groups; for in vivo data, we focus on a group of patients with right mesial temporal lobe epilepsy.

  9. Effect of inter-annual variability in pasture growth and irrigation response on farm productivity and profitability based on biophysical and farm systems modelling.

    PubMed

    Vogeler, Iris; Mackay, Alec; Vibart, Ronaldo; Rendel, John; Beautrais, Josef; Dennis, Samuel

    2016-09-15

    Farm system and nutrient budget models are increasingly being used in analysis to inform on farm decision making and evaluate land use policy options at regional scales. These analyses are generally based on the use of average annual pasture yields. In New Zealand (NZ), like in many countries, there is considerable inter-annual variation in pasture growth rates, due to climate. In this study a modelling approach was used to (i) include inter-annual variability as an integral part of the analysis and (ii) test the approach in an economic analysis of irrigation in a case study within the Hawkes Bay Region of New Zealand. The Agricultural Production Systems Simulator (APSIM) was used to generate pasture dry matter yields (DMY) for 20 different years and under both dryland and irrigation. The generated DMY were linked to outputs from farm-scale modelling for both Sheep and Beef Systems (Farmaxx Pro) and Dairy Systems (Farmax® Dairy Pro) to calculate farm production over 20 different years. Variation in DMY and associated livestock production due to inter-annual variation in climate was large, with a coefficient of variations up to 20%. Irrigation decreased this inter-annual variation. On average irrigation, with unlimited available water, increased income by $831 to 1195/ha, but when irrigation was limited to 250mm/ha/year income only increased by $525 to 883/ha. Using pasture responses in individual years to capturing the inter-annual variation, rather than the pasture response averaged over 20years resulted in lower financial benefits. In the case study income from irrigation based on an average year were 10 to >20% higher compared with those obtained from individual years. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy

    PubMed Central

    Saruwatari, Junji; Ishitsu, Takateru; Nakagawa, Kazuko

    2010-01-01

    Genetic polymorphisms in the genes that encode drug-metabolizing enzymes are implicated in the inter-individual variability in the pharmacokinetics and pharmaco-dynamics of antiepileptic drugs (AEDs). However, the clinical impact of these polymorphisms on AED therapy still remains controversial. The defective alleles of cytochrome P450 (CYP) 2C9 and/or CYP2C19 could affect not only the pharmacokinetics, but also the pharmacodynamics of phenytoin therapy. CYP2C19 deficient genotypes were associated with the higher serum concentration of an active metabolite of clobazam, N-desmethylclobazam, and with the higher clinical efficacy of clobazam therapy than the other CYP2C19 genotypes. The defective alleles of CYP2C9 and/or CYP2C19 were also found to have clinically significant effects on the inter-individual variabilities in the population pharmacokinetics of phenobarbital, valproic acid and zonisamide. EPHX1 polymorphisms may be associated with the pharmacokinetics of carbamazepine and the risk of phenytoin-induced congenital malformations. Similarly, the UDP-glucuronosyltransferase 2B7 genotype may affect the pharmacokinetics of lamotrigine. Gluthatione S-transferase null genotypes are implicated in an increased risk of hepatotoxicity caused by carbamazepine and valproic acid. This article summarizes the state of research on the effects of mutations of drug-metabolizing enzymes on the pharmacokinetics and pharmacodynamics of AED therapies. Future directions for the dose-adjustment of AED are discussed. PMID:27713373

  11. Assessing the inter-observer variability of Computer-Aided Nodule Assessment and Risk Yield (CANARY) to characterize lung adenocarcinomas.

    PubMed

    Nakajima, Erica C; Frankland, Michael P; Johnson, Tucker F; Antic, Sanja L; Chen, Heidi; Chen, Sheau-Chiann; Karwoski, Ronald A; Walker, Ronald; Landman, Bennett A; Clay, Ryan D; Bartholmai, Brian J; Rajagopalan, Srinivasan; Peikert, Tobias; Massion, Pierre P; Maldonado, Fabien

    2018-01-01

    Lung adenocarcinoma (ADC), the most common lung cancer type, is recognized increasingly as a disease spectrum. To guide individualized patient care, a non-invasive means of distinguishing indolent from aggressive ADC subtypes is needed urgently. Computer-Aided Nodule Assessment and Risk Yield (CANARY) is a novel computed tomography (CT) tool that characterizes early ADCs by detecting nine distinct CT voxel classes, representing a spectrum of lepidic to invasive growth, within an ADC. CANARY characterization has been shown to correlate with ADC histology and patient outcomes. This study evaluated the inter-observer variability of CANARY analysis. Three novice observers segmented and analyzed independently 95 biopsy-confirmed lung ADCs from Vanderbilt University Medical Center/Nashville Veterans Administration Tennessee Valley Healthcare system (VUMC/TVHS) and the Mayo Clinic (Mayo). Inter-observer variability was measured using intra-class correlation coefficient (ICC). The average ICC for all CANARY classes was 0.828 (95% CI 0.76, 0.895) for the VUMC/TVHS cohort, and 0.852 (95% CI 0.804, 0.901) for the Mayo cohort. The most invasive voxel classes had the highest ICC values. To determine whether nodule size influenced inter-observer variability, an additional cohort of 49 sub-centimeter nodules from Mayo were also segmented by three observers, with similar ICC results. Our study demonstrates that CANARY ADC classification between novice CANARY users has an acceptably low degree of variability, and supports the further development of CANARY for clinical application.

  12. The forcing of monthly precipitation variability over Southwest Asia during the Boreal cold season

    USGS Publications Warehouse

    Hoell, Andrew; Shukla, Shraddhanand; Barlow, Mathew; Cannon, Forest; Kelley, Colin; Funk, Christopher C.

    2015-01-01

    Southwest Asia, deemed as the region containing the countries of Afghanistan, Iran, Iraq and Pakistan, is water scarce and receives nearly 75% of its annual rainfall during8 the boreal cold season of November-April. The forcing of Southwest Asia precipitation has been previously examined for the entire boreal cold season from the perspective of climate variability originating over the Atlantic and tropical Indo-Pacific Oceans. Here, we examine the inter-monthly differences in precipitation variability over Southwest Asia and the atmospheric conditions directly responsible in forcing monthly November-April precipitation. Seasonally averaged November-April precipitation over Southwest Asia is significantly correlated with sea surface temperature (SST) patterns consistent with Pacific Decadal Variability (PDV), the El Nino-Southern Oscillation (ENSO) and the warming trend of SST (Trend). On the contrary, the precipitation variability during individual months of November-April are unrelated and are correlated with SST signatures that include PDV, ENSO and Trend in different combinations. Despite strong inter-monthly differences in precipitation variability during November- April over Southwest Asia, similar atmospheric circulations, highlighted by a stationary equivalent barotropic Rossby wave centered over Iraq, force the monthly spatial distributions of precipitation. Tropospheric waves on the eastern side of the equivalent barotropic Rossby wave modifies the flux of moisture and advects the mean temperature gradient, resulting in temperature advection that is balanced by vertical motions over Southwest Asia. The forcing of monthly Southwest Asia precipitation by equivalent barotropic Rossby waves is different than the forcing by baroclinic Rossby waves associated with tropically-forced-only modes of climate variability.

  13. Detection of Diffusion Heterogeneity in Single Particle Tracking Trajectories Using a Hidden Markov Model with Measurement Noise Propagation

    PubMed Central

    Slator, Paddy J.; Cairo, Christopher W.; Burroughs, Nigel J.

    2015-01-01

    We develop a Bayesian analysis framework to detect heterogeneity in the diffusive behaviour of single particle trajectories on cells, implementing model selection to classify trajectories as either consistent with Brownian motion or with a two-state (diffusion coefficient) switching model. The incorporation of localisation accuracy is essential, as otherwise false detection of switching within a trajectory was observed and diffusion coefficient estimates were inflated. Since our analysis is on a single trajectory basis, we are able to examine heterogeneity between trajectories in a quantitative manner. Applying our method to the lymphocyte function-associated antigen 1 (LFA-1) receptor tagged with latex beads (4 s trajectories at 1000 frames s−1), both intra- and inter-trajectory heterogeneity were detected; 12–26% of trajectories display clear switching between diffusive states dependent on condition, whilst the inter-trajectory variability is highly structured with the diffusion coefficients being related by D 1 = 0.68D 0 − 1.5 × 104 nm2 s−1, suggestive that on these time scales we are detecting switching due to a single process. Further, the inter-trajectory variability of the diffusion coefficient estimates (1.6 × 102 − 2.6 × 105 nm2 s−1) is very much larger than the measurement uncertainty within trajectories, suggesting that LFA-1 aggregation and cytoskeletal interactions are significantly affecting mobility, whilst the timescales of these processes are distinctly different giving rise to inter- and intra-trajectory variability. There is also an ‘immobile’ state (defined as D < 3.0 × 103 nm2 s−1) that is rarely involved in switching, immobility occurring with the highest frequency (47%) under T cell activation (phorbol-12-myristate-13-acetate (PMA) treatment) with enhanced cytoskeletal attachment (calpain inhibition). Such ‘immobile’ states frequently display slow linear drift, potentially reflecting binding to a dynamic actin cortex. Our methods allow significantly more information to be extracted from individual trajectories (ultimately limited by time resolution and time-series length), and allow statistical comparisons between trajectories thereby quantifying inter-trajectory heterogeneity. Such methods will be highly informative for the construction and fitting of molecule mobility models within membranes incorporating aggregation, binding to the cytoskeleton, or traversing membrane microdomains. PMID:26473352

  14. Population Pharmacokinetics of Intravenous Methotrexate in Patients with Hematological Malignancies: Utilization of Routine Clinical Monitoring Parameters.

    PubMed

    Nader, Ahmed; Zahran, Noran; Alshammaa, Aya; Altaweel, Heba; Kassem, Nancy; Wilby, Kyle John

    2017-04-01

    Clinical response to methotrexate in cancer is variable and depends on several factors including serum drug exposure. This study aimed to develop a population pharmacokinetic model describing methotrexate disposition in cancer patients using retrospective chart review data available from routine clinical practice. A retrospective review of medical records was conducted for cancer patients in Qatar. Relevant data (methotrexate dosing/concentrations from multiple occasions, patient history, and laboratory values) were extracted and analyzed using NONMEM VII ® . A population pharmacokinetic model was developed and used to estimate inter-individual and inter-occasion variability terms on methotrexate pharmacokinetic parameters, as well as patient factors affecting methotrexate pharmacokinetics. Methotrexate disposition was described by a two-compartment model with clearance (CL) of 15.7 L/h and central volume of distribution (V c ) of 79.2 L. Patient weight and hematocrit levels were significant covariates on methotrexate V c and CL, respectively. Methotrexate CL changed by 50 % with changes in hematocrit levels from 23 to 50 %. Inter-occasion variability in methotrexate CL was estimated for patients administered the drug on multiple occasions (48 and 31 % for 2nd and 3rd visits, respectively). Therapeutic drug monitoring data collected during routine clinical practice can provide a useful tool for understanding factors affecting methotrexate pharmacokinetics. Patient weight and hematocrit levels may play a clinically important role in determining methotrexate serum exposure and dosing requirements. Future prospective studies are needed to validate results of the developed model and evaluate its usefulness to predict methotrexate exposure and optimize dosing regimens.

  15. Magnitude and Temporal Variability of Inter-stimulus EEG Modulate the Linear Relationship Between Laser-Evoked Potentials and Fast-Pain Perception

    PubMed Central

    Li, Linling; Huang, Gan; Lin, Qianqian; Liu, Jia; Zhang, Shengli; Zhang, Zhiguo

    2018-01-01

    The level of pain perception is correlated with the magnitude of pain-evoked brain responses, such as laser-evoked potentials (LEP), across trials. The positive LEP-pain relationship lays the foundation for pain prediction based on single-trial LEP, but cross-individual pain prediction does not have a good performance because the LEP-pain relationship exhibits substantial cross-individual difference. In this study, we aim to explain the cross-individual difference in the LEP-pain relationship using inter-stimulus EEG (isEEG) features. The isEEG features (root mean square as magnitude and mean square successive difference as temporal variability) were estimated from isEEG data (at full band and five frequency bands) recorded between painful stimuli. A linear model was fitted to investigate the relationship between pain ratings and LEP response for fast-pain trials on a trial-by-trial basis. Then the correlation between isEEG features and the parameters of LEP-pain model (slope and intercept) was evaluated. We found that the magnitude and temporal variability of isEEG could modulate the parameters of an individual's linear LEP-pain model for fast-pain trials. Based on this, we further developed a new individualized fast-pain prediction scheme, which only used training individuals with similar isEEG features as the test individual to train the fast-pain prediction model, and obtained improved accuracy in cross-individual fast-pain prediction. The findings could help elucidate the neural mechanism of cross-individual difference in pain experience and the proposed fast-pain prediction scheme could be potentially used as a practical and feasible pain prediction method in clinical practice. PMID:29904336

  16. Sex-specific participation in inter-group conflicts within a multilevel society: the first evidence at the individual level.

    PubMed

    Zhao, Dapeng; Chen, Zhuoyue; Li, Baoguo; Romero, Teresa

    2013-12-01

    Inter-group conflicts are common among many group-living animals and involve potentially complex motivations and interactions. Mammals living in multilevel societies offer a good opportunity to study inter-group conflicts. This study is the first to explore the function of sex-specific participation during inter-group conflicts within a multilevel society at the individual level. The Sichuan snub-nosed monkey (Rhinopithecus roxellana) is an endangered seasonal breeding species living in a multilevel society. From Sep 2007 to May 2008 we recorded 290 inter-group conflicts of a free-ranging provisioned band of R. roxellana in the Qinling Mountains of China to investigate the function of individual aggression during inter-group encounters. Our findings show that adult males were the main participants in inter-group conflicts, while females took part in them only occasionally. The male participation rate during the mating season, when adult females were estrous, was significantly higher than that during the non-mating season. Furthermore, males directed their aggression to other males, and directed more intense aggression towards bachelor males than towards other resident males. For both sexes, the participation rate as initiators was higher in the winter than that in the spring; and there was a significant positive correlation between group size and the participation rate as initiators. Our results suggest that inter-group aggression in Sichuan snub-nosed monkeys is linked to both mate defense and resource defense. © 2013 Wiley Publishing Asia Pty Ltd, ISZS and IOZ/CAS.

  17. DPYD*2A and MTHFR C677T predict toxicity and efficacy, respectively, in patients on chemotherapy with 5-fluorouracil for colorectal cancer.

    PubMed

    Nahid, Noor Ahmed; Apu, Mohd Nazmul Hasan; Islam, Md Reazul; Shabnaz, Samia; Chowdhury, Surid Mohammad; Ahmed, Maizbha Uddin; Nahar, Zabun; Islam, Md Siddiqul; Islam, Mohammad Safiqul; Hasnat, Abul

    2018-01-01

    Significant inter-individual variation in the sensitivity to 5-fluorouracil (5-FU) represents a major therapeutic hindrance either by impairing drug response or inducing adverse drug reactions (ADRs). This study aimed at exploring the cause behind this inter-individual alterations in consequences of 5-fluorouracil-based chemotherapy by investigating the effects of DPYD*2A and MTHFR C677T polymorphisms on toxicity and response of 5-FU in Bangladeshi colorectal cancer patients. Colorectal cancer patients (n = 161) receiving 5-FU-based chemotherapy were prospectively enrolled. DPYD and MTHFR polymorphisms were assessed in peripheral leukocytes. Multivariate analyses were applied to evaluate which variables could predict chemotherapy-induced toxicity and efficacy. Multivariate analyses showed that DPYD*2A polymorphism was a predictive factor (P = 0.023) for grade 3 and grade 4 5-fluorouracil-related toxicities. Although MTHFR C677T polymorphism might act as forecasters for grade 3 or grade 4 neutropenia, diarrhea, and mucositis, this polymorphism was found to increase significantly (P = 0.006) the response of 5-FU. DPYD*2A and MTHFR C677T polymorphisms could explain 5-FU toxicity or clinical outcome in Bangladeshi colorectal patients.

  18. Analysis of trends and dominant periodicities in drought variables in India: A wavelet transform based approach

    NASA Astrophysics Data System (ADS)

    Joshi, Nitin; Gupta, Divya; Suryavanshi, Shakti; Adamowski, Jan; Madramootoo, Chandra A.

    2016-12-01

    In this study, seasonal trends as well as dominant and significant periods of variability of drought variables were analyzed for 30 rainfall subdivisions in India over 141 years (1871-2012). Standardized precipitation index (SPI) was used as a meteorological drought indicator, and various drought variables (monsoon SPI, non-monsoon SPI, yearly SPI, annual drought duration, annual drought severity and annual drought peak) were analyzed. Discrete wavelet transform was used in conjunction with the Mann-Kendall test to analyze trends and dominant periodicities associated with the drought variables. Furthermore, continuous wavelet transform (CWT) based global wavelet spectrum was used to analyze significant periods of variability associated with the drought variables. From the trend analysis, we observed that over the second half of the 20th century, drought occurrences increased significantly in subdivisions of Northeast and Central India. In both short-term (2-8 years) and decadal (16-32 years) periodicities, the drought variables were found to influence the trend. However, CWT analysis indicated that the dominant periodic components were not significant for most of the geographical subdivisions. Although inter-annual and inter-decadal periodic components play an important role, they may not completely explain the variability associated with the drought variables across the country.

  19. Environmental impact of omnivorous, ovo-lacto-vegetarian, and vegan diet.

    PubMed

    Rosi, Alice; Mena, Pedro; Pellegrini, Nicoletta; Turroni, Silvia; Neviani, Erasmo; Ferrocino, Ilario; Di Cagno, Raffaella; Ruini, Luca; Ciati, Roberto; Angelino, Donato; Maddock, Jane; Gobbetti, Marco; Brighenti, Furio; Del Rio, Daniele; Scazzina, Francesca

    2017-07-21

    Food and beverage consumption has a great impact on the environment, although there is a lack of information concerning the whole diet. The environmental impact of 153 Italian adults (51 omnivores, 51 ovo-lacto-vegetarians, 51 vegans) and the inter-individual variability within dietary groups were assessed in a real-life context. Food intake was monitored with a 7-d dietary record to calculate nutritional values and environmental impacts (carbon, water, and ecological footprints). The Italian Mediterranean Index was used to evaluate the nutritional quality of each diet. The omnivorous choice generated worse carbon, water and ecological footprints than other diets. No differences were found for the environmental impacts of ovo-lacto-vegetarians and vegans, which also had diets more adherent to the Mediterranean pattern. A high inter-individual variability was observed through principal component analysis, showing that some vegetarians and vegans have higher environmental impacts than those of some omnivores. Thus, regardless of the environmental benefits of plant-based diets, there is a need for thinking in terms of individual dietary habits. To our knowledge, this is the first time environmental impacts of three dietary regimens are evaluated using individual recorded dietary intakes rather than hypothetical diet or diets averaged over a population.

  20. Inter-individual variability and genetic influences on cytokine responses against bacterial and fungal pathogens

    PubMed Central

    Li, Yang; Oosting, Marije; Deelen, Patrick; Ricaño-Ponce, Isis; Smeekens, Sanne; Jaeger, Martin; Matzaraki, Vasiliki; Swertz, Morris A.; Xavier, Ramnik J.; Franke, Lude; Wijmenga, Cisca; Joosten, Leo A.B.; Kumar, Vinod; Netea, Mihai G.

    2016-01-01

    Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens, and to determine the impact of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort within the Human Functional Genomics Study (www.humanfunctionalgenomics.org), obtained over three different years. By comparing bacteria- and fungi-induced cytokine profiles, we show that most cytokine responses are organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide SNP genotypes with cytokine abundance and identified six cytokine QTLs. Among them, a cytokine QTL at NAA35-GOLM1 locus markedly modulates IL-6 production in response to multiple pathogens, and associated with susceptibility to candidemia. Furthermore, the cytokine QTLs we identified are enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens. PMID:27376574

  1. Factors associated with inter-municipality differences in dental caries experience among Danish adolescents. An ecological study.

    PubMed

    Ekstrand, K R; Christiansen, M E C; Qvist, V; Ismail, A

    2010-02-01

    Caries on children and adolescents in Denmark has declined significantly over the last 30 years. Our first analysis in 1999, however, disclosed huge inter-municipality disparities in mean DMFS values as well as in prevalence of caries on Danish children; that fluoride in the water supply and the length of the education of the mothers could explain up to 45% of the above-mentioned disparity and that very few municipalities were positive outliers, i.e. were providing significant better caries results than expected from the background variables. Three of the aims of this second analysis were to repeat the analyses done on the 1999 sample, but now on a 2004 sample and then compare it with the results from 1999. A fourth aim was by means of an interview of CDOs to determine their interpretation of relevant conditions in the public dental health service in relation dental health outcome. A total of 204 (99%) and 191 (93%) municipalities were involved in 1999 and 2004, respectively. Unit of analysis were the municipalities. Mean DMFS of 15-year-olds was used as outcome variable. Eight background variables were accounted for during the analysis: For the fourth aim, a sample of CDOs representing municipalities with positive (n = 10), with no change (n = 10), or with negative change (n = 10) in mean DMFS, relative to all municipalities, between 1999 and 2004 was selected. The inter-municipality variation in mean DMFS 1999 was 0.88 to 8.73 and in 2004 was 0.56 to 6.19. The analyses found that fluoride level of the drinking water and mothers' length of education were significant variables explaining about 44% of the variations in mean DMFS in both years. Only one municipality was characterized as a positive outlier in 1999 as well as in 2004. The dose-response relations between increasing fluoride concentrations in the water supply and DMF-S values diminished in both years at a level above 0.35 ppm. The structured interview disclosed that municipalities with significant improvement in mean DMFS from 1999 to 2004 had established goals and were committed to the prevention of dental caries at the individual level. Instability in manpower; number of children in the service and economy was associated to municipalities with negative changes in caries experience.

  2. An integrated workflow to assess technical and biological variability of cell population frequencies in human peripheral blood by flow cytometry

    PubMed Central

    Burel, Julie G.; Qian, Yu; Arlehamn, Cecilia Lindestam; Weiskopf, Daniela; Zapardiel-Gonzalo, Jose; Taplitz, Randy; Gilman, Robert H.; Saito, Mayuko; de Silva, Aruna D.; Vijayanand, Pandurangan; Scheuermann, Richard H.; Sette, Alessandro; Peters, Bjoern

    2016-01-01

    In the context of large-scale human system immunology studies, controlling for technical and biological variability is crucial to ensure that experimental data support research conclusions. Here, we report on a universal workflow to evaluate both technical and biological variation in multiparameter flow cytometry, applied to the development of a 10-color panel to identify all major cell populations and T cell subsets in cryopreserved PBMC. Replicate runs from a control donation and comparison of different gating strategies assessed technical variability associated with each cell population and permitted the calculation of a quality control score. Applying our panel to a large collection of PBMC samples, we found that most cell populations showed low intra-individual variability over time. In contrast, certain subpopulations such as CD56 T cells and Temra CD4 T cells were associated with high inter-individual variability. Age but not gender had a significant effect on the frequency of several populations, with a drastic decrease in naïve T cells observed in older donors. Ethnicity also influenced a significant proportion of immune cell population frequencies, emphasizing the need to account for these co-variates in immune profiling studies. Finally, we exemplify the usefulness of our workflow by identifying a novel cell-subset signature of latent tuberculosis infection. Thus, our study provides a universal workflow to establish and evaluate any flow cytometry panel in systems immunology studies. PMID:28069807

  3. Masting in ponderosa pine: comparisons of pollen and seed over space and time.

    PubMed

    Mooney, Kailen A; Linhart, Yan B; Snyder, Marc A

    2011-03-01

    Many plant species exhibit variable and synchronized reproduction, or masting, but less is known of the spatial scale of synchrony, effects of climate, or differences between patterns of pollen and seed production. We monitored pollen and seed cone production for seven Pinus ponderosa populations (607 trees) separated by up to 28 km and 1,350 m in elevation in Boulder County, Colorado, USA for periods of 4-31 years for a mean per site of 8.7 years for pollen and 12.1 for seed cone production. We also analyzed climate data and a published dataset on 21 years of seed production for an eighth population (Manitou) 100 km away. Individual trees showed high inter-annual variation in reproduction. Synchrony was high within populations, but quickly became asynchronous among populations with a combination of increasing distance and elevational difference. Inter-annual variation in temperature and precipitation had differing influences on seed production for Boulder County and Manitou. We speculate that geographically variable effects of climate on reproduction arise from environmental heterogeneity and population genetic differentiation, which in turn result in localized synchrony. Although individual pines produce pollen and seed, only one-third of the covariation within trees was shared. As compared to seed cones, pollen had lower inter-annual variation at the level of the individual tree and was more synchronous. However, pollen and seed production were similar with respect to inter-annual variation at the population level, spatial scales of synchrony and associations with climate. Our results show that strong masting can occur at a localized scale, and that reproductive patterns can differ between pollen and seed cone production in a hermaphroditic plant.

  4. Genetic Influences on Response to Alcohol and Response to Pharmacotherapies for Alcoholism

    PubMed Central

    Enoch, Mary-Anne

    2014-01-01

    Although very many individuals drink alcohol at safe levels, a significant proportion escalates their consumption with addiction as the end result. Alcoholism is a common, moderately heritable, psychiatric disorder that is accompanied by considerable morbidity and mortality. Variation in clinical presentation suggests inter-individual variation in mechanisms of vulnerability including genetic risk factors. The development of addiction is likely to involve numerous functional genetic variants of small effects. The first part of this review will focus on genetic factors underlying inter-individual variability in response to alcohol consumption, including variants in alcohol metabolizing genes that produce an aversive response (the flushing syndrome) and variants that predict the level of subjective and physiological response to alcohol. The second part of this review will report on genetic variants that identify subgroups of alcoholics who are more likely to respond to pharmacotherapy to reduce levels of drinking or maintain abstinence. Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5′ and 3′ functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs / ondansetron respectively. Because of large inter-ethnic variation in allele frequencies, the relevance of these functional polymorphisms will vary between ethnic groups. However there are relatively few published studies in this field, particularly with large sample sizes in pharmacogenetic studies, therefore it is premature to draw any conclusions at this stage. PMID:24220019

  5. Genetic influences on response to alcohol and response to pharmacotherapies for alcoholism.

    PubMed

    Enoch, Mary-Anne

    2014-08-01

    Although very many individuals drink alcohol at safe levels, a significant proportion escalates their consumption with addiction as the end result. Alcoholism is a common, moderately heritable, psychiatric disorder that is accompanied by considerable morbidity and mortality. Variation in clinical presentation suggests inter-individual variation in mechanisms of vulnerability including genetic risk factors. The development of addiction is likely to involve numerous functional genetic variants of small effects. The first part of this review will focus on genetic factors underlying inter-individual variability in response to alcohol consumption, including variants in alcohol metabolizing genes that produce an aversive response (the flushing syndrome) and variants that predict the level of subjective and physiological response to alcohol. The second part of this review will report on genetic variants that identify subgroups of alcoholics who are more likely to respond to pharmacotherapy to reduce levels of drinking or maintain abstinence. Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5' and 3' functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs/ondansetron respectively. Because of large inter-ethnic variation in allele frequencies, the relevance of these functional polymorphisms will vary between ethnic groups. However there are relatively few published studies in this field, particularly with large sample sizes in pharmacogenetic studies, therefore it is premature to draw any conclusions at this stage. Published by Elsevier Inc.

  6. Solving the puzzle of collective action through inter-individual differences

    PubMed Central

    von Rueden, Chris; Gavrilets, Sergey; Glowacki, Luke

    2015-01-01

    Models of collective action infrequently account for differences across individuals beyond a limited set of strategies, ignoring variation in endowment (e.g. physical condition, wealth, knowledge, personality, support), individual costs of effort, or expected gains from cooperation. However, behavioural research indicates these inter-individual differences can have significant effects on the dynamics of collective action. The papers contributed to this theme issue evaluate how individual differences affect the propensity to cooperate, and how they can catalyse others’ likelihood of cooperation (e.g. via leadership). Many of the papers emphasize the relationship between individual decisions and socio-ecological context, particularly the effect of group size. All together, the papers in this theme issue provide a more complete picture of collective action, by embracing the reality of inter-individual variation and its multiple roles in the success or failure of collective action. PMID:26503677

  7. Demographic Variables for Wild Asian Elephants Using Longitudinal Observations

    PubMed Central

    de Silva, Shermin; Webber, C. Elizabeth; Weerathunga, U. S.; Pushpakumara, T. V.; Weerakoon, Devaka K.; Wittemyer, George

    2013-01-01

    Detailed demographic data on wild Asian elephants have been difficult to collect due to habitat characteristics of much of the species’ remaining range. Such data, however, are critical for understanding and modeling population processes in this endangered species. We present data from six years of an ongoing study of Asian elephants (Elephas maximus) in Uda Walawe National Park, Sri Lanka. This relatively undisturbed population numbering over one thousand elephants is individually monitored, providing cohort-based information on mortality and reproduction. Reproduction was seasonal, such that most births occurred during the long inter-monsoon dry season and peaked in May. During the study, the average age at first reproduction was 13.4 years and the 50th percentile inter-birth interval was approximately 6 years. Birth sex ratios did not deviate significantly from parity. Fecundity was relatively stable throughout the observed reproductive life of an individual (ages 11–60), averaging between 0.13–0.17 female offspring per individual per year. Mortalities and injuries based on carcasses and disappearances showed that males were significantly more likely than females to be killed or injured through anthropogenic activity. Overall, however, most observed injuries did not appear to be fatal. This population exhibits higher fecundity and density relative to published estimates on other Asian elephant populations, possibly enhanced by present range constriction. Understanding the factors responsible for these demographic dynamics can shed insight on the future needs of this elephant population, with probable parallels to other populations in similar settings. PMID:24376581

  8. Demographic variables for wild Asian elephants using longitudinal observations.

    PubMed

    de Silva, Shermin; Webber, C Elizabeth; Weerathunga, U S; Pushpakumara, T V; Weerakoon, Devaka K; Wittemyer, George

    2013-01-01

    Detailed demographic data on wild Asian elephants have been difficult to collect due to habitat characteristics of much of the species' remaining range. Such data, however, are critical for understanding and modeling population processes in this endangered species. We present data from six years of an ongoing study of Asian elephants (Elephas maximus) in Uda Walawe National Park, Sri Lanka. This relatively undisturbed population numbering over one thousand elephants is individually monitored, providing cohort-based information on mortality and reproduction. Reproduction was seasonal, such that most births occurred during the long inter-monsoon dry season and peaked in May. During the study, the average age at first reproduction was 13.4 years and the 50(th) percentile inter-birth interval was approximately 6 years. Birth sex ratios did not deviate significantly from parity. Fecundity was relatively stable throughout the observed reproductive life of an individual (ages 11-60), averaging between 0.13-0.17 female offspring per individual per year. Mortalities and injuries based on carcasses and disappearances showed that males were significantly more likely than females to be killed or injured through anthropogenic activity. Overall, however, most observed injuries did not appear to be fatal. This population exhibits higher fecundity and density relative to published estimates on other Asian elephant populations, possibly enhanced by present range constriction. Understanding the factors responsible for these demographic dynamics can shed insight on the future needs of this elephant population, with probable parallels to other populations in similar settings.

  9. Contributions of Human Cytochrome P450 Enzymes to Glyburide Metabolism*

    PubMed Central

    Zhou, Lin; Naraharisetti, Suresh B.; Liu, Li; Wang, Honggang; Lin, Yvonne S.; Isoherranen, Nina; Unadkat, Jashvant D.; Hebert, Mary F.; Mao, Qingcheng

    2011-01-01

    Glyburide (GLB) is a widely used oral sulfonylurea for the treatment of gestational diabetes. Therapeutic use of GLB is often complicated by a substantial inter-individual variability in the pharmacokinetics and pharmacodynamics of the drug in human populations, which might be caused by inter-individual variations in factors such as GLB metabolism. Therefore, there has been a continued interest in identifying human cytochrome P450 (CYP) isoforms that play a major role in the metabolism of GLB. However, contrasting data are available in the present literature in this regard. In the present study, we systematically investigated the contributions of various human CYP isoforms (CYP3A4, CYP3A5, CYP2C8, CYP2C9, and CYP2C19) to in vitro metabolism of GLB. GLB depletion and metabolite formation in human liver microsomes were most significantly inhibited by the CYP3A inhibitor ketoconazole compared with the inhibitors of other CYP isoforms. Furthermore, multiple correlation analysis between GLB depletion and individual CYP activities was performed, demonstrating a significant correlation between GLB depletion and the CYP3A probe activity in 16 individual human liver microsomal preparations, but not between GLB depletion and the CYP2C19, CYP2C8, or CYP2C9 probe activity. By using recombinant supersomes overexpressing individual human CYP isoforms, we found that GLB could be depleted by all the enzymes tested; however, the intrinsic clearance (Vmax/Km) of CYP3A4 for GLB depletion was 4 – 17 times greater than that of other CYP isoforms. These results confirm that human CYP3A4 is the major enzyme invovled in the in vitro metabolism of GLB. PMID:20437462

  10. Mn/Ca intra- and inter-test variability in the benthic foraminifer Ammonia tepida

    NASA Astrophysics Data System (ADS)

    Petersen, Jassin; Barras, Christine; Bézos, Antoine; La, Carole; de Nooijer, Lennart J.; Meysman, Filip J. R.; Mouret, Aurélia; Slomp, Caroline P.; Jorissen, Frans J.

    2018-01-01

    The adaptation of some benthic foraminiferal species to low-oxygen conditions provides the prospect of using the chemical composition of their tests as proxies for bottom water oxygenation. Manganese may be particularly suitable as such a geochemical proxy because this redox element is soluble in reduced form (Mn2+) and hence can be incorporated into benthic foraminiferal tests under low-oxygen conditions. Therefore, intra- and inter-test differences in foraminiferal Mn/Ca ratios may hold important information about short-term variability in pore water Mn2+ concentrations and sediment redox conditions. Here, we studied Mn/Ca intra- and inter-test variability in living individuals of the shallow infaunal foraminifer Ammonia tepida sampled in Lake Grevelingen (the Netherlands) in three different months of 2012. The deeper parts of this lake are characterized by seasonal hypoxia/anoxia with associated shifts in microbial activity and sediment geochemistry, leading to seasonal Mn2+ accumulation in the pore water. Earlier laboratory experiments with similar seawater Mn2+ concentrations as encountered in the pore waters of Lake Grevelingen suggest that intra-test variability due to ontogenetic trends (i.e. size-related effects) and/or other vital effects occurring during calcification in A. tepida (11-25 % relative SD, RSD) is responsible for part of the observed variability in Mn/Ca. Our present results show that the seasonally highly dynamic environmental conditions in the study area lead to a strongly increased Mn/Ca intra- and inter-test variability (average of 45 % RSD). Within single specimens, both increasing and decreasing trends in Mn/Ca ratios with size are observed. Our results suggest that the variability in successive single-chamber Mn/Ca ratios reflects the temporal variability in pore water Mn2+. Additionally, active or passive migration of the foraminifera in the surface sediment may explain part of the observed Mn/Ca variability.

  11. Uncertainty of trial timing enhances acquisition of conditioned eyeblinks in anxiety vulnerable individuals.

    PubMed

    Allen, M T; Myers, C E; Servatius, R J

    2016-05-01

    Recent work has found that behaviorally inhibited (BI) individuals exhibit enhanced eyeblink conditioning in omission and yoked training as well as with schedules of partial reinforcement. We hypothesized that spacing CS-US paired trials over a longer period of time by extending and varying the inter-trial interval (ITI) would facilitate learning. All participants completed the Adult Measure of Behavioural Inhibition (AMBI) and were grouped as behaviorally inhibited (BI) and non-behaviorally inhibited (NI) based on a median split score of 15.5. All participants received 3 US alone trials and 30CS-US paired trials for acquisition training and 20CS alone trials for extinction training in one session. Conditioning stimuli were a 500 ms tone conditioned stimulus (CS) and a 50-ms air puff unconditional stimulus (US). Participants were randomly assigned to receive a short ITI (mean=30+/- 5s), a long ITI (mean=57+/- 5s) or a variable long ITI (mean=57 s, range 25-123 s). No significant ITI effects were observed for acquisition or extinction. Overall, anxiety vulnerable individuals exhibited enhanced conditioned eyeblink responses as compared to non-vulnerable individuals. This enhanced acquisition of CRs was significant in spaced training with a variable long ITI, but not the short or long ITI. There were no significant effects of ITI or BI on extinction. These findings are interpreted based on the idea that uncertainty plays a role in anxiety and can enhance associative learning in anxiety vulnerable individuals. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Plant Trait Variation along an Altitudinal Gradient in Mediterranean High Mountain Grasslands: Controlling the Species Turnover Effect

    PubMed Central

    Pescador, David S.; de Bello, Francesco; Valladares, Fernando; Escudero, Adrián

    2015-01-01

    Assessing changes in plant functional traits along gradients is useful for understanding the assembly of communities and their response to global and local environmental drivers. However, these changes may reflect the effects of species composition (i.e. composition turnover), species abundance (i.e. species interaction), and intra-specific trait variability (i.e. species plasticity). In order to determine the relevance of the latter, trait variation can be assessed under minimal effects of composition turnover. Nine sampling sites were established along an altitudinal gradient in a Mediterranean high mountain grassland community with low composition turnover (Madrid, Spain; 1940 m–2419 m). Nine functional traits were also measured for ten individuals of around ten plant species at each site, for a total of eleven species across all sites. The relative importance of different sources of variability (within/between site and intra-/inter-specific functional diversity) and trait variation at species and community level along the considered gradients were explored. We found a weak individual species response to altitude and other environmental variables although in some cases, individuals were smaller and leaves were thicker at higher elevations. This lack of species response was most likely due to greater within- than between-site species variation. At the community level, inter-specific functional diversity was generally greater than the intra-specific component except for traits linked to leaf element content (leaf carbon content, leaf nitrogen content, δ13C and δ15N). Inter-specific functional diversity decreased with lower altitude for four leaf traits (specific leaf area, leaf dry matter content, δ13C and δ15N), suggesting trait convergence between species at lower elevations, where water shortage may have a stronger environmental filtering effect than colder temperatures at higher altitudes. Our results suggest that, within a vegetation type encompassing various environmental gradients, both, changes in species abundance and intra-specific trait variability adjust for the community functional response to environmental changes. PMID:25774532

  13. Plant trait variation along an altitudinal gradient in mediterranean high mountain grasslands: controlling the species turnover effect.

    PubMed

    Pescador, David S; de Bello, Francesco; Valladares, Fernando; Escudero, Adrián

    2015-01-01

    Assessing changes in plant functional traits along gradients is useful for understanding the assembly of communities and their response to global and local environmental drivers. However, these changes may reflect the effects of species composition (i.e. composition turnover), species abundance (i.e. species interaction), and intra-specific trait variability (i.e. species plasticity). In order to determine the relevance of the latter, trait variation can be assessed under minimal effects of composition turnover. Nine sampling sites were established along an altitudinal gradient in a Mediterranean high mountain grassland community with low composition turnover (Madrid, Spain; 1940 m-2419 m). Nine functional traits were also measured for ten individuals of around ten plant species at each site, for a total of eleven species across all sites. The relative importance of different sources of variability (within/between site and intra-/inter-specific functional diversity) and trait variation at species and community level along the considered gradients were explored. We found a weak individual species response to altitude and other environmental variables although in some cases, individuals were smaller and leaves were thicker at higher elevations. This lack of species response was most likely due to greater within- than between-site species variation. At the community level, inter-specific functional diversity was generally greater than the intra-specific component except for traits linked to leaf element content (leaf carbon content, leaf nitrogen content, δ13C and δ15N). Inter-specific functional diversity decreased with lower altitude for four leaf traits (specific leaf area, leaf dry matter content, δ13C and δ15N), suggesting trait convergence between species at lower elevations, where water shortage may have a stronger environmental filtering effect than colder temperatures at higher altitudes. Our results suggest that, within a vegetation type encompassing various environmental gradients, both, changes in species abundance and intra-specific trait variability adjust for the community functional response to environmental changes.

  14. Variability in Humoral Immunity to Measles Vaccine: New Developments

    PubMed Central

    Haralambieva, Iana H.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Whitaker, Jennifer A.; Poland, Gregory A.

    2015-01-01

    Despite the existence of an effective measles vaccine, resurgence in measles cases in the United States and across Europe has occurred, including in individuals vaccinated with two doses of the vaccine. Host genetic factors result in inter-individual variation in measles vaccine-induced antibodies, and play a role in vaccine failure. Studies have identified HLA and non-HLA genetic influences that individually or jointly contribute to the observed variability in the humoral response to vaccination among healthy individuals. In this exciting era, new high-dimensional approaches and techniques including vaccinomics, systems biology, GWAS, epitope prediction and sophisticated bioinformatics/statistical algorithms, provide powerful tools to investigate immune response mechanisms to the measles vaccine. These might predict, on an individual basis, outcomes of acquired immunity post measles vaccination. PMID:26602762

  15. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women

    USDA-ARS?s Scientific Manuscript database

    A high degree of inter-individual variability in plasma lipid level response to hormone therapy (HT) has been reported. Variations in the estrogen receptor alpha gene (ESR1) and in genes involved in lipid metabolism may explain some of the variability in response to HT. We studied the effect of sin...

  16. Quantitative detection of cartilage surfaces and ligament geometry of the wrist using an imaging cryomicrotome system.

    PubMed

    Dvinskikh, N A; Blankevoort, L; Foumani, M; Spaan, J A E; Streekstra, G J

    2010-03-22

    Biomechanical models may aid in improving diagnosis and treatment of wrist joint disorders. As input, geometrical information is required for model development. Previous studies acquired some elements of the average wrist joint geometry. However, there is a close geometric functional match between articulating surfaces and ligament geometry. Therefore, biomechanical models need to be fed with the geometric data of individual joints. This study is aimed at acquiring geometric data of cartilage surfaces and ligaments from individual wrist joints by using a cryomicrotome imaging system and the evaluation of inter- and intra-observer variability of the data. The 3D geometry of 30 cartilage surfaces and 15 ligaments in three cadaver wrists was manually detected and quantitatively reconstructed. The inter- and intra-observer variability of the cartilage surface detection was 0.14 and 0.19 mm, respectively. For the position of the radius attachment of the dorsal radiocarpal ligament (DRC), the observer variations were 0.12 and 0.65 mm, for intra-/inter-observer, respectively. For the DRC attachment on the triquetrum, the observer variations were 0.22 and 1.19 mm. Anatomic reconstruction from 3D cryomicrotome images offer a method to obtain unique geometry data of the entire wrist joint for modeling purposes. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  17. Environment dominates over host genetics in shaping human gut microbiota.

    PubMed

    Rothschild, Daphna; Weissbrod, Omer; Barkan, Elad; Kurilshikov, Alexander; Korem, Tal; Zeevi, David; Costea, Paul I; Godneva, Anastasia; Kalka, Iris N; Bar, Noam; Shilo, Smadar; Lador, Dar; Vila, Arnau Vich; Zmora, Niv; Pevsner-Fischer, Meirav; Israeli, David; Kosower, Noa; Malka, Gal; Wolf, Bat Chen; Avnit-Sagi, Tali; Lotan-Pompan, Maya; Weinberger, Adina; Halpern, Zamir; Carmi, Shai; Fu, Jingyuan; Wijmenga, Cisca; Zhernakova, Alexandra; Elinav, Eran; Segal, Eran

    2018-03-08

    Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

  18. On the nature of motor planning variables during arm pointing movement: Compositeness and speed dependence.

    PubMed

    Vu, Van Hoan; Isableu, Brice; Berret, Bastien

    2016-07-22

    The purpose of this study was to investigate the nature of the variables and rules underlying the planning of unrestrained 3D arm reaching. To identify whether the brain uses kinematic, dynamic and energetic values in an isolated manner or combines them in a flexible way, we examined the effects of speed variations upon the chosen arm trajectories during free arm movements. Within the optimal control framework, we uncovered which (possibly composite) optimality criterion underlays at best the empirical data. Fifteen participants were asked to perform free-endpoint reaching movements from a specific arm configuration at slow, normal and fast speeds. Experimental results revealed that prominent features of observed motor behaviors were significantly speed-dependent, such as the chosen reach endpoint and the final arm posture. Nevertheless, participants exhibited different arm trajectories and various degrees of speed dependence of their reaching behavior. These inter-individual differences were addressed using a numerical inverse optimal control methodology. Simulation results revealed that a weighted combination of kinematic, energetic and dynamic cost functions was required to account for all the critical features of the participants' behavior. Furthermore, no evidence for the existence of a speed-dependent tuning of these weights was found, thereby suggesting subject-specific but speed-invariant weightings of kinematic, energetic and dynamic variables during the motor planning process of free arm movements. This suggested that the inter-individual difference of arm trajectories and speed dependence was not only due to anthropometric singularities but also to critical differences in the composition of the subjective cost function. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Localised residency and inter-annual fidelity to coastal foraging areas may place sea bass at risk to local depletion

    NASA Astrophysics Data System (ADS)

    Doyle, Thomas K.; Haberlin, Damien; Clohessy, Jim; Bennison, Ashley; Jessopp, Mark

    2017-04-01

    For many marine migratory fish, comparatively little is known about the movement of individuals rather than the population. Yet, such individual-based movement data is vitally important to understand variability in migratory strategies and fidelity to foraging locations. A case in point is the economically important European sea bass (Dicentrarchus labrax L.) that inhabits coastal waters during the summer months before migrating offshore to spawn and overwinter. Beyond this broad generalisation we have very limited information on the movements of individuals at coastal foraging grounds. We used acoustic telemetry to track the summer movements and seasonal migrations of individual sea bass in a large tidally and estuarine influenced coastal environment. We found that the vast majority of tagged sea bass displayed long-term residency (mean, 167 days) and inter-annual fidelity (93% return rate) to specific areas. We describe individual fish home ranges of 3 km or less, and while fish clearly had core resident areas, there was movement of fish between closely located receivers. The combination of inter-annual fidelity to localised foraging areas makes sea bass very susceptible to local depletion; however, the designation of protected areas for sea bass may go a long way to ensuring the sustainability of this species.

  20. Localised residency and inter-annual fidelity to coastal foraging areas may place sea bass at risk to local depletion

    PubMed Central

    Doyle, Thomas K.; Haberlin, Damien; Clohessy, Jim; Bennison, Ashley; Jessopp, Mark

    2017-01-01

    For many marine migratory fish, comparatively little is known about the movement of individuals rather than the population. Yet, such individual-based movement data is vitally important to understand variability in migratory strategies and fidelity to foraging locations. A case in point is the economically important European sea bass (Dicentrarchus labrax L.) that inhabits coastal waters during the summer months before migrating offshore to spawn and overwinter. Beyond this broad generalisation we have very limited information on the movements of individuals at coastal foraging grounds. We used acoustic telemetry to track the summer movements and seasonal migrations of individual sea bass in a large tidally and estuarine influenced coastal environment. We found that the vast majority of tagged sea bass displayed long-term residency (mean, 167 days) and inter-annual fidelity (93% return rate) to specific areas. We describe individual fish home ranges of 3 km or less, and while fish clearly had core resident areas, there was movement of fish between closely located receivers. The combination of inter-annual fidelity to localised foraging areas makes sea bass very susceptible to local depletion; however, the designation of protected areas for sea bass may go a long way to ensuring the sustainability of this species. PMID:28374772

  1. Indian Summer Monsoon Rainfall: Implications of Contrasting Trends in the Spatial Variability of Means and Extremes

    PubMed Central

    Ghosh, Subimal; Vittal, H.; Sharma, Tarul; Karmakar, Subhankar; Kasiviswanathan, K. S.; Dhanesh, Y.; Sudheer, K. P.; Gunthe, S. S.

    2016-01-01

    India’s agricultural output, economy, and societal well-being are strappingly dependent on the stability of summer monsoon rainfall, its variability and extremes. Spatial aggregate of intensity and frequency of extreme rainfall events over Central India are significantly increasing, while at local scale they are spatially non-uniform with increasing spatial variability. The reasons behind such increase in spatial variability of extremes are poorly understood and the trends in mean monsoon rainfall have been greatly overlooked. Here, by using multi-decadal gridded daily rainfall data over entire India, we show that the trend in spatial variability of mean monsoon rainfall is decreasing as exactly opposite to that of extremes. The spatial variability of extremes is attributed to the spatial variability of the convective rainfall component. Contrarily, the decrease in spatial variability of the mean rainfall over India poses a pertinent research question on the applicability of large scale inter-basin water transfer by river inter-linking to address the spatial variability of available water in India. We found a significant decrease in the monsoon rainfall over major water surplus river basins in India. Hydrological simulations using a Variable Infiltration Capacity (VIC) model also revealed that the water yield in surplus river basins is decreasing but it is increasing in deficit basins. These findings contradict the traditional notion of dry areas becoming drier and wet areas becoming wetter in response to climate change in India. This result also calls for a re-evaluation of planning for river inter-linking to supply water from surplus to deficit river basins. PMID:27463092

  2. Indian Summer Monsoon Rainfall: Implications of Contrasting Trends in the Spatial Variability of Means and Extremes.

    PubMed

    Ghosh, Subimal; Vittal, H; Sharma, Tarul; Karmakar, Subhankar; Kasiviswanathan, K S; Dhanesh, Y; Sudheer, K P; Gunthe, S S

    2016-01-01

    India's agricultural output, economy, and societal well-being are strappingly dependent on the stability of summer monsoon rainfall, its variability and extremes. Spatial aggregate of intensity and frequency of extreme rainfall events over Central India are significantly increasing, while at local scale they are spatially non-uniform with increasing spatial variability. The reasons behind such increase in spatial variability of extremes are poorly understood and the trends in mean monsoon rainfall have been greatly overlooked. Here, by using multi-decadal gridded daily rainfall data over entire India, we show that the trend in spatial variability of mean monsoon rainfall is decreasing as exactly opposite to that of extremes. The spatial variability of extremes is attributed to the spatial variability of the convective rainfall component. Contrarily, the decrease in spatial variability of the mean rainfall over India poses a pertinent research question on the applicability of large scale inter-basin water transfer by river inter-linking to address the spatial variability of available water in India. We found a significant decrease in the monsoon rainfall over major water surplus river basins in India. Hydrological simulations using a Variable Infiltration Capacity (VIC) model also revealed that the water yield in surplus river basins is decreasing but it is increasing in deficit basins. These findings contradict the traditional notion of dry areas becoming drier and wet areas becoming wetter in response to climate change in India. This result also calls for a re-evaluation of planning for river inter-linking to supply water from surplus to deficit river basins.

  3. Smoking and diabetes. Epigenetics involvement in osseointegration.

    PubMed

    Razzouk, Sleiman; Sarkis, Rami

    2013-03-01

    Bone quality is a poorly defined parameter for successful implant placement, which largely depends upon many environmental and genetic factors unique to every individual. Smoking and diabetes are among the environmental factors that most impact osseointegration. However, there is an inter-individual variability of bone response in smokers and diabetic patients. Recent data on gene-environment interactions highlight the major role of epigenetic changes to induce a specific phenotype. Histone acetylation and DNA methylation are the main events that occur and modulate the gene expression. In this paper, we emphasize the impact of epigenetics on diabetes and smoking and describe their significance in bone healing. Also, we underscore the importance of adopting a new approach in clinical management for implant placement by customizing the treatment according to the patient's specific characteristics.

  4. Variability in dentofacial phenotypes in four families with WNT10A mutations

    PubMed Central

    Vink, Christian P; Ockeloen, Charlotte W; ten Kate, Sietske; Koolen, David A; Ploos van Amstel, Johannes Kristian; Kuijpers-Jagtman, Anne-Marie; van Heumen, Celeste C; Kleefstra, Tjitske; Carels, Carine E L

    2014-01-01

    This article describes the inter- and intra-familial phenotypic variability in four families with WNT10A mutations. Clinical characteristics of the patients range from mild to severe isolated tooth agenesis, over mild symptoms of ectodermal dysplasia, to more severe syndromic forms like odonto-onycho-dermal dysplasia (OODD) and Schöpf–Schulz–Passarge syndrome (SSPS). Recurrent WNT10A mutations were identified in all affected family members and the associated symptoms are presented with emphasis on the dentofacial phenotypes obtained with inter alia three-dimensional facial stereophotogrammetry. A comprehensive overview of the literature regarding WNT10A mutations, associated conditions and developmental defects is presented. We conclude that OODD and SSPS should be considered as variable expressions of the same WNT10A genotype. In all affected individuals, a dished-in facial appearance was observed which might be helpful in the clinical setting as a clue to the underlying genetic etiology. PMID:24398796

  5. On the continuous differentiability of inter-spike intervals of synaptically connected cortical spiking neurons in a neuronal network.

    PubMed

    Kumar, Gautam; Kothare, Mayuresh V

    2013-12-01

    We derive conditions for continuous differentiability of inter-spike intervals (ISIs) of spiking neurons with respect to parameters (decision variables) of an external stimulating input current that drives a recurrent network of synaptically connected neurons. The dynamical behavior of individual neurons is represented by a class of discontinuous single-neuron models. We report here that ISIs of neurons in the network are continuously differentiable with respect to decision variables if (1) a continuously differentiable trajectory of the membrane potential exists between consecutive action potentials with respect to time and decision variables and (2) the partial derivative of the membrane potential of spiking neurons with respect to time is not equal to the partial derivative of their firing threshold with respect to time at the time of action potentials. Our theoretical results are supported by showing fulfillment of these conditions for a class of known bidimensional spiking neuron models.

  6. Systematic evaluation of the impact of stimulation intensity on neuroplastic after-effects induced by transcranial direct current stimulation.

    PubMed

    Jamil, Asif; Batsikadze, Giorgi; Kuo, Hsiao-I; Labruna, Ludovica; Hasan, Alkomiet; Paulus, Walter; Nitsche, Michael A

    2017-02-15

    Applications of transcranial direct current stimulation to modulate human neuroplasticity have increased in research and clinical settings. However, the need for longer-lasting effects, combined with marked inter-individual variability, necessitates a deeper understanding of the relationship between stimulation parameters and physiological effects. We systematically investigated the full DC intensity range (0.5-2.0 mA) for both anodal and cathodal tDCS in a sham-controlled repeated measures design, monitoring changes in motor-cortical excitability via transcranial magnetic stimulation up to 2 h after stimulation. For both tDCS polarities, the excitability after-effects did not linearly correlate with increasing DC intensity; effects of lower intensities (0.5, 1.0 mA) showed equal, if not greater effects in motor-cortical excitability. Further, while intra-individual responses showed good reliability, inter-individual sensitivity to TMS accounted for a modest percentage of the variance in the early after-effects of 1.0 mA anodal tDCS, which may be of practical relevance for future optimizations. Contemporary non-invasive neuromodulatory techniques, such as transcranial direct current stimulation (tDCS), have shown promising potential in both restituting impairments in cortical physiology in clinical settings, as well as modulating cognitive abilities in the healthy population. However, neuroplastic after-effects of tDCS are highly dependent on stimulation parameters, relatively short lasting, and not expectedly uniform between individuals. The present study systematically investigates the full range of current intensity between 0.5 and 2.0 mA on left primary motor cortex (M1) plasticity, as well as the impact of individual-level covariates on explaining inter-individual variability. Thirty-eight healthy subjects were divided into groups of anodal and cathodal tDCS. Five DC intensities (sham, 0.5, 1.0, 1.5 and 2.0 mA) were investigated in separate sessions. Using transcranial magnetic stimulation (TMS), 25 motor-evoked potentials (MEPs) were recorded before, and 10 time points up to 2 h following 15 min of tDCS. Repeated-measures ANOVAs indicated a main effect of intensity for both anodal and cathodal tDCS. With anodal tDCS, all active intensities resulted in equivalent facilitatory effects relative to sham while for cathodal tDCS, only 1.0 mA resulted in sustained excitability diminution. An additional experiment conducted to assess intra-individual variability revealed generally good reliability of 1.0 mA anodal tDCS (ICC(2,1) = 0.74 over the first 30 min). A post hoc analysis to discern sources of inter-individual variability confirmed a previous finding in which individual TMS SI 1mV (stimulus intensity for 1 mV MEP amplitude) sensitivity correlated negatively with 1.0 mA anodal tDCS effects on excitability. Our study thus provides further insights on the extent of non-linear intensity-dependent neuroplastic after-effects of anodal and cathodal tDCS. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  7. Intergrating in Vitro and In Silico Approaches to Assess Inter-individual Toxicokinetic Variability

    EPA Science Inventory

    This educational talk provided an introduction to what is currently known to contribute to differences in how various populations and life stages metabolize chemicals to which they are exposed. These differences will impact how different populations may be affected following chem...

  8. Attitudes towards Foreign Accents among Adult Multilingual Language Users

    ERIC Educational Resources Information Center

    Dewaele, Jean-Marc; McCloskey, James

    2015-01-01

    The present study investigates inter-individual variation (linked to personality traits, multilingualism and sociobiographical variables) in the attitudes that 2035 multilinguals have of their own and others' foreign accent (FA). Data were collected through an online questionnaire. We found that multilinguals who were extraverted, emotionally…

  9. Yearly fluctuations of flower landscape in a Mediterranean scrubland: Consequences for floral resource availability.

    PubMed

    Flo, Víctor; Bosch, Jordi; Arnan, Xavier; Primante, Clara; Martín González, Ana M; Barril-Graells, Helena; Rodrigo, Anselm

    2018-01-01

    Species flower production and flowering phenology vary from year to year due to extrinsic factors. Inter-annual variability in flowering patterns may have important consequences for attractiveness to pollinators, and ultimately, plant reproductive output. To understand the consequences of flowering pattern variability, a community approach is necessary because pollinator flower choice is highly dependent on flower context. Our objectives were: 1) To quantify yearly variability in flower density and phenology; 2) To evaluate whether changes in flowering patterns result in significant changes in pollen/nectar composition. We monitored weekly flowering patterns in a Mediterranean scrubland community (23 species) over 8 years. Floral resource availability was estimated based on field measures of pollen and nectar production per flower. We analysed inter-annual variation in flowering phenology (duration and date of peak bloom) and flower production, and inter-annual and monthly variability in flower, pollen and nectar species composition. We also investigated potential phylogenetic effects on inter-annual variability of flowering patterns. We found dramatic variation in yearly flower production both at the species and community levels. There was also substantial variation in flowering phenology. Importantly, yearly fluctuations were far from synchronous across species, and resulted in significant changes in floral resources availability and composition at the community level. Changes were especially pronounced late in the season, at a time when flowers are scarce and pollinator visitation rates are particularly high. We discuss the consequences of our findings for pollinator visitation and plant reproductive success in the current scenario of climate change.

  10. Yearly fluctuations of flower landscape in a Mediterranean scrubland: Consequences for floral resource availability

    PubMed Central

    Primante, Clara; Martín González, Ana M.; Barril-Graells, Helena

    2018-01-01

    Species flower production and flowering phenology vary from year to year due to extrinsic factors. Inter-annual variability in flowering patterns may have important consequences for attractiveness to pollinators, and ultimately, plant reproductive output. To understand the consequences of flowering pattern variability, a community approach is necessary because pollinator flower choice is highly dependent on flower context. Our objectives were: 1) To quantify yearly variability in flower density and phenology; 2) To evaluate whether changes in flowering patterns result in significant changes in pollen/nectar composition. We monitored weekly flowering patterns in a Mediterranean scrubland community (23 species) over 8 years. Floral resource availability was estimated based on field measures of pollen and nectar production per flower. We analysed inter-annual variation in flowering phenology (duration and date of peak bloom) and flower production, and inter-annual and monthly variability in flower, pollen and nectar species composition. We also investigated potential phylogenetic effects on inter-annual variability of flowering patterns. We found dramatic variation in yearly flower production both at the species and community levels. There was also substantial variation in flowering phenology. Importantly, yearly fluctuations were far from synchronous across species, and resulted in significant changes in floral resources availability and composition at the community level. Changes were especially pronounced late in the season, at a time when flowers are scarce and pollinator visitation rates are particularly high. We discuss the consequences of our findings for pollinator visitation and plant reproductive success in the current scenario of climate change. PMID:29346453

  11. Inter-annual and spatial variability in hillslope runoff and mercury flux during spring snowmelt.

    PubMed

    Haynes, Kristine M; Mitchell, Carl P J

    2012-08-01

    Spring snowmelt is an important period of mercury (Hg) export from watersheds. Limited research has investigated the potential effects of climate variability on hydrologic and Hg fluxes during spring snowmelt. The purpose of this research was to assess the potential impacts of inter-annual climate variability on Hg mobility in forested uplands, as well as spatial variability in hillslope hydrology and Hg fluxes. We compared hydrological flows, Hg and solute mobility from three adjacent hillslopes in the S7 watershed of the Marcell Experimental Forest, Minnesota during two very different spring snowmelt periods: one following a winter (2009-2010) with severely diminished snow accumulation (snow water equivalent (SWE) = 48 mm) with an early melt, and a second (2010-2011) with significantly greater winter snow accumulation (SWE = 98 mm) with average to late melt timing. Observed inter-annual differences in total Hg (THg) and dissolved organic carbon (DOC) yields were predominantly flow-driven, as the proportion by which solute yields increased was the same as the increase in runoff. Accounting for inter-annual differences in flow, there was no significant difference in THg and DOC export between the two snowmelt periods. The spring 2010 snowmelt highlighted the important contribution of melting soil frost in the timing of a considerable portion of THg exported from the hillslope, accounting for nearly 30% of the THg mobilized. Differences in slope morphology and soil depths to the confining till layer were important in controlling the large observed spatial variability in hydrological flowpaths, transmissivity feedback responses, and Hg flux trends across the adjacent hillslopes.

  12. Inter-annual Variability of Snowfall in the Lower Peninsula of Michigan, USA

    NASA Astrophysics Data System (ADS)

    Meng, L.

    2016-12-01

    Winter snowfall, particularly lake-effect snowfall, impacts all aspects of Michigan life in the wintertime, from motorsports and tourism to impacting the day-to-day lives of residents. Understanding the inter-annual variability of winter snowfall will provide sound basis for local community safety management and improve weather forecasting. This study attempts to understand the trend in winter snowfall and the influencing factors of winter snowfall variability in the Lower Peninsula of Michigan (LPM) using station snowfall measurements and statistical analysis. Our study demonstrates that snowfall has significantly increased from 1932 to 2015. Correlation analysis suggests that regionally average air temperatures have a strong negative relationship with snowfall in LPM. On average, approximately 27% of inter-annual variability in snowfall can be explained by regionally average air temperatures. ENSO events are also negatively related to snowfall in LPM and can explain 8% of inter-annual variability. North Atlantic Oscillation (NAO) does not have strong influence on snowfall. Composite analysis demonstrates that on annual basis, more winter snowfall occurs during the years with higher maximum ice cover (MIC) than during the years with lower MIC in Lake Michigan. Higher MIC is often associated with lower air temperatures which are negatively related to winter snowfall. This study could provide insight on future snow related climate model improvement and weather forecasting.

  13. MODELING OF HUMAN EXPOSURE TO IN-VEHICLE PM2.5 FROM ENVIRONMENTAL TOBACCO SMOKE

    PubMed Central

    Cao, Ye; Frey, H. Christopher

    2012-01-01

    Environmental tobacco smoke (ETS) is estimated to be a significant contributor to in-vehicle human exposure to fine particulate matter of 2.5 µm or smaller (PM2.5). A critical assessment was conducted of a mass balance model for estimating PM2.5 concentration with smoking in a motor vehicle. Recommendations for the range of inputs to the mass-balance model are given based on literature review. Sensitivity analysis was used to determine which inputs should be prioritized for data collection. Air exchange rate (ACH) and the deposition rate have wider relative ranges of variation than other inputs, representing inter-individual variability in operations, and inter-vehicle variability in performance, respectively. Cigarette smoking and emission rates, and vehicle interior volume, are also key inputs. The in-vehicle ETS mass balance model was incorporated into the Stochastic Human Exposure and Dose Simulation for Particulate Matter (SHEDS-PM) model to quantify the potential magnitude and variability of in-vehicle exposures to ETS. The in-vehicle exposure also takes into account near-road incremental PM2.5 concentration from on-road emissions. Results of probabilistic study indicate that ETS is a key contributor to the in-vehicle average and high-end exposure. Factors that mitigate in-vehicle ambient PM2.5 exposure lead to higher in-vehicle ETS exposure, and vice versa. PMID:23060732

  14. The influence of intra- and inter-annual meteorological variability on dengue transmission: a multi-level modeling analysis

    NASA Astrophysics Data System (ADS)

    Wen, Tzai-Hung; Chen, Tzu-Hsin

    2017-04-01

    Dengue fever is one of potentially life-threatening mosquito-borne diseases and IPCC Fifth Assessment Report (AR5) has confirmed that dengue incidence is sensitive to the critical weather conditions, such as effects of temperature. However, previous literature focused on the effects of monthly or weekly average temperature or accumulative precipitation on dengue incidence. The influence of intra- and inter-annual meteorological variability on dengue outbreak is under investigated. The purpose of the study focuses on measuring the effect of the intra- and inter-annual variations of temperature and precipitation on dengue outbreaks. We developed the indices of intra-annual temperature variability are maximum continuity, intermittent, and accumulation of most suitable temperature (MST) for dengue vectors; and also the indices of intra-annual precipitation variability, including the measure of continuity of wetness or dryness during a pre-epidemic period; and rainfall intensity during an epidemic period. We used multi-level modeling to investigate the intra- and inter-annual meteorological variations on dengue outbreaks in southern Taiwan from 1998-2015. Our results indicate that accumulation and maximum continuity of MST are more significant than average temperature on dengue outbreaks. The effect of continuity of wetness during the pre-epidemic period is significantly more positive on promoting dengue outbreaks than the rainfall effect during the epidemic period. Meanwhile, extremely high or low rainfall density during an epidemic period do not promote the spread of dengue epidemics. Our study differentiates the effects of intra- and inter-annual meteorological variations on dengue outbreaks and also provides policy implications for further dengue control under the threats of climate change. Keywords: dengue fever, meteorological variations, multi-level model

  15. Individual Differences in Pain: Understanding the Mosaic that Makes Pain Personal

    PubMed Central

    Fillingim, Roger B.

    2016-01-01

    The experience of pain is characterized by tremendous inter-individual variability. Multiple biological and psychosocial variables contribute to these individual differences in pain, including demographic variables, genetic factors, and psychosocial processes. For example, sex, age and ethnic group differences in the prevalence of chronic pain conditions have been widely reported. Moreover, these demographic factors have been associated with responses to experimentally-induced pain. Similarly, both genetic and psychosocial factors contribute to clinical and experimental pain responses. Importantly, these different biopsychosocial influences interact with each other in complex ways to sculpt the experience of pain. Some genetic associations with pain have been found to vary across sex and ethnic group. Moreover, genetic factors also interact with psychosocial factors, including stress and pain catastrophizing, to influence pain. The individual and combined influences of these biological and psychosocial variables results in a unique mosaic of factors that contributes pain in each individual. Understanding these mosaics is critically important in order to provide optimal pain treatment, and future research to further elucidate the nature of these biopsychosocial interactions is needed in order to provide more informed and personalized pain care. PMID:27902569

  16. Ocean acidification impacts on sperm mitochondrial membrane potential bring sperm swimming behaviour near its tipping point.

    PubMed

    Schlegel, Peter; Binet, Monique T; Havenhand, Jonathan N; Doyle, Christopher J; Williamson, Jane E

    2015-04-01

    Broadcast spawning marine invertebrates are susceptible to environmental stressors such as climate change, as their reproduction depends on the successful meeting and fertilization of gametes in the water column. Under near-future scenarios of ocean acidification, the swimming behaviour of marine invertebrate sperm is altered. We tested whether this was due to changes in sperm mitochondrial activity by investigating the effects of ocean acidification on sperm metabolism and swimming behaviour in the sea urchin Centrostephanus rodgersii. We used a fluorescent molecular probe (JC-1) and flow cytometry to visualize mitochondrial activity (measured as change in mitochondrial membrane potential, MMP). Sperm MMP was significantly reduced in ΔpH -0.3 (35% reduction) and ΔpH -0.5 (48% reduction) treatments, whereas sperm swimming behaviour was less sensitive with only slight changes (up to 11% decrease) observed overall. There was significant inter-individual variability in responses of sperm swimming behaviour and MMP to acidified seawater. We suggest it is likely that sperm exposed to these changes in pH are close to their tipping point in terms of physiological tolerance to acidity. Importantly, substantial inter-individual variation in responses of sperm swimming to ocean acidification may increase the scope for selection of resilient phenotypes, which, if heritable, could provide a basis for adaptation to future ocean acidification. © 2015. Published by The Company of Biologists Ltd.

  17. Interindividual variability in sweat electrolyte concentration in marathoners.

    PubMed

    Lara, Beatriz; Gallo-Salazar, César; Puente, Carlos; Areces, Francisco; Salinero, Juan José; Del Coso, Juan

    2016-01-01

    Sodium (Na(+)) intake during exercise aims to replace the Na(+) lost by sweat to avoid electrolyte imbalances, especially in endurance disciplines. However, Na(+) needs can be very different among individuals because of the great inter-individual variability in sweat electrolyte concentration. The aim of this investigation was to determine sweat electrolyte concentration in a large group of marathoners. A total of 157 experienced runners (141 men and 16 women) completed a marathon race (24.4 ± 3.6 °C and 27.7 ± 4.8 % of humidity). During the race, sweat samples were collected by using sweat patches placed on the runners' forearms. Sweat electrolyte concentration was measured by using photoelectric flame photometry. As a group, sweat Na(+) concentration was 42.9 ± 18.7 mmol·L(-1) (minimal-maximal value = 7.0-95.5 mmol·L(-1)), sweat Cl(-) concentration was 32.2 ± 15.6 mmol·L(-1) (7.3-90.6 mmol·L(-1)) and sweat K(+) concentration was 6.0 ± 0.9 mmol·L(-1) (3.1-8.0 mmol·L(-1)). Women presented lower sweat Na(+) (33.9 ± 12.1 vs 44.0 ± 19.1 mmol·L(-1); P = 0.04) and sweat Cl(-) concentrations (22.9 ± 10.5 vs 33.2 ± 15.8 mmol·L(-1); P = 0.01) than men. A 20 % of individuals presented a sweat Na(+) concentration higher than 60 mmol·L(-1) while this threshold was not surpassed by any female marathoner. Sweat electrolyte concentration did not correlate to sweat rate, age, body characteristics, experience or training. Although there was a significant correlation between sweat Na(+) concentration and running pace (r = 0.18; P = 0.03), this association was weak to interpret that sweat Na(+) concentration increased with running pace. The inter-individual variability in sweat electrolyte concentration was not explained by any individual characteristics except for individual running pace and sex. An important portion (20 %) of marathoners might need special sodium intake recommendations due to their high sweat salt losses.

  18. Physiologically Based Pharmacokinetic (PBPK) Modeling of ...

    EPA Pesticide Factsheets

    Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, inter-individual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data.Objectives: To evaluate the utility of genetically diverse mouse strains for estimating toxicokinetic population variability for risk assessment, using trichloroethylene (TCE) metabolism as a case study. Methods: We used data on oxidative and glutathione conjugation metabolism of TCE in 16 inbred and one hybrid mouse strains to calibrate and extend existing physiologically-based pharmacokinetic (PBPK) models. We added one-compartment models for glutathione metabolites and a two-compartment model for dichloroacetic acid (DCA). A Bayesian population analysis of inter-strain variability was used to quantify variability in TCE metabolism. Results: Concentration-time profiles for TCE metabolism to oxidative and glutathione conjugation metabolites varied across strains. Median predictions for the metabolic flux through oxidation was less variable (5-fold range) than that through glutathione conjugation (10-fold range). For oxidative metabolites, median predictions of trichloroacetic acid production was less variable (2-fold range) than DCA production (5-fold range), although uncertainty bounds for DCA exceeded the predicted variability. Conclusions:

  19. Does Body Mass Index Moderate the Association between Posttraumatic Stress Disorder Symptoms and Suicidal Ideation in Iraq/Afghanistan Veterans?

    PubMed Central

    Kittel, Julie A.; DeBeer, Bryann B.; Kimbrel, Nathan A.; Matthieu, Monica M.; Meyer, Eric C.; Gulliver, Suzy Bird; Morissette, Sandra B.

    2017-01-01

    Suicide, PTSD, and obesity co-occur at high rates among returning veterans, yet limited research exists regarding the relationship among these variables. Self-report and diagnostic interview data from a longitudinal study of Iraq and Afghanistan veterans (N = 130) enrolled in VA healthcare examined these inter-relations. As hypothesized, body mass index (BMI) significantly moderated the association between PTSD and suicidal ideation such that the association between PTSD and suicidal ideation was strongest among individuals with a high BMI. Programs that focus on health promotion, trauma treatment, and weight management should continue to monitor suicide risk. PMID:27479102

  20. Mapping the structure of perceptual and visual-motor abilities in healthy young adults.

    PubMed

    Wang, Lingling; Krasich, Kristina; Bel-Bahar, Tarik; Hughes, Lauren; Mitroff, Stephen R; Appelbaum, L Gregory

    2015-05-01

    The ability to quickly detect and respond to visual stimuli in the environment is critical to many human activities. While such perceptual and visual-motor skills are important in a myriad of contexts, considerable variability exists between individuals in these abilities. To better understand the sources of this variability, we assessed perceptual and visual-motor skills in a large sample of 230 healthy individuals via the Nike SPARQ Sensory Station, and compared variability in their behavioral performance to demographic, state, sleep and consumption characteristics. Dimension reduction and regression analyses indicated three underlying factors: Visual-Motor Control, Visual Sensitivity, and Eye Quickness, which accounted for roughly half of the overall population variance in performance on this battery. Inter-individual variability in Visual-Motor Control was correlated with gender and circadian patters such that performance on this factor was better for males and for those who had been awake for a longer period of time before assessment. The current findings indicate that abilities involving coordinated hand movements in response to stimuli are subject to greater individual variability, while visual sensitivity and occulomotor control are largely stable across individuals. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Variability in PAH-DNA adduct measurements in peripheral mononuclear cells: implications for quantitative cancer risk assessment.

    PubMed

    Dickey, C; Santella, R M; Hattis, D; Tang, D; Hsu, Y; Cooper, T; Young, T L; Perera, F P

    1997-10-01

    Biomarkers such as DNA adducts have significant potential to improve quantitative risk assessment by characterizing individual differences in metabolism of genotoxins and DNA repair and accounting for some of the factors that could affect interindividual variation in cancer risk. Inherent uncertainty in laboratory measurements and within-person variability of DNA adduct levels over time are putatively unrelated to cancer risk and should be subtracted from observed variation to better estimate interindividual variability of response to carcinogen exposure. A total of 41 volunteers, both smokers and nonsmokers, were asked to provide a peripheral blood sample every 3 weeks for several months in order to specifically assess intraindividual variability of polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels. The intraindividual variance in PAH-DNA adduct levels, together with measurement uncertainty (laboratory variability and unaccounted for differences in exposure), constituted roughly 30% of the overall variance. An estimated 70% of the total variance was contributed by interindividual variability and is probably representative of the true biologic variability of response to carcinogenic exposure in lymphocytes. The estimated interindividual variability in DNA damage after subtracting intraindividual variability and measurement uncertainty was 24-fold. Inter-individual variance was higher (52-fold) in persons who constitutively lack the Glutathione S-Transferase M1 (GSTM1) gene which is important in the detoxification pathway of PAH. Risk assessment models that do not consider the variability of susceptibility to DNA damage following carcinogen exposure may underestimate risks to the general population, especially for those people who are most vulnerable.

  2. Approaches for modeling within subject variability in pharmacometric count data analysis: dynamic inter-occasion variability and stochastic differential equations.

    PubMed

    Deng, Chenhui; Plan, Elodie L; Karlsson, Mats O

    2016-06-01

    Parameter variation in pharmacometric analysis studies can be characterized as within subject parameter variability (WSV) in pharmacometric models. WSV has previously been successfully modeled using inter-occasion variability (IOV), but also stochastic differential equations (SDEs). In this study, two approaches, dynamic inter-occasion variability (dIOV) and adapted stochastic differential equations, were proposed to investigate WSV in pharmacometric count data analysis. These approaches were applied to published count models for seizure counts and Likert pain scores. Both approaches improved the model fits significantly. In addition, stochastic simulation and estimation were used to explore further the capability of the two approaches to diagnose and improve models where existing WSV is not recognized. The results of simulations confirmed the gain in introducing WSV as dIOV and SDEs when parameters vary randomly over time. Further, the approaches were also informative as diagnostics of model misspecification, when parameters changed systematically over time but this was not recognized in the structural model. The proposed approaches in this study offer strategies to characterize WSV and are not restricted to count data.

  3. Presence and inter-individual variability of carboxylesterases (CES1 and CES2) in human lung.

    PubMed

    Gabriele, Morena; Puccini, Paola; Lucchi, Marco; Vizziello, Anna; Gervasi, Pier Giovanni; Longo, Vincenzo

    2018-04-01

    Lungs are pharmacologically active organs and the pulmonary drug metabolism is of interest for inhaled drugs design. Carboxylesterases (CESs) are enzymes catalyzing the hydrolysis of many structurally different ester, amide and carbamate chemicals, including prodrugs. For the first time, the presence, kinetics, inhibition and inter-individual variations of the major liver CES isozymes (CES1 and CES2) were investigated in cytosol and microsomes of human lungs from 20 individuals using 4-nitrophenyl acetate (pNPA), 4-methylumbelliferyl acetate (4-MUA), and fluorescein diacetate (FD) as substrates the rates of hydrolysis (V max ) for pNPA and 4-MUA, unlike FD, were double in microsomes than in cytosol. In these cellular fractions, the V max of pNPA, as CES1 marker, were much greater (30-50-fold) than those of FD, as a specific CES2 marker. Conversely, the K m values were comparable suggesting the involvement of the same enzymes. Inhibition studies revealed that the FD hydrolysis was inhibited by bis-p-nitrophenylphosphate, phenylmethanesulfonyl fluoride, and loperamide (specific for CES2), whereas the pNPA and 4-MUA hydrolysis inhibition was limited. Inhibitors selective for other esterases missed having any effect on above-mentioned activities. In cytosol and microsomes of 20 lung samples, inter-individual variations were found for the hydrolysis of pNPA (2.5-5-fold), FD or 4-MUA (8-15-fold). Similar variations were also observed in CES1 and CES2 gene expression, although determined in a small number (n = 9) of lung samples. The identification of CES1 and CES2 and their variability in human lungs are important for drug metabolism and design of prodrugs which need to be activated in this organ. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. PHENOTYPIC VARIABILITY IN INDIVIDUALS WITH TYPE V OSTEOGENESIS IMPERFECTA WITH IDENTICAL IFITM5 MUTATIONS

    PubMed Central

    Fitzgerald, Jamie; Holden, Paul; Wright, Hollis; Wilmot, Beth; Hata, Abigail; Steiner, Robert D.; Basel, Don

    2016-01-01

    Background Osteogenesis imperfecta (OI) type V is a dominantly inherited skeletal dysplasia characterized by fractures and progressive deformity of long bones. In addition, patients often present with radial head dislocation, hyperplastic callus, and calcification of the forearm interosseous membrane. Recently, a specific mutation in the IFITM5 gene was found to be responsible for OI type V. This mutation, a C to T transition 14 nucleotides upstream from the endogenous start codon, creates a new start methionine that appears to be preferentially used by the translational machinery. However, the mechanism by which the lengthened protein results in a dominant type of OI is unknown. Methods and Results We report 7 ethnically diverse (African-American, Caucasian, Hispanic, and African) individuals with OI type V from 2 families and 2 sporadic cases. Exome sequencing failed to identify a causative mutation. Using Sanger sequencing, we found that all affected individuals in our cohort possess the c.−14 IFITM5 variant, further supporting the notion that OI type V is caused by a single, discrete mutation. Our patient cohort demonstrated inter-and intrafamilial phenotypic variability, including a father with classic OI type V whose daughter had a phenotype similar to OI type I. This clinical variability suggests that modifier genes influence the OI type V phenotype. We also confirm that the mutation creates an aberrant IFITM5 protein containing an additional 5 amino acids at the N-terminus. Conclusions The variable clinical signs in these cases illustrate the significant variability of the OI type V phenotype caused by the c.−14 IFITM5 mutation. The affected individuals are more ethnically diverse than previously reported. PMID:28824928

  5. High internal noise and poor external noise filtering characterize perception in autism spectrum disorder.

    PubMed

    Park, Woon Ju; Schauder, Kimberly B; Zhang, Ruyuan; Bennetto, Loisa; Tadin, Duje

    2017-12-14

    An emerging hypothesis postulates that internal noise is a key factor influencing perceptual abilities in autism spectrum disorder (ASD). Given fundamental and inescapable effects of noise on nearly all aspects of neural processing, this could be a critical abnormality with broad implications for perception, behavior, and cognition. However, this proposal has been challenged by both theoretical and empirical studies. A crucial question is whether and how internal noise limits perception in ASD, independently from other sources of perceptual inefficiency, such as the ability to filter out external noise. Here, we separately estimated internal noise and external noise filtering in ASD. In children and adolescents with and without ASD, we computationally modeled individuals' visual orientation discrimination in the presence of varying levels of external noise. The results revealed increased internal noise and worse external noise filtering in individuals with ASD. For both factors, we also observed high inter-individual variability in ASD, with only the internal noise estimates significantly correlating with severity of ASD symptoms. We provide evidence for reduced perceptual efficiency in ASD that is due to both increased internal noise and worse external noise filtering, while highlighting internal noise as a possible contributing factor to variability in ASD symptoms.

  6. Patterns and Predictors of Tic Suppressibility in Youth With Tic Disorders

    PubMed Central

    Conelea, Christine A.; Wellen, Brianna; Woods, Douglas W.; Greene, Deanna J.; Black, Kevin J.; Specht, Matthew; Himle, Michael B.; Lee, Han-Joo; Capriotti, Matthew

    2018-01-01

    Tic suppression is the primary target of tic disorder treatment, but factors that influence voluntary tic inhibition are not well understood. Several studies using the Tic Suppression Task have demonstrated significant inter-individual variability in tic suppressibility but have individually been underpowered to address correlates of tic suppression. The present study explored patterns and clinical correlates of reward-enhanced tic suppression in youth with tic disorders using a large, pooled dataset. Individual-level data from nine studies using the Tic Suppression Task were pooled, yielding a sample of 99 youth with tic disorders. Analyses examined patterns of tic suppressibility and the relationship between tic suppressibility and demographic and clinical characteristics. A large majority of youth demonstrated a high degree of tic suppression, but heterogeneous patterns of tic suppressibility were also observed. Better tic suppressibility was related to older age and more frequent tics but unrelated to other clinical variables, including presence of psychiatric comorbidity, psychotropic medication status, tic and premonitory urge severity, and self-rated tic suppressibility. The mechanisms underlying the observed heterogeneity in reward-enhanced tic suppressibility warrant further investigation. The Tic Suppression Task is a promising method for testing mechanistic hypotheses related to tic suppression. PMID:29875706

  7. Patterns and Predictors of Tic Suppressibility in Youth With Tic Disorders.

    PubMed

    Conelea, Christine A; Wellen, Brianna; Woods, Douglas W; Greene, Deanna J; Black, Kevin J; Specht, Matthew; Himle, Michael B; Lee, Han-Joo; Capriotti, Matthew

    2018-01-01

    Tic suppression is the primary target of tic disorder treatment, but factors that influence voluntary tic inhibition are not well understood. Several studies using the Tic Suppression Task have demonstrated significant inter-individual variability in tic suppressibility but have individually been underpowered to address correlates of tic suppression. The present study explored patterns and clinical correlates of reward-enhanced tic suppression in youth with tic disorders using a large, pooled dataset. Individual-level data from nine studies using the Tic Suppression Task were pooled, yielding a sample of 99 youth with tic disorders. Analyses examined patterns of tic suppressibility and the relationship between tic suppressibility and demographic and clinical characteristics. A large majority of youth demonstrated a high degree of tic suppression, but heterogeneous patterns of tic suppressibility were also observed. Better tic suppressibility was related to older age and more frequent tics but unrelated to other clinical variables, including presence of psychiatric comorbidity, psychotropic medication status, tic and premonitory urge severity, and self-rated tic suppressibility. The mechanisms underlying the observed heterogeneity in reward-enhanced tic suppressibility warrant further investigation. The Tic Suppression Task is a promising method for testing mechanistic hypotheses related to tic suppression.

  8. Population pharmacokinetics of gabapentin in healthy Korean subjects with influence of genetic polymorphisms of ABCB1.

    PubMed

    Tran, Phuong; Yoo, Hee-Doo; Ngo, Lien; Cho, Hea-Young; Lee, Yong-Bok

    2017-12-01

    The objective of this study was to perform population pharmacokinetic (PK) analysis of gabapentin in healthy Korean subjects and to investigate the possible effect of genetic polymorphisms (1236C > T, 2677G > T/A, and 3435C > T) of ABCB1 gene on PK parameters of gabapentin. Data were collected from bioequivalence studies, in which 173 subjects orally received three different doses of gabapentin (300, 400, and 800 mg). Only data from reference formulation were used. Population pharmacokinetics (PKs) of gabapentin was estimated using a nonlinear mixed-effects model (NONMEM). Gabapentin showed considerable inter-individual variability (from 5.2- to 8.7-fold) in PK parameters. Serum concentration of gabapentin was well fitted by a one-compartment model with first-order absorption and lag time. An inhibitory Emax model was applied to describe the effect of dose on bioavailability. The oral clearance was estimated to be 11.1 L/h. The volume of distribution was characterized as 81.0 L. The absorption rate constant was estimated at 0.860 h -1 , and the lag time was predicted at 0.311 h. Oral bioavailability was estimated to be 68.8% at dose of 300 mg, 62.7% at dose of 400 mg, and 47.1% at dose of 800 mg. The creatinine clearance significantly influenced on the oral clearance (P < 0.005) and ABCB1 2677G > T/A genotypes significantly influenced on the absorption rate constant (P < 0.05) of gabapentin. However, ABCB1 1236C > T and 3435C > T genotypes showed no significant effect on gabapentin PK parameters. The results of the present study indicate that the oral bioavailability of gabapentin is decreased when its dosage is increased. In addition, ABCB1 2677G > T/A polymorphism can explain the substantial inter-individual variability in the absorption of gabapentin.

  9. Population Pharmacokinetic Analyses of Lithium: A Systematic Review.

    PubMed

    Methaneethorn, Janthima

    2018-02-01

    Even though lithium has been used for the treatment of bipolar disorder for several decades, its toxicities are still being reported. The major limitation in the use of lithium is its narrow therapeutic window. Several methods have been proposed to predict lithium doses essential to attain therapeutic levels. One of the methods used to guide lithium therapy is population pharmacokinetic approach which accounts for inter- and intra-individual variability in predicting lithium doses. Several population pharmacokinetic studies of lithium have been conducted. The objective of this review is to provide information on population pharmacokinetics of lithium focusing on nonlinear mixed effect modeling approach and to summarize significant factors affecting lithium pharmacokinetics. A literature search was conducted from PubMed database from inception to December, 2016. Studies conducted in humans, using lithium as a study drug, providing population pharmacokinetic analyses of lithium by means of nonlinear mixed effect modeling, were included in this review. Twenty-four articles were identified from the database. Seventeen articles were excluded based on the inclusion and exclusion criteria. A total of seven articles were included in this review. Of these, only one study reported a combined population pharmacokinetic-pharmacodynamic model of lithium. Lithium pharmacokinetics were explained using both one- and two-compartment models. The significant predictors of lithium clearance identified in most studies were renal function and body size. One study reported a significant effect of age on lithium clearance. The typical values of lithium clearance ranged from 0.41 to 9.39 L/h. The magnitude of inter-individual variability on lithium clearance ranged from 12.7 to 25.1%. Only two studies evaluated the models using external data sets. Model methodologies in each study are summarized and discussed in this review. For future perspective, a population pharmacokinetic-pharmacodynamic study of lithium is recommended. Moreover, external validation of previously published models should be performed.

  10. Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers.

    PubMed

    Zhang, Dong-mei; Wang, Kun; Zhao, Xia; Li, Yun-fei; Zheng, Qing-shan; Wang, Zi-ning; Cui, Yi-min

    2012-11-01

    To investigate the population pharmacokinetics (PK) and pharmacodynamics (PD) of bivalirudin, a synthetic bivalent direct thrombin inhibitor, in young healthy Chinese subjects. Thirty-six young healthy volunteers were randomly assigned into 4 groups received bivalirudin 0.5 mg/kg, 0.75 mg/kg, and 1.05 mg/kg intravenous bolus, 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg intravenous infusion per hour for 4 h. Blood samples were collected to measure bivalirudin plasma concentration and activated clotting time (ACT). Population PK-PD analysis was performed using the nonlinear mixed-effects model software NONMEM. The final models were validated with bootstrap and prediction-corrected visual predictive check (pcVPC) approaches. The final PK model was a two-compartment model without covariates. The typical PK population values of clearance (CL), apparent distribution volume of the central-compartment (V(1)), inter-compartmental clearance (Q) and apparent distribution volume of the peripheral compartment (V(2)) were 0.323 L·h(-1)·kg(-1), 0.086 L/kg, 0.0957 L·h(-1)·kg(-1), and 0.0554 L/kg, respectively. The inter-individual variabilities of these parameters were 14.8%, 24.2%, fixed to 0% and 15.6%, respectively. The final PK-PD model was a sigmoid E(max) model without the Hill coefficient. In this model, a covariate, red blood cell count (RBC(*)), had a significant effect on the EC(50) value. The typical PD population values of maximum effect (E(max)), EC(50), baseline ACT value (E(0)) and the coefficient of RBC(*) on EC(50) were 318 s, 2.44 mg/L, 134 s and 1.70, respectively. The inter-individual variabilities of E(max), EC(50), and E(0) were 6.80%, 46.4%, and 4.10%, respectively. Population PK-PD models of bivalirudin in healthy young Chinese subjects have been developed, which may provide a reference for future use of bivalirudin in China.

  11. Short-term quality of life after subthalamic stimulation depends on non-motor symptoms in Parkinson's disease.

    PubMed

    Dafsari, Haidar Salimi; Weiß, Luisa; Silverdale, Monty; Rizos, Alexandra; Reddy, Prashanth; Ashkan, Keyoumars; Evans, Julian; Reker, Paul; Petry-Schmelzer, Jan Niklas; Samuel, Michael; Visser-Vandewalle, Veerle; Antonini, Angelo; Martinez-Martin, Pablo; Ray-Chaudhuri, K; Timmermann, Lars

    2018-02-24

    Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in advanced Parkinson's disease (PD). However, considerable inter-individual variability has been observed for QoL outcome. We hypothesized that demographic and preoperative NMS characteristics can predict postoperative QoL outcome. In this ongoing, prospective, multicenter study (Cologne, Manchester, London) including 88 patients, we collected the following scales preoperatively and on follow-up 6 months postoperatively: PDQuestionnaire-8 (PDQ-8), NMSScale (NMSS), NMSQuestionnaire (NMSQ), Scales for Outcomes in PD (SCOPA)-motor examination, -complications, and -activities of daily living, levodopa equivalent daily dose. We dichotomized patients into "QoL responders"/"non-responders" and screened for factors associated with QoL improvement with (1) Spearman-correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions using aforementioned "responders/non-responders" as dependent variable. All outcomes improved significantly on follow-up. However, approximately 44% of patients were categorized as "QoL non-responders". Spearman-correlations, linear and logistic regression analyses were significant for NMSS and NMSQ but not for SCOPA-motor examination. Post-hoc, we identified specific NMS (flat moods, difficulties experiencing pleasure, pain, bladder voiding) as significant contributors to QoL outcome. Our results provide evidence that QoL improvement after STN-DBS depends on preoperative NMS characteristics. These findings are important in the advising and selection of individuals for DBS therapy. Future studies investigating motor and non-motor PD clusters may enable stratifying QoL outcomes and help predict patients' individual prospects of benefiting from DBS. Copyright © 2018. Published by Elsevier Inc.

  12. An evaluation of non-metric cranial traits used to estimate ancestry in a South African sample.

    PubMed

    L'Abbé, E N; Van Rooyen, C; Nawrocki, S P; Becker, P J

    2011-06-15

    Establishing ancestry from a skeleton for forensic purposes has been shown to be difficult. The purpose of this paper is to address the application of thirteen non-metric traits to estimate ancestry in three South African groups, namely White, Black and "Coloured". In doing so, the frequency distribution of thirteen non-metric traits among South Africans are presented; the relationship of these non-metric traits with ancestry, sex, age at death are evaluated; and Kappa statistics are utilized to assess the inter and intra-rater reliability. Crania of 520 known individuals were obtained from four skeletal samples in South Africa: the Pretoria Bone Collection, the Raymond A. Dart Collection, the Kirsten Collection and the Student Bone Collection from the University of the Free State. Average age at death was 51, with an age range between 18 and 90. Thirteen commonly used non-metric traits from the face and jaw were scored; definition and illustrations were taken from Hefner, Bass and Hauser and De Stephano. Frequency distributions, ordinal regression and Cohen's Kappa statistics were performed as a means to assess population variation and repeatability. Frequency distributions were highly variable among South Africans. Twelve of the 13 variables had a statistically significant relationship with ancestry. Sex significantly affected only one variable, inter-orbital breadth, and age at death affected two (anterior nasal spine and alveolar prognathism). The interaction of ancestry and sex independently affected three variables (nasal bone contour, nasal breadth, and interorbital breadth). Seven traits had moderate to excellent repeatability, while poor scoring consistency was noted for six variables. Difficulties in repeating several of the trait scores may require either a need for refinement of the definitions, or these character states may not adequately describe the observable morphology in the population. The application of the traditional experience-based approach for estimating ancestry in forensic case work is problematic. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Disruption to control network function correlates with altered dynamic connectivity in the wider autism spectrum.

    PubMed

    de Lacy, N; Doherty, D; King, B H; Rachakonda, S; Calhoun, V D

    2017-01-01

    Autism is a common developmental condition with a wide, variable range of co-occurring neuropsychiatric symptoms. Contrasting with most extant studies, we explored whole-brain functional organization at multiple levels simultaneously in a large subject group reflecting autism's clinical diversity, and present the first network-based analysis of transient brain states, or dynamic connectivity , in autism. Disruption to inter-network and inter-system connectivity, rather than within individual networks, predominated. We identified coupling disruption in the anterior-posterior default mode axis, and among specific control networks specialized for task start cues and the maintenance of domain-independent task positive status, specifically between the right fronto-parietal and cingulo-opercular networks and default mode network subsystems. These appear to propagate downstream in autism, with significantly dampened subject oscillations between brain states, and dynamic connectivity configuration differences. Our account proposes specific motifs that may provide candidates for neuroimaging biomarkers within heterogeneous clinical populations in this diverse condition.

  14. Reproducibility and reliability of the ankle-brachial index as assessed by vascular experts, family physicians and nurses.

    PubMed

    Holland-Letz, Tim; Endres, Heinz G; Biedermann, Stefanie; Mahn, Matthias; Kunert, Joachim; Groh, Sabine; Pittrow, David; von Bilderling, Peter; Sternitzky, Reinhardt; Diehm, Curt

    2007-05-01

    The reliability of ankle-brachial index (ABI) measurements performed by different observer groups in primary care has not yet been determined. The aims of the study were to provide precise estimates for all effects influencing the variability of the ABI (patients' individual variability, intra- and inter-observer variability), with particular focus on the performance of different observer groups. Using a partially balanced incomplete block design, 144 unselected individuals aged > or = 65 years underwent double ABI measurements by one vascular surgeon or vascular physician, one family physician and one nurse with training in Doppler sonography. Three groups comprising a total of 108 individuals were analyzed (only two with ABI < 0.90). Errors for two repeated measurements for all three observer groups did not differ (experts 8.5%, family physicians 7.7%, and nurses 7.5%, p = 0.39). There was no relevant bias among observer groups. Intra-observer variability expressed as standard deviation divided by the mean was 8%, and inter-observer variability was 9%. In conclusion, reproducibility of the ABI measurement was good in this cohort of elderly patients who almost all had values in the normal range. The mean error of 8-9% within or between observers is smaller than with established screening measures. Since there were no differences among observers with different training backgrounds, our study confirms the appropriateness of ABI assessment for screening peripheral arterial disease (PAD) and generalized atherosclerosis in the primary case setting. Given the importance of the early detection and management of PAD, this diagnostic tool should be used routinely as a standard for PAD screening. Additional studies will be required to confirm our observations in patients with PAD of various severities.

  15. Dopaminergic modulation of hemodynamic signal variability and the functional connectome during cognitive performance.

    PubMed

    Alavash, Mohsen; Lim, Sung-Joo; Thiel, Christiane; Sehm, Bernhard; Deserno, Lorenz; Obleser, Jonas

    2018-05-15

    Dopamine underlies important aspects of cognition, and has been suggested to boost cognitive performance. However, how dopamine modulates the large-scale cortical dynamics during cognitive performance has remained elusive. Using functional MRI during a working memory task in healthy young human listeners, we investigated the effect of levodopa (l-dopa) on two aspects of cortical dynamics, blood oxygen-level-dependent (BOLD) signal variability and the functional connectome of large-scale cortical networks. We here show that enhanced dopaminergic signaling modulates the two potentially interrelated aspects of large-scale cortical dynamics during cognitive performance, and the degree of these modulations is able to explain inter-individual differences in l-dopa-induced behavioral benefits. Relative to placebo, l-dopa increased BOLD signal variability in task-relevant temporal, inferior frontal, parietal and cingulate regions. On the connectome level, however, l-dopa diminished functional integration across temporal and cingulo-opercular regions. This hypo-integration was expressed as a reduction in network efficiency and modularity in more than two thirds of the participants and to different degrees. Hypo-integration co-occurred with relative hyper-connectivity in paracentral lobule and precuneus, as well as posterior putamen. Both, l-dopa-induced BOLD signal variability modulation and functional connectome modulations proved predictive of an individual's l-dopa-induced benefits in behavioral performance, namely response speed and perceptual sensitivity. Lastly, l-dopa-induced modulations of BOLD signal variability were correlated with l-dopa-induced modulation of nodal connectivity and network efficiency. Our findings underline the role of dopamine in maintaining the dynamic range of, and communication between, cortical systems, and their explanatory power for inter-individual differences in benefits from dopamine during cognitive performance. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Quantifying inter- and intra-population niche variability using hierarchical bayesian stable isotope mixing models.

    PubMed

    Semmens, Brice X; Ward, Eric J; Moore, Jonathan W; Darimont, Chris T

    2009-07-09

    Variability in resource use defines the width of a trophic niche occupied by a population. Intra-population variability in resource use may occur across hierarchical levels of population structure from individuals to subpopulations. Understanding how levels of population organization contribute to population niche width is critical to ecology and evolution. Here we describe a hierarchical stable isotope mixing model that can simultaneously estimate both the prey composition of a consumer diet and the diet variability among individuals and across levels of population organization. By explicitly estimating variance components for multiple scales, the model can deconstruct the niche width of a consumer population into relevant levels of population structure. We apply this new approach to stable isotope data from a population of gray wolves from coastal British Columbia, and show support for extensive intra-population niche variability among individuals, social groups, and geographically isolated subpopulations. The analytic method we describe improves mixing models by accounting for diet variability, and improves isotope niche width analysis by quantitatively assessing the contribution of levels of organization to the niche width of a population.

  17. Modeling the impacts of phenological and inter-annual changes in landscape metrics on local biodiversity of agricultural lands of Eastern Ontario using multi-spatial and multi-temporal remote sensing data

    NASA Astrophysics Data System (ADS)

    Alavi-Shoushtari, N.; King, D.

    2017-12-01

    Agricultural landscapes are highly variable ecosystems and are home to many local farmland species. Seasonal, phenological and inter-annual agricultural landscape dynamics have potential to affect the richness and abundance of farmland species. Remote sensing provides data and techniques which enable monitoring landscape changes in multiple temporal and spatial scales. MODIS high temporal resolution remote sensing images enable detection of seasonal and phenological trends, while Landsat higher spatial resolution images, with its long term archive enables inter-annual trend analysis over several decades. The objective of this study to use multi-spatial and multi-temporal remote sensing data to model the response of farmland species to landscape metrics. The study area is the predominantly agricultural region of eastern Ontario. 92 sample landscapes were selected within this region using a protocol designed to maximize variance in composition and configuration heterogeneity while controlling for amount of forest and spatial autocorrelation. Two sample landscape extents (1×1km and 3×3km) were selected to analyze the impacts of spatial scale on biodiversity response. Gamma diversity index data for four taxa groups (birds, butterflies, plants, and beetles) were collected during the summers of 2011 and 2012 within the cropped area of each landscape. To extract the seasonal and phenological metrics a 2000-2012 MODIS NDVI time-series was used, while a 1985-2012 Landsat time-series was used to model the inter-annual trends of change in the sample landscapes. The results of statistical modeling showed significant relationships between farmland biodiversity for several taxa and the phenological and inter-annual variables. The following general results were obtained: 1) Among the taxa groups, plant and beetles diversity was most significantly correlated with the phenological variables; 2) Those phenological variables which are associated with the variability in the start of season date across the sample landscapes and the variability in the corresponding NDVI values at that date showed the strongest correlation with the biodiversity indices; 3) The significance of the models improved when using 3×3km site extent both for MODIS and Landsat based models due most likely to the larger sample size over 3x3km.

  18. Variation of normal tissue complication probability (NTCP) estimates of radiation-induced hypothyroidism in relation to changes in delineation of the thyroid gland.

    PubMed

    Rønjom, Marianne F; Brink, Carsten; Lorenzen, Ebbe L; Hegedüs, Laszlo; Johansen, Jørgen

    2015-01-01

    To examine the variations of risk-estimates of radiation-induced hypothyroidism (HT) from our previously developed normal tissue complication probability (NTCP) model in patients with head and neck squamous cell carcinoma (HNSCC) in relation to variability of delineation of the thyroid gland. In a previous study for development of an NTCP model for HT, the thyroid gland was delineated in 246 treatment plans of patients with HNSCC. Fifty of these plans were randomly chosen for re-delineation for a study of the intra- and inter-observer variability of thyroid volume, Dmean and estimated risk of HT. Bland-Altman plots were used for assessment of the systematic (mean) and random [standard deviation (SD)] variability of the three parameters, and a method for displaying the spatial variation in delineation differences was developed. Intra-observer variability resulted in a mean difference in thyroid volume and Dmean of 0.4 cm(3) (SD ± 1.6) and -0.5 Gy (SD ± 1.0), respectively, and 0.3 cm(3) (SD ± 1.8) and 0.0 Gy (SD ± 1.3) for inter-observer variability. The corresponding mean differences of NTCP values for radiation-induced HT due to intra- and inter-observer variations were insignificantly small, -0.4% (SD ± 6.0) and -0.7% (SD ± 4.8), respectively, but as the SDs show, for some patients the difference in estimated NTCP was large. For the entire study population, the variation in predicted risk of radiation-induced HT in head and neck cancer was small and our NTCP model was robust against observer variations in delineation of the thyroid gland. However, for the individual patient, there may be large differences in estimated risk which calls for precise delineation of the thyroid gland to obtain correct dose and NTCP estimates for optimized treatment planning in the individual patient.

  19. Factors affecting variability in the urinary biomarker 1,6-hexamethylene diamine in workers exposed to 1,6-hexamethylene diisocyanate.

    PubMed

    Gaines, Linda G T; Fent, Kenneth W; Flack, Sheila L; Thomasen, Jennifer M; Whittaker, Stephen G; Nylander-French, Leena A

    2011-01-01

    Although urinary 1,6-hexamethylene diamine (HDA) is a useful biomarker of exposure to 1,6-hexamethylene diisocyanate (HDI), a large degree of unexplained intra- and inter-individual variability exists between estimated HDI exposure and urine HDA levels. We investigated the effect of individual and workplace factors on urine HDA levels using quantitative dermal and inhalation exposure data derived from a survey of automotive spray painters exposed to HDI. Painters' dermal and breathing-zone HDI-exposures were monitored over an entire workday for up to three separate workdays, spaced approximately one month apart. One urine sample was collected before the start of work with HDI-containing paints, and multiple samples were collected throughout the workday. Using mixed effects multiple linear regression modeling, coverall use resulted in significantly lower HDA levels (p = 0.12), and weekday contributed to significant variability in HDA levels (p = 0.056). We also investigated differences in urine HDA levels stratified by dichotomous and classification covariates using analysis of variance. Use of coveralls (p = 0.05), respirator type worn (p = 0.06), smoker status (p = 0.12), paint-booth type (p = 0.02), and more than one painter at the shop (p = 0.10) were all found to significantly affect urine HDA levels adjusted for creatinine concentration. Coverall use remained significant (p = 0.10), even after adjusting for respirator type. These results indicate that the variation in urine HDA level is mainly due to workplace factors and that appropriate dermal and inhalation protection is required to prevent HDI exposure.

  20. Genetic influences on phase synchrony of brain oscillations supporting response inhibition.

    PubMed

    Müller, Viktor; Anokhin, Andrey P; Lindenberger, Ulman

    2017-05-01

    Phase synchronization of neuronal oscillations is a fundamental mechanism underlying cognitive processing and behavior, including context-dependent response production and inhibition. Abnormalities in neural synchrony can lead to abnormal information processing and contribute to cognitive and behavioral deficits in neuropsychiatric disorders. However, little is known about genetic and environmental contributions to individual differences in cortical oscillatory dynamics underlying response inhibition. This study examined heritability of event-related phase synchronization of brain oscillations in 302 young female twins including 94 MZ and 57 DZ pairs performing a cued Go/No-Go version of the Continuous Performance Test (CPT). We used the Phase Locking Index (PLI) to assess inter-trial phase clustering (synchrony) in several frequency bands in two time intervals after stimulus onset (0-300 and 301-600ms). Response inhibition (i.e., successful response suppression in No-Go trials) was characterized by a transient increase in phase synchronization of delta- and theta-band oscillations in the fronto-central midline region. Genetic analysis showed significant heritability of the phase locking measures related to response inhibition, with 30 to 49% of inter-individual variability being accounted for by genetic factors. This is the first study providing evidence for heritability of task-related neural synchrony. The present results suggest that PLI can serve as an indicator of genetically transmitted individual differences in neural substrates of response inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Cardiac valve calcifications on low-dose unenhanced ungated chest computed tomography: inter-observer and inter-examination reliability, agreement and variability.

    PubMed

    van Hamersvelt, Robbert W; Willemink, Martin J; Takx, Richard A P; Eikendal, Anouk L M; Budde, Ricardo P J; Leiner, Tim; Mol, Christian P; Isgum, Ivana; de Jong, Pim A

    2014-07-01

    To determine inter-observer and inter-examination variability for aortic valve calcification (AVC) and mitral valve and annulus calcification (MC) in low-dose unenhanced ungated lung cancer screening chest computed tomography (CT). We included 578 lung cancer screening trial participants who were examined by CT twice within 3 months to follow indeterminate pulmonary nodules. On these CTs, AVC and MC were measured in cubic millimetres. One hundred CTs were examined by five observers to determine the inter-observer variability. Reliability was assessed by kappa statistics (κ) and intra-class correlation coefficients (ICCs). Variability was expressed as the mean difference ± standard deviation (SD). Inter-examination reliability was excellent for AVC (κ = 0.94, ICC = 0.96) and MC (κ = 0.95, ICC = 0.90). Inter-examination variability was 12.7 ± 118.2 mm(3) for AVC and 31.5 ± 219.2 mm(3) for MC. Inter-observer reliability ranged from κ = 0.68 to κ = 0.92 for AVC and from κ = 0.20 to κ = 0.66 for MC. Inter-observer ICC was 0.94 for AVC and ranged from 0.56 to 0.97 for MC. Inter-observer variability ranged from -30.5 ± 252.0 mm(3) to 84.0 ± 240.5 mm(3) for AVC and from -95.2 ± 210.0 mm(3) to 303.7 ± 501.6 mm(3) for MC. AVC can be quantified with excellent reliability on ungated unenhanced low-dose chest CT, but manual detection of MC can be subject to substantial inter-observer variability. Lung cancer screening CT may be used for detection and quantification of cardiac valve calcifications. • Low-dose unenhanced ungated chest computed tomography can detect cardiac valve calcifications. • However, calcified cardiac valves are not reported by most radiologists. • Inter-observer and inter-examination variability of aortic valve calcifications is sufficient for longitudinal studies. • Volumetric measurement variability of mitral valve and annulus calcifications is substantial.

  2. Using GAMM to examine inter-individual heterogeneity in thermal performance curves for Natrix natrix indicates bet hedging strategy by mothers.

    PubMed

    Vickers, Mathew J; Aubret, Fabien; Coulon, Aurélie

    2017-01-01

    The thermal performance curve (TPC) illustrates the dependence on body- and therefore environmental- temperature of many fitness-related aspects of ectotherm ecology and biology including foraging, growth, predator avoidance, and reproduction. The typical thermal performance curve model is linear in its parameters despite the well-known, strong, non-linearity of the response of performance to temperature. In addition, it is usual to consider a single model based on few individuals as descriptive of a species-level response to temperature. To overcome these issues, we used generalized additive mixed modeling (GAMM) to estimate thermal performance curves for 73 individual hatchling Natrix natrix grass snakes from seven clutches, taking advantage of the structure of GAMM to demonstrate that almost 16% of the deviance in thermal performance curves is attributed to inter-individual variation, while only 1.3% is attributable to variation amongst clutches. GAMM allows precise estimation of curve characteristics, which we used to test hypotheses on tradeoffs thought to constrain the thermal performance curve: hotter is better, the specialist-generalist trade off, and resource allocation/acquisition. We observed a negative relationship between maximum performance and performance breadth, indicating a specialist-generalist tradeoff, and a positive relationship between thermal optimum and maximum performance, suggesting "hotter is better". There was a significant difference among matrilines in the relationship between Area Under the Curve and maximum performance - relationship that is an indicator of evenness in acquisition or allocation of resources. As we used unfed hatchlings, the observed matriline effect indicates divergent breeding strategies among mothers, with some mothers provisioning eggs unequally resulting in some offspring being better than others, while other mothers provisioned the eggs more evenly, resulting in even performance throughout the clutch. This observation is reminiscent of bet-hedging strategies, and implies the possibility for intra-clutch variability in the TPCs to buffer N. natrix against unpredictable environmental variability. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Inter- and intra-population variability of the protein content of femoral gland secretions from a lacertid lizard

    PubMed Central

    Fumagalli, Marco; Scali, Stefano; Zuffi, Marco A L; Cagnone, Maddalena; Salvini, Roberta; Sacchi, Roberto

    2017-01-01

    Abstract Femoral glands of male lizards produce waxy secretions that are involved in inter- and intraspecific chemical communication. The main components of these secretions are proteins and lipids, the latter having been extensively studied and already associated to male quality. On the opposite, the composition and role of proteins are nearly unknown, the only available information coming from few studies on iguanids. These studies got the conclusion that proteins might have a communicative function, notably they could signal individual identity. A generalization of these findings requires the extension of protein analysis to other lizard families, and the primary detection of some patterns of individual variability. Using the common wall lizard Podarcis muralis as a model species, the protein fraction of the femoral pore secretions was investigated to provide the first characterization of this component in a lacertid lizard and to explore its source of variability, as a first step to support the hypothesized communicative role. Samples of proteins from femoral secretions were collected from 6 Italian populations and subjected to 1-dimensional electrophoresis. The binary vector of the band presence/absence was used to define the individual profiles. Protein fraction is found to have a structured pattern, with both an individual and a population component. Although the former supports the potential communicative role of proteins, the latter offers a double interpretation, phylogenetic or environmental, even though the phylogenetic effect seems more likely given the climatic resemblance of the considered sites. Further studies are necessary to shed light on both these issues. PMID:29492027

  4. Plasticity, Variability and Age in Second Language Acquisition and Bilingualism

    PubMed Central

    Birdsong, David

    2018-01-01

    Much of what is known about the outcome of second language acquisition and bilingualism can be summarized in terms of inter-individual variability, plasticity and age. The present review looks at variability and plasticity with respect to their underlying sources, and at age as a modulating factor in variability and plasticity. In this context we consider critical period effects vs. bilingualism effects, early and late bilingualism, nativelike and non-nativelike L2 attainment, cognitive aging, individual differences in learning, and linguistic dominance in bilingualism. Non-uniformity is an inherent characteristic of both early and late bilingualism. This review shows how plasticity and age connect with biological and experiential sources of variability, and underscores the value of research that reveals and explains variability. In these ways the review suggests how plasticity, variability and age conspire to frame fundamental research issues in L2 acquisition and bilingualism, and provides points of reference for discussion of the present Frontiers in Psychology Research Topic. PMID:29593590

  5. Variability in negative emotions among individuals with chronic low back pain: relationships with pain and function.

    PubMed

    Gerhart, James I; Burns, John W; Bruehl, Stephen; Smith, David A; Post, Kristina M; Porter, Laura S; Schuster, Erik; Buvanendran, Asokumar; Fras, Anne Marie; Keefe, Francis J

    2017-11-13

    Chronic pain is associated with elevated negative emotions, and resources needed to adaptively regulate these emotions can be depleted during prolonged pain. Studies of links between pain, function, and negative emotions in people with chronic pain, however, have focused almost exclusively on relationships among mean levels of these factors. Indexes that may reflect aspects of emotion regulation have typically not been analyzed. We propose that 1 index of emotion regulation is variability in emotion over time as opposed to average emotion over time. The sample was 105 people with chronic low back pain and 105 of their pain-free spouses. They completed electronic diary measures 5x/d for 14 consecutive days, producing 70 observations per person from which we derived estimates of within-subject variance in negative emotions. Location-scale models were used to simultaneously model predictors of both mean level and variance in patient negative emotions over time. Patients reported significantly more variability in negative emotions compared to their spouses. Patients who reported higher average levels of pain, pain interference, and downtime reported significantly higher levels of variability in negative emotions. Spouse-observed pain and pain behaviors were also associated with greater variability in patients' negative emotions. Test of the inverse associations between negative emotion level and variability in pain and function were significant but weaker in magnitude. These findings support the notion that chronic pain may erode negative emotion regulation resources, to the potential detriment of intra- and inter-personal function.

  6. Watershed-scale response of groundwater recharge to inter-annual and inter-decadal variability in precipitation (Alberta, Canada)

    NASA Astrophysics Data System (ADS)

    Hayashi, Masaki; Farrow, Christopher R.

    2014-12-01

    Groundwater recharge sets a constraint on aquifer water balance in the context of water management. Historical data on groundwater and other relevant hydrological processes can be used to understand the effects of climatic variability on recharge, but such data sets are rare. The climate of the Canadian prairies is characterized by large inter-annual and inter-decadal variability in precipitation, which provides opportunities to examine the response of groundwater recharge to changes in meteorological conditions. A decadal study was conducted in a small (250 km2) prairie watershed in Alberta, Canada. Relative magnitude of annual recharge, indicated by water-level rise, was significantly correlated with a combination of growing-season precipitation and snowmelt runoff, which drives depression-focussed infiltration of meltwater. Annual precipitation was greater than vapour flux at an experimental site in some years and smaller in other years. On average precipitation minus vapour flux was 10 mm y-1, which was comparable to the magnitude of watershed-scale groundwater recharge estimated from creek baseflow. Average baseflow showed a distinct shift from a low value (4 mm y-1) in 1982-1995 to a high value (15 mm y-1) in 2003-2013, indicating the sensitivity of groundwater recharge to a decadal-scale variability of meteorological conditions.

  7. Analytical variability of estimated platelet counts on canine blood smears.

    PubMed

    Paltrinieri, Saverio; Paciletti, Veronica; Zambarbieri, Jari

    2018-06-04

    The analytical variability of estimated platelet counts in dogs has not been reported. The purpose of this study was to assess the magnitude of analytical imprecision of platelet estimates and the possible impact of this imprecision on clinical decisions. Three independent observers counted the number of platelets in 3 different areas (LE = lateral edge; CM = central monolayer; FE = feathered edge) of 30 canine blood smears with different instrumental platelet counts. The coefficient of variation (CV) for each observer was calculated in different areas of each smear (intra-observer variability), among different regions of each smear (inter-area variability), and among different observers in each area (inter-observer variability). The influence of these variabilities on the classification of platelet estimates as adequate, increased, or decreased was also assessed. The CVs recorded in the different areas by each observer ranged from 8% to 88% and were negatively correlated (P < .001, r = -.65) with the mean number of platelets per field. The mean platelet number was significantly lower in the FE and significantly higher in the CM compared with the LE, but the magnitude of this difference varied with the operators. The concordance among operators regarding platelet estimates was fair (k = 0.36) to substantial (k = 0.71) depending on the area. The overall inter-area concordance was moderate (k = 0.59). Platelet estimates suffer from high variability that could lead to patient misclassification. Therefore, guidelines to standardize the platelet estimate are needed. © 2018 American Society for Veterinary Clinical Pathology.

  8. Laterality and grip strength influence hand bone micro-architecture in modern humans, an HRpQCT study.

    PubMed

    Reina, Nicolas; Cavaignac, Etienne; Trousdale, William H; Laffosse, Jean-Michel; Braga, José

    2017-06-01

    It is widely hypothesized that mechanical loading, specifically repetitive low-intensity tasks, influences the inner structure of cancellous bone. As such, there is likely a relationship between handedness and bone morphology. The aim of this study is to determine patterns in trabecular bone between dominant and non-dominant hands in modern humans. Seventeen healthy patients between 22 and 32 years old were included in the study. Radial carpal bones (lunate, capitate, scaphoid, trapezium, trapezoid, 1st, 2nd and 3rd metacarpals) were analyzed with high-resolution micro-computed tomography. Additionally, crush and pinch grip were recorded. Factorial analysis indicated that bone volume ratio, trabeculae number (Tb.N), bone surface to volume ratio (BS.BV), body weight, stature and crush grip were all positively correlated with principal components 1 and 2 explaining 78.7% of the variance. Volumetric and trabecular endostructural parameters (BV/TV, BS/BV or Tb.Th, Tb.N) explain the observed inter-individual variability better than anthropometric or clinical parameters. Factors analysis regressions showed correlations between these parameters and the dominant side for crush strength for the lunate (r 2 = 0.640, P < 0.0001), trapezium (r 2 = 0.836, P < 0.0001) and third metacarpal (r 2 = 0.763). However, despite a significant lateralization in grip strength for all patients, the endostructural variability between dominant and non-dominant sides was limited in perspective to inter-individual differences. In conclusion, handedness is unlikely to generate trabecular patterns of asymmetry. It appears, however, that crush strength can be considered for endostructural analysis in the modern human wrist. © 2017 Anatomical Society.

  9. Staging Sleep in Polysomnograms: Analysis of Inter-Scorer Variability

    PubMed Central

    Younes, Magdy; Raneri, Jill; Hanly, Patrick

    2016-01-01

    Study Objectives: To determine the reasons for inter-scorer variability in sleep staging of polysomnograms (PSGs). Methods: Fifty-six PSGs were scored (5-stage sleep scoring) by 2 experienced technologists, (first manual, M1). Months later, the technologists edited their own scoring (second manual, M2) based upon feedback from the investigators that highlighted differences between their scoring. The PSGs were then scored with an automatic system (Auto) and the technologists edited them, epoch-by-epoch (Edited-Auto). This resulted in 6 different manual scores for each PSG. Epochs were classified as scorer errors (one M1 score differed from the other 5 scores), scorer bias (all 3 scores of each technologist were similar, but differed from the other technologist) and equivocal (sleep scoring was inconsistent within and between technologists). Results: Percent agreement after M1 was 78.9% ± 9.0% and was unchanged after M2 (78.1% ± 9.7%) despite numerous edits (≈40/PSG) by the scorers. Agreement in Edited-Auto was higher (86.5% ± 6.4%, p < 1E−9). Scorer errors (< 2% of epochs) and scorer bias (3.5% ± 2.3% of epochs) together accounted for < 20% of M1 disagreements. A large number of epochs (92 ± 44/PSG) with scoring agreement in M1 were subsequently changed in M2 and/or Edited-Auto. Equivocal epochs, which showed scoring inconsistency, accounted for 28% ± 12% of all epochs, and up to 76% of all epochs in individual patients. Disagreements were largely between awake/NREM, N1/N2, and N2/N3 sleep. Conclusion: Inter-scorer variability is largely due to epochs that are difficult to classify. Availability of digitally identified events (e.g., spindles) or calculated variables (e.g., depth of sleep, delta wave duration) during scoring may greatly reduce scoring variability. Citation: Younes M, Raneri J, Hanly P. Staging sleep in polysomnograms: analysis of inter-scorer variability. J Clin Sleep Med 2016;12(6):885–894. PMID:27070243

  10. Sampling Modification Effects in the Subgingival Microbiome Profile of Healthy Children.

    PubMed

    Santigli, Elisabeth; Trajanoski, Slave; Eberhard, Katharina; Klug, Barbara

    2016-01-01

    Background: Oral microbiota are considered major players in the development of periodontal diseases. Thorough knowledge of intact subgingival microbiomes is required to elucidate microbial shifts from health to disease. Aims: This comparative study investigated the subgingival microbiome of healthy children, possible inter- and intra-individual effects of modified sampling, and basic comparability of subgingival microprints. Methods: In five 10-year-old children, biofilm was collected from the upper first premolars and first molars using sterilized, UV-treated paper-points inserted into the subgingival sulcus at eight sites. After supragingival cleaning using an electric toothbrush and water, sampling was performed, firstly, excluding (Mode A) and, secondly, including (Mode B) cleansing with sterile cotton pellets. DNA was extracted from the pooled samples, and primers targeting 16S rRNA hypervariable regions V5 and V6 were used for 454-pyrosequencing. Wilcoxon signed rank test and t -test were applied to compare sampling modes. Principal coordinate analysis (PCoA) and average agglomerative hierarchical clustering were calculated with unweighted UniFrac distance matrices. Sample grouping was tested with permutational MANOVA (Adonis). Results: Data filtering and quality control yielded 67,218 sequences with an average sequence length of 243bp (SD 6.52; range 231-255). Actinobacteria (2.8-24.6%), Bacteroidetes (9.2-25.1%), Proteobacteria (4.9-50.6%), Firmicutes (16.5-57.4%), and Fusobacteria (2.2-17.1%) were the five major phyla found in all samples. Differences in microbial abundances between sampling modes were not evident. High sampling numbers are needed to achieve significance for rare bacterial phyla. Samples taken from one individual using different sampling modes were more similar to each other than to other individuals' samples. PCoA and hierarchical clustering showed a grouping of the paired samples. Permutational MANOVA did not reveal sample grouping by sampling modes ( p = 0.914 by R 2 = 0.09). Conclusion: A slight modification of sampling mode has minor effects corresponding to a natural variability in the microbiome profiles of healthy children. The inter-individual variability in subgingival microprints is greater than intra-individual differences. Statistical analyses of microbial populations should consider this baseline variability and move beyond mere quantification with input from visual analytics. Comparative results are difficult to summarize as methods for studying huge datasets are still evolving. Advanced approaches are needed for sample size calculations in clinical settings.

  11. Regional deep hyperthermia: impact of observer variability in CT-based manual tissue segmentation on simulated temperature distribution

    NASA Astrophysics Data System (ADS)

    Aklan, Bassim; Hartmann, Josefin; Zink, Diana; Siavooshhaghighi, Hadi; Merten, Ricarda; Putz, Florian; Ott, Oliver; Fietkau, Rainer; Bert, Christoph

    2017-06-01

    The aim of this study was to systematically investigate the influence of the inter- and intra-observer segmentation variation of tumors and organs at risk on the simulated temperature coverage of the target. CT scans of six patients with tumors in the pelvic region acquired for radiotherapy treatment planning were used for hyperthermia treatment planning. To study the effect of inter-observer variation, three observers manually segmented in the CT images of each patient the following structures: fat, muscle, bone and the bladder. The gross tumor volumes (GTV) were contoured by three radiation oncology residents and used as the hyperthermia target volumes. For intra-observer variation, one of the observers of each group contoured the structures of each patient three times with a time span of one week between the segmentations. Moreover, the impact of segmentation variations in organs at risk (OARs) between the three inter-observers was investigated on simulated temperature distributions using only one GTV. The spatial overlap between individual segmentations was assessed by the Dice similarity coefficient (DSC) and the mean surface distance (MSD). Additionally, the temperatures T90/T10 delivered to 90%/10% of the GTV, respectively, were assessed for each observer combination. The results of the segmentation similarity evaluation showed that the DSC of the inter-observer variation of fat, muscle, the bladder, bone and the target was 0.68  ±  0.12, 0.88  ±  0.05, 0.73  ±  0.14, 0.91  ±  0.04 and 0.64  ±  0.11, respectively. Similar results were found for the intra-observer variation. The MSD results were similar to the DSCs for both observer variations. A statistically significant difference (p  <  0.05) was found for T90 and T10 in the predicted target temperature due to the observer variability. The conclusion is that intra- and inter-observer variations have a significant impact on the temperature coverage of the target. Furthermore, OARs, such as bone and the bladder, may essentially influence the homogeneity of the simulated target temperature distribution.

  12. Test-to-test variability in motor activity during the suggested immobilization test in restless legs patients.

    PubMed

    Haba-Rubio, José; Sforza, Emilia

    2006-10-01

    To evaluate the test-to-test variability of the suggested immobilization test (SIT) in patients with restless legs syndrome (RLS). Twenty patients with primary RLS (12 men and eight women; age: 53.3+/-11.3 years) were selected for the study. We compared the results of two SITs performed on two consecutive evenings prior to polysomnographic recordings. Overall, the periodic leg movement index during the SIT (SIT PLM) and the SIT PLM index associated with sensory manifestations (SIT PLM+) were not significantly different between tests. The number of PLM sequences per SIT, the mean PLM duration and the PLM interval did not significantly change between the two consecutive tests. The pattern of temporal evolution of motor activity across the SIT was very reproducible, SIT PLM showing a clear tendency to a progressive increase across the test, with the SIT PLM+ index decreasing in the second half of the test. Despite good reproducibility, there were marked intra-individual differences. Considering the proposed cut-off value of 12 for the SIT PLM index to confirm RLS, 11 patients were positive at the first test and four additional patients became positive at the second test. SIT PLM index changes did not correlate with age, severity of disease and polysomnographic measures. Quantitative analysis of motor activity during two consecutive SITs in RLS patients showed a significant inter-test intra-individual variability unrelated to demographic, clinical or polysomnographic parameters. SIT PLM index variability suggests that a single test would not be sensitive enough for diagnostic purposes in unclear cases and that new criteria need to be applied to increase its specificity and sensitivity.

  13. Inter- and intra-observer reliability of measurement of pedicle screw breach assessed by postoperative CT scans.

    PubMed

    Lavelle, William F; Ranade, Ashish; Samdani, Amer F; Gaughan, John P; D'Andrea, Linda P; Betz, Randal R

    2014-01-01

    Pedicle screws are used increasingly in spine surgery. Concerns of complications associated with screw breach necessitates accurate pedicle screw placement. Postoperative CT imaging helps to detect screw malposition and assess its severity. However, accuracy is dependent on the reading of the CT scans. Inter- and intra-observer variability could affect the reliability of CT scans to assess multiple screw types and sites. The purpose of this study was to assess the reliability of multi-observer analysis of CT scans for determining pedicle screw breach for various screw types and sites in patients with spinal deformity or degenerative pathologies. Axial CT scan images of 23 patients (286 screws) were read by four experienced spine surgeons. Pedicle screw placement was considered 'In' when the screw was fully contained and/or the pedicle wall breach was ≤2 mm. 'Out' was defined as a breach in the medial or lateral pedicle wall >2 mm. Intra-class coefficients (ICC) were calculated to assess the inter- and intra-observer reliability. Marked inter- and intra-observer variability was noticed. The overall inter-observer ICC was 0.45 (95% confidence limits 0.25 to 0.65). The intra-observer ICC was 0.49 (95% confidence limits 0.29 to 0.69). Underlying spinal pathology, screw type, and patient age did not seem to impact the reliability of our CT assessments. Our results indicate the evaluation of pedicle screw breach on CT by a single surgeon is highly variable, and care should be taken when using individual CT evaluations of millimeters of breach as a basis for screw removal. This was a Level III study.

  14. Functional Brain Network Modularity Captures Inter- and Intra-Individual Variation in Working Memory Capacity

    PubMed Central

    Stevens, Alexander A.; Tappon, Sarah C.; Garg, Arun; Fair, Damien A.

    2012-01-01

    Background Cognitive abilities, such as working memory, differ among people; however, individuals also vary in their own day-to-day cognitive performance. One potential source of cognitive variability may be fluctuations in the functional organization of neural systems. The degree to which the organization of these functional networks is optimized may relate to the effective cognitive functioning of the individual. Here we specifically examine how changes in the organization of large-scale networks measured via resting state functional connectivity MRI and graph theory track changes in working memory capacity. Methodology/Principal Findings Twenty-two participants performed a test of working memory capacity and then underwent resting-state fMRI. Seventeen subjects repeated the protocol three weeks later. We applied graph theoretic techniques to measure network organization on 34 brain regions of interest (ROI). Network modularity, which measures the level of integration and segregation across sub-networks, and small-worldness, which measures global network connection efficiency, both predicted individual differences in memory capacity; however, only modularity predicted intra-individual variation across the two sessions. Partial correlations controlling for the component of working memory that was stable across sessions revealed that modularity was almost entirely associated with the variability of working memory at each session. Analyses of specific sub-networks and individual circuits were unable to consistently account for working memory capacity variability. Conclusions/Significance The results suggest that the intrinsic functional organization of an a priori defined cognitive control network measured at rest provides substantial information about actual cognitive performance. The association of network modularity to the variability in an individual's working memory capacity suggests that the organization of this network into high connectivity within modules and sparse connections between modules may reflect effective signaling across brain regions, perhaps through the modulation of signal or the suppression of the propagation of noise. PMID:22276205

  15. Specific-age group sex estimation of infants through geometric morphometrics analysis of pubis and ischium.

    PubMed

    Estévez Campo, Enrique José; López-Lázaro, Sandra; López-Morago Rodríguez, Claudia; Alemán Aguilera, Inmaculada; Botella López, Miguel Cecilio

    2018-05-01

    Sex determination of unknown individuals is one of the primary goals of Physical and Forensic Anthropology. The adult skeleton can be sexed using both morphological and metric traits on a large number of bones. The human pelvis is often used as an important element of adult sex determination. However, studies carried out about the pelvic bone in subadult individuals present several limitations due the absence of sexually dimorphic characteristics. In this study, we analyse the sexual dimorphism of the immature pubis and ischium bones, attending to their shape (Procrustes residuals) and size (centroid size), using an identified sample of subadult individuals composed of 58 individuals for the pubis and 83 for the ischium, aged between birth and 1year of life, from the Granada osteological collection of identified infants (Granada, Spain). Geometric morphometric methods and discriminant analysis were applied to this study. The results of intra- and inter-observer error showed good and excellent agreement in the location of coordinates of landmarks and semilandmarks, respectively. Principal component analysis performed on shape and size variables showed superposition of the two sexes, suggesting a low degree of sexual dimorphism. Canonical variable analysis did not show significant changes between the male and female shapes. As a consequence, discriminant analysis with leave-one-out cross validation provided low classification accuracy. The results suggested a low degree of sexual dimorphism supported by significant sexual dimorphism in the subadult sample and poor cross-validated classification accuracy. The inclusion of centroid size as a discriminant variable does not imply a significant improvement in the results of the analysis. The similarities found between the sexes prevent consideration of pubic and ischial morphology as a sex estimator in early stages of development. The authors suggest extending this study by analysing the different trajectories of shape and size in later ontogeny between males and females. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Reliability of photogrammetry in the evaluation of the postural aspects of individuals with structural scoliosis.

    PubMed

    Saad, Karen Ruggeri; Colombo, Alexandra Siqueira; Ribeiro, Ana Paula; João, Sílvia Maria Amado

    2012-04-01

    The purpose of this study was to investigate the reliability of photogrammetry in the measurement of the postural deviations in individuals with idiopathic scoliosis. Twenty participants with scoliosis (17 women and three men), with a mean age of 23.1 ± 9 yrs, were photographed from the posterior and lateral views. The postural aspects were measured with CorelDRAW software. High inter-rater and test-retest reliability indices were found. It was observed that with more severity of scoliosis, greater were the variations between the thoracic kyphosis and lumbar lordosis measures obtained by the same examiner from the left lateral view photographs. A greater body mass index (BMI) was associated with greater variability of the trunk rotation measures obtained by two independent examiners from the right, lateral view (r = 0.656; p = 0.002). The severity of scoliosis was also associated with greater inter-rater variability measures of trunk rotation obtained from the left, lateral view (r = 0.483; p = 0.036). Photogrammetry demonstrated to be a reliable method for the measurement of postural deviations from the posterior and lateral views of individuals with idiopathic scoliosis and could be complementarily employed for the assessment procedures, which could reduce the number of X-rays used for the follow-up assessments of these individuals. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Impact of image quality on reliability of the measurements of left ventricular systolic function and global longitudinal strain in 2D echocardiography

    PubMed Central

    Nagata, Yasufumi; Kado, Yuichiro; Onoue, Takeshi; Otani, Kyoko; Nakazono, Akemi; Otsuji, Yutaka; Takeuchi, Masaaki

    2018-01-01

    Background Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) play important roles in diagnosis and management of cardiac diseases. However, the issue of the accuracy and reliability of LVEF and GLS remains to be solved. Image quality is one of the most important factors affecting measurement variability. The aim of this study was to investigate whether improved image quality could reduce observer variability. Methods Two sets of three apical images were acquired using relatively old- and new-generation ultrasound imaging systems (Vivid 7 and Vivid E95) in 308 subjects. Image quality was assessed by endocardial border delineation index (EBDI) using a 3-point scoring system. Three observers measured the LVEF and GLS, and these values and inter-observer variability were investigated. Results Image quality was significantly better with Vivid E95 (EBDI: 26.8 ± 5.9) than that with Vivid 7 (22.8 ± 6.3, P < 0.0001). Regarding the inter-observer variability of LVEF, the r-value, bias, 95% limit of agreement and intra-class correlation coefficient for Vivid 7 were comparable to those for Vivid E95. The % variabilities were significantly lower for Vivid E95 (5.3–6.5%) than those for Vivid 7 (6.5–7.5%). Regarding GLS, all observer variability parameters were better for Vivid E95 than for Vivid 7. Improvements in image quality yielded benefits to both LVEF and GLS measurement reliability. Multivariate analysis showed that image quality was indeed an important factor of observer variability in the measurement of LVEF and GLS. Conclusions The new-generation ultrasound imaging system offers improved image quality and reduces inter-observer variability in the measurement of LVEF and GLS. PMID:29432198

  18. Impact of image quality on reliability of the measurements of left ventricular systolic function and global longitudinal strain in 2D echocardiography.

    PubMed

    Nagata, Yasufumi; Kado, Yuichiro; Onoue, Takeshi; Otani, Kyoko; Nakazono, Akemi; Otsuji, Yutaka; Takeuchi, Masaaki

    2018-03-01

    Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) play important roles in diagnosis and management of cardiac diseases. However, the issue of the accuracy and reliability of LVEF and GLS remains to be solved. Image quality is one of the most important factors affecting measurement variability. The aim of this study was to investigate whether improved image quality could reduce observer variability. Two sets of three apical images were acquired using relatively old- and new-generation ultrasound imaging systems (Vivid 7 and Vivid E95) in 308 subjects. Image quality was assessed by endocardial border delineation index (EBDI) using a 3-point scoring system. Three observers measured the LVEF and GLS, and these values and inter-observer variability were investigated. Image quality was significantly better with Vivid E95 (EBDI: 26.8 ± 5.9) than that with Vivid 7 (22.8 ± 6.3, P  < 0.0001). Regarding the inter-observer variability of LVEF, the r -value, bias, 95% limit of agreement and intra-class correlation coefficient for Vivid 7 were comparable to those for Vivid E95. The % variabilities were significantly lower for Vivid E95 (5.3-6.5%) than those for Vivid 7 (6.5-7.5%). Regarding GLS, all observer variability parameters were better for Vivid E95 than for Vivid 7. Improvements in image quality yielded benefits to both LVEF and GLS measurement reliability. Multivariate analysis showed that image quality was indeed an important factor of observer variability in the measurement of LVEF and GLS. The new-generation ultrasound imaging system offers improved image quality and reduces inter-observer variability in the measurement of LVEF and GLS. © 2018 The authors.

  19. The impact of inter-annual rainfall variability on African savannas changes with mean rainfall.

    PubMed

    Synodinos, Alexis D; Tietjen, Britta; Lohmann, Dirk; Jeltsch, Florian

    2018-01-21

    Savannas are mixed tree-grass ecosystems whose dynamics are predominantly regulated by resource competition and the temporal variability in climatic and environmental factors such as rainfall and fire. Hence, increasing inter-annual rainfall variability due to climate change could have a significant impact on savannas. To investigate this, we used an ecohydrological model of stochastic differential equations and simulated African savanna dynamics along a gradient of mean annual rainfall (520-780 mm/year) for a range of inter-annual rainfall variabilities. Our simulations produced alternative states of grassland and savanna across the mean rainfall gradient. Increasing inter-annual variability had a negative effect on the savanna state under dry conditions (520 mm/year), and a positive effect under moister conditions (580-780 mm/year). The former resulted from the net negative effect of dry and wet extremes on trees. In semi-arid conditions (520 mm/year), dry extremes caused a loss of tree cover, which could not be recovered during wet extremes because of strong resource competition and the increased frequency of fires. At high mean rainfall (780 mm/year), increased variability enhanced savanna resilience. Here, resources were no longer limiting and the slow tree dynamics buffered against variability by maintaining a stable population during 'dry' extremes, providing the basis for growth during wet extremes. Simultaneously, high rainfall years had a weak marginal benefit on grass cover due to density-regulation and grazing. Our results suggest that the effects of the slow tree and fast grass dynamics on tree-grass interactions will become a major determinant of the savanna vegetation composition with increasing rainfall variability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Inter-laboratory analysis of selected genetically modified plant reference materials with digital PCR.

    PubMed

    Dobnik, David; Demšar, Tina; Huber, Ingrid; Gerdes, Lars; Broeders, Sylvia; Roosens, Nancy; Debode, Frederic; Berben, Gilbert; Žel, Jana

    2018-01-01

    Digital PCR (dPCR), as a new technology in the field of genetically modified (GM) organism (GMO) testing, enables determination of absolute target copy numbers. The purpose of our study was to test the transferability of methods designed for quantitative PCR (qPCR) to dPCR and to carry out an inter-laboratory comparison of the performance of two different dPCR platforms when determining the absolute GM copy numbers and GM copy number ratio in reference materials certified for GM content in mass fraction. Overall results in terms of measured GM% were within acceptable variation limits for both tested dPCR systems. However, the determined absolute copy numbers for individual genes or events showed higher variability between laboratories in one third of the cases, most possibly due to variability in the technical work, droplet size variability, and analysis of the raw data. GMO quantification with dPCR and qPCR was comparable. As methods originally designed for qPCR performed well in dPCR systems, already validated qPCR assays can most generally be used for dPCR technology with the purpose of GMO detection. Graphical abstract The output of three different PCR-based platforms was assessed in an inter-laboratory comparison.

  1. EDUCATION ENHANCES THE ACUITY OF THE NON-VERBAL APPROXIMATE NUMBER SYSTEM

    PubMed Central

    Piazza, Manuela; Pica, Pierre; Izard, Véronique; Spelke, Elizabeth; Dehaene, Stanislas

    2015-01-01

    All humans share a universal, evolutionarily ancient approximate number system (ANS) that estimates and combines the number of objects in sets with ratio-limited precision. Inter-individual variability in the acuity of the ANS correlates with mathematical achievement, but the causes of this correlation have never been established. We acquired psychophysical measures of ANS acuity in child and adult members of an indigene group in the Amazon, the Mundurucu, who have a very restricted numerical lexicon and highly variable access to mathematical education. By comparing Mundurucu subjects with or without access to schooling, we demonstrate that education significantly enhances the acuity with which sets of concrete objects are estimated. These results speak in favor of an important effect of culture and education on basic number perception. We hypothesize that symbolic and non-symbolic numerical thinking mutually enhance one another over the course of mathematics instruction. PMID:23625879

  2. Quantitative assessment of finger tapping characteristics in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease.

    PubMed

    Roalf, David R; Rupert, Petra; Mechanic-Hamilton, Dawn; Brennan, Laura; Duda, John E; Weintraub, Daniel; Trojanowski, John Q; Wolk, David; Moberg, Paul J

    2018-06-01

    Fine motor impairments are common in neurodegenerative disorders, yet standardized, quantitative measurements of motor abilities are uncommonly used in neurological practice. Thus, understanding and comparing fine motor abilities across disorders have been limited. The current study compared differences in finger tapping, inter-tap interval, and variability in Alzheimer's disease (AD), Parkinson's disease (PD), mild cognitive impairment (MCI), and healthy older adults (HOA). Finger tapping was measured using a highly sensitive light-diode finger tapper. Total number of finger taps, inter-tap interval, and intra-individual variability (IIV) of finger tapping was measured and compared in AD (n = 131), PD (n = 63), MCI (n = 46), and HOA (n = 62), controlling for age and sex. All patient groups had fine motor impairments relative to HOA. AD and MCI groups produced fewer taps with longer inter-tap interval and higher IIV compared to HOA. The PD group, however, produced more taps with shorter inter-tap interval and higher IIV compared to HOA. Disease-specific changes in fine motor function occur in the most common neurodegenerative diseases. The findings suggest that alterations in finger tapping patterns are common in AD, MCI, and PD. In addition, the present results underscore the importance of motor dysfunction even in neurodegenerative disorders without primary motor symptoms.

  3. Possible influence of atmospheric circulations on winter haze pollution in Beijing-Tianjin-Hebei region, northern China

    NASA Astrophysics Data System (ADS)

    Zhang, Z. Y.

    2016-12-01

    Using the daily records derived from the synoptic weather stations and the NCEP/NCAR and ERA-Interim reanalysis data, the variability of the winter haze pollutions (indicated by the mean visibility and number of hazy days) in Beijing-Tianjin-Hebei (BTH) region during the period 1981 to 2015 and its relationship to the atmospheric circulations in middle-high latitude were analyzed in this study. The winter haze pollution in BTH had distinct inter-annual and inter-decadal variabilities without a significant long-term trend. According to the spatial distribution of correlation coefficients, six atmospheric circulation indices (I1 to I6) were defined from the key areas in sea level pressure (SLP), zonal and meridional winds at 850 hPa (U850, V850), geopotential height field at 500 hPa (H500), zonal wind at 200 hPa (U200), and air temperature at 200 hPa (T200), respectively. All of the six indices have significant and stable correlations with the winter visibility and number of hazy days in BTH. The six circulation indices together can explain 77.7% (78.7%) and 61.7% (69.1%) variances of the winter visibility and number of hazy days in the year-to-year (inter-annual) variability, srespectively. The increase of Ic(a comprehensive index derived from the six individual circulation indices) can cause a shallowing of the East Asian trough at the middle troposphere and a weakening of the Siberian high pressure field at sea level, and then accompanied by a reduction (increase) of horizontal advection and vertical convection (relative humidity) in the lowest troposphere and a reduced boundary layer height in BTH and its neighboring areas, which are favorable for the formation of haze pollutions in BTH winter, and vice versa. The high level of the prediction statistics and the reasonable mechanism suggested that the winter haze pollutions in BTH can be forecasted or estimated credibly based on the optimized atmospheric circulation indices. Thus it is helpful for government decision-making departments to take actions in advance in dealing with probably severe haze pollutions in BTH indicated by the atmospheric circulation conditions.

  4. Human and methodological sources of variability in the measurement of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine.

    PubMed

    Barregard, Lars; Møller, Peter; Henriksen, Trine; Mistry, Vilas; Koppen, Gudrun; Rossner, Pavel; Sram, Radim J; Weimann, Allan; Poulsen, Henrik E; Nataf, Robert; Andreoli, Roberta; Manini, Paola; Marczylo, Tim; Lam, Patricia; Evans, Mark D; Kasai, Hiroshi; Kawai, Kazuaki; Li, Yun-Shan; Sakai, Kazuo; Singh, Rajinder; Teichert, Friederike; Farmer, Peter B; Rozalski, Rafal; Gackowski, Daniel; Siomek, Agnieszka; Saez, Guillermo T; Cerda, Concha; Broberg, Karin; Lindh, Christian; Hossain, Mohammad Bakhtiar; Haghdoost, Siamak; Hu, Chiung-Wen; Chao, Mu-Rong; Wu, Kuen-Yuh; Orhan, Hilmi; Senduran, Nilufer; Smith, Raymond J; Santella, Regina M; Su, Yali; Cortez, Czarina; Yeh, Susan; Olinski, Ryszard; Loft, Steffen; Cooke, Marcus S

    2013-06-20

    Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (rp 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.

  5. Investigation of summer monsoon rainfall variability in Pakistan

    NASA Astrophysics Data System (ADS)

    Hussain, Mian Sabir; Lee, Seungho

    2016-08-01

    This study analyzes the inter-annual and intra-seasonal rainfall variability in Pakistan using daily rainfall data during the summer monsoon season (June to September) recorded from 1980 to 2014. The variability in inter-annual monsoon rainfall ranges from 20 % in northeastern regions to 65 % in southwestern regions of Pakistan. The analysis reveals that the transition of the negative and positive anomalies was not uniform in the investigated dataset. In order to acquire broad observations of the intra-seasonal variability, an objective criterion, the pre-active period, active period and post-active periods of the summer monsoon rainfall have demarcated. The analysis also reveals that the rainfall in June has no significant contribution to the increase in intra-seasonal rainfall in Pakistan. The rainfall has, however, been enhanced in the summer monsoon in August. The rainfall of September demonstrates a sharp decrease, resulting in a high variability in the summer monsoon season. A detailed examination of the intra-seasonal rainfall also reveals frequent amplitude from late July to early August. The daily normal rainfall fluctuates significantly with its maximum in the Murree hills and its minimum in the northwestern Baluchistan.

  6. SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hou, Y; Aileen, C; Kozono, D

    Purpose: Quantification of volume changes on CBCT during SBRT for NSCLC may provide a useful radiological marker for radiation response and adaptive treatment planning, but the reproducibility of CBCT volume delineation is a concern. This study is to quantify inter-scan/inter-observer variability in tumor volume delineation on CBCT. Methods: Twenty earlystage (stage I and II) NSCLC patients were included in this analysis. All patients were treated with SBRT with a median dose of 54 Gy in 3 to 5 fractions. Two physicians independently manually contoured the primary gross tumor volume on CBCTs taken immediately before SBRT treatment (Pre) and after themore » same SBRT treatment (Post). Absolute volume differences (AVD) were calculated between the Pre and Post CBCTs for a given treatment to quantify inter-scan variability, and then between the two observers for a given CBCT to quantify inter-observer variability. AVD was also normalized with respect to average volume to obtain relative volume differences (RVD). Bland-Altman approach was used to evaluate variability. All statistics were calculated with SAS version 9.4. Results: The 95% limit of agreement (mean ± 2SD) on AVD and RVD measurements between Pre and Post scans were −0.32cc to 0.32cc and −0.5% to 0.5% versus −1.9 cc to 1.8 cc and −15.9% to 15.3% for the two observers respectively. The 95% limit of agreement of AVD and RVD between the two observers were −3.3 cc to 2.3 cc and −42.4% to 28.2% respectively. The greatest variability in inter-scan RVD was observed with very small tumors (< 5 cc). Conclusion: Inter-scan variability in RVD is greatest with small tumors. Inter-observer variability was larger than inter-scan variability. The 95% limit of agreement for inter-observer and inter-scan variability (∼15–30%) helps define a threshold for clinically meaningful change in tumor volume to assess SBRT response, with larger thresholds needed for very small tumors. Part of the work was funded by a Kaye award; Disclosure/Conflict of interest: Raymond H. Mak: Stock ownership: Celgene, Inc. Consulting: Boehringer-Ingelheim, Inc.« less

  7. The influence of redox status on inter-individual variability in the response of human peripheral blood lymphocytes to ionizing radiation.

    PubMed

    Pajic, Jelena; Rovcanin, Branislav; Kekic, Dusan; Jovicic, Dubravka; Milovanovic, Aleksandar P S

    2018-04-30

    Ionizing radiation (IR) can act on atomic structures, producing damage to biomolecules. Earlier investigations evaluating individual radiosensitivity in vitro were focused on cytogenetic biomarkers (chromosomal aberrations - CA and micronuclei - MN). Since IR can also cause oxidative damage by producing reactive oxygen species, the main goal of this investigation was to establish the influence of redox status on CA and MN frequency in human peripheral blood lymphocytes. Blood samples from 56 healthy donors were irradiated at doses of 0, 0.75, 1.5 and 3 Gy and then analyzed cytogenetically and biochemically. The results showed inter-individual variability in all analyzed parameters, as well as dose-dependent increases in almost all of them. Correlation analysis indicated no association between CA, MN and oxidative stress parameters. However, findings for overall response (HRR) parameters showed that donors with lower values for parameters of antioxidant status had increased levels of cytogenetic damage and higher responses to irradiation and vice versa. Besides well-established cytogenetic biomarkers of radiation exposure, our results indicated promising future use for biochemical oxidative status parameters in routine radiation protection practice, since together they can provide a complete radiation response profile in cases of continuous low-dose exposure, as well as in a radiation emergency.

  8. Neural Basis of Moral Elevation Demonstrated through Inter-Subject Synchronization of Cortical Activity during Free-Viewing

    PubMed Central

    Englander, Zoë A.; Haidt, Jonathan; Morris, James P.

    2012-01-01

    Background Most research investigating the neural basis of social emotions has examined emotions that give rise to negative evaluations of others (e.g. anger, disgust). Emotions triggered by the virtues and excellences of others have been largely ignored. Using fMRI, we investigated the neural basis of two “other-praising" emotions – Moral Elevation (a response to witnessing acts of moral beauty), and Admiration (which we restricted to admiration for physical skill). Methodology/Principal Findings Ten participants viewed the same nine video clips. Three clips elicited moral elevation, three elicited admiration, and three were emotionally neutral. We then performed pair-wise voxel-by-voxel correlations of the BOLD signal between individuals for each video clip and a separate resting-state run. We observed a high degree of inter-subject synchronization, regardless of stimulus type, across several brain regions during free-viewing of videos. Videos in the elevation condition evoked significant inter-subject synchronization in brain regions previously implicated in self-referential and interoceptive processes, including the medial prefrontal cortex, precuneus, and insula. The degree of synchronization was highly variable over the course of the videos, with the strongest synchrony occurring during portions of the videos that were independently rated as most emotionally arousing. Synchrony in these same brain regions was not consistently observed during the admiration videos, and was absent for the neutral videos. Conclusions/Significance Results suggest that the neural systems supporting moral elevation are remarkably consistent across subjects viewing the same emotional content. We demonstrate that model-free techniques such as inter-subject synchronization may be a useful tool for studying complex, context dependent emotions such as self-transcendent emotion. PMID:22745745

  9. Dopamine response to psychosocial stress in humans and its relationship to individual differences in personality traits.

    PubMed

    Suridjan, Ivonne; Boileau, Isabelle; Bagby, Michael; Rusjan, Pablo M; Wilson, Alan A; Houle, Sylvain; Mizrahi, Romina

    2012-07-01

    Previous studies have reported inter-individual variability in the dopamine (DA) response to stress. This variability might be related to individual differences in the vulnerability to experience the negative effect of stress. To investigate whether personality traits as measured by the revised NEO personality inventory explain variability in DA response to a psychosocial stress task. Eleven healthy adults, mean age of 26 ± 3.87 underwent two positron emission tomography (PET) scans using the dopamine D(2/3) agonist, [11C]-(+)-PHNO under a control and stress condition. The simplified reference tissue model (SRTM) was used to obtain [11C]-(+)-PHNO binding potential (BP(ND)). Stress-induced DA response was indexed as a percent change in [11C]-(+)-PHNO BP(ND) between control and stress conditions. The regions of interest were defined into D2-rich regions, which included the Associative and Sensorimotor Striatum (AST and SMST); D(2/3) mixed regions, which included the limbic striatum (LST) and globus pallidus (GP); and D3-rich region, which included the Substantia Nigra (SN). Several personality traits within the Neuroticism and Openness to Experience domain were significantly correlated with blunted DA response to stress. Specifically, the Angry-Hostility, Vulnerability, and Depression trait were associated with blunted DA stress response in the AST (r = -0.645, p = 0.032), LST (r = -0.677, p = 0.022) and GP (r = -0.736, p = 0.010), respectively. The Openness to Values was correlated with a decreased DA release in the SN (r = -0.706, p = 0.015). Variability in DA stress response might be related to individual differences in personality. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  10. Increased Intra-Participant Variability in Children with Autistic Spectrum Disorders: Evidence from Single-Trial Analysis of Evoked EEG

    PubMed Central

    Milne, Elizabeth

    2011-01-01

    Intra-participant variability in clinical conditions such as autistic spectrum disorder (ASD) is an important indicator of pathophysiological processing. The data reported here illustrate that trial-by-trial variability can be reliably measured from EEG, and that intra-participant EEG variability is significantly greater in those with ASD than in neuro-typical matched controls. EEG recorded at the scalp is a linear mixture of activity arising from muscle artifacts and numerous concurrent brain processes. To minimize these additional sources of variability, EEG data were subjected to two different methods of spatial filtering. (i) The data were decomposed using infomax independent component analysis, a method of blind source separation which un-mixes the EEG signal into components with maximally independent time-courses, and (ii) a surface Laplacian transform was performed (current source density interpolation) in order to reduce the effects of volume conduction. Data are presented from 13 high functioning adolescents with ASD without co-morbid ADHD, and 12 neuro-typical age-, IQ-, and gender-matched controls. Comparison of variability between the ASD and neuro-typical groups indicated that intra-participant variability of P1 latency and P1 amplitude was greater in the participants with ASD, and inter-trial α-band phase coherence was lower in the participants with ASD. These data support the suggestion that individuals with ASD are less able to synchronize the activity of stimulus-related cell assemblies than neuro-typical individuals, and provide empirical evidence in support of theories of increased neural noise in ASD. PMID:21716921

  11. Long-Term Species, Sexual and Individual Variations in Foraging Strategies of Fur Seals Revealed by Stable Isotopes in Whiskers

    PubMed Central

    Kernaléguen, Laëtitia; Cazelles, Bernard; Arnould, John P. Y.; Richard, Pierre; Guinet, Christophe; Cherel, Yves

    2012-01-01

    Background Individual variations in the use of the species niche are an important component of diversity in trophic interactions. A challenge in testing consistency of individual foraging strategy is the repeated collection of information on the same individuals. Methodology/Principal Findings The foraging strategies of sympatric fur seals (Arctocephalus gazella and A. tropicalis) were examined using the stable isotope signature of serially sampled whiskers. Most whiskers exhibited synchronous δ13C and δ15N oscillations that correspond to the seal annual movements over the long term (up to 8 years). δ13C and δ15N values were spread over large ranges, with differences between species, sexes and individuals. The main segregating mechanism operates at the spatial scale. Most seals favored foraging in subantarctic waters (where the Crozet Islands are located) where they fed on myctophids. However, A. gazella dispersed in the Antarctic Zone and A. tropicalis more in the subtropics. Gender differences in annual time budget shape the seal movements. Males that do not perform any parental care exhibited large isotopic oscillations reflecting broad annual migrations, while isotopic values of females confined to a limited foraging range during lactation exhibited smaller changes. Limited inter-individual isotopic variations occurred in female seals and in male A. tropicalis. In contrast, male A. gazella showed large inter-individual variations, with some males migrating repeatedly to high-Antarctic waters where they fed on krill, thus meaning that individual specialization occurred over years. Conclusions/Significance Whisker isotopic signature yields unique long-term information on individual behaviour that integrates the spatial, trophic and temporal dimensions of the ecological niche. The method allows depicting the entire realized niche of the species, including some of its less well-known components such as age-, sex-, individual- and migration-related changes. It highlights intrapopulation heterogeneity in foraging strategies that could have important implications for likely demographic responses to environmental variability. PMID:22431988

  12. Allometric modelling of peak oxygen uptake in male soccer players of 8-18 years of age.

    PubMed

    Valente-Dos-Santos, João; Coelho-E-Silva, Manuel J; Tavares, Óscar M; Brito, João; Seabra, André; Rebelo, António; Sherar, Lauren B; Elferink-Gemser, Marije T; Malina, Robert M

    2015-03-01

    Peak oxygen uptake (VO2peak) is routinely scaled as mL O2 per kilogram body mass despite theoretical and statistical limitations of using ratios. To examine the contribution of maturity status and body size descriptors to age-associated inter-individual variability in VO2peak and to present static allometric models to normalize VO2peak in male youth soccer players. Total body and estimates of total and regional lean mass were measured with dual energy X-ray absorptiometry in a cross-sectional sample of Portuguese male soccer players. The sample was divided into three age groups for analysis: 8-12 years, 13-15 years and 16-18 years. VO2peak was estimated using an incremental maximal exercise test on a motorized treadmill. Static allometric models were used to normalize VO2peak. The independent variables with the best statistical fit explained 72% in the younger group (lean body mass: k = 1.07), 52% in mid-adolescent players (lean body mass: k = 0.93) and 31% in the older group (body mass: k = 0.51) of variance in VO2peak. The inclusion of the exponential term pubertal status marginally increased the explained variance in VO2peak (adjusted R(2 )= 36-75%) and provided statistical adjustments to the size descriptors coefficients. The allometric coefficients and exponents evidenced the varying inter-relationship among size descriptors and maturity status with aerobic fitness from early to late-adolescence. Lean body mass, lean lower limbs mass and body mass combined with pubertal status explain most of the inter-individual variability in VO2peak among youth soccer players.

  13. Choice of surrogate tissue influences neonatal EWAS findings.

    PubMed

    Lin, Xinyi; Teh, Ai Ling; Chen, Li; Lim, Ives Yubin; Tan, Pei Fang; MacIsaac, Julia L; Morin, Alexander M; Yap, Fabian; Tan, Kok Hian; Saw, Seang Mei; Lee, Yung Seng; Holbrook, Joanna D; Godfrey, Keith M; Meaney, Michael J; Kobor, Michael S; Chong, Yap Seng; Gluckman, Peter D; Karnani, Neerja

    2017-12-05

    Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .

  14. The Effect of microRNAs in the Regulation of Human CYP3A4: a Systematic Study using a Mathematical Model

    NASA Astrophysics Data System (ADS)

    Wei, Zhiyun; Jiang, Songshan; Zhang, Yiting; Wang, Xiaofei; Peng, Xueling; Meng, Chunjie; Liu, Yichen; Wang, Honglian; Guo, Luo; Qin, Shengying; He, Lin; Shao, Fengmin; Zhang, Lirong; Xing, Qinghe

    2014-03-01

    CYP3A4 metabolizes more than 50% of the drugs on the market. The large inter-individual differences of CYP3A4 expression may contribute to the variability of human drug responses. Post-transcriptional regulation of CYP3A4 is poorly understood, whereas transcriptional regulation has been studied much more thoroughly. In this study, we used multiple software programs to predict miRNAs that might bind to CYP3A4 and identified 112 potentially functional miRNAs. Then a luciferase reporter system was used to assess the effect of the overexpression of each potentially functional miRNA in HEK 293T cells. Fourteen miRNAs that significantly decreased reporter activity were measured in human liver samples (N = 27) as candidate miRNAs. To establish a more effective way to analyze in vivo data for miRNA candidates, the relationship between functional miRNA and target mRNA was modeled mathematically. Taking advantage of this model, we found that hsa-miR-577, hsa-miR-1, hsa-miR-532-3p and hsa-miR-627 could significantly downregulate the translation efficiency of CYP3A4 mRNA in liver. This study used in silico, in vitro and in vivo methods to progressively screen functional miRNAs for CYP3A4 and to enhance our understanding of molecular events underlying the large inter-individual differences of CYP3A4 expression in human populations.

  15. The Continuity of College Students' Autonomous Learning Motivation and Its Predictors: A Three-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Pan, Yingqiu; Gauvain, Mary

    2012-01-01

    This study examined change in Chinese students' autonomous learning motivation in the first three years of college and how this change is accounted for by intra- and inter-individual variables. The sample included 633 (328 female) college freshmen. Results showed that students' autonomous learning motivation decreased over years in college.…

  16. The Link between Organizational Learning Culture and Customer Satisfaction: Confirming Relationship and Exploring Moderating Effect

    ERIC Educational Resources Information Center

    Pantouvakis, Angelos; Bouranta, Nancy

    2013-01-01

    Purpose: The aim of this paper is to develop a theoretical framework and conduct an empirical study across different service sectors to investigate the inter-relationships between organizational learning culture, employee job satisfaction and their impact on customer satisfaction. It also aims to examine an individual-level variable (educational…

  17. Brain composition and olfactory learning in honey bees

    PubMed Central

    Gronenberg, Wulfila; Couvillon, Margaret J.

    2015-01-01

    Correlations between brain or brain component size and behavioral measures are frequently studied by comparing different animal species, which sometimes introduces variables that complicate interpretation in terms of brain function. Here, we have analyzed the brain composition of honey bees (Apis mellifera) that have been individually tested in an olfactory learning paradigm. We found that the total brain size correlated with the bees’ learning performance. Among different brain components, only the mushroom body, a structure known to be involved in learning and memory, showed a positive correlation with learning performance. In contrast, visual neuropils were relatively smaller in bees that performed better in the olfactory learning task, suggesting modality-specific behavioral specialization of individual bees. This idea is also supported by inter-individual differences in brain composition. Some slight yet statistically significant differences in the brain composition of European and Africanized honey bees are reported. Larger bees had larger brains, and by comparing brains of different sizes, we report isometric correlations for all brain components except for a small structure, the central body. PMID:20060918

  18. Forecasting Sensorimotor Adaptability from Baseline Inter-Trial Correlations

    NASA Technical Reports Server (NTRS)

    Beaton, K. H.; Bloomberg, J. J.

    2016-01-01

    One of the greatest challenges for sensorimotor adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a "one-size-fits-all" approach is inappropriate. Therefore, it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. This information could guide individually customized countermeasures, which would enable more efficient use of crew time and provide better outcomes. The principal aim of this work is to look for baseline performance metrics that relate to locomotor adaptability. We propose a novel hypothesis that considers baseline inter-trial correlations, the trial-to-trial fluctuations ("noise") in motor performance, as a predictor of individual adaptive capabilities.

  19. X-ray computed tomography uncovers root-root interactions: quantifying spatial relationships between interacting root systems in three dimensions.

    PubMed

    Paya, Alexander M; Silverberg, Jesse L; Padgett, Jennifer; Bauerle, Taryn L

    2015-01-01

    Research in the field of plant biology has recently demonstrated that inter- and intra-specific interactions belowground can dramatically alter root growth. Our aim was to answer questions related to the effect of inter- vs. intra-specific interactions on the growth and utilization of undisturbed space by fine roots within three dimensions (3D) using micro X-ray computed tomography. To achieve this, Populus tremuloides (quaking aspen) and Picea mariana (black spruce) seedlings were planted into containers as either solitary individuals, or inter-/intra-specific pairs, allowed to grow for 2 months, and 3D metrics developed in order to quantify their use of belowground space. In both aspen and spruce, inter-specific root interactions produced a shift in the vertical distribution of the root system volume, and deepened the average position of root tips when compared to intra-specifically growing seedlings. Inter-specific interactions also increased the minimum distance between root tips belonging to the same root system. There was no effect of belowground interactions on the radial distribution of roots, or the directionality of lateral root growth for either species. In conclusion, we found that significant differences were observed more often when comparing controls (solitary individuals) and paired seedlings (inter- or intra-specific), than when comparing inter- and intra-specifically growing seedlings. This would indicate that competition between neighboring seedlings was more responsible for shifting fine root growth in both species than was neighbor identity. However, significant inter- vs. intra-specific differences were observed, which further emphasizes the importance of biological interactions in competition studies.

  20. Assessing fidelity of delivery of smoking cessation behavioural support in practice.

    PubMed

    Lorencatto, Fabiana; West, Robert; Christopherson, Charlotte; Michie, Susan

    2013-04-04

    Effectiveness of evidence-based behaviour change interventions is likely to be undermined by failure to deliver interventions as planned. Behavioural support for smoking cessation can be a highly cost-effective, life-saving intervention. However, in practice, outcomes are highly variable. Part of this may be due to variability in fidelity of intervention implementation. To date, there have been no published studies on this. The present study aimed to: evaluate a method for assessing fidelity of behavioural support; assess fidelity of delivery in two English Stop-Smoking Services; and compare the extent of fidelity according to session types, duration, individual practitioners, and component behaviour change techniques (BCTs). Treatment manuals and transcripts of 34 audio-recorded behavioural support sessions were obtained from two Stop-Smoking Services and coded into component BCTs using a taxonomy of 43 BCTs. Inter-rater reliability was assessed using percentage agreement. Fidelity was assessed by examining the proportion of BCTs specified in the manuals that were delivered in individual sessions. This was assessed by session type (i.e., pre-quit, quit, post-quit), duration, individual practitioner, and BCT. Inter-coder reliability was high (87.1%). On average, 66% of manual-specified BCTs were delivered per session (SD 15.3, range: 35% to 90%). In Service 1, average fidelity was highest for post-quit sessions (69%) and lowest for pre-quit (58%). In Service 2, fidelity was highest for quit-day (81%) and lowest for post-quit sessions (56%). Session duration was not significantly correlated with fidelity. Individual practitioner fidelity ranged from 55% to 78%. Individual manual-specified BCTs were delivered on average 63% of the time (SD 28.5, range: 0 to 100%). The extent to which smoking cessation behavioural support is delivered as specified in treatment manuals can be reliably assessed using transcripts of audiotaped sessions. This allows the investigation of the implementation of evidence-based practice in relation to smoking cessation, a first step in designing interventions to improve it. There are grounds for believing that fidelity in the English Stop-Smoking Services may be low and that routine monitoring is warranted.

  1. Multi-factorial modulation of hemispheric specialization and plasticity for language in healthy and pathological conditions: A review.

    PubMed

    Tzourio-Mazoyer, Nathalie; Perrone-Bertolotti, Marcela; Jobard, Gael; Mazoyer, Bernard; Baciu, Monica

    2017-01-01

    This review synthesizes anatomo-functional variability of language hemispheric representation and specialization (hemispheric specialization for language, HSL) as well as its modulation by several variables (demographic, anatomical, developmental, genetic, clinical, and psycholinguistic) in physiological and pathological conditions. The left hemisphere (LH) dominance for language, observed in approximately 90% of healthy individuals and in 70% of patients, is grounded by intra-hemispheric connections mediated by associative bundles such as the arcuate fasciculus and inter-hemispheric transcallosal connections mediated by the corpus callosum that connects homotopic regions of the left and right hemispheres (RH). In typical brains, inter-hemispheric inhibition, exerted from the LH to the RH, permits the LH to maintain language dominance. In pathological conditions, inter- and intra-hemispheric inhibition is decreased, inducing modifications on the degree of HSL and of language networks. HSL evaluation is classically performed in clinical practice with the Wada test and electro-cortical stimulation, gold standard methods. The advent of functional neuroimaging has allowed a more detailed assessment of the language networks and their lateralization, consistent with the results provided by the gold standard methods. In the first part, we describe anatomo-functional support for HSL in healthy conditions, its developmental course, its relationship with cognitive skills, and the various modulatory factors acting on HSL. The second section is devoted to the assessment of HSL in patients with focal and drug-resistant epilepsy (FDRE). FDRE is considered a neurological model associated with patterns of language plasticity, both before and after surgery: FDRE patients show significant modification of language networks induced by changes mediated by transcallosal connections (explaining inter-hemispheric patterns of language reorganization) or collateral connections (explaining intra-hemispheric patterns of language reorganization). Finally, we propose several predictive and explicative models of language organization and reorganization. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Networks of Food Sharing Reveal the Functional Significance of Multilevel Sociality in Two Hunter-Gatherer Groups.

    PubMed

    Dyble, Mark; Thompson, James; Smith, Daniel; Salali, Gul Deniz; Chaudhary, Nikhil; Page, Abigail E; Vinicuis, Lucio; Mace, Ruth; Migliano, Andrea Bamberg

    2016-08-08

    Like many other mammalian and primate societies [1-4], humans are said to live in multilevel social groups, with individuals situated in a series of hierarchically structured sub-groups [5, 6]. Although this multilevel social organization has been described among contemporary hunter-gatherers [5], questions remain as to the benefits that individuals derive from living in such groups. Here, we show that food sharing among two populations of contemporary hunter-gatherers-the Palanan Agta (Philippines) and Mbendjele BaYaka (Republic of Congo)-reveals similar multilevel social structures, with individuals situated in households, within sharing clusters of 3-4 households, within the wider residential camps, which vary in size. We suggest that these groupings serve to facilitate inter-sexual provisioning, kin provisioning, and risk reduction reciprocity, three levels of cooperation argued to be fundamental in human societies [7, 8]. Humans have a suite of derived life history characteristics including a long childhood and short inter-birth intervals that make offspring energetically demanding [9] and have moved to a dietary niche that often involves the exploitation of difficult to acquire foods with highly variable return rates [10-12]. This means that human foragers face both day-to-day and more long-term energetic deficits that conspire to make humans energetically interdependent. We suggest that a multilevel social organization allows individuals access to both the food sharing partners required to buffer themselves against energetic shortfalls and the cooperative partners required for skill-based tasks such as cooperative foraging. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Broca Pars Triangularis Constitutes a "Hub" of the Language-Control Network during Simultaneous Language Translation.

    PubMed

    Elmer, Stefan

    2016-01-01

    Until now, several branches of research have fundamentally contributed to a better understanding of the ramifications of bilingualism, multilingualism, and language expertise on psycholinguistic-, cognitive-, and neural implications. In this context, it is noteworthy to mention that from a cognitive perspective, there is a strong convergence of data pointing to an influence of multilingual speech competence on a variety of cognitive functions, including attention, short-term- and working memory, set shifting, switching, and inhibition. In addition, complementary neuroimaging findings have highlighted a specific set of cortical and subcortical brain regions which fundamentally contribute to administrate cognitive control in the multilingual brain, namely Broca's area, the middle-anterior cingulate cortex, the inferior parietal lobe, and the basal ganglia. However, a disadvantage of focusing on group analyses is that this procedure only enables an approximation of the neural networks shared within a population while at the same time smoothing inter-individual differences. In order to address both commonalities (i.e., within group analyses) and inter-individual variability (i.e., single-subject analyses) in language control mechanisms, here I measured five professional simultaneous interpreters while the participants overtly translated or repeated sentences with a simple subject-verb-object structure. Results demonstrated that pars triangularis was commonly activated across participants during backward translation (i.e., from L2 to L1), whereas the other brain regions of the "control network" showed a strong inter-individual variability during both backward and forward (i.e., from L1 to L2) translation. Thus, I propose that pars triangularis plays a crucial role within the language-control network and behaves as a fundamental processing entity supporting simultaneous language translation.

  4. Inter-annual variability of carbon fluxes in temperate forest ecosystems: effects of biotic and abiotic factors

    NASA Astrophysics Data System (ADS)

    Chen, M.; Keenan, T. F.; Hufkens, K.; Munger, J. W.; Bohrer, G.; Brzostek, E. R.; Richardson, A. D.

    2014-12-01

    Carbon dynamics in terrestrial ecosystems are influenced by both abiotic and biotic factors. Abiotic factors, such as variation in meteorological conditions, directly drive biophysical and biogeochemical processes; biotic factors, referring to the inherent properties of the ecosystem components, reflect the internal regulating effects including temporal dynamics and memory. The magnitude of the effect of abiotic and biotic factors on forest ecosystem carbon exchange has been suggested to vary at different time scales. In this study, we design and conduct a model-data fusion experiment to investigate the role and relative importance of the biotic and abiotic factors for inter-annual variability of the net ecosystem CO2 exchange (NEE) of temperate deciduous forest ecosystems in the Northeastern US. A process-based model (FöBAAR) is parameterized at four eddy-covariance sites using all available flux and biometric measurements. We conducted a "transplant" modeling experiment, that is, cross- site and parameter simulations with different combinations of site meteorology and parameters. Using wavelet analysis and variance partitioning techniques, analysis of model predictions identifies both spatial variant and spatially invariant parameters. Variability of NEE was primarily modulated by gross primary productivity (GPP), with relative contributions varying from hourly to yearly time scales. The inter-annual variability of GPP and NEE is more regulated by meteorological forcing, but spatial variability in certain model parameters (biotic response) has more substantial effects on the inter-annual variability of ecosystem respiration (Reco) through the effects on carbon pools. Both the biotic and abiotic factors play significant roles in modulating the spatial and temporal variability in terrestrial carbon cycling in the region. Together, our study quantifies the relative importance of both, and calls for better understanding of them to better predict regional CO2 exchanges.

  5. Cardiovascular Reactivity During Marital Conflict in Laboratory and Naturalistic Settings: Differential Associations with Relationship and Individual Functioning Across Contexts.

    PubMed

    Baucom, Brian R W; Baucom, Katherine J W; Hogan, Jasara N; Crenshaw, Alexander O; Bourne, Stacia V; Crowell, Sheila E; Georgiou, Panayiotis; Goodwin, Matthew S

    2018-03-25

    Cardiovascular reactivity during spousal conflict is considered to be one of the main pathways for relationship distress to impact physical, mental, and relationship health. However, the magnitude of association between cardiovascular reactivity during laboratory marital conflict and relationship functioning is small and inconsistent given the scope of its importance in theoretical models of intimate relationships. This study tests the possibility that cardiovascular data collected in laboratory settings downwardly bias the magnitude of these associations when compared to measures obtained in naturalistic settings. Ambulatory cardiovascular reactivity data were collected from 20 couples during two relationship conflicts in a research laboratory, two planned relationship conflicts at couples' homes, and two spontaneous relationship conflicts during couples' daily lives. Associations between self-report measures of relationship functioning, individual functioning, and cardiovascular reactivity across settings are tested using multilevel models. Cardiovascular reactivity was significantly larger during planned and spontaneous relationship conflicts in naturalistic settings than during planned relationship conflicts in the laboratory. Similarly, associations with relationship and individual functioning variables were statistically significantly larger for cardiovascular data collected in naturalistic settings than the same data collected in the laboratory. Our findings suggest that cardiovascular reactivity during spousal conflict in naturalistic settings is statistically significantly different from that elicited in laboratory settings both in magnitude and in the pattern of associations with a wide range of inter- and intrapersonal variables. These differences in findings across laboratory and naturalistic physiological responses highlight the value of testing physiological phenomena across interaction contexts in romantic relationships. © 2018 Family Process Institute.

  6. Inter-individual variability in copepod microbiomes reveals bacterial networks linked to host physiology.

    PubMed

    Datta, Manoshi S; Almada, Amalia A; Baumgartner, Mark F; Mincer, Tracy J; Tarrant, Ann M; Polz, Martin F

    2018-06-06

    Copepods harbor diverse bacterial communities, which collectively carry out key biogeochemical transformations in the ocean. However, bulk copepod sampling averages over the variability in their associated bacterial communities, thereby limiting our understanding of the nature and specificity of copepod-bacteria associations. Here, we characterize the bacterial communities associated with nearly 200 individual Calanus finmarchicus copepods transitioning from active growth to diapause. We find that all individual copepods sampled share a small set of "core" operational taxonomic units (OTUs), a subset of which have also been found associated with other marine copepod species in different geographic locations. However, most OTUs are patchily distributed across individual copepods, thereby driving community differences across individuals. Among patchily distributed OTUs, we identified groups of OTUs correlated with common ecological drivers. For instance, a group of OTUs positively correlated with recent copepod feeding served to differentiate largely active growing copepods from those entering diapause. Together, our results underscore the power of individual-level sampling for understanding host-microbiome relationships.

  7. Linking unfounded beliefs to genetic dopamine availability

    PubMed Central

    Schmack, Katharina; Rössler, Hannes; Sekutowicz, Maria; Brandl, Eva J.; Müller, Daniel J.; Petrovic, Predrag; Sterzer, Philipp

    2015-01-01

    Unfounded convictions involving beliefs in the paranormal, grandiosity ideas or suspicious thoughts are endorsed at varying degrees among the general population. Here, we investigated the neurobiopsychological basis of the observed inter-individual variability in the propensity toward unfounded beliefs. One hundred two healthy individuals were genotyped for four polymorphisms in the COMT gene (rs6269, rs4633, rs4818, and rs4680, also known as val158met) that define common functional haplotypes with substantial impact on synaptic dopamine degradation, completed a questionnaire measuring unfounded beliefs, and took part in a behavioral experiment assessing perceptual inference. We found that greater dopamine availability was associated with a stronger propensity toward unfounded beliefs, and that this effect was statistically mediated by an enhanced influence of expectations on perceptual inference. Our results indicate that genetic differences in dopaminergic neurotransmission account for inter-individual differences in perceptual inference linked to the formation and maintenance of unfounded beliefs. Thus, dopamine might be critically involved in the processes underlying one's interpretation of the relationship between the self and the world. PMID:26483654

  8. Spatial and Temporal Occurrence of Blue Whales off the U.S. West Coast, with Implications for Management

    PubMed Central

    Irvine, Ladd M.; Mate, Bruce R.; Winsor, Martha H.; Palacios, Daniel M.; Bograd, Steven J.; Costa, Daniel P.; Bailey, Helen

    2014-01-01

    Mortality and injuries caused by ship strikes in U.S. waters are a cause of concern for the endangered population of blue whales (Balaenoptera musculus) occupying the eastern North Pacific. We sought to determine which areas along the U.S. West Coast are most important to blue whales and whether those areas change inter-annually. Argos-monitored satellite tags were attached to 171 blue whales off California during summer/early fall from 1993 to 2008. We analyzed portions of the tracks that occurred within U.S. Exclusive Economic Zone waters and defined the ‘home range’ (HR) and ‘core areas’ (CAU) as the 90% and 50% fixed kernel density distributions, respectively, for each whale. We used the number of overlapping individual HRs and CAUs to identify areas of highest use. Individual HR and CAU sizes varied dramatically, but without significant inter-annual variation despite covering years with El Niño and La Niña conditions. Observed within-year differences in HR size may represent different foraging strategies for individuals. The main areas of HR and CAU overlap among whales were near highly productive, strong upwelling centers that were crossed by commercial shipping lanes. Tagged whales generally departed U.S. Exclusive Economic Zone waters from mid-October to mid-November, with high variability among individuals. One 504-d track allowed HR and CAU comparisons for the same individual across two years, showing similar seasonal timing, and strong site fidelity. Our analysis showed how satellite-tagged blue whales seasonally used waters off the U.S. West Coast, including high-risk areas. We suggest possible modifications to existing shipping lanes to reduce the likelihood of collisions with vessels. PMID:25054829

  9. Spatial and temporal occurrence of blue whales off the U.S. West Coast, with implications for management.

    PubMed

    Irvine, Ladd M; Mate, Bruce R; Winsor, Martha H; Palacios, Daniel M; Bograd, Steven J; Costa, Daniel P; Bailey, Helen

    2014-01-01

    Mortality and injuries caused by ship strikes in U.S. waters are a cause of concern for the endangered population of blue whales (Balaenoptera musculus) occupying the eastern North Pacific. We sought to determine which areas along the U.S. West Coast are most important to blue whales and whether those areas change inter-annually. Argos-monitored satellite tags were attached to 171 blue whales off California during summer/early fall from 1993 to 2008. We analyzed portions of the tracks that occurred within U.S. Exclusive Economic Zone waters and defined the 'home range' (HR) and 'core areas' (CAU) as the 90% and 50% fixed kernel density distributions, respectively, for each whale. We used the number of overlapping individual HRs and CAUs to identify areas of highest use. Individual HR and CAU sizes varied dramatically, but without significant inter-annual variation despite covering years with El Niño and La Niña conditions. Observed within-year differences in HR size may represent different foraging strategies for individuals. The main areas of HR and CAU overlap among whales were near highly productive, strong upwelling centers that were crossed by commercial shipping lanes. Tagged whales generally departed U.S. Exclusive Economic Zone waters from mid-October to mid-November, with high variability among individuals. One 504-d track allowed HR and CAU comparisons for the same individual across two years, showing similar seasonal timing, and strong site fidelity. Our analysis showed how satellite-tagged blue whales seasonally used waters off the U.S. West Coast, including high-risk areas. We suggest possible modifications to existing shipping lanes to reduce the likelihood of collisions with vessels.

  10. SU-G-206-07: Dual-Energy CT Inter- and Intra-Scanner Variability Within One Make and Model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jacobsen, M; Wood, C; Cody, D

    Purpose: It can be logistically quite difficult to scan patients on the same exact device for their repeat visits in multi-scanner facilities. The reliability between dual-energy CT scanners’ quantitative results is not known, nor is their individual repeatability. Therefore, we evaluated inter- and intra-scanner variability with respect to several key clinical quantitative metrics specific to dual-energy CT. Methods: Eleven identical GE HD-750 CT scanners in a busy clinical environment were used to perform dual-energy (DE) CT scans of a large elliptical quality control (QC) phantom (Gammex, Inc.; Middleton, WI) which contains many standard insert materials. The DE-QC phantom was scannedmore » bi-weekly during 2016; 3 to 4 scans were obtained from each scanner (a total of 35 data sets were used for analysis). Iodine accuracy for the 2mg/ml, 5mg/ml and 15mg/ml rods (from the Iodine(Water) image set) and soft tissue HU (40 HU based on NIST constants) from the 50keV data set were used to assess inter- and intra-scanner variability (standard deviation). Results: Intra-scanner variability average for 2mg/ml Iodine was 0.10 mg/ml (range 0.05–0.15 mg/ml), for 5mg/ml Iodine was 0.12 mg/ml (range 0.07–0.16 mg/ml), for 15 mg/ml Iodine was 0.25 mg/ml (range 0.16–0.37 mg/ml), and for the soft tissue inserts was 2.1 HU (range 1.8–2.6 HU). Inter-scanner variability average for 2mg/ml Iodine was 0.16 mg/ml (range 0.11–0.19 mg/ml), for 5mg/ml Iodine was 0.18 mg/ml (range 0.11–0.22 mg/ml), for 15 mg/ml Iodine was 0.35 mg/ml (range 0.23–0.44 mg/ml), and for the soft tissue inserts was 3.8 HU (range 3.1–4.5 HU). Conclusion: Intra-scanner variability for the iodine and soft tissue inserts averaged 3.1% and 5.2% respectively, and inter-scanner variability for these regions analyzed averaged 5.0% and 9.5%, respectively. Future work will include determination of smallest measurable change and acceptable limits for DE-CT scanner variability over longer time intervals. This research has been supported by funds from Dr. William Murphy, Jr., the John S. Dunn, Sr. Distinguished Chair in Diagnostic Imaging at MD Anderson Cancer Center.« less

  11. Inter-level Scaffolding and Sequences of Representational Activities in Teaching a Chemical System with Graphical Simulations

    NASA Astrophysics Data System (ADS)

    Li, Na; Black, John B.

    2016-10-01

    Chemistry knowledge can be represented at macro-, micro- and symbolic levels, and learning a chemistry topic requires students to engage in multiple representational activities. This study focused on scaffolding for inter-level connection-making in learning chemistry knowledge with graphical simulations. We also tested whether different sequences of representational activities produced different student learning outcomes in learning a chemistry topic. A sample of 129 seventh graders participated in this study. In a simulation-based environment, participants completed three representational activities to learn several ideal gas law concepts. We conducted a 2 × 3 factorial design experiment. We compared two scaffolding conditions: (1) the inter- level scaffolding condition in which participants received inter-level questions and experienced the dynamic link function in the simulation-based environment and (2) the intra- level scaffolding condition in which participants received intra-level questions and did not experience the dynamic link function. We also compared three different sequences of representational activities: macro-symbolic-micro, micro-symbolic-macro and symbolic-micro-macro. For the scaffolding variable, we found that the inter- level scaffolding condition produced significantly better performance in both knowledge comprehension and application, compared to the intra- level scaffolding condition. For the sequence variable, we found that the macro-symbolic-micro sequence produced significantly better knowledge comprehension performance than the other two sequences; however, it did not benefit knowledge application performance. There was a trend that the treatment group who experienced inter- level scaffolding and the micro-symbolic-macro sequence achieved the best knowledge application performance.

  12. Facilitatory non-invasive brain stimulation in older adults: the effect of stimulation type and duration on the induction of motor cortex plasticity.

    PubMed

    Puri, Rohan; Hinder, Mark R; Canty, Alison J; Summers, Jeffery J

    2016-12-01

    Despite holding significant promise for counteracting the deleterious effects of ageing on cognitive and motor function, little is known of the effects of facilitatory non-invasive brain stimulation (NBS) techniques on corticospinal excitability (CSE) in older adults. Thirty-three older adults (≥60 years) participated in four NBS sessions on separate days, receiving 10- and 20-min anodal transcranial direct current stimulation (atDCS), and 300 and 600 pulses of intermittent theta burst stimulation (iTBS) over the left M1. Motor-evoked potentials measured in the contralateral hand served as a measure of CSE before and for 30 min following each NBS intervention. At the group level, generalized post-stimulation CSE increases were observed (p < 0.001) with no significant differences between the two durations of each stimulation type (atDCS: p = 0.5; iTBS: p = 0.9). For individuals exhibiting overall facilitatory change to atDCS ('responders', n = 10), 20-min atDCS resulted in longer lasting CSE facilitation than 10 min. No such difference was observed between the two iTBS protocols. Considerable variability was observed inter-individually, where 52-58 % of the cohort exhibited the expected facilitation after each of the NBS protocols-as well as intra-individually, where 45-48 % of the cohort maintained consistent post-stimulation responses across the varying durations and types of stimulation. In conclusion, as shown previously in young adults, older adults demonstrate substantial variability in response to different facilitatory NBS protocols. Studies to assess the intra-individual reliability of these protocols are critical to progress towards translation of appropriate protocols (i.e. those that elicit the greatest response for each individual) into clinical practice.

  13. Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

    PubMed Central

    Follis, Jack L.; Dashti, Hassan S.; Tanaka, Toshiko; Graff, Mariaelisa; Fretts, Amanda M.; Kilpeläinen, Tuomas O.; Wojczynski, Mary K.; Richardson, Kris; Nalls, Mike A.; Schulz, Christina-Alexandra; Liu, Yongmei; Frazier-Wood, Alexis C.; van Eekelen, Esther; Wang, Carol; de Vries, Paul S.; Mikkilä, Vera; Rohde, Rebecca; Psaty, Bruce M.; Hansen, Torben; Feitosa, Mary F.; Lai, Chao-Qiang; Houston, Denise K.; Ferruci, Luigi; Ericson, Ulrika; Wang, Zhe; de Mutsert, Renée; Oddy, Wendy H.; de Jonge, Ester A. L.; Seppälä, Ilkka; Justice, Anne E.; Lemaitre, Rozenn N.; Sørensen, Thorkild I. A.; Province, Michael A.; Parnell, Laurence D.; Garcia, Melissa E.; Bandinelli, Stefania; Orho-Melander, Marju; Rich, Stephen S.; Rosendaal, Frits R.; Pennell, Craig E.; Kiefte-de Jong, Jessica C.; Kähönen, Mika; Young, Kristin L.; Pedersen, Oluf; Aslibekyan, Stella; Rotter, Jerome I.; Mook-Kanamori, Dennis O.; Zillikens, M. Carola; Raitakari, Olli T.; North, Kari E.; Overvad, Kim; Arnett, Donna K.; Hofman, Albert; Lehtimäki, Terho; Tjønneland, Anne; Uitterlinden, André G.; Rivadeneira, Fernando; Franco, Oscar H.; German, J. Bruce; Siscovick, David S.; Cupples, L. Adrienne; Ordovás, José M.

    2017-01-01

    Scope Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. Methods and results A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction<10−7), and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3′ of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 × 10−8) such that each serving of low-fat dairy was associated with 0.225 kg m−2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure. Conclusion Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight. PMID:28941034

  14. Living different lives: Early social differentiation identified through linking mortuary and isotopic variability in Late Neolithic/ Early Chalcolithic north-central Spain

    PubMed Central

    Schulting, Rick J.

    2017-01-01

    Variation in burial location and treatment is often observed in the prehistoric archaeological record, but its interpretation is usually highly ambiguous. Biomolecular approaches provide the means of addressing this variability in a way not previously possible, linking the lives of individuals to their funerary treatment. Here, we undertake stable carbon and nitrogen isotope analyses on a substantial sample of 166 individuals from a series of broadly contemporary Late Neolithic/ Early Chalcolithic (3500 to 2900 cal BC) mortuary monuments (El Sotillo, Alto de la Huesera, Chabola de la Hechicera and Longar) and caves (Las Yurdinas II, Los Husos I and Peña Larga) within a very spatially restricted area of north-central Spain, with sites separated by no more than 10 km on average. This spatial and temporal proximity allows us to focus on the question at the appropriate scale of analysis, avoiding confounding variables such as environmental change, diachronic trends in the subsistence economy, etc. The results demonstrate a statistically significant difference in human δ13C values between those interred in caves and those placed in monuments. The difference appears to be correlated with fine-grained environmental factors (elevation/ temperature/ precipitation), suggesting that use of the landscape was being divided at a very local scale. The reasons for this partitioning may involve differential social status (e.g. those interred in caves may be of lower standing with more restricted access to the valley’s arable resources) or economic specialization (e.g. upland herding vs. valley farming) within the same community or, alternatively, different populations performing different funerary practices and following distinct subsistence economies in some respect. Our results contribute to a better understanding of the development of social differentiation and community specialisation on the scale of the immediate lived landscape. PMID:28953890

  15. The Impact of Clinical Information on the Assessment of Endoscopic Activity: Characteristics of the Ulcerative Colitis Endoscopic Index Of Severity [UCEIS].

    PubMed

    Travis, Simon P L; Schnell, Dan; Feagan, Brian G; Abreu, Maria T; Altman, Douglas G; Hanauer, Stephen B; Krzeski, Piotr; Lichtenstein, Gary R; Marteau, Philippe R; Mary, Jean-Yves; Reinisch, Walter; Sands, Bruce E; Schnell, Patrick; Yacyshyn, Bruce R; Colombel, Jean-Frédéric; Bernhardt, Christian A; Sandborn, William J

    2015-08-01

    To determine whether clinical information influences endoscopic scoring by central readers using the Ulcerative Colitis Endoscopic Index of Severity [UCEIS; comprising 'vascular pattern', 'bleeding', 'erosions and ulcers']. Forty central readers performed 28 evaluations, including 2 repeats, from a library of 44 video sigmoidoscopies stratified by Mayo Clinic Score. Following training, readers were randomised to scoring with ['unblinded', n = 20, including 4 control videos with misleading information] or without ['blinded', n 20] clinical information. A total of 21 virtual Central Reader Groups [CRGs], of three blinded readers, were created. Agreement criteria were pre-specified. Kappa [κ] statistics quantified intra- and inter-reader variability. Mean UCEIS scores did not differ between blinded and unblinded readers for any of the 40 main videos. UCEIS standard deviations [SD] were similar [median blinded 0.94, unblinded 0.93; p = 0.97]. Correlation between UCEIS and visual analogue scale [VAS] assessment of overall severity was high [r blinded = 0.90, unblinded = 0.93; p = 0.02]. Scores for control videos were similar [UCEIS: p ≥ 0.55; VAS: p ≥ 0.07]. Intra- [κ 0.47-0.74] and inter-reader [κ 0.40-0.53] variability for items and full UCEIS was 'moderate'-to-'substantial', with no significant differences except for intra-reader variability for erosions and ulcers [κ blinded: 0.47 vs unblinded: 0.74; p 0.047]. The SD of CRGs was lower than for individual central readers [0.54 vs 0.95; p < 0.001]. Correlation between blinded UCEIS and patient-reported symptoms was high [stool frequency: 0.76; rectal bleeding: 0.82; both: 0.81]. The UCEIS is minimally affected by knowledge of clinical details, strongly correlates with patient-reported symptoms, and is a suitable instrument for trials. CRGs performed better than individuals. © European Crohn’s and Colitis Organisation 2015.

  16. A new approach for the quantification of synchrony of multivariate non-stationary psychophysiological variables during emotion eliciting stimuli

    PubMed Central

    Kelava, Augustin; Muma, Michael; Deja, Marlene; Dagdagan, Jack Y.; Zoubir, Abdelhak M.

    2015-01-01

    Emotion eliciting situations are accompanied by changes of multiple variables associated with subjective, physiological and behavioral responses. The quantification of the overall simultaneous synchrony of psychophysiological reactions plays a major role in emotion theories and has received increased attention in recent years. From a psychometric perspective, the reactions represent multivariate non-stationary intra-individual time series. In this paper, a new time-frequency based latent variable approach for the quantification of the synchrony of the responses is presented. The approach is applied to empirical data, collected during an emotion eliciting situation. The results are compared with a complementary inter-individual approach of Hsieh et al. (2011). Finally, the proposed approach is discussed in the context of emotion theories, and possible future applications and limitations are provided. PMID:25653624

  17. Perceptual control models of pursuit manual tracking demonstrate individual specificity and parameter consistency.

    PubMed

    Parker, Maximilian G; Tyson, Sarah F; Weightman, Andrew P; Abbott, Bruce; Emsley, Richard; Mansell, Warren

    2017-11-01

    Computational models that simulate individuals' movements in pursuit-tracking tasks have been used to elucidate mechanisms of human motor control. Whilst there is evidence that individuals demonstrate idiosyncratic control-tracking strategies, it remains unclear whether models can be sensitive to these idiosyncrasies. Perceptual control theory (PCT) provides a unique model architecture with an internally set reference value parameter, and can be optimized to fit an individual's tracking behavior. The current study investigated whether PCT models could show temporal stability and individual specificity over time. Twenty adults completed three blocks of 15 1-min, pursuit-tracking trials. Two blocks (training and post-training) were completed in one session and the third was completed after 1 week (follow-up). The target moved in a one-dimensional, pseudorandom pattern. PCT models were optimized to the training data using a least-mean-squares algorithm, and validated with data from post-training and follow-up. We found significant inter-individual variability (partial η 2 : .464-.697) and intra-individual consistency (Cronbach's α: .880-.976) in parameter estimates. Polynomial regression revealed that all model parameters, including the reference value parameter, contribute to simulation accuracy. Participants' tracking performances were significantly more accurately simulated by models developed from their own tracking data than by models developed from other participants' data. We conclude that PCT models can be optimized to simulate the performance of an individual and that the test-retest reliability of individual models is a necessary criterion for evaluating computational models of human performance.

  18. Association of Inter-arm Blood Pressure Difference with Asymptomatic Intracranial and Extracranial Arterial Stenosis in Hypertension Patients.

    PubMed

    Wang, Yan; Zhang, Jin; Qian, Yuesheng; Tang, Xiaofeng; Ling, Huawei; Chen, Kemin; Li, Yan; Gao, Pingjin; Zhu, Dingliang

    2016-07-14

    Inter-arm blood pressure (BP) difference has been associated with ischemic stroke. Local atherosclerosis of stroke differ among vulnerable individuals, whereas intracranial arterial stenosis (ICAS) is more frequently affected Asians, and extracranial arterial stenosis (ECAS) is more prevalent among whites. We hereby sought to explore the association of inter-arm BP difference with ICAS and ECAS in stroke-free hypertensive patients in Chinese population. All the 885 subjects were evaluated of ICAS and ECAS through computerized tomographic angiography. Both arm BP was measured simultaneously by Vascular Profiler-1000 device. In the continuous study, ICAS was significantly associated with age, male, average brachial SBP, diabetes, anti-hypertensive treatment and inter-arm DBP difference. ECAS was associated with age, inter-arm SBP and LDL. In the categorical study, subjects with the top quartile of inter-arm DBP difference (≥4 mmHg) showed significantly higher risk of ICAS (OR = 2.109; 95% CI, 1.24-3.587). And the participants with the top quartile of inter-arm SBP difference (≥6 mmHg) showed significantly higher risk of ECAS (OR = 2.288; 95% CI, 1.309-3.998). In conclusion, we reported a diverse association of inter-arm SBP/DBP difference with the ICAS/ECAS. Inter-arm DBP difference might be the early symbol of ICAS in Chinese population, which need further verification in long-term cohort study.

  19. Different Types of Sensation Seeking: A Person-Oriented Approach in Sensation-Seeking Research

    ERIC Educational Resources Information Center

    Suranyi, Zsuzsanna; Hitchcock, David B.; Hittner, James B.; Vargha, Andras; Urban, Robert

    2013-01-01

    Previous research on sensation seeking (SS) was dominated by a variable-oriented approach indicating that SS level has a linear relation with a host of problem behaviors. Our aim was to provide a person-oriented methodology--a probabilistic clustering--that enables examination of both inter- and intra-individual differences in not only the level,…

  20. A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.

    PubMed

    Ovsyannikova, Inna G; Schaid, Daniel J; Larrabee, Beth R; Haralambieva, Iana H; Kennedy, Richard B; Poland, Gregory A

    2017-01-01

    Human antibody response to measles vaccine is highly variable in the population. Host genes contribute to inter-individual antibody response variation. The killer cell immunoglobulin-like receptors (KIR) are recognized to interact with HLA molecules and possibly influence humoral immune response to viral antigens. To expand on and improve our previous work with HLA genes, and to explore the genetic contribution of KIR genes to the inter-individual variability in measles vaccine-induced antibody responses, we performed a large population-based study in 2,506 healthy immunized subjects (ages 11 to 41 years) to identify HLA and KIR associations with measles vaccine-induced neutralizing antibodies. After correcting for the large number of statistical tests of allele effects on measles-specific neutralizing antibody titers, no statistically significant associations were found for either HLA or KIR loci. However, suggestive associations worthy of follow-up in other cohorts include B*57:01, DQB1*06:02, and DRB1*15:05 alleles. Specifically, the B*57:01 allele (1,040 mIU/mL; p = 0.0002) was suggestive of an association with lower measles antibody titer. In contrast, the DQB1*06:02 (1,349 mIU/mL; p = 0.0004) and DRB1*15:05 (2,547 mIU/mL; p = 0.0004) alleles were suggestive of an association with higher measles antibodies. Notably, the associations with KIR genotypes were strongly nonsignificant, suggesting that KIR loci in terms of copy number and haplotypes are not likely to play a major role in antibody response to measles vaccination. These findings refine our knowledge of the role of HLA and KIR alleles in measles vaccine-induced immunity.

  1. Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine

    PubMed Central

    Lüneburg, Nicole; Lieb, Wolfgang; Zeller, Tanja; Chen, Ming-Huei; Maas, Renke; Carter, Angela M.; Xanthakis, Vanessa; Glazer, Nicole L; Schwedhelm, Edzard; Seshadri, Sudha; Ikram, M. Arfan; Longstreth, W.T.; Fornage, Myriam; König, Inke R.; Loley, Christina; Ojeda, Francisco M.; Schillert, Arne; Wang, Thomas J.; Sticht, Heinrich; Kittel, Anja; König, Jörg; Benjamin, Emelia J.; Sullivan, Lisa M.; Bernges, Isabel; Anderssohn, Maike; Ziegler, Andreas; Gieger, Christian; Illig, Thomas; Meisinger, Christa; Wichmann, H.-Erich; Wild, Philipp S.; Schunkert, Heribert; Psaty, Bruce M.; Wiggins, Kerri L.; Heckbert, Susan R.; Smith, Nicholas; Lackner, Karl; Lunetta, Kathryn L.; Blankenberg, Stefan; Erdmann, Jeanette; Munzel, Thomas; Grant, Peter J.; Vasan, Ramachandran S.; Böger, Rainer H.

    2016-01-01

    Background Dimethylarginines (DMA) interfere with nitric oxide (NO) formation by inhibiting NO synthase (asymmetric dimethylarginine, ADMA) and L-arginine uptake into the cell (ADMA and symmetric dimethylarginine, SDMA). In prospective clinical studies ADMA has been characterized as a cardiovascular risk marker whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterise the environmental and genetic contributions to inter-individual variability of these biomarkers. Methods and Results This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (FHS (n=2992), GHS (n=4354) and MONICA/KORA F3 (n=581)) and identified replicated loci (DDAH1, MED23, Arg1 and AGXT2) associated with the inter-individual variability in ADMA, L-arginine and SDMA. Experimental in-silico and in-vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants and various cardiometabolic risk factors. AGXT2 variants were not associated with post-stroke survival in the Leeds study, nor were they associated with incident stroke in the CHARGE consortium. Conclusion These GWAS support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and L-arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation. PMID:25245031

  2. Genetic diversity in natural populations of mangaba in Sergipe, the largest producer State in Brazil.

    PubMed

    Soares, A N R; Vitória, M F; Nascimento, A L S; Ledo, A S; Rabbani, A R C; Silva, A V C

    2016-08-19

    Mangaba (Hancornia speciosa Gomes) is found in areas of coastal tablelands in the Brazilian Northeast and Cerrado regions. This species has been subjected to habitat fragmentation that is mainly due to human activity, and requires conservation strategies. The aim of this study was to analyze the structure and inter- and intrapopulation genetic diversity of natural populations of H. speciosa Gomes using inter-simple sequence repeat (ISSR) molecular markers. A total of 155 individuals were sampled in 10 natural populations (ITA, PAC, IND, EST, BC, PIR, JAP, BG, NEO, and SANT) in the State of Sergipe, Brazil. Fifteen primers were used to generate 162 fragments with 100% polymorphism. Genetic analysis showed that the variability between populations (77%) was higher than within populations (23%). It was possible to identify five different groups by the unweighted pair group method with arithmetic mean and principal coordinate analysis, and only one individual (E10) remained isolated. Using ISSR markers it was possible to obtain a molecular profile of the populations evaluated, showing that these markers were effective and exhibited sufficient polymorphism to estimate the genetic variability of natural populations of H. speciosa Gomes.

  3. Extracting Message Inter-Departure Time Distributions from the Human Electroencephalogram

    PubMed Central

    Mišić, Bratislav; Vakorin, Vasily A.; Kovačević, Nataša; Paus, Tomáš; McIntosh, Anthony R.

    2011-01-01

    The complex connectivity of the cerebral cortex is a topic of much study, yet the link between structure and function is still unclear. The processing capacity and throughput of information at individual brain regions remains an open question and one that could potentially bridge these two aspects of neural organization. The rate at which information is emitted from different nodes in the network and how this output process changes under different external conditions are general questions that are not unique to neuroscience, but are of interest in multiple classes of telecommunication networks. In the present study we show how some of these questions may be addressed using tools from telecommunications research. An important system statistic for modeling and performance evaluation of distributed communication systems is the time between successive departures of units of information at each node in the network. We describe a method to extract and fully characterize the distribution of such inter-departure times from the resting-state electroencephalogram (EEG). We show that inter-departure times are well fitted by the two-parameter Gamma distribution. Moreover, they are not spatially or neurophysiologically trivial and instead are regionally specific and sensitive to the presence of sensory input. In both the eyes-closed and eyes-open conditions, inter-departure time distributions were more dispersed over posterior parietal channels, close to regions which are known to have the most dense structural connectivity. The biggest differences between the two conditions were observed at occipital sites, where inter-departure times were significantly more variable in the eyes-open condition. Together, these results suggest that message departure times are indicative of network traffic and capture a novel facet of neural activity. PMID:21673866

  4. Repeatability and Reproducibility of Decisions by Latent Fingerprint Examiners

    PubMed Central

    Ulery, Bradford T.; Hicklin, R. Austin; Buscaglia, JoAnn; Roberts, Maria Antonia

    2012-01-01

    The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. We tested latent print examiners on the extent to which they reached consistent decisions. This study assessed intra-examiner repeatability by retesting 72 examiners on comparisons of latent and exemplar fingerprints, after an interval of approximately seven months; each examiner was reassigned 25 image pairs for comparison, out of total pool of 744 image pairs. We compare these repeatability results with reproducibility (inter-examiner) results derived from our previous study. Examiners repeated 89.1% of their individualization decisions, and 90.1% of their exclusion decisions; most of the changed decisions resulted in inconclusive decisions. Repeatability of comparison decisions (individualization, exclusion, inconclusive) was 90.0% for mated pairs, and 85.9% for nonmated pairs. Repeatability and reproducibility were notably lower for comparisons assessed by the examiners as “difficult” than for “easy” or “moderate” comparisons, indicating that examiners' assessments of difficulty may be useful for quality assurance. No false positive errors were repeated (n = 4); 30% of false negative errors were repeated. One percent of latent value decisions were completely reversed (no value even for exclusion vs. of value for individualization). Most of the inter- and intra-examiner variability concerned whether the examiners considered the information available to be sufficient to reach a conclusion; this variability was concentrated on specific image pairs such that repeatability and reproducibility were very high on some comparisons and very low on others. Much of the variability appears to be due to making categorical decisions in borderline cases. PMID:22427888

  5. Variability in target delineation of cervical carcinoma: A Korean radiation oncology group study (KROG 15-06)

    PubMed Central

    Joo, Ji Hyeon; Cho, Byung Chul; Jeong, Chi Young; Park, Won; Kim, Hak Jae; Yoon, Won Sup; Yoon, Mee Sun; Kim, Ji-Yoon; Choi, Jin Hwa; Choi, Youngmin; Kim, Joo-Young

    2017-01-01

    Purpose To determine inter-observer variability in target volume definition of cervical cancer in radical and adjuvant radiotherapy (RT) settings. Methods Eight physicians contoured CTVs of 2 patients underwent definitive and postoperative RT. Each volume was analyzed using the individual/median volume ratio and generalized conformity index (CIgen). And center of mass (COM) of each contour was calculated. Expert agreement was quantified using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE). Results For definitive RT, the individual/median volume ratio ranged from 0.51 to 1.41, and CIgen was 0.531. Mean 3-dimensional distances of average to each COM were 7.8 mm. For postoperative RT setting, corresponding values were 0.65–1.38, 0.563, and 5.3 mm. Kappa value of expert agreement was 0.65 and 0.67, respectively. STAPLE estimates of the sensitivity, specificity, and kappa measures of inter-physician agreement were 0.73, 0.98, and 0.65 for the definitive and 0.75, 0.98, and 0.67 for the adjuvant radiotherapy setting. The largest difference was observed in the superior-inferior direction, particularly in the upper vagina and the common iliac area. Conclusion As there was still some variability in target delineation, more detailed guidelines for target volume delineation and continuing education would help to reduce this uncertainty. PMID:28301492

  6. Inter-individual variation in nutrient balancing in the honeybee (Apis mellifera).

    PubMed

    Reade, Abbie J; Naug, Dhruba

    2016-12-01

    The Geometric Framework approach in nutritional ecology postulates that animals attempt to balance the consumption of different nutrients rather than simply maximizing energetic gain. The intake target with respect to each nutrient maximizes fitness in a specific dimension and any difference between individuals in intake target therefore represents alternative behavioral and fitness maximization strategies. Nutritional interactions are a central component of all social groups and any inter-individual variation in intake target should therefore have a significant influence on social dynamics. Using the honeybee colony as an experimental model, we quantified differences in the carbohydrate intake target of individual foragers using a capillary feeder (CAFE) assay. Our results show that the bees did not simply maximize their net energetic gain, but combined sugar and water in their diet in a way that brought them to an intake target equivalent to a 33% sucrose solution. Although the mean intake target with respect to the nutrients sucrose and water was the same under different food choice regimens, there was significant inter-individual variation in intake target and the manner in which individuals reached this target, a variation which suggests different levels of tolerance to nutrient imbalance. We discuss our results in the context of how colony performance may be influenced by the different nutrient balancing strategies of individual members and how such nutritional constraints could have contributed to the evolution of sociality. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Differences in end-point force trajectories elicited by electrical stimulation of individual human calf muscles

    PubMed Central

    Giordano, S B; Segal, R L; Abelew, T A

    2009-01-01

    The purpose of this study was to investigate the end-point force trajectories of the fibularis longus (FIB), lateral gastrocnemius (LG) and medial gastrocnemius (MG) muscles. Most information about individual muscle function has come from studies which use models based on electromyographic (EMG) recordings. In this study (N=20 subjects) we used electrical stimulation (20Hz) to elicit activity in individual muscles, recorded the end-point forces at the foot and verified the selectivity of stimulation by using magnetic resonance imaging. Unexpectedly, no significant differences were found between LG and MG force directions. Stimulation of LG and MG resulted in downward and medial or lateral forces depending on the subject. We found FIB end-point forces to be significantly different than those of LG and MG. In all subjects, stimulation of FIB resulted in downward and lateral forces. Based on our results, we suggest that there are multiple factors determining when and whether LG or MG will produce a medial or lateral force and FIB consistently plays a significant role in eversion/abduction and plantarflexion. We suggest that the inter-subject variability we found is not simply an artifact of experimental or technical error but is functionally relevant and should be addressed in future studies and models. PMID:20095454

  8. Introducing a true internal standard for the Comet assay to minimize intra- and inter-experiment variability in measures of DNA damage and repair

    PubMed Central

    Zainol, Murizal; Stoute, Julia; Almeida, Gabriela M.; Rapp, Alexander; Bowman, Karen J.; Jones, George D. D.

    2009-01-01

    The Comet assay (CA) is a sensitive/simple measure of genotoxicity. However, many features of CA contribute variability. To minimize these, we have introduced internal standard materials consisting of ‘reference’ cells which have their DNA substituted with BrdU. Using a fluorescent anti-BrdU antibody, plus an additional barrier filter, comets derived from these cells could be readily distinguished from the ‘test’-cell comets, present in the same gel. In experiments to evaluate the reference cell comets as external and internal standards, the reference and test cells were present in separate gels on the same slide or mixed together in the same gel, respectively, before their co-exposure to X-irradiation. Using the reference cell comets as internal standards led to substantial reductions in the coefficient of variation (CoV) for intra- and inter-experimental measures of comet formation and DNA damage repair; only minor reductions in CoV were noted when the reference and test cell comets were in separate gels. These studies indicate that differences between individual gels appreciably contribute to CA variation. Further studies using the reference cells as internal standards allowed greater significance to be obtained between groups of replicate samples. Ultimately, we anticipate that development will deliver robust quality assurance materials for CA. PMID:19828597

  9. Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes.

    PubMed

    Rietschel, Liz; Streit, Fabian; Zhu, Gu; McAloney, Kerrie; Frank, Josef; Couvy-Duchesne, Baptiste; Witt, Stephanie H; Binz, Tina M; McGrath, John; Hickie, Ian B; Hansell, Narelle K; Wright, Margaret J; Gillespie, Nathan A; Forstner, Andreas J; Schulze, Thomas G; Wüst, Stefan; Nöthen, Markus M; Baumgartner, Markus R; Walker, Brian R; Crawford, Andrew A; Colodro-Conde, Lucía; Medland, Sarah E; Martin, Nicholas G; Rietschel, Marcella

    2017-11-10

    Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.

  10. Gonioscopy in the dog: inter-examiner variability and the search for a grading scheme.

    PubMed

    Oliver, J A C; Cottrell, B C; Newton, J R; Mellersh, C S

    2017-11-01

    To investigate inter-examiner variability in gonioscopic evaluation of pectinate ligament abnormality in dogs and to assess level of inter-examiner agreement for four different gonioscopy grading schemes. Two examiners performed gonioscopy in 98 eyes of 49 Welsh springer spaniel dogs and estimated the percentage circumference of iridocorneal angle affected by pectinate ligament abnormality to the nearest 5%. Percentage scores assigned to each eye by the two examiners were compared. Inter-examiner agreement was assessed following assignment of the percentage scores to each of four grading schemes by Cohen's kappa statistic. There was a strong positive correlation between the results of the two examiners (R=0·91). In general, Examiner 1 scored individual eyes higher than Examiner 2, especially for eyes in which both examiners diagnosed pectinate ligament abnormality. A "good" level of agreement could only be achieved with a gonioscopy grading scheme of no more than three categories and with a relatively large intermediate bandwidth (κ=0·68). A three-tiered grading scheme might represent an improvement on hereditary eye disease schemes which simply classify dogs to be either "affected" or "unaffected" for pectinate ligament abnormality. However, the large intermediate bandwidth of this scheme would only allow for the additional detection of those dogs with marked progression of pectinate ligament abnormality which would be considered most at risk of primary closed-angle glaucoma. © 2017 British Small Animal Veterinary Association.

  11. The marine side of a terrestrial carnivore: intra-population variation in use of allochthonous resources by arctic foxes.

    PubMed

    Tarroux, Arnaud; Bêty, Joël; Gauthier, Gilles; Berteaux, Dominique

    2012-01-01

    Inter-individual variation in diet within generalist animal populations is thought to be a widespread phenomenon but its potential causes are poorly known. Inter-individual variation can be amplified by the availability and use of allochthonous resources, i.e., resources coming from spatially distinct ecosystems. Using a wild population of arctic fox as a study model, we tested hypotheses that could explain variation in both population and individual isotopic niches, used here as proxy for the trophic niche. The arctic fox is an opportunistic forager, dwelling in terrestrial and marine environments characterized by strong spatial (arctic-nesting birds) and temporal (cyclic lemmings) fluctuations in resource abundance. First, we tested the hypothesis that generalist foraging habits, in association with temporal variation in prey accessibility, should induce temporal changes in isotopic niche width and diet. Second, we investigated whether within-population variation in the isotopic niche could be explained by individual characteristics (sex and breeding status) and environmental factors (spatiotemporal variation in prey availability). We addressed these questions using isotopic analysis and bayesian mixing models in conjunction with linear mixed-effects models. We found that: i) arctic fox populations can simultaneously undergo short-term (i.e., within a few months) reduction in both isotopic niche width and inter-individual variability in isotopic ratios, ii) individual isotopic ratios were higher and more representative of a marine-based diet for non-breeding than breeding foxes early in spring, and iii) lemming population cycles did not appear to directly influence the diet of individual foxes after taking their breeding status into account. However, lemming abundance was correlated to proportion of breeding foxes, and could thus indirectly affect the diet at the population scale.

  12. The Marine Side of a Terrestrial Carnivore: Intra-Population Variation in Use of Allochthonous Resources by Arctic Foxes

    PubMed Central

    Tarroux, Arnaud; Bêty, Joël; Gauthier, Gilles; Berteaux, Dominique

    2012-01-01

    Inter-individual variation in diet within generalist animal populations is thought to be a widespread phenomenon but its potential causes are poorly known. Inter-individual variation can be amplified by the availability and use of allochthonous resources, i.e., resources coming from spatially distinct ecosystems. Using a wild population of arctic fox as a study model, we tested hypotheses that could explain variation in both population and individual isotopic niches, used here as proxy for the trophic niche. The arctic fox is an opportunistic forager, dwelling in terrestrial and marine environments characterized by strong spatial (arctic-nesting birds) and temporal (cyclic lemmings) fluctuations in resource abundance. First, we tested the hypothesis that generalist foraging habits, in association with temporal variation in prey accessibility, should induce temporal changes in isotopic niche width and diet. Second, we investigated whether within-population variation in the isotopic niche could be explained by individual characteristics (sex and breeding status) and environmental factors (spatiotemporal variation in prey availability). We addressed these questions using isotopic analysis and Bayesian mixing models in conjunction with linear mixed-effects models. We found that: i) arctic fox populations can simultaneously undergo short-term (i.e., within a few months) reduction in both isotopic niche width and inter-individual variability in isotopic ratios, ii) individual isotopic ratios were higher and more representative of a marine-based diet for non-breeding than breeding foxes early in spring, and iii) lemming population cycles did not appear to directly influence the diet of individual foxes after taking their breeding status into account. However, lemming abundance was correlated to proportion of breeding foxes, and could thus indirectly affect the diet at the population scale. PMID:22900021

  13. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Diakov, Victor; Brinkman, Gregory; Denholm, Paul

    Using production-cost model (PLEXOS), we simulate the Western Interchange (WECC) at several levels of the yearly renewable energy (RE) generation, between 13% and 40% of the total load for the year. We look at the overall energy exchange between a region and the rest of the system (net interchange, NI), and find it useful to examine separately (i) (time-)variable and (ii) year-average components of the NI. Both contribute to inter-regional energy exchange, and are affected by wind and PV generation in the system. We find that net load variability (in relatively large portions of WECC) is the leading factor affectingmore » the variable component of inter-regional energy exchange, and the effect is quantifiable: higher regional net load correlation with the rest of the WECC lowers net interchange variability. Further, as the power mix significantly varies between WECC regions, effects of ‘flexibility import’ (regions ‘borrow’ ramping capability) are also observed.« less

  14. The intra-individual reproducibility of flash-evoked potentials in a sample of children.

    PubMed

    Schellberg, D; Gasser, T; Köhler, W

    1987-07-01

    Visual evoked potentials (VEPs) to flash stimuli were recorded twice from 26 children aged 10-13 years, with an intersession interval of about 10 months. Test-retest reliability was poor for recordings taken from scalp locations overlying non-specific cortex and somewhat better for specific cortex. The size of consistency coefficients (i.e. correlations within session) showed that noise and artefacts were not the decisive factors which lower reliability. A comparison with retest correlations of broad band parameters of the EEG at rest for the same sample showed, to our surprise, smaller retest reliability for VEP parameters. Variability of the VEP in children over time seems to be a substantial as its well-known inter-individual variability.

  15. Inter- and intraobserver variability of (semi-)quantitative parameters commonly used in feline thyroid scintigraphy.

    PubMed

    Volckaert, Veerle; Vandermeulen, Eva; Duchateau, Luc; Saunders, Jimmy H; Peremans, Kathelijne

    2016-04-01

    The aim of this study was to assess inter- and intraobserver variability of commonly used semi-quantitative and quantitative parameters in feline thyroid scintigraphy: thyroid to salivary gland ratio (T/S), thyroid to background ratio (T/B) and the percentage technetium pertechnetate uptake for the thyroid glands (%TcUT). These parameters are being used to diagnose thyroid disease and to assess its severity, but may be influenced by operator related factors when processing the images. Additionally, inter- and intraobserver variability of the percentage technetium pertechnetate uptake for the salivary glands was determined (%TcUSG). The study included technetium pertechnetate scans of 100 hyperthyroid cats. Variability within and between three observers was determined using a random effects model and variance components were estimated by the restricted maximum likelihood procedure. The %TcU for the thyroid and salivary glands, as well as the T/S ratio, showed little to no difference in inter- and intraobserver variability, whereas this was clearly present for the T/B ratio. Overall, the T/S ratio and %TcUSG showed a good repeatability and reproducibility with low inter- and intraobserver variabilities. Inter- and intraobserver variability was higher for the %TcUT, however variations were still considered to be acceptable. On the contrary, inter- and intraobserver variability was clearly larger for the T/B ratio. These findings suggest the preferential use of the T/S ratio or %TcU, especially in facilities with a less experienced staff. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  16. Multi-criteria Evaluation of Discharge Simulation in Dynamic Global Vegetation Models

    NASA Astrophysics Data System (ADS)

    Yang, H.; Piao, S.; Zeng, Z.; Ciais, P.; Yin, Y.; Friedlingstein, P.; Sitch, S.; Ahlström, A.; Guimberteau, M.; Huntingford, C.; Levis, S.; Levy, P. E.; Huang, M.; Li, Y.; Li, X.; Lomas, M.; Peylin, P. P.; Poulter, B.; Viovy, N.; Zaehle, S.; Zeng, N.; Zhao, F.; Wang, L.

    2015-12-01

    In this study, we assessed the performance of discharge simulations by coupling the runoff from seven Dynamic Global Vegetation Models (DGVMs; LPJ, ORCHIDEE, Sheffield-DGVM, TRIFFID, LPJ-GUESS, CLM4CN, and OCN) to one river routing model for 16 large river basins. The results show that the seasonal cycle of river discharge is generally modelled well in the low and mid latitudes, but not in the high latitudes, where the peak discharge (due to snow and ice melting) is underestimated. For the annual mean discharge, the DGVMs chained with the routing model show an underestimation. Furthermore the 30-year trend of discharge is also under-estimated. For the inter-annual variability of discharge, a skill score based on overlapping of probability density functions (PDFs) suggests that most models correctly reproduce the observed variability (correlation coefficient higher than 0.5; i.e. models account for 50% of observed inter-annual variability) except for the Lena, Yenisei, Yukon, and the Congo river basins. In addition, we compared the simulated runoff from different simulations where models were forced with either fixed or varying land use. This suggests that both seasonal and annual mean runoff has been little affected by land use change, but that the trend itself of runoff is sensitive to land use change. None of the models when considered individually show significantly better performances than any other and in all basins. This suggests that based on current modelling capability, a regional-weighted average of multi-model ensemble projections might be appropriate to reduce the bias in future projection of global river discharge.

  17. Neuroanatomical correlates of brain-computer interface performance.

    PubMed

    Kasahara, Kazumi; DaSalla, Charles Sayo; Honda, Manabu; Hanakawa, Takashi

    2015-04-15

    Brain-computer interfaces (BCIs) offer a potential means to replace or restore lost motor function. However, BCI performance varies considerably between users, the reasons for which are poorly understood. Here we investigated the relationship between sensorimotor rhythm (SMR)-based BCI performance and brain structure. Participants were instructed to control a computer cursor using right- and left-hand motor imagery, which primarily modulated their left- and right-hemispheric SMR powers, respectively. Although most participants were able to control the BCI with success rates significantly above chance level even at the first encounter, they also showed substantial inter-individual variability in BCI success rate. Participants also underwent T1-weighted three-dimensional structural magnetic resonance imaging (MRI). The MRI data were subjected to voxel-based morphometry using BCI success rate as an independent variable. We found that BCI performance correlated with gray matter volume of the supplementary motor area, supplementary somatosensory area, and dorsal premotor cortex. We suggest that SMR-based BCI performance is associated with development of non-primary somatosensory and motor areas. Advancing our understanding of BCI performance in relation to its neuroanatomical correlates may lead to better customization of BCIs based on individual brain structure. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Changes in Physiological Parameters after Combined Exercise according to the I/D Polymorphism of hUCP2 Gene in Middle-Aged Obese Females

    PubMed Central

    DUK OH, Sang

    2014-01-01

    Abstract Background The purpose of this study was to determine whether a 45 bp insertion/deletion (I/D) polymorphism in human uncoupling protein 2 (hUCP2) gene was associated with changes in several cardiovascular risk and physical fitness factors in response to combined exercise during 12 weeks in Korean middle-aged women. The changes in physiological parameters after combined exercise during 12 weeks were compared between each genotype subgroups of hUCP2 gene to clarify the inter-individual differences in exercised-induced changes according to genetic predisposition. Methods A total of 185 women aged over 40 years living in Seoul, Korea were participated in this study, and analyzed before and after 12 weeks on combined exercise including aerobic exercise and strength training for body composition, hemodynamic parameters, physical fitness and metabolic variables. A 45 bp I/D polymorphism in hUCP2 gene was genotyped by polymerase chain reaction (PCR) amplification and agarose gel electrophoresis method. Results Combined exercise program during 12 weeks indicated the significant health-promoting effects for our participants on multiple body composition, hemodynamic parameters, physical fitness factors and metabolic parameters, respectively. With respect to a 45 bp I/D polymorphism in hUCP2 gene, this polymorphism was significantly associated with baseline %body fat of our participants (P <.05). Moreover, this polymorphism was significantly associated with the changes in %body fat and serum triglyceride(TG) level after combined exercise program during 12 weeks(P <.05). Conclusion Our data suggest that a 45 bp I/D polymorphism in hUCP2 gene may at least in part contribute to the inter-individual differences on the changes in some clinical and metabolic parameters following combined exercise in middle-aged women. PMID:25909061

  19. Genetic influences on heart rate variability

    PubMed Central

    Golosheykin, Simon; Grant, Julia D.; Novak, Olga V.; Heath, Andrew C.; Anokhin, Andrey P.

    2016-01-01

    Heart rate variability (HRV) is the variation of cardiac inter-beat intervals over time resulting largely from the interplay between the sympathetic and parasympathetic branches of the autonomic nervous system. Individual differences in HRV are associated with emotion regulation, personality, psychopathology, cardiovascular health, and mortality. Previous studies have shown significant heritability of HRV measures. Here we extend genetic research on HRV by investigating sex differences in genetic underpinnings of HRV, the degree of genetic overlap among different measurement domains of HRV, and phenotypic and genetic relationships between HRV and the resting heart rate (HR). We performed electrocardiogram (ECG) recordings in a large population-representative sample of young adult twins (n = 1060 individuals) and computed HRV measures from three domains: time, frequency, and nonlinear dynamics. Genetic and environmental influences on HRV measures were estimated using linear structural equation modeling of twin data. The results showed that variability of HRV and HR measures can be accounted for by additive genetic and non-shared environmental influences (AE model), with no evidence for significant shared environmental effects. Heritability estimates ranged from 47 to 64%, with little difference across HRV measurement domains. Genetic influences did not differ between genders for most variables except the square root of the mean squared differences between successive R-R intervals (RMSSD, higher heritability in males) and the ratio of low to high frequency power (LF/HF, distinct genetic factors operating in males and females). The results indicate high phenotypic and especially genetic correlations between HRV measures from different domains, suggesting that >90% of genetic influences are shared across measures. Finally, about 40% of genetic variance in HRV was shared with HR. In conclusion, both HR and HRV measures are highly heritable traits in the general population of young adults, with high degree of genetic overlap across different measurement domains. PMID:27114045

  20. Evaluation of analgesic effect and absorption of buprenorphine after buccal administration in cats with oral disease.

    PubMed

    Stathopoulou, Thaleia-Rengina; Kouki, Maria; Pypendop, Bruno H; Johnston, Atholl; Papadimitriou, Serafeim; Pelligand, Ludovic

    2017-09-01

    Objectives The objective of this study was to evaluate the analgesic effect and absorption of buprenorphine after buccal administration in cats with oral disease. Methods Six adult client-owned cats with chronic gingivostomatitis (weighing 5.1 ± 1.1 kg) were recruited for a randomised, prospective, blinded, saline-controlled, crossover study. Pain scores, dental examination, stomatitis score and buccal pH measurement were conducted on day 1 under sedation in all cats. On day 2, animals were randomised into two groups and administered one of the two treatments buccally (group A received buprenorphine 0.02 mg/kg and group B received 0.9% saline) and vice versa on day 3. Pain scores and food consumption were measured at 30, 90 and 360 mins after the administration of buprenorphine. Blood samples were taken at the same time and plasma buprenorphine concentration was measured by liquid chromatography-mass spectrometry. Data were statistically analysed as non-parametric and the level of significance was set as P <0.05. Results There were no major side effects after buprenorphine administration. Buccal pH values ranged between 8.5 and 9.1 and the stomatitis disease activity index between 10 and 22 (17.8 ± 4.5) with the scale ranging from 0-30. The maximum buprenorphine plasma concentration (14.8 ng/ml) was observed 30 mins after administration and there was low inter-individual variability. There was a significant difference between baseline pain scores compared with pain scores after buprenorphine ( P <0.05 ) and between the saline and buprenorphine group at 30 mins ( P = 0.04) and 90 mins ( P = 0.04). There was also a significant effect of the stomatitis index on the pain score. Regarding the pharmacokinetic parameters, cats with stomatitis showed lower bioavailability and shorter absorption half-life after buccal administration of buprenorphine compared with normal cats in previous studies. Conclusions and relevance Buccal administration of buprenorphine in cats with gingivostomatitis produces an analgesic effect and low inter-individual variability in plasma concentration, and it can be incorporated in their multimodal analgesia plan.

  1. Ethnicity-Dependent and -Independent Heterogeneity in Healthy Normal Breast Hierarchy Impacts Tumor Characterization

    PubMed Central

    Nakshatri, Harikrishna; Anjanappa, Manjushree; Bhat-Nakshatri, Poornima

    2015-01-01

    Recent reports of widespread genetic variation affecting regulation of gene expression raise the possibility of significant inter-individual differences in stem-progenitor-mature cell hierarchy in adult organs. This has not been explored because of paucity of methods to quantitatively assess subpopulation of normal epithelial cells on individual basis. We report the remarkable inter-individual differences in differentiation capabilities as documented by phenotypic heterogeneity in stem-progenitor-mature cell hierarchy of the normal breast. Ethnicity and genetic predisposition are partly responsible for this heterogeneity, evidenced by the finding that CD44+/CD24- and PROCR+/EpCAM- multi-potent stem cells were elevated significantly in African American women compared with Caucasians. ALDEFLUOR+ luminal stem/progenitor cells were lower in BRCA1-mutation carriers compared with cells from healthy donors (p = 0.0014). Moreover, tumor and adjoining-normal breast cells of the same patients showed distinct CD49f+/EpCAM+ progenitor, CD271+/EpCAM- basal, and ALDEFLUOR+ cell profiles. These inter-individual differences in the rate of differentiation in the normal breast may contribute to a substantial proportion of transcriptome, epigenome, and signaling pathway alterations and consequently has the potential to spuriously magnify the extent of documented tumor-specific gene expression. Therefore, comparative analysis of phenotypically defined subpopulations of normal and tumor cells on an individual basis may be required to identify cancer-specific aberrations. PMID:26311223

  2. Ethnicity-Dependent and -Independent Heterogeneity in Healthy Normal Breast Hierarchy Impacts Tumor Characterization.

    PubMed

    Nakshatri, Harikrishna; Anjanappa, Manjushree; Bhat-Nakshatri, Poornima

    2015-08-27

    Recent reports of widespread genetic variation affecting regulation of gene expression raise the possibility of significant inter-individual differences in stem-progenitor-mature cell hierarchy in adult organs. This has not been explored because of paucity of methods to quantitatively assess subpopulation of normal epithelial cells on individual basis. We report the remarkable inter-individual differences in differentiation capabilities as documented by phenotypic heterogeneity in stem-progenitor-mature cell hierarchy of the normal breast. Ethnicity and genetic predisposition are partly responsible for this heterogeneity, evidenced by the finding that CD44+/CD24- and PROCR+/EpCAM- multi-potent stem cells were elevated significantly in African American women compared with Caucasians. ALDEFLUOR+ luminal stem/progenitor cells were lower in BRCA1-mutation carriers compared with cells from healthy donors (p = 0.0014). Moreover, tumor and adjoining-normal breast cells of the same patients showed distinct CD49f+/EpCAM+ progenitor, CD271+/EpCAM- basal, and ALDEFLUOR+ cell profiles. These inter-individual differences in the rate of differentiation in the normal breast may contribute to a substantial proportion of transcriptome, epigenome, and signaling pathway alterations and consequently has the potential to spuriously magnify the extent of documented tumor-specific gene expression. Therefore, comparative analysis of phenotypically defined subpopulations of normal and tumor cells on an individual basis may be required to identify cancer-specific aberrations.

  3. Individual Variation in Lipidomic Profiles of Healthy Subjects in Response to Omega-3 Fatty Acids

    PubMed Central

    Nording, Malin L.; Yang, Jun; Georgi, Katrin; Hegedus Karbowski, Christine; German, J. Bruce; Weiss, Robert H.; Hogg, Ronald J.; Trygg, Johan; Hammock, Bruce D.; Zivkovic, Angela M.

    2013-01-01

    Introduction Conflicting findings in both interventional and observational studies have resulted in a lack of consensus on the benefits of ω3 fatty acids in reducing disease risk. This may be due to individual variability in response. We used a multi-platform lipidomic approach to investigate both the consistent and inconsistent responses of individuals comprehensively to a defined ω3 intervention. Methods The lipidomic profile including fatty acids, lipid classes, lipoprotein distribution, and oxylipins was examined multi- and uni-variately in 12 healthy subjects pre vs. post six weeks of ω3 fatty acids (1.9 g/d eicosapentaenoic acid [EPA] and 1.5 g/d docosahexaenoic acid [DHA]). Results Total lipidomic and oxylipin profiles were significantly different pre vs. post treatment across all subjects (p=0.00007 and p=0.00002 respectively). There was a strong correlation between oxylipin profiles and EPA and DHA incorporated into different lipid classes (r2=0.93). However, strikingly divergent responses among individuals were also observed. Both ω3 and ω6 fatty acid metabolites displayed a large degree of variation among the subjects. For example, in half of the subjects, two arachidonic acid cyclooxygenase products, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), and a lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) significantly decreased post intervention, whereas in the other half they either did not change or increased. The EPA lipoxygenase metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) varied among subjects from an 82% decrease to a 5,000% increase. Conclusions Our results show that certain defined responses to ω3 fatty acid intervention were consistent across all subjects. However, there was also a high degree of inter-individual variability in certain aspects of lipid metabolism. This lipidomic based phenotyping approach demonstrated that individual responsiveness to ω3 fatty acids is highly variable and measurable, and could be used as a means to assess the effectiveness of ω3 interventions in modifying disease risk and determining metabolic phenotype. PMID:24204640

  4. A descriptive study of step alignment and foot positioning relative to the tee by professional rugby union goal-kickers.

    PubMed

    Cockcroft, John; Van Den Heever, Dawie

    2016-01-01

    This study describes foot positioning during the final two steps of the approach to the ball amongst professional rugby goal-kickers. A 3D optical motion capture system was used to test 15 goal-kickers performing 10 goal-kicks. The distance and direction of each step, as well as individual foot contact positions relative to the tee, were measured. The intra- and inter-subject variability was calculated as well as the correlation (Pearson) between the measurements and participant anthropometrics. Inter-subject variability for the final foot position was lowest (placed 0.03 ± 0.07 m behind and 0.33 ± 0.03 m lateral to the tee) and highest for the penultimate step distance (0.666 ± 0.149 m), performed at an angle of 36.1 ± 8.5° external to the final step. The final step length was 1.523 ± 0.124 m, executed at an external angle of 35.5 ± 7.4° to the target line. The intra-subject variability was very low; distances and angles for the 10 kicks varied per participant by 1.6-3.1 cm and 0.7-1.6°, respectively. The results show that even though the participants had variability in their run-up to the tee, final foot position next to the tee was very similar and consistent. Furthermore, the inter- and intra-subject variability could not be attributed to differences in anthropometry. These findings may be useful as normative reference data for coaching, although further work is required to understand the role of other factors such as approach speed and body alignment.

  5. Sampling Modification Effects in the Subgingival Microbiome Profile of Healthy Children

    PubMed Central

    Santigli, Elisabeth; Trajanoski, Slave; Eberhard, Katharina; Klug, Barbara

    2017-01-01

    Background: Oral microbiota are considered major players in the development of periodontal diseases. Thorough knowledge of intact subgingival microbiomes is required to elucidate microbial shifts from health to disease. Aims: This comparative study investigated the subgingival microbiome of healthy children, possible inter- and intra-individual effects of modified sampling, and basic comparability of subgingival microprints. Methods: In five 10-year-old children, biofilm was collected from the upper first premolars and first molars using sterilized, UV-treated paper-points inserted into the subgingival sulcus at eight sites. After supragingival cleaning using an electric toothbrush and water, sampling was performed, firstly, excluding (Mode A) and, secondly, including (Mode B) cleansing with sterile cotton pellets. DNA was extracted from the pooled samples, and primers targeting 16S rRNA hypervariable regions V5 and V6 were used for 454-pyrosequencing. Wilcoxon signed rank test and t-test were applied to compare sampling modes. Principal coordinate analysis (PCoA) and average agglomerative hierarchical clustering were calculated with unweighted UniFrac distance matrices. Sample grouping was tested with permutational MANOVA (Adonis). Results: Data filtering and quality control yielded 67,218 sequences with an average sequence length of 243bp (SD 6.52; range 231–255). Actinobacteria (2.8–24.6%), Bacteroidetes (9.2–25.1%), Proteobacteria (4.9–50.6%), Firmicutes (16.5–57.4%), and Fusobacteria (2.2–17.1%) were the five major phyla found in all samples. Differences in microbial abundances between sampling modes were not evident. High sampling numbers are needed to achieve significance for rare bacterial phyla. Samples taken from one individual using different sampling modes were more similar to each other than to other individuals' samples. PCoA and hierarchical clustering showed a grouping of the paired samples. Permutational MANOVA did not reveal sample grouping by sampling modes (p = 0.914 by R2 = 0.09). Conclusion: A slight modification of sampling mode has minor effects corresponding to a natural variability in the microbiome profiles of healthy children. The inter-individual variability in subgingival microprints is greater than intra-individual differences. Statistical analyses of microbial populations should consider this baseline variability and move beyond mere quantification with input from visual analytics. Comparative results are difficult to summarize as methods for studying huge datasets are still evolving. Advanced approaches are needed for sample size calculations in clinical settings. PMID:28149291

  6. [Effects of water level fluctuation on the inter- and intra-specific relationships between Wedelia trilobata and W. chinensis].

    PubMed

    Bu, Xiang Qi; Liu, Lin; Mu, Ya Nan; Guan, Yu Ting; Li, Hong Li; Yu, Fei Hai

    2017-03-18

    A controlled greenhouse experiment was designed with the invasive Wedelia trilobata and native W. chinensis. Three water level fluctuation treatments (no fluctuation, change pattern by 15 cm-0 cm-15 cm, change pattern by 0 cm-15 cm-0 cm) were crossed with five plant arrangement treatments (an individual invasive plant per pot, an individual native plant per pot, 6 invasive plants per pot, 6 native plants per pot, six plants per pot with three invasive and three native plants) to explore the effects of water level fluctuation on inter- and intra-specific relationships between W. trilobata and W. chinensis. The results showed that water level fluctuation decreased signifi-cantly the total biomass, stem biomass, leaf biomass, root biomass, stem length, number of nodes, number of leaves and leaf area of W. trilobata and W. chinensis. Meantime it had significant effects on the inter- and intra-specific competition between W. trilobata and W. chinensis. Water level fluctuation changed the inter- and intra-specific competition of W. trilobata. It indicated that W. trilobata was more sensitive to water level fluctuation with stronger adaptability.

  7. Repeatability of shear wave elastography in liver fibrosis phantoms—Evaluation of five different systems

    PubMed Central

    2018-01-01

    This study aimed to assess and validate the repeatability and agreement of quantitative elastography of novel shear wave methods on four individual tissue-mimicking liver fibrosis phantoms with different known Young’s modulus. We used GE Logiq E9 2D-SWE, Philips iU22 ARFI (pSWE), Samsung TS80A SWE (pSWE), Hitachi Ascendus (SWM) and Transient Elastography (TE). Two individual investigators performed all measurements non-continued and in parallel. The methods were evaluated for inter- and intraobserver variability by intraclass correlation, coefficient of variation and limits of agreement using the median elastography value. All systems used in this study provided high repeatability in quantitative measurements in a liver fibrosis phantom and excellent inter- and intraclass correlations. All four elastography platforms showed excellent intra-and interobserver agreement (interclass correlation 0.981–1.000 and intraclass correlation 0.987–1.000) and no significant difference in mean elasticity measurements for all systems, except for TE on phantom 4. All four liver fibrosis phantoms could be differentiated by quantitative elastography, by all platforms (p<0.001). In the Bland-Altman analysis the differences in measurements were larger for the phantoms with higher Young’s modulus. All platforms had a coefficient of variation in the range 0.00–0.21 for all four phantoms, equivalent to low variance and high repeatability. PMID:29293527

  8. Use of a probabilistic PBPK/PD model to calculate Data Derived Extrapolation Factors for chlorpyrifos.

    PubMed

    Poet, Torka S; Timchalk, Charles; Bartels, Michael J; Smith, Jordan N; McDougal, Robin; Juberg, Daland R; Price, Paul S

    2017-06-01

    A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model combined with Monte Carlo analysis of inter-individual variation was used to assess the effects of the insecticide, chlorpyrifos and its active metabolite, chlorpyrifos oxon in humans. The PBPK/PD model has previously been validated and used to describe physiological changes in typical individuals as they grow from birth to adulthood. This model was updated to include physiological and metabolic changes that occur with pregnancy. The model was then used to assess the impact of inter-individual variability in physiology and biochemistry on predictions of internal dose metrics and quantitatively assess the impact of major sources of parameter uncertainty and biological diversity on the pharmacodynamics of red blood cell acetylcholinesterase inhibition. These metrics were determined in potentially sensitive populations of infants, adult women, pregnant women, and a combined population of adult men and women. The parameters primarily responsible for inter-individual variation in RBC acetylcholinesterase inhibition were related to metabolic clearance of CPF and CPF-oxon. Data Derived Extrapolation Factors that address intra-species physiology and biochemistry to replace uncertainty factors with quantitative differences in metrics were developed in these same populations. The DDEFs were less than 4 for all populations. These data and modeling approach will be useful in ongoing and future human health risk assessments for CPF and could be used for other chemicals with potential human exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Transdermal scopolamine in the prevention of motion sickness - Evaluation of the time course of efficacy

    NASA Technical Reports Server (NTRS)

    Homick, J. L.; Reschke, M. F.; Degioanni, J.; Cintron-Trevino, N. M.; Kohl, R. L.

    1983-01-01

    This study evaluated the time course of efficacy of transdermal scopolamine in the prevention of motion sickness induced by exposure to coriolis stimulation in a rotating chair. We measured levels of efficacy, quantified side effects and symptoms, and determined inter- and intra-subject variability following use of transdermal scopolamine. The response to transdermal scopolamine was highly variable, although overall we recorded a 40 percent improvement in test scores 16-72 h after application of the transdermal system. This variability could not be explained solely by the levels of scopolamine present in the blood. The improvement was not due to the artifactual repression by scopolamine of selected symptoms of motion sickness. An unexpectedly high incidence of side effects was reported. It was concluded that the therapeutic use of transdermal scopolamine be evaluated individually and that individuals be cautioned that subsequent usage may not always be effective.

  10. Keeping an Eye on Noisy Movements: On Different Approaches to Perceptual-Motor Skill Research and Training.

    PubMed

    Dicks, Matt; Button, Chris; Davids, Keith; Chow, Jia Yi; van der Kamp, John

    2017-04-01

    Contemporary theorizing on the complementary nature of perception and action in expert performance has led to different emphases in the study of movement coordination and gaze behavior. On the one hand, coordination research has examined the role of variability in movement control, evidencing that variability facilitates individualized adaptations during both learning and performance. On the other hand, and at odds with this principle, the majority of gaze behavior studies have tended to average data over participants and trials, proposing the importance of universal 'optimal' gaze patterns in a given task, for all performers, irrespective of stage of learning. In this article, we discuss new lines of inquiry with the aim of reconciling these two distinct approaches. We consider the role of inter- and intra-individual variability in gaze behaviors and suggest directions for future research.

  11. Prediction of BRCA1 and BRCA2 mutation status using post-irradiation assays of lymphoblastoid cell lines is compromised by inter-cell-line phenotypic variability.

    PubMed

    Lovelock, Paul K; Wong, Ee Ming; Sprung, Carl N; Marsh, Anna; Hobson, Karen; French, Juliet D; Southey, Melissa; Sculley, Tom; Pandeya, Nirmala; Brown, Melissa A; Chenevix-Trench, Georgia; Spurdle, Amanda B; McKay, Michael J

    2007-09-01

    Assays to determine the pathogenicity of unclassified sequence variants in disease-associated genes include the analysis of lymphoblastoid cell lines (LCLs). We assessed the ability of several assays of LCLs to distinguish carriers of germline BRCA1 and BRCA2 gene mutations from mutation-negative controls to determine their utility for use in a diagnostic setting. Post-ionising radiation cell viability and micronucleus formation, and telomere length were assayed in LCLs carrying BRCA1 or BRCA2 mutations, and in unaffected mutation-negative controls. Post-irradiation cell viability and micronucleus induction assays of LCLs from individuals carrying pathogenic BRCA1 mutations, unclassified BRCA1 sequence variants or wildtype BRCA1 sequence showed significant phenotypic heterogeneity within each group. Responses were not consistent with predicted functional consequences of known pathogenic or normal sequences. Telomere length was also highly heterogeneous within groups of LCLs carrying pathogenic BRCA1 or BRCA2 mutations, and normal BRCA1 sequences, and was not predictive of mutation status. Given the significant degree of phenotypic heterogeneity of LCLs after gamma-irradiation, and the lack of association with BRCA1 or BRCA2 mutation status, we conclude that the assays evaluated in this study should not be used as a means of differentiating pathogenic and non-pathogenic sequence variants for clinical application. We suggest that a range of normal controls must be included in any functional assays of LCLs to ensure that any observed differences between samples reflect the genotype under investigation rather than generic inter-individual variation.

  12. The Effect of microRNAs in the Regulation of Human CYP3A4: a Systematic Study using a Mathematical Model

    PubMed Central

    Wei, Zhiyun; Jiang, Songshan; Zhang, Yiting; Wang, Xiaofei; Peng, Xueling; Meng, Chunjie; Liu, Yichen; Wang, Honglian; Guo, Luo; Qin, Shengying; He, Lin; Shao, Fengmin; Zhang, Lirong; Xing, Qinghe

    2014-01-01

    CYP3A4 metabolizes more than 50% of the drugs on the market. The large inter-individual differences of CYP3A4 expression may contribute to the variability of human drug responses. Post-transcriptional regulation of CYP3A4 is poorly understood, whereas transcriptional regulation has been studied much more thoroughly. In this study, we used multiple software programs to predict miRNAs that might bind to CYP3A4 and identified 112 potentially functional miRNAs. Then a luciferase reporter system was used to assess the effect of the overexpression of each potentially functional miRNA in HEK 293T cells. Fourteen miRNAs that significantly decreased reporter activity were measured in human liver samples (N = 27) as candidate miRNAs. To establish a more effective way to analyze in vivo data for miRNA candidates, the relationship between functional miRNA and target mRNA was modeled mathematically. Taking advantage of this model, we found that hsa-miR-577, hsa-miR-1, hsa-miR-532-3p and hsa-miR-627 could significantly downregulate the translation efficiency of CYP3A4 mRNA in liver. This study used in silico, in vitro and in vivo methods to progressively screen functional miRNAs for CYP3A4 and to enhance our understanding of molecular events underlying the large inter-individual differences of CYP3A4 expression in human populations. PMID:24594634

  13. Towards standardization of 18F-FET PET imaging: do we need a consistent method of background activity assessment?

    PubMed

    Unterrainer, Marcus; Vettermann, Franziska; Brendel, Matthias; Holzgreve, Adrien; Lifschitz, Michael; Zähringer, Matthias; Suchorska, Bogdana; Wenter, Vera; Illigens, Ben M; Bartenstein, Peter; Albert, Nathalie L

    2017-12-01

    PET with O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference. Therefore, we evaluated the intra- and inter-reader variability of commonly applied approaches for clinical 18 F-FET PET reading. The background activity of 20 18 F-FET PET scans was independently evaluated by 6 readers using a (i) simple 2D-ROI, (ii) spherical VOI with 3.0 cm diameter, and (iii) VOI consisting of crescent-shaped ROIs; each in the contralateral, non-affected hemisphere including white and gray matter in line with the European Association of Nuclear Medicine (EANM) and German guidelines. To assess intra-reader variability, each scan was evaluated 10 times by each reader. The coefficient of variation (CoV) was assessed for determination of intra- and inter-reader variability. In a second step, the best method was refined by instructions for a guided background activity assessment and validated by 10 further scans. Compared to the other approaches, the crescent-shaped VOIs revealed most stable results with the lowest intra-reader variabilities (median CoV 1.52%, spherical VOI 4.20%, 2D-ROI 3.69%; p < 0.001) and inter-reader variabilities (median CoV 2.14%, spherical VOI 4.02%, 2D-ROI 3.83%; p = 0.001). Using the guided background assessment, both intra-reader variabilities (median CoV 1.10%) and inter-reader variabilities (median CoV 1.19%) could be reduced even more. The commonly applied methods for background activity assessment show different variability which might hamper 18 F-FET PET quantification and comparability in multicenter settings. The proposed background activity assessment using a (guided) crescent-shaped VOI allows minimization of both intra- and inter-reader variability and might facilitate comprehensive methodological standardization of amino acid PET which is of interest in the light of the anticipated EANM technical guidelines.

  14. Drivers of inter-year variability of plant production and decomposers across contrasting island ecosystems.

    PubMed

    Wardle, David A; Jonsson, Micael; Kalela-Brundin, Maarit; Lagerström, Anna; Bardgett, Richard D; Yeates, Gregor W; Nilsson, Marie-Charlotte

    2012-03-01

    Despite the likely importance of inter-year dynamics of plant production and consumer biota for driving community- and ecosystem-level processes, very few studies have explored how and why these dynamics vary across contrasting ecosystems. We utilized a well-characterized system of 30 lake islands in the boreal forest zone of northern Sweden across which soil fertility and productivity vary considerably, with larger islands being more fertile and productive than smaller ones. In this system we assessed the inter-year dynamics of several measures of plant production and the soil microbial community (primary consumers in the decomposer food web) for each of nine years, and soil microfaunal groups (secondary and tertiary consumers) for each of six of those years. We found that, for measures of plant production and each of the three consumer trophic levels, inter-year dynamics were strongly affected by island size. Further, many variables were strongly affected by island size (and thus bottom-up regulation by soil fertility and resources) in some years, but not in other years, most likely due to inter-year variation in climatic conditions. For each of the plant and microbial variables for which we had nine years of data, we also determined the inter-year coefficient of variation (CV), an inverse measure of stability. We found that CVs of some measures of plant productivity were greater on large islands, whereas those of other measures were greater on smaller islands; CVs of microbial variables were unresponsive to island size. We also found that the effects of island size on the temporal dynamics of some variables were related to inter-year variability of macroclimatic variables. As such, our results show that the inter-year dynamics of both plant productivity and decomposer biota across each of three trophic levels, as well as the inter-year stability of plant productivity, differ greatly across contrasting ecosystems, with potentially important but largely overlooked implications for community and ecosystem processes.

  15. Space availability in confined sheep during pregnancy, effects in movement patterns and use of space.

    PubMed

    Averós, Xavier; Lorea, Areta; Beltrán de Heredia, Ignacia; Arranz, Josune; Ruiz, Roberto; Estevez, Inma

    2014-01-01

    Space availability is essential to grant the welfare of animals. To determine the effect of space availability on movement and space use in pregnant ewes (Ovis aries), 54 individuals were studied during the last 11 weeks of gestation. Three treatments were tested (1, 2, and 3 m2/ewe; 6 ewes/group). Ewes' positions were collected for 15 minutes using continuous scan samplings two days/week. Total and net distance, net/total distance ratio, maximum and minimum step length, movement activity, angular dispersion, nearest, furthest and mean neighbour distance, peripheral location ratio, and corrected peripheral location ratio were calculated. Restriction in space availability resulted in smaller total travelled distance, net to total distance ratio, maximum step length, and angular dispersion but higher movement activity at 1 m2/ewe as compared to 2 and 3 m2/ewe (P<0.01). On the other hand, nearest and furthest neighbour distances increased from 1 to 3 m2/ewe (P<0.001). Largest total distance, maximum and minimum step length, and movement activity, as well as lowest net/total distance ratio and angular dispersion were observed during the first weeks (P<0.05) while inter-individual distances increased through gestation. Results indicate that movement patterns and space use in ewes were clearly restricted by limitations of space availability to 1 m2/ewe. This reflected in shorter, more sinuous trajectories composed of shorter steps, lower inter-individual distances and higher movement activity potentially linked with higher restlessness levels. On the contrary, differences between 2 and 3 m2/ewe, for most variables indicate that increasing space availability from 2 to 3 m2/ewe would appear to have limited benefits, reflected mostly in a further increment in the inter-individual distances among group members. No major variations in spatial requirements were detected through gestation, except for slight increments in inter-individual distances and an initial adaptation period, with ewes being restless and highly motivated to explore their new environment.

  16. Inter-Labeler and Intra-Labeler Variability of Condition Severity Classification Models Using Active and Passive Learning Methods

    PubMed Central

    Nissim, Nir; Shahar, Yuval; Boland, Mary Regina; Tatonetti, Nicholas P; Elovici, Yuval; Hripcsak, George; Moskovitch, Robert

    2018-01-01

    Background and Objectives Labeling instances by domain experts for classification is often time consuming and expensive. To reduce such labeling efforts, we had proposed the application of active learning (AL) methods, introduced our CAESAR-ALE framework for classifying the severity of clinical conditions, and shown its significant reduction of labeling efforts. The use of any of three AL methods (one well known [SVM-Margin], and two that we introduced [Exploitation and Combination_XA]) significantly reduced (by 48% to 64%) condition labeling efforts, compared to standard passive (random instance-selection) SVM learning. Furthermore, our new AL methods achieved maximal accuracy using 12% fewer labeled cases than the SVM-Margin AL method. However, because labelers have varying levels of expertise, a major issue associated with learning methods, and AL methods in particular, is how to best to use the labeling provided by a committee of labelers. First, we wanted to know, based on the labelers’ learning curves, whether using AL methods (versus standard passive learning methods) has an effect on the Intra-labeler variability (within the learning curve of each labeler) and inter-labeler variability (among the learning curves of different labelers). Then, we wanted to examine the effect of learning (either passively or actively) from the labels created by the majority consensus of a group of labelers. Methods We used our CAESAR-ALE framework for classifying the severity of clinical conditions, the three AL methods and the passive learning method, as mentioned above, to induce the classifications models. We used a dataset of 516 clinical conditions and their severity labeling, represented by features aggregated from the medical records of 1.9 million patients treated at Columbia University Medical Center. We analyzed the variance of the classification performance within (intra-labeler), and especially among (inter-labeler) the classification models that were induced by using the labels provided by seven labelers. We also compared the performance of the passive and active learning models when using the consensus label. Results The AL methods produced, for the models induced from each labeler, smoother Intra-labeler learning curves during the training phase, compared to the models produced when using the passive learning method. The mean standard deviation of the learning curves of the three AL methods over all labelers (mean: 0.0379; range: [0.0182 to 0.0496]), was significantly lower (p = 0.049) than the Intra-labeler standard deviation when using the passive learning method (mean: 0.0484; range: [0.0275 to 0.0724). Using the AL methods resulted in a lower mean Inter-labeler AUC standard deviation among the AUC values of the labelers’ different models during the training phase, compared to the variance of the induced models’ AUC values when using passive learning. The Inter-labeler AUC standard deviation, using the passive learning method (0.039), was almost twice as high as the Inter-labeler standard deviation using our two new AL methods (0.02 and 0.019, respectively). The SVM-Margin AL method resulted in an Inter-labeler standard deviation (0.029) that was higher by almost 50% than that of our two AL methods. The difference in the inter-labeler standard deviation between the passive learning method and the SVM-Margin learning method was significant (p = 0.042). The difference between the SVM-Margin and Exploitation method was insignificant (p = 0.29), as was the difference between the Combination_XA and Exploitation methods (p = 0.67). Finally, using the consensus label led to a learning curve that had a higher mean intra-labeler variance, but resulted eventually in an AUC that was at least as high as the AUC achieved using the gold standard label and that was always higher than the expected mean AUC of a randomly selected labeler, regardless of the choice of learning method (including a passive learning method). Using a paired t-test, the difference between the intra-labeler AUC standard deviation when using the consensus label, versus that value when using the other two labeling strategies, was significant only when using the passive learning method (p = 0.014), but not when using any of the three AL methods. Conclusions The use of AL methods, (a) reduces intra-labeler variability in the performance of the induced models during the training phase, and thus reduces the risk of halting the process at a local minimum that is significantly different in performance from the rest of the learned models; and (b) reduces Inter-labeler performance variance, and thus reduces the dependence on the use of a particular labeler. In addition, the use of a consensus label, agreed upon by a rather uneven group of labelers, might be at least as good as using the gold standard labeler, who might not be available, and certainly better than randomly selecting one of the group’s individual labelers. Finally, using the AL methods when provided by the consensus label reduced the intra-labeler AUC variance during the learning phase, compared to using passive learning. PMID:28456512

  17. Inter-labeler and intra-labeler variability of condition severity classification models using active and passive learning methods.

    PubMed

    Nissim, Nir; Shahar, Yuval; Elovici, Yuval; Hripcsak, George; Moskovitch, Robert

    2017-09-01

    Labeling instances by domain experts for classification is often time consuming and expensive. To reduce such labeling efforts, we had proposed the application of active learning (AL) methods, introduced our CAESAR-ALE framework for classifying the severity of clinical conditions, and shown its significant reduction of labeling efforts. The use of any of three AL methods (one well known [SVM-Margin], and two that we introduced [Exploitation and Combination_XA]) significantly reduced (by 48% to 64%) condition labeling efforts, compared to standard passive (random instance-selection) SVM learning. Furthermore, our new AL methods achieved maximal accuracy using 12% fewer labeled cases than the SVM-Margin AL method. However, because labelers have varying levels of expertise, a major issue associated with learning methods, and AL methods in particular, is how to best to use the labeling provided by a committee of labelers. First, we wanted to know, based on the labelers' learning curves, whether using AL methods (versus standard passive learning methods) has an effect on the Intra-labeler variability (within the learning curve of each labeler) and inter-labeler variability (among the learning curves of different labelers). Then, we wanted to examine the effect of learning (either passively or actively) from the labels created by the majority consensus of a group of labelers. We used our CAESAR-ALE framework for classifying the severity of clinical conditions, the three AL methods and the passive learning method, as mentioned above, to induce the classifications models. We used a dataset of 516 clinical conditions and their severity labeling, represented by features aggregated from the medical records of 1.9 million patients treated at Columbia University Medical Center. We analyzed the variance of the classification performance within (intra-labeler), and especially among (inter-labeler) the classification models that were induced by using the labels provided by seven labelers. We also compared the performance of the passive and active learning models when using the consensus label. The AL methods: produced, for the models induced from each labeler, smoother Intra-labeler learning curves during the training phase, compared to the models produced when using the passive learning method. The mean standard deviation of the learning curves of the three AL methods over all labelers (mean: 0.0379; range: [0.0182 to 0.0496]), was significantly lower (p=0.049) than the Intra-labeler standard deviation when using the passive learning method (mean: 0.0484; range: [0.0275-0.0724). Using the AL methods resulted in a lower mean Inter-labeler AUC standard deviation among the AUC values of the labelers' different models during the training phase, compared to the variance of the induced models' AUC values when using passive learning. The Inter-labeler AUC standard deviation, using the passive learning method (0.039), was almost twice as high as the Inter-labeler standard deviation using our two new AL methods (0.02 and 0.019, respectively). The SVM-Margin AL method resulted in an Inter-labeler standard deviation (0.029) that was higher by almost 50% than that of our two AL methods The difference in the inter-labeler standard deviation between the passive learning method and the SVM-Margin learning method was significant (p=0.042). The difference between the SVM-Margin and Exploitation method was insignificant (p=0.29), as was the difference between the Combination_XA and Exploitation methods (p=0.67). Finally, using the consensus label led to a learning curve that had a higher mean intra-labeler variance, but resulted eventually in an AUC that was at least as high as the AUC achieved using the gold standard label and that was always higher than the expected mean AUC of a randomly selected labeler, regardless of the choice of learning method (including a passive learning method). Using a paired t-test, the difference between the intra-labeler AUC standard deviation when using the consensus label, versus that value when using the other two labeling strategies, was significant only when using the passive learning method (p=0.014), but not when using any of the three AL methods. The use of AL methods, (a) reduces intra-labeler variability in the performance of the induced models during the training phase, and thus reduces the risk of halting the process at a local minimum that is significantly different in performance from the rest of the learned models; and (b) reduces Inter-labeler performance variance, and thus reduces the dependence on the use of a particular labeler. In addition, the use of a consensus label, agreed upon by a rather uneven group of labelers, might be at least as good as using the gold standard labeler, who might not be available, and certainly better than randomly selecting one of the group's individual labelers. Finally, using the AL methods: when provided by the consensus label reduced the intra-labeler AUC variance during the learning phase, compared to using passive learning. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Association of Inter-arm Blood Pressure Difference with Asymptomatic Intracranial and Extracranial Arterial Stenosis in Hypertension Patients

    PubMed Central

    Wang, Yan; Zhang, Jin; Qian, Yuesheng; Tang, Xiaofeng; Ling, Huawei; Chen, Kemin; Li, Yan; Gao, Pingjin; Zhu, Dingliang

    2016-01-01

    Inter-arm blood pressure (BP) difference has been associated with ischemic stroke. Local atherosclerosis of stroke differ among vulnerable individuals, whereas intracranial arterial stenosis (ICAS) is more frequently affected Asians, and extracranial arterial stenosis (ECAS) is more prevalent among whites. We hereby sought to explore the association of inter-arm BP difference with ICAS and ECAS in stroke-free hypertensive patients in Chinese population. All the 885 subjects were evaluated of ICAS and ECAS through computerized tomographic angiography. Both arm BP was measured simultaneously by Vascular Profiler-1000 device. In the continuous study, ICAS was significantly associated with age, male, average brachial SBP, diabetes, anti-hypertensive treatment and inter-arm DBP difference. ECAS was associated with age, inter-arm SBP and LDL. In the categorical study, subjects with the top quartile of inter-arm DBP difference (≥4 mmHg) showed significantly higher risk of ICAS (OR = 2.109; 95% CI, 1.24–3.587). And the participants with the top quartile of inter-arm SBP difference (≥6 mmHg) showed significantly higher risk of ECAS (OR = 2.288; 95% CI, 1.309–3.998). In conclusion, we reported a diverse association of inter-arm SBP/DBP difference with the ICAS/ECAS. Inter-arm DBP difference might be the early symbol of ICAS in Chinese population, which need further verification in long-term cohort study. PMID:27412818

  19. Inter-Annual and Shorter-Term Variability in Physical and Biological Characteristics Across Barrow Canyon in August - September 2005-2014

    NASA Astrophysics Data System (ADS)

    Ashjian, C. J.; Okkonen, S. R.; Campbell, R. G.; Alatalo, P.

    2014-12-01

    Late summer physical and biological conditions along a 37-km transect crossing Barrow Canyon have been described for the past ten years as part of an ongoing program, supported by multiple funding sources including the NSF AON, focusing on inter-annual variability and the formation of a bowhead whale feeding hotspot near Barrow. These repeated transects (at least two per year, separated in time by days-weeks) provide an opportunity to assess the inter-annual and shorter term (days-weeks) changes in hydrographic structure, ocean temperature, current velocity and transport, chlorophyll fluorescence, nutrients, and micro- and mesozooplankton community composition and abundance. Inter-annual variability in all properties was high and was associated with larger scale, meteorological forcing. Shorter-term variability could also be high but was strongly influenced by changes in local wind forcing. The sustained sampling at this location provided critical measures of inter-annual variability that should permit detection of longer-term trends that are associated with ongoing climate change.

  20. A review of interventions to reduce inter-observer variability in volume delineation in radiation oncology.

    PubMed

    Vinod, Shalini K; Min, Myo; Jameson, Michael G; Holloway, Lois C

    2016-06-01

    Inter-observer variability (IOV) in target volume and organ-at-risk (OAR) delineation is a source of potential error in radiation therapy treatment. The aims of this study were to identify interventions shown to reduce IOV in volume delineation. Medline and Pubmed databases were queried for relevant articles using various keywords to identify articles which evaluated IOV in target or OAR delineation for multiple (>2) observers. The search was limited to English language articles and to those published from 1 January 2000 to 31 December 2014. Reference lists of identified articles were scrutinised to identify relevant studies. Studies were included if they reported IOV in contouring before and after an intervention including the use of additional or alternative imaging. Fifty-six studies were identified. These were grouped into evaluation of guidelines (n = 9), teaching (n = 9), provision of an autocontour (n = 7) and the impact of imaging (n = 31) on IOV. Guidelines significantly reduced IOV in 7/9 studies. Teaching interventions reduced IOV in 8/9 studies, statistically significant in 4. The provision of an autocontour improved consistency of contouring in 6/7 studies, statistically significant in 5. The effect of additional imaging on IOV was variable. Pre-operative CT was useful in reducing IOV in contouring breast and liver cancers, PET scans in lung cancer, rectal cancer and lymphoma and MRI scans in OARs in head and neck cancers. Inter-observer variability in volume delineation can be reduced with the use of guidelines, provision of autocontours and teaching. The use of multimodality imaging is useful in certain tumour sites. © 2016 The Royal Australian and New Zealand College of Radiologists.

  1. The role of fasciae in Civinini–Morton's syndrome

    PubMed Central

    Stecco, Carla; Fantoni, Ilaria; Macchi, Veronica; Del Borrello, Mario; Porzionato, Andrea; Biz, Carlo; De Caro, Raffaele

    2015-01-01

    This study evaluates the pathogenetic role of the perineural connective tissue and foot fasciae in Civinini–Morton's neuroma. Eleven feet (seven male, four female; mean age: 70.9 years) were dissected to analyse the anatomy of inter-metatarsal space, particularly the dorsal and plantar fasciae and metatarsal transverse ligament (DMTL). The macrosections were prepared for microscopic analysis. Ten Civinini–Morton neuromas obtained from surgery were also analysed. Magnetic resonance images (MRIs) from 40 patients and 29 controls were compared. Dissections showed that the width of the inter-metatarsal space is established by two fibrous structures: the dorsal foot fascia and the DMTL, which, together, connect the metatarsal bones and resist their splaying. Interosseous muscles spread out into the dorsal fascia of the foot, defining its basal tension. The common digital plantar nerve (CDPN) is encased in concentric layers of fibrous and loose connective tissue, continuous with the vascular sheath and deep foot fascia. Outside this sheath, fibroelastic septa, from DMTL to plantar fascia, and little fat lobules are present, further protecting the nerve against compressive stress. The MRI study revealed high inter-individual variability in the forefoot structures, although only the thickness of the dorsal fascia represented a statistically significant difference between cases and controls. It was hypothesized that alterations in foot support and altered biomechanics act on the interosseous muscles, increasing the stiffness of the dorsal fascia, particularly at the points where these muscles are inserted. Chronic rigidity of this fascia increases the stiffness of the inter-metatarsal space, leading to entrapment of the CDPN. PMID:26467241

  2. Measuring the needs of mental health patients in Greece: reliability and validity of the Greek version of the Camberwell assessment of need.

    PubMed

    Stefanatou, Pentagiotissa; Giannouli, Eleni; Konstantakopoulos, George; Vitoratou, Silia; Mavreas, Venetsanos

    2014-11-01

    Evaluation of mental health services based on patients' needs assessments has never taken place in Greece, although it is a crucial factor for the efficient use of their limited resources. To examine the inter-rater and test-retest reliability and the concurrent/convergent validity of the Greek research version of the Camberwell Assessment of Need-Research (CAN-R). A total of 53 schizophrenic patient-staff pairs were interviewed twice to test the inter-rater and test-retest reliability of the Greek version of the CAN-R. The World Health Organization Quality of Life-Brief Form (WHOQOL-BREF) and World Health Organization Disability Assessment Schedule-2.0 (WHODAS-2.0) were administered to the patients to examine concurrent validity. The inter-rater and test-retest reliability of patient and staff interviews for the 22 individual items and the eight summary scores of the instrument's four sections were good to excellent. Significant correlations emerged between CAN scores and the WHOQOL-BREF and WHODAS-2.0 domains for both patient and staff ratings, indicating good concurrent validity. Our results suggest that the Greek version of the CAN-R is a reliable instrument for assessing mental health patients' needs. Moreover, it is the first CAN-R validity study with satisfactory results using WHOQOL-BREF and WHODAS-2.0 as criterion variables. © The Author(s) 2013.

  3. Pharmacokinetics of oral hydrocortisone - Results and implications from a randomized controlled trial.

    PubMed

    Werumeus Buning, Jorien; Touw, Daan J; Brummelman, Pauline; Dullaart, Robin P F; van den Berg, Gerrit; van der Klauw, Melanie M; Kamp, Jasper; Wolffenbuttel, Bruce H R; van Beek, André P

    2017-06-01

    This study aimed at comparing pharmacokinetics of two different doses of hydrocortisone (HC) in patients with secondary adrenal insufficiency (SAI). Forty-six patients with SAI participated in this randomized double-blind crossover study. Patients received two different doses of HC (0.2-0.3mg HC/kg body weight/day and 0.4-0.6mg HC/kg body weight/day). One- and two-compartment population models for plasma free cortisol, plasma total cortisol and salivary cortisol were parameterized. The individual pharmacokinetic parameters clearance (CL), volume of distribution (V d ), elimination half-life (t 1/2 ), maximum concentration (C max ), and area under the curve (AUC) were calculated. The one-compartment models gave a better description of the data compared to the two-compartment models. Weight-adjusted dosing reduced variability in cortisol exposure with comparable AUCs between weight groups. However, there was large inter-individual variation in CL and V d of plasma free cortisol, plasma total cortisol and salivary cortisol. As a consequence, AUC 24h varied more than 10 fold. Cortisol exposure was increased with the higher dose, but this was dose proportional only for free cortisol concentrations and not for total cortisol. Cortisol concentrations after a doubling of the dose were only dose proportional for free cortisol. HC pharmacokinetics can differ up to 10-fold inter-individually and individual adjustment of treatment doses may be necessary. Doubling of the HC dose in fast metabolizers (patients that showed relative low AUC and thus high clearance compared to other patients), does not result in significantly enhanced exposure during large parts of the day and these patients may need other management strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Repair of O6-alkylguanines in the nuclear DNA of human lymphocytes and leukaemic cells: analysis at the single-cell level.

    PubMed Central

    Thomale, J.; Seiler, F.; Müller, M. R.; Seeber, S.; Rajewsky, M. F.

    1994-01-01

    Inter-individual and cell-cell variability of repair of O6-alkylguanines (O6-AlkGua) in nuclear DNA was studied at the single-cell level in peripheral lymphocytes from healthy donors and in leukaemic cells isolated from patients with chronic lymphatic leukaemia (CLL) or acute myeloid leukaemia (AML). Cells were pulse exposed to N-ethyl- or N-(n-)butyl-N-nitrosourea in vitro, and O6-AlkGua residues in DNA were quantified using an anti-(O6-AlkGua) monoclonal antibody and electronically intensified fluorescence. The kinetics of O6-AlkGua elimination revealed considerable inter-individual differences in O6-ethylguanine (O6-EtGua) half-life (t1/2) values in DNA, ranging from 1.5 to 4.5 h (five AML patients), from 0.8 to 2.8 h (five CLL patients) and from 1.2 to 7.3 h (five healthy donors). The elimination from DNA of equimolar amounts of O6-butylguanine was generally 3-5 times slower in comparison with O6-EtGua. The t1/2 values of individual samples varied in parallel for both DNA alkylation products. Upon preincubation with O6-benzylguanine, the activity of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AT) in both lymphocytes and leukaemic blasts was reduced to < or = 1%. However, while the rate of O6-EtGua elimination from DNA was decelerated it was not abolished, suggesting the possible involvement of additional repair systems that might be co-regulated with AT. Within individual samples, no major cell subpopulations were observed whose repair kinetics would differ significantly from the remaining cells. Images Figure 1 PMID:8142257

  5. Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies.

    PubMed

    Smith, Jennifer A; Zhao, Wei; Yasutake, Kalyn; August, Carmella; Ratliff, Scott M; Faul, Jessica D; Boerwinkle, Eric; Chakravarti, Aravinda; Diez Roux, Ana V; Gao, Yan; Griswold, Michael E; Heiss, Gerardo; Kardia, Sharon L R; Morrison, Alanna C; Musani, Solomon K; Mwasongwe, Stanford; North, Kari E; Rose, Kathryn M; Sims, Mario; Sun, Yan V; Weir, David R; Needham, Belinda L

    2017-12-18

    Inter-individual variability in blood pressure (BP) is influenced by both genetic and non-genetic factors including socioeconomic and psychosocial stressors. A deeper understanding of the gene-by-socioeconomic/psychosocial factor interactions on BP may help to identify individuals that are genetically susceptible to high BP in specific social contexts. In this study, we used a genomic region-based method for longitudinal analysis, Longitudinal Gene-Environment-Wide Interaction Studies (LGEWIS), to evaluate the effects of interactions between known socioeconomic/psychosocial and genetic risk factors on systolic and diastolic BP in four large epidemiologic cohorts of European and/or African ancestry. After correction for multiple testing, two interactions were significantly associated with diastolic BP. In European ancestry participants, outward/trait anger score had a significant interaction with the C10orf107 genomic region ( p = 0.0019). In African ancestry participants, depressive symptom score had a significant interaction with the HFE genomic region ( p = 0.0048). This study provides a foundation for using genomic region-based longitudinal analysis to identify subgroups of the population that may be at greater risk of elevated BP due to the combined influence of genetic and socioeconomic/psychosocial risk factors.

  6. Contact Networks in a Wildlife-Livestock Host Community: Identifying High-Risk Individuals in the Transmission of Bovine TB among Badgers and Cattle

    PubMed Central

    Böhm, Monika; Hutchings, Michael R.; White, Piran C. L.

    2009-01-01

    Background The management of many pathogens, which are of concern to humans and their livestock, is complicated by the pathogens' ability to cross-infect multiple host species, including wildlife. This has major implications for the management of such diseases, since the dynamics of infection are dependent on the rates of both intra- and inter-specific transmission. However, the difficulty of studying transmission networks in free-living populations means that the relative opportunities for intra- versus inter-specific disease transmission have not previously been demonstrated empirically within any wildlife-livestock disease system. Methodology/Principal Findings Using recently-developed proximity data loggers, we quantify both intra-and inter-specific contacts in a wildlife-livestock disease system, using bovine tuberculosis (bTB) in badgers and cattle in the UK as our example. We assess the connectedness of individuals within the networks in order to identify whether there are certain ‘high-risk’ individuals or groups of individuals for disease transmission within and between species. Our results show that contact patterns in both badger and cattle populations vary widely, both between individuals and over time. We recorded only infrequent interactions between badger social groups, although all badgers fitted with data loggers were involved in these inter-group contacts. Contacts between badgers and cattle occurred more frequently than contacts between different badger groups. Moreover, these inter-specific contacts involved those individual cows, which were highly connected within the cattle herd. Conclusions/Significance This work represents the first continuous time record of wildlife-host contacts for any free-living wildlife-livestock disease system. The results highlight the existence of specific individuals with relatively high contact rates in both livestock and wildlife populations, which have the potential to act as hubs in the spread of disease through complex contact networks. Targeting testing or preventive measures at high-contact groups and individuals within livestock populations would enhance the effectiveness and efficiency of disease management strategies. PMID:19401755

  7. The stress response and exploratory behaviour in Yucatan minipigs (Sus scrofa): Relations to sex and social rank.

    PubMed

    Adcock, Sarah J J; Martin, Gerard M; Walsh, Carolyn J

    2015-12-01

    According to the coping styles hypothesis, an individual demonstrates an integrated behavioural and physiological response to environmental challenge that is consistent over time and across situations. Individual consistency in behavioural responses to challenge has been documented across the animal kingdom. Comparatively few studies, however, have examined inter-individual variation in the physiological response, namely glucocorticoid and catecholamine levels, the stress hormones secreted by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, respectively. Variation in coping styles between individuals may be explained in part by differences in social rank and sex. Using 20 Yucatan minipigs (Sus scrofa) we: (1) investigated the existence of consistent inter-individual variation in exploratory behaviour and the hormonal stress response, and tested for correlations as predicted by the coping styles hypothesis; and (2) evaluated whether inter-individual behavioural and hormonal variation is related to social rank and sex. Salivary stress biomarkers (cortisol, alpha-amylase, chromogranin A) were assessed in the presence and absence of a stressor consisting of social isolation in a crate for 10 min. Principal components analysis on a set of behavioural variables revealed two traits, which we labelled exploratory tendency and neophobia. Neither exploratory tendency nor neophobia predicted the physiological stress response. Subordinate pigs exhibited higher catecholamine levels compared to dominant conspecifics. We observed sex differences in the repeatability of salivary stress markers and reactivity of the stress systems. The results do not provide support for the existence of behavioural-physiological coping styles in pigs. Sex is an important determinant of the physiological stress response and warrants consideration in research addressing behavioural and hormonal variation. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers

    PubMed Central

    D’Sa, Carrol; Dileone, Ralph J.; Anderson, George M.; Sinha, Rajita

    2013-01-01

    Although the effects of alcohol on brain-derived neurotrophic factor (BDNF) have been extensively studied in rodents, BDNF levels have rarely been measured in abstinent, alcohol-dependent (AD) individuals. Interpretation of reported group comparisons of serum BDNF levels is difficult due to limited information regarding analytical variance, biological variability, and the relative contribution of platelet and plasma pools to serum BDNF. Analytical variance (intra- and inter-assay coefficients of variation) of the enzyme-linked immunosorbent assay (ELISA) was characterized. Within- and between-subject variability, and group differences in serum and plasma BDNF, was assessed on three separate days in 16, 4-week abstinent AD individuals (7M/9F) and 16 social drinkers (SDs; 8M/8F). Significantly higher mean (±sd) serum BDNF levels were observed for the AD group compared to the SD (p = 0.003). No significant difference in mean baseline plasma BDNF levels was observed between AD and SD groups. The low analytical variance, high day-to-day within-individual stability and the high degree of individuality demonstrates the potential clinical utility of measuring serum BDNF levels. The low correlations that we observed between plasma and serum levels are congruent with their representing separate pools of BDNF. The observation of higher basal serum BDNF in the AD group without a concomitant elevation in plasma BDNF levels indicates that the elevated serum BDNF in AD patients is not due to greater BDNF exposure. Further research is warranted to fully elucidate mechanisms underlying this alteration and determine the utility of serum BDNF as a predictor or surrogate marker of chronic alcohol abuse. PMID:22364688

  9. A Case for Pharmacogenomics in Management of Cardiac Arrhythmias

    PubMed Central

    Kandoi, Gaurav; Nanda, Anjali; Scaria, Vinod; Sivasubbu, Sridhar

    2012-01-01

    Disorders of the cardiac rhythm are quite prevalent in clinical practice. Though the variability in drug response between individuals has been extensively studied, this information has not been widely used in clinical practice. Rapid advances in the field of pharmacogenomics have provided us with crucial insights on inter-individual genetic variability and its impact on drug metabolism and action. Technologies for faster and cheaper genetic testing and even personal genome sequencing would enable clinicians to optimize prescription based on the genetic makeup of the individual, which would open up new avenues in the area of personalized medicine. We have systematically looked at literature evidence on pharmacogenomics markers for anti-arrhythmic agents from the OpenPGx consortium collection and reason the applicability of genetics in the management of arrhythmia. We also discuss potential issues that need to be resolved before personalized pharmacogenomics becomes a reality in regular clinical practice. PMID:22557843

  10. Forecasting Sensorimotor Adaptability from Baseline Inter-Trial Correlations

    NASA Technical Reports Server (NTRS)

    Beaton, K. H.; Bloomberg, J. J.

    2014-01-01

    One of the greatest challenges surrounding adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a "one-size-fits-all" approach is inappropriate. Therefore, it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. Such knowledge could guide individually customized countermeasures, which would enable more efficient use of crew time, both preflight and inflight, and provide better outcomes. The primary goal of this project is to look for a baseline performance metric that can forecast sensorimotor adaptability without exposure to an adaptive stimulus. We propose a novel hypothesis that considers baseline inter-trial correlations, the trial-to-trial fluctuations in motor performance, as a predictor of individual sensorimotor adaptive capabilities. To-date, a strong relationship has been found between baseline inter-trial correlations and adaptability in two oculomotor systems. For this project, we will explore an analogous predictive mechanism in the locomotion system. METHODS: Baseline Inter-trial Correlations: Inter-trial correlations specify the relationships among repeated trials of a given task that transpire as a consequence of correcting for previous performance errors over multiple timescales. We can quantify the strength of inter-trial correlations by measuring the decay of the autocorrelation function (ACF), which describes how rapidly information from past trials is "forgotten." Processes whose ACFs decay more slowly exhibit longer-term inter-trial correlations (longer memory processes), while processes whose ACFs decay more rapidly exhibit shorterterm inter-trial correlations (shorter memory processes). Longer-term correlations reflect low-frequency activity, which is more easily measured in the frequency domain. Therefore, we use the power spectrum (PS), which is the Fourier transform of the ACF, to describe our inter-trial correlations. The decay of the PS yields a straight line on a log-log frequency plot, which we quantify by Beta = - (slope of PS on log-log axes). Hence, Beta is a measure of the strength of inter- trial correlations in the baseline data. Larger Beta values are indicative of longer inter-trial correlations. Experimental Approach: We will begin by performing a retrospective analysis of treadmill-gait adaptation data previously collected by Dr. Bloomberg and colleagues. Specifically, we will quantify the strength of inter-trial correlations in the baseline step cadence and heart rate data and compare it to the locomotor adaptability performance results already described by these investigators. Incorporating these datasets will also allow us to explore the applicability of (and potential limitations surrounding) the use of Beta in forecasting physiological performance. We will also perform a new experiment, in which Beta will be derived from baseline data collected during over-ground (non-treadmill) walking, which will enable us to consider locomotor performance, through the parameter Beta, under the most functionallyrelevant, natural gait condition. This experiment will incorporate two baseline and five post-training over-ground locomotion tests to explore the consistency and potential adaptability of the Beta values themselves. HYPOTHESES: We hypothesize that the strength of baseline inter-trial correlations of step cadence and heart rate will relate to locomotor adaptability. Specifically, we anticipate that individuals who show weaker longer-term inter-trial correlations in baseline step cadence data will be the better adaptors, as step cadence can be modified in real-time (i.e., online corrections are an inherent property of the locomotor system; analogous to results observed in the VOR). Conversely, because heart rate is not altered mid-beat, we expect that individuals who demonstrate stronger longer-term correlations in heart rate will be the better adaptors (analogous to results observed in the saccadic system). CONCLUSIONS: At the conclusion of this project we hope to uncover a baseline predictor of locomotor adaptability. If our hypotheses hold true, our results will demonstrate that the temporal structure of baseline behavioral data contains important information that may aid in forecasting adaptive capacities. The ability to predict such adaptability in the sensorimotor system has significant implications for spaceflight, where astronauts must adjust their motor programs following a change in g-level to retain movement accuracy.

  11. Effects of climatic factors and ecosystem responses on the inter-annual variability of evapotranspiration in a coniferous plantation in subtropical China.

    PubMed

    Xu, Mingjie; Wen, Xuefa; Wang, Huimin; Zhang, Wenjiang; Dai, Xiaoqin; Song, Jie; Wang, Yidong; Fu, Xiaoli; Liu, Yunfen; Sun, Xiaomin; Yu, Guirui

    2014-01-01

    Because evapotranspiration (ET) is the second largest component of the water cycle and a critical process in terrestrial ecosystems, understanding the inter-annual variability of ET is important in the context of global climate change. Eight years of continuous eddy covariance measurements (2003-2010) in a subtropical coniferous plantation were used to investigate the impacts of climatic factors and ecosystem responses on the inter-annual variability of ET. The mean and standard deviation of annual ET for 2003-2010 were 786.9 and 103.4 mm (with a coefficient of variation of 13.1%), respectively. The inter-annual variability of ET was largely created in three periods: March, May-June, and October, which are the transition periods between seasons. A set of look-up table approaches were used to separate the sources of inter-annual variability of ET. The annual ETs were calculated by assuming that (a) both the climate and ecosystem responses among years are variable (Vcli-eco), (b) the climate is variable but the ecosystem responses are constant (Vcli), and (c) the climate is constant but ecosystem responses are variable (Veco). The ETs that were calculated under the above assumptions suggested that the inter-annual variability of ET was dominated by ecosystem responses and that there was a negative interaction between the effects of climate and ecosystem responses. These results suggested that for long-term predictions of water and energy balance in global climate change projections, the ecosystem responses must be taken into account to better constrain the uncertainties associated with estimation.

  12. Effects of Climatic Factors and Ecosystem Responses on the Inter-Annual Variability of Evapotranspiration in a Coniferous Plantation in Subtropical China

    PubMed Central

    Xu, Mingjie; Wen, Xuefa; Wang, Huimin; Zhang, Wenjiang; Dai, Xiaoqin; Song, Jie; Wang, Yidong; Fu, Xiaoli; Liu, Yunfen; Sun, Xiaomin; Yu, Guirui

    2014-01-01

    Because evapotranspiration (ET) is the second largest component of the water cycle and a critical process in terrestrial ecosystems, understanding the inter-annual variability of ET is important in the context of global climate change. Eight years of continuous eddy covariance measurements (2003–2010) in a subtropical coniferous plantation were used to investigate the impacts of climatic factors and ecosystem responses on the inter-annual variability of ET. The mean and standard deviation of annual ET for 2003–2010 were 786.9 and 103.4 mm (with a coefficient of variation of 13.1%), respectively. The inter-annual variability of ET was largely created in three periods: March, May–June, and October, which are the transition periods between seasons. A set of look-up table approaches were used to separate the sources of inter-annual variability of ET. The annual ETs were calculated by assuming that (a) both the climate and ecosystem responses among years are variable (Vcli-eco), (b) the climate is variable but the ecosystem responses are constant (Vcli), and (c) the climate is constant but ecosystem responses are variable (Veco). The ETs that were calculated under the above assumptions suggested that the inter-annual variability of ET was dominated by ecosystem responses and that there was a negative interaction between the effects of climate and ecosystem responses. These results suggested that for long-term predictions of water and energy balance in global climate change projections, the ecosystem responses must be taken into account to better constrain the uncertainties associated with estimation. PMID:24465610

  13. Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2′-deoxyguanosine

    PubMed Central

    Møller, Peter; Henriksen, Trine; Mistry, Vilas; Koppen, Gudrun; Rossner, Pavel; Sram, Radim J.; Weimann, Allan; Poulsen, Henrik E.; Nataf, Robert; Andreoli, Roberta; Manini, Paola; Marczylo, Tim; Lam, Patricia; Evans, Mark D.; Kasai, Hiroshi; Kawai, Kazuaki; Li, Yun-Shan; Sakai, Kazuo; Singh, Rajinder; Teichert, Friederike; Farmer, Peter B.; Rozalski, Rafal; Gackowski, Daniel; Siomek, Agnieszka; Saez, Guillermo T.; Cerda, Concha; Broberg, Karin; Lindh, Christian; Hossain, Mohammad Bakhtiar; Haghdoost, Siamak; Hu, Chiung-Wen; Chao, Mu-Rong; Wu, Kuen-Yuh; Orhan, Hilmi; Senduran, Nilufer; Smith, Raymond J.; Santella, Regina M.; Su, Yali; Cortez, Czarina; Yeh, Susan; Olinski, Ryszard; Loft, Steffen

    2013-01-01

    Abstract Aims: Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed ‘spot’ samples showed strong correlations with 24 h excretion (the ‘gold’ standard) of urinary 8-oxodG (rp 0.67–0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended. Antioxid. Redox Signal. 18, 2377–2391. PMID:23198723

  14. Assessment of Soil Water Composition in the Northern Taiga Coniferous Forests of Background Territories in the Industrially Developed Region

    NASA Astrophysics Data System (ADS)

    Lukina, N. V.; Ershov, V. V.; Gorbacheva, T. T.; Orlova, M. A.; Isaeva, L. G.; Teben'kova, D. N.

    2018-03-01

    The composition of soil water under coniferous forests of Murmansk oblast—an industrially developed region of northern Russia—was investigated. The studied objects were dwarf-shrub-green-moss spruce forests and dwarf-shrub-lichen pine forests on Al-Fe-humus podzols ( Albic Rustic Podzols) that are widespread in the boreal zone. The concentrations and removal of organic carbon performing the most important biogeochemical and pedogenic functions were estimated. The results proved significant intra- and inter-biogeocenotic variability in the composition of atmospheric depositions and soil water. Carbon removal with soil water from organic and mineral horizons within elementary biogeoareas (EBGA) under tree crowns was 2-5 and 2-3 times (in some cases, up to 10 times) greater than that in the intercrown areas, respectively. The lowest critical level of mineral nitrogen (0.2 mg/L) was, as a rule, exceeded in tree EBGAs contrary to intercrown areas. Concentrations of sulfates and heavy metals in water of tree EBGA were 3-5 times greater than those in inter-crown areas. Significant inter-biogeocenotic variations related to differences in the height of trees and tree stand density were found. It is argued that adequate characterization of biochemical cycles and assessment of critical levels of components in soil water of forest ecosystems should be performed with due account for the intra- and inter-biogeocenotic variability.

  15. The effect of flash-freezing temperature on stallion sperm DNA structure.

    PubMed

    Serafini, R; Varner, D D; Bissett, W; Blanchard, T L; Teague, S R; Love, C C

    2017-06-01

    The effect of flash-freezing storage temperature on stallion sperm DNA has not been evaluated. Commonly, sperm are flash-frozen at various temperatures to preserve sperm DNA prior to analysis. It is unclear whether the temperature at which sperm are frozen and stored may affect the results of DNA assays. In this study, the neutral comet assay was used to evaluate the effect of flash-freezing storage temperature (freezer [-60 °C], dry ice [-78.5 °C], liquid nitrogen [-196 °C]) compared to fresh sperm DNA structure. In addition, intra- and inter-assay and intra- and inter-stallion variabilities were determined. All comet tail measures were higher following any flash-freezing method, as compared to fresh sperm DNA (P < 0.05), with no difference among flash-frozen treatments (P > 0.05). For most comet variables, intra- and inter-assay variabilities were <10%. Intra- and inter-stallion variabilities revealed that comet head length (HL) and width (CW) were less variable as compared to comet tail values, i.e., % comet tail DNA (T-DNA), tail length (TL), tail moment (OTM), and tail migration (TM). Certain comet tail values in fresh (% T-DNA, and OTM) and flash-frozen sperm (OTM, % T-DNA, TL, and TM) were correlated to the Sperm Chromatin Structure Assay (SCSA) variable, COMP-α t . The comet tail measures were negatively correlated to % morphologically normal sperm (P < 0.05) and positively correlated to % abnormal heads and premature germ cells (P < 0.05). Variables COMP-α t and % total sperm motility were not correlated to any morphologic sperm feature in this group of stallions (P > 0.05). While significant differences in the structure of the sperm DNA were identified in the flash-frozen as compared to the fresh sperm DNA with the neutral comet assay, it cannot be assumed that these changes are fertility limiting. Copyright © 2017. Published by Elsevier Inc.

  16. Application of point-process statistical tools to stable isotopes in xylem water for the study of inter- and intra-specific interactions in water uptake patterns in a mixed stand of Pinus halepensis Mill. and Quercus ilex L.

    NASA Astrophysics Data System (ADS)

    Comas, Carles; del Castillo, Jorge; Voltas, Jordi; Ferrio, Juan Pedro

    2013-04-01

    The stable isotope composition of xylem water reflects has been used to assess inter-specific differences in uptake patterns, revealing synergistic and competition processes in the use of water resources (see e.g. Dawson et al. 1993). However, there is a lack of detailed studies on spatial and temporal variability of inter- and intra-specific competition within forest stands. In this context, the aim of this work was to compare the isotope composition of xylem water (δ18O , δ2H) in two common Mediterranean tree species, Quercus ilex L. and Pinus halepensis Mill, in order to understand their water uptake patterns throughout the growing season. In addition, we analyze the spatial variability of xylem water, to get insight into inter-specific strategies employed to cope with drought and the interaction between the individuals. Our first hypothesis was that both species used different strategies to cope with drought by uptaking water at different depths; and our second hypothesis was that individual trees would behave in different manner according to the distance to their neighbours as well as to whether the neighbour is from one species or the other. The study was performed in a mixed stand where both species are nearly co-dominant, adding up to a total of 33 oaks and 77 pines (plot area= 893 m2). We sampled sun-exposed branches of each tree six times over the growing season, and extracted the xylem water with a cryogenic trap. The isotopic composition of the water was determined using a Picarro Water Analizer L2130-i. Tree mapping for spatial analysis was done using a high resolution GPS technology (Trimble GeoExplorer 6000). For the spatial analysis, we used the pair-correlation function to study intra-specific tree configuration and the bivariate pair correlation function to analyse the inter-specific spatial configurations (Stoyan et al 1995). Moreover, the isotopic composition of xylem water was assumed to be a mark associated to each tree and analysed as a marked point pattern. Preliminary results showed significant differences between species, but only during drought periods, confirming our first hypothesis. For example, in late-summer and early-autumn, the values for Q. Ilex (δ18O= -4.9 ±0.3 permille, δ2H=-53.5±1.2 permille) were significantly lower than for P. halepensis (δ18O= -1.1±0.2 permille, δ2H = -27.8±0.8 permille), pointing to the use of deeper soil layers by Q. ilex. On the other hand, point process analyses showed intra-specific interactions, whereas inter-specific interactions were not detected. Acknowledgements: This work was funded by MC-ERG-246725 (FP7, EU) and AGL 2012-40039-C02-02 (MINECO, Spain). JdC and JPF are supported by FPI fellowship (MCINN) and Ramón y Cajal programme (RYC-2008-02050, MINECO), respectively. References Dawson TE et al. 1993. In: Ehleringer JR, Hall AE, Farquhar GD (eds) Stable isotopes and plant carbon-water relations. Academic Press, Inc. IPCC. 2007 Climate Change 2007: The Physical Science Basis. Cambridge UP. Stoyan D et al. 1995. Stochastic Geometry and its Applications. Wiley&Sons.

  17. Language Learning Variability within the Dorsal and Ventral Streams as a Cue for Compensatory Mechanisms in Aphasia Recovery

    PubMed Central

    López-Barroso, Diana; de Diego-Balaguer, Ruth

    2017-01-01

    Dorsal and ventral pathways connecting perisylvian language areas have been shown to be functionally and anatomically segregated. Whereas the dorsal pathway integrates the sensory-motor information required for verbal repetition, the ventral pathway has classically been associated with semantic processes. The great individual differences characterizing language learning through life partly correlate with brain structure and function within these dorsal and ventral language networks. Variability and plasticity within these networks also underlie inter-individual differences in the recovery of linguistic abilities in aphasia. Despite the division of labor of the dorsal and ventral streams, studies in healthy individuals have shown how the interaction of them and the redundancy in the areas they connect allow for compensatory strategies in functions that are usually segregated. In this mini-review we highlight the need to examine compensatory mechanisms between streams in healthy individuals as a helpful guide to choosing the most appropriate rehabilitation strategies, using spared functions and targeting preserved compensatory networks for brain plasticity. PMID:29021751

  18. The predicted CLARREO sampling error of the inter-annual SW variability

    NASA Astrophysics Data System (ADS)

    Doelling, D. R.; Keyes, D. F.; Nguyen, C.; Macdonnell, D.; Young, D. F.

    2009-12-01

    The NRC Decadal Survey has called for SI traceability of long-term hyper-spectral flux measurements in order to monitor climate variability. This mission is called the Climate Absolute Radiance and Refractivity Observatory (CLARREO) and is currently defining its mission requirements. The requirements are focused on the ability to measure decadal change of key climate variables at very high accuracy. The accuracy goals are set using anticipated climate change magnitudes, but the accuracy achieved for any given climate variable must take into account the temporal and spatial sampling errors based on satellite orbits and calibration accuracy. The time period to detect a significant trend in the CLARREO record depends on the magnitude of the sampling calibration errors relative to the current inter-annual variability. The largest uncertainty in climate feedbacks remains the effect of changing clouds on planetary energy balance. Some regions on earth have strong diurnal cycles, such as maritime stratus and afternoon land convection; other regions have strong seasonal cycles, such as the monsoon. However, when monitoring inter-annual variability these cycles are only important if the strength of these cycles vary on decadal time scales. This study will attempt to determine the best satellite constellations to reduce sampling error and to compare the error with the current inter-annual variability signal to ensure the viability of the mission. The study will incorporate Clouds and the Earth's Radiant Energy System (CERES) (Monthly TOA/Surface Averages) SRBAVG product TOA LW and SW climate quality fluxes. The fluxes are derived by combining Terra (10:30 local equator crossing time) CERES fluxes with 3-hourly 5-geostationary satellite estimated broadband fluxes, which are normalized using the CERES fluxes, to complete the diurnal cycle. These fluxes were saved hourly during processing and considered the truth dataset. 90°, 83° and 74° inclination precessionary orbits as well as sun-synchronous orbits will be evaluated. This study will focus on the SW radiance, since these low earth orbits are only in daylight for half the orbit. The precessionary orbits were designed to cycle through all solar zenith angles over the course of a year. The inter-annual variability sampling error will be stratified globally/zonally and annually/seasonally and compared with the corresponding truth anomalies.

  19. The cognitive-behavioral system of leadership: cognitive antecedents of active and passive leadership behaviors

    PubMed Central

    Dóci, Edina; Stouten, Jeroen; Hofmans, Joeri

    2015-01-01

    In the present paper, we propose a cognitive-behavioral understanding of active and passive leadership. Building on core evaluations theory, we offer a model that explains the emergence of leaders’ active and passive behaviors, thereby predicting stable, inter-individual, as well as variable, intra-individual differences in both types of leadership behavior. We explain leaders’ stable behavioral tendencies by their fundamental beliefs about themselves, others, and the world (core evaluations), while their variable, momentary behaviors are explained by the leaders’ momentary appraisals of themselves, others, and the world (specific evaluations). By introducing interactions between the situation the leader enters, the leader’s beliefs, appraisals, and behavior, we propose a comprehensive system of cognitive mechanisms that underlie active and passive leadership behavior. PMID:26441721

  20. Inter-hospital transfer is associated with increased mortality and costs in severe sepsis and septic shock: An instrumental variables approach.

    PubMed

    Mohr, Nicholas M; Harland, Karisa K; Shane, Dan M; Ahmed, Azeemuddin; Fuller, Brian M; Torner, James C

    2016-12-01

    The objective of this study was to evaluate the impact of regionalization on sepsis survival, to describe the role of inter-hospital transfer in rural sepsis care, and to measure the cost of inter-hospital transfer in a predominantly rural state. Observational case-control study using statewide administrative claims data from 2005 to 2014 in a predominantly rural Midwestern state. Mortality and marginal costs were estimated with multivariable generalized estimating equations models and with instrumental variables models. A total of 18 246 patients were included, of which 59% were transferred between hospitals. Transferred patients had higher mortality and longer hospital length-of-stay than non-transferred patients. Using a multivariable generalized estimating equations (GEE) model to adjust for potentially confounding factors, inter-hospital transfer was associated with increased mortality (aOR 1.7, 95% CI 1.5-1.9). Using an instrumental variables model, transfer was associated with a 9.2% increased risk of death. Transfer was associated with additional costs of $6897 (95% CI $5769-8024). Even when limiting to only those patients who received care in the largest hospitals, transfer was still associated with $5167 (95% CI $3696-6638) in additional cost. The majority of rural sepsis patients are transferred, and these transferred patients have higher mortality and significantly increased cost of care. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Inter-Hospital Transfer is Associated with Increased Mortality and Costs in Severe Sepsis and Septic Shock: An Instrumental Variables Approach

    PubMed Central

    Mohr, Nicholas M.; Harland, Karisa K.; Shane, Dan M.; Ahmed, Azeemuddin; Fuller, Brian M.; Torner, James C.

    2016-01-01

    Purpose The objective of this study was to evaluate the impact of regionalization on sepsis survival, to describe the role of inter-hospital transfer in rural sepsis care, and to measure the cost of inter-hospital transfer in a predominantly rural state. Materials and Methods Observational case-control study using statewide administrative claims data from 2005-2014 in a predominantly rural Midwestern state. Mortality and marginal costs were estimated with multivariable generalized estimating equations (GEE) models and with instrumental variables models. Results A total of 18,246 patients were included, of which 59% were transferred between hospitals. Transferred patients had higher mortality and longer hospital length-of-stay than non-transferred patients. Using a multivariable GEE model to adjust for potentially confounding factors, inter-hospital transfer was associated with increased mortality (aOR 1.7, 95%CI 1.5 – 1.9). Using an instrumental variables model, transfer was associated with a 9.2% increased risk of death. Transfer was associated with additional costs of $6,897 (95%CI $5,769-8,024). Even when limiting to only those patients who received care in the largest hospitals, transfer was still associated with $5,167 (95%CI $3,696-6,638) in additional cost. Conclusions The majority of rural sepsis patients are transferred, and these transferred patients have higher mortality and significantly increased cost of care. PMID:27546770

  2. Mixed conditional logistic regression for habitat selection studies.

    PubMed

    Duchesne, Thierry; Fortin, Daniel; Courbin, Nicolas

    2010-05-01

    1. Resource selection functions (RSFs) are becoming a dominant tool in habitat selection studies. RSF coefficients can be estimated with unconditional (standard) and conditional logistic regressions. While the advantage of mixed-effects models is recognized for standard logistic regression, mixed conditional logistic regression remains largely overlooked in ecological studies. 2. We demonstrate the significance of mixed conditional logistic regression for habitat selection studies. First, we use spatially explicit models to illustrate how mixed-effects RSFs can be useful in the presence of inter-individual heterogeneity in selection and when the assumption of independence from irrelevant alternatives (IIA) is violated. The IIA hypothesis states that the strength of preference for habitat type A over habitat type B does not depend on the other habitat types also available. Secondly, we demonstrate the significance of mixed-effects models to evaluate habitat selection of free-ranging bison Bison bison. 3. When movement rules were homogeneous among individuals and the IIA assumption was respected, fixed-effects RSFs adequately described habitat selection by simulated animals. In situations violating the inter-individual homogeneity and IIA assumptions, however, RSFs were best estimated with mixed-effects regressions, and fixed-effects models could even provide faulty conclusions. 4. Mixed-effects models indicate that bison did not select farmlands, but exhibited strong inter-individual variations in their response to farmlands. Less than half of the bison preferred farmlands over forests. Conversely, the fixed-effect model simply suggested an overall selection for farmlands. 5. Conditional logistic regression is recognized as a powerful approach to evaluate habitat selection when resource availability changes. This regression is increasingly used in ecological studies, but almost exclusively in the context of fixed-effects models. Fitness maximization can imply differences in trade-offs among individuals, which can yield inter-individual differences in selection and lead to departure from IIA. These situations are best modelled with mixed-effects models. Mixed-effects conditional logistic regression should become a valuable tool for ecological research.

  3. The emotion potential of words and passages in reading Harry Potter--an fMRI study.

    PubMed

    Hsu, Chun-Ting; Jacobs, Arthur M; Citron, Francesca M M; Conrad, Markus

    2015-03-01

    Previous studies suggested that the emotional connotation of single words automatically recruits attention. We investigated the potential of words to induce emotional engagement when reading texts. In an fMRI experiment, we presented 120 text passages from the Harry Potter book series. Results showed significant correlations between affective word (lexical) ratings and passage ratings. Furthermore, affective lexical ratings correlated with activity in regions associated with emotion, situation model building, multi-modal semantic integration, and Theory of Mind. We distinguished differential influences of affective lexical, inter-lexical, and supra-lexical variables: differential effects of lexical valence were significant in the left amygdala, while effects of arousal-span (the dynamic range of arousal across a passage) were significant in the left amygdala and insula. However, we found no differential effect of passage ratings in emotion-associated regions. Our results support the hypothesis that the emotion potential of short texts can be predicted by lexical and inter-lexical affective variables. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Sensitivity of soil respiration to variability in soil moisture and temperature in a humid tropical forest

    Treesearch

    Tana Wood; M. Detto; W.L. Silver

    2013-01-01

    Precipitation and temperature are important drivers of soil respiration. The role of moisture and temperature are generally explored at seasonal or inter-annual timescales; however, significant variability also occurs on hourly to daily time-scales. We used small (1.54 m2), throughfall exclusion shelters to evaluate the role soil moisture and temperature as temporal...

  5. Modeling the influence of precipitation and nitrogen deposition on forest understory fuel connectivity in Sierra Nevada mixed-conifer forest

    Treesearch

    M. Hurteau; M. North; T. Foines

    2009-01-01

    Climate change models for California’s Sierra Nevada predict greater inter-annual variability in precipitation over the next 50 years. These increases in precipitation variability coupled with increases in nitrogen deposition fromfossil fuel consumption are likely to result in increased productivity levels and significant increases in...

  6. Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time

    PubMed Central

    Forest, Marie; O'Donnell, Kieran J.; Voisin, Greg; Gaudreau, Helene; MacIsaac, Julia L.; McEwen, Lisa M.; Silveira, Patricia P.; Steiner, Meir; Kobor, Michael S.; Meaney, Michael J.; Greenwood, Celia M.T.

    2018-01-01

    ABSTRACT Epigenome-wide association studies (EWAS) have focused primarily on DNA methylation as a chemically stable and functional epigenetic modification. However, the stability and accuracy of the measurement of methylation in different tissues and extraction types is still being actively studied, and the longitudinal stability of DNA methylation in commonly studied peripheral tissues is of great interest. Here, we used data from two studies, three tissue types, and multiple time points to assess the stability of DNA methylation measured with the Illumina Infinium HumanMethylation450 BeadChip array. Redundancy analysis enabled visual assessment of agreement of replicate samples overall and showed good agreement after removing effects of tissue type, age, and sex. At the probe level, analysis of variance contrasts separating technical and biological replicates clearly showed better agreement between technical replicates versus longitudinal samples, and suggested increased stability for buccal cells versus blood or blood spots. Intraclass correlations (ICCs) demonstrated that inter-individual variability is of similar magnitude to within-sample variability at many probes; however, as inter-individual variability increased, so did ICC. Furthermore, we were able to demonstrate decreasing agreement in methylation levels with time, despite a maximal sampling interval of only 576 days. Finally, at 6 popular candidate genes, there was a large range of stability across probes. Our findings highlight important sources of technical and biological variation in DNA methylation across different tissues over time. These data will help to inform longitudinal sampling strategies of future EWAS. PMID:29381404

  7. Experimental forensic and bioanthropological aspects of soft tissue taphonomy: 1. Factors influencing postmortem tissue desiccation rate.

    PubMed

    Aturaliya, S; Lukasewycz, A

    1999-09-01

    Euthanized rats' carcasses were exposed in an environmental chamber to multiple variables including: (1) position, (2) enveloping clothing, and (3) soil interment in an effort to determine the individual variables' effect on postmortem rate of body and visceral organ water loss. Results indicated that body water loss was enhanced by a horizontal position versus vertical, probably because of wider spread of bacteria- and enzyme-laden abdominal fluid secondary to diaphragm digestion with consequent greater tissue digestion and liquefaction. Clothing also accelerated the desiccation rate. Desiccation was about equally as effective by soil interment as by air exposure, though simulating windy conditions by tripling the air flow rate resulted in much more rapid desiccation in the air-exposed specimen. These studies suggest that the single most important factor influencing postmortem body water loss rate is the environment at the skin surface that acts to enhance or impair water removal from the skin surface and thus influences the water concentration gradient between the skin and underlying deeper tissues.

  8. Measurement of temperature induced in bone during drilling in minimally invasive foot surgery.

    PubMed

    Omar, Noor Azzizah; McKinley, John C

    2018-02-19

    There has been growing interest in minimally invasive foot surgery due to the benefits it delivers in post-operative outcomes in comparison to conventional open methods of surgery. One of the major factors determining the protocol in minimally invasive surgery is to prevent iatrogenic thermal osteonecrosis. The aim of the study is to look at various drilling parameters in a minimally invasive surgery setting that would reduce the risk of iatrogenic thermal osteonecrosis. Sixteen fresh-frozen tarsal bones and two metatarsal bones were retrieved from three individuals and drilled using various settings. The parameters considered were drilling speed, drill diameter, and inter-individual cortical variability. Temperature measurements of heat generated at the drilling site were collected using two methods; thermocouple probe and infrared thermography. The data obtained were quantitatively analysed. There was a significant difference in the temperatures generated with different drilling speeds (p<0.05). However, there was no significant difference in temperatures recorded between the bones of different individuals and in bones drilled using different drill diameters. Thermocouple showed significantly more sensitive tool in measuring temperature compared to infrared thermography. Drilling at an optimal speed significantly reduced the risk of iatrogenic thermal osteonecrosis by maintaining temperature below the threshold level. Although different drilling diameters did not produce significant differences in temperature generation, there is a need for further study on the mechanical impact of using different drill diameters. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Impact of childhood adversity on the onset and course of subclinical psychosis symptoms--results from a 30-year prospective community study.

    PubMed

    Rössler, Wulf; Hengartner, Michael P; Ajdacic-Gross, Vladeta; Haker, Helene; Angst, Jules

    2014-03-01

    The study objective was to examine childhood adversity in association with intra-individual changes and inter-individual differences in subclinical psychosis in a representative community cohort over a 30-year period of observation. We analyzed two psychosis syndromes derived from the SCL-90-R - schizotypal signs and schizophrenia nuclear symptoms - in 335 participants. Participants were repeatedly assessed between 1978 (around age 20) and 2008 (around age 50). We focused specifically on inter-individual differences and intra-individual changes over time by applying structural equation modeling, generalized linear models, and generalized estimating equations. Several weak inter-individual differences revealed that increased schizotypal signs are related to various childhood adversities, such as being repeatedly involved in fights and parents having severe conflicts among themselves. We also found a significant positive association between schizotypal signs and the total number of adversities a subject experienced. This pointed toward a modest dose-response relationship. The intra-individual change in schizotypal signs over time was rather weak, although some adjustment did occur. In contrast, inter-individual schizophrenia nuclear symptoms were mainly unrelated to childhood adversity. However, some striking intra-individual changes in distress were noted over time, especially those linked with severe punishment and the total adversity score. In conclusion, we have confirmed previous positive findings about the association between childhood adversity and subsequent subclinical psychosis symptoms: An increase in adversity is weakly related to an increase of the psychosis symptom load. However, depending on the kind of adversity experienced the psychosis symptom load decreases gradually in adult life. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Model-Based Segmentation of Cortical Regions of Interest for Multi-subject Analysis of fMRI Data

    NASA Astrophysics Data System (ADS)

    Engel, Karin; Brechmann, Andr'e.; Toennies, Klaus

    The high inter-subject variability of human neuroanatomy complicates the analysis of functional imaging data across subjects. We propose a method for the correct segmentation of cortical regions of interest based on the cortical surface. First results on the segmentation of Heschl's gyrus indicate the capability of our approach for correct comparison of functional activations in relation to individual cortical patterns.

  11. Effects of modified Pilates on variability of inter-joint coordination during walking in the elderly.

    PubMed

    Yoon, Sukhoon; Kim, Joo Nyeon; Lim, Hee Sung

    2016-12-01

    [Purpose] This study aimed to examine the effects of an 8-week modified Pilates program on the variability of inter-joint coordination in the elderly during walking. [Subjects and Methods] Twenty elderly participants with no recent history of orthopedic abnormalities (age, 67.9 ± 2.7 years; height, 163.7 ± 8.9 cm; weight, 67.1 ± 11.6 kg) were recruited for this study and randomly allocated to a modified Pilates exercise group or a control group. Three-dimensional motion analysis was performed on both groups to evaluate the effects of the Pilates exercise. [Results] There was no significant difference in the joint variability of the ankle, knee, and hip joints between the groups, both before training and after training. However, there was a significant increase in the hip-knee deviation phase value in the exercise group after the program was completed, and this increase was also significant when compared with that in the control group. [Conclusion] This study has demonstrated that an 8-week modified Pilates exercise program can have a positive impact on the gait of elderly participants, potentially by enhancing neuromuscular adjustment, which may have positive implications for reducing their fall risk.

  12. Scaling left ventricular mass in adolescent boys aged 11-15 years.

    PubMed

    Valente-Dos-Santos, João; Coelho-E-Silva, Manuel J; Ferraz, António; Castanheira, Joaquim; Ronque, Enio R; Sherar, Lauren B; Elferink-Gemser, Marije T; Malina, Robert M

    2014-01-01

    Normalizing left ventricular mass (LVM) for inter-individual variation in body size is a central issue in human biology. During the adolescent growth spurt, variability in body size descriptors needs to be interpreted in combination with biological maturation. To examine the contribution of biological maturation, stature, sitting height, body mass, fat-free mass (FFM) and fat mass (FM) to inter-individual variability in LVM in boys, using proportional allometric modelling. The cross-sectional sample included 110 boys of 11-15 years (12.9-1.0 years). Stature, sitting height, body mass, cardiac chamber dimensions and LVM were measured. Age at peak height velocity (APHV) was predicted and used as an indicator of biological maturation. Percentage fat was estimated from triceps and subscapular skinfolds; FM and FFM were derived. Exponents for body size descriptors were k = 2.33 for stature, k = 2.18 for sitting height, k = 0.68 for body mass, k = 0.17 for FM and k = 0.80 for FFM (adjusted R(2 )= 19-62%). The combination of body descriptors and APHV increased the explained variance in LVM (adjusted R(2)( )= 56-69%). Stature, FM and FFM are the best combination for normalizing LVM in adolescent boys; when body composition is not available, an indicator of biological maturity should be included with stature.

  13. Biologically-variable rhythmic auditory cues are superior to isochronous cues in fostering natural gait variability in Parkinson's disease.

    PubMed

    Dotov, D G; Bayard, S; Cochen de Cock, V; Geny, C; Driss, V; Garrigue, G; Bardy, B; Dalla Bella, S

    2017-01-01

    Rhythmic auditory cueing improves certain gait symptoms of Parkinson's disease (PD). Cues are typically stimuli or beats with a fixed inter-beat interval. We show that isochronous cueing has an unwanted side-effect in that it exacerbates one of the motor symptoms characteristic of advanced PD. Whereas the parameters of the stride cycle of healthy walkers and early patients possess a persistent correlation in time, or long-range correlation (LRC), isochronous cueing renders stride-to-stride variability random. Random stride cycle variability is also associated with reduced gait stability and lack of flexibility. To investigate how to prevent patients from acquiring a random stride cycle pattern, we tested rhythmic cueing which mimics the properties of variability found in healthy gait (biological variability). PD patients (n=19) and age-matched healthy participants (n=19) walked with three rhythmic cueing stimuli: isochronous, with random variability, and with biological variability (LRC). Synchronization was not instructed. The persistent correlation in gait was preserved only with stimuli with biological variability, equally for patients and controls (p's<0.05). In contrast, cueing with isochronous or randomly varying inter-stimulus/beat intervals removed the LRC in the stride cycle. Notably, the individual's tendency to synchronize steps with beats determined the amount of negative effects of isochronous and random cues (p's<0.05) but not the positive effect of biological variability. Stimulus variability and patients' propensity to synchronize play a critical role in fostering healthier gait dynamics during cueing. The beneficial effects of biological variability provide useful guidelines for improving existing cueing treatments. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Intra-individual metameric variation expressed at the enamel-dentine junction of lower post-canine dentition of South African fossil hominins and modern humans.

    PubMed

    Pan, Lei; Thackeray, John Francis; Dumoncel, Jean; Zanolli, Clément; Oettlé, Anna; de Beer, Frikkie; Hoffman, Jakobus; Duployer, Benjamin; Tenailleau, Christophe; Braga, José

    2017-08-01

    The aim of this study is to compare the degree and patterning of inter- and intra-individual metameric variation in South African australopiths, early Homo and modern humans. Metameric variation likely reflects developmental and taxonomical issues, and could also be used to infer ecological and functional adaptations. However, its patterning along the early hominin postcanine dentition, particularly among South African fossil hominins, remains unexplored. Using microfocus X-ray computed tomography (µXCT) and geometric morphometric tools, we studied the enamel-dentine junction (EDJ) morphology and we investigated the intra- and inter-individual EDJ metameric variation among eight australopiths and two early Homo specimens from South Africa, as well as 32 modern humans. Along post-canine dentition, shape changes between metameres represented by relative positions and height of dentine horns, outlines of the EDJ occlusal table are reported in modern and fossil taxa. Comparisons of EDJ mean shapes and multivariate analyses reveal substantial variation in the direction and magnitude of metameric shape changes among taxa, but some common trends can be found. In modern humans, both the direction and magnitude of metameric shape change show increased variability in M 2 -M 3 compared to M 1 -M 2 . Fossil specimens are clustered together showing similar magnitudes of shape change. Along M 2 -M 3 , the lengths of their metameric vectors are not as variable as those of modern humans, but they display considerable variability in the direction of shape change. The distalward increase of metameric variation along the modern human molar row is consistent with the odontogenetic models of molar row structure (inhibitory cascade model). Though much remains to be tested, the variable trends and magnitudes in metamerism in fossil hominins reported here, together with differences in the scale of shape change between modern humans and fossil hominins may provide valuable information regarding functional morphology and developmental processes in fossil species. © 2017 Wiley Periodicals, Inc.

  15. Dissecting the space-time structure of tree-ring datasets using the partial triadic analysis.

    PubMed

    Rossi, Jean-Pierre; Nardin, Maxime; Godefroid, Martin; Ruiz-Diaz, Manuela; Sergent, Anne-Sophie; Martinez-Meier, Alejandro; Pâques, Luc; Rozenberg, Philippe

    2014-01-01

    Tree-ring datasets are used in a variety of circumstances, including archeology, climatology, forest ecology, and wood technology. These data are based on microdensity profiles and consist of a set of tree-ring descriptors, such as ring width or early/latewood density, measured for a set of individual trees. Because successive rings correspond to successive years, the resulting dataset is a ring variables × trees × time datacube. Multivariate statistical analyses, such as principal component analysis, have been widely used for extracting worthwhile information from ring datasets, but they typically address two-way matrices, such as ring variables × trees or ring variables × time. Here, we explore the potential of the partial triadic analysis (PTA), a multivariate method dedicated to the analysis of three-way datasets, to apprehend the space-time structure of tree-ring datasets. We analyzed a set of 11 tree-ring descriptors measured in 149 georeferenced individuals of European larch (Larix decidua Miller) during the period of 1967-2007. The processing of densitometry profiles led to a set of ring descriptors for each tree and for each year from 1967-2007. The resulting three-way data table was subjected to two distinct analyses in order to explore i) the temporal evolution of spatial structures and ii) the spatial structure of temporal dynamics. We report the presence of a spatial structure common to the different years, highlighting the inter-individual variability of the ring descriptors at the stand scale. We found a temporal trajectory common to the trees that could be separated into a high and low frequency signal, corresponding to inter-annual variations possibly related to defoliation events and a long-term trend possibly related to climate change. We conclude that PTA is a powerful tool to unravel and hierarchize the different sources of variation within tree-ring datasets.

  16. Modelling personality, plasticity and predictability in shelter dogs

    PubMed Central

    2017-01-01

    Behavioural assessments of shelter dogs (Canis lupus familiaris) typically comprise standardized test batteries conducted at one time point, but test batteries have shown inconsistent predictive validity. Longitudinal behavioural assessments offer an alternative. We modelled longitudinal observational data on shelter dog behaviour using the framework of behavioural reaction norms, partitioning variance into personality (i.e. inter-individual differences in behaviour), plasticity (i.e. inter-individual differences in average behaviour) and predictability (i.e. individual differences in residual intra-individual variation). We analysed data on interactions of 3263 dogs (n = 19 281) with unfamiliar people during their first month after arrival at the shelter. Accounting for personality, plasticity (linear and quadratic trends) and predictability improved the predictive accuracy of the analyses compared to models quantifying personality and/or plasticity only. While dogs were, on average, highly sociable with unfamiliar people and sociability increased over days since arrival, group averages were unrepresentative of all dogs and predictions made at the individual level entailed considerable uncertainty. Effects of demographic variables (e.g. age) on personality, plasticity and predictability were observed. Behavioural repeatability was higher one week after arrival compared to arrival day. Our results highlight the value of longitudinal assessments on shelter dogs and identify measures that could improve the predictive validity of behavioural assessments in shelters. PMID:28989764

  17. Daytime variation in ambient temperature affects skin temperatures and blood pressure: Ambulatory winter/summer comparison in healthy young women.

    PubMed

    Martinez-Nicolas, Antonio; Meyer, Martin; Hunkler, Stefan; Madrid, Juan Antonio; Rol, Maria Angeles; Meyer, Andrea H; Schötzau, Andy; Orgül, Selim; Kräuchi, Kurt

    2015-10-01

    It is widely accepted that cold exposure increases peripheral vascular resistance and arterial blood pressure (BP) and, hence, increases cardiovascular risk primarily in the elderly. However, there is a lack of concomitantly longitudinal recordings at personal level of environmental temperature (PET) and cardiophysiological variables together with skin temperatures (STs, the “interface-variable” between the body core and ambient temperature). To investigate the intra-individual temporal relationships between PET, STs and BP 60 healthy young women (52 completed the entire study) were prospectively studied in a winter/summer design for 26 h under real life conditions. The main hypothesis was tested whether distal ST (Tdist)mediates the effect of PET-changes on mean arterial BP (MAP). Diurnal profiles of cardiophysiological variables (including BP), STs and PET were ambulatory recorded. Daytime variations between 0930 and 2030 h were analyzed in detail by intra-individual longitudinal path analysis. Additionally, time segments before, during and after outdoor exposure were separately analyzed. In both seasons short-term variations in PET were positively associated with short-term changes in Tdist (not proximal ST, Tprox) and negatively with those in MAP. However, long-term seasonal differences in daytime mean levels were observed in STs but not in BP leading to non-significant inter-individual correlation between STs and BP. Additionally, higher individual body mass index (BMI) was significantly associated with lower daytime mean levels of Tprox and higher MAP suggesting Tprox as potential mediator variable for the association of BMI with MAP. In healthy young women the thermoregulatory and BP-regulatory systems are closely linked with respect to short-term, but not long-term changes in PET. One hypothetical explanation could serve recent findings that thermogenesis in brown adipose tissue is activated in a cool environment, which could be responsible for the counter-regulation of cold induced increase of BP in winter leading to no seasonal differences in MAP. Our findings suggest that the assessment of diurnal patterns of STs and PET, in addition to the conventional ambulatory BP monitoring, might improve individual cardiovascular risk prediction.

  18. Chromosomal Radiosensitivity in Lymphocytes of Cervix Cancer Patients—Correlation with Side Effect after Radiotherapy

    NASA Astrophysics Data System (ADS)

    Wegierek-Ciuk, Aneta; Lankoff, Anna; Lisowska, Halina; Banasik-Nowak, Anna; Arabski, Michał; Kedzierawski, Piotr; Florek, Agnieszka; Wojcik, Andrzej

    2010-01-01

    It is well known that cancer patients receiving similar radiotherapy treatments differ widely in normal tissue reactions ranging from undetectable to unacceptably severe levels. Therefore, an important goal of radiobiological research is to establish a test which would allow identifying individual radiosensitivity of patients prior to radiotherapy. The aim of the presented study is to assess the relationship between lymphocyte intrinsic radiosensitivity in vitro and early reaction of normal tissue in cervix cancer patients treated by radiotherapy. The following endpoints are analyzed in vitro: frequency of micronuclei, the kinetics of DNA repair and apoptosis. Acute normal tissue reaction to radiotherapy in the skin, bladder and rectum are scored according to the EORTC/RTOG scale. Our results show a wide inter-individual variability in chromosomal radiosensitivity in vitro. The majority of patients show a Grade 0, 1 or 2 reaction for all organs studied. No statistically significant correlation has been observed between the in vitro results in lymphocytes and the degree of early normal tissue and organ reaction.

  19. Sampling-based ensemble segmentation against inter-operator variability

    NASA Astrophysics Data System (ADS)

    Huo, Jing; Okada, Kazunori; Pope, Whitney; Brown, Matthew

    2011-03-01

    Inconsistency and a lack of reproducibility are commonly associated with semi-automated segmentation methods. In this study, we developed an ensemble approach to improve reproducibility and applied it to glioblastoma multiforme (GBM) brain tumor segmentation on T1-weigted contrast enhanced MR volumes. The proposed approach combines samplingbased simulations and ensemble segmentation into a single framework; it generates a set of segmentations by perturbing user initialization and user-specified internal parameters, then fuses the set of segmentations into a single consensus result. Three combination algorithms were applied: majority voting, averaging and expectation-maximization (EM). The reproducibility of the proposed framework was evaluated by a controlled experiment on 16 tumor cases from a multicenter drug trial. The ensemble framework had significantly better reproducibility than the individual base Otsu thresholding method (p<.001).

  20. Analysis of copy number variations in Holstein-Friesian cow genomes based on whole-genome sequence data.

    PubMed

    Mielczarek, M; Frąszczak, M; Giannico, R; Minozzi, G; Williams, John L; Wojdak-Maksymiec, K; Szyda, J

    2017-07-01

    Thirty-two whole genome DNA sequences of cows were analyzed to evaluate inter-individual variability in the distribution and length of copy number variations (CNV) and to functionally annotate CNV breakpoints. The total number of deletions per individual varied between 9,731 and 15,051, whereas the number of duplications was between 1,694 and 5,187. Most of the deletions (81%) and duplications (86%) were unique to a single cow. No relation between the pattern of variant sharing and a family relationship or disease status was found. The animal-averaged length of deletions was from 5,234 to 9,145 bp and the average length of duplications was between 7,254 and 8,843 bp. Highly significant inter-individual variation in length and number of CNV was detected for both deletions and duplications. The majority of deletion and duplication breakpoints were located in intergenic regions and introns, whereas fewer were identified in noncoding transcripts and splice regions. Only 1.35 and 0.79% of the deletion and duplication breakpoints were observed within coding regions. A gene with the highest number of deletion breakpoints codes for protein kinase cGMP-dependent type I, whereas the T-cell receptor α constant gene had the most duplication breakpoints. The functional annotation of genes with the largest incidence of deletion/duplication breakpoints identified 87/112 Kyoto Encyclopedia of Genes and Genomes pathways, but none of the pathways were significantly enriched or depleted with breakpoints. The analysis of Gene Ontology (GO) terms revealed that a cluster with the highest enrichment score among genes with many deletion breakpoints was represented by GO terms related to ion transport, whereas the GO term cluster mostly enriched among the genes with many duplication breakpoints was related to binding of macromolecules. Furthermore, when considering the number of deletion breakpoints per gene functional category, no significant differences were observed between the "housekeeping" and "strong selection" categories, but genes representing the "low selection pressure" group showed a significantly higher number of breakpoints. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. An in vitro study to assess the impact of tetracycline on the human intestinal microbiome.

    PubMed

    Jung, Ji Young; Ahn, Youngbeom; Khare, Sangeeta; Gokulan, Kuppan; Piñeiro, Silvia A; Cerniglia, Carl E

    2018-02-01

    The human intestinal microbiome, a generally stable ecosystem, could be potentially altered by the ingestion of antimicrobial drug residues in foods derived from animals. Data and the scientific published literature on the effects of antimicrobial residues on the human intestinal microbiome are reviewed by national regulatory authorities as part of the human food safety evaluation of veterinary antimicrobial agents used in food-producing animals. In this study, we determined if tetracycline, at low residue concentrations, could impact the human intestinal microbiome structure and the resistance-gene profile, following acute and subchronic exposure. The effects of 0.15, 1.5, 15, and 150 μg/ml of tetracycline, after 24 h and 40 days of exposure, in 3% human fecal suspensions, collected from three individuals (A, B, and C) were investigated using in vitro batch cultures. Results were variable, with either no change or minor changes in total bacterial 16S rRNA gene copies after exposure of fecal samples to tetracycline, because of the inter-individual variation of human gastrointestinal tract microbiota. Bacterial community analysis using rRNA-based pyrosequencing revealed that Firmicutes and Bacteroidetes were the predominant phyla in the three fecal samples; the ratio of phylotypes varied among individuals. The evaluation of bacterial community changes at the genus level, from control to tetracycline-treated fecal samples, suggested that tetracycline under the conditions of this study could lead to slight differences in the composition of intestinal microbiota. The genus Bacteroides (of the Bacteroidetes) was consistently altered from 1.68 to 5.70% and 4.82-8.22% at tetracycline concentrations of 0.15 μg/ml or above at both time points for individual A, respectively, and increased 5.13-13.50% and 10.92-22.18% for individual B, respectively. Clostridium family XI increased 3.50-25.34% in the presence of tetracycline at 40 days for individual C. Principal Component Analysis (PCA) confirmed the pyrosequencing findings of inter-individual variability of the ratio of phylotypes and the effect of tetracycline. Among the 23 tetracycline resistance genes (TRGs) screened, four tet genes (tetO, Q, W, and X) were major TRGs in control and tetracycline-dosed fecal samples. A variable to slight increase of copy number of TRGs appeared to be related to tetracycline treatment, interindividual variability and duration of exposure. Despite, the inherent variability of the intestinal microbiota observed among or within individuals, this pilot study contributes to the knowledge base of the impact of low residue concentrations of tetracycline on the human intestinal microbiome on the potential for antimicrobial resistance. Published by Elsevier Ltd.

  2. Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy.

    PubMed

    Graziani, Manuela; Nisticò, Robert

    2015-01-01

    Gender-related differences in the pharmacological effects of drug are an emerging topic. This review examines gender differences in both pharmacokinetic and pharmacodynamic aspects of methadone, a long-acting opioid agonist that is prescribed as a treatment for opioid dependence and the management of chronic pain. We performed a search in the Medline database from 1990 to 2014 in order to find published literature related to gender differences in pharmacokinetics (PK) and pharmacodynamics (PD) of methadone. None of the studies were carried out with the primary or secondary aim to identify any gender differences in the pharmacokinetic profile of methadone. Importantly; high inter-subjects variability in PK parameters was found also intra female population. The reported differences in volume of distribution could be ascribed to the physiological differences between men and women in body weight and composition, taking into account that the dose of methadone was established irrespective of body weight of patients (Peles and Adelson, 2006). On the other hand, the few studies present in literature found no gender difference in some direct pharmacodynamic parameters. Some reports have suggested that female gender is associated with an increased risk for long-QT-related cardiac arrhythmias in methadone maintenance subjects. Even though it may be too simplistic to expect variability only in one parameter to explain inter-individual variation in methadone response, we believe that a better knowledge of gender-related differences might have significant implications for better outcomes in opioid dependence substitution therapy in women.

  3. Interannual variability in global mean sea level estimated from the CESM Large and Last Millennium Ensembles

    DOE PAGES

    Fasullo, John T.; Nerem, Robert S.

    2016-10-31

    To better understand global mean sea level (GMSL) as an indicator of climate variability and change, contributions to its interannual variation are quantified in the Community Earth System Model (CESM) Large Ensemble and Last Millennium Ensemble. Consistent with expectations, the El Niño/Southern Oscillation (ENSO) is found to exert a strong influence due to variability in rainfall over land (PL) and terrestrial water storage (TWS). Other important contributors include changes in ocean heat content (OHC) and precipitable water (PW). The temporal evolution of individual contributing terms is documented. The magnitude of peak GMSL anomalies associated with ENSO generally are of themore » order of 0.5 mm·K -1 with significant inter-event variability, with a standard deviation (σ) that is about half as large The results underscore the exceptional rarity of the 2010/2011 La Niña-related GMSL drop and estimate the frequency of such an event to be about only once in every 75 years. In addition to ENSO, major volcanic eruptions are found to be a key driver of interannual variability. Associated GMSL variability contrasts with that of ENSO as TWS and PW anomalies initially offset the drop due to OHC reductions but short-lived relative to them. Furthermore, responses up to 25 mm are estimated for the largest eruptions of the Last Millennium.« less

  4. Interannual variability in global mean sea level estimated from the CESM Large and Last Millennium Ensembles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fasullo, John T.; Nerem, Robert S.

    To better understand global mean sea level (GMSL) as an indicator of climate variability and change, contributions to its interannual variation are quantified in the Community Earth System Model (CESM) Large Ensemble and Last Millennium Ensemble. Consistent with expectations, the El Niño/Southern Oscillation (ENSO) is found to exert a strong influence due to variability in rainfall over land (PL) and terrestrial water storage (TWS). Other important contributors include changes in ocean heat content (OHC) and precipitable water (PW). The temporal evolution of individual contributing terms is documented. The magnitude of peak GMSL anomalies associated with ENSO generally are of themore » order of 0.5 mm·K -1 with significant inter-event variability, with a standard deviation (σ) that is about half as large The results underscore the exceptional rarity of the 2010/2011 La Niña-related GMSL drop and estimate the frequency of such an event to be about only once in every 75 years. In addition to ENSO, major volcanic eruptions are found to be a key driver of interannual variability. Associated GMSL variability contrasts with that of ENSO as TWS and PW anomalies initially offset the drop due to OHC reductions but short-lived relative to them. Furthermore, responses up to 25 mm are estimated for the largest eruptions of the Last Millennium.« less

  5. Inter-individual variability of stone marten behavioral responses to a highway.

    PubMed

    Ascensão, Fernando; Grilo, Clara; LaPoint, Scott; Tracey, Jeff; Clevenger, Anthony P; Santos-Reis, Margarida

    2014-01-01

    Efforts to reduce the negative impacts of roads on wildlife may be hindered if individuals within the population vary widely in their responses to roads and mitigation strategies ignore this variability. This knowledge is particularly important for medium-sized carnivores as they are vulnerable to road mortality, while also known to use available road passages (e.g., drainage culverts) for safely crossing highways. Our goal in this study was to assess whether this apparently contradictory pattern of high road-kill numbers associated with a regular use of road passages is attributable to the variation in behavioral responses toward the highway between individuals. We investigated the responses of seven radio-tracked stone martens (Martes foina) to a highway by measuring their utilization distribution, response turning angles and highway crossing patterns. We compared the observed responses to simulated movement parameterized by the observed space use and movement characteristics of each individual, but naïve to the presence of the highway. Our results suggested that martens demonstrate a diversity of responses to the highway, including attraction, indifference, or avoidance. Martens also varied in their highway crossing patterns, with some crossing repeatedly at the same location (often coincident with highway passages). We suspect that the response variability derives from the individual's familiarity of the landscape, including their awareness of highway passage locations. Because of these variable yet potentially attributable responses, we support the use of exclusionary fencing to guide transient (e.g., dispersers) individuals to existing passages to reduce the road-kill risk.

  6. Inter-Individual Variability of Stone Marten Behavioral Responses to a Highway

    PubMed Central

    Ascensão, Fernando; Grilo, Clara; LaPoint, Scott; Tracey, Jeff; Clevenger, Anthony P.; Santos-Reis, Margarida

    2014-01-01

    Efforts to reduce the negative impacts of roads on wildlife may be hindered if individuals within the population vary widely in their responses to roads and mitigation strategies ignore this variability. This knowledge is particularly important for medium-sized carnivores as they are vulnerable to road mortality, while also known to use available road passages (e.g., drainage culverts) for safely crossing highways. Our goal in this study was to assess whether this apparently contradictory pattern of high road-kill numbers associated with a regular use of road passages is attributable to the variation in behavioral responses toward the highway between individuals. We investigated the responses of seven radio-tracked stone martens (Martes foina) to a highway by measuring their utilization distribution, response turning angles and highway crossing patterns. We compared the observed responses to simulated movement parameterized by the observed space use and movement characteristics of each individual, but naïve to the presence of the highway. Our results suggested that martens demonstrate a diversity of responses to the highway, including attraction, indifference, or avoidance. Martens also varied in their highway crossing patterns, with some crossing repeatedly at the same location (often coincident with highway passages). We suspect that the response variability derives from the individual's familiarity of the landscape, including their awareness of highway passage locations. Because of these variable yet potentially attributable responses, we support the use of exclusionary fencing to guide transient (e.g., dispersers) individuals to existing passages to reduce the road-kill risk. PMID:25072639

  7. Glomerular epithelial foot processes in normal man and rats. Distribution of true width and its intra- and inter-individual variation.

    PubMed

    Gundersen, H J; Seefeldt, T; Osterby, R

    1980-01-01

    The width of individual glomerular epithelial foot processes appears very different on electron micrographs. A method for obtainining distributions of the true width of foot processes from that of their apparent width on electron micrographs has been developed based on geometric probability theory pertaining to a specific geometric model. Analyses of foot process width in humans and rats show a remarkable interindividual invariance implying rigid control and therefore great biological significance of foot process width or a derivative thereof. The very low inter-individual variation of the true width, shown in the present paper, makes it possible to demonstrate slight changes in rather small groups of patients or experimental animals.

  8. Retinotopic Maps, Spatial Tuning, and Locations of Human Visual Areas in Surface Coordinates Characterized with Multifocal and Blocked fMRI Designs

    PubMed Central

    Henriksson, Linda; Karvonen, Juha; Salminen-Vaparanta, Niina; Railo, Henry; Vanni, Simo

    2012-01-01

    The localization of visual areas in the human cortex is typically based on mapping the retinotopic organization with functional magnetic resonance imaging (fMRI). The most common approach is to encode the response phase for a slowly moving visual stimulus and to present the result on an individual's reconstructed cortical surface. The main aims of this study were to develop complementary general linear model (GLM)-based retinotopic mapping methods and to characterize the inter-individual variability of the visual area positions on the cortical surface. We studied 15 subjects with two methods: a 24-region multifocal checkerboard stimulus and a blocked presentation of object stimuli at different visual field locations. The retinotopic maps were based on weighted averaging of the GLM parameter estimates for the stimulus regions. In addition to localizing visual areas, both methods could be used to localize multiple retinotopic regions-of-interest. The two methods yielded consistent retinotopic maps in the visual areas V1, V2, V3, hV4, and V3AB. In the higher-level areas IPS0, VO1, LO1, LO2, TO1, and TO2, retinotopy could only be mapped with the blocked stimulus presentation. The gradual widening of spatial tuning and an increase in the responses to stimuli in the ipsilateral visual field along the hierarchy of visual areas likely reflected the increase in the average receptive field size. Finally, after registration to Freesurfer's surface-based atlas of the human cerebral cortex, we calculated the mean and variability of the visual area positions in the spherical surface-based coordinate system and generated probability maps of the visual areas on the average cortical surface. The inter-individual variability in the area locations decreased when the midpoints were calculated along the spherical cortical surface compared with volumetric coordinates. These results can facilitate both analysis of individual functional anatomy and comparisons of visual cortex topology across studies. PMID:22590626

  9. Methylation at Global LINE-1 Repeats in Human Blood Are Affected by Gender but Not by Age or Natural Hormone Cycles

    PubMed Central

    El-Maarri, Osman; Singer, Heike; Diaz-Lacava, Amalia; Nüsgen, Nicole; Niemann, Barbara; Watzka, Matthias; Reinsberg, Jochen; van der Ven, Hans; Wienker, Thomas; Stoffel-Wagner, Birgit; Schwaab, Rainer; Oldenburg, Johannes

    2011-01-01

    Previously, we reported on inter-individual and gender specific variations of LINE-1 methylation in healthy individuals. In this study, we investigated whether this variability could be influenced by age or sex hormones in humans. To this end, we studied LINE-1 methylation in vivo in blood-derived DNA from individuals aged 18 to 64 years and from young healthy females at various hormone levels during the menstrual cycle. Our results show that no significant association with age was observed. However, the previously reported increase of LINE-1 methylation in males was reconfirmed. In females, although no correlation between LINE-1 or Alu methylation and hormone levels was observed, a significant stable individual specific level of methylation was noted. In vitro results largely confirmed these findings, as neither estrogen nor dihydrotestosterone affected LINE-1 or Alu methylation in Hek293T, HUVEC, or MDA-kb2 cell lines. In contrast, a decrease in methylation was observed in estrogen-treated T47-Kbluc cell lines strongly expressing estrogen receptor. The very low expression of estrogen receptor in blood cells could explain the observed insensitivity of methylation at LINE-1 to natural hormonal variations in females. In conclusion, neither natural cycle of hormones nor age has a detectable effect on the LINE-1 methylation in peripheral blood cells, while gender remains an important factor. PMID:21311577

  10. VO2 and VCO2 variabilities through indirect calorimetry instrumentation.

    PubMed

    Cadena-Méndez, Miguel; Escalante-Ramírez, Boris; Azpiroz-Leehan, Joaquín; Infante-Vázquez, Oscar

    2013-01-01

    The aim of this paper is to understand how to measure the VO2 and VCO2 variabilities in indirect calorimetry (IC) since we believe they can explain the high variation in the resting energy expenditure (REE) estimation. We propose that variabilities should be separately measured from the VO2 and VCO2 averages to understand technological differences among metabolic monitors when they estimate the REE. To prove this hypothesis the mixing chamber (MC) and the breath-by-breath (BbB) techniques measured the VO2 and VCO2 averages and their variabilities. Variances and power spectrum energies in the 0-0.5 Hertz band were measured to establish technique differences in steady and non-steady state. A hybrid calorimeter with both IC techniques studied a population of 15 volunteers that underwent the clino-orthostatic maneuver in order to produce the two physiological stages. The results showed that inter-individual VO2 and VCO2 variabilities measured as variances were negligible using the MC while variabilities measured as spectral energies using the BbB underwent 71 and 56% (p < 0.05), increase respectively. Additionally, the energy analysis showed an unexpected cyclic rhythm at 0.025 Hertz only during the orthostatic stage, which is new physiological information, not reported previusly. The VO2 and VCO2 inter-individual averages increased to 63 and 39% by the MC (p < 0.05) and 32 and 40% using the BbB (p < 0.1), respectively, without noticeable statistical differences among techniques. The conclusions are: (a) metabolic monitors should simultaneously include the MC and the BbB techniques to correctly interpret the steady or non-steady state variabilities effect in the REE estimation, (b) the MC is the appropriate technique to compute averages since it behaves as a low-pass filter that minimizes variances, (c) the BbB is the ideal technique to measure the variabilities since it can work as a high-pass filter to generate discrete time series able to accomplish spectral analysis, and (d) the new physiological information in the VO2 and VCO2 variabilities can help to understand why metabolic monitors with dissimilar IC techniques give different results in the REE estimation.

  11. Variability of activity profile during medium-sided games in professional soccer.

    PubMed

    Rago, Vincenzo; Silva, João R; Mohr, Magni; Barreira, Daniel; Krustrup, Peter; Rebelo, António N

    2018-04-24

    In Southern European countries it is very frequent to perform medium-sized games (MSG) as last training drill. We analyzed the individual variability and changes in activity patterns during MSG throughout the preseason. Activity profile during MSGs (10v10+goalkeepers, duration: 10-min, field length: 50 m, width: 90 m, area per player: 204.5 m2) was quantified using a GPS in 14 professional male players (6 defenders, 5 midfielders 5 and attackers). Inter-individual variability was higher for high-intensity (HIR), very-high speed (VHS), maximum acceleration (Accmax) and maximum deceleration (Decmax) distance (CV=25.2 to 43.3%), compared to total distance (TD), total acceleration (Acctot) and total deceleration (Dectot) distance (CV= 8.3 to 18.3 %). Defenders showed higher variability in TD, HIR, VHS, Acctot and Dectot (ES= 1.30 to 11.28) compared to the other field positions, whereas attackers showed higher variability in HIR, VHS Accmax and Decmax (ES=-4.92 to 2.07) than other the field positions. Variability in TD regularly increased (ES= -2.13 to -0.91) towards the end of the preseason, while HIR and VHS variability tended to increase over the 3rd and the 4th preseason week (ES=-0.94 to -3.05). However, the behavior of variability across the preseason period was more unpredictable for Acctot and Dectot, both decreasing in the 3rd week (ES= 0.70 to 1.20), while Decmax increased in the 4th week (ES=-0.91±0.59). During MSGs, individual variability of activity differs among field positions, and tends to increase with either speed or acceleration intensity, underlining the need of an individualized approach for training load monitoring.

  12. Parameter Stability of the Functional–Structural Plant Model GREENLAB as Affected by Variation within Populations, among Seasons and among Growth Stages

    PubMed Central

    Ma, Yuntao; Li, Baoguo; Zhan, Zhigang; Guo, Yan; Luquet, Delphine; de Reffye, Philippe; Dingkuhn, Michael

    2007-01-01

    Background and Aims It is increasingly accepted that crop models, if they are to simulate genotype-specific behaviour accurately, should simulate the morphogenetic process generating plant architecture. A functional–structural plant model, GREENLAB, was previously presented and validated for maize. The model is based on a recursive mathematical process, with parameters whose values cannot be measured directly and need to be optimized statistically. This study aims at evaluating the stability of GREENLAB parameters in response to three types of phenotype variability: (1) among individuals from a common population; (2) among populations subjected to different environments (seasons); and (3) among different development stages of the same plants. Methods Five field experiments were conducted in the course of 4 years on irrigated fields near Beijing, China. Detailed observations were conducted throughout the seasons on the dimensions and fresh biomass of all above-ground plant organs for each metamer. Growth stage-specific target files were assembled from the data for GREENLAB parameter optimization. Optimization was conducted for specific developmental stages or the entire growth cycle, for individual plants (replicates), and for different seasons. Parameter stability was evaluated by comparing their CV with that of phenotype observation for the different sources of variability. A reduced data set was developed for easier model parameterization using one season, and validated for the four other seasons. Key Results and Conclusions The analysis of parameter stability among plants sharing the same environment and among populations grown in different environments indicated that the model explains some of the inter-seasonal variability of phenotype (parameters varied less than the phenotype itself), but not inter-plant variability (parameter and phenotype variability were similar). Parameter variability among developmental stages was small, indicating that parameter values were largely development-stage independent. The authors suggest that the high level of parameter stability observed in GREENLAB can be used to conduct comparisons among genotypes and, ultimately, genetic analyses. PMID:17158141

  13. Characterizing the nature and variability of avalanche hazard in western Canada

    NASA Astrophysics Data System (ADS)

    Shandro, Bret; Haegeli, Pascal

    2018-04-01

    The snow and avalanche climate types maritime, continental and transitional are well established and have been used extensively to characterize the general nature of avalanche hazard at a location, study inter-seasonal and large-scale spatial variabilities and provide context for the design of avalanche safety operations. While researchers and practitioners have an experience-based understanding of the avalanche hazard associated with the three climate types, no studies have described the hazard character of an avalanche climate in detail. Since the 2009/2010 winter, the consistent use of Statham et al. (2017) conceptual model of avalanche hazard in public avalanche bulletins in Canada has created a new quantitative record of avalanche hazard that offers novel opportunities for addressing this knowledge gap. We identified typical daily avalanche hazard situations using self-organizing maps (SOMs) and then calculated seasonal prevalence values of these situations. This approach produces a concise characterization that is conducive to statistical analyses, but still provides a comprehensive picture that is informative for avalanche risk management due to its link to avalanche problem types. Hazard situation prevalence values for individual seasons, elevations bands and forecast regions provide unprecedented insight into the inter-seasonal and spatial variability of avalanche hazard in western Canada.

  14. Inter- and Intrasubject Similarity of Muscle Synergies During Bench Press With Slow and Fast Velocity.

    PubMed

    Samani, Afshin; Kristiansen, Mathias

    2018-01-01

    We investigated the effect of low and high bar velocity on inter- and intrasubject similarity of muscle synergies during bench press. A total of 13 trained male subjects underwent two exercise conditions: a slow- and a fast-velocity bench press. Surface electromyography was recorded from 13 muscles, and muscle synergies were extracted using a nonnegative matrix factorization algorithm. The intrasubject similarity across conditions and intersubject similarity within conditions were computed for muscle synergy vectors and activation coefficients. Two muscle synergies were sufficient to describe the dataset variability. For the second synergy activation coefficient, the intersubject similarity within the fast-velocity condition was greater than the intrasubject similarity of the activation coefficient across the conditions. An opposite pattern was observed for the first muscle synergy vector. We concluded that the activation coefficients are robust within conditions, indicating a robust temporal pattern of muscular activity across individuals, but the muscle synergy vector seemed to be individually assigned.

  15. CK-MM gene polymorphism does not influence the blood CK activity levels after exhaustive eccentric exercise.

    PubMed

    Yamin, C; Oliveira, J; Meckel, Y; Eynon, N; Sagiv, M; Ayalon, M; Alves, A J; Duarte, J A

    2010-03-01

    Gene variants, such as creatine kinase (CK) polymorphisms, have been suggested to explain the inter-individual blood CK response to eccentric exercise. However, since this association is still doubtful, the purpose of this study was to analyse the relationship between the magnitudes of the CK response to exercise with the occurrence of muscle CK-MM NcoI polymorphism in young healthy subjects. Blood CK activity was assessed in 70 subjects immediately before and 3, 24, 48, 72, 96, 120, 168 h after strenuous eccentric exercise. Based on the amount of CK release by each subject, the sample was distributed in quartiles and the genotype and allele frequency distribution was compared among quartiles. Despite the inter-individual variability of CK response observed between subjects, there were no differences in genotype and allele frequencies among quartiles. The results allowed us to conclude that CK response after exhaustive eccentric exercise is not associated with CK-MM Ncol polymorphism. Georg Thieme Verlag KG Stuttgart.New York.

  16. Individual Brain Charting, a high-resolution fMRI dataset for cognitive mapping.

    PubMed

    Pinho, Ana Luísa; Amadon, Alexis; Ruest, Torsten; Fabre, Murielle; Dohmatob, Elvis; Denghien, Isabelle; Ginisty, Chantal; Becuwe-Desmidt, Séverine; Roger, Séverine; Laurier, Laurence; Joly-Testault, Véronique; Médiouni-Cloarec, Gaëlle; Doublé, Christine; Martins, Bernadette; Pinel, Philippe; Eger, Evelyn; Varoquaux, Gaël; Pallier, Christophe; Dehaene, Stanislas; Hertz-Pannier, Lucie; Thirion, Bertrand

    2018-06-12

    Functional Magnetic Resonance Imaging (fMRI) has furthered brain mapping on perceptual, motor, as well as higher-level cognitive functions. However, to date, no data collection has systematically addressed the functional mapping of cognitive mechanisms at a fine spatial scale. The Individual Brain Charting (IBC) project stands for a high-resolution multi-task fMRI dataset that intends to provide the objective basis toward a comprehensive functional atlas of the human brain. The data refer to a cohort of 12 participants performing many different tasks. The large amount of task-fMRI data on the same subjects yields a precise mapping of the underlying functions, free from both inter-subject and inter-site variability. The present article gives a detailed description of the first release of the IBC dataset. It comprises a dozen of tasks, addressing both low- and high- level cognitive functions. This openly available dataset is thus intended to become a reference for cognitive brain mapping.

  17. Changes in physical activity during the retirement transition: a series of novel n-of-1 natural experiments.

    PubMed

    McDonald, Suzanne; Vieira, Rute; Godfrey, Alan; O'Brien, Nicola; White, Martin; Sniehotta, Falko F

    2017-12-08

    Existing evidence about the impact of retirement on physical activity (PA) has primarily focused on the average change in PA level after retirement in group-based studies. It is unclear whether findings regarding the direction of PA change after retirement from group-based studies apply to individuals. This study aimed to explore changes in PA, PA determinants and their inter-relationships during the retirement transition at the individual level. A series of n-of-1 natural experiments were conducted with seven individuals who were aged 55-76 years and approaching retirement. PA was measured by tri-axial accelerometry. Twice-daily self-report and ecological momentary assessments of evidence- and theory-based determinants of PA (e.g. sleep length/quality, happiness, tiredness, stress, time pressure, pain, intention, perceived behavioural control, priority, goal conflict and goal facilitation) were collected via a questionnaire for a period of between 3 and 7 months, which included time before and after the participant's retirement date. A personalised PA determinant was also identified by each participant and measured daily for the duration of the study. Dynamic regression models for discrete time binary data were used to analyse data for each individual participant. Two participants showed a statistically significant increase in the probability of engaging in PA bouts after retirement and two participants showed a significant time trend for a decrease and increase in PA bouts over time during the pre- to post-retirement period, respectively. There was no statistically significant change in PA after retirement for the remaining participants. Most of the daily questionnaire variables were significantly associated with PA for one or more participants but there were no consistent pattern of PA predictors across participants. For some participants, the relationship between questionnaire variables and PA changed from pre- to post-retirement. The findings from this study demonstrate the impact of retirement on individual PA trajectories. Using n-of-1 methods can provide information about unique patterns and determinants of individual behaviour over time, which has been obscured in previous research. N-of-1 methods can be used as a tool to inform personalised PA interventions for individuals within the retirement transition.

  18. Cumulative biomedical risk and social cognition in the second year of life: prediction and moderation by responsive parenting.

    PubMed

    Wade, Mark; Madigan, Sheri; Akbari, Emis; Jenkins, Jennifer M

    2015-01-01

    At 18 months, children show marked variability in their social-cognitive skill development, and the preponderance of past research has focused on constitutional and contextual factors in explaining this variability. Extending this literature, the current study examined whether cumulative biomedical risk represents another source of variability in social cognition at 18 months. Further, we aimed to determine whether responsive parenting moderated the association between biomedical risk and social cognition. A prospective community birth cohort of 501 families was recruited at the time of the child's birth. Cumulative biomedical risk was measured as a count of 10 prenatal/birth complications. Families were followed up at 18 months, at which point social-cognitive data was collected on children's joint attention, empathy, cooperation, and self-recognition using previously validated tasks. Concurrently, responsive maternal behavior was assessed through observational coding of mother-child interactions. After controlling for covariates (e.g., age, gender, child language, socioeconomic variables), both cumulative biomedical risk and maternal responsivity significantly predicted social cognition at 18 months. Above and beyond these main effects, there was also a significant interaction between biomedical risk and maternal responsivity, such that higher biomedical risk was significantly associated with compromised social cognition at 18 months, but only in children who experienced low levels of responsive parenting. For those receiving comparatively high levels of responsive parenting, there was no apparent effect of biomedical risk on social cognition. This study shows that cumulative biomedical risk may be one source of inter-individual variability in social cognition at 18 months. However, positive postnatal experiences, particularly high levels of responsive parenting, may protect children against the deleterious effects of these risks on social cognition.

  19. Effect of inter- and intra-annual thermohaline variability on acoustic propagation

    NASA Astrophysics Data System (ADS)

    Chu, Peter C.; McDonald, Colleen M.; Kucukosmanoglu, Murat; Judono, Albert; Margolina, Tetyana; Fan, Chenwu

    2017-05-01

    This paper is to answer the question "How can inter- and intra-annual variability in the ocean be leveraged by the submarine Force?" through quantifying inter- and intra-annual variability in (T, S) fields and in turn underwater acoustic characteristics such as transmission loss, signal excess, and range of detection. The Navy's Generalized Digital Environmental Model (GDEM) is the climatological monthly mean data and represents mean annual variability. An optimal spectral decomposition method is used to produce a synoptic monthly gridded (SMG) (T, S) dataset for the world oceans with 1° ×1° horizontal resolution, 28 vertical levels (surface to 3,000 m depth), monthly time increment from January 1945 to December 2014 now available at the NOAA/NCEI website: http://data.nodc.noaa.gov/cgibin/iso?id=gov.noaa.nodc:0140938. The sound velocity decreases from 1945 to 1975 and increases afterwards due to global climate change. Effect of the inter- and intra-annual (T, S) variability on acoustic propagation in the Yellow Sea is investigated using a well-developed acoustic model (Bellhop) in frequencies from 3.5 kHz to 5 kHz with sound velocity profile (SVP) calculated from GDEM and SMG datasets, various bottom types (silty clay, fine sand, gravelly mud, sandy mud, and cobble or gravel) from the NAVOCEANO`s High Frequency Environmental Algorithms (HFEVA), source and receiver depths. Acoustic propagation ranges are extended drastically due to the inter-annual variability in comparison with the climatological SVP (from GDEM). Submarines' vulnerability of detection as its depth varies and avoidance of short acoustic range due to inter-annual variability are also discussed.

  20. Physiological and psychological individual differences influence resting brain function measured by ASL perfusion.

    PubMed

    Kano, M; Coen, S J; Farmer, A D; Aziz, Q; Williams, S C R; Alsop, D C; Fukudo, S; O'Gorman, R L

    2014-09-01

    Effects of physiological and/or psychological inter-individual differences on the resting brain state have not been fully established. The present study investigated the effects of individual differences in basal autonomic tone and positive and negative personality dimensions on resting brain activity. Whole-brain resting cerebral perfusion images were acquired from 32 healthy subjects (16 males) using arterial spin labeling perfusion MRI. Neuroticism and extraversion were assessed with the Eysenck Personality Questionnaire-Revised. Resting autonomic activity was assessed using a validated measure of baseline cardiac vagal tone (CVT) in each individual. Potential associations between the perfusion data and individual CVT (27 subjects) and personality score (28 subjects) were tested at the level of voxel clusters by fitting a multiple regression model at each intracerebral voxel. Greater baseline perfusion in the dorsal anterior cingulate cortex (ACC) and cerebellum was associated with lower CVT. At a corrected significance threshold of p < 0.01, strong positive correlations were observed between extraversion and resting brain perfusion in the right caudate, brain stem, and cingulate gyrus. Significant negative correlations between neuroticism and regional cerebral perfusion were identified in the left amygdala, bilateral insula, ACC, and orbitofrontal cortex. These results suggest that individual autonomic tone and psychological variability influence resting brain activity in brain regions, previously shown to be associated with autonomic arousal (dorsal ACC) and personality traits (amygdala, caudate, etc.) during active task processing. The resting brain state may therefore need to be taken into account when interpreting the neurobiology of individual differences in structural and functional brain activity.

  1. The inter-rater reliability test of the modified Morse Fall Scale among patients ≥ 55 years old in an acute care hospital in Singapore.

    PubMed

    Tang, Wing Sze; Chow, Yeow Leng; Koh, Serena Siew Lin

    2014-02-01

    A prospective, descriptive study was conducted in an acute care hospital in Singapore to determine the inter-rater reliability of the modified Morse Fall Scale by evaluating the degrees of agreement on the ratings of the individual items and overall score between the 'gold standard' assessor and the facility assessors. One hundred and forty-two subjects were recruited during the 1.5 month data collection period. The simple and weighted κ-values were all > 0.8 except for the item 'effects of medications' (κ and κw  = 0.63), and the correlation coefficient (rs  = 0.89) was significantly high at a significance level of < 0.001. The modified Morse Fall Scale was shown to be a reliable fall risk assessment tool having a relative high inter-rater reliability level for the overall score and individual items. This study provides evidence-based psychometric support for the clinical application of this tool. © 2013 Wiley Publishing Asia Pty Ltd.

  2. The key kinematic determinants of undulatory underwater swimming at maximal velocity.

    PubMed

    Connaboy, Chris; Naemi, Roozbeh; Brown, Susan; Psycharakis, Stelios; McCabe, Carla; Coleman, Simon; Sanders, Ross

    2016-01-01

    The optimisation of undulatory underwater swimming is highly important in competitive swimming performance. Nineteen kinematic variables were identified from previous research undertaken to assess undulatory underwater swimming performance. The purpose of the present study was to determine which kinematic variables were key to the production of maximal undulatory underwater swimming velocity. Kinematic data at maximal undulatory underwater swimming velocity were collected from 17 skilled swimmers. A series of separate backward-elimination analysis of covariance models was produced with cycle frequency and cycle length as dependent variables (DVs) and participant as a fixed factor, as including cycle frequency and cycle length would explain 100% of the maximal swimming velocity variance. The covariates identified in the cycle-frequency and cycle-length models were used to form the saturated model for maximal swimming velocity. The final parsimonious model identified three covariates (maximal knee joint angular velocity, maximal ankle angular velocity and knee range of movement) as determinants of the variance in maximal swimming velocity (adjusted-r2 = 0.929). However, when participant was removed as a fixed factor there was a large reduction in explained variance (adjusted r2 = 0.397) and only maximal knee joint angular velocity continued to contribute significantly, highlighting its importance to the production of maximal swimming velocity. The reduction in explained variance suggests an emphasis on inter-individual differences in undulatory underwater swimming technique and/or anthropometry. Future research should examine the efficacy of other anthropometric, kinematic and coordination variables to better understand the production of maximal swimming velocity and consider the importance of individual undulatory underwater swimming techniques when interpreting the data.

  3. Inter-subject variability modulates phonological advance planning in the production of adjective-noun phrases.

    PubMed

    Michel Lange, Violaine; Laganaro, Marina

    2014-01-01

    The literature on advance phonological planning in adjective-noun phrases (NPs) presents diverging results: while many experimental studies suggest that the entire NP is encoded before articulation, other results favor a span of encoding limited to the first word. Although cross-linguistic differences in the structure of adjective-NPs may account for some of these contrasting results, divergences have been reported even among similar languages and syntactic structures. Here we examined whether inter-individual differences account for variability in the span of phonological planning in the production of French NPs, where previous results indicated encoding limited to the first word. The span of phonological encoding is tested with the picture-word interference (PWI) paradigm using phonological distractors related to the noun or to the adjective of the NPs. In Experiment 1, phonological priming effects were limited to the first word in adjective NPs whichever the position of the adjective (pre-nominal or post-nominal). Crucially, phonological priming effects on the second word interacted with speakers' production speed suggesting different encoding strategies for participants. In Experiment 2, we tested this hypothesis further with a larger group of participants. Results clearly showed that slow and fast initializing participants presented different phonological priming patterns on the last element of adjective-NPs: while the first word was primed by a distractor for all speakers, only the slow speaker group presented a priming effect on the second element of the NP. These results show that the span of phonological encoding is modulated by inter-individual strategies: in experimental paradigms some speakers plan word by word whereas others encode beyond the initial word. We suggest that the diverging results reported in the literature on advance phonological planning may partly be reconciled in light of the present results.

  4. Native-likeness in second language lexical categorization reflects individual language history and linguistic community norms.

    PubMed

    Zinszer, Benjamin D; Malt, Barbara C; Ameel, Eef; Li, Ping

    2014-01-01

    SECOND LANGUAGE LEARNERS FACE A DUAL CHALLENGE IN VOCABULARY LEARNING: First, they must learn new names for the 100s of common objects that they encounter every day. Second, after some time, they discover that these names do not generalize according to the same rules used in their first language. Lexical categories frequently differ between languages (Malt et al., 1999), and successful language learning requires that bilinguals learn not just new words but new patterns for labeling objects. In the present study, Chinese learners of English with varying language histories and resident in two different language settings (Beijing, China and State College, PA, USA) named 67 photographs of common serving dishes (e.g., cups, plates, and bowls) in both Chinese and English. Participants' response patterns were quantified in terms of similarity to the responses of functionally monolingual native speakers of Chinese and English and showed the cross-language convergence previously observed in simultaneous bilinguals (Ameel et al., 2005). For English, bilinguals' names for each individual stimulus were also compared to the dominant name generated by the native speakers for the object. Using two statistical models, we disentangle the effects of several highly interactive variables from bilinguals' language histories and the naming norms of the native speaker community to predict inter-personal and inter-item variation in L2 (English) native-likeness. We find only a modest age of earliest exposure effect on L2 category native-likeness, but importantly, we find that classroom instruction in L2 negatively impacts L2 category native-likeness, even after significant immersion experience. We also identify a significant role of both L1 and L2 norms in bilinguals' L2 picture naming responses.

  5. Native-likeness in second language lexical categorization reflects individual language history and linguistic community norms

    PubMed Central

    Zinszer, Benjamin D.; Malt, Barbara C.; Ameel, Eef; Li, Ping

    2014-01-01

    Second language learners face a dual challenge in vocabulary learning: First, they must learn new names for the 100s of common objects that they encounter every day. Second, after some time, they discover that these names do not generalize according to the same rules used in their first language. Lexical categories frequently differ between languages (Malt et al., 1999), and successful language learning requires that bilinguals learn not just new words but new patterns for labeling objects. In the present study, Chinese learners of English with varying language histories and resident in two different language settings (Beijing, China and State College, PA, USA) named 67 photographs of common serving dishes (e.g., cups, plates, and bowls) in both Chinese and English. Participants’ response patterns were quantified in terms of similarity to the responses of functionally monolingual native speakers of Chinese and English and showed the cross-language convergence previously observed in simultaneous bilinguals (Ameel et al., 2005). For English, bilinguals’ names for each individual stimulus were also compared to the dominant name generated by the native speakers for the object. Using two statistical models, we disentangle the effects of several highly interactive variables from bilinguals’ language histories and the naming norms of the native speaker community to predict inter-personal and inter-item variation in L2 (English) native-likeness. We find only a modest age of earliest exposure effect on L2 category native-likeness, but importantly, we find that classroom instruction in L2 negatively impacts L2 category native-likeness, even after significant immersion experience. We also identify a significant role of both L1 and L2 norms in bilinguals’ L2 picture naming responses. PMID:25386149

  6. A matter of hand: Causal links between hand dominance, structural organization of fronto-parietal attention networks, and variability in behavioural responses to transcranial magnetic stimulation.

    PubMed

    Cazzoli, Dario; Chechlacz, Magdalena

    2017-01-01

    Considerable evidence suggests that, on a group level, human visuospatial attention is asymmetrically organized, with a right-hemispheric dominance. The asymmetrical organization of the superior longitudinal fasciculus (SLF) has been shown to account for the right-hemispheric dominance in visual attention. However, such account is by no means universal, and large individual differences in asymmetrical performance on visuospatial tasks have been reported. Furthermore, the variability in the SLF lateralization has been shown to correlate with behavioural asymmetries. Continuous theta burst stimulation (cTBS) enables to temporarily interfere with cortical activity. cTBS applied over the posterior parietal cortex (PPC) has been previously used to systematically study attentional asymmetries. Interestingly, large individual differences in the effectiveness of stimulation have been reported. In accordance with earlier both animal and human studies, one possible cause underlying these striking individual differences might lie in the structural organization of frontoparietal pathways subserving visuospatial attention. Thus, the current study employed diffusion tractography to examine the relationship between the variability in the structural organization of the SLF and the individual differences in attentional shifts induced by a modified cTBS (cTBS mod ; triplets of pulses at 30 Hz, repeated at 6 Hz) applied over the IPS, as measured by a line bisection task. Consistent with previous studies, on a group level, cTBS mod applied over the right intraparietal sulcus (IPS) triggered a rightward bisection bias shift, and there were no significant effects of cTBS mod applied over the left IPS. However, further analyses demonstrated that both handedness and structural variability (as assessed based on hindrance modulated orientational anisotropy) within the middle and the ventral branches of the SLF predicted individual differences in the cTBS mod -induced attentional shifts. Our study thus suggests that the effects of cTBS mod over the IPS may depend on intra-hemispheric interactions between cortical loci controlling visual attention. To conclude, our findings provide converging evidence for the notion put forward previously that inter-individual variability in the structural organization of intra-hemispheric frontoparietal connections has important implications for the functional models of human visual attention. Moreover, we hypothesize that this may also be relevant for the understanding of attentional disorders and their rehabilitation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Spatio-temporal analysis of annual rainfall in Crete, Greece

    NASA Astrophysics Data System (ADS)

    Varouchakis, Emmanouil A.; Corzo, Gerald A.; Karatzas, George P.; Kotsopoulou, Anastasia

    2018-03-01

    Analysis of rainfall data from the island of Crete, Greece was performed to identify key hydrological years and return periods as well as to analyze the inter-annual behavior of the rainfall variability during the period 1981-2014. The rainfall spatial distribution was also examined in detail to identify vulnerable areas of the island. Data analysis using statistical tools and spectral analysis were applied to investigate and interpret the temporal course of the available rainfall data set. In addition, spatial analysis techniques were applied and compared to determine the rainfall spatial distribution on the island of Crete. The analysis presented that in contrast to Regional Climate Model estimations, rainfall rates have not decreased, while return periods vary depending on seasonality and geographic location. A small but statistical significant increasing trend was detected in the inter-annual rainfall variations as well as a significant rainfall cycle almost every 8 years. In addition, statistically significant correlation of the island's rainfall variability with the North Atlantic Oscillation is identified for the examined period. On the other hand, regression kriging method combining surface elevation as secondary information improved the estimation of the annual rainfall spatial variability on the island of Crete by 70% compared to ordinary kriging. The rainfall spatial and temporal trends on the island of Crete have variable characteristics that depend on the geographical area and on the hydrological period.

  8. The development of an instrument to match individuals with disabilities and service animals.

    PubMed

    Zapf, S A; Rough, R B

    There has been an increase in the use of service animals assisting persons with disabilities in the past decade. However many of the service dog agencies do not utilize an assessment that is designed to match the person to the animal in the rehabilitation and psycho-social domains. The purpose of this study was to develop the Service Animal Adaptive Intervention Assessment (SAAIA) and to measure the content validity, inter-rater reliability and clinical utility of the assessment. Two subject groups were used. Subject group one had 43 subjects who measured the content validity and clinical utility of the SAAIA Survey. Subject group two had 12 subjects who measured the inter-rater reliability by completing the SAAIA using information obtained through a video-taped client case scenario. Content validity results indicated a good to high percentage of agreement and a fair percentage of agreement for clinical utility. Inter-rater reliability results indicate good to high agreement on six of the eight variables of the SAAIA. However, the Kappa score indicates low inter-rater reliability. Results indicate the SAAIA has good content validity and inter-rater reliability and fair clinical utility based on percent agreement. However, further research is needed on the reliability of the SAAIA.

  9. Inter-rater reliability of motor unit number estimates and quantitative motor unit analysis in the tibialis anterior muscle.

    PubMed

    Boe, S G; Dalton, B H; Harwood, B; Doherty, T J; Rice, C L

    2009-05-01

    To establish the inter-rater reliability of decomposition-based quantitative electromyography (DQEMG) derived motor unit number estimates (MUNEs) and quantitative motor unit (MU) analysis. Using DQEMG, two examiners independently obtained a sample of needle and surface-detected motor unit potentials (MUPs) from the tibialis anterior muscle from 10 subjects. Coupled with a maximal M wave, surface-detected MUPs were used to derive a MUNE for each subject and each examiner. Additionally, size-related parameters of the individual MUs were obtained following quantitative MUP analysis. Test-retest MUNE values were similar with high reliability observed between examiners (ICC=0.87). Additionally, MUNE variability from test-retest as quantified by a 95% confidence interval was relatively low (+/-28 MUs). Lastly, quantitative data pertaining to MU size, complexity and firing rate were similar between examiners. MUNEs and quantitative MU data can be obtained with high reliability by two independent examiners using DQEMG. Establishing the inter-rater reliability of MUNEs and quantitative MU analysis using DQEMG is central to the clinical applicability of the technique. In addition to assessing response to treatments over time, multiple clinicians may be involved in the longitudinal assessment of the MU pool of individuals with disorders of the central or peripheral nervous system.

  10. Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

    PubMed Central

    Goodrich, Jaclyn M.; Wang, Yi; Gillespie, Brenda; Werner, Robert; Franzblau, Alfred; Basu, Niladri

    2012-01-01

    Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n=515), and total mercury content was measured. Average urine (1.06±1.24 ug/L) and hair mercury levels (0.49±0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5’), or both (SEPP1 3’UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption). PMID:21967774

  11. Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma.

    PubMed

    Göttler, Jens; Lukas, Mathias; Kluge, Anne; Kaczmarz, Stephan; Gempt, Jens; Ringel, Florian; Mustafa, Mona; Meyer, Bernhard; Zimmer, Claus; Schwaiger, Markus; Förster, Stefan; Preibisch, Christine; Pyka, Thomas

    2017-03-01

    18 F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV. Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined. While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p < 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average. Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology.

  12. Proposal and validation of a clinical trunk control test in individuals with spinal cord injury.

    PubMed

    Quinzaños, J; Villa, A R; Flores, A A; Pérez, R

    2014-06-01

    One of the problems that arise in spinal cord injury (SCI) is alteration in trunk control. Despite the need for standardized scales, these do not exist for evaluating trunk control in SCI. To propose and validate a trunk control test in individuals with SCI. National Institute of Rehabilitation, Mexico. The test was developed and later evaluated for reliability and criteria, content, and construct validity. We carried out 531 tests on 177 patients and found high inter- and intra-rater reliability. In terms of criterion validity, analysis of variance demonstrated a statistically significant difference in the test score of patients with adequate or inadequate trunk control according to the assessment of a group of experts. A receiver operating characteristic curve was plotted for optimizing the instrument's cutoff point, which was determined at 13 points, with a sensitivity of 98% and a specificity of 92.2%. With regard to construct validity, the correlation between the proposed test and the spinal cord independence measure (SCIM) was 0.873 (P=0.001) and that with the evolution time was 0.437 (P=0.001). For testing the hypothesis with qualitative variables, the Kruskal-Wallis test was performed, which resulted in a statistically significant difference between the scores in the proposed scale of each group defined by these variables. It was proven experimentally that the proposed trunk control test is valid and reliable. Furthermore, the test can be used for all patients with SCI despite the type and level of injury.

  13. Diffusion-weighted imaging of the prostate: should we use quantitative metrics to better characterize focal lesions originating in the peripheral zone?

    PubMed

    Pierre, Thibaut; Cornud, Francois; Colléter, Loïc; Beuvon, Frédéric; Foissac, Frantz; Delongchamps, Nicolas B; Legmann, Paul

    2018-05-01

    To compare inter-reader concordance and accuracy of qualitative diffusion-weighted (DW) PIRADSv2.0 score with those of quantitative DW-MRI for the diagnosis of peripheral zone prostate cancer. Two radiologists independently assigned a DW-MRI-PIRADS score to 92 PZ-foci, in 74 patients (64.3±5.6 years old; median PSA level: 8 ng/ml, normal DRE in 70 men). A standardised ADCmean and nine ADC-derived parameters were measured, including ADCratios with the whole-prostate (WP-ADCratio) or the mirror-PZ (mirror-ADCratio) as reference areas. Surgical histology and MRI-TRUS fusion-biopsy were the reference for tumours and benign foci, respectively. Inter-reader agreement was assessed by the Cohen-kappa-coefficient and the intraclass correlation coefficient (ICC). Univariate-multivariate regressions determined the most predictive factor for cancer. Fifty lesions were malignant. Inter-reader concordance was fair for qualitative assessment, but excellent for quantitative assessment for all quantitative variables. At univariate analysis, ADCmean, WP-ADCratio and WL-ADCmean performed equally, but significantly better than the mirror-ADCratio (p<0.001). At multivariate analysis, the only independent variable significantly associated with malignancy was the whole-prostate-ADCratio. At a cut-off value of 0.68, sensitivity was 94-90 % and specificity was 60-38 % for readers 1 and 2, respectively. The whole-prostate-ADCratio improved the qualitative inter-reader concordance and characterisation of focal PZ-lesions. • Inter-reader concordance of DW PI-RADSv2.0 score for PZ lesions was only fair. • Using a standardised ADCmean measurement and derived DW-quantitative parameters, concordance was excellent. • The whole-prostate ADCratio performed significantly better than the mirror-ADCratio for cancer detection. • At a cut-off of 0.68, sensitivity values of WP-ADCratio were 94-90 %. • The whole-prostate ADCratio may circumvent variations of ADC metrics across centres.

  14. Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect.

    PubMed

    Solymosi, Tamás; Ötvös, Zsolt; Angi, Réka; Ordasi, Betti; Jordán, Tamás; Molnár, László; McDermott, John; Zann, Vanessa; Church, Ann; Mair, Stuart; Filipcsei, Genovéva; Heltovics, Gábor; Glavinas, Hristos

    2017-10-01

    Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers. The study was conducted in 11 healthy men aged 47-57 years. All subjects received 3 consecutive single doses of the novel formulation of AA (100 and 200 mg in the fasted state and 200 mg in the fed state). Data were compared with pharmacokinetic and safety data reported for 1000 mg Zytiga, the marketed drug. The novel formulation of AA allows rapid absorption of the compound with t max values within 1 hour. Based on AUC values, a ~250 mg dose of the novel formulation is predicted to give the same exposure as 1000 mg Zytiga in the fasted state. The significant positive food effect was also eliminated; actually, a slight, but statistically significant negative food effect was observed. Variability of exposure was significantly reduced when compared to Zytiga. AA administered in the novel formulation was well tolerated with no IMP-related safety AEs reported. The novel formulation might allow a 75% dose reduction with significant reduction of inter-individual variability. The negative food effect observed requires further investigations; however, elimination of the significant positive food effect could be adequate to negate the restriction of a food label.

  15. Relationships between lumbar inter-vertebral motion and lordosis in healthy adult males: a cross sectional cohort study.

    PubMed

    du Rose, Alister; Breen, Alan

    2016-03-10

    Intervertebral motion impairment is widely thought to be related to chronic back disability, however, the movements of inter-vertebral pairs are not independent of each other and motion may also be related to morphology. Furthermore, maximum intervertebral range of motion (IV-RoMmax) is difficult to measure accurately in living subjects. The purpose of this study was to explore possible relationships between (IV-RoMmax) and lordosis, initial attainment rate and IV-RoMmax at other levels during weight-bearing flexion using quantitative fluoroscopy (QF). Continuous QF motion sequences were recorded during controlled active sagittal flexion of 60° in 18 males (mean age 27.6 SD 4.4) with no history of low back pain in the previous year. IV-RoMmax, lordotic angle, and initial attainment rate at all inter-vertebral levels from L2-S1 were extracted. Relationships between IV-RoMmax and the other variables were explored using correlation coefficients, and simple linear regression was used to determine the effects of any significant relationships. Within and between observer repeatability of IV-RoMmax and initial attainment rate measurements were assessed in a sub-set of ten participants, using the intra-class correlation coefficient (ICC) and standard error of measurement (SEM). QF measurements were highly repeatable, the lowest ICC for IV-RoMmax, being 0.94 (0.80-0.99) and highest SEM (0.76°). For initial attainment rate the lowest ICC was 0.84 (0.49-0.96) and the highest SEM (0.036). The results also demonstrated significant positive and negative correlations between IV-RoMmax and IV-RoMmax at other lumbar levels (r = -0.64-0.65), lordosis (r = -0.52-0.54), and initial attainment rate (r = -0.64-0.73). Simple linear regression analysis of all significant relationships showed that these predict between 28 and 42 % of the variance in IV-RoMmax. This study found weak to moderate effects of individual kinematic variables and lumbar lordosis on IV-RoMmax at other intervertebral levels. These effects, when combined, may be important when such levels are being considered by healthcare professionals as potential sources of pain generation. Multivariate investigations in larger samples are warranted.

  16. Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses.

    PubMed

    Chung, Jee-Eun; Lee, Kyung Eun; Chang, Byung Chul; Gwak, Hye Sun

    2018-01-30

    The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements. The rs4072879 of VKORC1L1 (A>G) was significantly associated with stable warfarin doses; wild homozygote carriers (AA) required significantly lower stable warfarin doses than those with the variant G allele (5.02±1.56 vs. 5.96±2.01mg; p=0.001). Multivariate analysis showed that EPHX1 rs1877724 and VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability. Adding EPHX1 and VKORC1L1 SNPs to the base model including non-genetic variables (operation age, body weight and the therapy of ACEI or ARB) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 34. This study showed that polymorphisms of EPHX1 and VKORC1L1 could be determinants of stable warfarin doses. Copyright © 2017. Published by Elsevier B.V.

  17. Standardization for Ki-67 Assessment in Moderately Differentiated Breast Cancer. A Retrospective Analysis of the SAKK 28/12 Study

    PubMed Central

    Varga, Zsuzsanna; Cassoly, Estelle; Li, Qiyu; Oehlschlegel, Christian; Tapia, Coya; Lehr, Hans Anton; Klingbiel, Dirk; Thürlimann, Beat; Ruhstaller, Thomas

    2015-01-01

    Background Proliferative activity (Ki-67 Labelling Index) in breast cancer increasingly serves as an additional tool in the decision for or against adjuvant chemotherapy in midrange hormone receptor positive breast cancer. Ki-67 Index has been previously shown to suffer from high inter-observer variability especially in midrange (G2) breast carcinomas. In this study we conducted a systematic approach using different Ki-67 assessments on large tissue sections in order to identify the method with the highest reliability and the lowest variability. Materials and Methods Five breast pathologists retrospectively analyzed proliferative activity of 50 G2 invasive breast carcinomas using large tissue sections by assessing Ki-67 immunohistochemistry. Ki-67-assessments were done on light microscopy and on digital images following these methods: 1) assessing five regions, 2) assessing only darkly stained nuclei and 3) considering only condensed proliferative areas (‘hotspots’). An individual review (the first described assessment from 2008) was also performed. The assessments on light microscopy were done by estimating. All measurements were performed three times. Inter-observer and intra-observer reliabilities were calculated using the approach proposed by Eliasziw et al. Clinical cutoffs (14% and 20%) were tested using Fleiss’ Kappa. Results There was a good intra-observer reliability in 5 of 7 methods (ICC: 0.76–0.89). The two highest inter-observer reliability was fair to moderate (ICC: 0.71 and 0.74) in 2 methods (region-analysis and individual-review) on light microscopy. Fleiss’-kappa-values (14% cut-off) were the highest (moderate) using the original recommendation on light-microscope (Kappa 0.58). Fleiss’ kappa values (20% cut-off) were the highest (Kappa 0.48 each) in analyzing hotspots on light-microscopy and digital-analysis. No methodologies using digital-analysis were superior to the methods on light microscope. Conclusion Our results show that all methods on light-microscopy for Ki-67 assessment in large tissue sections resulted in a good intra-observer reliability. Region analysis and individual review (the original recommendation) on light-microscopy yielded the highest inter-observer reliability. These results show slight improvement to previously published data on poor-reproducibility and thus might be a practical-pragmatic way for routine assessment of Ki-67 Index in G2 breast carcinomas. PMID:25885288

  18. Better Alone or in Ill Company? The Effect of Migration and Inter-Species Comingling on Fascioloides magna Infection in Elk.

    PubMed

    Pruvot, Mathieu; Lejeune, Manigandan; Kutz, Susan; Hutchins, Wendy; Musiani, Marco; Massolo, Alessandro; Orsel, Karin

    2016-01-01

    Migratory movements and alteration of host communities through livestock production are examples of ecological processes that may have consequences on wildlife pathogens. We studied the effect of co-grazing of cattle and wild elk, and of elk migratory behaviour on the occurrence of the giant liver fluke, Fascioloides magna, in elk. Migratory elk and elk herds with a higher proportion of migratory individuals were significantly less likely to be infected with F. magna. This may indicate a decreased risk of infection for migratory individuals, known as the "migratory escape" hypothesis. Elk herds overlapping with higher cattle densities also had a lower prevalence of this parasite, even after adjustment for landscape and climate variables known to influence its life cycle. Serological evidence suggests that even in low-prevalence areas, F. magna is circulating in both elk and cattle. Cattle are "dead-end" hosts for F. magna, and this may, therefore, indicate a dilution effect where cattle and elk are co-grazing. Migratory behaviour and host community composition have significant effects on the dynamics of this wildlife parasite; emphasizing the potential impacts of decisions regarding the management of migratory corridors and livestock-wildlife interface.

  19. Genetic variants of age at menopause are not related to timing of ovarian failure in breast cancer survivors

    PubMed Central

    Homer, Michael V.; Charo, Lindsey M.; Natarajan, Loki; Haunschild, Carolyn; Chung, Karine; Mao, Jun J.; DeMichele, Angela M.; Su, H. Irene

    2016-01-01

    Objective To determine if inter-individual genetic variation in single nucleotide polymorphisms related to age at natural menopause are associated with risk of ovarian failure in breast cancer survivors. Methods A prospective cohort of 169 premenopausal breast cancer survivors recruited at diagnosis with Stages 0 to III disease were followed longitudinally for menstrual pattern via self-reported daily menstrual diaries. Participants were genotyped for 13 single nucleotide polymorphisms (SNPs) previously found to be associated with age at natural menopause: EXO1, TLK1, HELQ, UIMC1, PRIM1, POLG, TMEM224, BRSK1, and MCM8. A risk variable summed the total number of risk alleles in each participant. The association between individual genotypes, as well as the risk variable, and time to ovarian failure (> 12 months of amenorrhea) was tested using time-to-event methods. Results Median age at enrollment was 40.5 years old (range 20.6–46.1). The majority of participants were white (69%) and underwent chemotherapy (76%). Thirty-eight participants (22%) experienced ovarian failure. None of the candidate SNPs or the summary risk variable were significantly associated with time to ovarian failure. Sensitivity analysis restricted to whites or only to participants receiving chemotherapy yielded similar findings. Older age, chemotherapy exposure and lower BMI were related to shorter time to ovarian failure. Conclusions Thirteen previously identified genetic variants associated with time to natural menopause were not related to timing of ovarian failure in breast cancer survivors. PMID:28118297

  20. Comparison of Inter-Observer Variability and Diagnostic Performance of the Fifth Edition of BI-RADS for Breast Ultrasound of Static versus Video Images.

    PubMed

    Youk, Ji Hyun; Jung, Inkyung; Yoon, Jung Hyun; Kim, Sung Hun; Kim, You Me; Lee, Eun Hye; Jeong, Sun Hye; Kim, Min Jung

    2016-09-01

    Our aim was to compare the inter-observer variability and diagnostic performance of the Breast Imaging Reporting and Data System (BI-RADS) lexicon for breast ultrasound of static and video images. Ninety-nine breast masses visible on ultrasound examination from 95 women 19-81 y of age at five institutions were enrolled in this study. They were scheduled to undergo biopsy or surgery or had been stable for at least 2 y of ultrasound follow-up after benign biopsy results or typically benign findings. For each mass, representative long- and short-axis static ultrasound images were acquired; real-time long- and short-axis B-mode video images through the mass area were separately saved as cine clips. Each image was reviewed independently by five radiologists who were asked to classify ultrasound features according to the fifth edition of the BI-RADS lexicon. Inter-observer variability was assessed using kappa (κ) statistics. Diagnostic performance on static and video images was compared using the area under the receiver operating characteristic curve. No significant difference was found in κ values between static and video images for all descriptors, although κ values of video images were higher than those of static images for shape, orientation, margin and calcifications. After receiver operating characteristic curve analysis, the video images (0.83, range: 0.77-0.87) had higher areas under the curve than the static images (0.80, range: 0.75-0.83; p = 0.08). Inter-observer variability and diagnostic performance of video images was similar to that of static images on breast ultrasonography according to the new edition of BI-RADS. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  1. Demography of a forest elephant population

    PubMed Central

    Turkalo, Andrea K.; Wrege, Peter H.

    2018-01-01

    African forest elephants face severe threats from illegal killing for ivory and bushmeat and habitat conversion. Due to their cryptic nature and inaccessible range, little information on the biology of this species has been collected despite its iconic status. Compiling individual based monitoring data collected over 20 years from the Dzanga Bai population in Central African Republic, we summarize sex and age specific survivorship and female age specific fecundity for a cohort of 1625 individually identified elephants. Annual mortality (average = 3.5%) and natality (average = 5.3%) were lower and markedly less variable relative to rates reported for savanna elephant populations. New individuals consistently entered the study system, leading to a 2.5% average annual increase in the registered population. Calf sex ratios among known birth did not differ from parity. A weak seasonal signal in births was detected suggesting increased conceptions during the wet season. Inter-calf intervals and age of primiparity were longer relative to savanna elephant populations. Within the population, females between the ages of 25–39 demonstrated the shortest inter-calf intervals and highest fecundity, and previous calf sex had no influence on the interval. Calf survivorship was high (97%) the first two years after birth and did not differ by sex. Male and female survival began to differ by the age of 13 years, and males demonstrated significantly lower survival relative to females by the age of 20. It is suspected these differences are driven by human selection for ivory. Forest elephants were found to have one of the longest generation times recorded for any species at 31 years. These data provide fundamental understanding of forest elephant demography, providing baseline data for projecting population status and trends. PMID:29447207

  2. An Examination of the Multi-Faceted Motivation System in Healthy Young Adults.

    PubMed

    Da Silva, Susana; Apatsidou, Areti; Saperia, Sarah; Siddiqui, Ishraq; Jeffay, Eliyas; Voineskos, Aristotle N; Daskalakis, Zafiris J; Remington, Gary; Zakzanis, Konstantine K; Foussias, George

    2018-01-01

    Background: Amotivation is a prevalent symptom in schizophrenia (SZ) and depression (MDD), and is linked to poor functional outcomes in affected individuals. Conceptualizations of motivation have outlined a multi-faceted construct comprised of reward responsiveness, reward expectancy, reward valuation, effort valuation, and action selection/preference-based decision making. To date, findings from studies utilizing variable-centered approaches to examining isolated facets of motivation in SZ and MDD have been inconsistent. Thus, the present study adopted a person-centered approach, and comprehensively examined the reward system in a non-clinical sample in an attempt to explore potential subtypes of motivation impairments, while minimizing the effects of illness-related confounds. Methods: Ninety-six healthy undergraduate students were evaluated for amotivation, schizotypal traits, depressive symptoms, and cognition, and administered objective computerized tasks to measure the different facets of motivation. Cluster analysis was performed to explore subgroups of individuals based on similar motivation task performance. Additionally, correlational analyses were conducted in order to examine inter-relationships between motivation facets, and relations between clinical measures and facets of motivation. Results: Cluster analysis identified two subgroups of individuals with differential motivation performance profiles. Correlational analyses revealed that reward responsiveness was associated with amotivation, depressive symptoms, and negative schizotypy. Further, significant inter-correlations were found between reward responsiveness and reward expectancy, as well as between reward valuation and effort valuation. Conclusions: Our results mark important steps forward in understanding motivation in a non-clinical sample, and guide future dimensional and comprehensive analyses of the multi-faceted reward system. It remains to be seen whether these patterns of results will be similar in clinical populations such as SZ and MDD.

  3. An Examination of the Multi-Faceted Motivation System in Healthy Young Adults

    PubMed Central

    Da Silva, Susana; Apatsidou, Areti; Saperia, Sarah; Siddiqui, Ishraq; Jeffay, Eliyas; Voineskos, Aristotle N.; Daskalakis, Zafiris J.; Remington, Gary; Zakzanis, Konstantine K.; Foussias, George

    2018-01-01

    Background: Amotivation is a prevalent symptom in schizophrenia (SZ) and depression (MDD), and is linked to poor functional outcomes in affected individuals. Conceptualizations of motivation have outlined a multi-faceted construct comprised of reward responsiveness, reward expectancy, reward valuation, effort valuation, and action selection/preference-based decision making. To date, findings from studies utilizing variable-centered approaches to examining isolated facets of motivation in SZ and MDD have been inconsistent. Thus, the present study adopted a person-centered approach, and comprehensively examined the reward system in a non-clinical sample in an attempt to explore potential subtypes of motivation impairments, while minimizing the effects of illness-related confounds. Methods: Ninety-six healthy undergraduate students were evaluated for amotivation, schizotypal traits, depressive symptoms, and cognition, and administered objective computerized tasks to measure the different facets of motivation. Cluster analysis was performed to explore subgroups of individuals based on similar motivation task performance. Additionally, correlational analyses were conducted in order to examine inter-relationships between motivation facets, and relations between clinical measures and facets of motivation. Results: Cluster analysis identified two subgroups of individuals with differential motivation performance profiles. Correlational analyses revealed that reward responsiveness was associated with amotivation, depressive symptoms, and negative schizotypy. Further, significant inter-correlations were found between reward responsiveness and reward expectancy, as well as between reward valuation and effort valuation. Conclusions: Our results mark important steps forward in understanding motivation in a non-clinical sample, and guide future dimensional and comprehensive analyses of the multi-faceted reward system. It remains to be seen whether these patterns of results will be similar in clinical populations such as SZ and MDD.

  4. Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids.

    PubMed

    Laugsand, Eivor A; Skorpen, Frank; Kaasa, Stein; Sabatowski, Rainer; Strasser, Florian; Fayers, Peter; Klepstad, Pål

    2015-06-18

    To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (P<0.01). Age, gender, body mass index, cancer diagnosis, time on opioids, opioid dose, and type of opioid did not contribute to the inter-individual differences in constipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (P<0.01). Only rs2020917 in COMT passed the Benjamini-Hochberg criterion for a 10% false discovery rate. Type of laxative, mobility, hospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment.

  5. High individual consistency in fear of humans throughout the adult lifespan of rural and urban burrowing owls

    NASA Astrophysics Data System (ADS)

    Carrete, Martina; Tella, José L.

    2013-12-01

    Human-induced rapid environmental changes challenge individuals by creating evolutionarily novel scenarios, where species encounter novel enemies, the new species sometimes being humans themselves. However, little is known about how individuals react to human presence, specifically whether they are able to habituate to human presence, as frequently assumed, or are selected based on their fear of humans. We tested whether fear of humans (measured as flight initiation distance in a diurnal owl) is reduced through habituation to human presence (plasticity) or whether it remains unchanged throughout the individuals' life. Results show an unusually high level of individual consistency in fear of humans throughout the adult lifespan of both rural (r = 0.96) and urban (r = 0.90) birds, lending no support to habituation. Further research should assess the role of inter-individual variability in fear of humans in shaping the distribution of individuals and species in an increasingly humanized world.

  6. Diversity and association of phenotypic and metabolomic traits in the close model grasses Brachypodium distachyon, B. stacei and B. hybridum

    PubMed Central

    López-Álvarez, Diana; Zubair, Hassan; Beckmann, Manfred; Draper, John

    2017-01-01

    Abstract Background and Aims Morphological traits in combination with metabolite fingerprinting were used to investigate inter- and intraspecies diversity within the model annual grasses Brachypodium distachyon, Brachypodium stacei and Brachypodium hybridum. Methods Phenotypic variation of 15 morphological characters and 2219 nominal mass (m/z) signals generated using flow infusion electrospray ionization–mass spectrometry (FIE–MS) were evaluated in individuals from a total of 174 wild populations and six inbred lines, and 12 lines, of the three species, respectively. Basic statistics and multivariate principal component analysis and discriminant analysis were used to differentiate inter- and intraspecific variability of the two types of variable, and their association was assayed with the rcorr function. Key Results Basic statistics and analysis of variance detected eight phenotypic characters [(stomata) leaf guard cell length, pollen grain length, (plant) height, second leaf width, inflorescence length, number of spikelets per inflorescence, lemma length, awn length] and 434 tentatively annotated metabolite signals that significantly discriminated the three species. Three phenotypic traits (pollen grain length, spikelet length, number of flowers per inflorescence) might be genetically fixed. The three species showed different metabolomic profiles. Discriminant analysis significantly discriminated the three taxa with both morphometric and metabolome traits and the intraspecific phenotypic diversity within B. distachyon and B. stacei. The populations of B. hybridum were considerably less differentiated. Conclusions Highly explanatory metabolite signals together with morphological characters revealed concordant patterns of differentiation of the three taxa. Intraspecific phenotypic diversity was observed between northern and southern Iberian populations of B. distachyon and between eastern Mediterranean/south-western Asian and western Mediterranean populations of B. stacei. Significant association was found for pollen grain length and lemma length and ten and six metabolomic signals, respectively. These results would guide the selection of new germplasm lines of the three model grasses in ongoing genome-wide association studies. PMID:28040672

  7. Assessing Agreement between Multiple Raters with Missing Rating Information, Applied to Breast Cancer Tumour Grading

    PubMed Central

    Ellis, Ian O.; Green, Andrew R.; Hanka, Rudolf

    2008-01-01

    Background We consider the problem of assessing inter-rater agreement when there are missing data and a large number of raters. Previous studies have shown only ‘moderate’ agreement between pathologists in grading breast cancer tumour specimens. We analyse a large but incomplete data-set consisting of 24177 grades, on a discrete 1–3 scale, provided by 732 pathologists for 52 samples. Methodology/Principal Findings We review existing methods for analysing inter-rater agreement for multiple raters and demonstrate two further methods. Firstly, we examine a simple non-chance-corrected agreement score based on the observed proportion of agreements with the consensus for each sample, which makes no allowance for missing data. Secondly, treating grades as lying on a continuous scale representing tumour severity, we use a Bayesian latent trait method to model cumulative probabilities of assigning grade values as functions of the severity and clarity of the tumour and of rater-specific parameters representing boundaries between grades 1–2 and 2–3. We simulate from the fitted model to estimate, for each rater, the probability of agreement with the majority. Both methods suggest that there are differences between raters in terms of rating behaviour, most often caused by consistent over- or under-estimation of the grade boundaries, and also considerable variability in the distribution of grades assigned to many individual samples. The Bayesian model addresses the tendency of the agreement score to be biased upwards for raters who, by chance, see a relatively ‘easy’ set of samples. Conclusions/Significance Latent trait models can be adapted to provide novel information about the nature of inter-rater agreement when the number of raters is large and there are missing data. In this large study there is substantial variability between pathologists and uncertainty in the identity of the ‘true’ grade of many of the breast cancer tumours, a fact often ignored in clinical studies. PMID:18698346

  8. Space Availability in Confined Sheep during Pregnancy, Effects in Movement Patterns and Use of Space

    PubMed Central

    Averós, Xavier; Lorea, Areta; Beltrán de Heredia, Ignacia; Arranz, Josune; Ruiz, Roberto; Estevez, Inma

    2014-01-01

    Space availability is essential to grant the welfare of animals. To determine the effect of space availability on movement and space use in pregnant ewes (Ovis aries), 54 individuals were studied during the last 11 weeks of gestation. Three treatments were tested (1, 2, and 3 m2/ewe; 6 ewes/group). Ewes' positions were collected for 15 minutes using continuous scan samplings two days/week. Total and net distance, net/total distance ratio, maximum and minimum step length, movement activity, angular dispersion, nearest, furthest and mean neighbour distance, peripheral location ratio, and corrected peripheral location ratio were calculated. Restriction in space availability resulted in smaller total travelled distance, net to total distance ratio, maximum step length, and angular dispersion but higher movement activity at 1 m2/ewe as compared to 2 and 3 m2/ewe (P<0.01). On the other hand, nearest and furthest neighbour distances increased from 1 to 3 m2/ewe (P<0.001). Largest total distance, maximum and minimum step length, and movement activity, as well as lowest net/total distance ratio and angular dispersion were observed during the first weeks (P<0.05) while inter-individual distances increased through gestation. Results indicate that movement patterns and space use in ewes were clearly restricted by limitations of space availability to 1 m2/ewe. This reflected in shorter, more sinuous trajectories composed of shorter steps, lower inter-individual distances and higher movement activity potentially linked with higher restlessness levels. On the contrary, differences between 2 and 3 m2/ewe, for most variables indicate that increasing space availability from 2 to 3 m2/ewe would appear to have limited benefits, reflected mostly in a further increment in the inter-individual distances among group members. No major variations in spatial requirements were detected through gestation, except for slight increments in inter-individual distances and an initial adaptation period, with ewes being restless and highly motivated to explore their new environment. PMID:24733027

  9. The role of pelvis-thorax coupling in controlling within-golf club swing speed.

    PubMed

    Lamb, Peter F; Pataky, Todd C

    2018-02-23

    Pelvis-thorax coordination has been recognised to be associated with swing speed. Increasing angular separation between the pelvis and thorax has been thought to initiate the stretch shortening cycle and lead to increased clubhead speed. The purpose of this study was to determine whether pelvis-thorax coupling played a significant role in regulating clubhead speed, in a group of low-handicap golfers (mean handicap = 4.1). Sixteen participants played shots to target distances determined based on their typical 5- and 6-iron shot distances. Half the difference between median 5- and 6-iron distance for each participant was used to create three swing effort conditions: "minus", "norm", and "plus". Ten shots were played under each swing effort condition using both the 5-iron and 6-iron, resulting in six shot categories and 60 shots per participant. No significant differences were found for X-factor for club or swing effort. X-factor stretch showed significant differences for club and swing effort. Continuous relative phase (CRP) results mainly showed evidence of the stretch shortening cycle in the downswing and that it was more pronounced late in the downswing as swing effort increased. Substantial inter-individual CRP variability demonstrated the need for individual analyses when investigating coordination in the golf swing.

  10. Reproducibility of aortic intima-media thickness in infants using edge-detection software and manual caliper measurements.

    PubMed

    McCloskey, Kate; Ponsonby, Anne-Louise; Carlin, John B; Jachno, Kim; Cheung, Michael; Skilton, Michael R; Koleff, Jane; Vuillermin, Peter; Burgner, David

    2014-06-03

    Aortic intima-media thickness measured by transabdominal ultrasound (aIMT) is an intermediate phenotype of cardiovascular risk. We aimed to (1) investigate the reproducibility of aIMT in a population-derived cohort of infants; (2) establish the distribution of aIMT in early infancy; (3) compare measurement by edge-detection software to that by manual sonographic calipers; and (4) assess the effect of individual and environmental variables on image quality. Participants were term infants recruited to a population-derived birth cohort study. Transabdominal ultrasound was performed at six weeks of age by one of two trained operators. Thirty participants had ultrasounds performed by both operators on the same day. Data were collected on environmental (infant sleeping, presence of a sibling, use of sucrose, timing during study visit) and individual (post-conception age, weight, gender) variables. Two readers assessed image quality and measured aIMT by edge-detection software and a subset by manual sonographic calipers. Measurements were repeated by the same reader and between readers to obtain intra-observer and inter-observer reliability. Aortic IMT was measured successfully using edge-detection in 814 infants, and 290 of these infants also had aIMT measured using manual sonographic calipers. The intra-reader intra-class correlation (ICC) (n = 20) was 0.90 (95% CI 0.76, 0.96), mean difference 1.5 μm (95% LOA -39, 59). The between reader ICC using edge-detection (n = 20) was 0.92 (95% CI 0.82, 0.97) mean difference 2 μm (95% LOA -45.0, 49.0) and with manual caliper measurement (n = 290) the ICC was 0.84 (95% CI 0.80, 0.87) mean difference 5 μm (95% LOA -51.8, 61.8). Edge-detection measurements were greater than those from manual sonographic calipers (mean aIMT 618 μm (50) versus mean aIMT 563 μm (49) respectively; p < 0.001, mean difference 44 μm, 95% LOA -54, 142). With the exception of infant crying (p = 0.001), no associations were observed between individual and environmental variables and image quality. In a population-derived cohort of term infants, aIMT measurement has a high level of intra and inter-reader reproducibility. Measurement of aIMT using edge-detection software gives higher inter-reader ICC than manual sonographic calipers. Image quality is not substantially affected by individual and environmental factors.

  11. Population Pharmacokinetics of Artesunate and Dihydroartemisinin following Intra-Rectal Dosing of Artesunate in Malaria Patients

    PubMed Central

    Simpson, Julie A; Agbenyega, Tsiri; Barnes, Karen I; Perri, Gianni Di; Folb, Peter; Gomes, Melba; Krishna, Sanjeev; Krudsood, Srivicha; Looareesuwan, Sornchai; Mansor, Sharif; McIlleron, Helen; Miller, Raymond; Molyneux, Malcolm; Mwenechanya, James; Navaratnam, Visweswaran; Nosten, Francois; Olliaro, Piero; Pang, Lorrin; Ribeiro, Isabela; Tembo, Madalitso; van Vugt, Michele; Ward, Steve; Weerasuriya, Kris; Win, Kyaw; White, Nicholas J

    2006-01-01

    Background Intra-rectal artesunate has been developed as a potentially life-saving treatment of severe malaria in rural village settings where administration of parenteral antimalarial drugs is not possible. We studied the population pharmacokinetics of intra-rectal artesunate and the relationship with parasitological responses in patients with moderately severe falciparum malaria. Methods and Findings Adults and children in Africa and Southeast Asia with moderately severe malaria were recruited in two Phase II studies (12 adults from Southeast Asia and 11 children from Africa) with intensive sampling protocols, and three Phase III studies (44 children from Southeast Asia, and 86 children and 26 adults from Africa) with sparse sampling. All patients received 10 mg/kg artesunate as a single intra-rectal dose of suppositories. Venous blood samples were taken during a period of 24 h following dosing. Plasma artesunate and dihydroartemisinin (DHA, the main biologically active metabolite) concentrations were measured by high-performance liquid chromatography with electrochemical detection. The pharmacokinetic properties of DHA were determined using nonlinear mixed-effects modelling. Artesunate is rapidly hydrolysed in vivo to DHA, and this contributes the majority of antimalarial activity. For DHA, a one-compartment model assuming complete conversion from artesunate and first-order appearance and elimination kinetics gave the best fit to the data. The mean population estimate of apparent clearance (CL/F) was 2.64 (l/kg/h) with 66% inter-individual variability. The apparent volume of distribution (V/F) was 2.75 (l/kg) with 96% inter-individual variability. The estimated DHA population mean elimination half-life was 43 min. Gender was associated with increased mean CL/F by 1.14 (95% CI: 0.36–1.92) (l/kg/h) for a male compared with a female, and weight was positively associated with V/F. Larger V/Fs were observed for the patients requiring early rescue treatment compared with the remainder, independent of any confounders. No associations between the parasitological responses and the posterior individual estimates of V/F, CL/F, and AUC0–6h were observed. Conclusions The pharmacokinetic properties of DHA were affected only by gender and body weight. Patients with the lowest area under the DHA concentration curve did not have slower parasite clearance, suggesting that rectal artesunate is well absorbed in most patients with moderately severe malaria. However, a number of modelling assumptions were required due to the large intra- and inter-individual variability of the DHA concentrations. PMID:17132053

  12. Seasonal and inter-annual variability of the net ecosystem CO2 exchange of a temperate mountain grassland: effects of climate and management.

    PubMed

    Wohlfahrt, Georg; Hammerle, Albin; Haslwanter, Alois; Bahn, Michael; Tappeiner, Ulrike; Cernusca, Alexander

    2008-04-27

    The role and relative importance of climate and cutting for the seasonal and inter-annual variability of the net ecosystem CO 2 (NEE) of a temperate mountain grassland was investigated. Eddy covariance CO 2 flux data and associated measurements of the green area index and the major environmental driving forces acquired during 2001-2006 at the study site Neustift (Austria) were analyzed. Driven by three cutting events per year which kept the investigated grassland in a stage of vigorous growth, the seasonal variability of NEE was primarily modulated by gross primary productivity (GPP). The role of environmental parameters in modulating the seasonal variability of NEE was obscured by the strong response of GPP to changes in the amount of green area, as well as the cutting-mediated decoupling of phenological development and the seasonal course of climate drivers. None of the climate and management metrics examined was able to explain the inter-annual variability of annual NEE. This is thought to result from (1) a high covariance between GPP and ecosystem respiration (R eco ) at the annual time scale which results in a comparatively small inter-annual variation of NEE, (2) compensating effects between carbon exchange during and outside the management period, and (3) changes in the biotic response to rather than the climate variables per se. GPP was more important in modulating inter-annual variations in NEE in spring and before the first and second cut, while R eco explained a larger fraction of the inter-annual variability of NEE during the remaining, in particular the post-cut, periods.

  13. A stepwedge-based method for measuring breast density: observer variability and comparison with human reading

    NASA Astrophysics Data System (ADS)

    Diffey, Jenny; Berks, Michael; Hufton, Alan; Chung, Camilla; Verow, Rosanne; Morrison, Joanna; Wilson, Mary; Boggis, Caroline; Morris, Julie; Maxwell, Anthony; Astley, Susan

    2010-04-01

    Breast density is positively linked to the risk of developing breast cancer. We have developed a semi-automated, stepwedge-based method that has been applied to the mammograms of 1,289 women in the UK breast screening programme to measure breast density by volume and area. 116 images were analysed by three independent operators to assess inter-observer variability; 24 of these were analysed on 10 separate occasions by the same operator to determine intra-observer variability. 168 separate images were analysed using the stepwedge method and by two radiologists who independently estimated percentage breast density by area. There was little intra-observer variability in the stepwedge method (average coefficients of variation 3.49% - 5.73%). There were significant differences in the volumes of glandular tissue obtained by the three operators. This was attributed to variations in the operators' definition of the breast edge. For fatty and dense breasts, there was good correlation between breast density assessed by the stepwedge method and the radiologists. This was also observed between radiologists, despite significant inter-observer variation. Based on analysis of thresholds used in the stepwedge method, radiologists' definition of a dense pixel is one in which the percentage of glandular tissue is between 10 and 20% of the total thickness of tissue.

  14. Variability of argon laser-induced sensory and pain thresholds on human oral mucosa and skin.

    PubMed Central

    Svensson, P.; Bjerring, P.; Arendt-Nielsen, L.; Kaaber, S.

    1991-01-01

    The variability of laser-induced pain perception on human oral mucosa and hairy skin was investigated in order to establish a new method for evaluation of pain in the orofacial region. A high-energy argon laser was used for experimental pain stimulation, and sensory and pain thresholds were determined. The intra-individual coefficients of variation for oral thresholds were comparable to cutaneous thresholds. However, inter-individual variation was smaller for oral thresholds, which could be due to larger variation in cutaneous optical properties. The short-term and 24-hr changes in thresholds on both surfaces were less than 9%. The results indicate that habituation to laser thresholds may account for part of the intra-individual variation observed. However, the subjective ratings of the intensity of the laser stimuli were constant. Thus, oral thresholds may, like cutaneous thresholds, be used for assessment and quantification of analgesic efficacies and to investigate various pain conditions. PMID:1814248

  15. Enhancing the effectiveness of human-robot teaming with a closed-loop system.

    PubMed

    Teo, Grace; Reinerman-Jones, Lauren; Matthews, Gerald; Szalma, James; Jentsch, Florian; Hancock, Peter

    2018-02-01

    With technological developments in robotics and their increasing deployment, human-robot teams are set to be a mainstay in the future. To develop robots that possess teaming capabilities, such as being able to communicate implicitly, the present study implemented a closed-loop system. This system enabled the robot to provide adaptive aid without the need for explicit commands from the human teammate, through the use of multiple physiological workload measures. Such measures of workload vary in sensitivity and there is large inter-individual variability in physiological responses to imposed taskload. Workload models enacted via closed-loop system should accommodate such individual variability. The present research investigated the effects of the adaptive robot aid vs. imposed aid on performance and workload. Results showed that adaptive robot aid driven by an individualized workload model for physiological response resulted in greater improvements in performance compared to aid that was simply imposed by the system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Captive bottlenose dolphins and killer whales harbor a species-specific skin microbiota that varies among individuals.

    PubMed

    Chiarello, M; Villéger, S; Bouvier, C; Auguet, J C; Bouvier, T

    2017-11-10

    Marine animals surfaces host diverse microbial communities, which play major roles for host's health. Most inventories of marine animal surface microbiota have focused on corals and fishes, while cetaceans remain overlooked. The few studies focused on wild cetaceans, making difficult to distinguish intrinsic inter- and/or intraspecific variability in skin microbiota from environmental effects. We used high-throughput sequencing to assess the skin microbiota from 4 body zones of 8 bottlenose dolphins (Tursiops truncatus) and killer whales (Orcinus orca), housed in captivity (Marineland park, France). Overall, cetacean skin microbiota is more diverse than planktonic communities and is dominated by different phylogenetic lineages and functions. In addition, the two cetacean species host different skin microbiotas. Within each species, variability was higher between individuals than between body parts, suggesting a high individuality of cetacean skin microbiota. Overall, the skin microbiota of the assessed cetaceans related more to the humpback whale and fishes' than to microbiotas of terrestrial mammals.

  17. Ayurgenomics for stratified medicine: TRISUTRA consortium initiative across ethnically and geographically diverse Indian populations.

    PubMed

    Prasher, Bhavana; Varma, Binuja; Kumar, Arvind; Khuntia, Bharat Krushna; Pandey, Rajesh; Narang, Ankita; Tiwari, Pradeep; Kutum, Rintu; Guin, Debleena; Kukreti, Ritushree; Dash, Debasis; Mukerji, Mitali

    2017-02-02

    Genetic differences in the target proteins, metabolizing enzymes and transporters that contribute to inter-individual differences in drug response are not integrated in contemporary drug development programs. Ayurveda, that has propelled many drug discovery programs albeit for the search of new chemical entities incorporates inter-individual variability "Prakriti" in development and administration of drug in an individualized manner. Prakriti of an individual largely determines responsiveness to external environment including drugs as well as susceptibility to diseases. Prakriti has also been shown to have molecular and genomic correlates. We highlight how integration of Prakriti concepts can augment the efficiency of drug discovery and development programs through a unique initiative of Ayurgenomics TRISUTRA consortium. Five aspects that have been carried out are (1) analysis of variability in FDA approved pharmacogenomics genes/SNPs in exomes of 72 healthy individuals including predominant Prakriti types and matched controls from a North Indian Indo-European cohort (2) establishment of a consortium network and development of five genetically homogeneous cohorts from diverse ethnic and geo-climatic background (3) identification of parameters and development of uniform standard protocols for objective assessment of Prakriti types (4) development of protocols for Prakriti evaluation and its application in more than 7500 individuals in the five cohorts (5) Development of data and sample repository and integrative omics pipelines for identification of genomic correlates. Highlight of the study are (1) Exome sequencing revealed significant differences between Prakriti types in 28 SNPs of 11 FDA approved genes of pharmacogenomics relevance viz. CYP2C19, CYP2B6, ESR1, F2, PGR, HLA-B, HLA-DQA1, HLA-DRB1, LDLR, CFTR, CPS1. These variations are polymorphic in diverse Indian and world populations included in 1000 genomes project. (2) Based on the phenotypic attributes of Prakriti we identified anthropometry for anatomical features, biophysical parameters for skin types, HRV for autonomic function tests, spirometry for vital capacity and gustometry for taste thresholds as objective parameters. (3) Comparison of Prakriti phenotypes across different ethnic, age and gender groups led to identification of invariant features as well as some that require weighted considerations across the cohorts. Considering the molecular and genomics differences underlying Prakriti and relevance in disease pharmacogenomics studies, this novel integrative platform would help in identification of differently susceptible and drug responsive population. Additionally, integrated analysis of phenomic and genomic variations would not only allow identification of clinical and genomic markers of Prakriti for application in personalized medicine but also its integration in drug discovery and development programs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Biosocial correlates of inter-generational social mobility in a British cohort.

    PubMed

    Krzyżanowska, Monika; Mascie-Taylor, C G Nicholas

    2013-07-01

    The relationship between inter-generational social mobility of sons and daughters between 1958 and 1991 and biosocial variables, i.e. birth order, number of children in family, father's social class, region, educational attainment of child and father, educational and cognitive test scores (reading, mathematics, verbal and non-verbal IQ tests), was studied in a large British cohort study. The data used were collected as part of the British National Child Development Study (NCDS). The extent of social class mobility was determined inter-generationally and was categorized as none (no change in social class between the father's and index child's social class), upwardly mobile (where the index child moved up one or more social classes compared with their father) or downwardly mobile (where the index child moved down one or more social classes compared with their father). All of the biosocial variables were associated with social mobility when analysed separately. Multivariate analyses revealed that the most significant predictor of mobility categories in both sexes was education of the cohort member, followed by social class of the father. In both sexes mathematics score was a significant predicator, while in sons reading and non-verbal IQ scores were also important predictors. In the light of these results, it appears that social mobility in Britain takes place largely on meritocratic principles.

  19. Inter-rater Agreement of Clinicians' Treatment Recommendations Based on Modified Barium Swallow Study Reports.

    PubMed

    Slovarp, Laurie; Danielson, Jennifer; Liss, Julie

    2018-06-07

    The modified barium swallow study (MBSS) is a commonly used radiographic procedure for diagnosis and treatment of swallowing disorders. Despite attempts by dysphagia specialists to standardize the MBSS, most institutions have not adopted such standardized procedures. High variability of assessment patterns arguably contribute to variability of treatment recommendations made from diagnostic information derived from the MBSS report. An online survey was distributed to speech-language pathologists (SLPs) participating in American Speech Language Hearing Association (ASHA) listservs. Sixty-three SLPs who treat swallowing disorders participated. Participating SLPs reviewed two MBSS reports and chose physiologic treatment targets (e.g., tongue base retraction) based on each report. One report primarily contained symptomatology (e.g., aspiration, pharyngeal residue) with minimal information on impaired physiology (e.g., laryngeal incompetence, reduced hyolaryngeal elevation/excursion). In contrast, the second report contained a clear description of impaired physiology to explain the dysphagia symptoms. Fleiss kappa coefficients were used to analyze inter-rater agreement across the high and low physiology report types. Results revealed significantly higher inter-rater agreement across clinicians when reviewing reports with clear explanation(s) of physiologic impairment relative to reports that primarily focused on symptomatology. Clinicians also reported significantly greater satisfaction and treatment confidence following review of reports with clear description(s) of impaired physiology.

  20. Multi-tissue analyses reveal limited inter-annual and seasonal variation in mercury exposure in an Antarctic penguin community.

    PubMed

    Brasso, Rebecka L; Polito, Michael J; Emslie, Steven D

    2014-10-01

    Inter-annual variation in tissue mercury concentrations in birds can result from annual changes in the bioavailability of mercury or shifts in dietary composition and/or trophic level. We investigated potential annual variability in mercury dynamics in the Antarctic marine food web using Pygoscelis penguins as biomonitors. Eggshell membrane, chick down, and adult feathers were collected from three species of sympatrically breeding Pygoscelis penguins during the austral summers of 2006/2007-2010/2011. To evaluate the hypothesis that mercury concentrations in penguins exhibit significant inter-annual variation and to determine the potential source of such variation (dietary or environmental), we compared tissue mercury concentrations with trophic levels as indicated by δ(15)N values from all species and tissues. Overall, no inter-annual variation in mercury was observed in adult feathers suggesting that mercury exposure, on an annual scale, was consistent for Pygoscelis penguins. However, when examining tissues that reflected more discrete time periods (chick down and eggshell membrane) relative to adult feathers, we found some evidence of inter-annual variation in mercury exposure during penguins' pre-breeding and chick rearing periods. Evidence of inter-annual variation in penguin trophic level was also limited suggesting that foraging ecology and environmental factors related to the bioavailability of mercury may provide more explanatory power for mercury exposure compared to trophic level alone. Even so, the variable strength of relationships observed between trophic level and tissue mercury concentrations across and within Pygoscelis penguin species suggest that caution is required when selecting appropriate species and tissue combinations for environmental biomonitoring studies in Antarctica.

  1. Effects of modified Pilates on variability of inter-joint coordination during walking in the elderly

    PubMed Central

    Roh, SuYeon; Yoon, Sukhoon; Kim, Joo Nyeon; Lim, Hee Sung

    2016-01-01

    [Purpose] This study aimed to examine the effects of an 8-week modified Pilates program on the variability of inter-joint coordination in the elderly during walking. [Subjects and Methods] Twenty elderly participants with no recent history of orthopedic abnormalities (age, 67.9 ± 2.7 years; height, 163.7 ± 8.9 cm; weight, 67.1 ± 11.6 kg) were recruited for this study and randomly allocated to a modified Pilates exercise group or a control group. Three-dimensional motion analysis was performed on both groups to evaluate the effects of the Pilates exercise. [Results] There was no significant difference in the joint variability of the ankle, knee, and hip joints between the groups, both before training and after training. However, there was a significant increase in the hip-knee deviation phase value in the exercise group after the program was completed, and this increase was also significant when compared with that in the control group. [Conclusion] This study has demonstrated that an 8-week modified Pilates exercise program can have a positive impact on the gait of elderly participants, potentially by enhancing neuromuscular adjustment, which may have positive implications for reducing their fall risk. PMID:28174474

  2. Seasonal variation in pans in relation to limno-chemistry, size, hydroperiod, and river connectivity in a semi-arid subtropical region

    NASA Astrophysics Data System (ADS)

    Nhiwatiwa, Tamuka; Dalu, Tatenda

    2017-02-01

    Seasonal pans are hydrologically dynamic, with significant changes in water volume and depth in response to high evaporation, infiltration rates and inundation events. Intra-seasonal and inter-seasonal changes in endorheic and floodplain pans in relation to limnology, size, hydroperiod, and river connectivity were studied over two rainfall seasons across 36 pans at the Save Valley Conservancy. In the study region, floodplain pans were identified as pans that had connectivity with the Save River, while the endorheic pans (large and small) were hydrologically isolated basins. Seasonal trends for physico-chemical variables were initial low and gradual increased for both rainfall seasons. Significant inter-seasonal differences for several physico-chemical variables were observed. No significant differences in physico-chemical variables were observed between large and small endorheic pans, with the except for vegetation cover, which was higher in large pans. Floodplain pans differed from the endorheic systems in pH, conductivity, nutrients and suspended solids. Connectivity was found to be insignificant, as connections between these systems were probably too infrequent. Seasonal pans were uniquely distinguished by their morphometric, physico-chemical and hydrological characteristics. Inevitably, they are vulnerable to climate change with the extent of their resilience currently unknown.

  3. Validation of a digital audio recording method for the objective assessment of cough in the horse.

    PubMed

    Duz, M; Whittaker, A G; Love, S; Parkin, T D H; Hughes, K J

    2010-10-01

    To validate the use of digital audio recording and analysis for quantification of coughing in horses. Part A: Nine simultaneous digital audio and video recordings were collected individually from seven stabled horses over a 1 h period using a digital audio recorder attached to the halter. Audio files were analysed using audio analysis software. Video and audio recordings were analysed for cough count and timing by two blinded operators on two occasions using a randomised study design for determination of intra-operator and inter-operator agreement. Part B: Seventy-eight hours of audio recordings obtained from nine horses were analysed once by two blinded operators to assess inter-operator repeatability on a larger sample. Part A: There was complete agreement between audio and video analyses and inter- and intra-operator analyses. Part B: There was >97% agreement between operators on number and timing of 727 coughs recorded over 78 h. The results of this study suggest that the cough monitor methodology used has excellent sensitivity and specificity for the objective assessment of cough in horses and intra- and inter-operator variability of recorded coughs is minimal. Crown Copyright 2010. Published by Elsevier India Pvt Ltd. All rights reserved.

  4. The use of a brief mental health screener to enhance the ability of police officers to identify persons with serious mental disorders.

    PubMed

    Hoffman, Ron; Hirdes, John; Brown, Gregory P; Dubin, Joel A; Barbaree, Howard

    2016-01-01

    Police agencies in Canada and elsewhere have received much criticism over how they respond to persons with serious mental disorders. The adequacy of training provided to police officers on mental health issues and in particular on recognizing indicators of serious mental disorders has been a major concern. This paper describes the process that led to the development of a new brief mental health screener (interRAI Brief Mental Health Screener, BMHS) designed to assist police officers to better identify persons with serious mental disorders. The interRAI BMHS was developed in collaboration with interRAI, an international, not-for-profit consortium of researchers. The government of Ontario had previously partnered with interRAI to develop and implement the Resident Assessment Instrument for Mental Health (RAI-MH), the assessment system mandated for use on all persons admitted into inpatient psychiatric care in the province. Core items on the interRAI BMHS were obtained through analysis (N=41,019) of RAI-MH data together with input from representatives from health care, police services, and patient groups. Two police services in southwestern Ontario completed forms (N=235) on persons thought to have a mental disorder. Patient records were later accessed to determine patient disposition. The use of summary and inferential statistics revealed that the variables significantly associated with being taken to hospital by police included performing a self-injurious act in the past 30days, and others being concerned over the person's risk for self-injury. Variables significantly associated with being admitted included abnormal thought process, delusions, and hallucinations. The results of the study indicate that the 14-variable algorithm used to construct the interRAI BMHS is a good predictor of who was most likely to be taken to hospital by police officers and who was most likely to be admitted. The instrument is an effective means of capturing and standardizing police officer observations enabling them to provide more and better quality information to emergency department (ED) staff. Teaching police officers to use the form constitutes enhanced training on major indicators of serious mental disorders. Further, given that items on the interRAI BMHS are written in the language of the health system, language acts as common currency between police officers and ED staff laying the foundation for a more collaborative approach between the systems. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Tobacco smoking and depression: time to move on to a new research paradigm in medicine?

    PubMed

    de Jonge, Peter; Bos, Elisabeth Henriette

    2013-05-24

    A recent paper published in BMC Cardiovascular Disorders reported on a study into whether tobacco smoking may serve as a risk factor for depression in patients with heart disease. In the current paper, we discuss several limitations of that study, of which many apply not just to the study itself but to the nomothetic research design that was used. Particularly when bidirectionality between variables is expected, fluctuation in variables over time takes place, and/or inter-individual differences are considerable, a nomothetic research approach does not seem appropriate, and may lead to false conclusions. As an alternative, we describe an idiographic approach in which individuals are followed up over time using many repeated measurements, and from which individual models are estimated. Such intensive time-series studies are not common in medicine, but are well described in the fields of econometrics and meteorology. Combining idiographic research designs with more traditional nomothetic designs may lead to research findings that are not only useful for society but also valid in individuals. See related research article here http://www.biomedcentral.com/1471-2261/13/35.

  6. Tobacco smoking and depression: time to move on to a new research paradigm in medicine?

    PubMed Central

    2013-01-01

    A recent paper published in BMC Cardiovascular Disorders reported on a study into whether tobacco smoking may serve as a risk factor for depression in patients with heart disease. In the current paper, we discuss several limitations of that study, of which many apply not just to the study itself but to the nomothetic research design that was used. Particularly when bidirectionality between variables is expected, fluctuation in variables over time takes place, and/or inter-individual differences are considerable, a nomothetic research approach does not seem appropriate, and may lead to false conclusions. As an alternative, we describe an idiographic approach in which individuals are followed up over time using many repeated measurements, and from which individual models are estimated. Such intensive time-series studies are not common in medicine, but are well described in the fields of econometrics and meteorology. Combining idiographic research designs with more traditional nomothetic designs may lead to research findings that are not only useful for society but also valid in individuals. See related research article here http://www.biomedcentral.com/1471-2261/13/35. PMID:23705867

  7. Spatial-frequency variability of the eddy kinetic energy in the South Atlantic Ocean

    NASA Astrophysics Data System (ADS)

    Cecilio, C. M.; Gherardi, D. F.; Souza, R.; Correa-Ramirez, M.

    2013-05-01

    In the South Atlantic Ocean (SAO) part of the inter-oceanic flow is accomplished through the issuance of anticyclonic eddies by the Agulhas Retroflection. This region, known as Agulhas Leakage (AL), is responsible by the intermittent shedding of eddies in the SAO. The propagation of these eddies into the SAO induces wave processes that allows the interaction between modes of variability of different basins, ranging from high to low frequency. Modelling studies suggests that the Indian-Atlantic inter-ocean exchange is strongly related to the structure of the wind field, in particular with the position of the maximum Southern Hemisphere westerly winds. This study aims to investigate the variations of the large-scale and regional mesoscale eddy field over the SAO using a frequency domain technique, Multiple Taper Method with Singular Value Decomposition (MTM-SVD). The MTM-SVD approach is applied to examine the individual and joint spatiotemporal variability modes of eddy kinetic energy (EKE) and winds stress. The EKE is estimated from geostrophic velocity anomalies data distributed by Aviso and winds stress from winds dataset of Cross-Calibrated Multi-Platform (CCMP) project from PO.DAAC. The impact of the AL in the SAO, was assessed first for the entire region and subsequently applied in the regions of higher mesoscale activity, which are the Brazil-Malvinas Confluence (BMC), the AL, and the Brazilian Current (BC) region. The results of local fractional variance (LFV) of EKE obtained by the MTM-SVD method show a strong significant annual variability in SAO and BC region while in BMC and in AL this frequency is weaker. In the most energetic mesoscale activity regions (BMC and AL) the pattern of variability is distinct. In the BMC region the interannual variability is dominated while in the AL region the most part of variability is associated by high frequency. The joint LFV spectrum of wind and EKE show an out-of-phase relationship between the AL region and BMC region in the interannual frequencies (3 to 5 years). The dominant frequencies can be seen in 1,5 to 3 years period band and in the intrasazonal frequencies, 0,3 to 0,5 years. The results suggests that the EKE variability patterns are different in the SAO wich might be related to the influence of eddies from AL.

  8. Plasma and Urinary Phenolic Profiles after Acute and Repetitive Intake of Wild Blueberry.

    PubMed

    Feliciano, Rodrigo P; Istas, Geoffrey; Heiss, Christian; Rodriguez-Mateos, Ana

    2016-08-25

    Recent studies have shown that blueberries may have cardiovascular and cognitive health benefits. In this work, we investigated the profile of plasma and urine (poly)phenol metabolites after acute and daily consumption of wild blueberries for 30 days in 18 healthy men. The inter-individual variability in plasma and urinary polyphenol levels was also investigated. Blood samples were collected at baseline and 2 h post-consumption on day 1 and day 30. Twenty-four-hour urine was also collected on both days. A total of 61 phenolic metabolites were quantified in plasma at baseline, of which 43 increased after acute or chronic consumption of blueberries over one month. Benzoic and catechol derivatives represented more than 80% of the changes in phenolic profile after 2 h consumption on day 1, whereas hippuric and benzoic derivatives were the major compounds that increased at 0 and 2 h on day 30, respectively. The total (poly)phenol urinary excretion remained unchanged after 30 days of wild blueberry intake. The inter-individual variability ranged between 40%-48% in plasma and 47%-54% in urine. Taken together, our results illustrate that blueberry (poly)phenols are absorbed and extensively metabolized by phase II enzymes and by the gut microbiota, leading to a whole array of metabolites that may be responsible for the beneficial effects observed after blueberry consumption.

  9. Polymorphisms in genes involved in fatty acid β-oxidation interact with dietary fat intakes to modulate the plasma TG response to a fish oil supplementation.

    PubMed

    Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

    2014-03-18

    A large inter-individual variability in the plasma triglyceride (TG) response to an omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs) within genes involved in fatty acid β-oxidation and dietary fat intakes. Two hundred and eight (208) participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9-2.2 g EPA and 1.1 g DHA). Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187) and ACOX1 (rs17583163) genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid β-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation.

  10. Confirmation of model-based dose selection for a Japanese phase III study of rivaroxaban in non-valvular atrial fibrillation patients.

    PubMed

    Kaneko, Masato; Tanigawa, Takahiko; Hashizume, Kensei; Kajikawa, Mariko; Tajiri, Masahiro; Mueck, Wolfgang

    2013-01-01

    This study was designed to confirm the appropriateness of the dose setting for a Japanese phase III study of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), which had been based on model simulation employing phase II study data. The previously developed mixed-effects pharmacokinetic/pharmacodynamic (PK-PD) model, which consisted of an oral one-compartment model parameterized in terms of clearance, volume and a first-order absorption rate, was rebuilt and optimized using the data for 597 subjects from the Japanese phase III study, J-ROCKET AF. A mixed-effects modeling technique in NONMEM was used to quantify both unexplained inter-individual variability and inter-occasion variability, which are random effect parameters. The final PK and PK-PD models were evaluated to identify influential covariates. The empirical Bayes estimates of AUC and C(max) from the final PK model were consistent with the simulated results from the Japanese phase II study. There was no clear relationship between individual estimated exposures and safety-related events, and the estimated exposure levels were consistent with the global phase III data. Therefore, it was concluded that the dose selected for the phase III study with Japanese NVAF patients by means of model simulation employing phase II study data had been appropriate from the PK-PD perspective.

  11. Measurement of thermally ablated lesions in sonoelastographic images using level set methods

    NASA Astrophysics Data System (ADS)

    Castaneda, Benjamin; Tamez-Pena, Jose Gerardo; Zhang, Man; Hoyt, Kenneth; Bylund, Kevin; Christensen, Jared; Saad, Wael; Strang, John; Rubens, Deborah J.; Parker, Kevin J.

    2008-03-01

    The capability of sonoelastography to detect lesions based on elasticity contrast can be applied to monitor the creation of thermally ablated lesion. Currently, segmentation of lesions depicted in sonoelastographic images is performed manually which can be a time consuming process and prone to significant intra- and inter-observer variability. This work presents a semi-automated segmentation algorithm for sonoelastographic data. The user starts by planting a seed in the perceived center of the lesion. Fast marching methods use this information to create an initial estimate of the lesion. Subsequently, level set methods refine its final shape by attaching the segmented contour to edges in the image while maintaining smoothness. The algorithm is applied to in vivo sonoelastographic images from twenty five thermal ablated lesions created in porcine livers. The estimated area is compared to results from manual segmentation and gross pathology images. Results show that the algorithm outperforms manual segmentation in accuracy, inter- and intra-observer variability. The processing time per image is significantly reduced.

  12. Cortical activation and inter-hemispheric sensorimotor coherence in individuals with arm dystonia due to childhood stroke

    PubMed Central

    Kukke, Sahana N.; de Campos, Ana Carolina; Damiano, Diane; Alter, Katharine E.; Patronas, Nicholas; Hallett, Mark

    2014-01-01

    Objective Dystonia is a disabling motor disorder often without effective therapies. To better understand the genesis of dystonia after childhood stroke, we analyzed electroencephalographic (EEG) recordings in this population. Methods Resting spectral power of EEG signals over bilateral sensorimotor cortices (Powrest), resting inter-hemispheric sensorimotor coherence (Cohrest), and task-related changes in power (TRPow) and coherence (TRCoh) during wrist extension were analyzed in individuals with dystonia (age 20±3 years) and healthy volunteers (age 17±5 years). Results Ipsilesional TRPow decrease was significantly lower in patients than controls during the more affected wrist task. Force deficits of the affected wrist correlated with reduced alpha TRPow decrease on the ipsilesional and not the contralesional hemisphere. Cohrest was significantly lower in patients than controls, and correlated with more severe dystonia and poorer hand function. Powrest and TRCoh were similar between groups. Conclusions The association between weakness and cortical activation during wrist extension highlights the importance of ipsilesional sensorimotor activation on function. Reduction of Cohrest in patients reflects a loss of inter-hemispheric connectivity that may result from structural changes and neuroplasticity, potentially contributing to the development of dystonia. Significance Cortical and motor dysfunction are correlated in patients with childhood stroke and may in part explain the genesis of dystonia. PMID:25499610

  13. Quality by design: optimization of a freeze-drying cycle via design space in case of heterogeneous drying behavior and influence of the freezing protocol.

    PubMed

    Pisano, Roberto; Fissore, Davide; Barresi, Antonello A; Brayard, Philippe; Chouvenc, Pierre; Woinet, Bertrand

    2013-02-01

    This paper shows how to optimize the primary drying phase, for both product quality and drying time, of a parenteral formulation via design space. A non-steady state model, parameterized with experimentally determined heat and mass transfer coefficients, is used to define the design space when the heat transfer coefficient varies with the position of the vial in the array. The calculations recognize both equipment and product constraints, and also take into account model parameter uncertainty. Examples are given of cycles designed for the same formulation, but varying the freezing conditions and the freeze-dryer scale. These are then compared in terms of drying time. Furthermore, the impact of inter-vial variability on design space, and therefore on the optimized cycle, is addressed. With this regard, a simplified method is presented for the cycle design, which reduces the experimental effort required for the system qualification. The use of mathematical modeling is demonstrated to be very effective not only for cycle development, but also for solving problem of process transfer. This study showed that inter-vial variability remains significant when vials are loaded on plastic trays, and how inter-vial variability can be taken into account during process design.

  14. Towards a new standardized method for circulating miRNAs profiling in clinical studies: Interest of the exogenous normalization to improve miRNA signature accuracy.

    PubMed

    Vigneron, Nicolas; Meryet-Figuière, Matthieu; Guttin, Audrey; Issartel, Jean-Paul; Lambert, Bernard; Briand, Mélanie; Louis, Marie-Hélène; Vernon, Mégane; Lebailly, Pierre; Lecluse, Yannick; Joly, Florence; Krieger, Sophie; Lheureux, Stéphanie; Clarisse, Bénédicte; Leconte, Alexandra; Gauduchon, Pascal; Poulain, Laurent; Denoyelle, Christophe

    2016-08-01

    Circulating miRNAs are promising biomarkers in oncology but have not yet been implemented in the clinic given the lack of concordance across studies. In order to increase the cross-studies reliability, we attempted to reduce and to control the circulating miRNA expression variability between patients. First, to maximize profiling signals and to reduce miRNA expression variability, three isolation kits were compared and the NucleoSpin(®) kit provided higher miRNA concentrations than the other widely used kits. Second, to control inter-sample variability during the profiling step, the exogenous miRNAs normalization method commonly used for RT-qPCR validation step was adapted to microarray experiments. Importantly, exogenous miRNAs presented two-fold lower inter-sample variability than the widely used endogenous miR-16-5p reflecting that the latter is subject to both biological and technical variability. Although Caenorhabditis elegans miRNAs isolation yields were heterogeneous, they correlated to each other and to their geometrical mean across samples. The normalization based on the geometrical mean of three exogenous miRNAs increased the correlation up-to 0.97 between the microarrays and individual RT-qPCR steps of circulating miRNAs expression. Overall, this new strategy open new avenue to identify reliable circulating miRNA signatures for translation into clinical practice. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Does bisphenol A induce superfeminization in Marisa cornuarietis? Part I: intra- and inter-laboratory variability in test endpoints.

    PubMed

    Forbes, Valery E; Selck, Henriette; Palmqvist, Annemette; Aufderheide, John; Warbritton, Ryan; Pounds, Nadine; Thompson, Roy; van der Hoeven, Nelly; Caspers, Norbert

    2007-03-01

    It has been claimed that bisphenol A (BPA) induces superfeminization in the freshwater gastropod, Marisa cornuarietis. To explore the reproducibility of prior work, here we present results from a three-laboratory study, the objectives of which were to determine the mean and variability in test endpoints (i.e., adult fecundity, egg hatchability, and juvenile growth) under baseline conditions and to identify the sources of variability. A major source of variability for all of the measured endpoints was due to differences within and among individuals. With few exceptions, variability among laboratories and among replicate tanks within laboratories contributed little to the observed variability in endpoints. The results highlight the importance of obtaining basic knowledge of husbandry requirements and baseline information on life-history traits of potential test species prior to designing toxicity test protocols. Understanding of the levels and sources of endpoint variability is essential so that statistically robust and ecologically relevant tests of chemicals can be conducted.

  16. Contribution of three CYP3A isoforms to metabolism of R- and S-warfarin.

    PubMed

    Jones, Drew R; Kim, So-Young; Boysen, Gunnar; Yun, Chul-Ho; Miller, Grover P

    2010-12-01

    Effective coumadin (R/S-warfarin) therapy is complicated by inter-individual variability in metabolism. Recent studies have demonstrated that CYP3A isoforms likely contribute to patient responses and clinical outcomes. Despite a significant focus on CYP3A4, little is known about CYP3A5 and CYP3A7 metabolism of warfarin. Based on our studies, recombinant CYP3A4, CYP3A5 and CYP3A7 metabolized R- and S-warfarin to 10- and 4'-hydroxywarfarin with efficiencies that depended on the individual enzymes. For R-warfarin, CYP3A4, CYP3A7, and CYP3A5 demonstrated decreasing preference for 10-hydroxylation over 4'-hydroxylation. By contrast, there was no regioselectivity toward S-warfarin. While all enzymes preferentially metabolized R-warfarin, CYP3A4 was the most efficient at metabolizing all reactions. Individuals, namely African-Americans and children, with higher relative levels of CYP3A5 and/or CYP3A7, respectively, compared to CYP3A4 may metabolize warfarin less efficiently and thus may require lower doses and be at risk for adverse drug-drug interactions related to the contributions of the respective enzymes.

  17. Factors determining the average body size of geographically separated Arctodiaptomus salinus (Daday, 1885) populations.

    PubMed

    Anufriieva, Elena V; Shadrin, Nickolai V

    2014-03-01

    Arctodiaptomus salinus inhabits water bodies across Eurasia and North Africa. Based on our own data and that from the literature, we analyzed the influences of several factors on the intra- and inter-population variability of this species. A strong negative linear correlation between temperature and average body size in the Crimean and African populations was found, in which the parameters might be influenced by salinity. Meanwhile, a significant negative correlation between female body size and the altitude of habitats was found by comparing body size in populations from different regions. Individuals from environments with highly varying abiotic parameters, e.g. temporary reservoirs, had a larger body size than individuals from permanent water bodies. The changes in average body mass in populations were at 11.4 times, whereas, those in individual metabolic activities were at 6.2 times. Moreover, two size groups of A. salinus in the Crimean and the Siberian lakes were observed. The ratio of female length to male length fluctuated between 1.02 and 1.30. The average size of A. salinus in populations and its variations were determined by both genetic and environmental factors. However, the parities of these factors were unequal in either spatial or temporal scales.

  18. Creatinine as a normalization factor to estimate the representativeness of urine sample - Intra-subject and inter-subject variability studies.

    PubMed

    Sawant, Pramilla D; Kumar, Suja Arun; Wankhede, Sonal; Rao, D D

    2018-06-01

    In-vitro bioassay monitoring generally involves analysis of overnight urine samples (~12 h) collected from radiation workers to estimate the excretion rate of radionuclides from the body. The unknown duration of sample collection (10-16 h) adds to the overall uncertainty in computation of internal dose. In order to minimize this, IAEA recommends measurement of specific gravity or creatinine excretion rate in urine. Creatinine is excreted at a steady rate with normally functioning kidneys therefore, can be used as a normalization factor to infer the duration of collection and/or dilution of the sample, if any. The present study reports the chemical procedure standardized and its application for the estimation of creatinine as well as creatinine co-efficient in normal healthy individuals. Observations indicate higher inter-subject variability and lower constancy in daily excretion of creatinine for the same subject. Thus creatinine excretion rate may not be a useful indicator for extrapolating to 24 h sample collection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Individual laboratory-measured discount rates predict field behavior

    PubMed Central

    Chabris, Christopher F.; Laibson, David; Morris, Carrie L.; Schuldt, Jonathon P.; Taubinsky, Dmitry

    2009-01-01

    We estimate discount rates of 555 subjects using a laboratory task and find that these individual discount rates predict inter-individual variation in field behaviors (e.g., exercise, BMI, smoking). The correlation between the discount rate and each field behavior is small: none exceeds 0.28 and many are near 0. However, the discount rate has at least as much predictive power as any variable in our dataset (e.g., sex, age, education). The correlation between the discount rate and field behavior rises when field behaviors are aggregated: these correlations range from 0.09-0.38. We present a model that explains why specific intertemporal choice behaviors are only weakly correlated with discount rates, even though discount rates robustly predict aggregates of intertemporal decisions. PMID:19412359

  20. Individual laboratory-measured discount rates predict field behavior.

    PubMed

    Chabris, Christopher F; Laibson, David; Morris, Carrie L; Schuldt, Jonathon P; Taubinsky, Dmitry

    2008-12-01

    We estimate discount rates of 555 subjects using a laboratory task and find that these individual discount rates predict inter-individual variation in field behaviors (e.g., exercise, BMI, smoking). The correlation between the discount rate and each field behavior is small: none exceeds 0.28 and many are near 0. However, the discount rate has at least as much predictive power as any variable in our dataset (e.g., sex, age, education). The correlation between the discount rate and field behavior rises when field behaviors are aggregated: these correlations range from 0.09-0.38. We present a model that explains why specific intertemporal choice behaviors are only weakly correlated with discount rates, even though discount rates robustly predict aggregates of intertemporal decisions.

  1. The InterLACE study: Design, data harmonization and characteristics across 20 studies on women's health.

    PubMed

    Mishra, Gita D; Chung, Hsin-Fang; Pandeya, Nirmala; Dobson, Annette J; Jones, Lee; Avis, Nancy E; Crawford, Sybil L; Gold, Ellen B; Brown, Daniel; Sievert, Lynette L; Brunner, Eric; Cade, Janet E; Burley, Victoria J; Greenwood, Darren C; Giles, Graham G; Bruinsma, Fiona; Goodman, Alissa; Hayashi, Kunihiko; Lee, Jung Su; Mizunuma, Hideki; Kuh, Diana; Cooper, Rachel; Hardy, Rebecca; Obermeyer, Carla Makhlouf; Lee, Kathryn A; Simonsen, Mette Kildevæld; Yoshizawa, Toyoko; Woods, Nancy F; Mitchell, Ellen S; Hamer, Mark; Demakakos, Panayotes; Sandin, Sven; Adami, Hans-Olov; Weiderpass, Elisabete; Anderson, Debra

    2016-10-01

    The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE. InterLACE is an individual-level pooled study of 20 observational studies (12 of which are longitudinal) from ten countries. Variables were harmonized across studies to create a new and systematic synthesis of life-course data. Harmonized data were derived in three domains: 1) socio-demographic and lifestyle factors, 2) female reproductive characteristics, and 3) chronic disease outcomes (cardiovascular disease (CVD) and diabetes). InterLACE pooled data from 229,054 mid-aged women. Overall, 76% of the women were Caucasian and 22% Japanese; other ethnicities (of 300 or more participants) included Hispanic/Latin American (0.2%), Chinese (0.2%), Middle Eastern (0.3%), African/black (0.5%), and Other (1.0%). The median age at baseline was 47 years (Inter-quartile range (IQR): 41-53), and that at the last follow-up was 56 years (IQR: 48-64). Regarding reproductive characteristics, half of the women (49.8%) had their first menstruation (menarche) at 12-13 years of age. The distribution of menopausal status and the prevalence of chronic disease varied considerably among studies. At baseline, most women (57%) were pre- or peri-menopausal, 20% reported a natural menopause (range 0.8-55.6%) and the remainder had surgery or were taking hormones. By the end of follow-up, the prevalence rates of CVD and diabetes were 7.2% (range 0.9-24.6%) and 5.1% (range 1.3-13.2%), respectively. The scale and heterogeneity of InterLACE data provide an opportunity to strengthen evidence concerning the relationships between reproductive health through life and subsequent risks of chronic disease, including cross-cultural comparisons. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Effects of inter- and intra-observer variability on echocardiographic measurements in awake cats.

    PubMed

    Chetboul, V; Concordet, D; Pouchelon, J L; Athanassiadis, N; Muller, C; Benigni, L; Munari, A C; Lefebvre, H P

    2003-08-01

    The objective of this study was to determine intra- and inter-observer variability of echocardiographic measurements in awake cats. Four observers with different levels of experience in echocardiography performed 96 echocardiographic examinations in four cats on four different days over a 3-week period. The examinations were randomized and blinded. The maximum within-day and between-day CV values were 17.4 and 18.5% for inter-ventricular septal thickness in diastole, 18.7 and 22.6% for left ventricular free-wall thickness in diastole, 9.8 and 14.9% for left ventricular end-diastolic diameter, 20.8 and 15.2% for left ventricular end-systolic diameter, and 21.2 and 18.4% for left ventricular shortening fraction. The maximum within-day CV values were most often associated with the least competent observer (i.e. the graduate student) and, the minimum CV values with the most competent observer (i.e. the associate professor in cardiology). A significant interaction between cat and observer was also evidenced. Thus, the most competent observer could not be replaced by any of the other observers.

  3. Spatial variability of metals in the inter-tidal sediments of the Medway Estuary, Kent, UK.

    PubMed

    Spencer, Kate L

    2002-09-01

    Concentrations of major and trace metals were determined in eight sediment cores collected from the inter-tidal zone of the Medway Estuary, Kent, UK. Metal associations and potential sources have been investigated using principal component analysis. These data provide the first detailed geochemical survey of recent sediments in the Medway Estuary. Metal concentrations in surface sediments lie in the mid to lower range for UK estuarine sediments indicating that the Medway receives low but appreciable contaminant inputs. Vertical metal distributions reveal variable redox zonation across the estuary and historically elevated anthropogenic inputs. Peak concentrations of Cu, Pb and Zn can be traced laterally across the estuary and their positions indicate periods of past erosion and/or non-deposition. However, low rates of sediment accumulation do not allow these sub surface maxima to be used as accurate geochemical marker horizons. The salt marshes and inter-tidal mud flats in the Medway Estuary are experiencing erosion, however the erosion of historically contaminated sediments is unlikely to re-release significant amounts of heavy metals to the estuarine system.

  4. Trend Extraction in Functional Data of Amplitudes of R and T Waves in Exercise Electrocardiogram

    NASA Astrophysics Data System (ADS)

    Cammarota, Camillo; Curione, Mario

    The amplitudes of R and T waves of the electrocardiogram (ECG) recorded during the exercise test show both large inter- and intra-individual variability in response to stress. We analyze a dataset of 65 normal subjects undergoing ambulatory test. We model the dataset of R and T series in the framework of functional data, assuming that the individual series are realizations of a non-stationary process, centered at the population trend. We test the time variability of this trend computing a simultaneous confidence band and the zero crossing of its derivative. The analysis shows that the amplitudes of the R and T waves have opposite responses to stress, consisting respectively in a bump and a dip at the early recovery stage. Our findings support the existence of a relationship between R and T wave amplitudes and respectively diastolic and systolic ventricular volumes.

  5. Relative importance of precipitation frequency and intensity in inter-annual variation of precipitation in Singapore during 1980-2013

    NASA Astrophysics Data System (ADS)

    Li, Xin; Babovic, Vladan

    2017-04-01

    Observed studies on inter-annual variation of precipitation provide insight into the response of precipitation to anthropogenic climate change and natural climate variability. Inter-annual variation of precipitation results from the concurrent variations of precipitation frequency and intensity, understanding of the relative importance of frequency and intensity in the variability of precipitation can help fathom its changing properties. Investigation of the long-term changes of precipitation schemes has been extensively carried out in many regions across the world, however, detailed studies of the relative importance of precipitation frequency and intensity in inter-annual variation of precipitation are still limited, especially in the tropics. Therefore, this study presents a comprehensive framework to investigate the inter-annual variation of precipitation and the dominance of precipitation frequency and intensity in a tropical urban city-state, Singapore, based on long-term (1980-2013) daily precipitation series from 22 rain gauges. First, an iterative Mann-Kendall trend test method is applied to detect long-term trends in precipitation total, frequency and intensity at both annual and seasonal time scales. Then, the relative importance of precipitation frequency and intensity in inducing the inter-annual variation of wet-day precipitation total is analyzed using a dominance analysis method based on linear regression. The results show statistically significant upward trends in wet-day precipitation total, frequency and intensity at annual time scale, however, these trends are not evident during the monsoon seasons. The inter-annual variation of wet-day precipitation is mainly dominated by precipitation intensity for most of the stations at annual time scale and during the Northeast monsoon season. However, during the Southwest monsoon season, the inter-annual variation of wet-day precipitation is mainly dominated by precipitation frequency. These results have implications for water resources management practices in Singapore.

  6. Comparison of total energy expenditure assessed by two devices in controlled and free-living conditions.

    PubMed

    Rousset, Sylvie; Fardet, Anthony; Lacomme, Philippe; Normand, Sylvie; Montaurier, Christophe; Boirie, Yves; Morio, Béatrice

    2015-01-01

    The objective of this study was to evaluate the validity of total energy expenditure (TEE) provided by Actiheart and Armband. Normal-weight adult volunteers wore both devices either for 17 hours in a calorimetric chamber (CC, n = 49) or for 10 days in free-living conditions (FLC) outside the laboratory (n = 41). The two devices and indirect calorimetry or doubly labelled water, respectively, were used to estimate TEE in the CC group and FLC group. In the CC, the relative value of TEE error was not significant (p > 0.05) for Actiheart but significantly different from zero for Armband, showing TEE underestimation (-4.9%, p < 0.0001). However, the mean absolute values of errors were significantly different between Actiheart and Armband: 8.6% and 6.7%, respectively (p = 0.05). Armband was more accurate for estimating TEE during sleeping, rest, recovery periods and sitting-standing. Actiheart provided better estimation during step and walking. In FLC, no significant error in relative value was detected. Nevertheless, Armband produced smaller errors in absolute value than Actiheart (8.6% vs. 12.8%). The distributions of differences were more scattered around the means, suggesting a higher inter-individual variability in TEE estimated by Actiheart than by Armband. Our results show that both monitors are appropriate for estimating TEE. Armband is more effective than Actiheart at the individual level for daily light-intensity activities.

  7. Atlas based brain volumetry: How to distinguish regional volume changes due to biological or physiological effects from inherent noise of the methodology.

    PubMed

    Opfer, Roland; Suppa, Per; Kepp, Timo; Spies, Lothar; Schippling, Sven; Huppertz, Hans-Jürgen

    2016-05-01

    Fully-automated regional brain volumetry based on structural magnetic resonance imaging (MRI) plays an important role in quantitative neuroimaging. In clinical trials as well as in clinical routine multiple MRIs of individual patients at different time points need to be assessed longitudinally. Measures of inter- and intrascanner variability are crucial to understand the intrinsic variability of the method and to distinguish volume changes due to biological or physiological effects from inherent noise of the methodology. To measure regional brain volumes an atlas based volumetry (ABV) approach was deployed using a highly elastic registration framework and an anatomical atlas in a well-defined template space. We assessed inter- and intrascanner variability of the method in 51 cognitively normal subjects and 27 Alzheimer dementia (AD) patients from the Alzheimer's Disease Neuroimaging Initiative by studying volumetric results of repeated scans for 17 compartments and brain regions. Median percentage volume differences of scan-rescans from the same scanner ranged from 0.24% (whole brain parenchyma in healthy subjects) to 1.73% (occipital lobe white matter in AD), with generally higher differences in AD patients as compared to normal subjects (e.g., 1.01% vs. 0.78% for the hippocampus). Minimum percentage volume differences detectable with an error probability of 5% were in the one-digit percentage range for almost all structures investigated, with most of them being below 5%. Intrascanner variability was independent of magnetic field strength. The median interscanner variability was up to ten times higher than the intrascanner variability. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Variation in Foot Strike Patterns among Habitually Barefoot and Shod Runners in Kenya.

    PubMed

    Lieberman, Daniel E; Castillo, Eric R; Otarola-Castillo, Erik; Sang, Meshack K; Sigei, Timothy K; Ojiambo, Robert; Okutoyi, Paul; Pitsiladis, Yannis

    2015-01-01

    Runners are often categorized as forefoot, midfoot or rearfoot strikers, but how much and why do individuals vary in foot strike patterns when running on level terrain? This study used general linear mixed-effects models to explore both intra- and inter-individual variations in foot strike pattern among 48 Kalenjin-speaking participants from Kenya who varied in age, sex, body mass, height, running history, and habitual use of footwear. High speed video was used to measure lower extremity kinematics at ground contact in the sagittal plane while participants ran down 13 meter-long tracks with three variables independently controlled: speed, track stiffness, and step frequency. 72% of the habitually barefoot and 32% of the habitually shod participants used multiple strike types, with significantly higher levels of foot strike variation among individuals who ran less frequently and who used lower step frequencies. There was no effect of sex, age, height or weight on foot strike angle, but individuals were more likely to midfoot or forefoot strike when they ran on a stiff surface, had a high preferred stride frequency, were habitually barefoot, and had more experience running. It is hypothesized that strike type variation during running, including a more frequent use of forefoot and midfoot strikes, used to be greater before the introduction of cushioned shoes and paved surfaces.

  9. Lack of Support for the Association between Facial Shape and Aggression: A Reappraisal Based on a Worldwide Population Genetics Perspective

    PubMed Central

    Gómez-Valdés, Jorge; Hünemeier, Tábita; Quinto-Sánchez, Mirsha; Paschetta, Carolina; de Azevedo, Soledad; González, Marina F.; Martínez-Abadías, Neus; Esparza, Mireia; Pucciarelli, Héctor M.; Salzano, Francisco M.; Bau, Claiton H. D.; Bortolini, Maria Cátira; González-José, Rolando

    2013-01-01

    Antisocial and criminal behaviors are multifactorial traits whose interpretation relies on multiple disciplines. Since these interpretations may have social, moral and legal implications, a constant review of the evidence is necessary before any scientific claim is considered as truth. A recent study proposed that men with wider faces relative to facial height (fWHR) are more likely to develop unethical behaviour mediated by a psychological sense of power. This research was based on reports suggesting that sexual dimorphism and selection would be responsible for a correlation between fWHR and aggression. Here we show that 4,960 individuals from 94 modern human populations belonging to a vast array of genetic and cultural contexts do not display significant amounts of fWHR sexual dimorphism. Further analyses using populations with associated ethnographical records as well as samples of male prisoners of the Mexico City Federal Penitentiary condemned by crimes of variable level of inter-personal aggression (homicide, robbery, and minor faults) did not show significant evidence, suggesting that populations/individuals with higher levels of bellicosity, aggressive behaviour, or power-mediated behaviour display greater fWHR. Finally, a regression analysis of fWHR on individual's fitness showed no significant correlation between this facial trait and reproductive success. Overall, our results suggest that facial attributes are poor predictors of aggressive behaviour, or at least, that sexual selection was weak enough to leave a signal on patterns of between- and within-sex and population facial variation. PMID:23326328

  10. When to simulate and when to associate? Accounting for inter-talker variability in the speech signal.

    PubMed

    Trude, Alison M

    2013-08-01

    Pickering & Garrod's (P&G's) theory could be modified to describe how listeners rapidly incorporate context to generate predictions about speech despite inter-talker variability. However, in order to do so, the content of "impoverished" predicted percepts must be expanded to include phonetic information. Further, the way listeners identify and represent inter-talker differences and subsequently determine which prediction method to use would require further specification.

  11. Home range overlap as a driver of intelligence in primates.

    PubMed

    Grueter, Cyril C

    2015-04-01

    Various socioecological factors have been suggested to influence cognitive capacity in primates, including challenges associated with foraging and dealing with the complexities of social life. Alexander [Alexander, 1989]. Evolution of the human psyche. In: Mellars P, Stringer C, editors. The human revolution: Behavioural and biological perspectives on the origins of modern humans. Princeton: Princeton University Press. p 455-513] proposed an integrative model for the evolution of human cognitive abilities and complex sociality that incorporates competition among coalitions of conspecifics (inter-group conflict) as a major selective pressure. However, one of the premises of this model, i.e., that when confronted with inter-group conflict selection should favor enhanced cognition, has remained empirically untested. Using a comparative approach on species data, I aimed to test the prediction that primate species (n = 104) that face greater inter-group conflict have higher cognitive abilities (indexed by endocranial volume). The degree of inter-group conflict/complexity was approximated via the variable home range overlap among groups. I found a significant relationship between home range overlap and endocranial volume, even after controlling for other predictor variables and covariates such as group size and body mass. I conclude that brain size evolution cannot be attributed exclusively to social factors such as group size, but likely reflects a variety of social and ecological determinants including inter-group conflict which poses cognitive demands on monitoring both the wider social milieu as well as spatial attributes of the habitat. © 2014 Wiley Periodicals, Inc.

  12. The reliability of three psoriasis assessment tools: Psoriasis area and severity index, body surface area and physician global assessment.

    PubMed

    Bożek, Agnieszka; Reich, Adam

    2017-08-01

    A wide variety of psoriasis assessment tools have been proposed to evaluate the severity of psoriasis in clinical trials and daily practice. The most frequently used clinical instrument is the psoriasis area and severity index (PASI); however, none of the currently published severity scores used for psoriasis meets all the validation criteria required for an ideal score. The aim of this study was to compare and assess the reliability of 3 commonly used assessment instruments for psoriasis severity: the psoriasis area and severity index (PASI), body surface area (BSA) and physician global assessment (PGA). On the scoring day, 10 trained dermatologists evaluated 9 adult patients with plaque-type psoriasis using the PASI, BSA and PGA. All the subjects were assessed twice by each physician. Correlations between the assessments were analyzed using the Pearson correlation coefficient. Intra-class correlation coefficient (ICC) was calculated to analyze intra-rater reliability, and the coefficient of variation (CV) was used to assess inter-rater variability. Significant correlations were observed among the 3 scales in both assessments. In all 3 scales the ICCs were > 0.75, indicating high intra-rater reliability. The highest ICC was for the BSA (0.96) and the lowest one for the PGA (0.87). The CV for the PGA and PASI were 29.3 and 36.9, respectively, indicating moderate inter-rater variability. The CV for the BSA was 57.1, indicating high inter-rater variability. Comparing the PASI, PGA and BSA, it was shown that the PGA had the highest inter-rater reliability, whereas the BSA had the highest intra-rater reliability. The PASI showed intermediate values in terms of interand intra-rater reliability. None of the 3 assessment instruments showed a significant advantage over the other. A reliable assessment of psoriasis severity requires the use of several independent evaluations simultaneously.

  13. Do Physical Proximity and Availability of Adequate Infrastructure at Public Health Facility Increase Institutional Delivery? A Three Level Hierarchical Model Approach

    PubMed Central

    Patel, Rachana; Ladusingh, Laishram

    2015-01-01

    This study aims to examine the inter-district and inter-village variation of utilization of health services for institutional births in EAG states in presence of rural health program and availability of infrastructures. District Level Household Survey-III (2007–08) data on delivery care and facility information was used for the purpose. Bivariate results examined the utilization pattern by states in presence of correlates of women related while a three-level hierarchical multilevel model illustrates the effect of accessibility, availability of health facility and community health program variables on the utilization of health services for institutional births. The study found a satisfactory improvement in state Rajasthan, Madhya Pradesh and Orissa, importantly, in Bihar and Uttaranchal. The study showed that increasing distance from health facility discouraged institutional births and there was a rapid decline of more than 50% for institutional delivery as the distance to public health facility exceeded 10 km. Additionally, skilled female health worker (ANM) and observed improved public health facility led to significantly increase the probability of utilization as compared to non-skilled ANM and not-improved health centers. Adequacy of essential equipment/laboratory services required for maternal care significantly encouraged deliveries at public health facility. District/village variables neighborhood poverty was negatively related to institutional delivery while higher education levels in the village and women’s residing in more urbanized districts increased the utilization. “Inter-district” variation was 14 percent whereas “between-villages” variation for the utilization was 11 percent variation once controlled for all the three-level variables in the model. This study suggests that the mere availability of health facilities is necessary but not sufficient condition to promote utilization until the quality of service is inadequate and inaccessible considering the inter-districts variation for the program implementation. PMID:26689199

  14. Do Physical Proximity and Availability of Adequate Infrastructure at Public Health Facility Increase Institutional Delivery? A Three Level Hierarchical Model Approach.

    PubMed

    Patel, Rachana; Ladusingh, Laishram

    2015-01-01

    This study aims to examine the inter-district and inter-village variation of utilization of health services for institutional births in EAG states in presence of rural health program and availability of infrastructures. District Level Household Survey-III (2007-08) data on delivery care and facility information was used for the purpose. Bivariate results examined the utilization pattern by states in presence of correlates of women related while a three-level hierarchical multilevel model illustrates the effect of accessibility, availability of health facility and community health program variables on the utilization of health services for institutional births. The study found a satisfactory improvement in state Rajasthan, Madhya Pradesh and Orissa, importantly, in Bihar and Uttaranchal. The study showed that increasing distance from health facility discouraged institutional births and there was a rapid decline of more than 50% for institutional delivery as the distance to public health facility exceeded 10 km. Additionally, skilled female health worker (ANM) and observed improved public health facility led to significantly increase the probability of utilization as compared to non-skilled ANM and not-improved health centers. Adequacy of essential equipment/laboratory services required for maternal care significantly encouraged deliveries at public health facility. District/village variables neighborhood poverty was negatively related to institutional delivery while higher education levels in the village and women's residing in more urbanized districts increased the utilization. "Inter-district" variation was 14 percent whereas "between-villages" variation for the utilization was 11 percent variation once controlled for all the three-level variables in the model. This study suggests that the mere availability of health facilities is necessary but not sufficient condition to promote utilization until the quality of service is inadequate and inaccessible considering the inter-districts variation for the program implementation.

  15. Profiling of steroid metabolites after transdermal and oral administration of testosterone by ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

    PubMed

    Badoud, F; Boccard, J; Schweizer, C; Pralong, F; Saugy, M; Baume, N

    2013-11-01

    The screening of testosterone (T) misuse for doping control is based on the urinary steroid profile, including T, its precursors and metabolites. Modifications of individual levels and ratio between those metabolites are indicators of T misuse. In the context of screening analysis, the most discriminant criterion known to date is based on the T glucuronide (TG) to epitestosterone glucuronide (EG) ratio (TG/EG). Following the World Anti-Doping Agency (WADA) recommendations, there is suspicion of T misuse when the ratio reaches 4 or beyond. While this marker remains very sensitive and specific, it suffers from large inter-individual variability, with important influence of enzyme polymorphisms. Moreover, use of low dose or topical administration forms makes the screening of endogenous steroids difficult while the detection window no longer suits the doping habit. As reference limits are estimated on the basis of population studies, which encompass inter-individual and inter-ethnic variability, new strategies including individual threshold monitoring and alternative biomarkers were proposed to detect T misuse. The purpose of this study was to evaluate the potential of ultra-high pressure liquid chromatography (UHPLC) coupled with a new generation high resolution quadrupole time-of-flight mass spectrometer (QTOF-MS) to investigate the steroid metabolism after transdermal and oral T administration. An approach was developed to quantify 12 targeted urinary steroids as direct glucuro- and sulfo-conjugated metabolites, allowing the conservation of the phase II metabolism information, reflecting genetic and environmental influences. The UHPLC-QTOF-MS(E) platform was applied to clinical study samples from 19 healthy male volunteers, having different genotypes for the UGT2B17 enzyme responsible for the glucuroconjugation of T. Based on reference population ranges, none of the traditional markers of T misuse could detect doping after topical administration of T, while the detection window was short after oral TU ingestion. The detection ability of the 12 targeted steroids was thus evaluated by using individual thresholds following both transdermal and oral administration. Other relevant biomarkers and minor metabolites were studied for complementary information to the steroid profile, including sulfoconjugated analytes and hydroxy forms of glucuroconjugated metabolites. While sulfoconjugated steroids may provide helpful screening information for individuals with homozygotous UGT2B17 deletion, hydroxy-glucuroconjugated analytes could enhance the detection window of oral T undecanoate (TU) doping. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Faithful or not: direct and indirect effects of climate on extra-pair paternities in a population of Alpine marmots

    PubMed Central

    Allainé, Dominique; Sauzet, Sandrine; Cohas, Aurélie

    2016-01-01

    Despite being identified an area that is poorly understood regarding the effects of climate change, behavioural responses to climatic variability are seldom explored. Climatic variability is likely to cause large inter-annual variation in the frequency of extra-pair litters produced, a widespread alternative mating tactic to help prevent, correct or minimize the negative consequences of sub-optimal mate choice. In this study, we investigated how climatic variability affects the inter-annual variation in the proportion of extra-pair litters in a wild population of Alpine marmots. During 22 years of monitoring, the annual proportion of extra-pair litters directly increased with the onset of earlier springs and indirectly with increased snow in winters. Snowier winters resulted in a higher proportion of families with sexually mature male subordinates and thus, created a social context within which extra-pair paternity was favoured. Earlier spring snowmelt could create this pattern by relaxing energetic, movement and time constraints. Further, deeper snow in winter could also contribute by increasing litter size and juvenile survival. Optimal mate choice is particularly relevant to generate adaptive genetic diversity. Understanding the influence of environmental conditions and the capacity of the individuals to cope with them is crucial within the context of rapid climate change. PMID:28003452

  17. Faithful or not: direct and indirect effects of climate on extra-pair paternities in a population of Alpine marmots.

    PubMed

    Bichet, Coraline; Allainé, Dominique; Sauzet, Sandrine; Cohas, Aurélie

    2016-12-28

    Despite being identified an area that is poorly understood regarding the effects of climate change, behavioural responses to climatic variability are seldom explored. Climatic variability is likely to cause large inter-annual variation in the frequency of extra-pair litters produced, a widespread alternative mating tactic to help prevent, correct or minimize the negative consequences of sub-optimal mate choice. In this study, we investigated how climatic variability affects the inter-annual variation in the proportion of extra-pair litters in a wild population of Alpine marmots. During 22 years of monitoring, the annual proportion of extra-pair litters directly increased with the onset of earlier springs and indirectly with increased snow in winters. Snowier winters resulted in a higher proportion of families with sexually mature male subordinates and thus, created a social context within which extra-pair paternity was favoured. Earlier spring snowmelt could create this pattern by relaxing energetic, movement and time constraints. Further, deeper snow in winter could also contribute by increasing litter size and juvenile survival. Optimal mate choice is particularly relevant to generate adaptive genetic diversity. Understanding the influence of environmental conditions and the capacity of the individuals to cope with them is crucial within the context of rapid climate change. © 2016 The Author(s).

  18. On the implications of the classical ergodic theorems: analysis of developmental processes has to focus on intra-individual variation.

    PubMed

    Molenaar, Peter C M

    2008-01-01

    It is argued that general mathematical-statistical theorems imply that standard statistical analysis techniques of inter-individual variation are invalid to investigate developmental processes. Developmental processes have to be analyzed at the level of individual subjects, using time series data characterizing the patterns of intra-individual variation. It is shown that standard statistical techniques based on the analysis of inter-individual variation appear to be insensitive to the presence of arbitrary large degrees of inter-individual heterogeneity in the population. An important class of nonlinear epigenetic models of neural growth is described which can explain the occurrence of such heterogeneity in brain structures and behavior. Links with models of developmental instability are discussed. A simulation study based on a chaotic growth model illustrates the invalidity of standard analysis of inter-individual variation, whereas time series analysis of intra-individual variation is able to recover the true state of affairs. (c) 2007 Wiley Periodicals, Inc.

  19. Orthodontic camouflage versus orthognathic surgery for class III deformity: comparative cephalometric analysis.

    PubMed

    Martinez, P; Bellot-Arcís, C; Llamas, J M; Cibrian, R; Gandia, J L; Paredes-Gallardo, V

    2017-04-01

    The objective of this study was to compare different cephalometric variables in adult patients with class III malocclusions before and after treatment, in order to determine which variables are indicative of orthodontic camouflage or orthognathic surgery. The cases of 156 adult patients were assessed: 77 treated with orthodontic camouflage and 79 treated with orthodontics and orthognathic surgery. The following cephalometric variables were measured on pre-treatment (T1) and post-treatment (T2) lateral cephalograms: sella-nasion-A-point (SNA), sella-nasion-B-point (SNB), and A-point-nasion-B-point (ANB) angles, Wits appraisal, facial axis angle, mandibular plane angle, upper and lower incisor inclination, and inter-incisal angle. There were statistically significant differences in cephalometric variables before and after treatment between the two groups. The percentage of normal pre-treatment measurements in the camouflage orthodontics group was 30.7%, which worsened slightly to 28.4% post-treatment. However in the group receiving surgery, this was 24.5% pre-treatment, improving to 33.5% after surgery. SNA, SNB, Wits appraisal, lower incisor inclination, and inter-incisal angle showed differences between the two groups before and after treatment. Wits appraisal, lower incisor inclination, and inter-incisal angle were indicative of one or other treatment. Upper and lower incisor decompensation in both groups did not reach ideal values, which impeded complete skeletal correction in 52% of surgical cases. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  20. Improving the Accuracy of Laplacian Estimation with Novel Variable Inter-Ring Distances Concentric Ring Electrodes

    PubMed Central

    Makeyev, Oleksandr; Besio, Walter G.

    2016-01-01

    Noninvasive concentric ring electrodes are a promising alternative to conventional disc electrodes. Currently, the superiority of tripolar concentric ring electrodes over disc electrodes, in particular, in accuracy of Laplacian estimation, has been demonstrated in a range of applications. In our recent work, we have shown that accuracy of Laplacian estimation can be improved with multipolar concentric ring electrodes using a general approach to estimation of the Laplacian for an (n + 1)-polar electrode with n rings using the (4n + 1)-point method for n ≥ 2. This paper takes the next step toward further improving the Laplacian estimate by proposing novel variable inter-ring distances concentric ring electrodes. Derived using a modified (4n + 1)-point method, linearly increasing and decreasing inter-ring distances tripolar (n = 2) and quadripolar (n = 3) electrode configurations are compared to their constant inter-ring distances counterparts. Finite element method modeling and analytic results are consistent and suggest that increasing inter-ring distances electrode configurations may decrease the truncation error resulting in more accurate Laplacian estimates compared to respective constant inter-ring distances configurations. For currently used tripolar electrode configuration, the truncation error may be decreased more than two-fold, while for the quadripolar configuration more than a six-fold decrease is expected. PMID:27294933

  1. Improving the Accuracy of Laplacian Estimation with Novel Variable Inter-Ring Distances Concentric Ring Electrodes.

    PubMed

    Makeyev, Oleksandr; Besio, Walter G

    2016-06-10

    Noninvasive concentric ring electrodes are a promising alternative to conventional disc electrodes. Currently, the superiority of tripolar concentric ring electrodes over disc electrodes, in particular, in accuracy of Laplacian estimation, has been demonstrated in a range of applications. In our recent work, we have shown that accuracy of Laplacian estimation can be improved with multipolar concentric ring electrodes using a general approach to estimation of the Laplacian for an (n + 1)-polar electrode with n rings using the (4n + 1)-point method for n ≥ 2. This paper takes the next step toward further improving the Laplacian estimate by proposing novel variable inter-ring distances concentric ring electrodes. Derived using a modified (4n + 1)-point method, linearly increasing and decreasing inter-ring distances tripolar (n = 2) and quadripolar (n = 3) electrode configurations are compared to their constant inter-ring distances counterparts. Finite element method modeling and analytic results are consistent and suggest that increasing inter-ring distances electrode configurations may decrease the truncation error resulting in more accurate Laplacian estimates compared to respective constant inter-ring distances configurations. For currently used tripolar electrode configuration, the truncation error may be decreased more than two-fold, while for the quadripolar configuration more than a six-fold decrease is expected.

  2. Finite element method modeling to assess Laplacian estimates via novel variable inter-ring distances concentric ring electrodes.

    PubMed

    Makeyev, Oleksandr; Besio, Walter G

    2016-08-01

    Noninvasive concentric ring electrodes are a promising alternative to conventional disc electrodes. Currently, superiority of tripolar concentric ring electrodes over disc electrodes, in particular, in accuracy of Laplacian estimation has been demonstrated in a range of applications. In our recent work we have shown that accuracy of Laplacian estimation can be improved with multipolar concentric ring electrodes using a general approach to estimation of the Laplacian for an (n + 1)-polar electrode with n rings using the (4n + 1)-point method for n ≥ 2. This paper takes the next step toward further improving the Laplacian estimate by proposing novel variable inter-ring distances concentric ring electrodes. Derived using a modified (4n + 1)-point method, linearly increasing and decreasing inter-ring distances tripolar (n = 2) and quadripolar (n = 3) electrode configurations are compared to their constant inter-ring distances counterparts using finite element method modeling. Obtained results suggest that increasing inter-ring distances electrode configurations may decrease the estimation error resulting in more accurate Laplacian estimates compared to respective constant inter-ring distances configurations. For currently used tripolar electrode configuration the estimation error may be decreased more than two-fold while for the quadripolar configuration more than six-fold decrease is expected.

  3. Biologic variability and correlation of platelet function testing in healthy dogs.

    PubMed

    Blois, Shauna L; Lang, Sean T; Wood, R Darren; Monteith, Gabrielle

    2015-12-01

    Platelet function tests are influenced by biologic variability, including inter-individual (CVG ) and intra-individual (CVI ), as well as analytic (CVA ) variability. Variability in canine platelet function testing is unknown, but if excessive, would make it difficult to interpret serial results. Additionally, the correlation between platelet function tests is poor in people, but not well described in dogs. The aims were to: (1) identify the effect of variation in preanalytic factors (venipuncture, elapsed time until analysis) on platelet function tests; (2) calculate analytic and biologic variability of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced thromboelastograph platelet mapping (TEG-PM), ADP-, AA-, and collagen-induced whole blood platelet aggregometry (WBA), and collagen/ADP and collagen/epinephrine platelet function analysis (PFA-CADP, PFA-CEPI); and (3) determine the correlation between these variables. In this prospective observational trial, platelet function was measured once every 7 days, for 4 consecutive weeks, in 9 healthy dogs. In addition, CBC, TEG-PM, WBA, and PFA were performed. Overall coefficients of variability ranged from 13.3% to 87.8% for the platelet function tests. Biologic variability was highest for AA-induced maximum amplitude generated during TEG-PM (MAAA; CVG = 95.3%, CVI = 60.8%). Use of population-based reference intervals (RI) was determined appropriate only for PFA-CADP (index of individuality = 10.7). There was poor correlation between most platelet function tests. Use of population-based RI appears inappropriate for most platelet function tests, and tests poorly correlate with one another. Future studies on biologic variability and correlation of platelet function tests should be performed in dogs with platelet dysfunction and those treated with antiplatelet therapy. © 2015 American Society for Veterinary Clinical Pathology.

  4. Ochratoxin A and its metabolites in urines of German adults-An assessment of variables in biomarker analysis.

    PubMed

    Ali, Nurshad; Muñoz, Katherine; Degen, Gisela H

    2017-06-05

    Ochratoxin A (OTA), a mycotoxin known for its nephrotoxic and carcinogenic properties, is a worldwide occurring contaminant in a variety of food commodities. Biomonitoring (i.e. analysis in biological fluids) can serve to assess human internal exposure from all consumed foods and beverages. We now determined the concentration of OTA and its metabolite ochratoxin alpha (OTα) in plasma and in urine of two male volunteers with different food habits, in order to assess intra-individual temporal fluctuations and inter-individual differences in their biomarker levels. Moreover, the urinary levels of both OTA and OTα were analyzed in a cohort of German adults (23 males, 27 females) on their regular diet. All samples were subjected to an enzymatic hydrolysis of biomarker conjugates prior to clean-up by liquid-liquid extraction and HPLC-FD analysis. The profile in the first individual showed small fluctuations over time: mean levels in plasma were 0.42 and 0.45ng/mL for OTA and OTα, respectively, and in urine means of 0.06ng/mL for both analytes. The other individual had mean levels of 1.64 and 0.20ng/mL for OTA and OTα in plasma, and 0.24 and 2.22ng/mL for these analytes in urine. It is concluded that inter-individual differences in biomarker levels reflect dissimilar dietary exposure and/or disposition of ingested mycotoxin, with an apparently more efficient detoxification of OTA to OTα in the second individual. In the German cohort (n=50), analytes were detected in 100% (OTA: range 0.02-1.82ng/mL mean level 0.21±0.31ng/mL) and 78% (OTα: range 0.01-14.25ng/mL, mean level 1.33±2.63ng/mL) of all urines. Parameters such as gender, age and body mass index did not show a significant association with urine biomarker levels. This study indicates frequent exposure to OTA among German adults. The new results are discussed in the context of biomarker data from other countries and some methodological issues. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Pharmacokinetic variability of long-acting stimulants in the treatment of children and adults with attention-deficit hyperactivity disorder.

    PubMed

    Ermer, James C; Adeyi, Ben A; Pucci, Michael L

    2010-12-01

    Methylphenidate- and amfetamine-based stimulants are first-line pharmacotherapies for attention-deficit hyperactivity disorder, a common neurobehavioural disorder in children and adults. A number of long-acting stimulant formulations have been developed with the aim of providing once-daily dosing, employing various means to extend duration of action, including a transdermal delivery system, an osmotic-release oral system, capsules with a mixture of immediate- and delayed-release beads, and prodrug technology. Coefficients of variance of pharmacokinetic measures can estimate the levels of pharmacokinetic variability based on the measurable variance between different individuals receiving the same dose of stimulant (interindividual variability) and within the same individual over multiple administrations (intraindividual variability). Differences in formulation clearly impact pharmacokinetic profiles. Many medications exhibit wide interindividual variability in clinical response. Stimulants with low levels of inter- and intraindividual variability may be better suited to provide consistent levels of medication to patients. The pharmacokinetic profile of stimulants using pH-dependent bead technology can vary depending on food consumption or concomitant administration of medications that alter gastric pH. While delivery of methylphenidate with the transdermal delivery system would be unaffected by gastrointestinal factors, intersubject variability is nonetheless substantial. Unlike the beaded formulations and, to some extent (when considering total exposure) the osmotic-release formulation, systemic exposure to amfetamine with the prodrug stimulant lisdexamfetamine dimesylate appears largely unaffected by such factors, likely owing to its dependence on systemic enzymatic cleavage of the precursor molecule, which occurs primarily in the blood involving red blood cells. The high capacity but as yet unidentified enzymatic system for conversion of lisdexamfetamine dimesylate may contribute to its consistent pharmacokinetic profile. The reasons underlying observed differential responses to stimulants are likely to be multifactorial, including pharmacodynamic factors. While the use of stimulants with low inter- and intrapatient pharmacokinetic variability does not obviate the need to titrate stimulant doses, stimulants with low intraindividual variation in pharmacokinetic parameters may reduce the likelihood of patients falling into subtherapeutic drug concentrations or reaching drug concentrations at which the risk of adverse events increases. As such, clinicians are urged both to adjust stimulant doses based on therapeutic response and the risk for adverse events and to monitor patients for potential causes of pharmacokinetic variability.

  6. Cartography and Connectomes Perspective article for Neuron 25th Anniversary Issue

    PubMed Central

    Van Essen, David C.

    2013-01-01

    The past 25 years have seen great progress in parcellating the cerebral cortex into a mosaic of many distinct areas in mice, monkeys, and humans. Quantitative studies of inter-areal connectivity have revealed unexpectedly many pathways and a wide range of connection strengths in mouse and macaque cortex. In humans, advances in analyzing ‘structural’ and ‘functional’ connectivity using powerful but indirect noninvasive neuroimaging methods are yielding intriguing insights about brain circuits, their variability across individuals, and their relationship to behavior. PMID:24183027

  7. A new analysis of heart rate variability in the assessment of fetal parasympathetic activity: An experimental study in a fetal sheep model.

    PubMed

    Garabedian, C; Champion, C; Servan-Schreiber, E; Butruille, L; Aubry, E; Sharma, D; Logier, R; Deruelle, P; Storme, L; Houfflin-Debarge, V; De Jonckheere, J

    2017-01-01

    Analysis of heart rate variability (HRV) is a recognized tool in the assessment of autonomic nervous system (ANS) activity. Indeed, both time and spectral analysis techniques enable us to obtain indexes that are related to the way the ANS regulates the heart rate. However, these techniques are limited in terms of the lack of thresholds of the numerical indexes, which is primarily due to high inter-subject variability. We proposed a new fetal HRV analysis method related to the parasympathetic activity of the ANS. The aim of this study was to evaluate the performance of our method compared to commonly used HRV analysis, with regard to i) the ability to detect changes in ANS activity and ii) inter-subject variability. This study was performed in seven sheep fetuses. In order to evaluate the sensitivity and specificity of our index in evaluating parasympathetic activity, we directly administered 2.5 mg intravenous atropine, to inhibit parasympathetic tone, and 5 mg propranolol to block sympathetic activity. Our index, as well as time analysis (root mean square of the successive differences; RMSSD) and spectral analysis (high frequency (HF) and low frequency (LF) spectral components obtained via fast Fourier transform), were measured before and after injection. Inter-subject variability was estimated by the coefficient of variance (%CV). In order to evaluate the ability of HRV parameters to detect fetal parasympathetic decrease, we also estimated the effect size for each HRV parameter before and after injections. As expected, our index, the HF spectral component, and the RMSSD were reduced after the atropine injection. Moreover, our index presented a higher effect size. The %CV was far lower for our index than for RMSSD, HF, and LF. Although LF decreased after propranolol administration, fetal stress index, RMSSD, and HF were not significantly different, confirming the fact that those indexes are specific to the parasympathetic nervous system. In conclusion, our method appeared to be effective in detecting parasympathetic inhibition. Moreover, inter-subject variability was much lower, and effect size higher, with our method compared to other HRV analysis methods.

  8. Reproducibility of manual pressure force on provocation of the sacroiliac joint.

    PubMed

    Levin, U; Nilsson-Wikmar, L; Stenström, C H; Lundeberg, T

    1998-01-01

    Previous studies of pain-provocation sacroiliac (SI) joint tests have revealed conflicting results. The aim of the present study was to evaluate the intra- and inter-test reliability of pressure force applied during distraction test, compression test and pressure on the apex sacralis. Seventeen physiotherapists (PTs), median age 43 years and median clinical experience 11 years, all experienced in musculoskeletal evaluation and therapy, participated in the study. Each PT performed each test on the same healthy volunteer for 20 s, on three separate occasions, at intervals of one week using a specially constructed examination table which registered pressure force. The PTs were capable of maintaining a relatively constant pressure force for 20 s. The intra-test reliability was acceptable even though there were individual differences on different occasions between those PTs who used the SI joint tests often and those who seldom or never used them. The inter-test reliability was insufficient. The findings indicate the advantage of registering pressure force as a complement for standardized methods for pain-provoking tests and when learning provocation tests, since individual variability was considerable.

  9. Monte Carlo study of x-ray cross talk in a variable resolution x-ray detector

    NASA Astrophysics Data System (ADS)

    Melnyk, Roman; DiBianca, Frank A.

    2003-06-01

    A variable resolution x-ray (VRX) detector provides a great increase in the spatial resolution of a CT scanner. An important factor that limits the spatial resolution of the detector is x-ray cross-talk. A theoretical study of the x-ray cross-talk is presented in this paper. In the study, two types of the x-ray cross-talk were considered: inter-cell and inter-arm cross-talk. Both types of the x-ray cross-talk were simulated, using the Monte Carlo method, as functions of the detector field of view (FOV). The simulation was repeated for lead and tungsten separators between detector cells. The inter-cell x-ray cross-talk was maximum at the 34-36 cm FOV, but it was low at small and the maximum FOVs. The inter-arm x-ray cross-talk was high at small and medium FOVs, but it was greatly reduced when variable width collimators were placed on the front surfaces of the detector. The inter-cell, but not inter-arm, x-ray cross-talk was lower for tungsten than for lead separators. From the results, x-ray cross-talk in a VRX detector can be minimized by imaging all objects between 24 cm and 40 cm in diameter with the 40 cm FOV, using tungsten separators, and placing variable width collimators in front of the detector.

  10. Perceived stress predicts altered reward and loss feedback processing in medial prefrontal cortex

    PubMed Central

    Treadway, Michael T.; Buckholtz, Joshua W.; Zald, David H.

    2013-01-01

    Stress is a significant risk factor for the development of psychopathology, particularly symptoms related to reward processing. Importantly, individuals display marked variation in how they perceive and cope with stressful events, and such differences are strongly linked to risk for developing psychiatric symptoms following stress exposure. However, many questions remain regarding the neural architecture that underlies inter-subject variability in perceptions of stressors. Using functional magnetic resonance imaging (fMRI) during a Monetary Incentive Delay (MID) paradigm, we examined the effects of self-reported perceived stress levels on neural activity during reward anticipation and feedback in a sample of healthy individuals. We found that subjects reporting more uncontrollable and overwhelming stressors displayed blunted neural responses in medial prefrontal cortex (mPFC) following feedback related to monetary gains as well monetary losses. This is consistent with preclinical models that implicate the mPFC as a key site of vulnerability to the noxious effects of uncontrollable stressors. Our data help translate these findings to humans, and elucidate some of the neural mechanisms that may underlie stress-linked risk for developing reward-related psychiatric symptoms. PMID:23730277

  11. A critical review of field techniques employed in the survey of large woody debris in river corridors: a central European perspective.

    PubMed

    Máčka, Zdeněk; Krejčí, Lukáš; Loučková, Blanka; Peterková, Lucie

    2011-10-01

    In forested watersheds, large woody debris (LWD) is an integral component of river channels and floodplains. Fallen trees have a significant impact on physical and ecological processes in fluvial ecosystems. An enormous body of literature concerning LWD in river corridors is currently available. However, synthesis and statistical treatment of the published data are hampered by the heterogeneity of methodological approaches. Likewise, the precision and accuracy of data arising out of published surveys have yet to be assessed. For this review, a literature scrutiny of 100 randomly selected research papers was made to examine the most frequently surveyed LWD variables and field procedures. Some 29 variables arose for individual LWD pieces, and 15 variables for wood accumulations. The literature survey revealed a large variability in field procedures for LWD surveys. In many studies (32), description of field procedure proved less than adequate, rendering the results impossible to reproduce in comparable fashion by other researchers. This contribution identifies the main methodological problems and sources of error associated with the mapping and measurement of the most frequently surveyed variables of LWD, both as individual pieces and in accumulations. The discussion stems from our own field experience with LWD survey in river systems of various geomorphic styles and types of riparian vegetation in the Czech Republic in the 2004-10 period. We modelled variability in terms of LWD number, volume, and biomass for three geomorphologically contrasting river systems. The results appeared to be sensitive, in the main, to sampling strategy and prevailing field conditions; less variability was produced by errors of measurement. Finally, we propose a comprehensive standard field procedure for LWD surveyors, including a total of 20 variables describing spatial position, structural characteristics and the functions and dynamics of LWD. However, resources are only rarely available for highly time-demanding surveys. We therefore include a set of core LWD metrics for routine baseline surveys of individual LWD pieces (diameter, length, rootwad size, preservation of branches and rootwad, geomorphological/ecological function, stability/mobility) and wood accumulations (number of LWD pieces, geometrical dimensions, channel blockage, wood/air ratio), which may provide useful background information for river management, hydromorphological assessment, habitat evaluation, and inter-regional comparisons.

  12. Exploring the impact of climate variability during the Last Glacial Maximum on the pattern of human occupation of Iberia.

    PubMed

    Burke, Ariane; Levavasseur, Guillaume; James, Patrick M A; Guiducci, Dario; Izquierdo, Manuel Arturo; Bourgeon, Lauriane; Kageyama, Masa; Ramstein, Gilles; Vrac, Mathieu

    2014-08-01

    The Last Glacial Maximum (LGM) was a global climate event, which had significant repercussions for the spatial distribution and demographic history of prehistoric populations. In Eurasia, the LGM coincides with a potential bottleneck for modern humans and may mark the divergence date for Asian and European populations (Keinan et al., 2007). In this research, the impact of climate variability on human populations in the Iberian Peninsula during the Last Glacial Maximum (LGM) is examined with the aid of downscaled high-resolution (16 × 16 km) numerical climate experiments. Human sensitivity to short time-scale (inter-annual) climate variability during this key time period, which follows the initial modern human colonisation of Eurasia and the extinction of the Neanderthals, is tested using the spatial distribution of archaeological sites. Results indicate that anatomically modern human populations responded to small-scale spatial patterning in climate variability, specifically inter-annual variability in precipitation levels as measured by the standard precipitation index. Climate variability at less than millennial scale, therefore, is shown to be an important component of ecological risk, one that played a role in regulating the spatial behaviour of prehistoric human populations and consequently affected their social networks. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Genetic background in nonalcoholic fatty liver disease: A comprehensive review

    PubMed Central

    Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore

    2015-01-01

    In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease. PMID:26494964

  14. The Neural Underpinnings of Cognitive Flexibility and their Disruption in Psychotic Illness

    PubMed Central

    Waltz, James A.

    2016-01-01

    Schizophrenia has long been associated with a variety of cognitive deficits, including reduced cognitive flexibility. More recent findings, however, point to tremendous inter-individual variability among patients on measures of cognitive flexibility/set-shifting. With an eye toward shedding light on potential sources of variability in set-shifting abilities among schizophrenia patients, I examine the neural substrates of underlying probabilistic reversal learning (PRL) – a paradigmatic measure of cognitive flexibility – as well as neuromodulatory influences upon these systems. Finally, I report on behavioral and neuroimaging studies of PRL in schizophrenia patients, discussing the potentially influences of illness profile and antipsychotic medications on cognitive flexibility in schizophrenia. PMID:27282085

  15. Movement Pattern Variability in Stone Knapping: Implications for the Development of Percussive Traditions

    PubMed Central

    Rein, Robert; Nonaka, Tetsushi; Bril, Blandine

    2014-01-01

    The earliest direct evidence for tool-use by our ancestors are 2.6 million year old stone tools from Africa. These earliest artifacts show that, already, early hominins had developed the required advanced movement skills and cognitive capacities to manufacture stone tools. Currently, it is not well understood, however, which specific movement skills are required for successful stone knapping and accordingly it is unknown how these skills emerged during early hominin evolution. In particular, it is not clear which striking movements are indicative of skilled performance, how striking movement patterns vary with task and environmental constraints, and how movement patterns are passed on within social groups. The present study addresses these questions by investigating striking movement patterns and striking variability in 18 modern stone knappers (nine experienced and nine novices). The results suggest that no single movement pattern characterizes successful stone knapping. Participants showed large inter-individual movement variability of the elementary knapping action irrespective of knapping experience and knapping performance. Changes in task- and environmental constraints led knappers to adapt their elementary striking actions using a combination of individual and common strategies. Investigation of striking pattern similarities within social groups showed only partial overlap of striking patterns across related individuals. The results therefore suggest that striking movement patterns in modern stone knappers are largely specific to the individual and movement variability is not indicative of knapping performance. The implications of these results for the development of percussive traditions are discussed. PMID:25426630

  16. Qiviut cortisol in muskoxen as a potential tool for informing conservation strategies

    PubMed Central

    Navarro-Gonzalez, Nora; Wynne-Edwards, Katherine; Peacock, Stephanie; Leclerc, Lisa-Marie; Tomaselli, Matilde; Davison, Tracy; Carlsson, Anja

    2017-01-01

    Abstract Muskoxen (Ovibos moschatus) are increasingly subject to multiple new stressors associated with unprecedented climate change and increased anthropogenic activities across much of their range. Hair may provide a measurement of stress hormones (glucocorticoids) over periods of weeks to months. We developed a reliable method to quantify cortisol in the qiviut (wooly undercoat) of muskoxen using liquid chromatography coupled to tandem mass spectrometry. We then applied this technique to determine the natural variability in qiviut cortisol levels among 150 wild muskoxen, and to assess differences between sexes, seasons and years of collection. Qiviut samples were collected from the rump of adult muskoxen by subsistence and sport hunters in seven different locations in Nunavut and the Northwest Territories between 2013 and 2016. Results showed a high inter-individual variability in qiviut cortisol concentrations, with levels ranging from 3.5 to 48.9 pg/mg (median 11.7 pg/mg). Qiviut cortisol levels were significantly higher in males than females, and varied seasonally (summer levels were significantly lower than in fall and winter), and by year (levels significantly increased from 2013 to 2015). These differences may reflect distinct environmental conditions and the diverse stressors experienced, as well as physiological and/or behavioural characteristics. Quantification of qiviut cortisol may serve as a valuable tool for monitoring health and informing conservation and management efforts. PMID:28948023

  17. Using Digital Repeat Photography to Link Vegetative Phenology and Carbon Fluxes to Biotic and Abiotic Drivers in Three Semi-arid Systems (New Mexico, USA)

    NASA Astrophysics Data System (ADS)

    Hallmark, A.; Litvak, M. E.; Collins, S. L.

    2015-12-01

    Arid and semi-arid ecosystems account for over 45% of global land cover. While mean annual carbon uptake in these ecosystems is relatively low, aridlands collectively store a significant amount of carbon. There is high inter- and intra-annual variability of plant growth in aridlands, depending largely on the timing and size of rainfall events. This variation is also of great significance, as the variation in annual semi-aridland carbon uptake accounts for ~39% of the inter-annual variability of the global terrestrial carbon sink, the largest percentage of any land cover type. Although arid and semi-arid ecosystems are of global importance, they are understudied. To better understand the drivers and variability of carbon uptake in these critical ecosystems, we utilize a six-year record of digital images (45,000+ images), carbon flux and meteorological data, soil water content, and associated ecological measurements from three eddy covariance tower sites in central New Mexico. These sites include a Chihuahuan Desert/short-grass Plains grassland site, and post-fire successional grassland site, and a creosote-encroached shrubland site, each of which have unique species compositions, carbon fluxes, and reactions to disturbance and resource addition. All images used are co-registered and corrected for radial lens distortions (when necessary) and greenness indices (2GRBi, gcc, and/or NDVI) are calculated for each scene's overall "canopy" and for individual species and plant functional types therein. At all three sites, camera-derived greenness is correlated to measured carbon uptake with fine resolution (R2 up to 0.8), capturing temporal and spatial variation usually not seen in satellite-based imagery. At sites with lower LAI, species-specific ROI's were more correlated to the site's measured carbon flux across shorter time scales. Understanding the biota comprising each image and its contribution to changing scene greenness at different times of year can lead to more accurate carbon flux predictions in semi-arid systems, with species-specific biotic constraints (maximum growth rate, lifespan, and seasonality), growth parameters (light availability, VPD, soil water content, and temperature) as well as community-wide abiotic drivers considered.

  18. Inward Leakage Variability between Respirator Fit Test Panels – Part I. Deterministic Approach

    PubMed Central

    Zhuang, Ziqing; Liu, Yuewei; Coffey, Christopher C.; Miller, Colleen; Szalajda, Jonathan

    2015-01-01

    Inter-panel variability has never been investigated. The objective of this study was to determine the variability between different anthropometric panels used to determine the inward leakage (IL) of N95 filtering facepiece respirators (FFRs) and elastomeric half-mask respirators (EHRs). A total of 144 subjects, who were both experienced and non-experienced N95 FFR users, were recruited. Five N95 FFRs and five N95 EHRs were randomly selected from among those models tested previously in our laboratory. The PortaCount Pro+ (without N95-Companion) was used to measure IL of the ambient particles with a detectable size range of 0.02 to 1 μm. The Occupational Safety and Health Administration standard fit test exercises were used for this study. IL test were performed for each subject using each of the 10 respirators. Each respirator/subject combination was tested in duplicate, resulting in a total 20 IL tests for each subject. Three 35-member panels were randomly selected without replacement from the 144 study subjects stratified by the National Institute for Occupational Safety and Health bivariate panel cell for conducting statistical analyses. The geometric mean (GM) IL values for all 10 studied respirators were not significantly different among the three randomly selected 35-member panels. Passing rate was not significantly different among the three panels for all respirators combined or by each model. This was true for all IL pass/fail levels of 1%, 2%, and 5%. Using 26 or more subjects to pass the IL test, all three panels had consistent passing/failing results for pass/fail levels of 1% and 5%. Some disagreement was observed for the 2% pass/fail level. Inter-panel variability exists, but it is small relative to the other sources of variation in fit testing data. The concern about inter-panel variability and other types of variability can be alleviated by properly selecting: pass/fail level (IL 1–5%); panel size (e.g., 25 or 35); and minimum number of subjects required to pass (e.g., 26 of 35 or 23 of 35). PMID:26011282

  19. Inter-annual variability and long term predictability of exchanges through the Strait of Gibraltar

    NASA Astrophysics Data System (ADS)

    Boutov, Dmitri; Peliz, Álvaro; Miranda, Pedro M. A.; Soares, Pedro M. M.; Cardoso, Rita M.; Prieto, Laura; Ruiz, Javier; García-Lafuente, Jesus

    2014-03-01

    Inter-annual variability of calculated barotropic (netflow) and simulated baroclinic (inflow and outflow) exchanges through the Strait of Gibraltar is analyzed and their response to the main modes of atmospheric variability is investigated. Time series of the outflow obtained by high resolution simulations and estimated from in-situ Acoustic Doppler Current Profiler (ADCP) current measurements are compared. The time coefficients (TC) of the leading empirical orthogonal function (EOF) modes that describe zonal atmospheric circulation in the vicinity of the Strait (1st and 3rd of Sea-Level Pressure (SLP) and 1st of the wind) show significant covariance with the inflow and outflow. Based on these analyses, a regression model between these SLP TCs and outflow of the Mediterranean Water was developed. This regression outflow time series was compared with estimates based on current meter observations and the predictability and reconstruction of past exchange variability based on atmospheric pressure fields are discussed. The simple regression model seems to reproduce the outflow evolution fairly reasonably, with the exception of the year 2008, which is apparently anomalous without available physical explanation yet. The exchange time series show a reduced inter-annual variability (less than 1%, 2.6% and 3.1% of total 2-day variability, for netflow, inflow and outflow, respectively). From a statistical point of view no clear long-term tendencies were revealed. Anomalously high baroclinic fluxes are reported for the years of 2000-2001 that are coincident with strong impact on the Alboran Sea ecosystem. The origin of the anomalous flow is associated with a strong negative anomaly (~ - 9 hPa) in atmospheric pressure fields settled north of Iberian Peninsula and extending over the central Atlantic, favoring an increased zonal circulation in winter 2000/2001. These low pressure fields forced intense and durable westerly winds in the Gulf of Cadiz-Alboran system. The signal of this anomaly is also seen in time coefficients of the most significant EOF modes. The predictability of the exchanges for future climate is discussed.

  20. Quality of pathology reporting is crucial for cancer care and registration: a baseline assessment for breast cancers diagnosed in Belgium in 2008.

    PubMed

    De Schutter, H; Van Damme, N; Colpaert, C; Galant, C; Lambein, K; Cornelis, A; Neven, P; Van Eycken, E

    2015-04-01

    Given the crucial role of pathology reporting in the management of breast cancers, we aimed to investigate the quality and variability of breast cancer pathology reporting in Belgium. Detailed information on non-molecular and molecular parameters was retrieved from the pathology protocols available at the Belgian Cancer Registry for 10,007 breast cancers diagnosed in Belgium in 2008. Substantial underreporting was shown for several clinically relevant non-molecular parameters, such as lymphovascular invasion. High-volume laboratories performed only slightly better than others, and analyses at the individual laboratory level showed clear inter-laboratory variability in reporting for all volume categories. Information on ER/PR and HER2 IHC was mentioned in respectively 91.7% and 90.8% of evaluative cases. HER2 ISH data were available for 78.5% of the cases judged to be 2+ for HER2 IHC. For cases with different specimens analysed, discordance between these specimens was highest for HER2, followed by PR. For HER2, results obtained from different laboratories were even less concordant. In addition, inter-laboratory differences were noted in the used ER/PR scoring systems, the proportion of ER-/PR+ cases, and the relation between histological grade and ER/PR positivity. Data on Ki67 were only available for 43.8% of the investigated cases, and showed inconsistent use of cut-off values. Breast pathology reporting in Belgium in 2008 was suboptimal and showed considerable inter-laboratory variability. Synoptic reporting has been proposed as a facilitator towards increased reporting quality and harmonization, but the lack of aligned informatics remains a major hurdle in its concrete implementation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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