Sample records for marked interindividual differences

  1. 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.

  2. Comparative Biochemistry and Metabolism: Part 2. Naphthalene Lung Toxicity

    DTIC Science & Technology

    1984-10-14

    naphthalene, produces a highly selective lesion of the pulmonary bronchiolar epithelium in mice. This lesion appears to depend upon the cytochrome P450...predominating. The rates of metabolism were lower than in rodent lung and there were marked interindividual differences. Pulmonary microsome...54 Effect of Cobalt Protoporphyrin on Naphthalene and 2-Methylnaphthalene-Induced Pulmonary Bronchiolar Necrosis

  3. Session 2: Personalised nutrition. Epigenomics: a basis for understanding individual differences?

    PubMed

    Mathers, John C

    2008-11-01

    Epigenetics encompasses changes to marks on the genome that are copied from one cell generation to the next, which may alter gene expression but which do not involve changes in the primary DNA sequence. These marks include DNA methylation (methylation of cytosines within CpG dinucleotides) and post-translational modifications (acetylation, methylation, phosphorylation and ubiquitination) of the histone tails protruding from nucleosome cores. The sum of genome-wide epigenetic patterns is known as the epigenome. It is hypothesised that altered epigenetic marking is a means through which evidence of environmental exposures (including nutritional status and dietary exposure) is received and recorded by the genome. At least some of these epigenetic marks are remembered through multiple cell generations and their effects may be revealed in altered gene expression and cell function. Altered epigenetic marking allows plasticity of phenotype in a fixed genotype. Despite their identical genotypes, monozygotic twins show increasing epigenetic diversity with age and with divergent lifestyles. Differences in epigenetic markings may explain some inter-individual variation in disease risk and in response to nutritional interventions.

  4. 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.

  5. 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

  6. Diet dominates host genotype in shaping the murine gut microbiota

    PubMed Central

    Carmody, Rachel N.; Gerber, Georg K.; Luevano, Jesus M.; Gatti, Daniel M.; Somes, Lisa; Svenson, Karen L.; Turnbaugh, Peter J.

    2014-01-01

    SUMMARY Mammals exhibit marked inter-individual variations in their gut microbiota, but it remains unclear if this is primarily driven by host genetics or by extrinsic factors like dietary intake. To address this, we examined the effect of dietary perturbations on the gut microbiota of five inbred mouse strains, mice deficient for genes relevant to host-microbial interactions (MyD88−/−, NOD2−/−, ob/ob, and Rag1−/−), and >200 outbred mice. In each experiment, consumption of a high-fat, high-sugar diet reproducibly altered the gut microbiota despite differences in host genotype. The gut microbiota exhibited a linear dose response to dietary perturbations, taking an average of 3.5 days for each diet-responsive bacterial groups to reach a new steady state. Repeated dietary shifts demonstrated that most changes to the gut microbiota are reversible, while also uncovering bacteria whose abundance depends on prior consumption. These results emphasize the dominant role that diet plays in shaping inter-individual variations in host-associated microbial communities. PMID:25532804

  7. Prediction of interindividual differences in hepatic functions and drug sensitivity by using human iPS-derived hepatocytes.

    PubMed

    Takayama, Kazuo; Morisaki, Yuta; Kuno, Shuichi; Nagamoto, Yasuhito; Harada, Kazuo; Furukawa, Norihisa; Ohtaka, Manami; Nishimura, Ken; Imagawa, Kazuo; Sakurai, Fuminori; Tachibana, Masashi; Sumazaki, Ryo; Noguchi, Emiko; Nakanishi, Mahito; Hirata, Kazumasa; Kawabata, Kenji; Mizuguchi, Hiroyuki

    2014-11-25

    Interindividual differences in hepatic metabolism, which are mainly due to genetic polymorphism in its gene, have a large influence on individual drug efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells have the potential to predict interindividual differences in drug metabolism capacity and drug response. However, it remains uncertain whether human iPSC-derived HLCs can reproduce the interindividual difference in hepatic metabolism and drug response. We found that cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary human hepatocytes (PHH)-iPS-HLCs were highly correlated with those of PHHs, suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity and drug responsiveness. We also demonstrated that the interindividual differences, which are due to the diversity of individual SNPs in the CYP gene, could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our knowledge, the first PHH-iPS-HLC panel that reflects the interindividual differences of hepatic drug-metabolizing capacity and drug responsiveness.

  8. Habit strength is predicted by activity dynamics in goal-directed brain systems during training.

    PubMed

    Zwosta, Katharina; Ruge, Hannes; Goschke, Thomas; Wolfensteller, Uta

    2018-01-15

    Previous neuroscientific research revealed insights into the brain networks supporting goal-directed and habitual behavior, respectively. However, it remains unclear how these contribute to inter-individual differences in habit strength which is relevant for understanding not only normal behavior but also more severe dysregulations between these types of action control, such as in addiction. In the present fMRI study, we trained subjects on approach and avoidance behavior for an extended period of time before testing the habit strength of the acquired stimulus-response associations. We found that stronger habits were associated with a stronger decrease in inferior parietal lobule activity for approach and avoidance behavior and weaker vmPFC activity at the end of training for avoidance behavior, areas associated with the anticipation of outcome identity and value. VmPFC in particular showed markedly different activity dynamics during the training of approach and avoidance behavior. Furthermore, while ongoing training was accompanied by increasing functional connectivity between posterior putamen and premotor cortex, consistent with previous assumptions about the neural basis of increasing habitualization, this was not predictive of later habit strength. Together, our findings suggest that inter-individual differences in habitual behavior are driven by differences in the persistent involvement of brain areas supporting goal-directed behavior during training. Copyright © 2017. Published by Elsevier Inc.

  9. 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

  10. 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.

  11. Individual Differences in Autobiographical Memory.

    PubMed

    Palombo, Daniela J; Sheldon, Signy; Levine, Brian

    2018-07-01

    Although humans have a remarkable capacity to recall a wealth of detail from the past, there are marked interindividual differences in the quantity and quality of our mnemonic experiences. Such differences in autobiographical memory may appear self-evident, yet there has been little research on this topic. In this review, we synthesize an emerging body of research regarding individual differences in autobiographical memory. We focus on two syndromes that fall at the extremes of the 'remembering' dimension: highly superior autobiographical memory (HSAM) and severely deficient autobiographical memory (SDAM). We also discuss findings from research on less extreme individual differences in autobiographical memory. This avenue of research is pivotal for a full description of the behavioral and neural substrates of autobiographical memory. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. 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

  13. Does oxygen delivery explain interindividual variation in forearm critical impulse?

    PubMed

    Kellawan, J Mikhail; Bentley, Robert F; Bravo, Michael F; Moynes, Jackie S; Tschakovsky, Michael E

    2014-11-01

    Within individuals, critical power appears sensitive to manipulations in O2 delivery. We asked whether interindividual differences in forearm O2 delivery might account for a majority of the interindividual differences in forearm critical force impulse (critical impulse), the force analog of critical power. Ten healthy men (24.6 ± 7.10 years) completed a maximal effort rhythmic handgrip exercise test (1 sec contraction-2 sec relaxation) for 10 min. The average of contraction impulses over the last 30 sec quantified critical impulse. Forearm brachial artery blood flow (FBF; echo and Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured continuously. O2 delivery (FBF arterial oxygen content (venous blood [hemoglobin] and oxygen saturation from pulse oximetry)) and forearm vascular conductance (FVC; FBF·MAP(-1)) were calculated. There was a wide range in O2 delivery (59.98-121.15 O2 mL·min(-1)) and critical impulse (381.5-584.8 N) across subjects. During maximal effort exercise, O2 delivery increased rapidly, plateauing well before the declining forearm impulse and explained most of the interindividual differences in critical impulse (r(2) = 0.85, P < 0.01). Both vasodilation (r(2) = 0.64, P < 0.001) and the exercise pressor response (r(2) = 0.33, P < 0.001) independently contributed to interindividual differences in FBF. In conclusion, interindividual differences in forearm O2 delivery account for most of the interindividual variation in critical impulse. Furthermore, individual differences in pressor response play an important role in determining differences in O2 delivery in addition to vasodilation. The mechanistic origins of this vasodilatory and pressor response heterogeneity across individuals remain to be determined. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  14. Does oxygen delivery explain interindividual variation in forearm critical impulse?

    PubMed Central

    Kellawan, J. Mikhail; Bentley, Robert F.; Bravo, Michael F.; Moynes, Jackie S.; Tschakovsky, Michael E.

    2014-01-01

    Abstract Within individuals, critical power appears sensitive to manipulations in O2 delivery. We asked whether interindividual differences in forearm O2 delivery might account for a majority of the interindividual differences in forearm critical force impulse (critical impulse), the force analog of critical power. Ten healthy men (24.6 ± 7.10 years) completed a maximal effort rhythmic handgrip exercise test (1 sec contraction‐2 sec relaxation) for 10 min. The average of contraction impulses over the last 30 sec quantified critical impulse. Forearm brachial artery blood flow (FBF; echo and Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured continuously. O2 delivery (FBF arterial oxygen content (venous blood [hemoglobin] and oxygen saturation from pulse oximetry)) and forearm vascular conductance (FVC; FBF·MAP−1) were calculated. There was a wide range in O2 delivery (59.98–121.15 O2 mL·min−1) and critical impulse (381.5–584.8 N) across subjects. During maximal effort exercise, O2 delivery increased rapidly, plateauing well before the declining forearm impulse and explained most of the interindividual differences in critical impulse (r2 = 0.85, P < 0.01). Both vasodilation (r2 = 0.64, P < 0.001) and the exercise pressor response (r2 = 0.33, P < 0.001) independently contributed to interindividual differences in FBF. In conclusion, interindividual differences in forearm O2 delivery account for most of the interindividual variation in critical impulse. Furthermore, individual differences in pressor response play an important role in determining differences in O2 delivery in addition to vasodilation. The mechanistic origins of this vasodilatory and pressor response heterogeneity across individuals remain to be determined. PMID:25413323

  15. The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.

    PubMed

    Teh, Ai Ling; Pan, Hong; Chen, Li; Ong, Mei-Lyn; Dogra, Shaillay; Wong, Johnny; MacIsaac, Julia L; Mah, Sarah M; McEwen, Lisa M; Saw, Seang-Mei; Godfrey, Keith M; Chong, Yap-Seng; Kwek, Kenneth; Kwoh, Chee-Keong; Soh, Shu-E; Chong, Mary F F; Barton, Sheila; Karnani, Neerja; Cheong, Clara Y; Buschdorf, Jan Paul; Stünkel, Walter; Kobor, Michael S; Meaney, Michael J; Gluckman, Peter D; Holbrook, Joanna D

    2014-07-01

    Integrating the genotype with epigenetic marks holds the promise of better understanding the biology that underlies the complex interactions of inherited and environmental components that define the developmental origins of a range of disorders. The quality of the in utero environment significantly influences health over the lifecourse. Epigenetics, and in particular DNA methylation marks, have been postulated as a mechanism for the enduring effects of the prenatal environment. Accordingly, neonate methylomes contain molecular memory of the individual in utero experience. However, interindividual variation in methylation can also be a consequence of DNA sequence polymorphisms that result in methylation quantitative trait loci (methQTLs) and, potentially, the interaction between fixed genetic variation and environmental influences. We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctuate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. MethQTLs were readily detected in neonatal methylomes, and genotype alone best explained ∼25% of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age, and birth order. Our study sheds new light on the complex relationship between biological inheritance as represented by genotype and individual prenatal experience and suggests the importance of considering both fixed genetic variation and environmental factors in interpreting epigenetic variation. © 2014 Teh et al.; Published by Cold Spring Harbor Laboratory Press.

  16. An Observational Investigation of Behavioral Contagion in Common Marmosets (Callithrix jacchus): Indications for Contagious Scent-Marking

    PubMed Central

    Massen, Jorg J. M.; Šlipogor, Vedrana; Gallup, Andrew C.

    2016-01-01

    Behavioral contagion is suggested to promote group coordination that may facilitate activity transitions, increased vigilance, and state matching. Apart from contagious yawning, however, very little attention has been given to this phenomenon, and studies on contagious yawning in primates have so far only focused on Old World monkeys and apes. Here we studied behavioral contagion in common marmosets, a species for which group coordination and vigilance are paramount. In particular, we investigated the contagiousness of yawning, stretching, scratching, tongue protrusion, gnawing, and scent-marking. We coded these behaviors from 14 adult marmosets, from two different social groups. During testing sessions, animals were separated into groups of four individuals for 20-min observation periods, across three distinct diurnal time points (morning, midday, and afternoon) to test for circadian patterns. We observed almost no yawning (0.12 yawns/h) and very little stretching behavior. For all other behaviors, which were more common, we found several temporal and inter-individual differences (i.e., sex, age, dominance status) predictive of these responses. Moreover, we found that gnawing and scent-marking, which almost always co-occurred as a fixed-action pattern, were highly temporally clustered within observation sessions. We discuss the relative absence of yawning in marmosets as well as the possible function of contagious scent-marking, and provide suggestions for future research into the proximate and ultimate functions of these behaviors in marmosets. PMID:27563294

  17. Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

    PubMed

    Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

    2012-02-01

    There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  18. 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.

  19. 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.

  20. Inter-individual Differences in the Effects of Aircraft Noise on Sleep Fragmentation

    PubMed Central

    McGuire, Sarah; Müller, Uwe; Elmenhorst, Eva-Maria; Basner, Mathias

    2016-01-01

    Study Objectives: Environmental noise exposure disturbs sleep and impairs recuperation, and may contribute to the increased risk for (cardiovascular) disease. Noise policy and regulation are usually based on average responses despite potentially large inter-individual differences in the effects of traffic noise on sleep. In this analysis, we investigated what percentage of the total variance in noise-induced awakening reactions can be explained by stable inter-individual differences. Methods: We investigated 69 healthy subjects polysomnographically (mean ± standard deviation 40 ± 13 years, range 18–68 years, 32 male) in this randomized, balanced, double-blind, repeated measures laboratory study. This study included one adaptation night, 9 nights with exposure to 40, 80, or 120 road, rail, and/or air traffic noise events (including one noise-free control night), and one recovery night. Results: Mixed-effects models of variance controlling for reaction probability in noise-free control nights, age, sex, number of noise events, and study night showed that 40.5% of the total variance in awakening probability and 52.0% of the total variance in EEG arousal probability were explained by inter-individual differences. If the data set was restricted to nights (4 exposure nights with 80 noise events per night), 46.7% of the total variance in awakening probability and 57.9% of the total variance in EEG arousal probability were explained by inter-individual differences. The results thus demonstrate that, even in this relatively homogeneous, healthy, adult study population, a considerable amount of the variance observed in noise-induced sleep disturbance can be explained by inter-individual differences that cannot be explained by age, gender, or specific study design aspects. Conclusions: It will be important to identify those at higher risk for noise induced sleep disturbance. Furthermore, the custom to base noise policy and legislation on average responses should be re-assessed based on these findings. Citation: McGuire S, Müller U, Elmenhorst EM, Basner M. Inter-individual differences in the effects of aircraft noise on sleep fragmentation. SLEEP 2016;39(5):1107–1110. PMID:26856901

  1. 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.

  2. 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

  3. Understanding the utility of emotional approach coping: evidence from a laboratory stressor and daily life

    PubMed Central

    Juth, Vanessa; Dickerson, Sally S.; Zoccola, Peggy M.; Lam, Suman

    2015-01-01

    Background Dispositional emotional approach coping (EAC) marks an adaptive tendency to process and express emotions. EAC’s association with cognitions, affect, and intra- and interindividual characteristics that may account for its utility was examined in response to an acute stressor and in daily life. Design This study included a laboratory stress task and ecological momentary assessment. Methods Healthy undergraduate students (n = 124; mean age: 20; women: 56%) completed a laboratory component (baseline survey, speech stress task, pre- and posttask measures) and five subsequent days of surveys via palm pilot (six surveys/day). Results Controlling for sex, neuroticism, and social support, greater EAC was associated with more positive cognitive appraisals, personal resources, and positive affect and less-negative affect during the lab stressor, and with more perceived control and positive affect in daily life. Significant EAC × sex interactions were found for poststressor affect: men with high EAC reported more positive affect and women with high EAC reported less negative affect. Conclusions Findings provide support that EAC’s utility may be independent of intra- and interindividual characteristics, and that men and women may benefit from EAC in different ways in regards to affect. The proclivity to use EAC may come with a resiliency that protects against stress and promotes general well-being. PMID:24804564

  4. Understanding the utility of emotional approach coping: evidence from a laboratory stressor and daily life.

    PubMed

    Juth, Vanessa; Dickerson, Sally S; Zoccola, Peggy M; Lam, Suman

    2015-01-01

    Dispositional emotional approach coping (EAC) marks an adaptive tendency to process and express emotions. EAC's association with cognitions, affect, and intra- and interindividual characteristics that may account for its utility was examined in response to an acute stressor and in daily life. This study included a laboratory stress task and ecological momentary assessment. Healthy undergraduate students (n = 124; mean age: 20; women: 56%) completed a laboratory component (baseline survey, speech stress task, pre- and posttask measures) and five subsequent days of surveys via palm pilot (six surveys/day). Controlling for sex, neuroticism, and social support, greater EAC was associated with more positive cognitive appraisals, personal resources, and positive affect and less-negative affect during the lab stressor, and with more perceived control and positive affect in daily life. Significant EAC × sex interactions were found for poststressor affect: men with high EAC reported more positive affect and women with high EAC reported less negative affect. Findings provide support that EAC's utility may be independent of intra- and interindividual characteristics, and that men and women may benefit from EAC in different ways in regards to affect. The proclivity to use EAC may come with a resiliency that protects against stress and promotes general well-being.

  5. 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...

  6. Inter-individual Differences in the Effects of Aircraft Noise on Sleep Fragmentation.

    PubMed

    McGuire, Sarah; Müller, Uwe; Elmenhorst, Eva-Maria; Basner, Mathias

    2016-05-01

    Environmental noise exposure disturbs sleep and impairs recuperation, and may contribute to the increased risk for (cardiovascular) disease. Noise policy and regulation are usually based on average responses despite potentially large inter-individual differences in the effects of traffic noise on sleep. In this analysis, we investigated what percentage of the total variance in noise-induced awakening reactions can be explained by stable inter-individual differences. We investigated 69 healthy subjects polysomnographically (mean ± standard deviation 40 ± 13 years, range 18-68 years, 32 male) in this randomized, balanced, double-blind, repeated measures laboratory study. This study included one adaptation night, 9 nights with exposure to 40, 80, or 120 road, rail, and/or air traffic noise events (including one noise-free control night), and one recovery night. Mixed-effects models of variance controlling for reaction probability in noise-free control nights, age, sex, number of noise events, and study night showed that 40.5% of the total variance in awakening probability and 52.0% of the total variance in EEG arousal probability were explained by inter-individual differences. If the data set was restricted to nights (4 exposure nights with 80 noise events per night), 46.7% of the total variance in awakening probability and 57.9% of the total variance in EEG arousal probability were explained by inter-individual differences. The results thus demonstrate that, even in this relatively homogeneous, healthy, adult study population, a considerable amount of the variance observed in noise-induced sleep disturbance can be explained by inter-individual differences that cannot be explained by age, gender, or specific study design aspects. It will be important to identify those at higher risk for noise induced sleep disturbance. Furthermore, the custom to base noise policy and legislation on average responses should be re-assessed based on these findings. © 2016 Associated Professional Sleep Societies, LLC.

  7. Use of Physiologically Based Pharmacokinetic (PBPK) Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk (Final Report)

    EPA Science Inventory

    EPA announced the availability of the final report, Use of Physiologically Based Pharmacokinetic (PBPK) Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk Final Report for Cooperative Agreement. Th...

  8. 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

  9. Reward modulation of cognitive function in adult attention-deficit/hyperactivity disorder: a pilot study on the role of striatal dopamine.

    PubMed

    Aarts, Esther; van Holstein, Mieke; Hoogman, Martine; Onnink, Marten; Kan, Cornelis; Franke, Barbara; Buitelaar, Jan; Cools, Roshan

    2015-02-01

    Attention-deficit/hyperactivity disorder (ADHD) is accompanied by impairments in cognitive control, such as task-switching deficits. We investigated whether such problems, and their remediation by medication, reflect abnormal reward motivation and associated striatal dopamine transmission in ADHD. We used functional genetic neuroimaging to assess the effects of dopaminergic medication and reward motivation on task-switching and striatal BOLD signal in 23 adults with ADHD, ON and OFF methylphenidate, and 26 healthy controls. Critically, we took into account interindividual variability in striatal dopamine by exploiting a common genetic polymorphism (3'-UTR VNTR) in the DAT1 gene coding for the dopamine transporter. The results showed a highly significant group by genotype interaction in the striatum. This was because a subgroup of patients with ADHD showed markedly exaggerated effects of reward on the striatal BOLD signal during task-switching when they were OFF their dopaminergic medication. Specifically, patients carrying the 9R allele showed a greater striatal signal than healthy controls carrying this allele, whereas no effect of diagnosis was observed in 10R homozygotes. Aberrant striatal responses were normalized when 9R-carrying patients with ADHD were ON medication. These pilot data indicate an important role for aberrant reward motivation, striatal dopamine and interindividual genetic differences in cognitive processes in adult ADHD.

  10. Reward modulation of cognitive function in adult attention-deficit/hyperactivity disorder: a pilot study on the role of striatal dopamine

    PubMed Central

    Aarts, Esther; Hoogman, Martine; Onnink, Marten; Kan, Cornelis; Franke, Barbara; Buitelaar, Jan; Cools, Roshan

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is accompanied by impairments in cognitive control, such as task-switching deficits. We investigated whether such problems, and their remediation by medication, reflect abnormal reward motivation and associated striatal dopamine transmission in ADHD. We used functional genetic neuroimaging to assess the effects of dopaminergic medication and reward motivation on task-switching and striatal BOLD signal in 23 adults with ADHD, ON and OFF methylphenidate, and 26 healthy controls. Critically, we took into account interindividual variability in striatal dopamine by exploiting a common genetic polymorphism (3′-UTR VNTR) in the DAT1 gene coding for the dopamine transporter. The results showed a highly significant group by genotype interaction in the striatum. This was because a subgroup of patients with ADHD showed markedly exaggerated effects of reward on the striatal BOLD signal during task-switching when they were OFF their dopaminergic medication. Specifically, patients carrying the 9R allele showed a greater striatal signal than healthy controls carrying this allele, whereas no effect of diagnosis was observed in 10R homozygotes. Aberrant striatal responses were normalized when 9R-carrying patients with ADHD were ON medication. These pilot data indicate an important role for aberrant reward motivation, striatal dopamine and interindividual genetic differences in cognitive processes in adult ADHD. PMID:25485641

  11. Functional relevance of interindividual differences in temporal lobe callosal pathways: a DTI tractography study.

    PubMed

    Westerhausen, René; Grüner, Renate; Specht, Karsten; Hugdahl, Kenneth

    2009-06-01

    The midsagittal corpus callosum is topographically organized, that is, with regard to their cortical origin several subtracts can be distinguished within the corpus callosum that belong to specific functional brain networks. Recent diffusion tensor tractography studies have also revealed remarkable interindividual differences in the size and exact localization of these tracts. To examine the functional relevance of interindividual variability in callosal tracts, 17 right-handed male participants underwent structural and diffusion tensor magnetic resonance imaging. Probabilistic tractography was carried out to identify the callosal subregions that interconnect left and right temporal lobe auditory processing areas, and the midsagittal size of this tract was seen as indicator of the (anatomical) strength of this connection. Auditory information transfer was assessed applying an auditory speech perception task with dichotic presentations of consonant-vowel syllables (e.g., /ba-ga/). The frequency of correct left ear reports in this task served as a functional measure of interhemispheric transfer. Statistical analysis showed that a stronger anatomical connection between the superior temporal lobe areas supports a better information transfer. This specific structure-function association in the auditory modality supports the general notion that interindividual differences in callosal topography possess functional relevance.

  12. The Importance of Encoding-Related Neural Dynamics in the Prediction of Inter-Individual Differences in Verbal Working Memory Performance

    PubMed Central

    Majerus, Steve; Salmon, Eric; Attout, Lucie

    2013-01-01

    Studies of brain-behaviour interactions in the field of working memory (WM) have associated WM success with activation of a fronto-parietal network during the maintenance stage, and this mainly for visuo-spatial WM. Using an inter-individual differences approach, we demonstrate here the equal importance of neural dynamics during the encoding stage, and this in the context of verbal WM tasks which are characterized by encoding phases of long duration and sustained attentional demands. Participants encoded and maintained 5-word lists, half of them containing an unexpected word intended to disturb WM encoding and associated task-related attention processes. We observed that inter-individual differences in WM performance for lists containing disturbing stimuli were related to activation levels in a region previously associated with task-related attentional processing, the left intraparietal sulcus (IPS), and this during stimulus encoding but not maintenance; functional connectivity strength between the left IPS and lateral prefrontal cortex (PFC) further predicted WM performance. This study highlights the critical role, during WM encoding, of neural substrates involved in task-related attentional processes for predicting inter-individual differences in verbal WM performance, and, more generally, provides support for attention-based models of WM. PMID:23874935

  13. 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.

  14. Power Doppler ultrasonographic assessment of the joint-draining lymph node complex in rheumatoid arthritis: a prospective, proof-of-concept study on treatment with tumor necrosis factor inhibitors.

    PubMed

    Manzo, Antonio; Benaglio, Francesca; Vitolo, Barbara; Bortolotto, Chandra; Zibera, Francesca; Todoerti, Monica; Alpini, Claudia; Bugatti, Serena; Caporali, Roberto; Calliada, Fabrizio; Montecucco, Carlomaurizio

    2016-10-22

    Emerging research on the mechanisms of disease chronicity in experimental arthritis has included a new focus on the draining lymph node (LN). Here, we combined clinical-serological analyses and power Doppler ultrasound (PDUS) imaging to delineate noninvasively the reciprocal relationship in vivo between the joint and the draining LN in patients with rheumatoid arthritis (RA). Forty consecutive patients refractory to conventional synthetic disease-modifying anti-rheumatic drugs were examined through parallel PDUS of the hand-wrist joints and axillary LNs and compared with 20 healthy subjects. A semiquantitative score for LN gray-scale (GS) parameters (nodal hypertrophy and cortical structure) and LN PD signal was developed. A 6-month follow-up study with serial sonographic assessments was then performed on initiation of tumor necrosis factor (TNF) inhibitors. PDUS analysis of RA axillary LNs revealed the existence of marked inter-individual heterogeneity and of quantitative differences compared with healthy individuals in both GS and PD characteristics. RA LN changes were plastic, responsive to anti-TNF treatment, and displayed a degree of concordance with synovitis activity in peripheral joints. However, low LN PD signal at baseline despite active arthritis was strongly associated with a poor clinical response to TNF blockade. PDUS analysis of the draining LN in RA allows capture of measurable inter-individual differences and dynamic changes linked to the underlying pathologic process. LN and joint sonographic assessments are nonredundant approaches that may provide independent perspectives on peripheral disease and its evolution over time.

  15. Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

    PubMed

    Yang, Lun; Price, Elvin T; Chang, Ching-Wei; Li, Yan; Huang, Ying; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang

    2013-01-01

    Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

  16. Interindividual differences of corneal sensitivity. Genetic aspects.

    PubMed

    Draeger, J; Schloot, W; Wirt, H

    1985-08-01

    By means of an electronic optical esthesiometer corneal sensitivity was examined in 91 volunteers of different age groups. Additionally, the anesthetic duration of the local anesthetic benoxinate was investigated. Corneal sensitivity decreases with advancing age. Comparing male and female subjects, we can suppose that there are age and sex specific differences of corneal sensitivity. There might be additional genetic factors. There are great interindividual differences in the anesthetic duration of benoxinate. It can be assumed that benoxinate is metabolized by pseudocholinesterase. One possible explanation for the great differences in the anesthetic duration of benoxinate can be seen in the genetically determined variants of pseudocholinesterase.

  17. Reduced spontaneous but relatively normal deliberate vicarious representations in psychopathy

    PubMed Central

    Meffert, Harma; Gazzola, Valeria; den Boer, Johan A.; Bartels, Arnold A. J.

    2013-01-01

    Psychopathy is a personality disorder associated with a profound lack of empathy. Neuroscientists have associated empathy and its interindividual variation with how strongly participants activate brain regions involved in their own actions, emotions and sensations while viewing those of others. Here we compared brain activity of 18 psychopathic offenders with 26 control subjects while viewing video clips of emotional hand interactions and while experiencing similar interactions. Brain regions involved in experiencing these interactions were not spontaneously activated as strongly in the patient group while viewing the video clips. However, this group difference was markedly reduced when we specifically instructed participants to feel with the actors in the videos. Our results suggest that psychopathy is not a simple incapacity for vicarious activations but rather reduced spontaneous vicarious activations co-existing with relatively normal deliberate counterparts. PMID:23884812

  18. 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

  19. Human Occipital and Parietal GABA Selectively Influence Visual Perception of Orientation and Size.

    PubMed

    Song, Chen; Sandberg, Kristian; Andersen, Lau Møller; Blicher, Jakob Udby; Rees, Geraint

    2017-09-13

    GABA is the primary inhibitory neurotransmitter in human brain. The level of GABA varies substantially across individuals, and this variability is associated with interindividual differences in visual perception. However, it remains unclear whether the association between GABA level and visual perception reflects a general influence of visual inhibition or whether the GABA levels of different cortical regions selectively influence perception of different visual features. To address this, we studied how the GABA levels of parietal and occipital cortices related to interindividual differences in size, orientation, and brightness perception. We used visual contextual illusion as a perceptual assay since the illusion dissociates perceptual content from stimulus content and the magnitude of the illusion reflects the effect of visual inhibition. Across individuals, we observed selective correlations between the level of GABA and the magnitude of contextual illusion. Specifically, parietal GABA level correlated with size illusion magnitude but not with orientation or brightness illusion magnitude; in contrast, occipital GABA level correlated with orientation illusion magnitude but not with size or brightness illusion magnitude. Our findings reveal a region- and feature-dependent influence of GABA level on human visual perception. Parietal and occipital cortices contain, respectively, topographic maps of size and orientation preference in which neural responses to stimulus sizes and stimulus orientations are modulated by intraregional lateral connections. We propose that these lateral connections may underlie the selective influence of GABA on visual perception. SIGNIFICANCE STATEMENT GABA, the primary inhibitory neurotransmitter in human visual system, varies substantially across individuals. This interindividual variability in GABA level is linked to interindividual differences in many aspects of visual perception. However, the widespread influence of GABA raises the question of whether interindividual variability in GABA reflects an overall variability in visual inhibition and has a general influence on visual perception or whether the GABA levels of different cortical regions have selective influence on perception of different visual features. Here we report a region- and feature-dependent influence of GABA level on human visual perception. Our findings suggest that GABA level of a cortical region selectively influences perception of visual features that are topographically mapped in this region through intraregional lateral connections. Copyright © 2017 Song, Sandberg et al.

  20. Age differences and interindividual variation in cognition in community-dwelling elderly.

    PubMed

    Christensen, H; Mackinnon, A; Jorm, A F; Henderson, A S; Scott, L R; Korten, A E

    1994-09-01

    The cognitive test performance of 897 community-dwelling elderly Ss, aged 70 years and over, was examined for age trends and interindividual variation. Data were subjected to factor analysis, and 3 factors emerged (Crystallized Intelligence, Fluid Intelligence, and Memory). Over the age span sampled, Crystallized Intelligence, Fluid Intelligence, and Memory all decreased with the decrease being greatest for Fluid Intelligence and least for Crystallized Intelligence. Interindividual variation increased for Fluid Intelligence and Memory, but not for Crystallized Intelligence. These findings give support to the view that crystallized intelligence is lower in the very old and that there is a greater degree of variability in test performance with advancing age.

  1. 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.

  2. 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

  3. Individual responses to short-term heat acclimatisation as predictors of football performance in a hot, dry environment.

    PubMed

    Racinais, Sebastien; Mohr, Magni; Buchheit, Martin; Voss, Sven Christian; Gaoua, Nadia; Grantham, Justin; Nybo, Lars

    2012-09-01

    To identify the relationship between field performance in a hot environment and individual heat acclimatisation responses in football players. Nineteen semiprofessional football players completed a match in 21°C followed by 6 days of acclimatisation in dry heat (38-43°C, 12-30% relative humidity) and a match in ~43°C. A heat-response test (30 min walk+30 min seated; 44°C) was performed at the beginning and end of the acclimatisation period. The acclimatisation period increased sweat rate by 34% during a standard heat-exposure test and reduced sweat sodium concentration by 18% (both p≤0.005). Plasma volume changes showed large interindividual differences (-10 to +20%). Match-running performance was impaired in hot ambient condition and demonstrated marked interindividual differences (total distance -6.0±5.8%, high-intensity running -16.4±21.5%, both p≤0.002). Only haematological markers investigated during the heat-response test correlated with the ability of the player to cope with heat stress in a competitive situation; that is, changes in haematocrit between the heat-response tests were correlated to changes in total running during the game, r=-0.75; 90%CI [-0.88 to -0.51]. Heat acclimatisation responses and in turn, match-running performance in the heat, are highly individual. The players displaying the largest haematological adaptations were able to maintain the same activity when playing in the heat as when playing in temperate conditions. As such, team doctors might use acclimatisation indicators obtained from a heat-response test to predict the ability of individual players to cope with heat in competitive situations and individualise their preparation accordingly.

  4. Interindividual differences in motor network connectivity and behavioral response to iTBS in stroke patients.

    PubMed

    Diekhoff-Krebs, Svenja; Pool, Eva-Maria; Sarfeld, Anna-Sophia; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

    2017-01-01

    Cerebral plasticity-inducing approaches like repetitive transcranial magnetic stimulation (rTMS) are of high interest in situations where reorganization of neural networks can be observed, e.g., after stroke. However, an increasing number of studies suggest that improvements in motor performance of the stroke-affected hand following modulation of primary motor cortex (M1) excitability by rTMS shows a high interindividual variability. We here tested the hypothesis that in stroke patients the interindividual variability of behavioral response to excitatory rTMS is related to interindividual differences in network connectivity of the stimulated region. Chronic stroke patients ( n  = 14) and healthy controls ( n  = 12) were scanned with functional magnetic resonance imaging (fMRI) while performing a simple hand motor task. Dynamic causal modeling (DCM) was used to investigate effective connectivity of key motor regions. On two different days after the fMRI experiment, patients received either intermittent theta-burst stimulation (iTBS) over ipsilesional M1 or control stimulation over the parieto-occipital cortex. Motor performance and TMS parameters of cortical excitability were measured before and after iTBS. Our results revealed that patients with better motor performance of the affected hand showed stronger endogenous coupling between supplemental motor area (SMA) and M1 before starting the iTBS intervention. Applying iTBS to ipsilesional M1 significantly increased ipsilesional M1 excitability and decreased contralesional M1 excitability as compared to control stimulation. Individual behavioral improvements following iTBS specifically correlated with neural coupling strengths in the stimulated hemisphere prior to stimulation, especially for connections targeting the stimulated M1. Combining endogenous connectivity and behavioral parameters explained 82% of the variance in hand motor performance observed after iTBS. In conclusion, the data suggest that the individual susceptibility to iTBS after stroke is influenced by interindividual differences in motor network connectivity of the lesioned hemisphere.

  5. 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.

  6. 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.

  7. Interindividual variation in thermal sensitivity of maximal sprint speed, thermal behavior, and resting metabolic rate in a lizard.

    PubMed

    Artacho, Paulina; Jouanneau, Isabelle; Le Galliard, Jean-François

    2013-01-01

    Studies of the relationship of performance and behavioral traits with environmental factors have tended to neglect interindividual variation even though quantification of this variation is fundamental to understanding how phenotypic traits can evolve. In ectotherms, functional integration of locomotor performance, thermal behavior, and energy metabolism is of special interest because of the potential for coadaptation among these traits. For this reason, we analyzed interindividual variation, covariation, and repeatability of the thermal sensitivity of maximal sprint speed, preferred body temperature, thermal precision, and resting metabolic rate measured in ca. 200 common lizards (Zootoca vivipara) that varied by sex, age, and body size. We found significant interindividual variation in selected body temperatures and in the thermal performance curve of maximal sprint speed for both the intercept (expected trait value at the average temperature) and the slope (measure of thermal sensitivity). Interindividual differences in maximal sprint speed across temperatures, preferred body temperature, and thermal precision were significantly repeatable. A positive relationship existed between preferred body temperature and thermal precision, implying that individuals selecting higher temperatures were more precise. The resting metabolic rate was highly variable but was not related to thermal sensitivity of maximal sprint speed or thermal behavior. Thus, locomotor performance, thermal behavior, and energy metabolism were not directly functionally linked in the common lizard.

  8. Host‐related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

    PubMed Central

    Desmarchelier, Charles; Dragsted, Lars O.; Nielsen, Charlotte S.; Stahl, Wilhelm; Rühl, Ralph; Keijer, Jaap; Borel, Patrick

    2017-01-01

    Carotenoid dietary intake and their endogenous levels have been associated with a decreased risk of several chronic diseases. There are indications that carotenoid bioavailability depends, in addition to the food matrix, on host factors. These include diseases (e.g. colitis), life‐style habits (e.g. smoking), gender and age, as well as genetic variations including single nucleotide polymorphisms that govern carotenoid metabolism. These are expected to explain interindividual differences that contribute to carotenoid uptake, distribution, metabolism and excretion, and therefore possibly also their association with disease risk. For instance, digestion enzymes fostering micellization (PNLIP, CES), expression of uptake/efflux transporters (SR‐BI, CD36, NPC1L1), cleavage enzymes (BCO1/2), intracellular transporters (FABP2), secretion into chylomicrons (APOB, MTTP), carotenoid metabolism in the blood and liver (LPL, APO C/E, LDLR), and distribution to target tissues such as adipose tissue or macula (GSTP1, StARD3) depend on the activity of these proteins. In addition, human microbiota, e.g. via altering bile‐acid concentrations, may play a role in carotenoid bioavailability. In order to comprehend individual, variable responses to these compounds, an improved knowledge on intra‐/interindividual factors determining carotenoid bioavailability, including tissue distribution, is required. Here, we highlight the current knowledge on factors that may explain such intra‐/interindividual differences. PMID:28101967

  9. Polymorphisms in the Wilms Tumor Gene Are Associated With Interindividual Variations in Rubella Virus-Specific Cellular Immunity After Measles-Mumps-Rubella II Vaccination.

    PubMed

    Voigt, Emily A; Haralambieva, Iana H; Larrabee, Beth L; Kennedy, Richard B; Ovsyannikova, Inna G; Schaid, Daniel J; Poland, Gregory A

    2018-01-30

    Rubella vaccination induces widely variable immune responses in vaccine recipients. While rubella vaccination is effective at inducing immunity to rubella infection in most subjects, up to 5% of individuals do not achieve or maintain long-term protective immunity. To expand upon our previous work identifying genetic polymorphisms that are associated with these interindividual differences in humoral immunity to rubella virus, we performed a genome-wide association study in a large cohort of 1843 subjects to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus-specific cellular immune responses. We identified SNPs in the Wilms tumor protein gene (WT1) that were significantly associated (P < 5 × 10-8) with interindividual variations in rubella-specific interleukin 6 secretion from subjects' peripheral blood mononuclear cells postvaccination. No SNPs were found to be significantly associated with variations in rubella-specific interferon-γ secretion. Our findings demonstrate that genetic polymorphisms in the WT1 gene in subjects of European ancestry are associated with interindividual differences in rubella virus-specific cellular immunity after measles-mumps-rubella II vaccination. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  10. The role of interindividual variation in human carcinogenesis.

    PubMed

    Lai, C; Shields, P G

    1999-02-01

    The process of chemical carcinogenesis is a complex multistage process initiated by DNA damage in growth control genes. Carcinogens enter the body from a variety of sources, but most require metabolic activation before they can damage DNA. There are multiple protective processes that include detoxification and conjugation, DNA repair and programmed cell death. Most of these functions exhibit wide interindividual variation in the population and thus are thought to affect cancer risk. The role of gene-environment interactions is being explored, and current data indicate that genetic susceptibilities can modify carcinogen exposures from the diet and tobacco smoking, although much more data exist for the latter. This review addresses the relationships of human carcinogenesis to these interindividual differences of phase I, phase II and DNA repair enzymes.

  11. 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.

  12. An epigenomics approach to individual differences and its translation to neuropsychiatric conditions.

    PubMed

    Sweatt, J David; Tamminga, Carol A

    2016-09-01

    This review concerns epigenetic mechanisms and their roles in conferring interindividual differences, especially as related to experientially acquired and genetically driven changes in central nervous system (CNS) function. In addition, the review contains commentary regarding the possible ways in which epigenomic changes may contribute to neuropsychiatric conditions and disorders and ways in which epigenotyping might be cross-correlated with clinical phenotyping in the context of precision medicine. The review begins with a basic description of epigenetic marking in the CNS and how these changes are powerful regulators of gene readout. Means for characterizing the individual epigenotype are briefly described, with a focus on DNA cytosine methylation as a readily measurable, stable epigenetic mark. This background enables a discussion of how "epigenotyping" might be integrated along with genotyping and deep phenotyping as a means of implementing advanced precision medicine. Finally, the commentary addresses two exemplars when considering how epigenotype may correlate with and modulate cognitive and behavioral phenotype: schizophrenia and Rett syndrome. These two disorders provide an interesting compare-and-contrast example regarding possible epigenotypic regulation of behavior: whereas Rett syndrome is clearly established as being caused by disruption of the function of an epigenetic "reader" of the DNA cytosine methylome-methyl-CpG-binding protein 2 (MeCP2)-the case for a role for epigenetic mechanisms in schizophrenia is still quite speculative.

  13. Age-related, interindividual, and right/left differences in anterior-posterior foot pressure ratio in preschool children

    PubMed Central

    2013-01-01

    Background This study aimed to examine age-related, interindividual, and right/left differences in anterior-posterior foot pressure ratio in 764 preschool children (364 boys and 400 girls) aged 3.5-6.5 years. Methods Subjects maintained an upright standing posture for 10 seconds on the Footview Clinic, an instrument designed to calculate the anterior-posterior foot pressure ratio. The ratio of anterior foot pressure in each subject’s right and left feet was selected as a variable, and the mean of a 10 s measurement was used for analysis. Results The ratio of anterior foot pressure was significantly larger in the right foot than in the left foot. With regard to age, the ratio of anterior foot pressure was significantly larger in children aged over 4.5 years than in children aged 3.5 years. It was also larger in children aged 6 and 6.5 years than in children aged 4 years. Interindividual differences in variables were large, and coefficients of variance were highest in children aged 3.5 years and lowest in children aged 6.5 years. Conclusions In conclusion, anterior foot pressure increases with age in preschool children. Interindividual differences in anterior foot pressure are large and tend to decrease with age. Furthermore, the anterior foot pressure is slightly higher in the right foot than in the left foot. These results will be useful for various studies, such as examining relationships between the anterior-posterior foot pressure ratio and factors, such as untouched toes, physical fitness, and level of exercise. PMID:23601375

  14. Intra- and Inter-Individual Differences in Adolescent Depressive Mood: the Role of Relationships with Parents and Friends.

    PubMed

    Zhang, Shiyu; Baams, Laura; van de Bongardt, Daphne; Dubas, Judith Semon

    2018-05-01

    Utilizing four waves of data from 1126 secondary school Dutch adolescents (Mage = 13.95 at the first wave; 53% boys), the current study examined the interplay between parent-adolescent and friend-adolescent relationship quality (satisfaction and conflict) in relation to adolescents' depressive mood. Using multilevel analyses, the interacting effects of parent/friend relationship quality on depressive mood were tested at both the intra- and inter-individual level. Analyses at the intra-individual level investigated whether individual depressive mood fluctuated along with changes in their social relationships regardless of one's general level of depressive mood; and analyses at the inter-individual level examined whether the average differences in depressive mood between adolescents were associated with different qualities of social relationships. We interpreted the patterns of interactions between parent and friend relationships using four theoretical models: the reinforcement, toxic friends, compensation, and additive model. The results demonstrate the covariation of parent- and friend- relationship quality with adolescents' depressive mood, and highlight that parent and peer effects are not independent from each other-affirming the compensation and additive models at the intra-individual and the reinforcement and additive models at the inter-individual level. The findings highlight the robustness of the protective effects of parent and peer support and the deleterious effects of conflictual relationships for adolescent mental health. The results have implications for both the theoretical and practical design of (preventive) interventions aimed at decreasing adolescents' depressive mood.

  15. Disparities in visuo-spatial constructive abilities in Williams syndrome patients with typical deletion on chromosome 7q11.23.

    PubMed

    Muramatsu, Yukako; Tokita, Yoshihito; Mizuno, Seiji; Nakamura, Miho

    2017-02-01

    Williams syndrome (WS) is known for its uneven cognitive abilities, especially the difficulty in visuo-spatial cognition, though there are some inter-individual phenotypic differences. It has been proposed that the difficulty in visuo-spatial cognition of WS patients can be attributed to a haploinsufficiency of some genes located on the deleted region in 7q11.23, based on an examination of atypical deletions identified in WS patients with atypical cognitive deficits. According to this hypothesis, the inter-individual differences in visuo-spatial cognitive ability arise from variations in deletion. We investigated whether there were inter-individual differences in the visuo-spatial constructive abilities of five unrelated WS patients with the typical deletion on chromosome 7q11.23 that includes the candidate genes contributing visuo-spatial difficulty in WS patients. We used tests with three-dimensional factors such as Benton's three-dimensional block construction test, which are considered to be more sensitive than those with only two-dimensional factors. There were diverse inter-individual differences in the visuo-spatial constructive abilities among the present participants who shared the same typical genomic deletion of WS. One of the participants showed almost equivalent performances to typically developing adults in those tests. In the present study, we found a wide range of cognitive abilities in visuo-spatial construction even among the patients with a common deletion pattern of WS. The findings suggest that attributing differences in the phenotypes entirely to genetic factors such as an atypical deletion may not be always correct. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  16. Pharmacokinetics and concentration-effect relationships of therapeutic monoclonal antibodies and fusion proteins.

    PubMed

    Ternant, David; Paintaud, Gilles

    2005-09-01

    Although monoclonal antibodies (mAbs) constitute a major advance in therapeutics, their pharmacokinetic (PK) and pharmacodynamic (PD) properties are not fully understood. Saturable mechanisms are thought to occur in distribution and elimination of mAbs, which are protected from degradation by the Brambell's receptor (FcRn). The binding of mAbs to their target antigen explains part of their nonlinear PK and PD properties. The interindividual variability in mAb PK can be explained by several factors, including immune response against the biodrug and differences in the number of antigenic sites. The concentration-effect relationships of mAbs are complex and dependent on their mechanism of action. Interindividual differences in mAb PD can be explained by factors such as genetics and clinical status. PK and concentration-effect studies are necessary to design optimal dosing regimens. Because of their above-mentioned characteristics, the interindividual variability in their dose-response relationships must be studied by PK-PD modelling.

  17. Inter-individual differences in decision-making, flexible and goal-directed behaviors: novel insights within the prefronto-striatal networks.

    PubMed

    Fitoussi, Aurélie; Renault, Prisca; Le Moine, Catherine; Coutureau, Etienne; Cador, Martine; Dellu-Hagedorn, Françoise

    2018-03-01

    Inflexible behavior is a hallmark of several decision-making-related disorders such as ADHD and addiction. As in humans, a subset of healthy rats makes poor decisions and prefers immediate larger rewards despite suffering large losses in a rat gambling task (RGT). They also display a combination of traits reminiscent of addiction, notably inflexible behavior and perseverative responses. The goal of the present work was twofold: (1) to elucidate if behavioral inflexibility of poor decision-makers could be related to a lower quality of goal-directed behavior (action-outcome associations); (2) to uncover the neural basis of inter-individual differences in goal-directed behavior. We specifically assessed inter-individual differences in decision-making in the RGT, flexibility in the RGT-reversed version and goal-directed behavior in a contingency degradation test, i.e., response adaptation when dissociating reward delivery from the animal's action. The contributions of the medial prefrontal cortex and the dorsal striatum to action-outcome associations were assessed using Zif268 immunodetection. Inflexible behavior was related to a lower sensitivity to contingency degradation in all poor decision-makers and only in a few good decision-makers. This poorer sensitivity was associated with a lower immunoreactivity in prelimbic and infralimbic cortices and a higher one in the dorsomedial and dorsolateral striatum. These findings suggest that an imbalanced prefronto-striatal activity could underlie inaccurate goal representation in changing environments and may promote maladaptive habit formation among poor decision-makers. These data strengthen our previous work identifying biomarkers of vulnerability to develop psychiatric disorders and demonstrate the relevance of inter-individual differences to model maladaptive behaviors.

  18. Inter-individual differences in trait negative affect moderate cortisol's effects on memory formation: preliminary findings from two studies.

    PubMed

    Abercrombie, Heather C; Wirth, Michelle M; Hoks, Roxanne M

    2012-05-01

    Acute emotional arousal moderates the effects of cortisol on memory. However, it is currently unknown how stable inter-individual differences (i.e., traits) moderate cortisol's effects on memory. In two studies using within-subjects designs - 31 healthy males in Study 1 and 42 healthy subjects (22 female) in Study 2 - we measured trait negative affect (NA) and presented emotional and neutral pictures. In Study 1, we manipulated endogenous cortisol levels using a speech stressor following encoding. In Study 2, using a randomized placebo-controlled design, we pharmacologically manipulated cortisol levels prior to encoding (0.1mg/kg hydrocortisone vs. saline infused over 30min). Free recall for pictures was subsequently assessed. Trait NA repeatedly moderated the relationship between cortisol and memory formation. Findings suggested the speculative conclusion that the direction of effects may vary by sex. In males, cortisol was related to memory facilitation in subjects with lower Trait NA. Conversely, females with higher Trait NA showed greater cortisol-related increases in memory. Trait NA may be a stable inter-individual difference predicting neurocognitive effects of cortisol during stressors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Interindividual and intraindividual variations in postprandial glycemia peak time complicate precise recommendations for self-monitoring of glucose in persons with type 1 diabetes mellitus.

    PubMed

    Johansen, Mette Dencker; Gjerløv, Irene; Christiansen, Jens Sandahl; Hejlesen, Ole K

    2012-03-01

    In glycemic control, postprandial glycemia may be important to monitor and optimize as it reveals glycemic control quality, and postprandial hyperglycemia partly predicts late diabetic complications. Self-monitoring of blood glucose (SMBG) may be an appropriate technology to use, but recommendations on measurement time are crucial. We retrospectively analyzed interindividual and intraindividual variations in postprandial glycemic peak time. Continuous glucose monitoring (CGM) and carbohydrate intake were collected in 22 patients with type 1 diabetes mellitus. Meals were identified from carbohydrate intake data. For each meal, peak time was identified as time from meal to CGM zenith within 40-150 min after meal start. Interindividual (one-way Anova) and intraindividual (intraclass correlation coefficient) variation was calculated. Nineteen patients were included with sufficient meal data quality. Mean peak time was 87 ± 29 min. Mean peak time differed significantly between patients (p = 0.02). Intraclass correlation coefficient was 0.29. Significant interindividual and intraindividual variations exist in postprandial glycemia peak time, thus hindering simple and general advice regarding postprandial SMBG for detection of maximum values. © 2012 Diabetes Technology Society.

  20. Use of Physiologically Based Pharmacokinetic (PBPK) Models ...

    EPA Pesticide Factsheets

    EPA announced the availability of the final report, Use of Physiologically Based Pharmacokinetic (PBPK) Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk Final Report for Cooperative Agreement. This report describes and demonstrates techniques necessary to extrapolate and incorporate in vitro derived metabolic rate constants in PBPK models. It also includes two case study examples designed to demonstrate the applicability of such data for health risk assessment and addresses the quantification, extrapolation and interpretation of advanced biochemical information on human interindividual variability of chemical metabolism for risk assessment application. It comprises five chapters; topics and results covered in the first four chapters have been published in the peer reviewed scientific literature. Topics covered include: Data Quality ObjectivesExperimental FrameworkRequired DataTwo example case studies that develop and incorporate in vitro metabolic rate constants in PBPK models designed to quantify human interindividual variability to better direct the choice of uncertainty factors for health risk assessment. This report is intended to serve as a reference document for risk assors to use when quantifying, extrapolating, and interpretating advanced biochemical information about human interindividual variability of chemical metabolism.

  1. Generalisation within specialization: inter-individual diet variation in the only specialized salamander in the world

    PubMed Central

    Costa, Andrea; Salvidio, Sebastiano; Posillico, Mario; Matteucci, Giorgio; De Cinti, Bruno; Romano, Antonio

    2015-01-01

    Specialization is typically inferred at population and species level but in the last decade many authors highlighted this trait at the individual level, finding that generalist populations can be composed by both generalist and specialist individual. Despite hundreds of reported cases of individual specialization there is a complete lack of information on inter-individual diet variation in specialist species. We studied the diet of the Italian endemic Spectacled Salamander (Salamandrina perspicillata), in a temperate forest ecosystem, to disclose the realised trophic niche, prey selection strategy in function of phenotypic variation and inter-individual diet variation. Our results showed that Salamandrina is highly specialized on Collembola and the more specialized individuals are the better performing ones. Analyses of inter-individual diet variation showed that a subset of animals exhibited a broader trophic niche, adopting different foraging strategies. Our findings reflects the optimal foraging theory both at population and individual level, since animals in better physiological conditions are able to exploit the most profitable prey, suggesting that the two coexisting strategies are not equivalent. At last this species, feeding on decomposers of litter detritus, could play a key role determining litter retention rate, nutrient cycle and carbon sequestration. PMID:26292804

  2. 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

  3. The Stability of Social Desirability: A Latent Change Analysis.

    PubMed

    Haberecht, Katja; Schnuerer, Inga; Gaertner, Beate; John, Ulrich; Freyer-Adam, Jennis

    2015-08-01

    Social desirability has been shown to be stable in samples with higher school education. However, little is known about the stability of social desirability in more heterogeneous samples differing in school education. This study aimed to investigate the stability of social desirability and which factors predict interindividual differences in intraindividual change. As part of a randomized controlled trial, 1,243 job seekers with unhealthy alcohol use were systematically recruited at three job agencies. A total of 1,094 individuals (87.8%) participated in at least one of two follow-ups (6 and 15 months after baseline) and constitute this study's sample. The Social Desirability Scale-17 was applied. Two latent change models were conducted: Model 1 tested for interindividual differences in intraindividual change of social desirability between both follow-ups; Model 2 included possible predictors (age, sex, education, current employment status) of interindividual differences in intraindividual change. Model 1 revealed a significant decrease of social desirability over time. Model 2 revealed school education to be the only significant predictor of change. These findings indicate that stability of social desirability may depend on school education. It may not be as stable in individuals with higher school education as in individuals with lower education. © 2014 Wiley Periodicals, Inc.

  4. Key interindividual determinants in MDMA pharmacodynamics.

    PubMed

    Papaseit, E; Torrens, M; Pérez-Mañá, C; Muga, R; Farré, M

    2018-02-01

    MDMA, 3,4-methylenedioxymethamphetamine, is a synthetic phenethylamine derivative with structural and pharmacological similarities to both amphetamines and mescaline. MDMA produces characteristic amphetamine-like actions (euphoria, well-being), increases empathy, and induces pro-social effects that seem to motivate its recreational consumption and provide a basis for its potential therapeutic use. Areas covered: The aim of this review is to present the main interindividual determinants in MDMA pharmacodynamics. The principal sources of pharmacodynamic variability are reviewed, with special emphasis on sex-gender, race-ethnicity, genetic differences, interactions, and MDMA acute toxicity, as well as possible therapeutic use. Expert opinion: Acute MDMA effects are more pronounced in women than they are in men. Very limited data on the relationship between race-ethnicity and MDMA effects are available. MDMA metabolism includes some polymorphic enzymes that can slightly modify plasma concentrations and effects. Although a considerable number of studies exist about the acute effects of MDMA, the small number of subjects in each trial limits evaluation of the different interindividual factors and does not permit a clear conclusion about their influence. These issues should be considered when studying possible MDMA therapeutic use.

  5. Inter-individual variation and temperature-dependent antipredator behavior in the snake Tomodon dorsatus (Dipsadidae).

    PubMed

    Citadini, Jessyca Michele; Navas, Carlos Arturo

    2013-07-01

    Although many studies assessed the influence of temperature on the behavior of ectotermic vertebrates, little attention has been given to interindividual variation in the defensive responses of reptiles. In the present study we investigated the defensive behavior of the snake Tomodon dorsatus, in order to test the hypotheses that (1) individuals differ in their antipredator behavior consistently with the concept of behavioral syndromes, (2) temperature influences the defensive behavior, and (3) these two factors interact with each other. There was significant interindividual variation in defensive behavior, as well as consistently aggressive, passive or evasive behaviors. Temperature influenced aggressiveness, which was slightly higher when body temperature was lower, but this trend was only evident in animals with aggressive disposition. Our results corroborate the hypothesis of interaction between individuality of behavior and temperature-dependent defensive behavior in T. dorsatus. These results, together with results from previous studies, suggest that the evolution of temperature-dependent defensive behavior differs among lineages of ectothermic tetrapods. This article is part of a Special Issue entitled: insert SI title. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. 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

  7. Comparative Analysis of Arterial Parameters Variations Associated with Inter-Individual Variations in Peripheral and Aortic Blood Pressure: Cross-Sectional Study in Healthy Subjects Aged 2-84 years.

    PubMed

    Zócalo, Yanina; Curcio, Santiago; García-Espinosa, Victoria; Chiesa, Pedro; Giachetto, Gustavo; Bia, Daniel

    2017-12-01

    The association between arterial parameters and blood pressure (BP) interindividual variations could depend on the arterial segment, BP component (systolic, SBP; diastolic, DBP; pulse pressure, PP) and/or on whether central (cBP) or peripheral (pBP) BP variations are considered. To assess and compare arterial parameters variations associated with interindividual variations in cBP and pBP. Healthy subjects (n = 923; 488 males, 2-84 years) were included. pBP and cBP waves were obtained (Mobil-O-Graph; SphygmoCor). Arterial diameter, intima-media thickness, local elastic modulus (carotid, CEM; brachial, BEM; femoral, FEM) and regional (carotid-radial and carotid-femoral pulse wave velocity; crPWV and cfPWV) arterial stiffness were determined. Associations between BP and arterial parameters interindividual variations were analyzed and compared (correlations; linear regressions; slopes comparisons) considering data transformed into z-scores. Given a variation in z-cSBP or z-pSBP, z-CEM, z-FEM and z-cfPWV (stiffness indexes), were among the parameters with major BP-associated variations. z-crPWV and z-cfPWV, rather than local stiffness indexes were the parameters with major variations associated with z-DBP variations. z-cPP or z-pPP were associated with z-CEM and z-FEM variations, but not with brachial or regional stiffness variations. Most of the arterial parameters-BP slopes did not show significant differences when considering a variation in z-cSBP and z-pSBP. z-CEM and z-FEM were mainly associated with z-cPP and z-pPP variations, respectively. Disregard of age and sex, the variations in arterial parameters associated with BP interindividual variations showed differences depending on whether variations were central or peripheral; in SBP, DBP or PP and depending on the arterial segment considered.

  8. 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.

  9. 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.

  10. Eliminating the Attentional Blink through Binaural Beats: A Case for Tailored Cognitive Enhancement.

    PubMed

    Reedijk, Susan A; Bolders, Anne; Colzato, Lorenza S; Hommel, Bernhard

    2015-01-01

    Enhancing human cognitive performance is a topic that continues to spark scientific interest. Studies into cognitive-enhancement techniques often fail to take inter-individual differences into account, however, which leads to underestimation of the effectiveness of these techniques. The current study investigated the effect of binaural beats, a cognitive-enhancement technique, on attentional control in an attentional blink (AB) task. As predicted from a neurocognitive approach to cognitive control, high-frequency binaural beats eliminated the AB, but only in individuals with low spontaneous eye-blink rates (indicating low striatal dopamine levels). This suggests that the way in which cognitive-enhancement techniques, such as binaural beats, affect cognitive performance depends on inter-individual differences.

  11. Standard metabolism and growth dynamics of laboratory-reared larvae of Sardina pilchardus.

    PubMed

    Moyano, M; Garrido, S; Teodósio, M A; Peck, M A

    2014-04-01

    This study provides the first measurements of the standard respiration rate (R(S)) and growth dynamics of European sardine Sardina pilchardus larvae reared in the laboratory. At 15° C, the relationship between RS (µl O(2) individual(-1)  h(-1)) and larval dry mass (M(D), µg) was equal to: R(S) = 0·0057(±0·0007, ± s.e.)·M(D) (0·8835(±0·0268)), (8-11% M(D) day(-1)). Interindividual differences in RS were not related to interindividual differences in growth rate or somatic (Fulton's condition factor) or biochemical-based condition (RNA:DNA). © 2014 The Fisheries Society of the British Isles.

  12. Medical and Genetic Differences in the Adverse Impact of Sleep Loss on Performance: Ethical Considerations for the Medical Profession

    PubMed Central

    Czeisler, Charles A.

    2009-01-01

    The Institute of Medicine recently concluded that-on average-medical residents make more serious medical errors and have more motor vehicle crashes when they are deprived of sleep. In the interest of public safety, society has required limitations on work hours in many other safety sensitive occupations, including transportation and nuclear power generation. Those who argue in favor of traditional extended duration resident work hours often suggest that there are inter- individual differences in response to acute sleep loss or chronic sleep deprivation, implying that physicians may be more resistant than the average person to the detrimental effects of sleep deprivation on performance, although there is no evidence that physicians are particularly resistant to such effects. Indeed, recent investigations have identified genetic polymorphisms that may convey a relative resistance to the effects of prolonged wakefulness on a subset of the healthy population, although there is no evidence that physicians are over-represented in this cohort. Conversely, there are also genetic polymorphisms, sleep disorders and other inter-individual differences that appear to convey an increased vulnerability to the performance-impairing effects of 24 hours of wakefulness. Given the magnitude of inter-individual differences in the effect of sleep loss on cognitive performance, and the sizeable proportion of the population affected by sleep disorders, hospitals face a number of ethical dilemmas. How should the work hours of physicians be limited to protect patient safety optimally? For example, some have argued that, in contrast to other professions, work schedules that repeatedly induce acute and chronic sleep loss are uniquely essential to the training of physicians. If evidence were to prove this premise to be correct, how should such training be ethically accomplished in the quartile of physicians and surgeons who are most vulnerable to the effects of sleep loss on performance without unacceptably compromising patient safety? Moreover, once it is possible to identify reliably those most vulnerable to the adverse effects of sleep loss on performance, will academic medical centers have an obligation to evaluate the proficiency of both residents and staff physicians under conditions of acute and chronic sleep deprivation? Should work-hour policy limits be modified to ensure that they are not hazardous for the patients of the most vulnerable quartile of physicians, or should the limits be personalized to enable the most resistant quartile to work longer hours? Given that the prevalence of sleep disorders has increased in our society overall, and increases markedly with age, how should fitness for extended duration work hours be monitored over a physician's career? In the spirit of the dictum to do no harm, advances in understanding the medical and genetic basis of inter-individual differences in the performance vulnerability to sleep loss should be incorporated into the development of work-hour policy limits for both physicians and surgeons. PMID:19768182

  13. Medical and genetic differences in the adverse impact of sleep loss on performance: ethical considerations for the medical profession.

    PubMed

    Czeisler, Charles A

    2009-01-01

    The Institute of Medicine recently concluded that-on average-medical residents make more serious medical errors and have more motor vehicle crashes when they are deprived of sleep. In the interest of public safety, society has required limitations on work hours in many other safety sensitive occupations, including transportation and nuclear power generation. Those who argue in favor of traditional extended duration resident work hours often suggest that there are inter- individual differences in response to acute sleep loss or chronic sleep deprivation, implying that physicians may be more resistant than the average person to the detrimental effects of sleep deprivation on performance, although there is no evidence that physicians are particularly resistant to such effects. Indeed, recent investigations have identified genetic polymorphisms that may convey a relative resistance to the effects of prolonged wakefulness on a subset of the healthy population, although there is no evidence that physicians are over-represented in this cohort. Conversely, there are also genetic polymorphisms, sleep disorders and other inter-individual differences that appear to convey an increased vulnerability to the performance-impairing effects of 24 hours of wakefulness. Given the magnitude of inter-individual differences in the effect of sleep loss on cognitive performance, and the sizeable proportion of the population affected by sleep disorders, hospitals face a number of ethical dilemmas. How should the work hours of physicians be limited to protect patient safety optimally? For example, some have argued that, in contrast to other professions, work schedules that repeatedly induce acute and chronic sleep loss are uniquely essential to the training of physicians. If evidence were to prove this premise to be correct, how should such training be ethically accomplished in the quartile of physicians and surgeons who are most vulnerable to the effects of sleep loss on performance without unacceptably compromising patient safety? Moreover, once it is possible to identify reliably those most vulnerable to the adverse effects of sleep loss on performance, will academic medical centers have an obligation to evaluate the proficiency of both residents and staff physicians under conditions of acute and chronic sleep deprivation? Should work-hour policy limits be modified to ensure that they are not hazardous for the patients of the most vulnerable quartile of physicians, or should the limits be personalized to enable the most resistant quartile to work longer hours? Given that the prevalence of sleep disorders has increased in our society overall, and increases markedly with age, how should fitness for extended duration work hours be monitored over a physician's career? In the spirit of the dictum to do no harm, advances in understanding the medical and genetic basis of inter-individual differences in the performance vulnerability to sleep loss should be incorporated into the development of work-hour policy limits for both physicians and surgeons.

  14. Tracking the sources of polybrominated diphenyl ethers in birds: Foraging in waste management facilities results in higher DecaBDE exposure in males

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

    Gentes, Marie-Line, E-mail: gentes.marie_line@courrier.uqam.ca; Mazerolle, Marc J., E-mail: Marc.Mazerolle@uqat.ca; Giroux, Jean-François, E-mail: giroux.jean-francois@uqam.ca

    Differences in feeding ecology are now recognized as major determinants of inter-individual variations in contaminant profiles of free-ranging animals, but exceedingly little attention has been devoted to the role of habitat use. Marked inter-individual variations and high levels of polybrominated diphenyl ethers (PBDEs) (e.g., DecaBDE) have previously been documented in ring-billed gulls (Larus delawarensis) breeding in a colony near Montreal (QC, Canada). However, the environmental sources of these compounds, and thus the reasons causing these large inter-individual variations remain unidentified. In the present study, we used GPS-based telemetry (±5 to 10 m precision) to track ring-billed gulls from this colonymore » to reconstruct their movements at the landscape level. We related habitat use of individual gulls (n=76) to plasma concentrations (ng/g ww) and relative contributions (percentages) to Σ{sub 38}PBDEs of major congeners in the internationally restricted PentaBDE and current-use DecaBDE mixtures. Male gulls that visited waste management facilities (WMFs; i.e., landfills, wastewater treatment plants and related facilities; 25% of all GPS-tracked males) exhibited greater DecaBDE (concentrations and percentages) and lower PentaBDE (percentages) relative to those that did not. In contrast, no such relationships were found in females. Moreover, in males, DecaBDE (concentrations and percentages) increased with percentages of time spent in WMFs (i.e., ~5% of total foraging time), while PentaBDE (percentages) decreased. No relationships between percentages of time spent in other habitats (i.e., urban areas, agriculture fields, and St. Lawrence River) were found in either sex. These findings suggest that animals breeding in the vicinity of WMFs as well as mobile species that only use these sites for short stopovers to forage, could be at risk of enhanced DecaBDE exposure. - Highlights: • The study was conducted on breeding gulls with high levels of flame retardants. • Ring-billed gulls were GPS-tracked to associate habitat use with plasma PBDEs. • Males that visited waste management facilities had greater DecaBDE. • DecaBDE also increased with time spent in waste management facilities in males. • No relationships between habitat use and PBDEs were found in females.« less

  15. Spatial and Temporal Variations in Arsenic Exposure via Drinking-water in Northern Argentina

    PubMed Central

    Concha, Gabriela; Nermell, Barbro

    2006-01-01

    This study evaluated the spatial, temporal and inter-individual variations in exposure to arsenic via drinking-water in Northern Argentina, based on measurements of arsenic in water, urine, and hair. Arsenic concentrations in drinking-water varied markedly among locations, from <1 to about 200 μg/L. Over a 10-year period, water from the same source in San Antonio de los Cobres fluctuated within 140 and 220 μg/L, with no trend of decreasing concentration. Arsenic concentrations in women's urine (3–900 μg/L, specific weight 1.018 g/mL) highly correlated with concentrations in water on a group level, but showed marked variations between individuals. Arsenic concentrations in hair (range 20–1,500 μg/kg) rather poorly correlated with urinary arsenic, possibly due to external contamination. Thus, arsenic concentration in urine seems to be a better marker of individual arsenic exposure than concentrations in drinking-water and hair. PMID:17366773

  16. Money talks: neural substrate of modulation of fairness by monetary incentives

    PubMed Central

    Zhou, Yuan; Wang, Yun; Rao, Li-Lin; Yang, Liu-Qing; Li, Shu

    2014-01-01

    A unique feature of the human species is compliance with social norms, e.g., fairness, even though this normative decision means curbing self-interest. However, sometimes people prefer to pursue wealth at the expense of moral goodness. Specifically, deviations from a fairness-related normative choice have been observed in the presence of a high monetary incentive. The neural mechanism underlying this deviation from the fairness-related normative choice has yet to be determined. In order to address this issue, using functional magnetic resonance imaging we employed an ultimatum game (UG) paradigm in which fairness and a proposed monetary amount were orthogonally varied. We found evidence for a significant modulation by the proposed amount on fairness in the right lateral prefrontal cortex (PFC) and the bilateral insular cortices. Additionally, the insular subregions showed dissociable modulation patterns. Inter-individual differences in the modulation effects in the left inferior frontal gyrus (IFG) accounted for inter-individual differences in the behavioral modulation effect as measured by the rejection rate, supporting the concept that the PFC plays a critical role in making fairness-related normative decisions in a social interaction condition. Our findings provide neural evidence for the modulation of fairness by monetary incentives as well as accounting for inter-individual differences. PMID:24834034

  17. Demystifying animal 'personality' (or not): why individual variation matters to experimental biologists.

    PubMed

    Roche, Dominique G; Careau, Vincent; Binning, Sandra A

    2016-12-15

    Animal 'personality', defined as repeatable inter-individual differences in behaviour, is a concept in biology that faces intense controversy. Critics argue that the field is riddled with terminological and methodological inconsistencies and lacks a sound theoretical framework. Nevertheless, experimental biologists are increasingly studying individual differences in physiology and relating these to differences in behaviour, which can lead to fascinating insights. We encourage this trend, and in this Commentary we highlight some of the benefits of estimating variation in (and covariation among) phenotypic traits at the inter- and intra-individual levels. We focus on behaviour while drawing parallels with physiological and performance-related traits. First, we outline some of the confusion surrounding the terminology used to describe repeatable inter-individual differences in behaviour. Second, we argue that acknowledging individual behavioural differences can help researchers avoid sampling and experimental bias, increase explanatory power and, ultimately, understand how selection acts on physiological traits. Third, we summarize the latest methods to collect, analyse and present data on individual trait variation. We note that, while measuring the repeatability of phenotypic traits is informative in its own right, it is only the first step towards understanding how natural selection and genetic architecture shape intra-specific variation in complex, labile traits. Thus, understanding how and why behavioural traits evolve requires linking repeatable inter-individual behavioural differences with core aspects of physiology (e.g. neurophysiology, endocrinology, energy metabolism) and evolutionary biology (e.g. selection gradients, heritability). © 2016. Published by The Company of Biologists Ltd.

  18. 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.

  19. Effects of gonadectomy and serotonin depletion on inter-individual differences in anxiety-like behaviour in male Wistar rats.

    PubMed

    Näslund, Jakob; Studer, Erik; Johansson, Elin; Eriksson, Elias

    2016-07-15

    Previous studies in Wistar rats suggest inter-individual differences in anxiety-like behaviour as assessed using the elevated plus maze (EPM), both between sexes and among males, to be abolished by serotonin depletion. To shed further light on the influence of sex steroids and serotonin - and on the interplay between the two - on proneness for EPM-assessed anxiety in males, outbred Wistar rats were divided into those with high and low anxiety, respectively, and exposed to gonadectomy or sham operation followed by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine, or saline. Whereas gonadectomy enhanced anxiety-like behaviour in low anxiety rats so that these no longer differed in this regard from the high anxiety group, serotonin depletion reversed this effect, and also reduced anxiety in the low anxiety group regardless of gonadal state. A previously observed association between high anxiety-like behaviour and high expression of the serotonin-synthesizing enzyme tryptophan hydroxylase 2 (Tph2) in the raphe was confirmed in sham-operated animals but absent in gonadectomised rats, an ANCOVA revealing a significant interactive effect of baseline anxiety and gonadal state on Tph2 expression. It is suggested that androgens may contribute to upholding inter-individual differences in anxiety-like behaviour in male rats by interacting with serotonergic neurotransmission. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. 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.

  1. 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

  2. H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

    PubMed Central

    Fernández, Agustín F.; Bayón, Gustavo F.; Urdinguio, Rocío G.; Toraño, Estela G.; García, María G.; Carella, Antonella; Petrus-Reurer, Sandra; Ferrero, Cecilia; Martinez-Camblor, Pablo; Cubillo, Isabel; García-Castro, Javier; Delgado-Calle, Jesús; Pérez-Campo, Flor M.; Riancho, José A.; Bueno, Clara; Menéndez, Pablo; Mentink, Anouk; Mareschi, Katia; Claire, Fabian; Fagnani, Corrado; Medda, Emanuela; Toccaceli, Virgilia; Brescianini, Sonia; Moran, Sebastián; Esteller, Manel; Stolzing, Alexandra; de Boer, Jan; Nisticò, Lorenza; Stazi, Maria A.

    2015-01-01

    In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type–independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors. PMID:25271306

  3. Neural Correlates of Interindividual Differences in Children’s Audiovisual Speech Perception

    PubMed Central

    Nath, Audrey R.; Fava, Eswen E.; Beauchamp, Michael S.

    2011-01-01

    Children use information from both the auditory and visual modalities to aid in understanding speech. A dramatic illustration of this multisensory integration is the McGurk effect, an illusion in which an auditory syllable is perceived differently when it is paired with an incongruent mouth movement. However, there are significant interindividual differences in McGurk perception: some children never perceive the illusion, while others always do. Because converging evidence suggests that the posterior superior temporal sulcus (STS) is a critical site for multisensory integration, we hypothesized that activity within the STS would predict susceptibility to the McGurk effect. To test this idea, we used blood-oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) in seventeen children aged 6 to 12 years to measure brain responses to three audiovisual stimulus categories: McGurk incongruent, non-McGurk incongruent and congruent syllables. Two separate analysis approaches, one using independent functional localizers and another using whole-brain voxel-based regression, showed differences in the left STS between perceivers and non-perceivers. The STS of McGurk perceivers responded significantly more than non-perceivers to McGurk syllables, but not to other stimuli, and perceivers’ hemodynamic responses in the STS were significantly prolonged. In addition to the STS, weaker differences between perceivers and non-perceivers were observed in the FFA and extrastriate visual cortex. These results suggest that the STS is an important source of interindividual variability in children’s audiovisual speech perception. PMID:21957257

  4. Eliminating the Attentional Blink through Binaural Beats: A Case for Tailored Cognitive Enhancement

    PubMed Central

    Reedijk, Susan A.; Bolders, Anne; Colzato, Lorenza S.; Hommel, Bernhard

    2015-01-01

    Enhancing human cognitive performance is a topic that continues to spark scientific interest. Studies into cognitive-enhancement techniques often fail to take inter-individual differences into account, however, which leads to underestimation of the effectiveness of these techniques. The current study investigated the effect of binaural beats, a cognitive-enhancement technique, on attentional control in an attentional blink (AB) task. As predicted from a neurocognitive approach to cognitive control, high-frequency binaural beats eliminated the AB, but only in individuals with low spontaneous eye-blink rates (indicating low striatal dopamine levels). This suggests that the way in which cognitive-enhancement techniques, such as binaural beats, affect cognitive performance depends on inter-individual differences. PMID:26089802

  5. 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.

  6. Beyond the group mind: a quantitative review of the interindividual-intergroup discontinuity effect.

    PubMed

    Wildschut, Tim; Pinter, Brad; Vevea, Jack L; Insko, Chester A; Schopler, John

    2003-09-01

    This quantitative review of 130 comparisons of interindividual and intergroup interactions in the context of mixed-motive situations reveals that intergroup interactions are generally more competitive than interindividual interactions. The authors identify 4 moderators of this interindividual-intergroup discontinuity effect, each based on the theoretical perspective that the discontinuity effect flows from greater fear and greed in intergroup relative to interindividual interactions. Results reveal that each moderator shares a unique association with the magnitude of the discontinuity effect. The discontinuity effect is larger when (a) participants interact with an opponent whose behavior is unconstrained by the experimenter or constrained by the experimenter to be cooperative rather than constrained by the experimenter to be reciprocal, (b) group members make a group decision rather than individual decisions, (c) unconstrained communication between participants is present rather than absent, and (d) conflict of interest is severe rather than mild.

  7. 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

  8. 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.

  9. 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.

  10. Invasiveness of fibroblast-like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis.

    PubMed

    Tolboom, Tanja C A; van der Helm-Van Mil, Annette H M; Nelissen, Rob G H H; Breedveld, Ferdinand C; Toes, René E M; Huizinga, Tom W J

    2005-07-01

    Rheumatoid arthritis (RA) is characterized by inflammation and destruction of synovial joints. Fibroblast-like synoviocytes (FLS) harvested from synovial tissue of patients with RA can invade normal human cartilage in severe combined immunodeficient (SCID) mice and Matrigel basement membrane matrix in vitro. This study was undertaken to investigate the association of these in vitro characteristics with disease characteristics in patients with RA. Synovial tissue samples from 72 RA and 49 osteoarthritis (OA) patients were obtained. Samples of different joints were collected from 7 patients with RA. The FLS invasiveness in Matrigel was studied, and the intraindividual and interindividual differences were compared. From the patients with FLS who exhibited the most extreme differences in in vitro ingrowth (most and least invasive FLS), radiographs of the hands and feet were collected and scored according to the Sharp/van der Heijde method to determine the relationship between in vitro invasion data and estimated yearly joint damage progression. FLS from patients with RA were more invasive than FLS from patients with OA (P < 0.001). The mean intraindividual variation in FLS invasion was much less than the mean interindividual variation (mean +/- SD 1,067 +/- 926 and 3,845 +/- 2,367 for intraindividual and interindividual variation, respectively; P = 0.035), which shows that the level of FLS invasion is a patient characteristic. The mean +/- SEM Sharp score on radiographs of the hands or feet divided by the disease duration was 4.4 +/- 1.1 units per year of disease duration in patients with the least invasive FLS (n = 9), which was much lower compared with the 21.8 +/- 3.1 units per year of disease duration in patients with the most invasive FLS (n = 9) (P < 0.001). The ex vivo invasive behavior of FLS from RA patients is associated with the rate of joint destruction and is a patient characteristic, given the much smaller intraindividual than interindividual FLS variation.

  11. No Associations between Interindividual Differences in Sleep Parameters and Episodic Memory Consolidation

    PubMed Central

    Ackermann, Sandra; Hartmann, Francina; Papassotiropoulos, Andreas; de Quervain, Dominique J.F.; Rasch, Björn

    2015-01-01

    Study Objectives: Sleep and memory are stable and heritable traits that strongly differ between individuals. Sleep benefits memory consolidation, and the amount of slow wave sleep, sleep spindles, and rapid eye movement sleep have been repeatedly identified as reliable predictors for the amount of declarative and/or emotional memories retrieved after a consolidation period filled with sleep. These studies typically encompass small sample sizes, increasing the probability of overestimating the real association strength. In a large sample we tested whether individual differences in sleep are predictive for individual differences in memory for emotional and neutral pictures. Design: Between-subject design. Setting: Cognitive testing took place at the University of Basel, Switzerland. Sleep was recorded at participants' homes, using portable electroencephalograph-recording devices. Participants: Nine hundred-twenty-nine healthy young participants (mean age 22.48 ± 3.60 y standard deviation). Interventions: None. Measurements and results: In striking contrast to our expectations as well as numerous previous findings, we did not find any significant correlations between sleep and memory consolidation for pictorial stimuli. Conclusions: Our results indicate that individual differences in sleep are much less predictive for pictorial memory processes than previously assumed and suggest that previous studies using small sample sizes might have overestimated the association strength between sleep stage duration and pictorial memory performance. Future studies need to determine whether intraindividual differences rather than interindividual differences in sleep stage duration might be more predictive for the consolidation of emotional and neutral pictures during sleep. Citation: Ackermann S, Hartmann F, Papassotiropoulos A, de Quervain DJF, Rasch B. No associations between interindividual differences in sleep parameters and episodic memory consolidation. SLEEP 2015;38(6):951–959. PMID:25325488

  12. Consistent Individual Differences Drive Collective Behavior and Group Functioning of Schooling Fish.

    PubMed

    Jolles, Jolle W; Boogert, Neeltje J; Sridhar, Vivek H; Couzin, Iain D; Manica, Andrea

    2017-09-25

    The ubiquity of consistent inter-individual differences in behavior ("animal personalities") [1, 2] suggests that they might play a fundamental role in driving the movements and functioning of animal groups [3, 4], including their collective decision-making, foraging performance, and predator avoidance. Despite increasing evidence that highlights their importance [5-16], we still lack a unified mechanistic framework to explain and to predict how consistent inter-individual differences may drive collective behavior. Here we investigate how the structure, leadership, movement dynamics, and foraging performance of groups can emerge from inter-individual differences by high-resolution tracking of known behavioral types in free-swimming stickleback (Gasterosteus aculeatus) shoals. We show that individual's propensity to stay near others, measured by a classic "sociability" assay, was negatively linked to swim speed across a range of contexts, and predicted spatial positioning and leadership within groups as well as differences in structure and movement dynamics between groups. In turn, this trait, together with individual's exploratory tendency, measured by a classic "boldness" assay, explained individual and group foraging performance. These effects of consistent individual differences on group-level states emerged naturally from a generic model of self-organizing groups composed of individuals differing in speed and goal-orientedness. Our study provides experimental and theoretical evidence for a simple mechanism to explain the emergence of collective behavior from consistent individual differences, including variation in the structure, leadership, movement dynamics, and functional capabilities of groups, across social and ecological scales. In addition, we demonstrate individual performance is conditional on group composition, indicating how social selection may drive behavioral differentiation between individuals. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Artemisia supplementation differentially affects the mucosal and luminal ileal microbiota of diet-induced obese mice

    PubMed Central

    Shawna, Wicks; M., Taylor Christopher; Meng, Luo; Eugene, Blanchard IV; David, Ribnicky; T., Cefalu William; L., Mynatt Randall; A., Welsh David

    2014-01-01

    Objective The gut microbiome has been implicated in obesity and metabolic syndrome; however, most studies have focused on fecal or colonic samples. Several species of Artemisia have been reported to ameliorate insulin signaling both in vitro and in vivo. The aim of this study was to characterize the mucosal and luminal bacterial populations in the terminal ileum with or without supplementation with Artemisia extracts. Materials/Methods Following 4 weeks of supplementation with different Artemisia extracts (PMI 5011, Santa or Scopa), diet-induced obese mice were sacrificed and luminal and mucosal samples of terminal ileum were used to evaluate microbial community composition by pyrosequencing of 16S rDNA hypervariable regions. Results Significant differences in community structure and membership were observed between luminal and mucosal samples, irrespective of diet group. All Artemisia extracts increased the Bacteroidetes:Firmicutes ratio in mucosal samples. This effect was not observed in the luminal compartment. There was high inter-individual variability in the phylogenetic assessments of the ileal microbiota, limiting the statistical power of this pilot investigation. Conclusions Marked differences in bacterial communities exist dependent upon the biogeographic compartment in the terminal ileum. Future studies testing the effects of Artemisia or other botanical supplements require larger sample sizes for adequate statistical power. PMID:24985102

  14. Several methods to determine heavy metals in the human brain

    NASA Astrophysics Data System (ADS)

    Andrási, Erzsébet; Igaz, Sarolta; Szoboszlai, Norbert; Farkas, Éva; Ajtony, Zsolt

    1999-05-01

    The determination of naturally occurring heavy metals in various parts of the human brain is discussed. The patients had no diseases in their central nervous systems (five individuals, mean age 70 years). Twenty brain parts were selected from both hemispheres. The analysis was carried out by graphite furnace atomic absorption spectrometry, inductively coupled plasma atomic emission spectrometry and instrumental neutron activation analysis methods. Accuracy and precision of the applied techniques were tested by using standard reference materials. Two digestion methods were used to dissolve the brain samples for ICP-AES and GF-AAS. One was performed in a Parr-bomb and the second in a microwave oven. The present results show a non-homogeneous distribution of the essential elements (Cu, Fe, Mn, Zn) in normal human brain. Corresponding regions in both hemispheres showed an almost identical concentration of these elements. In the case of toxic elements (Pb, Cd) an average value in different brain regions can not be established because of the high variability of individual data. This study indicates that beside differences in Pb and Cd intake with foods or cigarette smoke inhalation, the main factors of the high inter-individual variability of these element concentrations in human brain parts may be a marked difference in individual elimination or accumulation capabilities.

  15. 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...

  16. From Human to Artificial Mouth, From Basics to Results

    NASA Astrophysics Data System (ADS)

    Mielle, Patrick; Tarrega, Amparo; Gorria, Patrick; Liodenot, Jean Jacques; Liaboeuf, Joël; Andrejewski, Jean-Luc; Salles, Christian

    2009-05-01

    Sensory perception of the flavor release during the eating of a food piece is highly dependent upon mouth parameters. Major limitations have been reported during in-vivo flavor release studies, such as marked intra- and inter-individual variability. To overcome these limitations, a chewing simulator has been developed to mimic the human mastication of food samples. The device faithfully reproduces most of the functions of the human mouth. The active cell comprises several mobile parts that can accurately reproduce shear and compression strengths and tongue functions in real-time, according to data previously collected in-vivo. The mechanical functionalities of the system were validated using peanuts, with a fair agreement with the human data. Flavor release can be monitored on-line using either API-MS or chemical sensors, or off-line using HPLC for non-volatile compounds. Couplings with API-MS detectors have shown differences in the kinetics of flavour release, as a function of the cheeses composition. Data were also collected for the analysis of taste compounds released during the human chewing but are not available yet for the Artificial Mouth.

  17. Gender Differences in Mathematics: Does the Story Need to Be Rewritten?

    ERIC Educational Resources Information Center

    Brunner, Martin; Krauss, Stefan; Kunter, Mareike

    2008-01-01

    Empirical studies of high school mathematics typically report small gender differences in favor of boys. The present article challenges this established finding by comparing two competing structural conceptions of mathematical ability. The standard model assumes mathematical ability alone to account for the interindividual differences observed on…

  18. H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells.

    PubMed

    Fernández, Agustín F; Bayón, Gustavo F; Urdinguio, Rocío G; Toraño, Estela G; García, María G; Carella, Antonella; Petrus-Reurer, Sandra; Ferrero, Cecilia; Martinez-Camblor, Pablo; Cubillo, Isabel; García-Castro, Javier; Delgado-Calle, Jesús; Pérez-Campo, Flor M; Riancho, José A; Bueno, Clara; Menéndez, Pablo; Mentink, Anouk; Mareschi, Katia; Claire, Fabian; Fagnani, Corrado; Medda, Emanuela; Toccaceli, Virgilia; Brescianini, Sonia; Moran, Sebastián; Esteller, Manel; Stolzing, Alexandra; de Boer, Jan; Nisticò, Lorenza; Stazi, Maria A; Fraga, Mario F

    2015-01-01

    In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors. © 2015 Fernández et al.; Published by Cold Spring Harbor Laboratory Press.

  19. Jump frequency may contribute to risk of jumper's knee: a study of interindividual and sex differences in a total of 11,943 jumps video recorded during training and matches in young elite volleyball players.

    PubMed

    Bahr, Martin A; Bahr, Roald

    2014-09-01

    Male sex, total training volume (number of hours per week) and match exposure (number of sets played per week) are risk factors for jumper's knee among young elite volleyball players. However, it is not known whether jump frequency differs among players on the same squad. To examine interindividual and sex differences in jump frequency during training and matches in young elite volleyball players. Observational study. Norwegian elite volleyball boarding school training programme. Student-athletes (26 boys and 18 girls, 16-18 years). Individual jump counts were recorded based on visual analysis of video recordings obtained from 1 week of volleyball training (9 training sessions for boys and 10 for girls, 14.1 h and 17.8 h of training, respectively) and 10 matches (5.9 h for boys (16 sets) and 7.7 h for girls (21 sets). A total of 11,943 jumps were recorded, 4138 during matches and 7805 during training. As training attendance and jump frequency varied substantially between players, the total exposure in training ranged from 50 to 666 jumps/week among boys and from 11 to 251 jumps/week among girls. On average, this corresponded to 35.7 jumps/h for boys and 13.7 jumps/h for girls (Student t test, p=0.002). Total jump exposure during matches ranged between 1 and 339 jumps among boys and between 0 and 379 jumps among girls, corresponding to an average jump frequency of 62.2 jumps/h for boys and 41.9 jumps/h for girls (Student t test, p<0.039). The interindividual differences in jump frequency were substantially greater than any differences observed among player functions. Jump frequency has substantial interindividual and sex differences during training and matches in young elite volleyball players. Total jump volume may represent a more important risk factor for jumper's knee than total training volume, warranting further research attention. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Parsing interindividual drug variability: an emerging role for systems pharmacology

    PubMed Central

    Turner, Richard M; Park, B Kevin; Pirmohamed, Munir

    2015-01-01

    There is notable interindividual heterogeneity in drug response, affecting both drug efficacy and toxicity, resulting in patient harm and the inefficient utilization of limited healthcare resources. Pharmacogenomics is at the forefront of research to understand interindividual drug response variability, but although many genotype-drug response associations have been identified, translation of pharmacogenomic associations into clinical practice has been hampered by inconsistent findings and inadequate predictive values. These limitations are in part due to the complex interplay between drug-specific, human body and environmental factors influencing drug response and therefore pharmacogenomics, whilst intrinsically necessary, is by itself unlikely to adequately parse drug variability. The emergent, interdisciplinary and rapidly developing field of systems pharmacology, which incorporates but goes beyond pharmacogenomics, holds significant potential to further parse interindividual drug variability. Systems pharmacology broadly encompasses two distinct research efforts, pharmacologically-orientated systems biology and pharmacometrics. Pharmacologically-orientated systems biology utilizes high throughput omics technologies, including next-generation sequencing, transcriptomics and proteomics, to identify factors associated with differential drug response within the different levels of biological organization in the hierarchical human body. Increasingly complex pharmacometric models are being developed that quantitatively integrate factors associated with drug response. Although distinct, these research areas complement one another and continual development can be facilitated by iterating between dynamic experimental and computational findings. Ultimately, quantitative data-derived models of sufficient detail will be required to help realize the goal of precision medicine. WIREs Syst Biol Med 2015, 7:221–241. doi: 10.1002/wsbm.1302 PMID:25950758

  1. GENOTYPE AND PHENOTYPE IN THE METABOLISM, TOXICITY AND CARCINOGENICITY OF ARSENIC

    EPA Science Inventory

    This research will study the role of genetic factors in the expression of arsenic toxicity. The project will determine whether the interindividual variation in response is related to differences in the capacity to metabolize inorganic arsenic, if these differences in metabolic c...

  2. The Differential role of parenting, peers, and temperament for explaining interindividual differences in 18-months-olds' comforting and helping.

    PubMed

    Schuhmacher, Nils; Collard, Jenny; Kärtner, Joscha

    2017-02-01

    This study analyzes temperamental and social correlates of 18-month-olds' (N=58) instrumental helping (i.e., handing over out-of-reach objects) and comforting (i.e., alleviating experimenter's distress). While out-of-reach helping as a basic type of prosocial behavior was not associated with any of the social and temperamental variables, comforting was associated with maternal responsible parenting, day care attendance, and temperamental fear, accounting for 34% of the total variance in a corresponding regression model. The data of the present study suggest that, while simple instrumental helping seems to be a robust developmental phenomenon, comforting is associated with specific social experiences and child temperament that constitute interindividual differences and thereby help to explain the domain-specific development of prosociality. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 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.

  4. Exposure to Total and Protein-Unbound Rifampin Is Not Affected by Malnutrition in Indonesian Tuberculosis Patients

    PubMed Central

    Ruslami, R.; Later-Nijland, H.; Mooren, F.; Teulen, M.; Apriani, L.; Koenderink, J. B.; Russel, F. G.; Burger, D. M.; Alisjahbana, B.; Wieringa, F.; van Crevel, R.; Aarnoutse, R. E.

    2015-01-01

    Nutritional status may have a profound impact on the pharmacokinetics of drugs, yet only few data are available for tuberculosis (TB) drugs. As malnutrition occurs frequently among TB patients, we assessed the effect of malnutrition on the steady-state pharmacokinetics of total and protein-unbound rifampin during the intensive phase of TB treatment. In a descriptive pharmacokinetic study in Bandung, Indonesia, patients received a fixed standard rifampin dose of 450 mg once daily during the intensive phase of TB treatment. A full pharmacokinetic curve for rifampin was recorded, and total and unbound concentrations of rifampin were analyzed in all samples. Rifampin pharmacokinetic parameters were compared between severely malnourished (BMI of <16.0 kg/m2), malnourished (BMI of <18.5 kg/m2), and well-nourished (BMI of ≥18.5 kg/m2) individuals. No difference in total and protein-unbound pharmacokinetic parameters between severely malnourished (n = 7), malnourished (n = 11), and well-nourished (n = 25) patients could be demonstrated. In addition, no significant correlation between BMI and exposure (area under the concentration-time curve from 0 to 24 h [AUC0–24] and maximum concentration of drug in serum [Cmax]) was found. Females had significantly higher total AUC0–24 (geometric mean, 59.2 versus 48.2 h · mg/liter; P = 0.02) and higher unbound AUC0–24 (geometric mean, 6.2 versus 4.8 h · mg/liter; P = 0.02) than males. Overall, a marked 2-fold interindividual variation in the free fraction was observed (7.6 to 15.0%; n = 36). Nutritional status and BMI do not appear to have a major effect on total and protein-unbound pharmacokinetic parameters of rifampin in Indonesian subjects. The large interindividual variability in the free fraction of rifampin suggests that protein-unbound rather than total rifampin concentrations should preferably be used to study exposure-response relationships. PMID:25801554

  5. Gender identity better than sex explains individual differences in episodic and semantic components of autobiographical memory and future thinking.

    PubMed

    Compère, Laurie; Rari, Eirini; Gallarda, Thierry; Assens, Adèle; Nys, Marion; Coussinoux, Sandrine; Machefaux, Sébastien; Piolino, Pascale

    2018-01-01

    A recently tested hypothesis suggests that inter-individual differences in episodic autobiographical memory (EAM) are better explained by individual identification of typical features of a gender identity than by sex. This study aimed to test this hypothesis by investigating sex and gender related differences not only in EAM but also during retrieval of more abstract self-knowledge (i.e., semantic autobiographical memory, SAM, and conceptual self, CS), and considering past and future perspectives. No sex-related differences were identified, but regardless of the sex, feminine gender identity was associated with clear differences in emotional aspects that were expressed in both episodic and more abstract forms of AM, and in the past and future perspectives, while masculine gender identity was associated with limited effects. In conclusion, our results support the hypothesis that inter-individual differences in AM are better explained by gender identity than by sex, extending this assumption to both episodic and semantic forms of AM and future thinking. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. 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.

  7. Parenting and Trajectories of Children's Maladaptive Behaviors: A 12-Year Prospective Community Study

    ERIC Educational Resources Information Center

    Luyckx, Koen; Tildesley, Elizabeth A.; Soenens, Bart; Andrews, Judy A.; Hampson, Sarah E.; Peterson, Missy; Duriez, Bart

    2011-01-01

    This study investigated how parenting accounted for interindividual differences in developmental trajectories of different child behaviors across childhood and adolescence. In a cohort sequential community sample of 1,049 children, latent class growth analysis was applied to three parent-reported dimensions (monitoring, positive parenting,…

  8. 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…

  9. Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance

    PubMed Central

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

    2014-01-01

    Aims A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. Methods A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. Results The average donepezil clearance was 7.3 l h−1 with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. Conclusion The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment. PMID:24433464

  10. Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.

    PubMed

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

    2014-07-01

    A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. The average donepezil clearance was 7.3 l h(-1) with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment. © 2014 The British Pharmacological Society.

  11. Postmortem Cholesterol Levels in Peripheral Nerve Tissue: Preliminar Considerations on Interindividual and Intraindividual Variation.

    PubMed

    Vacchiano, Giuseppe; Luna Maldonado, Aurelio; Matas Ros, Maria; Fiorenza, Elisa; Silvestre, Angela; Simonetti, Biagio; Pieri, Maria

    2018-06-01

    The study reports the evolution of the demyelinization process based on cholesterol ([CHOL]) levels quantified in median nerve samples and collected at different times-from death from both right and left wrists. The statistical data show that the phenomenon evolves differently in the right and left nerves. Such a difference can reasonably be attributed to a different multicenter evolution of the demyelinization. For data analysis, the enrolled subjects were grouped by similar postmortem intervals (PMIs), considering 3 intervals: PMI < 48 hours, 48 hours < PMI < 78 hours, and PMI > 78 hours. Data obtained from tissue dissected within 48 hours of death allowed for a PMI estimation according to the following equations: PMI = 0.000 + 0.7623 [CHOL]right (R = 0.581) for the right wrist and PMI = 0.000 + 0.8911 [CHOL]left (R = 0.794) for the left wrist.At present, this correlation cannot be considered to be definitive because of the limitation of the small size of the samples analyzed, because the differences in the sampling time and the interindividual and intraindividual variation may influence the demyelinization process.

  12. Host genetic variation influences gene expression response to rhinovirus infection.

    PubMed

    Çalışkan, Minal; Baker, Samuel W; Gilad, Yoav; Ober, Carole

    2015-04-01

    Rhinovirus (RV) is the most prevalent human respiratory virus and is responsible for at least half of all common colds. RV infections may result in a broad spectrum of effects that range from asymptomatic infections to severe lower respiratory illnesses. The basis for inter-individual variation in the response to RV infection is not well understood. In this study, we explored whether host genetic variation is associated with variation in gene expression response to RV infections between individuals. To do so, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. We mapped local and distant genetic variation that is associated with inter-individual differences in gene expression levels (eQTLs) in both uninfected and RV-infected cells. We focused specifically on response eQTLs (reQTLs), namely, genetic associations with inter-individual variation in gene expression response to RV infection. We identified local reQTLs for 38 genes, including genes with known functions in viral response (UBA7, OAS1, IRF5) and genes that have been associated with immune and RV-related diseases (e.g., ITGA2, MSR1, GSTM3). The putative regulatory regions of genes with reQTLs were enriched for binding sites of virus-activated STAT2, highlighting the role of condition-specific transcription factors in genotype-by-environment interactions. Overall, we suggest that the 38 loci associated with inter-individual variation in gene expression response to RV-infection represent promising candidates for affecting immune and RV-related respiratory diseases.

  13. 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

  14. Relevant principal factors affecting the reproducibility of insect primary culture.

    PubMed

    Ogata, Norichika; Iwabuchi, Kikuo

    2017-06-01

    The primary culture of insect cells often suffers from problems with poor reproducibility in the quality of the final cell preparations. The cellular composition of the explants (cell number and cell types), surgical methods (surgical duration and surgical isolation), and physiological and genetic differences between donors may be critical factors affecting the reproducibility of culture. However, little is known about where biological variation (interindividual differences between donors) ends and technical variation (variance in replication of culture conditions) begins. In this study, we cultured larval fat bodies from the Japanese rhinoceros beetle, Allomyrina dichotoma, and evaluated, using linear mixed models, the effect of interindividual variation between donors on the reproducibility of the culture. We also performed transcriptome analysis of the hemocyte-like cells mainly seen in the cultures using RNA sequencing and ultrastructural analyses of hemocytes using a transmission electron microscope, revealing that the cultured cells have many characteristics of insect hemocytes.

  15. Does Self-Determination Predict the School Engagement of Four Different Motivation Types in Adolescence?

    ERIC Educational Resources Information Center

    Raufelder, Diana; Regner, Nicola; Drury, Kate; Eid, Michael

    2016-01-01

    In order to enhance our understanding of inter-individual differences in scholastic motivation, this study examined if self-determination predicts the school engagement of four different motivation types (MT) in a large sample of adolescent students (N = 1088) from Brandenburg, Germany: (1) peer-dependent MT, (2) teacher-dependent MT, (3)…

  16. 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.

  17. Brain structure correlates of emotion-based rash impulsivity

    PubMed Central

    Muhlert, N.; Lawrence, A.D.

    2015-01-01

    Negative urgency (the tendency to engage in rash, ill-considered action in response to intense negative emotions), is a personality trait that has been linked to problematic involvement in several risky and impulsive behaviours, and to various forms of disinhibitory psychopathology, but its neurobiological correlates are poorly understood. Here, we explored whether inter-individual variation in levels of trait negative urgency was associated with inter-individual variation in regional grey matter volumes. Using voxel-based morphometry (VBM) in a sample (n = 152) of healthy participants, we found that smaller volumes of the dorsomedial prefrontal cortex and right temporal pole, regions previously linked to emotion appraisal, emotion regulation and emotion-based decision-making, were associated with higher levels of trait negative urgency. When controlling for other impulsivity linked personality traits (sensation seeking, lack of planning/perseverance) and negative emotionality per se (neuroticism), these associations remained, and an additional relationship was found between higher levels of trait negative urgency and smaller volumes of the left ventral striatum. This latter finding mirrors recent VBM findings in an animal model of impulsivity. Our findings offer novel insight into the brain structure correlates of one key source of inter-individual differences in impulsivity. PMID:25957991

  18. 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

  19. Preparation of a standardised faecal slurry for ex-vivo microbiota studies which reduces inter-individual donor bias.

    PubMed

    O'Donnell, Michelle M; Rea, Mary C; O'Sullivan, Órla; Flynn, Cal; Jones, Beth; McQuaid, Albert; Shanahan, Fergus; Ross, R Paul

    2016-10-01

    In-vitro gut fermentation systems provide suitable models for studying gut microbiota composition and functionality. However, such methods depend on the availability of donors and the assumption of reproducibility between microbial communities before experimental treatments commence. The aim of this study was to develop a frozen standardised inoculum (FSI) which minimizes inter-individual variation and to determine its stability over time using culture-dependent and culture-independent techniques. A method for the preparation difference of a FSI is described which involves pooling the faecal samples, centrifugation and pelleting of the cell biomass and finally homogenising the cell pellets with phosphate buffer and glycerol. Using this approach, no significant difference in total anaerobe cell viability was observed between the fresh standardised inoculum (before freezing) and the 12days post freezing FSI. Moreover, Quantitative PCR revealed no significant alterations in the estimated bacterial numbers in the FSI preparations for any of the phyla. MiSeq sequencing revealed minute differences in the relative abundance at phylum, family and genus levels between the FSI preparations. Differences in the microbiota denoted as significant were limited between preparations in the majority of cases to changes in percentage relative abundance of ±0.5%. The independently prepared FSIs revealed a high degree of reproducibility in terms of microbial composition between the three preparations. This study provides a method to produce a standardised human faecal inoculum suitable for freezing. Based on culture-dependent and independent analysis, the method ensures a degree of reproducibility between preparations by lessening the effect of inter-individual variation among the donors, thereby making the system more suitable for the accurate interpretation of the effects of experimental treatments. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Innate immunity in the vagina (Part II): Anti-HIV activity and antiviral content of human vaginal secretions.

    PubMed

    Patel, Mickey V; Ghosh, Mimi; Fahey, John V; Ochsenbauer, Christina; Rossoll, Richard M; Wira, Charles R

    2014-07-01

    Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions change across the menstrual cycle is unknown. Using a menstrual cup, vaginal secretions from pre-menopausal women were recovered at the proliferative (d6-8), mid-cycle (d13-15), and secretory (d21-23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. CCL20, RANTES, elafin, HBD2, SDF-1α, and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women and in consecutive cycles from the same woman. The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and interindividual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. © 2014 John Wiley & Sons Ltd.

  1. Reticulocyte profile in top-level alpine skiers during four consecutive competitive seasons.

    PubMed

    Banfi, Giuseppe; Tavana, Rodolfo; Freschi, Marco; Lundby, Carsten

    2010-06-01

    The role of reticulocytes (Ret) in sports medicine became clear when the count of immature erythrocytes was introduced in protocols used for anti-doping purposes. Because specific research regarding seasonal variations in Ret is lacking, we assessed Ret (and [Hb]) in top-level male and female skiers during four consecutive competitive seasons. A difference (P < 0.05) between males and females was found for [Hb] and Ret values: [Hb] was lower and Ret was higher in females. The difference was maintained across all four competitive seasons. Marked within-subject differences in [Hb], Ret and immature reticulocyte fraction values were noted; the within-subject variability was greater than the between-subject variability in both genders. For instance, a difference for Ret was consistently shown between first and second blood drawings, i.e. between basal value, before the start of training and competition, and the value at middle of season, when training workload was at highest level. Unlike Ret%, the analysis of variance showed significant changes in [Hb] values across competitive seasons for both genders. Comparison between consecutive seasons (e.g., 2005-2006 vs. 2006-2007) showed significant differences for both parameters. The behaviour of [Hb] and Ret during the various seasons was parallel in females, whereas a discrepancy existed in males. In general, inter-individual variability is quite high, thus, Ret and [Hb] modifications should be referred only to the single athlete. We confirm the validity of the use of Ret counts for anti-doping purposes.

  2. Biomarker Variance Component Estimation for Exposure Surrogate Selection and Toxicokinetic Inference

    EPA Science Inventory

    Biomarkers are useful exposure surrogates given their ability to integrate exposures through all routes and to reflect interindividual differences in toxicokinetic processes. Also, biomarker concentrations tend to vary less than corresponding environmental measurements, making th...

  3. Accountability Accentuates Interindividual-Intergroup Discontinuity by Enforcing Parochialism.

    PubMed

    Wildschut, Tim; van Horen, Femke; Hart, Claire

    2015-01-01

    Interindividual-intergroup discontinuity is the tendency for relations between groups to be more competitive than relations between individuals. We examined whether the discontinuity effect arises in part because group members experience normative pressure to favor the ingroup (parochialism). Building on the notion that accountability enhances normative pressure, we hypothesized that the discontinuity effect would be larger when accountability is present (compared to absent). A prisoner's dilemma game experiment supported this prediction. Specifically, intergroup (compared to interindividual) interaction activated an injunctive ingroup-favoring norm, and accountability enhanced the influence of this norm on competitive behavior.

  4. 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…

  5. Clinical Heterogeneity in Patients with the Hypermobility Type of Ehlers-Danlos Syndrome

    ERIC Educational Resources Information Center

    De Wandele, Inge; Rombaut, Lies; Malfait, Fransiska; De Backer, Tine; De Paepe, Anne; Calders, Patrick

    2013-01-01

    EDS-HT is a connective tissue disorder characterized by large inter-individual differences in the clinical presentation, complicating diagnosis and treatment. We aim to describe the clinical heterogeneity and to investigate whether differences in the symptom profile are also reflected as disparity in functional impairment and pain experience. In…

  6. How Brooding Minds Inhibit Negative Material: An Event-Related fMRI Study

    ERIC Educational Resources Information Center

    Vanderhasselt, Marie-Anne; Baeken, Chris; Van Schuerbeek, Peter; Luypaert, Rob; De Mey, Johan; De Raedt, Rudi

    2013-01-01

    Depressive brooding--a passive ruminative focus on one's problems, negative mood and their consequences--is a thinking style that places individuals at a greater risk to develop future psychopathology. In this study, we investigated whether inter-individual differences in depressive brooding are related to neural differences underlying the…

  7. Inquiry into terminal decline: five objectives for future study.

    PubMed

    Gerstorf, Denis; Ram, Nilam

    2013-10-01

    Notions of terminal decline propose that late-life change is primarily driven by processes closely tied to pathology and mortality rather than chronological age. We use the rationales of longitudinal research as outlined by Baltes and Nesselroade (Baltes, P., & Nesselroade, J. [1979]. History and rationale of longitudinal research. In J. R. Nesselroade & P. Baltes (Eds.), Longitudinal research in the study of behavior and development [pp. 1-39]. San Diego, CA: Academic Press) as a framework for organizing research on terminal decline. In doing so, we note that there are relatively robust descriptions of terminal decline across a variety of different domains, as well as the extent of interindividual differences in the levels of function, rates of change, and timing of terminal decline (research rationales 1 and 2). However, there is much more to learn about the interrelations among change in different domains, the underlying mechanisms of change, and the factors that contribute to interindividual differences in change (research rationales 3-5). Needed are new study designs and analytical models that better address the structural, temporal, and causal interrelations that contribute to and protect against terminal decline.

  8. Evidence of cryptic individual specialization in an opportunistic insectivorous bat

    USGS Publications Warehouse

    Cryan, Paul M.; Stricker, Craig A.; Wunder, Michael B.

    2012-01-01

    Habitat use and feeding behaviors of cryptic animals are often poorly understood. Analyses of stable isotope ratios in animal body tissues can help reveal an individual's location and resource use during tissue growth. We investigated variation in stable isotope ratios of 4 elements (H, C, N, and S) in the hair of a sedentary species of insectivorous bat (Eptesicus fuscus) inhabiting a chemically complex urban landscape. Our objective was to quantify population-level isotopic variation and test for evidence of resource specialization by individuals. Bats were sampled over 3 annual molt cycles at maternity roosts in buildings and variance components analysis was used to test whether intraindividual isotopic variation among molts differed from interindividual variation, after controlling for year and roost-group effects. Consistent with prior evidence that E. fuscus is opportunistic in its habitat use and foraging at the population level, we observed wide population-level variation for all isotopes. This variation likely reflects the chemical complexity of the urban landscape studied. However, isotopic variation among years within marked individuals was lower than variation among marked individuals within year for all isotopes, and carbon signatures indicated resource specialization by roost groups and individuals. This is the 1st study to examine variation in stable isotope ratios of individual wild bats over multiple years. Although our results suggest this population tends toward opportunistic habitat use or prey selection, or both, during molt periods, results also indicate that individuals and groups of bats composing the population might be habitat or dietary specialists—a novel finding for insectivorous bats.

  9. 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

  10. Interindividual differences in embodied marginalization: Osteological and stable isotope analyses of antebellum enslaved individuals.

    PubMed

    Dent, Sophia C

    2017-07-08

    Through pathological and stable isotope analyses, this study probes the stressors, disease ecology, and diets of enslaved individuals from an antebellum plantation cemetery. The study aims to highlight how interindividual isotopic differences reveal that marginalization is not uniformly experienced or embodied. The cemetery population consists of 16 individuals; dental and skeletal pathological indicators were collected for all individuals, and light stable isotope ratios (δ 15 N, δ 13 C) were generated from the collagen and hydroxyapatite of nine individuals. The analyzed individuals have high frequencies of enamel defects-similar to contemporaneous enslaved cemetery individuals-and particularly high frequencies of carious lesions. Skeletal analysis shows evidence of chronic conditions among several individuals, two of whom likely have tuberculosis. Although the sample size is small, stable isotope values display interesting trends: there is interindividual heterogeneity in δ 13 C values, and most subadults from the cemetery have lower δ 15 N and higher δ 13 C values than the sampled adults. These relationships can be tested with larger datasets and have the potential to reveal important information about slave foodways and the broader experience of enslavement. The results of this study suggest that racial discrimination, enslavement, and age do not fully account for the heterogeneity in degree of embodied stressors. There are likely other factors at play, intersecting with the aforementioned, that influenced the lived experience of slavery and the degree of marginalization. © 2017 Wiley Periodicals, Inc.

  11. Subjective Technology Adaptivity Predicts Technology Use in Old Age.

    PubMed

    Kamin, Stefan T; Lang, Frieder R; Beyer, Anja

    2017-01-01

    To date, not much is known about the psychological and motivational factors underlying technology use in late life. What are the interindividual determinants that lead older adults to invest in using technological innovations despite the age-related physiological changes that impose challenges on behavioral plasticity in everyday life? This research explores interindividual differences in subjective technology adaptivity - a general technology-related motivational resource that accounts for technology use in late life. More specifically, we investigate the influence of this factor relative to demographic characteristics, personality traits, and functional limitations in a longitudinal sample of community-dwelling older adults. We report results from a paper-and-pencil survey with 136 older adults between 59 and 92 years of age (mean = 71.4, SD = 7.4). Of those participants, 77 participated in a 2-year follow-up. We assessed self-reports of technology use, subjective technology adaptivity, functional limitations, and the personality traits openness to new experiences and neuroticism. Higher levels of subjective technology adaptivity were associated with technology use at the first measurement as well as increased use over the course of 2 years. Subjective technology adaptivity is a significant predictor of technology use in old age. Our findings contribute to improving the understanding of interindividual differences when using technological innovation in late life. Moreover, our findings have implications in the context of user involvement and may contribute to the successful development of innovative technology for older adults. © 2017 S. Karger AG, Basel.

  12. Impaired skeletal growth in mice with haploinsufficiency of IGF-I: genetic evidence that differences in IGF-I expression could contribute to peak bone mineral density differences

    PubMed Central

    Mohan, S; Baylink, D J

    2010-01-01

    Although it is well established that there is considerable inter-individual variation in the circulating levels of IGF-I in normal, healthy individuals and that a genetic component contributes substantially to this variation, the direct evidence that inter-individual variation in IGF-I contributes to differences in peak bone mineral density (BMD) is lacking. To examine if differences in IGF-I expression could contribute to peak BMD differences, we measured skeletal changes at days 23 (prepubertal), 31 (pubertal) and 56 (postpubertal) in mice with haploinsufficiency of IGF-I (+/−) and corresponding control mice (+/+). Mice (MF1/DBA) heterozygous for the IGF-I knockout allele were bred to generate +/+ and +/− mice (n=18–20 per group). Serum IGF-I was decreased by 23% (P<0·001) in mice with IGF-I haploinsufficiency (+/−) group at day 56 compared with the control (+/+) group. Femoral bone mineral content and BMD, as determined by dual energy X-ray absorptiometry, were reduced by 20% (P<0·001) and 12% respectively in the IGF-I (+/−) group at day 56 compared with the control group. The peripheral quantitative computed tomography measurements at the femoral mid-diaphysis revealed that periosteal circumference (7%, P<0·01) and total volumetric BMD (5%, P<0·05) were decreased significantly in the +/− group compared with the +/+ group. Furthermore, serum IGF-I showed significant positive correlations with both areal BMD (r=0·55) and periosteal circumference (r=0·66) in the pooled data from the +/+ and +/− groups. Our findings that haploinsufficiency of IGF-I caused significant reductions in serum IGF-I level, BMD and bone size, together with the previous findings, are consistent with the notion that genetic variations in IGF-I expression could, in part, contribute to inter-individual differences in peak BMD among a normal population. PMID:15930167

  13. Does self-prepared food taste better? Effects of food preparation on liking.

    PubMed

    Dohle, Simone; Rall, Sina; Siegrist, Michael

    2016-05-01

    The aim was to examine whether self-preparation of food increases the liking of healthy and unhealthy foods. The study used a 2 (preparation: self-prepared vs. other-prepared) × 2 (healthiness: healthy vs. unhealthy) between-subjects design. Female participants (N = 120) tasted food that was either self-prepared or other-prepared, and that either contained markedly healthy or unhealthy ingredients. Interindividual differences in dietary restraint were also assessed. Liking and perceived healthiness of the food served as the main dependent variables. A significant interaction effect of food preparation and healthiness of the food on liking was revealed: Self-preparation increased the liking of the healthy but not of the unhealthy food. This effect was particularly strong for individuals with high levels of dietary restraint. Moreover, the combined effect of food preparation and healthiness of the food on liking was mediated by perceived healthiness of the food. The results bolster public health programs trying to encourage people to eat less prepared ready-to-eat foods and more self-prepared food. Because time available for home food preparation is often limited, programmatic efforts to encourage food preparation could be extended to schools and workplaces. (c) 2016 APA, all rights reserved).

  14. Development of motor speed and associated movements from 5 to 18 years.

    PubMed

    Gasser, Theo; Rousson, Valentin; Caflisch, Jon; Jenni, Oskar G

    2010-03-01

    To study the development of motor speed and associated movements in participants aged 5 to 18 years for age, sex, and laterality. Ten motor tasks of the Zurich Neuromotor Assessment (repetitive and alternating movements of hands and feet, repetitive and sequential finger movements, the pegboard, static and dynamic balance, diadochokinesis) were administered to 593 right-handed participants (286 males, 307 females). A strong improvement with age was observed in motor speed from age 5 to 10, followed by a levelling-off between 12 and 18 years. Simple tasks and the pegboard matured early and complex tasks later. Simple tasks showed no associated movements beyond early childhood; in complex tasks associated movements persisted until early adulthood. The two sexes differed only marginally in speed, but markedly in associated movements. A significant laterality (p<0.001) in speed was found for all tasks except for static balance; the pegboard was most lateralized, and sequential finger movements least. Associated movements were lateralized only for a few complex tasks. We also noted a substantial interindividual variability. Motor speed and associated movements improve strongly in childhood, weakly in adolescence, and are both of developmental relevance. Because they correlate weakly, they provide complementary information.

  15. Not accounting for interindividual variability can mask habitat selection patterns: a case study on black bears.

    PubMed

    Lesmerises, Rémi; St-Laurent, Martin-Hugues

    2017-11-01

    Habitat selection studies conducted at the population scale commonly aim to describe general patterns that could improve our understanding of the limiting factors in species-habitat relationships. Researchers often consider interindividual variation in selection patterns to control for its effects and avoid pseudoreplication by using mixed-effect models that include individuals as random factors. Here, we highlight common pitfalls and possible misinterpretations of this strategy by describing habitat selection of 21 black bears Ursus americanus. We used Bayesian mixed-effect models and compared results obtained when using random intercept (i.e., population level) versus calculating individual coefficients for each independent variable (i.e., individual level). We then related interindividual variability to individual characteristics (i.e., age, sex, reproductive status, body condition) in a multivariate analysis. The assumption of comparable behavior among individuals was verified only in 40% of the cases in our seasonal best models. Indeed, we found strong and opposite responses among sampled bears and individual coefficients were linked to individual characteristics. For some covariates, contrasted responses canceled each other out at the population level. In other cases, interindividual variability was concealed by the composition of our sample, with the majority of the bears (e.g., old individuals and bears in good physical condition) driving the population response (e.g., selection of young forest cuts). Our results stress the need to consider interindividual variability to avoid misinterpretation and uninformative results, especially for a flexible and opportunistic species. This study helps to identify some ecological drivers of interindividual variability in bear habitat selection patterns.

  16. 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.

  17. A Mixture Approach to Vagueness and Ambiguity

    PubMed Central

    Verheyen, Steven; Storms, Gert

    2013-01-01

    When asked to indicate which items from a set of candidates belong to a particular natural language category inter-individual differences occur: Individuals disagree which items should be considered category members. The premise of this paper is that these inter-individual differences in semantic categorization reflect both ambiguity and vagueness. Categorization differences are said to be due to ambiguity when individuals employ different criteria for categorization. For instance, individuals may disagree whether hiking or darts is the better example of sports because they emphasize respectively whether an activity is strenuous and whether rules apply. Categorization differences are said to be due to vagueness when individuals employ different cut-offs for separating members from non-members. For instance, the decision to include hiking in the sports category or not, may hinge on how strenuous different individuals require sports to be. This claim is supported by the application of a mixture model to categorization data for eight natural language categories. The mixture model can identify latent groups of categorizers who regard different items likely category members (i.e., ambiguity) with categorizers within each of the groups differing in their propensity to provide membership responses (i.e., vagueness). The identified subgroups are shown to emphasize different sets of category attributes when making their categorization decisions. PMID:23667627

  18. 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...

  19. Accountability Accentuates Interindividual-Intergroup Discontinuity by Enforcing Parochialism

    PubMed Central

    Wildschut, Tim; van Horen, Femke; Hart, Claire

    2015-01-01

    Interindividual-intergroup discontinuity is the tendency for relations between groups to be more competitive than relations between individuals. We examined whether the discontinuity effect arises in part because group members experience normative pressure to favor the ingroup (parochialism). Building on the notion that accountability enhances normative pressure, we hypothesized that the discontinuity effect would be larger when accountability is present (compared to absent). A prisoner’s dilemma game experiment supported this prediction. Specifically, intergroup (compared to interindividual) interaction activated an injunctive ingroup-favoring norm, and accountability enhanced the influence of this norm on competitive behavior. PMID:26635691

  20. Interindividual Differences in Neonatal Imitation and the Development of Action Chains in Rhesus Macaques

    ERIC Educational Resources Information Center

    Ferrari, Pier Francesco; Paukner, Annika; Ruggiero, Angela; Darcey, Lisa; Unbehagen, Sarah; Suomi, Stephen J.

    2009-01-01

    The capacity to imitate facial gestures is highly variable in rhesus macaques and this variability may be related to differences in specific neurobehavioral patterns of development. This study evaluated the differential neonatal imitative response of 41 macaques in relation to the development of sensory, motor, and cognitive skills throughout the…

  1. Judgment of Daytime Sleepiness in Self-Reported Short, Long and Midrange Sleepers

    ERIC Educational Resources Information Center

    Mairesse, Olivier; Neu, Daniel; Migeotte, Pierre-Francois; Pattyn, Nathalie; Hofmans, Joeri; Theuns, Peter; Cluydts, Raymond; De Valck, Elke

    2012-01-01

    Sleep-wake behavior, as well as sleepiness, is regulated by the joint action of an exponentially increasing drive for sleep--sleep homeostasis--and by variations in sleep propensity due to a biological circadian oscillator. However, large inter-individual differences remain. Short and long sleepers have been known to differ in the amount of…

  2. Interindividual Differences in Learning Performance: The Effects of Age, Intelligence, and Strategic Task Approach

    ERIC Educational Resources Information Center

    Kliegel, Matthias; Altgassen, Mareike

    2006-01-01

    The present study investigated fluid and crystallized intelligence as well as strategic task approaches as potential sources of age-related differences in adult learning performance. Therefore, 45 young and 45 old adults were asked to learn pictured objects. Overall, young participants outperformed old participants in this learning test. However,…

  3. Intra- and Interindividual Variability in the Behavioral, Affective, and Perceptual Effects of Alcohol Consumption in a Social Context.

    PubMed

    Franzen, Minita; Sadikaj, Gentiana; Moskowitz, Debbie S; Ostafin, Brian D; Aan Het Rot, Marije

    2018-05-01

    We examined the influence of interindividual differences in alcohol use on the intraindividual associations of drinking occurrence with interpersonal behaviors, affect, and perceptions of others during naturally occurring social interactions. For 14 consecutive days, 219 psychology freshmen (55% female; M age  = 20.7 years, SD = 2.18) recorded their behaviors, affect, and perceptions in social interactions soon after an interpersonal event occurred. Interpersonal behaviors and perceptions were assessed in terms of dominance-submissiveness and agreeableness-quarrelsomeness. Participants also reported the number of alcoholic drinks consumed within 3 hours of each interaction. We considered the intraindividual associations of (i) having a drinking episode and (ii) the number of drinks during an episode with behaviors, affect, and perceptions and examined interindividual differences in drinking frequency and intensity during social interactions as potential moderators of these associations. Social drinking frequency and intensity moderated the associations between drinking episode and behaviors, affect, and perceptions in social interactions. During a drinking episode, more frequent social drinkers perceived others as more dominant than less frequent social drinkers. During a drinking episode in which more alcohol was consumed than usual, more frequent social drinkers also reported behaving more dominantly and experiencing less pleasant affect. As more frequent social drinkers had different interpersonal responses to drinking than less frequent social drinkers, including when they had consumed larger amounts of alcohol than usual, our results suggest a differential susceptibility to the effects of alcohol during naturally occurring social interactions among drinkers with varying drinking frequency. Copyright © 2018 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals, Inc. on behalf of Research Society on Alcoholism.

  4. Use of Mechanistic Modeling to Assess Interindividual Variability and Interspecies Differences in Active Uptake in Human and Rat Hepatocytes

    PubMed Central

    Ménochet, Karelle; Kenworthy, Kathryn E.; Houston, J. Brian

    2012-01-01

    Interindividual variability in activity of uptake transporters is evident in vivo, yet limited data exist in vitro, confounding in vitro-in vivo extrapolation. The uptake kinetics of seven organic anion-transporting polypeptide substrates was investigated over a concentration range in plated cryopreserved human hepatocytes. Active uptake clearance (CLactive, u), bidirectional passive diffusion (Pdiff), intracellular binding, and metabolism were estimated for bosentan, pitavastatin, pravastatin, repaglinide, rosuvastatin, telmisartan, and valsartan in HU4122 donor using a mechanistic two-compartment model in Matlab. Full uptake kinetics of rosuvastatin and repaglinide were also characterized in two additional donors, whereas for the remaining drugs CLactive, u was estimated at a single concentration. The unbound affinity constant (Km, u) and Pdiff values were consistent across donors, whereas Vmax was on average up to 2.8-fold greater in donor HU4122. Consistency in Km, u values allowed extrapolation of single concentration uptake activity data and assessment of interindividual variability in CLactive across donors. The maximal contribution of active transport to total uptake differed among donors, for example, 85 to 96% and 68 to 87% for rosuvastatin and repaglinide, respectively; however, in all cases the active process was the major contributor. In vitro-in vivo extrapolation indicated a general underprediction of hepatic intrinsic clearance, an average empirical scaling factor of 17.1 was estimated on the basis of seven drugs investigated in three hepatocyte donors, and donor-specific differences in empirical factors are discussed. Uptake Km, u and CLactive, u were on average 4.3- and 7.1-fold lower in human hepatocytes compared with our previously published rat data. A strategy for the use of rat uptake data to facilitate the experimental design in human hepatocytes is discussed. PMID:22665271

  5. 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...

  6. 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.

  7. Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

    PubMed

    Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

    2012-06-01

    Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

  8. Clinical Correlates of Carbon Dioxide Hypersensitivity in Children.

    PubMed

    Rappaport, Lance M; Sheerin, Christina; Carney, Dever M; Towbin, Kenneth E; Leibenluft, Ellen; Pine, Daniel S; Brotman, Melissa A; Roberson-Nay, Roxann; Hettema, John M

    2017-12-01

    Hypersensitivity to carbon dioxide (CO 2 )-enriched air may be a promising risk marker for anxiety disorders. Among adult and adolescent samples, heterogeneity in distress response to the CO 2 challenge task indexes 3 underlying classes of individuals, which distinguish between sustained and acute threat response as markers for internalizing disorders, broadly, and anxiety disorders, specifically. The present study examines latent classes in children's response to the CO 2 challenge task to clarify the association of CO 2 hypersensitivity with anxiety and internalizing symptomatology in childhood. Healthy children from a community twin sample (N = 538; age 9-13 years) rated anxious distress every 2 minutes while breathing air enriched to 7.5% CO 2 for 8 minutes. Latent growth mixture modeling evaluated potential classes of individuals with characteristic trajectories of distress during the task to clarify the association with internalizing disorder symptoms and related traits (e.g., anxiety sensitivity, irritability). Although all participants reported increased distress during the task, interindividual heterogeneity in distress indexed 3 underlying classes: a consistently low class ("low"), a consistently high class ("high"), and participants who demonstrated markedly increased acute distress ("acute"). Compared to the low class, the high class reported greater internalizing psychopathology, whereas membership in the acute class was associated with experiencing a panic-like event during the task. As in older individuals, 3 distinct trajectories emerged to capture interindividual heterogeneity in children's distress during the CO 2 challenge task. These classes were distinguished by clinical validators that reinforce the association of CO 2 hypersensitivity and internalizing disorder phenotypes in children. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. All rights reserved.

  9. Polymorphisms in HLA-DPB1 Are Associated With Differences in Rubella Virus–Specific Humoral Immunity After Vaccination

    PubMed Central

    Lambert, Nathaniel D.; Haralambieva, Iana H.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Pankratz, Vernon Shane; Poland, Gregory A.

    2015-01-01

    Vaccination with live attenuated rubella virus induces a strong immune response in most individuals. However, small numbers of subjects never reach or maintain protective antibody levels, and there is a high degree of variability in immune response. We have previously described genetic polymorphisms in HLA and other candidate genes that are associated with interindividual differences in humoral immunity to rubella virus. To expand our previous work, we performed a genome-wide association study (GWAS) to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus–specific neutralizing antibodies. We identified rs2064479 in the HLA-DPB1 genetic region as being significantly associated with humoral immune response variations after rubella vaccination (P = 8.62 × 10−8). All other significant SNPs in this GWAS were located near the HLA-DPB1 gene (P ≤ 1 × 10−7). These findings demonstrate that polymorphisms in HLA-DPB1 are strongly associated with interindividual differences in neutralizing antibody levels to rubella vaccination and represent a validation of our previous HLA work. PMID:25293367

  10. Sucrose Responsiveness, Learning Success, and Task Specialization in Ants

    ERIC Educational Resources Information Center

    Perez, Margot; Rolland, Uther; Giurfa,, Martin; d'Ettorre, Patrizia

    2013-01-01

    Social insects possess remarkable learning capabilities, which are crucial for their ecological success. They also exhibit interindividual differences in responsiveness to environmental stimuli, which underlie task specialization and division of labor. Here we investigated for the first time the relationships between sucrose responsiveness,…

  11. 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...

  12. 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

  13. INTERINDIVIDUAL VARIATION IN THE METABOLISM OF ARSENIC IN CULTURED PRIMARY HUMAN HEPATOCYTES

    EPA Science Inventory

    Liver is a prime site for conversion of inorganic arsenic (iAs) to methylated metabolites, including methylarsenicals (MAs) and dimethylarsenicals (DMAs). To assess interindividual variation in the capacity of liver to metabolize iAs, we examined the metabolic fate of arsenite (...

  14. 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.

  15. Consistent inter-individual differences in common marmosets (Callithrix jacchus) in Boldness-Shyness, Stress-Activity, and Exploration-Avoidance.

    PubMed

    Šlipogor, Vedrana; Gunhold-de Oliveira, Tina; Tadić, Zoran; Massen, Jorg J M; Bugnyar, Thomas

    2016-09-01

    The study of animal personality, defined as consistent inter-individual differences in correlated behavioral traits stable throughout time and/or contexts, has recently become one of the fastest growing areas in animal biology, with study species ranging from insects to non-human primates. The latter have, however, only occasionally been tested with standardized experiments. Instead their personality has usually been assessed using questionnaires. Therefore, this study aimed to test 21 common marmosets (Callithrix jacchus) living in three family groups, in five different experiments, and their corresponding controls. We found that behavioral differences between our animals were not only consistent over time, but also across different contexts. Moreover, the consistent behaviors formed a construct of four major non-social personality components: Boldness-Shyness in Foraging, Boldness-Shyness in Predation, Stress-Activity, and Exploration-Avoidance. We found no sex or age differences in these components, but our results did reveal differences in Exploration-Avoidance between the three family groups. As social environment can have a large influence on behavior of individuals, our results may suggest group-level similarity in personality (i.e., "group personality") in common marmosets, a species living in highly cohesive social groups. Am. J. Primatol. 78:961-973, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Stability of Individual Maillard Reaction Products in the Presence of the Human Colonic Microbiota.

    PubMed

    Hellwig, Michael; Bunzel, Diana; Huch, Melanie; Franz, Charles M A P; Kulling, Sabine E; Henle, Thomas

    2015-08-05

    Maillard reaction products (MRPs) are taken up in substantial amounts with the daily diet, but the majority are not transported across the intestinal epithelium. The aim of this study was to obtain first insights into the stability of dietary MRPs in the presence of the intestinal microbiota. Four individual MRPs, namely, N-ε-fructosyllysine (FL), N-ε-carboxymethyllysine (CML), pyrraline (PYR), and maltosine (MAL), were anaerobically incubated with fecal suspensions from eight human volunteers at 37 °C for up to 72 h. The stability of the MRPs was measured by HPLC with UV and MS/MS detections. The Amadori product FL could no longer be detected after 4 h of incubation. Marked interindividual differences were observed for CML metabolism: Depending on the individual, at least 40.7 ± 1.5% of CML was degraded after 24 h of incubation, and the subjects could thus be tentatively grouped into fast and slow metabolizers of this compound. PYR was degraded by 20.3 ± 4.4% during 24 h by all subjects. The concentration of MAL was not significantly lowered in the presence of fecal suspensions. In no case could metabolites be identified and quantified by different mass spectrometric techniques. This is the first study showing that the human colonic microbiota is able to degrade selected glycated amino acids and possibly use them as a source of energy, carbon, and/or nitrogen.

  17. 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

  18. Interindividual registration and dose mapping for voxelwise population analysis of rectal toxicity in prostate cancer radiotherapy

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

    Dréan, Gaël; Acosta, Oscar, E-mail: Oscar.Acosta@univ-rennes1.fr; Simon, Antoine

    2016-06-15

    Purpose: Recent studies revealed a trend toward voxelwise population analysis in order to understand the local dose/toxicity relationships in prostate cancer radiotherapy. Such approaches require, however, an accurate interindividual mapping of the anatomies and 3D dose distributions toward a common coordinate system. This step is challenging due to the high interindividual variability. In this paper, the authors propose a method designed for interindividual nonrigid registration of the rectum and dose mapping for population analysis. Methods: The method is based on the computation of a normalized structural description of the rectum using a Laplacian-based model. This description takes advantage of themore » tubular structure of the rectum and its centerline to be embedded in a nonrigid registration-based scheme. The performances of the method were evaluated on 30 individuals treated for prostate cancer in a leave-one-out cross validation. Results: Performance was measured using classical metrics (Dice score and Hausdorff distance), along with new metrics devised to better assess dose mapping in relation with structural deformation (dose-organ overlap). Considering these scores, the proposed method outperforms intensity-based and distance maps-based registration methods. Conclusions: The proposed method allows for accurately mapping interindividual 3D dose distributions toward a single anatomical template, opening the way for further voxelwise statistical analysis.« less

  19. Revisiting the Dedifferentiation Hypothesis with Longitudinal Multi-Cohort Data

    ERIC Educational Resources Information Center

    de Frias, Cindy M.; Lovden, Martin; Lindenberger, Ulman; Nilsson, Lars-Goran

    2007-01-01

    The present longitudinal multi-cohort study examines whether interindividual variability in cognitive performance and change increases in old age, and whether associations among developments of different cognitive functions increase with adult age. Multivariate multiple-group latent growth modeling was applied to data from narrow cohorts separated…

  20. INDIVIDUAL VARIATION IN THE FREQUENCY OF SPERM ANEUPLOIDY IN HUMANS

    EPA Science Inventory

    To examine interindividual differences in sperm chromosome aneuploidy, repeated semen specimens were obtained from a group of ten healthy men, aged 20-21 at the start of the study, and analyzed by multi-color fluorescence in situ hybridization (FISH) analysis to determine the fre...

  1. Application of in Vitro Biotransformation Data and ...

    EPA Pesticide Factsheets

    The adverse biological effects of toxic substances are dependent upon the exposure concentration and the duration of exposure. Pharmacokinetic models can quantitatively relate the external concentration of a toxicant in the environment to the internal dose of the toxicant in the target tissues of an exposed organism. The exposure concentration of a toxic substance is usually not the same as the concentration of the active form of the toxicant that reaches the target tissues following absorption, distribution, and biotransformation of the parent toxicant. Biotransformation modulates the biological activity of chemicals through bioactivation and detoxication pathways. Many toxicants require biotransformation to exert their adverse biological effects. Considerable species differences in biotransformation and other pharmacokinetic processes can make extrapolation of toxicity data from laboratory animals to humans problematic. Additionally, interindividual differences in biotransformation among human populations with diverse genetics and lifestyles can lead to considerable variability in the bioactivation of toxic chemicals. Compartmental pharmacokinetic models of animals and humans are needed to understand the quantitative relationships between chemical exposure and target tissue dose as well as animal to human differences and interindividual differences in human populations. The data-based compartmental pharmacokinetic models widely used in clinical pharmacology ha

  2. More than just noise: Inter-individual differences in fear acquisition, extinction and return of fear in humans - Biological, experiential, temperamental factors, and methodological pitfalls.

    PubMed

    Lonsdorf, Tina B; Merz, Christian J

    2017-09-01

    Why do only some individuals develop pathological anxiety following adverse events? Fear acquisition, extinction and return of fear paradigms serve as experimental learning models for the development, treatment and relapse of anxiety. Individual differences in experimental performance were however mostly regarded as 'noise' by researchers interested in basic associative learning principles. Our work for the first time presents a comprehensive literature overview and methodological discussion on inter-individual differences in fear acquisition, extinction and return of fear. We tell a story from noise that steadily develops into a meaningful tune and converges to a model of mechanisms contributing to individual risk/resilience with respect to fear and anxiety-related behavior. Furthermore, in light of the present 'replicability crisis' we identify methodological pitfalls and provide suggestions for study design and analyses tailored to individual difference research in fear conditioning. Ultimately, synergistic transdisciplinary and collaborative efforts hold promise to not only improve our mechanistic understanding but can also be expected to contribute to the development of specifically tailored ('individualized') intervention and targeted prevention programs in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Immunity in the Vagina (Part II): Anti-HIV Activity and Antiviral Content of Human Vaginal Secretions

    PubMed Central

    Patel, Mickey V.; Ghosh, Mimi; Fahey, John V.; Ochsenbauer, Christina; Rossoll, Richard M.; Wira, Charles R.

    2015-01-01

    Problem Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions changes across the menstrual cycle is unknown. Method of Study Using a menstrual cup, vaginal secretions from premenopausal women were recovered at the proliferative (d6–8), mid-cycle (d13–15) and secretory (d21–23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. Results CCL20, RANTES, elafin, HBD2, SDF-1α and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women, and in consecutive cycles from the same woman. Conclusion The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and inter-individual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. PMID:24806967

  4. Neural Control of the Circulation: How Sex and Age Differences Interact in Humans

    PubMed Central

    Joyner, Michael J.; Barnes, Jill N.; Hart, Emma C.; Wallin, B. Gunnar; Charkoudian, Nisha

    2015-01-01

    The autonomic nervous system is a key regulator of cardiovascular system. In this review we focus on how sex and aging influence autonomic regulation of blood pressure in humans in an effort to understand general issues related to how the autonomic nervous system regulates blood pressure, and the cardiovascular system as a whole. Younger women generally have lower blood pressure and sympathetic activity than younger men. However, both sexes show marked inter-individual variability across age groups with significant overlap seen. Additionally, while men across the lifespan show a clear relationship between markers of whole body sympathetic activity and vascular resistance, such a relationship is not seen in young women. In this context, the ability of the sympathetic nerves to evoke vasoconstriction is lower in young women likely as a result of concurrent β2 mediated vasodilation that offsets α-adrenergic vasoconstriction. These differences reflect both central sympatho-inhibitory effects of estrogen and also its influence on peripheral vasodilation at the level of the vascular smooth muscle and endothelium. By contrast post-menopausal women show a clear relationship between markers of whole body sympathetic traffic and vascular resistance, and sympathetic activity rises progressively in both sexes with aging. These central findings in humans are discussed in the context of differences in population-based trends in blood pressure and orthostatic intolerance. The many areas where there is little sex-specific data on how the autonomic nervous system participates in the regulation of the human cardiovascular system are highlighted. PMID:25589269

  5. Elemental mercury neurotoxicity and clinical recovery of function: A review of findings, and implications for occupational health.

    PubMed

    Calabrese, Edward J; Iavicoli, Ivo; Calabrese, Vittorio; Cory-Slechta, Deborah A; Giordano, James

    2018-05-01

    This paper assessed approximately 30 studies, mostly involving occupationally exposed subjects, concerning the extent to which those who developed elemental mercury (Hg)-induced central and/or peripheral neurotoxicities from chronic or acute exposures recover functionality and/or performance. While some recovery occurred in the vast majority of cases, the extent of such recoveries varied considerably by individual and endpoint. Factors accounting for the extensive inter-individual variation in toxicity and recovery were not specifically assessed such as age, gender, diet, environmental enrichment, chelation strategies and dose-rate. While the data indicate that psychomotor endpoints often show substantial and relatively rapid (i.e., 2-6 months) recovery and that neuropsychological endpoints display slower and less complete recovery, generalizations are difficult due to highly variable study designs, use of different endpoints measured between studies, different Hg exposures based on blood/urine concentrations and Hg dose-rates, the poor capacity for replicating findings due to the unpredictable/episodic nature of harmful exposures to elemental Hg, and the inconsistency of the initiation of studies after induced toxicities and the differing periods of follow up during recovery periods. Finally, there is strikingly limited animal model literature on the topic of recovery/reversibility of elemental Hg toxicity, a factor which significantly contributes to the overall marked uncertainties for predicting the rate and magnitude of recovery and the factors that affect it. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity

    USDA-ARS?s Scientific Manuscript database

    The estimated heritability of human BMI is close to 75%, but identified genetic variants explain only a small fraction of interindividual body-weight variation. Inherited epigenetic variants identified in mouse models named "metastable epialleles" could in principle explain this "missing heritabilit...

  7. 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…

  8. INTERINDIVIDUAL VARIATION IN THE METABOLISM OF ARSENIC IN HUMAN HEPATOCYTES

    EPA Science Inventory


    The liver is the major site for the enzymatic methylation of inorganic arsenic (iAs) in humans. Primary cultures of normal human hepatocytes isolated from tissue obtained at surgery or from donor livers have been used to study interindividual variation in the capacity of live...

  9. Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups.

    PubMed

    Schinkel, Christian; Scherens, A; Köller, M; Roellecke, G; Muhr, G; Maier, C

    2009-03-17

    The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory parameters is not yet helpful in diagnostic and follow-up of CRPS I.

  10. 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

  11. 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.

  12. Static lung compliance and body pressures in Tupinambis merianae with and without post-hepatic septum.

    PubMed

    Klein, Wilfried; Abe, Augusto S; Perry, Steven F

    2003-04-15

    The surgical removal of the post-hepatic septum (PHS) in the tegu lizard, Tupinambis merianae, significantly reduces resting lung volume (V(Lr)) and maximal lung volume (V(Lm)) when compared with tegus with intact PHS. Standardised for body mass (M(B)), static lung compliance was significantly less in tegus without PHS. Pleural and abdominal pressures followed, like ventilation, a biphasic pattern. In general, pressures increased during expiration and decreased during inspiration. However, during expiration pressure changes showed a marked intra- and interindividual variation. The removal of the PHS resulted in a lower cranio-caudal intracoelomic pressure differential, but had no effect on the general pattern of pressure changes accompanying ventilation. These results show that a perforated PHS that lacks striated muscle has significant influence on static breathing mechanics in Tupinambis and by analogy provides valuable insight into similar processes that led to the evolution of the mammalian diaphragm.

  13. A mathematical model describing the glycemic response of diabetic patients to meal and i.v. infusion of insulin.

    PubMed

    Fabietti, P G; Calabrese, G; Iorio, M; Bistoni, S; Brunetti, P; Sarti, E; Benedetti, M M

    2001-10-01

    Nine type 1 diabetic patients were studied for 24 hours. During this period they were given three calibrated meals. The glycemia was feedback-controlled by means of an artificial pancreas. The blood concentration of glucose and the infusion speed of the insulin were measured every minute. The experimental data referring to each of the three meals were used to estimate the parameters of a mathematical model suitable for describing the glycemic response of diabetic patients at meals and at the i.v. infusion of exogenous insulin. From the estimate a marked dispersion of the parameters was found, both interindividual and intraindividual. Nevertheless the models thus obtained seem to be usable for the synthesis of a feedback controller, especially in view of creating a portable artificial pancreas that now seems possible owing to the realization (so far experimental) of sufficiently reliable glucose concentration sensors.

  14. The Association of Macro- and Microstructure of the Corpus Callosum and Language Lateralisation

    ERIC Educational Resources Information Center

    Westerhausen, Rene; Kreuder, Frank; Sequeira, Sarah Dos Santos; Walter, Christof; Woerner, Wolfgang; Wittling, Ralf Arne; Schweiger, Elisabeth; Wittling, Werner

    2006-01-01

    The present study aimed to examine how differences in functional lateralisation of language are related to interindividual variations in interhemispheric connectivity. Utilising an fMRI silent word-generation paradigm, 89 left- and right-handed subjects were subdivided into four lateralisation subgroups. Applying morphological and diffusion-tensor…

  15. The Specificity of Autobiographical Memories in Early Adolescence: The Role of Mother-Child Communication and Attachment-Related Beliefs

    ERIC Educational Resources Information Center

    Bosmans, Guy; Dujardin, Adinda; Raes, Filip; Braet, Caroline

    2013-01-01

    Although autobiographical memory specificity is an important developmental feature fostering adaptation throughout life, little is known about factors related to interindividual differences in autobiographical memory specificity. The current study investigated associations with early adolescents' communication with mother about their experiences…

  16. Development of Legal Expertise

    ERIC Educational Resources Information Center

    Glöckner, Andreas; Towfigh, Emanuel; Traxler, Christian

    2013-01-01

    In a comprehensive empirical investigation (N = 71,405) we analyzed the development of legal expertise in a critical 1-year period of academic legal training in which advanced law students start practicing to solve complex cases. We were particularly interested in the functional form of the learning curve and inter-individual differences in…

  17. Trajectories of Victimization in Ethnic Diaspora Immigrant and Native Adolescents: Separating Acculturation from Development

    ERIC Educational Resources Information Center

    Jugert, Philipp; Titzmann, Peter F.

    2017-01-01

    This longitudinal study aimed to differentiate between acculturative and developmental processes by (a) comparing levels and change rates in victimization among ethnic German immigrants and native German adolescents in Germany and Russian Jewish immigrants in Israel, and (b) testing whether interindividual differences in victimization among…

  18. Intergenerational Grandparent/Grandchild Relations: The Socioeducational Role of Grandparents

    ERIC Educational Resources Information Center

    Bernal, Jeronimo Gonzalez; Anuncibay, Raquel de la Fuente

    2008-01-01

    Intergenerational relationships established between grandparents and grandchildren have aroused great scientific interest in recent years. It is true that, nowadays, different studies have been conducted in which the typology of these relationships has been researched. Studies have used variables such as intra- and interindividual styles in the…

  19. Testing Adaptive Toolbox Models: A Bayesian Hierarchical Approach

    ERIC Educational Resources Information Center

    Scheibehenne, Benjamin; Rieskamp, Jorg; Wagenmakers, Eric-Jan

    2013-01-01

    Many theories of human cognition postulate that people are equipped with a repertoire of strategies to solve the tasks they face. This theoretical framework of a cognitive toolbox provides a plausible account of intra- and interindividual differences in human behavior. Unfortunately, it is often unclear how to rigorously test the toolbox…

  20. 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…

  1. Statistical Modeling of the Individual: Rationale and Application of Multivariate Stationary Time Series Analysis

    ERIC Educational Resources Information Center

    Hamaker, Ellen L.; Dolan, Conor V.; Molenaar, Peter C. M.

    2005-01-01

    Results obtained with interindividual techniques in a representative sample of a population are not necessarily generalizable to the individual members of this population. In this article the specific condition is presented that must be satisfied to generalize from the interindividual level to the intraindividual level. A way to investigate…

  2. Quantifying interindividual variability and asymmetry of face-selective regions: a probabilistic functional atlas.

    PubMed

    Zhen, Zonglei; Yang, Zetian; Huang, Lijie; Kong, Xiang-Zhen; Wang, Xu; Dang, Xiaobin; Huang, Yangyue; Song, Yiying; Liu, Jia

    2015-06-01

    Face-selective regions (FSRs) are among the most widely studied functional regions in the human brain. However, individual variability of the FSRs has not been well quantified. Here we use functional magnetic resonance imaging (fMRI) to localize the FSRs and quantify their spatial and functional variabilities in 202 healthy adults. The occipital face area (OFA), posterior and anterior fusiform face areas (pFFA and aFFA), posterior continuation of the superior temporal sulcus (pcSTS), and posterior and anterior STS (pSTS and aSTS) were delineated for each individual with a semi-automated procedure. A probabilistic atlas was constructed to characterize their interindividual variability, revealing that the FSRs were highly variable in location and extent across subjects. The variability of FSRs was further quantified on both functional (i.e., face selectivity) and spatial (i.e., volume, location of peak activation, and anatomical location) features. Considerable interindividual variability and rightward asymmetry were found in all FSRs on these features. Taken together, our work presents the first effort to characterize comprehensively the variability of FSRs in a large sample of healthy subjects, and invites future work on the origin of the variability and its relation to individual differences in behavioral performance. Moreover, the probabilistic functional atlas will provide an adequate spatial reference for mapping the face network. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. The role of oxytocin in social bonding, stress regulation and mental health: an update on the moderating effects of context and interindividual differences.

    PubMed

    Olff, Miranda; Frijling, Jessie L; Kubzansky, Laura D; Bradley, Bekh; Ellenbogen, Mark A; Cardoso, Christopher; Bartz, Jennifer A; Yee, Jason R; van Zuiden, Mirjam

    2013-09-01

    In this review we summarize the results and conclusions of five studies as presented in a symposium at the 42nd annual meeting of the International Society for Psychoneuroendocrinology, in New York in September 2012. Oxytocin administration has received increasing attention for its role in promoting positive social behavior and stress regulation, and its potential as a therapeutic intervention for addressing various aspects of psychiatric disorders. However, it has been noted that the observed effects are not uniformly beneficial. In this paper we present five new studies each concluding that contextual and interindividual factors moderate the effects of oxytocin, as well as peripheral oxytocin levels. These findings are in accordance with the recent idea that oxytocin administration may increase sensitivity to social salience cues and that the interpretation of these cues may be influenced by contextual (i.e. presence of a stranger versus friend) or interindividual factors (i.e. sex, attachment style, or the presence of psychiatric symptoms). When social cues in the environment are interpreted as "safe" oxytocin may promote prosociality but when the social cues are interpreted as "unsafe" oxytocin may promote more defensive and, in effect, "anti-social" emotions and behaviors. Likewise, oxytocin appears to promote such agonistic tendencies in individuals who are chronically pre-disposed to view the social milieu in uncertain and/or in negative terms (e.g., those with borderline personality disorder, severe attachment anxiety and/or childhood maltreatment). In all, these studies in pre-clinical animal, healthy humans and patients samples further reinforce the importance of considering both contextual and interindividual factors when trying to understand the role of oxytocin as a biological substrate underlying social bonding and stress regulatory processes and when studying the effects of oxytocin administration in particular in patients with (increased risk for) psychiatric disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Environmental enrichment alters dentate granule cell morphology in oldest-old rat.

    PubMed

    Darmopil, Sanja; Petanjek, Zdravko; Mohammed, Abdul H; Bogdanović, Nenad

    2009-08-01

    The hippocampus of aged rats shows marked age-related morphological changes that could cause memory deficits. Experimental evidence has established that environmental enrichment attenuates memory deficits in aged rats. We therefore studied whether environmental enrichment produces morphological changes on the dentate granule cells of aged rats. Fifteen male Sprague-Dawley rats, 24 months of age, were randomly distributed in two groups that were housed under standard (n = 7) or enriched (n = 8) environmental conditions for 26 days. Quantitative data of dendritic morphology from dentate gyrus granule cells were obtained on Golgi-Cox stained sections. Environmental enrichment significantly increased the complexity and size of dendritic tree (total number of segments increased by 61% and length by 116%), and spine density (88% increase). There were large interindividual differences within the enriched group, indicating differential individual responses to environmental stimulation. Previous studies in young animals have shown changes produced by environmental enrichment in the morphology of dentate gyrus granule cells. The results of the present study show that environmental enrichment can also produce changes in dentate granule cell morphology in the senescent brain. In conclusion, the hippocampus retains its neuroplastic capacity during aging, and enriched environmental housing conditions can attenuate age-related dendritic regression and synaptic loss, thus preserving memory functions.

  6. Scalp-recorded slow EEG responses generated in response to hemodynamic changes in the human brain.

    PubMed

    Vanhatalo, S; Tallgren, P; Becker, C; Holmes, M D; Miller, J W; Kaila, K; Voipio, J

    2003-09-01

    To study whether hemodynamic changes in human brain generate scalp-EEG responses. Direct current EEG (DC-EEG) was recorded from 12 subjects during 5 non-invasive manipulations that affect intracranial hemodynamics by different mechanisms: bilateral jugular vein compression (JVC), head-up tilt (HUT), head-down tilt (HDT), Valsalva maneuver (VM), and Mueller maneuver (MM). DC shifts were compared to changes in cerebral blood volume (CBV) measured by near-infrared spectroscopy (NIRS). DC shifts were observed during all manipulations with highest amplitudes (up to 250 microV) at the midline electrodes, and the most pronounced changes (up to 15 microV/cm) in the DC voltage gradient around vertex. In spite of inter-individual variation in both amplitude and polarity, the DC shifts were consistent and reproducible for each subject and they showed a clear temporal correlation with changes in CBV. Our results indicate that hemodynamic changes in human brain are associated with marked DC shifts that cannot be accounted for by intracortical neuronal or glial currents. Instead, the data are consistent with a non-neuronal generator mechanism that is associated with the blood-brain barrier. These findings have direct implications for mechanistic interpretation of slow EEG responses in various experimental paradigms.

  7. Polymorphisms in HLA-DPB1 are associated with differences in rubella virus-specific humoral immunity after vaccination.

    PubMed

    Lambert, Nathaniel D; Haralambieva, Iana H; Kennedy, Richard B; Ovsyannikova, Inna G; Pankratz, Vernon Shane; Poland, Gregory A

    2015-03-15

    Vaccination with live attenuated rubella virus induces a strong immune response in most individuals. However, small numbers of subjects never reach or maintain protective antibody levels, and there is a high degree of variability in immune response. We have previously described genetic polymorphisms in HLA and other candidate genes that are associated with interindividual differences in humoral immunity to rubella virus. To expand our previous work, we performed a genome-wide association study (GWAS) to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus-specific neutralizing antibodies. We identified rs2064479 in the HLA-DPB1 genetic region as being significantly associated with humoral immune response variations after rubella vaccination (P = 8.62 × 10(-8)). All other significant SNPs in this GWAS were located near the HLA-DPB1 gene (P ≤ 1 × 10(-7)). These findings demonstrate that polymorphisms in HLA-DPB1 are strongly associated with interindividual differences in neutralizing antibody levels to rubella vaccination and represent a validation of our previous HLA work. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Empathy matters: ERP evidence for inter-individual differences in social language processing

    PubMed Central

    Van Berkum, Jos J.A.; Bastiaansen, Marcel C.M.; Tesink, Cathelijne M.J.Y.; Kos, Miriam; Buitelaar, Jan K.; Hagoort, Peter

    2012-01-01

    When an adult claims he cannot sleep without his teddy bear, people tend to react surprised. Language interpretation is, thus, influenced by social context, such as who the speaker is. The present study reveals inter-individual differences in brain reactivity to social aspects of language. Whereas women showed brain reactivity when stereotype-based inferences about a speaker conflicted with the content of the message, men did not. This sex difference in social information processing can be explained by a specific cognitive trait, one’s ability to empathize. Individuals who empathize to a greater degree revealed larger N400 effects (as well as a larger increase in γ-band power) to socially relevant information. These results indicate that individuals with high-empathizing skills are able to rapidly integrate information about the speaker with the content of the message, as they make use of voice-based inferences about the speaker to process language in a top-down manner. Alternatively, individuals with lower empathizing skills did not use information about social stereotypes in implicit sentence comprehension, but rather took a more bottom-up approach to the processing of these social pragmatic sentences. PMID:21148175

  9. 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

  10. Prenatal Arsenic Exposure and Shifts in the Newborn Proteome: Interindividual Differences in Tumor Necrosis Factor (TNF)-Responsive Signaling

    PubMed Central

    Bailey, Kathryn A.; Laine, Jessica; Rager, Julia E.; Sebastian, Elizabeth; Olshan, Andrew; Smeester, Lisa; Drobná, Zuzana; Stýblo, Miroslav; Rubio-Andrade, Marisela; García-Vargas, Gonzalo; Fry, Rebecca C.

    2014-01-01

    Exposure to inorganic arsenic (iAs) early in life is associated with adverse health effects in infants, children, and adults, and yet the biological mechanisms that underlie these effects are understudied. The objective of this research was to examine the proteomic shifts associated with prenatal iAs exposure using cord blood samples isolated from 50 newborns from Gómez Palacio, Mexico. Levels of iAs in maternal drinking water (DW-iAs) and the sum of iAs and iAs metabolites in maternal urine (U-tAs) were determined. Cord blood samples representing varying iAs exposure levels during the prenatal period (DW-iAs ranging from <1 to 236 μg As/l) were analyzed for altered expression of proteins associated with U-tAs using a high throughput, antibody-based method. A total of 111 proteins were identified that had a significant association between protein level in newborn cord blood and maternal U-tAs. Many of these proteins are regulated by tumor necrosis factor and are enriched in functionality related to immune/inflammatory response and cellular development/proliferation. Interindividual differences in proteomic response were observed in which 30 newborns were “activators,” displaying a positive relationship between protein expression and maternal U-tAs. For 20 “repressor” newborns, a negative relationship between protein expression level and maternal U-tAs was observed. The activator/repressor status was significantly associated with maternal U-tAs and head circumference in newborn males. These results may provide a critical groundwork for understanding the diverse health effects associated with prenatal arsenic exposure and highlight interindividual responses to arsenic that likely influence differential susceptibility to adverse health outcomes. PMID:24675094

  11. 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.

  12. 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.

  13. Association of sequence variations in vitamin K epoxide reductase and gamma-glutamyl carboxylas genes with biochemical measures of vitamin K status

    USDA-ARS?s Scientific Manuscript database

    Genetic factors, specifically the VKORC1 and GGCX genes, have been shown to contribute to the interindividual variability in response to the vitamin K-antagonist, warfarin, which influences the dose required to achieve the desired anticoagulation response. These differences in warfarin sensitivity ...

  14. Goal Attainment Scaling as an Outcome Measure in Randomized Controlled Trials of Psychosocial Interventions in Autism

    ERIC Educational Resources Information Center

    Ruble, Lisa; McGrew, John H.; Toland, Michael D.

    2012-01-01

    Goal attainment scaling (GAS) holds promise as an idiographic approach for measuring outcomes of psychosocial interventions in community settings. GAS has been criticized for untested assumptions of scaling level (i.e., interval or ordinal), inter-individual equivalence and comparability, and reliability of coding across different behavioral…

  15. What It Means to Be an Adolescent Teacher-and-Peer-Independent Motivation Type

    ERIC Educational Resources Information Center

    Krunke, Hannah Marei; Raufelder, Diana

    2014-01-01

    In order to enhance our understanding of interindividual differences in academic motivation, the present study examined the interplay of personality, psychosocial adjustment and socio-academic factors in a subsample of adolescent students identified as teacher-and-peer-independent motivation type (MT) (N = 295; M[subscript Age] = 13.71) in…

  16. INTERINDIVIDUAL VARIANCE OF CYTOCHROME P450 FORMS IN HUMAN HEPATIC MICROSOMES: CORRELATION OF INDIVIDUAL FORMS WITH XENOBIOTIC METABOLISM AND IMPLICATIONS IN RISK ASSESSMENT

    EPA Science Inventory

    Differences in biotransformation activities may alter the bioavailability or efficacy of drugs, provide protection from certain xenobiotic and environmental agents, or increase toxicity of others. Cytochrome P450 (CYP450) enzymes are responsible for the majority of oxidation reac...

  17. Using Simple and Complex Growth Models to Articulate Developmental Change: Matching Theory to Method

    ERIC Educational Resources Information Center

    Ram, Nilam; Grimm, Kevin

    2007-01-01

    Growth curve modeling has become a mainstay in the study of development. In this article we review some of the flexibility provided by this technique for describing and testing hypotheses about: (1) intraindividual change across multiple occasions of measurement, and (2) interindividual differences in intraindividual change. Through empirical…

  18. 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

  19. Do interindividual differences in cardiac output during submaximal exercise explain differences in exercising muscle oxygenation and ratings of perceived exertion?

    PubMed

    Bentley, Robert F; Jones, Joshua H; Hirai, Daniel M; Zelt, Joel T; Giles, Matthew D; Raleigh, James P; Quadrilatero, Joe; Gurd, Brendon J; Neder, J Alberto; Tschakovsky, Michael E

    2018-01-01

    Considerable interindividual differences in the Q˙-V˙O2 relationship during exercise have been documented but implications for submaximal exercise tolerance have not been considered. We tested the hypothesis that these interindividual differences were associated with differences in exercising muscle deoxygenation and ratings of perceived exertion (RPE) across a range of submaximal exercise intensities. A total of 31 (21 ± 3 years) healthy recreationally active males performed an incremental exercise test to exhaustion 24 h following a resting muscle biopsy. Cardiac output (Q˙ L/min; inert gas rebreathe), oxygen uptake (V˙O2 L/min; breath-by-breath pulmonary gas exchange), quadriceps saturation (near infrared spectroscopy) and exercise tolerance (6-20; Borg Scale RPE) were measured. The Q˙-V˙O2 relationship from 40 to 160 W was used to partition individuals post hoc into higher (n = 10; 6.3 ± 0.4) versus lower (n = 10; 3.7 ± 0.4, P < 0.001) responders. The Q˙-V˙O2 difference between responder types was not explained by arterial oxygen content differences (P = 0.5) or peripheral skeletal muscle characteristics (P from 0.1 to 0.8) but was strongly associated with stroke volume (P < 0.05). Despite considerable Q˙-V˙O2 difference between groups, no difference in quadriceps deoxygenation was observed during exercise (all P > 0.4). Lower cardiac responders had greater leg (P = 0.027) and whole body (P = 0.03) RPE only at 185 W, but this represented a higher %peak V˙O2 in lower cardiac responders (87 ± 15% vs. 66 ± 12%, P = 0.005). Substantially lower Q˙-V˙O2 in the lower responder group did not result in altered RPE or exercising muscle deoxygenation. This suggests substantial recruitment of blood flow redistribution in the lower responder group as part of protecting matching of exercising muscle oxygen delivery to demand. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  20. 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

  1. Inter-individual Differences in Exercise-Induced Spatial Working Memory Improvement: A Near-Infrared Spectroscopy Study.

    PubMed

    Yamazaki, Yudai; Sato, Daisuke; Yamashiro, Koya; Tsubaki, Atsuhiro; Yamaguchi, Yui; Takehara, Nana; Maruyama, Atsuo

    2017-01-01

    Acute aerobic exercise at a mild intensity improves cognitive function. However, the response to exercise exhibits inter-individual differences, and the mechanisms underlying these differences remain unclear. The objective of this study was to determine potential factors in the brain that underlie differential responses to exercise in terms of cognitive improvement using functional near-infrared spectroscopy. Fourteen healthy subjects participated in these experiments. Participants performed a low intensity cycling exercise at 30% maximal oxygen uptake (VO 2peak ) for 10 min and performed a spatial memory task before and after exercising (5 and 30 min). The spatial memory task comprised two levels of difficulty (low: 1-dot EXERCISE, high: 3-dot EXERCISE). Cortical oxy-hemoglobin (O 2 Hb) levels were recorded using near-infrared spectroscopy during both the exercise and the spatial memory task phases. Regions of interests included the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and frontopolar area (FPA). The participants were divided into two groups depending on whether they were responders (improved task reaction time) or non-responders (no improvement). Subsequently, we analyzed the group characteristics and differences in the change in O 2 Hb levels during exercise and spatial working memory tasks. Acute mild exercise significantly improved mean reaction times in the 1-dot memory task but not in the 3-dot task across the participants. In the 1-dot EXERCISE, 10 subjects were responders and four subjects were non-responders, whereas in the 3-dot EXERCISE, seven subjects were non-responders. In responders, during exercise, we found higher O 2 Hb levels in the right VLPFC response for the 1-dot memory task. Acute mild exercise caused inter-individual differences in spatial memory improvement, which were associated with changes in O 2 Hb activity in the prefrontal area during the exercise phase but not during the actual spatial memory task. Therefore, individuals who respond with higher reactivity to mild intensity exercise in the VLPFC might obtain larger spatial working memory improvements following exercise than non-responders.

  2. Interindividual differences in cognitive flexibility: influence of gray matter volume, functional connectivity and trait impulsivity

    PubMed Central

    Langner, Robert; Cieslik, Edna C.; Rottschy, Claudia; Eickhoff, Simon B.

    2016-01-01

    Cognitive flexibility, a core aspect of executive functioning, is required for the speeded shifting between different tasks and sets. Using an interindividual differences approach, we examined whether cognitive flexibility, as assessed by the Delis–Kaplan card-sorting test, is associated with gray matter volume (GMV) and functional connectivity (FC) of regions of a core network of multiple cognitive demands as well as with different facets of trait impulsivity. The core multiple-demand network was derived from three large-scale neuroimaging meta-analyses and only included regions that showed consistent associations with sustained attention, working memory as well as inhibitory control. We tested to what extent self-reported impulsivity as well as GMV and resting-state FC in this core network predicted cognitive flexibility independently and incrementally. Our analyses revealed that card-sorting performance correlated positively with GMV of the right anterior insula, FC between bilateral anterior insula and midcingulate cortex/supplementary motor area as well as the impulsivity dimension “Premeditation.” Importantly, GMV, FC and impulsivity together accounted for more variance of card-sorting performance than every parameter alone. Our results therefore indicate that various factors contribute individually to cognitive flexibility, underlining the need to search across multiple modalities when aiming to unveil the mechanisms behind executive functioning. PMID:24878823

  3. The system neurophysiological basis of backward inhibition.

    PubMed

    Zhang, Rui; Stock, Ann-Kathrin; Fischer, Rico; Beste, Christian

    2016-12-01

    Task switching is regularly required in our everyday life. To succeed in switching, it is important to inhibit the most recently performed task and instead activate the currently relevant task. The process that inhibits a recently performed task when a new task is to be performed is referred to as 'backward inhibition' (BI). While the BI effect has been subject to intense research in cognitive psychology, little is known about the neuronal mechanisms that are related to the BI effect and those that relate to differences in the magnitude of the BI effect. In the current study, we examined the system neurophysiological basis of BI processes using event-related potentials (ERPs) and sLORETA by also taking inter-individual differences in the magnitude of the BI into account. The results suggest that BI processes and inter-individual differences in them strongly depend upon attentional selection mechanisms (reflected by N1-ERP modulations in the current task/trial) mediated via networks consisting of extrastriate occipital areas, the temporo-parietal junction and the inferior frontal gyrus. Other processes and mechanisms related to conflict monitoring, response selection, or the updating, organization and implementation of a new task-set (i.e. N2 and P3 processes) were not shown to be modulated by BI processes and differences in their magnitude, as evoked with a common BI paradigm.

  4. Analysis of the in vivo confocal Raman spectral variability in human skin

    NASA Astrophysics Data System (ADS)

    Mogilevych, Borys; dos Santos, Laurita; Rangel, Joao L.; Grancianinov, Karen J. S.; Sousa, Mariane P.; Martin, Airton A.

    2015-06-01

    Biochemical composition of the skin changes in each layer and, therefore, the skin spectral profile vary with the depth. In this work, in vivo Confocal Raman spectroscopy studies were performed at different skin regions and depth profile (from the surface down to 10 μm) of the stratum corneum, to verify the variability and reproducibility of the intra- and interindividual Raman data. The Raman spectra were collected from seven healthy female study participants using a confocal Raman system from Rivers Diagnostic, with 785 nm excitation line and a CCD detector. Measurements were performed in the volar forearm region, at three different points at different depth, with the step of 2 μm. For each depth point, three spectra were acquired. Data analysis included the descriptive statistics (mean, standard deviation and residual) and Pearson's correlation coefficient calculation. Our results show that inter-individual variability is higher than intraindividual variability, and variability inside the SC is higher than on the skin surface. In all these cases we obtained r values, higher than 0.94, which correspond to high correlation between Raman spectra. It reinforces the possibility of the data reproducibility and direct comparison of in vivo results obtained with different study participants of the same age group and phototype.

  5. Dealing with consumer differences in liking during repeated exposure to food; typical dynamics in rating behavior.

    PubMed

    Dalenberg, Jelle R; Nanetti, Luca; Renken, Remco J; de Wijk, René A; Ter Horst, Gert J

    2014-01-01

    Consumers show high interindividual variability in food liking during repeated exposure. To investigate consumer liking during repeated exposure, data is often interpreted on a product level by averaging results over all consumers. However, a single product may elicit inconsistent behaviors in consumers; averaging will mix and hide possible subgroups of consumer behaviors, leading to a misinterpretation of the results. To deal with the variability in consumer liking, we propose to use clustering on data from consumer-product combinations to investigate the nature of the behavioral differences within the complete dataset. The resulting behavioral clusters can then be used to describe product acceptance. To test this approach we used two independent data sets in which young adults were repeatedly exposed to drinks and snacks, respectively. We found that five typical consumer behaviors existed in both datasets. These behaviors differed both in the average level of liking as well as its temporal dynamics. By investigating the distribution of a single product across typical consumer behaviors, we provide more precise insight in how consumers divide in subgroups based on their product liking (i.e. product modality). This work shows that taking into account and using interindividual differences can unveil information about product acceptance that would otherwise be ignored.

  6. Dealing with Consumer Differences in Liking during Repeated Exposure to Food; Typical Dynamics in Rating Behavior

    PubMed Central

    Dalenberg, Jelle R.; Nanetti, Luca; Renken, Remco J.; de Wijk, René A.; ter Horst, Gert J.

    2014-01-01

    Consumers show high interindividual variability in food liking during repeated exposure. To investigate consumer liking during repeated exposure, data is often interpreted on a product level by averaging results over all consumers. However, a single product may elicit inconsistent behaviors in consumers; averaging will mix and hide possible subgroups of consumer behaviors, leading to a misinterpretation of the results. To deal with the variability in consumer liking, we propose to use clustering on data from consumer-product combinations to investigate the nature of the behavioral differences within the complete dataset. The resulting behavioral clusters can then be used to describe product acceptance. To test this approach we used two independent data sets in which young adults were repeatedly exposed to drinks and snacks, respectively. We found that five typical consumer behaviors existed in both datasets. These behaviors differed both in the average level of liking as well as its temporal dynamics. By investigating the distribution of a single product across typical consumer behaviors, we provide more precise insight in how consumers divide in subgroups based on their product liking (i.e. product modality). This work shows that taking into account and using interindividual differences can unveil information about product acceptance that would otherwise be ignored. PMID:24667832

  7. 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.

  8. A Comparative Study of Finland and Chile: The Culture-Dependent Significance of the Individual and Interindividual Levels of the Mathematics-Related Affect

    ERIC Educational Resources Information Center

    Tuohilampi, Laura; Laine, Anu; Hannula, Markku S.; Varas, Leonor

    2016-01-01

    Mathematics-related affect is established regarding both individual and interindividual levels. However, the interaction between the levels has not been elaborated. Furthermore, it is known that people may draw either from intrinsic or extrinsic experiences to construct their identities depending on their cultural environment. Thus, affective…

  9. Ability-Based Pairing Strategies in the Team-Based Training of a Complex Skill: Does the Intelligence of Your Training Partner Matter?

    ERIC Educational Resources Information Center

    Day, Eric Anthony; Arthur, Winfred Jr.; Bell, Suzanne T.; Edwards, Bryan D.; Bennett, Winston Jr.; Mendoza, Jorge L.; Tubre, Travis C.

    2005-01-01

    Intelligence researchers traditionally focus their attention on the individual level and overlook the role of intelligence at the interindividual level. This research investigated the interplay of the effects of intelligence at the individual and interindividual levels by manipulating the intelligence-based composition of dyadic training teams.…

  10. The Development of Interindividual Sharing of Knowledge and Beliefs in 5- to 9-Year-Old Children

    ERIC Educational Resources Information Center

    Bradmetz, Joel; Gauthier, Cecile

    2005-01-01

    The authors studied the evolution of interindividual intentionality in children and showed that the sharing of knowledge and beliefs requires more complex operations than those involved in usual false-belief tasks. The authors conducted 3 experiments on 380 children (aged 5 years, 0 months to 9 years, 6 months). They assessed the children's…

  11. Intra-individual and inter-individual variations in sperm aneuploidy frequencies in normal men.

    PubMed

    Tempest, Helen G; Ko, Evelyn; Rademaker, Alfred; Chan, Peter; Robaire, Bernard; Martin, Renée H

    2009-01-01

    To investigate whether there are intra-individual and/or inter-individual variations in sperm aneuploidy frequencies within the normal male population, and, if this is the case, whether they are sporadic or time-stable variants. Prospective study. University research laboratory. Ten men aged 18-32 years. None. Fluorescence in situ hybridization was used to investigate sperm aneuploidy frequencies for chromosomes X, Y, 13, and 21 in serial semen samples collected over a period of 12-18 months. Intra-individual and inter-individual variations were investigated by comparing serial samples from the same donor and by comparing the donors with each other, respectively. Intra-individual variations were found in all 10 donors for at least one investigated chromosome; variations tended to be sporadic events affecting only one time point. Inter-individual variations were found for all chromosomes (except XX and YY disomy and disomy 21), with three men identified as stable variants, consistently producing higher levels of aneuploidy for at least one of the following aneuploidies: sex chromosome nullisomy; disomy 13, or diploidy. These results suggest that there are a number of factors and mechanisms that have the potential to sporadically or consistently affect sperm aneuploidy.

  12. Specific substrate-driven changes in human faecal microbiota composition contrast with functional redundancy in short-chain fatty acid production.

    PubMed

    Reichardt, Nicole; Vollmer, Maren; Holtrop, Grietje; Farquharson, Freda M; Wefers, Daniel; Bunzel, Mirko; Duncan, Sylvia H; Drew, Janice E; Williams, Lynda M; Milligan, Graeme; Preston, Thomas; Morrison, Douglas; Flint, Harry J; Louis, Petra

    2018-02-01

    The diet provides carbohydrates that are non-digestible in the upper gut and are major carbon and energy sources for the microbial community in the lower intestine, supporting a complex metabolic network. Fermentation produces the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, which have health-promoting effects for the human host. Here we investigated microbial community changes and SCFA production during in vitro batch incubations of 15 different non-digestible carbohydrates, at two initial pH values with faecal microbiota from three different human donors. To investigate temporal stability and reproducibility, a further experiment was performed 1 year later with four of the carbohydrates. The lower pH (5.5) led to higher butyrate and the higher pH (6.5) to more propionate production. The strongest propionigenic effect was found with rhamnose, followed by galactomannans, whereas fructans and several α- and β-glucans led to higher butyrate production. 16S ribosomal RNA gene-based quantitative PCR analysis of 22 different microbial groups together with 454 sequencing revealed significant stimulation of specific bacteria in response to particular carbohydrates. Some changes were ascribed to metabolite cross-feeding, for example, utilisation by Eubacterium hallii of 1,2-propanediol produced from fermentation of rhamnose by Blautia spp. Despite marked inter-individual differences in microbiota composition, SCFA production was surprisingly reproducible for different carbohydrates, indicating a level of functional redundancy. Interestingly, butyrate formation was influenced not only by the overall % butyrate-producing bacteria in the community but also by the initial pH, consistent with a pH-dependent shift in the stoichiometry of butyrate production.

  13. Sirolimus formulation with improved pharmacokinetic properties produced by a continuous flow method.

    PubMed

    Solymosi, Tamás; Angi, Réka; Basa-Dénes, Orsolya; Ránky, Soma; Ötvös, Zsolt; Glavinas, Hristos; Filipcsei, Genovéva; Heltovics, Gábor

    2015-08-01

    The oral bioavailability of Sirolimus is limited by poor dissolution of the compound in the gastrointestinal tract resulting in a low bioavailability and large inter-individual differences in blood levels. Several different formulation approaches were applied to overcome these disadvantageous pharmacokinetic properties including the marketed oral solution and a tablet form containing wet milled nanocrystals. These approaches deliver improved pharmacokinetics, yet, they share the characteristics of complex production method and composition. We have developed a nanostructured Sirolimus formulation prepared by the controlled continuous flow precipitation of the compound from its solution in the presence of stabilizers. We have shown that contrary to the batch production the process could be easily intensified and scaled up; apparently the uniformity of the precipitation is heavily dependent on the production parameters, most likely the mixing of the solvent and antisolvent. We compared the physicochemical and pharmacokinetic properties of the nanostructured formula with the marketed nanoformula. We found that our method produces particles in the size range of less than 100nm. The solid form redispersed instantaneously in water and in biorelevant media. Both the solid form and the redispersed colloid solution showed excellent stability even in accelerated test conditions. The oral administration of the nanostructured formula resulted in faster absorption, higher exposure and higher trough concentrations when compared to the marked form. These advantageous properties could allow the development of solid oral Sirolimus formulae with lower strength and gel based topical delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Predicting planning performance from structural connectivity between left and right mid-dorsolateral prefrontal cortex: moderating effects of age during postadolescence and midadulthood.

    PubMed

    Kaller, Christoph P; Reisert, Marco; Katzev, Michael; Umarova, Roza; Mader, Irina; Hennig, Jürgen; Weiller, Cornelius; Köstering, Lena

    2015-04-01

    Complex cognitive abilities such as planning are known to critically rely on activity of bilateral mid-dorsolateral prefrontal cortex (mid-dlPFC). However, the functional relevance of the structural connectivity between left and right mid-dlPFC is yet unknown. Here, we applied global tractography to derive streamline counts as estimates of the structural connectivity between mid-dlPFC homologs and related it to planning performance in the Tower of London task across early to midadulthood, assuming a moderating effect of age. Multiple regression analyses with interaction effects revealed that streamline counts between left and right mid-dlPFC were negatively associated with planning performance specifically in early postadolescence. From the fourth life decade on, there was a trend for a reversed, positive association. These differential findings were corroborated by converging results from fractional anisotropy and white-matter density estimates in the genu of the corpus callosum where fibers connecting mid-dlPFC homologs traversed. Moreover, the results for streamline counts were regionally specific, marking the strength of mid-dlPFC connectivity as critical in predicting interindividual differences in planning performance across different stages of adulthood. Taken together, present findings provide first evidence for nonadditive effects of age on the relation between complex cognitive abilities and the structural connectivity of mid-dlPFC homologs. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. The dynamic time course of memory recovery in transient global amnesia.

    PubMed

    Guillery-Girard, B; Desgranges, B; Urban, C; Piolino, P; de la Sayette, V; Eustache, F

    2004-11-01

    To investigate the dynamic time course of transient global amnesia (TGA)--that is, the process of recovery and the interindividual variability--by testing four patients during the day of TGA itself (on three occasions) and at follow up (on two occasions). A specially designed protocol focusing on semantic (both conceptual and autobiographical knowledge) and episodic (both anterograde and retrograde components) memory. Every patient showed marked impairment of both anterograde and retrograde episodic memory during the acute phase, with a relative preservation of personal and conceptual semantic knowledge. During the following phase, the authors observed similarities and differences among the patients' patterns of recovery. In general, retrograde amnesia recovered before the anterograde amnesia and anterograde episodic memory was recovered gradually in every case. In contrast, shrinkage of retrograde amnesia was more heterogeneous. In two of the patients, this shrinkage followed a chronological gradient and the most remote events were recovered first. In the two other patients, it depended more on the strength of the trace, and there was no temporal gradient. For the latter, an executive deficit could account for difficulties in accessing both conceptual knowledge and autobiographical memories. This profile of recovery suggests a "neocortical to medial temporal" process in every case, and the possibility of an additional frontal dysfunction in some cases. Hence, the acute phase seems to be characterised by a common episodic impairment. This variability between subjects appears in the recovery phase with two different patterns of impairment.

  16. Interindividual Difference in Metabolism of Carcinogens as a Risk Factor for Breast Cancer

    DTIC Science & Technology

    1999-09-01

    Cancer Risk’ where I will primarily describe an earlier competed study on CYP1A1 expression and genotype . Conclusions Because of the potential...and endocrine response pathways by 2.3.7.8-tetrachlorodibenzo-p-dioxin and related compounds. Pharmac. Ther. 67:247-281. 3. Larsen, M.C. Angus , W.G

  17. Patterns of Social Support in the Middle Childhood to Early Adolescent Transition: Implications for Adjustment

    ERIC Educational Resources Information Center

    Levitt, Mary J.; Levitt, Jerome; Bustos, Gaston L.; Crooks, Noel A.; Santos, Jennifer D.; Telan, Paige; Hodgetts, Jennifer; Milevsky, Avidan

    2005-01-01

    Children's social networks often include close family members, extended family members, and friends, but little is known about interindividual differences in the patterning of support from these sources. In this study, we used person-oriented analyses to differentiate patterns of support for children undergoing the transition to adolescence.…

  18. The Roles of Ability, Personality, and Interests in Acquiring Current Events Knowledge: A Longitudinal Study

    ERIC Educational Resources Information Center

    Hambrick, David Z.; Pink, Jeffrey E.; Meinz, Elizabeth J.; Pettibone, Jonathan C.; Oswald, Frederick L.

    2008-01-01

    The purpose of this study was to investigate sources of inter-individual differences in current events knowledge. The study occurred in two sessions. In the initial session, 579 participants completed tests to ability, personality, and interest factors, as well as prior knowledge of current events. Approximately 10 weeks later, participants…

  19. The Reliability and Validity of Protocols for the Assessment of Endurance Sports Performance: An Updated Review

    ERIC Educational Resources Information Center

    Stevens, Christopher John; Dascombe, Ben James

    2015-01-01

    Sports performance testing is one of the most common and important measures used in sport science. Performance testing protocols must have high reliability to ensure any changes are not due to measurement error or inter-individual differences. High validity is also important to ensure test performance reflects true performance. Time-trial…

  20. 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.

  1. N1 Magnitude of Auditory Evoked Potentials and Spontaneous Functional Connectivity Between Bilateral Heschl's Gyrus Are Coupled at Interindividual Level.

    PubMed

    Tan, Ao; Hu, Li; Tu, Yiheng; Chen, Rui; Hung, Yeung Sam; Zhang, Zhiguo

    2016-07-01

    N1 component of auditory evoked potentials is extensively used to investigate the propagation and processing of auditory inputs. However, the substantial interindividual variability of N1 could be a possible confounding factor when comparing different individuals or groups. Therefore, identifying the neuronal mechanism and origin of the interindividual variability of N1 is crucial in basic research and clinical applications. This study is aimed to use simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data to investigate the coupling between N1 and spontaneous functional connectivity (FC). EEG and fMRI data were simultaneously collected from a group of healthy individuals during a pure-tone listening task. Spontaneous FC was estimated from spontaneous blood oxygenation level-dependent (BOLD) signals that were isolated by regressing out task evoked BOLD signals from raw BOLD signals and then was correlated to N1 magnitude across individuals. It was observed that spontaneous FC between bilateral Heschl's gyrus was significantly and positively correlated with N1 magnitude across individuals (Spearman's R = 0.829, p < 0.001). The specificity of this observation was further confirmed by two whole-brain voxelwise analyses (voxel-mirrored homotopic connectivity analysis and seed-based connectivity analysis). These results enriched our understanding of the functional significance of the coupling between event-related brain responses and spontaneous brain connectivity, and hold the potential to increase the applicability of brain responses as a probe to the mechanism underlying pathophysiological conditions.

  2. Do PTK2 gene polymorphisms contribute to the interindividual variability in muscle strength and the response to resistance training? A preliminary report.

    PubMed

    Erskine, Robert M; Williams, Alun G; Jones, David A; Stewart, Claire E; Degens, Hans

    2012-04-01

    The protein tyrosine kinase-2 (PTK2) gene encodes focal adhesion kinase, a structural protein involved in lateral transmission of muscle fiber force. We investigated whether single-nucleotide polymorphisms (SNPs) of the PTK2 gene were associated with various indexes of human skeletal muscle strength and the interindividual variability in the strength responses to resistance training. We determined unilateral knee extension single repetition maximum (1-RM), maximum isometric voluntary contraction (MVC) knee joint torque, and quadriceps femoris muscle specific force (maximum force per unit physiological cross-sectional area) before and after 9 wk of knee extension resistance training in 51 untrained young men. All participants were genotyped for the PTK2 intronic rs7843014 A/C and 3'-untranslated region (UTR) rs7460 A/T SNPs. There were no genotype associations with baseline measures or posttraining changes in 1-RM or MVC. Although the training-induced increase in specific force was similar for all PTK2 genotypes, baseline specific force was higher in PTK2 rs7843014 AA and rs7460 TT homozygotes than in the respective rs7843014 C- (P = 0.016) and rs7460 A-allele (P = 0.009) carriers. These associations between muscle specific force and PTK2 SNPs suggest that interindividual differences exist in the way force is transmitted from the muscle fibers to the tendon. Therefore, our results demonstrate for the first time the impact of genetic variation on the intrinsic strength of human skeletal muscle.

  3. A Comprehensive Assessment of Regional Variation in the Impact of Head Micromovements on Functional Connectomics

    PubMed Central

    Yan, Chao-Gan; Cheung, Brian; Kelly, Clare; Colcombe, Stan; Craddock, R. Cameron; Di Martino, Adriana; Li, Qingyang; Zuo, Xi-Nian; Castellanos, F. Xavier; Milham, Michael P.

    2014-01-01

    Functional connectomics is one of the most rapidly expanding areas of neuroimaging research. Yet, concerns remain regarding the use of resting-state fMRI (R-fMRI) to characterize inter-individual variation in the functional connectome. In particular, recent findings that “micro” head movements can introduce artifactual inter-individual and group-related differences in R-fMRI metrics have raised concerns. Here, we first build on prior demonstrations of regional variation in the magnitude of framewise displacements associated with a given head movement, by providing a comprehensive voxel-based examination of the impact of motion on the BOLD signal (i.e., motion-BOLD relationships). Positive motion-BOLD relationships were detected in primary and supplementary motor areas, particularly in low motion datasets. Negative motion-BOLD relationships were most prominent in prefrontal regions, and expanded throughout the brain in high motion datasets (e.g., children). Scrubbing of volumes with FD > 0.2 effectively removed negative but not positive correlations; these findings suggest that positive relationships may reflect neural origins of motion while negative relationships are likely to originate from motion artifact. We also examined the ability of motion correction strategies to eliminate artifactual differences related to motion among individuals and between groups for a broad array of voxel-wise R-fMRI metrics. Residual relationships between motion and the examined R-fMRI metrics remained for all correction approaches, underscoring the need to covary motion effects at the group-level. Notably, global signal regression reduced relationships between motion and inter-individual differences in correlation-based R-fMRI metrics; Z-standardization (mean-centering and variance normalization) of subject-level maps for R-fMRI metrics prior to group-level analyses demonstrated similar advantages. Finally, our test-retest (TRT) analyses revealed significant motion effects on TRT reliability for R-fMRI metrics. Generally, motion compromised reliability of R-fMRI metrics, with the exception of those based on frequency characteristics – particularly, amplitude of low frequency fluctuations (ALFF). The implications of our findings for decision-making regarding the assessment and correction of motion are discussed, as are insights into potential differences among volume-based metrics of motion. PMID:23499792

  4. Dose-response effects of aerobic exercise on energy compensation in postmenopausal women: combined results from two randomized controlled trials.

    PubMed

    McNeil, J; Brenner, D R; Courneya, K S; Friedenreich, C M

    2017-08-01

    Despite the clear health benefits of exercise, exercised-induced weight loss is often less than expected. The term 'exercise energy compensation' is used to define the amount of weight loss below what is expected for the amount of exercise energy expenditure. We examined the dose-response effects of exercise volume on energy compensation in postmenopausal women. Data from Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were combined for the present analysis. The ALPHA and BETA trials were two-centred, two-armed, 12-month randomized controlled trials. The ALPHA trial included 160 participants randomized to 225 min per week of aerobic exercise, and the BETA trial randomized 200 participants to each 150 and 300 min per week of aerobic exercise. All participants were aged 50-74 years, moderately inactive (<90 min per week of exercise), had no previous cancer diagnosis and a body mass index between 22 and 40 kg m -2 . Energy compensation was based on changes in body composition (dual-energy X-ray absorptiometry scan) and estimated exercise energy expenditure from completed exercise volume. Associations between Δenergy intake, ΔVO 2peak and Δphysical activity time with energy compensation were assessed. No differences in energy compensation were noted between interventions. However, there were large inter-individual differences in energy compensation between participants; 9.4% experienced body composition changes that were greater than expected based on exercise energy expenditure, 64% experienced some degree of energy compensation and 26.6% experienced weight gain based on exercise energy expenditure. Increases in VO 2peak were associated with reductions in energy compensation (β=-3.44 ml kg -1  min -1 , 95% confidence interval for β=-4.71 to -2.17 ml kg -1  min -1 ; P=0.0001). Large inter-individual differences in energy compensation were noted, despite no differences between activity doses. In addition, increases in VO 2peak were associated with lower energy compensation. Future studies are needed to identify behavioral and metabolic factors that may contribute to this large inter-individual variability in energy compensation.

  5. 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.

  6. 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.

  7. No Associations between Interindividual Differences in Sleep Parameters and Episodic Memory Consolidation.

    PubMed

    Ackermann, Sandra; Hartmann, Francina; Papassotiropoulos, Andreas; de Quervain, Dominique J-F; Rasch, Björn

    2015-06-01

    Sleep and memory are stable and heritable traits that strongly differ between individuals. Sleep benefits memory consolidation, and the amount of slow wave sleep, sleep spindles, and rapid eye movement sleep have been repeatedly identified as reliable predictors for the amount of declarative and/or emotional memories retrieved after a consolidation period filled with sleep. These studies typically encompass small sample sizes, increasing the probability of overestimating the real association strength. In a large sample we tested whether individual differences in sleep are predictive for individual differences in memory for emotional and neutral pictures. Between-subject design. Cognitive testing took place at the University of Basel, Switzerland. Sleep was recorded at participants' homes, using portable electroencephalograph-recording devices. Nine hundred-twenty-nine healthy young participants (mean age 22.48 ± 3.60 y standard deviation). None. In striking contrast to our expectations as well as numerous previous findings, we did not find any significant correlations between sleep and memory consolidation for pictorial stimuli. Our results indicate that individual differences in sleep are much less predictive for pictorial memory processes than previously assumed and suggest that previous studies using small sample sizes might have overestimated the association strength between sleep stage duration and pictorial memory performance. Future studies need to determine whether intraindividual differences rather than interindividual differences in sleep stage duration might be more predictive for the consolidation of emotional and neutral pictures during sleep. © 2015 Associated Professional Sleep Societies, LLC.

  8. 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.

  9. Explaining interindividual differences in toddlers' collaboration with unfamiliar peers: individual, dyadic, and social factors

    PubMed Central

    Schuhmacher, Nils; Kärtner, Joscha

    2015-01-01

    During their third year of life, toddlers become increasingly skillful at coordinating their actions with peer partners and they form joint commitments in collaborative situations. However, little effort has been made to explain interindividual differences in collaboration among toddlers. Therefore, we examined the relative influence of distinct individual, dyadic, and social factors on toddlers' collaborative activities (i.e., level of coordination and preference for joint activity) in joint problem-solving situations with unfamiliar peer partners (n = 23 dyads aged M = 35.7 months). We analyzed the dyadic nonindependent data with mixed models. Results indicated that mothers' expectations regarding their children's social behaviors significantly predicted toddlers' level of coordination. Furthermore, the models revealed that toddlers' positive mutual experiences with the unfamiliar partner assessed during an initial free play period (Phase 1) and their level of coordination in an obligatory collaboration task (Phase 2) promoted toddlers' preference for joint activity in a subsequent optional collaboration task (Phase 3). In contrast, children's mastery motivation and shyness conflicted with their collaborative efforts. We discuss the role of parents' socialization goals in toddlers' development toward becoming active collaborators and discuss possible mechanisms underlying the differences in toddlers' commitment to joint activities, namely social preferences and the trust in reliable cooperation partners. PMID:25983696

  10. Neural mirroring and social interaction: Motor system involvement during action observation relates to early peer cooperation.

    PubMed

    Endedijk, H M; Meyer, M; Bekkering, H; Cillessen, A H N; Hunnius, S

    2017-04-01

    Whether we hand over objects to someone, play a team sport, or make music together, social interaction often involves interpersonal action coordination, both during instances of cooperation and entrainment. Neural mirroring is thought to play a crucial role in processing other's actions and is therefore considered important for social interaction. Still, to date, it is unknown whether interindividual differences in neural mirroring play a role in interpersonal coordination during different instances of social interaction. A relation between neural mirroring and interpersonal coordination has particularly relevant implications for early childhood, since successful early interaction with peers is predictive of a more favorable social development. We examined the relation between neural mirroring and children's interpersonal coordination during peer interaction using EEG and longitudinal behavioral data. Results showed that 4-year-old children with higher levels of motor system involvement during action observation (as indicated by lower beta-power) were more successful in early peer cooperation. This is the first evidence for a relation between motor system involvement during action observation and interpersonal coordination during other instances of social interaction. The findings suggest that interindividual differences in neural mirroring are related to interpersonal coordination and thus successful social interaction. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. The pain of a model in the personality of an onlooker: influence of state-reactivity and personality traits on embodied empathy for pain.

    PubMed

    Avenanti, Alessio; Minio-Paluello, Ilaria; Bufalari, Ilaria; Aglioti, Salvatore M

    2009-01-01

    The study of inter-individual differences at behavioural and neural levels represents a new avenue for neuroscience. The response to socio-emotional stimuli varies greatly across individuals. For example, identification with the feelings of a movie character may be total for some people or virtually absent for others. Inter-individual differences may reflect both the on-line effect (state) of the observed stimuli and more stable personal characteristics (trait). Here we show that somatomotor mirror responses when viewing others' pain are modulated by both state- and trait-differences in empathy. We recorded motor-evoked potentials (MEPs) induced by Transcranial Magnetic Stimulation (TMS) in healthy individuals observing needles penetrating a model's hand. We found a reduction of corticospinal excitability that was specific for the muscle that subjects observed being penetrated. This inhibition correlated with sensory qualities of the pain ascribed to the model. Moreover, it was greater in subjects with high trait-cognitive empathy and lower in subjects with high trait-personal distress and in those with high aversion for the observed movies. Results indicate that somatomotor responses to others' pain are influenced by specific onlookers' personality traits and self-oriented emotional reactions. Our findings suggest that multiple distinct mechanisms shape mirror mapping of others' pain.

  12. The Importance of Patient-Specific Factors for Hepatic Drug Response and Toxicity

    PubMed Central

    Lauschke, Volker M.; Ingelman-Sundberg, Magnus

    2016-01-01

    Responses to drugs and pharmacological treatments differ considerably between individuals. Importantly, only 50%–75% of patients have been shown to react adequately to pharmacological interventions, whereas the others experience either a lack of efficacy or suffer from adverse events. The liver is of central importance in the metabolism of most drugs. Because of this exposed status, hepatotoxicity is amongst the most common adverse drug reactions and hepatic liabilities are the most prevalent reason for the termination of development programs of novel drug candidates. In recent years, more and more factors were unveiled that shape hepatic drug responses and thus underlie the observed inter-individual variability. In this review, we provide a comprehensive overview of different principle mechanisms of drug hepatotoxicity and illustrate how patient-specific factors, such as genetic, physiological and environmental factors, can shape drug responses. Furthermore, we highlight other parameters, such as concomitantly prescribed medications or liver diseases and how they modulate drug toxicity, pharmacokinetics and dynamics. Finally, we discuss recent progress in the field of in vitro toxicity models and evaluate their utility in reflecting patient-specific factors to study inter-individual differences in drug response and toxicity, as this understanding is necessary to pave the way for a patient-adjusted medicine. PMID:27754327

  13. 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

  14. 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.

  15. When stereotypes become 'scientific' statements: dealing with gender issues.

    PubMed

    Madureira, Ana Flávia do Amaral

    2009-06-01

    The theoretical analysis by Watzlawik (Integrative Psychological & Behavioral Science 2009) demonstrates the scientific fragility of the constructs of masculinity and femininity based on the oversimplification and overlapping between three levels of analysis: group differences, inter-individual differences and intra-individual differences. Watzlawik presents fresh and relevant contributions in terms of methodological issues, especially about the construction of scientific generalizations. Here I focus on issues related to the transformation of stereotypes in statements about gender differences that claim to be 'scientific'--outlining the socio-political agendas of such statements.

  16. Haptic spatial matching in near peripersonal space.

    PubMed

    Kaas, Amanda L; Mier, Hanneke I van

    2006-04-01

    Research has shown that haptic spatial matching at intermanual distances over 60 cm is prone to large systematic errors. The error pattern has been explained by the use of reference frames intermediate between egocentric and allocentric coding. This study investigated haptic performance in near peripersonal space, i.e. at intermanual distances of 60 cm and less. Twelve blindfolded participants (six males and six females) were presented with two turn bars at equal distances from the midsagittal plane, 30 or 60 cm apart. Different orientations (vertical/horizontal or oblique) of the left bar had to be matched by adjusting the right bar to either a mirror symmetric (/ \\) or parallel (/ /) position. The mirror symmetry task can in principle be performed accurately in both an egocentric and an allocentric reference frame, whereas the parallel task requires an allocentric representation. Results showed that parallel matching induced large systematic errors which increased with distance. Overall error was significantly smaller in the mirror task. The task difference also held for the vertical orientation at 60 cm distance, even though this orientation required the same response in both tasks, showing a marked effect of task instruction. In addition, men outperformed women on the parallel task. Finally, contrary to our expectations, systematic errors were found in the mirror task, predominantly at 30 cm distance. Based on these findings, we suggest that haptic performance in near peripersonal space might be dominated by different mechanisms than those which come into play at distances over 60 cm. Moreover, our results indicate that both inter-individual differences and task demands affect task performance in haptic spatial matching. Therefore, we conclude that the study of haptic spatial matching in near peripersonal space might reveal important additional constraints for the specification of adequate models of haptic spatial performance.

  17. The primate vaginal microbiome: comparative context and implications for human health and disease.

    PubMed

    Stumpf, Rebecca M; Wilson, Brenda A; Rivera, Angel; Yildirim, Suleyman; Yeoman, Carl J; Polk, John D; White, Bryan A; Leigh, Steven R

    2013-12-01

    The primate body hosts trillions of microbes. Interactions between primate hosts and these microbes profoundly affect primate physiology, reproduction, health, survival, and ultimately, evolution. It is increasingly clear that primate health cannot be understood fully without knowledge of host-microbial interactions. Our goals here are to review what is known about microbiomes of the female reproductive tract and to explore several factors that influence variation within individuals, as well as within and between primate species. Much of our knowledge of microbial variation derives from studies of humans, and from microbes located in nonreproductive regions (e.g., the gut). We review work suggesting that the vaginal microbiota affects female health, fecundity, and pregnancy outcomes, demonstrating the selective potential for these agents. We explore the factors that correlate with microbial variation within species. Initial colonization by microbes depends on the manner of birth; most microbial variation is structured by estrogen levels that change with age (i.e., at puberty and menopause) and through the menstrual cycle. Microbial communities vary by location within the vagina and can depend on the sampling methods used (e.g., swab, lavage, or pap smear). Interindividual differences also exist, and while this variation is not completely understood, evidence points more to differences in estrogen levels, rather than differences in external physical environment. When comparing across species, reproductive-age humans show distinct microbial communities, generally dominated by Lactobacillus, unlike other primates. We develop evolutionary hypotheses to explain the marked differences in microbial communities. While much remains to be done to test these hypotheses, we argue that the ample variation in primate mating and reproductive behavior offers excellent opportunities to evaluate host-microbe coevolution and adaptation. Copyright © 2013 Wiley Periodicals, Inc.

  18. 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.

  19. 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.

  20. An analysis of diversity in the cognitive performance of elderly community dwellers: individual differences in change scores as a function of age.

    PubMed

    Christensen, H; Mackinnon, A J; Korten, A E; Jorm, A F; Henderson, A S; Jacomb, P; Rodgers, B

    1999-09-01

    This longitudinal study investigated whether age is associated with increases in interindividual variability across 4 ability domains using a sample of 426 elderly community dwellers followed over 3.5 years. Interindividual variability in change scores increased with age for memory, spatial functioning, and speed but not for crystallized intelligence for the full sample and in a subsample that excluded dementia or probable dementia cases. Hierarchical regression analyses indicated that being female, having weaker muscle strength, and having greater symptoms of illness and greater depression were associated with overall greater variability in cognitive scores. Having a higher level of education was associated with reduced variability. These findings are consistent with the view that there is a greater range of responses at older ages, that certain domains of intelligence are less susceptible to variation than others and that variables other than age affect cognitive performance in later life.

  1. Reading behind the Lines: The Factors Affecting the Text Reception Threshold in Hearing Aid Users

    ERIC Educational Resources Information Center

    Zekveld, Adriana A.; Pronk, Marieke; Danielsson, Henrik; Rönnberg, Jerker

    2018-01-01

    Purpose: The visual Text Reception Threshold (TRT) test (Zekveld et al., 2007) has been designed to assess modality-general factors relevant for speech perception in noise. In the last decade, the test has been adopted in audiology labs worldwide. The 1st aim of this study was to examine which factors best predict interindividual differences in…

  2. [Pharmaceutical drugs containing lactose can as a rule be used by persons with lactose intolerance].

    PubMed

    Vinther, Siri; Rumessen, Jöri Johannes; Christensen, Mikkel

    2015-03-09

    Lactose is often used as an excipient in pharmaceutical drugs. Current evidence indicates that the amount of lactose in most drugs is not sufficient to cause symptoms in persons with lactose intolerance, although interindividual differences in sensitivity probably exist. Patient preferences and/or suboptimal treatment adherence could be reasons for considering lactose-free drug alternatives.

  3. METHYLATION OF ARSENIC BY RECOMBINANT HUMAN AS3MT/287M AND AS3MT/287T POLYMORPHS

    EPA Science Inventory

    Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). AS3MT polymorphism is, in part, responsible for interindividual differences in iAs metabolism. AS3MT/M287T polymorphism that is found in ~ 10% of C...

  4. Fluid Intelligence as a Predictor of Learning: A Longitudinal Multilevel Approach Applied to Math

    ERIC Educational Resources Information Center

    Primi, Ricardo; Ferrao, Maria Eugenia; Almeida, Leandro S.

    2010-01-01

    The association between fluid intelligence and inter-individual differences was investigated using multilevel growth curve modeling applied to data measuring intra-individual improvement on math achievement tests. A sample of 166 students (88 boys and 78 girls), ranging in age from 11 to 14 (M = 12.3, SD = 0.64), was tested. These individuals took…

  5. Intra- and Interindividual Differences in Lateralized Cognitive Performance and Asymmetrical EEG Activity in the Frontal Cortex

    ERIC Educational Resources Information Center

    Papousek, Ilona; Murhammer, Daniela; Schulter, Gunter

    2011-01-01

    The study shows that changes in relative verbal vs. figural working memory and fluency performance from one session to a second session two to 3 weeks apart covary with spontaneously occurring changes of cortical asymmetry in the lateral frontal and central cortex, measured by electroencephalography (EEG) in resting conditions before the execution…

  6. Inter-individual differences in how presentation modality affects verbal learning performance in children aged 5 to 16.

    PubMed

    Meijs, Celeste; Hurks, Petra P M; Wassenberg, Renske; Feron, Frans J M; Jolles, Jelle

    2016-01-01

    This study examines inter-individual differences in how presentation modality affects verbal learning performance. Children aged 5 to 16 performed a verbal learning test within one of three presentation modalities: pictorial, auditory, or textual. The results indicated that a beneficial effect of pictures exists over auditory and textual presentation modalities and that this effect increases with age. However, this effect is only found if the information to be learned is presented once (or at most twice) and only in children above the age of 7. The results may be explained in terms of single or dual coding of information in which the phonological loop is involved. Development of the (sub)vocal rehearsal system in the phonological loop is believed to be a gradual process that begins developing around the age of 7. The developmental trajectories are similar for boys and girls. Additionally, auditory information and textual information both seemed to be processed in a similar manner, namely without labeling or recoding, leading to single coding. In contrast, pictures are assumed to be processed by the dual coding of both the visual information and a (verbal) labeling of the pictures.

  7. Analysis of manual segmentation in paranasal CT images.

    PubMed

    Tingelhoff, Kathrin; Eichhorn, Klaus W G; Wagner, Ingo; Kunkel, Maria E; Moral, Analia I; Rilk, Markus E; Wahl, Friedrich M; Bootz, Friedrich

    2008-09-01

    Manual segmentation is often used for evaluation of automatic or semi-automatic segmentation. The purpose of this paper is to describe the inter and intraindividual variability, the dubiety of manual segmentation as a gold standard and to find reasons for the discrepancy. We realized two experiments. In the first one ten ENT surgeons, ten medical students and one engineer outlined the right maxillary sinus and ethmoid sinuses manually on a standard CT dataset of a human head. In the second experiment two participants outlined maxillary sinus and ethmoid sinuses five times consecutively. Manual segmentation was accomplished with custom software using a line segmentation tool. The first experiment shows the interindividual variability of manual segmentation which is higher for ethmoidal sinuses than for maxillary sinuses. The variability can be caused by the level of experience, different interpretation of the CT data or different levels of accuracy. The second experiment shows intraindividual variability which is lower than interindividual variability. Most variances in both experiments appear during segmentation of ethmoidal sinuses and outlining hiatus semilunaris. Concerning the inter and intraindividual variances the segmentation result of one manual segmenter could not directly be used as gold standard for the evaluation of automatic segmentation algorithms.

  8. Inter-individual differences in audio-motor learning of piano melodies and white matter fiber tract architecture.

    PubMed

    Engel, Annerose; Hijmans, Brenda S; Cerliani, Leonardo; Bangert, Marc; Nanetti, Luca; Keller, Peter E; Keysers, Christian

    2014-05-01

    Humans vary substantially in their ability to learn new motor skills. Here, we examined inter-individual differences in learning to play the piano, with the goal of identifying relations to structural properties of white matter fiber tracts relevant to audio-motor learning. Non-musicians (n = 18) learned to perform three short melodies on a piano keyboard in a pure audio-motor training condition (vision of their own fingers was occluded). Initial learning times ranged from 17 to 120 min (mean ± SD: 62 ± 29 min). Diffusion-weighted magnetic resonance imaging was used to derive the fractional anisotropy (FA), an index of white matter microstructural arrangement. A correlation analysis revealed that higher FA values were associated with faster learning of piano melodies. These effects were observed in the bilateral corticospinal tracts, bundles of axons relevant for the execution of voluntary movements, and the right superior longitudinal fasciculus, a tract important for audio-motor transformations. These results suggest that the speed with which novel complex audio-motor skills can be acquired may be determined by variability in structural properties of white matter fiber tracts connecting brain areas functionally relevant for audio-motor learning. Copyright © 2013 Wiley Periodicals, Inc.

  9. Attentional bias for emotional information in older adults: the role of emotion and future time perspective.

    PubMed

    Demeyer, Ineke; De Raedt, Rudi

    2013-01-01

    Research suggests that older adults display a positivity bias at the level of information processing. However, because studies investigating attentional bias for emotional information in older adults have produced mixed findings, research identifying inter-individual differences that may explain these inconsistent results is necessary. Therefore, we investigated whether mood, symptoms of depression, symptoms of anxiety and future time perspective are related to attentional bias in older adults. Thirty-seven healthy older adults and 25 healthy middle-aged adults completed questionnaires to assess mood, symptoms of depression, symptoms of anxiety and future time perspective. Attentional bias towards happy, sad and neutral information was measured using a modified exogenous cueing paradigm with long cue presentations, to measure maintained attention versus avoidance of emotional stimuli. Older adults showed attentional avoidance for all emotional faces, whereas no attentional biases were found in the middle-aged group. Moreover, in the older adult group, avoidance for negative information was related to anxiety. Future time perspective was unrelated to attentional bias. These findings suggest that anxiety may lead to inter-individual differences in attentional bias in older adults, and that avoidance from negative information may be an emotion regulation strategy.

  10. Secrets of virtuoso: neuromuscular attributes of motor virtuosity in expert musicians

    PubMed Central

    Furuya, Shinichi; Oku, Takanori; Miyazaki, Fumio; Kinoshita, Hiroshi

    2015-01-01

    Musical performance requires extremely fast and dexterous limb movements. The underlying biological mechanisms have been an object of interest among scientists and non-scientists for centuries. Numerous studies of musicians and non-musicians have demonstrated that neuroplastic adaptations through early and deliberate musical training endowed superior motor skill. However, little has been unveiled about what makes inter-individual differences in motor skills among musicians. Here we determined the attributes of inter-individual differences in the maximum rate of repetitive piano keystrokes in twenty-four pianists. Among various representative factors of neuromuscular functions, anatomical characteristics, and training history, a stepwise multiple regression analysis and generalized linear model identified two predominant predictors of the maximum rate of repetitive piano keystrokes; finger tapping rate and muscular strength of the elbow extensor. These results suggest a non-uniform role of individual limb muscles in the production of extremely fast repetitive multi-joint movements. Neither age of musical training initiation nor the amount of extensive musical training before age twenty was a predictor. Power grip strength was negatively related to the maximum rate of piano keystrokes only during the smallest tone production. These findings highlight the importance of innate biological nature and explicit training for motor virtuosity. PMID:26502770

  11. Individual variation in habituation: behaviour over time toward different stimuli in threespine sticklebacks (Gasterosteus aculeatus)

    PubMed Central

    Bell, Alison M.; Peeke, Harman V.S.

    2014-01-01

    Habituation, or the relatively permanent waning of a response as a result of repeated stimulation, is a form of behavioural plasticity that allows animals to filter out irrelevant stimuli and to focus selectively on important stimuli. Individuals that fail to habituate might be at a disadvantage if they continue to respond to irrelevant stimuli; therefore, habituation can have adaptive significance. In this study we compared rates of behaviour over time toward three different ecologically-relevant stimuli (food, a male intruder and a gravid female) in threespine sticklebacks (Gasterosteus aculeatus). We detected evidence for habituation to the stimuli, and males in this study were especially aggressive toward both male and female conspecifics. Although there were some clear temporal patterns that could be detected by looking at average behaviour, not all individuals behaved in the same ‘average’ way. We detected substantial inter-individual variation in behaviour toward all three stimuli, inter-individual variation in rates of habituation to both male and female conspecifics, but no evidence for correlations between behaviours across stimuli (behavioural syndromes). These results suggest that individual animals vary in rates of habituation, and prompt hypotheses about the causes and consequences of variation in rates of habituation. PMID:25678715

  12. Secrets of virtuoso: neuromuscular attributes of motor virtuosity in expert musicians

    NASA Astrophysics Data System (ADS)

    Furuya, Shinichi; Oku, Takanori; Miyazaki, Fumio; Kinoshita, Hiroshi

    2015-10-01

    Musical performance requires extremely fast and dexterous limb movements. The underlying biological mechanisms have been an object of interest among scientists and non-scientists for centuries. Numerous studies of musicians and non-musicians have demonstrated that neuroplastic adaptations through early and deliberate musical training endowed superior motor skill. However, little has been unveiled about what makes inter-individual differences in motor skills among musicians. Here we determined the attributes of inter-individual differences in the maximum rate of repetitive piano keystrokes in twenty-four pianists. Among various representative factors of neuromuscular functions, anatomical characteristics, and training history, a stepwise multiple regression analysis and generalized linear model identified two predominant predictors of the maximum rate of repetitive piano keystrokes; finger tapping rate and muscular strength of the elbow extensor. These results suggest a non-uniform role of individual limb muscles in the production of extremely fast repetitive multi-joint movements. Neither age of musical training initiation nor the amount of extensive musical training before age twenty was a predictor. Power grip strength was negatively related to the maximum rate of piano keystrokes only during the smallest tone production. These findings highlight the importance of innate biological nature and explicit training for motor virtuosity.

  13. 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

  14. Individual modulation of pain sensitivity under stress.

    PubMed

    Reinhardt, Tatyana; Kleindienst, Nikolaus; Treede, Rolf-Detlef; Bohus, Martin; Schmahl, Christian

    2013-05-01

    Stress has a strong influence on pain sensitivity. However, the direction of this influence is unclear. Recent studies reported both decreased and increased pain sensitivities under stress, and one hypothesis is that interindividual differences account for these differences. The aim of our study was to investigate the effect of stress on individual pain sensitivity in a relatively large female sample. Eighty female participants were included. Pain thresholds and temporal summation of pain were tested before and after stress, which was induced by the Mannheim Multicomponent Stress Test. In an independent sample of 20 women, correlation coefficients between 0.45 and 0.89 indicated relatively high test-retest reliability for pain measurements. On average, there were significant differences between pain thresholds under non-stress and stress conditions, indicating an increased sensitivity to pain under stress. No significant differences between non-stress and stress conditions were found for temporal summation of pain. On an individual basis, both decreased and increased pain sensitivities under stress conditions based on Jacobson's criteria for reliable change were observed. Furthermore, we found significant negative associations between pain sensitivity under non-stress conditions and individual change of pain sensitivity under stress. Participants with relatively high pain sensitivity under non-stress conditions became less sensitive under stress and vice versa. These findings support the view that pain sensitivity under stress shows large interindividual variability, and point to a possible dichotomy of altered pain sensitivity under stress. Wiley Periodicals, Inc.

  15. Influence of Different Patellofemoral Design Variations Based on Genesis II Total Knee Endoprosthesis on Patellofemoral Pressure and Kinematics.

    PubMed

    Leichtle, Ulf G; Lange, Barbara; Herzog, Yvonne; Schnauffer, Peter; Leichtle, Carmen I; Wülker, Nikolaus; Lorenz, Andrea

    2017-01-01

    In total knee arthroplasty (TKA), patellofemoral groove design varies greatly and likely has a distinct influence on patellofemoral biomechanics. To analyse the selective influence, five patellofemoral design variations were developed based on Genesis II total knee endoprosthesis (original design, being completely flat, being laterally elevated, being medially elevated, and both sides elevated) and made from polyamide using rapid prototyping. Muscle-loaded knee flexion was simulated on 10 human knee specimens using a custom-made knee simulator, measuring the patellofemoral pressure distribution and tibiofemoral and patellofemoral kinematics. The measurements were carried out in the native knee as well as after TKA with the 5 design prototypes. The overall influence of the different designs on the patellofemoral kinematics was small, but we found detectable effects for mediolateral tilt ( p < 0.05 for 35°-80° flexion) and translation of the patella ( p < 0.045 for 20°-65° and 75°-90°), especially for the completely flat design. Considering patellofemoral pressures, major interindividual differences were seen between the designs, which, on average, largely cancelled each other out. These results suggest that the elevation of the lateral margin of the patellofemoral groove is essential for providing mediolateral guidance, but smooth contouring as with original Genesis II design seems to be sufficient. The pronounced interindividual differences identify a need for more patellofemoral design options in TKA.

  16. [Cognitive capacity in advanced age: initial results of the Berlin Aging Study].

    PubMed

    Lindenberger, U; Baltes, P B

    1995-01-01

    This study reports data on intellectual functioning in old and very old age from the Berlin Aging Study (N = 516; age range = 70-103 years; mean age = 85 years). A psychometric battery of 14 tests was used to assess five cognitive abilities: reasoning, memory, and perceptual speed from the broad fluid-mechanical as well as knowledge and fluency from the broad crystallized-pragmatic domains. Cognitive abilities had a negative linear relationship with age, with more pronounced age-based reductions in fluid-mechanical than crystallized-pragmatic abilities. At the same time, ability intercorrelations formed a highly positive manifold, and did not follow the fluid-crystallized distinction. Interindividual variability was of about equal magnitude across the entire age range studied. There was, however, no evidence for substantial sex differences. As to origins of individual differences, indicators of sensory and sensorimotor functioning were more powerful predictors of intellectual functioning than cultural-biographical variables, and the two sets of predictors were, consistent with theoretical expectations, differentially related to measures of fluid-mechanical (perceptual speed) and crystallized pragmatic (knowledge) functioning. Results, in general indicative of sizeable and general losses with age, are consistent with the view that aging-induced biological influences are a prominent source of individual differences in intellectual functioning in old and very old age. Longitudinal follow-ups are underway to examine the role of cohort effects, selective mortality, and interindividual differences in change trajectories.

  17. Impact of personality on the cerebral processing of emotional prosody.

    PubMed

    Brück, Carolin; Kreifelts, Benjamin; Kaza, Evangelia; Lotze, Martin; Wildgruber, Dirk

    2011-09-01

    While several studies have focused on identifying common brain mechanisms governing the decoding of emotional speech melody, interindividual variations in the cerebral processing of prosodic information, in comparison, have received only little attention to date: Albeit, for instance, differences in personality among individuals have been shown to modulate emotional brain responses, personality influences on the neural basis of prosody decoding have not been investigated systematically yet. Thus, the present study aimed at delineating relationships between interindividual differences in personality and hemodynamic responses evoked by emotional speech melody. To determine personality-dependent modulations of brain reactivity, fMRI activation patterns during the processing of emotional speech cues were acquired from 24 healthy volunteers and subsequently correlated with individual trait measures of extraversion and neuroticism obtained for each participant. Whereas correlation analysis did not indicate any link between brain activation and extraversion, strong positive correlations between measures of neuroticism and hemodynamic responses of the right amygdala, the left postcentral gyrus as well as medial frontal structures including the right anterior cingulate cortex emerged, suggesting that brain mechanisms mediating the decoding of emotional speech melody may vary depending on differences in neuroticism among individuals. Observed trait-specific modulations are discussed in the light of processing biases as well as differences in emotion control or task strategies which may be associated with the personality trait of neuroticism. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Human Hippocampal Structure: A Novel Biomarker Predicting Mnemonic Vulnerability to, and Recovery from, Sleep Deprivation.

    PubMed

    Saletin, Jared M; Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Stark, Shauna; Stark, Craig E; Walker, Matthew P

    2016-02-24

    Sleep deprivation impairs the formation of new memories. However, marked interindividual variability exists in the degree to which sleep loss compromises learning, the mechanistic reasons for which are unclear. Furthermore, which physiological sleep processes restore learning ability following sleep deprivation are similarly unknown. Here, we demonstrate that the structural morphology of human hippocampal subfields represents one factor determining vulnerability (and conversely, resilience) to the impact of sleep deprivation on memory formation. Moreover, this same measure of brain morphology was further associated with the quality of nonrapid eye movement slow wave oscillations during recovery sleep, and by way of such activity, determined the success of memory restoration. Such findings provide a novel human biomarker of cognitive susceptibility to, and recovery from, sleep deprivation. Moreover, this metric may be of special predictive utility for professions in which memory function is paramount yet insufficient sleep is pervasive (e.g., aviation, military, and medicine). Copyright © 2016 the authors 0270-6474/16/362355-09$15.00/0.

  19. Medical management of neurocysticercosis.

    PubMed

    Takayanagui, Osvaldo Massaiti; Odashima, Newton Satoru; Bonato, Pierina S; Lima, Jose Eduardo; Lanchote, Vera Lucia

    2011-12-01

    Neurocysticercosis (NCC) is considered to be the most common cause of acquired epilepsy worldwide. Formerly restricted to palliative measures, therapy for NCC has advanced with the advent of two drugs that are considered to be effective: praziquantel (PZQ) and albendazole (ALB). All available articles regarding research related to the treatment of NCC were searched. Relevant articles were then reviewed and used as sources of information for this review. Anticysticercal therapy has been marked by intense controversy. Recent descriptions of spontaneous resolution of parenchymal cysticercosis with benign evolution, risks of complications and reports of no long-term benefits have reinforced the debate over the usefulness and safety of anticysticercal therapy. High interindividual variability and complex pharmacological interactions will require the close monitoring of plasma concentrations of ALB and PZQ metabolites in future trials. Given the relative scarcity of clinical trials, more comparative interventional studies - especially randomized controlled trials in long-term clinical evolution - are required to clarify the controversy over the validity of parasitic therapy in patients with NCC.

  20. Introduction to the human gut microbiota.

    PubMed

    Thursby, Elizabeth; Juge, Nathalie

    2017-05-16

    The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host-microbe interactions. © 2017 The Author(s).

  1. Introduction to the human gut microbiota

    PubMed Central

    Thursby, Elizabeth

    2017-01-01

    The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions. PMID:28512250

  2. Motion patterns in acupuncture needle manipulation.

    PubMed

    Seo, Yoonjeong; Lee, In-Seon; Jung, Won-Mo; Ryu, Ho-Sun; Lim, Jinwoong; Ryu, Yeon-Hee; Kang, Jung-Won; Chae, Younbyoung

    2014-10-01

    In clinical practice, acupuncture manipulation is highly individualised for each practitioner. Before we establish a standard for acupuncture manipulation, it is important to understand completely the manifestations of acupuncture manipulation in the actual clinic. To examine motion patterns during acupuncture manipulation, we generated a fitted model of practitioners' motion patterns and evaluated their consistencies in acupuncture manipulation. Using a motion sensor, we obtained real-time motion data from eight experienced practitioners while they conducted acupuncture manipulation using their own techniques. We calculated the average amplitude and duration of a sampled motion unit for each practitioner and, after normalisation, we generated a true regression curve of motion patterns for each practitioner using a generalised additive mixed modelling (GAMM). We observed significant differences in rotation amplitude and duration in motion samples among practitioners. GAMM showed marked variations in average regression curves of motion patterns among practitioners but there was strong consistency in motion parameters for individual practitioners. The fitted regression model showed that the true regression curve accounted for an average of 50.2% of variance in the motion pattern for each practitioner. Our findings suggest that there is great inter-individual variability between practitioners, but remarkable intra-individual consistency within each practitioner. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Epigenetic mechanisms underlying the role of brain-derived neurotrophic factor in depression and response to antidepressants

    PubMed Central

    Duclot, Florian; Kabbaj, Mohamed

    2015-01-01

    Major depressive disorder (MDD) is a devastating neuropsychiatric disorder encompassing a wide range of cognitive and emotional dysfunctions. The prevalence of MDD is expected to continue its growth to become the second leading cause of disease burden (after HIV) by 2030. Despite an extensive research effort, the exact etiology of MDD remains elusive and the diagnostics uncertain. Moreover, a marked inter-individual variability is observed in the vulnerability to develop depression, as well as in response to antidepressant treatment, for nearly 50% of patients. Although a genetic component accounts for some cases of MDD, it is now clearly established that MDD results from strong gene and environment interactions. Such interactions could be mediated by epigenetic mechanisms, defined as chromatin and DNA modifications that alter gene expression without changing the DNA structure itself. Some epigenetic mechanisms have recently emerged as particularly relevant molecular substrates, promoting vulnerability or resilience to the development of depressive-like symptoms. Although the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of MDD remains unclear, its modulation of the efficacy of antidepressants is clearly established. Therefore, in this review, we focus on the epigenetic mechanisms regulating the expression of BDNF in humans and in animal models of depression, and discuss their role in individual differences in vulnerability to depression and response to antidepressant drugs. PMID:25568448

  4. Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk

    PubMed Central

    Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E.; Geddes, Donna T.; Kakulas, Foteini

    2016-01-01

    Human milk (HM) contains regulatory biomolecules including miRNAs, the origin and functional significance of which are still undetermined. We used TaqMan OpenArrays to profile 681 mature miRNAs in HM cells and fat, and compared them with maternal peripheral blood mononuclear cells (PBMCs) and plasma, and bovine and soy infant formulae. HM cells and PBMCs (292 and 345 miRNAs, respectively) had higher miRNA content than HM fat and plasma (242 and 219 miRNAs, respectively) (p < 0.05). A strong association in miRNA profiles was found between HM cells and fat, whilst PBMCs and plasma were distinctly different to HM, displaying marked inter-individual variation. Considering the dominance of epithelial cells in mature milk of healthy women, these results suggest that HM miRNAs primarily originate from the mammary epithelium, whilst the maternal circulation may have a smaller contribution. Our findings demonstrate that unlike infant formulae, which contained very few human miRNA, HM is a rich source of lactation-specific miRNA, which could be used as biomarkers of the performance and health status of the lactating mammary gland. Given the recently identified stability, uptake and functionality of food- and milk-derived miRNA in vivo, HM miRNA are likely to contribute to infant protection and development. PMID:26854194

  5. Age- and gender-related regional variations of human brain cortical thickness, complexity, and gradient in the third decade.

    PubMed

    Creze, Maud; Versheure, Leslie; Besson, Pierre; Sauvage, Chloe; Leclerc, Xavier; Jissendi-Tchofo, Patrice

    2014-06-01

    Brain functional and cytoarchitectural maturation continue until adulthood, but little is known about the evolution of the regional pattern of cortical thickness (CT), complexity (CC), and intensity or gradient (CG) in young adults. We attempted to detect global and regional age- and gender-related variations of brain CT, CC, and CG, in 28 healthy young adults (19-33 years) using a three-dimensional T1 -weighted magnetic resonance imaging sequence and surface-based methods. Whole brain interindividual variations of CT and CG were similar to that in the literature. As a new finding, age- and gender-related variations significantly affected brain complexity (P < 0.01) on posterior cingulate and middle temporal cortices (age), and the fronto-orbital cortex (gender), all in the right hemisphere. Regions of interest analyses showed age and gender significant interaction (P < 0.05) on the temporopolar, inferior, and middle temporal-entorrhinal cortices bilaterally, as well as left inferior parietal. In addition, we found significant inverse correlations between CT and CC and between CT and CG over the whole brain and markedly in precentral and occipital areas. Our findings differ in details from previous reports and may correlate with late brain maturation and learning plasticity in young adults' brain in the third decade. Copyright © 2013 Wiley Periodicals, Inc.

  6. Effects of Erythropoietin Administration on Adrenal Glands of Landrace/Large White Pigs after Ventricular Fibrillation.

    PubMed

    Faa, Armando; Faa, Gavino; Papalois, Apostolos; Obinu, Eleonora; Locci, Giorgia; Pais, Maria Elena; Lelovas, Pavlos; Barouxis, Dimitrios; Pantazopoulos, Charalampos; Vasileiou, Panagiotis V; Iacovidou, Nicoletta; Xanthos, Theodoros

    2016-01-01

    Aim. To evaluate the effects of erythropoietin administration on the adrenal glands in a swine model of ventricular fibrillation and resuscitation. Methods. Ventricular fibrillation was induced via pacing wire forwarded into the right ventricle in 20 female Landrace/Large White pigs, allocated into 2 groups: experimental group treated with bolus dose of erythropoietin (EPO) and control group which received normal saline. Cardiopulmonary resuscitation (CPR) was performed immediately after drug administration as per the 2010 European Resuscitation Council (ERC) guidelines for Advanced Life Support (ALS) until return of spontaneous circulation (ROSC) or death. Animals who achieved ROSC were monitored, mechanically ventilated, extubated, observed, and euthanized. At necroscopy, adrenal glands samples were formalin-fixed, paraffin-embedded, and routinely processed. Sections were stained with hematoxylin-eosin. Results. Oedema and apoptosis were the most frequent histological changes and were detected in all animals in the adrenal cortex and in the medulla. Mild and focal endothelial lesions were also detected. A marked interindividual variability in the degree of the intensity of apoptosis and oedema at cortical and medullary level was observed within groups. Comparing the two groups, higher levels of pathological changes were detected in the control group. No significant difference between the two groups was observed regarding the endothelial changes. Conclusions. In animals exposed to ventricular fibrillation, EPO treatment has protective effects on the adrenal gland.

  7. Distribution of genetic polymorphisms of genes encoding drug metabolizing enzymes & drug transporters - a review with Indian perspective.

    PubMed

    Umamaheswaran, Gurusamy; Kumar, Dhakchinamoorthi Krishna; Adithan, Chandrasekaran

    2014-01-01

    Phase I and II drug metabolizing enzymes (DME) and drug transporters are involved in the absorption, distribution, metabolism as well as elimination of many therapeutic agents, toxins and various pollutants. Presence of genetic polymorphisms in genes encoding these proteins has been associated with marked inter-individual variability in their activity that could result in variation in drug response, toxicity as well as in disease predisposition. The emergent field pharmacogenetics and pharmacogenomics (PGx) is a promising discipline, as it predicts disease risk, selection of proper medication with regard to response and toxicity, and appropriate drug dosage guidance based on an individual's genetic make-up. Consequently, genetic variations are essential to understand the ethnic differences in disease occurrence, development, prognosis, therapeutic response and toxicity. For that reason, it is necessary to establish the normative frequency of these genes in a particular population before unraveling the genotype-phenotype associations. Although a fair amount of allele frequency data are available in Indian populations, the existing pharmacogenetic data have not been compiled into a database. This review was intended to compile the normative frequency distribution of the variants of genes encoding DMEs (CYP450s, TPMT, GSTs, COMT, SULT1A1, NAT2 and UGTs) and transporter proteins (MDR1, OCT1 and SLCO1B1) with Indian perspective.

  8. Idiosyncratic Adverse Drug Reactions: Current Concepts

    PubMed Central

    Naisbitt, Dean J.

    2013-01-01

    Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. The major targets are skin, liver, and bone marrow. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. However, rigorous mechanistic studies are very difficult to perform, especially in the absence of valid animal models. Models to explain how drugs or reactive metabolites interact with the MHC/T-cell receptor complex include the hapten and P-I models, and most recently it was found that abacavir can interact reversibly with MHC to alter the endogenous peptides that are presented to T cells. The discovery of HLA molecules as important risk factors for some IDRs has also significantly contributed to our understanding of these adverse reactions, but it is not yet clear what fraction of IDRs have a strong HLA dependence. In addition, with the exception of abacavir, most patients who have the HLA that confers a higher IDR risk with a specific drug will not have an IDR when treated with that drug. Interindividual differences in T-cell receptors and other factors also presumably play a role in determining which patients will have an IDR. The immune response represents a delicate balance, and immune tolerance may be the dominant response to a drug that can cause IDRs. PMID:23476052

  9. Three-dimensional morphology of the palate in subjects with isolated cleft palate at the stage of permanent dentition.

    PubMed

    Smahel, Zbynek; Trefný, Pavel; Formánek, Pavel; Müllerová, Ziva; Peterka, Miroslav

    2003-11-01

    Three-dimensional analysis of palate size and shape in patients with isolated cleft palate at the stage of permanent dentition. Cross-sectional study using Fourier transform profilometry. Twenty-nine randomly selected dental casts of approximately 15-year-old boys with isolated cleft palate and 28 dental casts of normal boys of the same age. All patients were operated on by the same method (pushback and pharyngeal flap surgery) at a mean age of 4.5 years. Data on the palate height in 210 defined locations (pixels). The palate in isolated clefts is narrower throughout its whole extent and lower from the level of the first premolars. The difference, as compared with controls, increases in a posterior direction. At the level of the first molars, palatal height is reduced by one-quarter, the area of the transversal section by more than one-third. The shaping of the palate vault is, on average, symmetrical with a marked interindividual variability. Palatal height does not depend on the width of the dentoalveolar arch, and the height of the primary palate is not reduced. The smaller width and reduced height from the level of the first premolars posteriorly confirm the substantially reduced space available for the tongue in patients with isolated cleft palate. Deviations are on the average symmetrical, and the anterior part of the palate is not shallower.

  10. Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk.

    PubMed

    Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E; Geddes, Donna T; Kakulas, Foteini

    2016-02-08

    Human milk (HM) contains regulatory biomolecules including miRNAs, the origin and functional significance of which are still undetermined. We used TaqMan OpenArrays to profile 681 mature miRNAs in HM cells and fat, and compared them with maternal peripheral blood mononuclear cells (PBMCs) and plasma, and bovine and soy infant formulae. HM cells and PBMCs (292 and 345 miRNAs, respectively) had higher miRNA content than HM fat and plasma (242 and 219 miRNAs, respectively) (p < 0.05). A strong association in miRNA profiles was found between HM cells and fat, whilst PBMCs and plasma were distinctly different to HM, displaying marked inter-individual variation. Considering the dominance of epithelial cells in mature milk of healthy women, these results suggest that HM miRNAs primarily originate from the mammary epithelium, whilst the maternal circulation may have a smaller contribution. Our findings demonstrate that unlike infant formulae, which contained very few human miRNA, HM is a rich source of lactation-specific miRNA, which could be used as biomarkers of the performance and health status of the lactating mammary gland. Given the recently identified stability, uptake and functionality of food- and milk-derived miRNA in vivo, HM miRNA are likely to contribute to infant protection and development.

  11. Cognitive Enhancement or Cognitive Cost: Trait-Specific Outcomes of Brain Stimulation in the Case of Mathematics Anxiety

    PubMed Central

    Sarkar, Amar; Dowker, Ann

    2014-01-01

    The surge in noninvasive brain stimulation studies investigating cognitive enhancement has neglected the effect of interindividual differences, such as traits, on stimulation outcomes. Using the case of mathematics anxiety in a sample of healthy human participants in a placebo-controlled, double-blind, crossover experiment, we show that identical transcranial direct current stimulation (tDCS) exerts opposite behavioral and physiological effects depending on individual trait levels. Mathematics anxiety is the negative emotional response elicited by numerical tasks, impairing mathematical achievement. tDCS was applied to the dorsolateral prefrontal cortex, a frequent target for modulating emotional regulation. It improved reaction times on simple arithmetic decisions and decreased cortisol concentrations (a biomarker of stress) in high mathematics anxiety individuals. In contrast, tDCS impaired reaction times for low mathematics anxiety individuals and prevented a decrease in cortisol concentration compared with sham stimulation. Both groups showed a tDCS-induced side effect—impaired executive control in a flanker task—a cognitive function subserved by the stimulated region. These behavioral and physiological double dissociations have implications for brain stimulation research by highlighting the role of individual traits in experimental findings. Brain stimulation clearly does not produce uniform benefits, even applied in the same configuration during the same tasks, but may interact with traits to produce markedly opposed outcomes. PMID:25505313

  12. Cognitive enhancement or cognitive cost: trait-specific outcomes of brain stimulation in the case of mathematics anxiety.

    PubMed

    Sarkar, Amar; Dowker, Ann; Cohen Kadosh, Roi

    2014-12-10

    The surge in noninvasive brain stimulation studies investigating cognitive enhancement has neglected the effect of interindividual differences, such as traits, on stimulation outcomes. Using the case of mathematics anxiety in a sample of healthy human participants in a placebo-controlled, double-blind, crossover experiment, we show that identical transcranial direct current stimulation (tDCS) exerts opposite behavioral and physiological effects depending on individual trait levels. Mathematics anxiety is the negative emotional response elicited by numerical tasks, impairing mathematical achievement. tDCS was applied to the dorsolateral prefrontal cortex, a frequent target for modulating emotional regulation. It improved reaction times on simple arithmetic decisions and decreased cortisol concentrations (a biomarker of stress) in high mathematics anxiety individuals. In contrast, tDCS impaired reaction times for low mathematics anxiety individuals and prevented a decrease in cortisol concentration compared with sham stimulation. Both groups showed a tDCS-induced side effect-impaired executive control in a flanker task-a cognitive function subserved by the stimulated region. These behavioral and physiological double dissociations have implications for brain stimulation research by highlighting the role of individual traits in experimental findings. Brain stimulation clearly does not produce uniform benefits, even applied in the same configuration during the same tasks, but may interact with traits to produce markedly opposed outcomes. Copyright © 2014 Sarkar et al.

  13. Longitudinal Growth Curves of Brain Function Underlying Inhibitory Control through Adolescence

    PubMed Central

    Foran, William; Velanova, Katerina; Luna, Beatriz

    2013-01-01

    Neuroimaging studies suggest that developmental improvements in inhibitory control are primarily supported by changes in prefrontal executive function. However, studies are contradictory with respect to how activation in prefrontal regions changes with age, and they have yet to analyze longitudinal data using growth curve modeling, which allows characterization of dynamic processes of developmental change, individual differences in growth trajectories, and variables that predict any interindividual variability in trajectories. In this study, we present growth curves modeled from longitudinal fMRI data collected over 302 visits (across ages 9 to 26 years) from 123 human participants. Brain regions within circuits known to support motor response control, executive control, and error processing (i.e., aspects of inhibitory control) were investigated. Findings revealed distinct developmental trajectories for regions within each circuit and indicated that a hierarchical pattern of maturation of brain activation supports the gradual emergence of adult-like inhibitory control. Mean growth curves of activation in motor response control regions revealed no changes with age, although interindividual variability decreased with development, indicating equifinality with maturity. Activation in certain executive control regions decreased with age until adolescence, and variability was stable across development. Error-processing activation in the dorsal anterior cingulate cortex showed continued increases into adulthood and no significant interindividual variability across development, and was uniquely associated with task performance. These findings provide evidence that continued maturation of error-processing abilities supports the protracted development of inhibitory control over adolescence, while motor response control regions provide early-maturing foundational capacities and suggest that some executive control regions may buttress immature networks as error processing continues to mature. PMID:24227721

  14. 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.

  15. Controlling stimulation strength and focality in electroconvulsive therapy via current amplitude and electrode size and spacing: comparison with magnetic seizure therapy.

    PubMed

    Deng, Zhi-De; Lisanby, Sarah H; Peterchev, Angel V

    2013-12-01

    Understanding the relationship between the stimulus parameters of electroconvulsive therapy (ECT) and the electric field characteristics could guide studies on improving risk/benefit ratio. We aimed to determine the effect of current amplitude and electrode size and spacing on the ECT electric field characteristics, compare ECT focality with magnetic seizure therapy (MST), and evaluate stimulus individualization by current amplitude adjustment. Electroconvulsive therapy and double-cone-coil MST electric field was simulated in a 5-shell spherical human head model. A range of ECT electrode diameters (2-5 cm), spacing (1-25 cm), and current amplitudes (0-900 mA) was explored. The head model parameters were varied to examine the stimulus current adjustment required to compensate for interindividual anatomical differences. By reducing the electrode size, spacing, and current, the ECT electric field can be more focal and superficial without increasing scalp current density. By appropriately adjusting the electrode configuration and current, the ECT electric field characteristics can be made to approximate those of MST within 15%. Most electric field characteristics in ECT are more sensitive to head anatomy variation than in MST, especially for close electrode spacing. Nevertheless, ECT current amplitude adjustment of less than 70% can compensate for interindividual anatomical variability. The strength and focality of ECT can be varied over a wide range by adjusting the electrode size, spacing, and current. If desirable, ECT can be made as focal as MST while using simpler stimulation equipment. Current amplitude individualization can compensate for interindividual anatomical variability.

  16. [13C]Nandrolone excretion in trained athletes: interindividual variability in metabolism.

    PubMed

    Baume, Norbert; Avois, Lidia; Schweizer, Carine; Cardis, Christine; Dvorak, Jiri; Cauderay, Michel; Mangin, Patrice; Saugy, Martial

    2004-02-01

    Nandrolone is one of the most abused anabolic steroids, and its use in doping is increasing, as revealed by numerous positive cases during recent years in various sports. Different authors have reported the possible natural production of nandrolone metabolites in humans, and some of these authors argued that exhaustive exercise could increase nandrolone production in the body or induce dehydration and consequently lead to an increase of nandrolone metabolites in urine. Volunteers (n = 22) ingested two 25-mg doses of [(13)C]nandrolone at 24-h intervals and collected urine specimens for 5 days. The labeled nandrolone metabolites 19-norandrosterone and 19-noretiocholanolone were identified and quantified by gas chromatography-mass spectrometry. Interindividual variability was observed in nandrolone excretion patterns and kinetics, as well as for the noretiocholanolone:norandrosterone ratio. The amounts of nandrolone metabolites measured at the excretion peak varied between 1180 and 38 661 microg/L for norandrosterone and 576 and 12 328 microg/L for noretiocholanolone. At the end of the excretion period, the noretiocholanolone:norandrosterone ratio was sometimes >1. The analysis of numerous spot-urine samples allowed the determination of an acceptable correlation between urinary creatinine and specific gravity for placebo- and steroid-treated individuals: y = 0.0052ln(x) + 1.0178 (r(2) = 0.8142) and y = 0.0068ln(x) + 1.0172 (r(2) = 0.7730), respectively. The excretion kinetics and patterns of labeled nandrolone show interindividual variability. More investigations are currently underway to estimate the influence of exhaustive exercises on excretion of labeled nandrolone metabolites in urine.

  17. Intra- and inter-individual variations of blood and urinary water-soluble vitamins in Japanese young adults consuming a semi-purified diet for 7 days.

    PubMed

    Shibata, Katsumi; Fukuwatari, Tsutomu; Watanabe, Toshiaki; Nishimuta, Mamoru

    2009-12-01

    We have previously reported the levels of water-soluble vitamins in the blood and urine of Japanese young adults. In the present paper, to assess the variations in these water-soluble vitamin markers during the above experiment, we comprehensively determined the intra- and inter-individual variations of blood and urinary water-soluble vitamins to exactly the same amount of water-soluble vitamin intakes in the same experiment. The blood samples before breakfast and the 24-h urine samples were periodically collected from Japanese college male (n=10) and female (n=10) students consuming a semi-purified diet with water-soluble vitamins based on Japanese Dietary Reference Intakes for 7 d, and the intra- and inter-individual variations of blood and urinary water-soluble vitamins or their metabolites in blood and urine samples after adaptation were calculated. Although urinary excretion of vitamin B(12) and vitamin C showed high intra-individual variations in both males and females, other urinary vitamins and all blood vitamins showed less than 20% of within-subject coefficients of variance in either male or female. Those showing more than 20% of between-subject coefficients of variances in both male and female were blood vitamin B(6), vitamin B(12) and folate levels, and urinary vitamin B(1), vitamin B(2), vitamin B(12), nicotinamide metabolites, pantothenic acid, biotin and vitamin C. These results showed that oral administration of constant of water-soluble vitamins generally decreased intra-individual variation, while individual differences in urinary vitamin excretion were observed.

  18. 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.

  19. EEG Beta Power but Not Background Music Predicts the Recall Scores in a Foreign-Vocabulary Learning Task.

    PubMed

    Küssner, Mats B; de Groot, Annette M B; Hofman, Winni F; Hillen, Marij A

    2016-01-01

    As tantalizing as the idea that background music beneficially affects foreign vocabulary learning may seem, there is-partly due to a lack of theory-driven research-no consistent evidence to support this notion. We investigated inter-individual differences in the effects of background music on foreign vocabulary learning. Based on Eysenck's theory of personality we predicted that individuals with a high level of cortical arousal should perform worse when learning with background music compared to silence, whereas individuals with a low level of cortical arousal should be unaffected by background music or benefit from it. Participants were tested in a paired-associate learning paradigm consisting of three immediate word recall tasks, as well as a delayed recall task one week later. Baseline cortical arousal assessed with spontaneous EEG measurement in silence prior to the learning rounds was used for the analyses. Results revealed no interaction between cortical arousal and the learning condition (background music vs. silence). Instead, we found an unexpected main effect of cortical arousal in the beta band on recall, indicating that individuals with high beta power learned more vocabulary than those with low beta power. To substantiate this finding we conducted an exact replication of the experiment. Whereas the main effect of cortical arousal was only present in a subsample of participants, a beneficial main effect of background music appeared. A combined analysis of both experiments suggests that beta power predicts the performance in the word recall task, but that there is no effect of background music on foreign vocabulary learning. In light of these findings, we discuss whether searching for effects of background music on foreign vocabulary learning, independent of factors such as inter-individual differences and task complexity, might be a red herring. Importantly, our findings emphasize the need for sufficiently powered research designs and exact replications of theory-driven experiments when investigating effects of background music and inter-individual variation on task performance.

  20. EEG Beta Power but Not Background Music Predicts the Recall Scores in a Foreign-Vocabulary Learning Task

    PubMed Central

    de Groot, Annette M. B.; Hofman, Winni F.; Hillen, Marij A.

    2016-01-01

    As tantalizing as the idea that background music beneficially affects foreign vocabulary learning may seem, there is—partly due to a lack of theory-driven research—no consistent evidence to support this notion. We investigated inter-individual differences in the effects of background music on foreign vocabulary learning. Based on Eysenck’s theory of personality we predicted that individuals with a high level of cortical arousal should perform worse when learning with background music compared to silence, whereas individuals with a low level of cortical arousal should be unaffected by background music or benefit from it. Participants were tested in a paired-associate learning paradigm consisting of three immediate word recall tasks, as well as a delayed recall task one week later. Baseline cortical arousal assessed with spontaneous EEG measurement in silence prior to the learning rounds was used for the analyses. Results revealed no interaction between cortical arousal and the learning condition (background music vs. silence). Instead, we found an unexpected main effect of cortical arousal in the beta band on recall, indicating that individuals with high beta power learned more vocabulary than those with low beta power. To substantiate this finding we conducted an exact replication of the experiment. Whereas the main effect of cortical arousal was only present in a subsample of participants, a beneficial main effect of background music appeared. A combined analysis of both experiments suggests that beta power predicts the performance in the word recall task, but that there is no effect of background music on foreign vocabulary learning. In light of these findings, we discuss whether searching for effects of background music on foreign vocabulary learning, independent of factors such as inter-individual differences and task complexity, might be a red herring. Importantly, our findings emphasize the need for sufficiently powered research designs and exact replications of theory-driven experiments when investigating effects of background music and inter-individual variation on task performance. PMID:27537520

  1. Effects of rearing environment on the gut antimicrobial responses of two broiler chicken lines.

    PubMed

    Butler, Vanessa L; Mowbray, Catherine A; Cadwell, Kevin; Niranji, Sherko S; Bailey, Richard; Watson, Kellie A; Ralph, John; Hall, Judith

    2016-10-01

    To reduce the risk of enteric disease in poultry, knowledge of how bird gut innate defences mature with age while also responding to different rearing environments is necessary. In this study the gut innate responses of two phylogenetically distinct lines of poultry raised from hatch to 35days, in conditions mimicing high hygiene (HH) and low hygiene (LH) rearing environments, were compared. Analyses focussed on the proximal gut antimicrobial activities and the duodenal and caecal AvBD1, 4 and 10 defensin profiles. Variability in microbial killing was observed between individual birds in each of the two lines at all ages, but samples from day 0 birds (hatch) of both lines exhibited marked killing properties, Line X: 19±11% (SEM) and Line Y: 8.5±12% (SEM). By day 7 a relaxation in killing was observed with bacterial survival increased from 3 (Line Y (LY)) to 11 (Line X (LX)) fold in birds reared in the HH environment. A less marked response was observed in the LH environment and delayed until day 14. At day 35 the gut antimicrobial properties of the two lines were comparable. The AvBD 1, 4 and 10 data relating to the duodenal and caecal tissues of day 0, 7 and 35 birds LX and LY birds revealed gene expression trends specific to each line and to the different rearing environments although the data were confounded by inter-individual variability. In summary elevated AvBD1 duodenal expression was detected in day 0 and day 7 LX, but not LY birds, maintained in LH environments; Line X and Y duodenal AvBD4 profiles were detected in day 7 birds reared in both environments although duodenal AvBD10 expression was less sensitive to bird age and rearing background. Caecal AvBD1 expression was particularly evident in newly hatched birds. These data suggest that proximal gut antimicrobial activity is related to the bird rearing environments although the roles of the AvBDs in such activities require further investigation. Copyright © 2016. Published by Elsevier B.V.

  2. Development and Validation of a Short-Form Adaptation of the Age-Related Vision Loss Scale: The AVL12

    ERIC Educational Resources Information Center

    Horowitz, Amy; Reinhardt, Joann P.; Raykov, Tenko

    2007-01-01

    This article describes the development and evaluation of a short form of the 24-item Adaptation to Age-Related Vision Loss (AVL) scale. The evaluation provided evidence of the reliability and validity of the short form (the AVL12), for significant interindividual differences at the baseline and for individual-level change in AVL scores over time.…

  3. 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.

  4. Changes in aerobic capacity and glycaemic control in response to reduced-exertion high-intensity interval training (REHIT) are not different between sedentary men and women.

    PubMed

    Metcalfe, Richard S; Tardif, Nicolas; Thompson, Dylan; Vollaard, Niels B J

    2016-11-01

    Previously it has been reported that reduced-exertion high-intensity interval training (REHIT; total training time of 3 × 10 min per week) improves maximal aerobic capacity in both sedentary men and women, but improves insulin sensitivity in men only. The aim of the present study was to determine whether there is a true sex difference in response to REHIT, or that these findings can be explained by the large interindividual variability in response inherent to all exercise training. Thirty-five sedentary participants (18 women; mean ± SD age for men and women, respectively: age, 33 ± 9 and 36 ± 9 years; body mass index, 25.1 ± 2.1 and 24.1 ± 3.5 kg·m -2 ; maximal aerobic capacity, 38.6 ± 8.3 and 31.6 ± 4.6 mL·kg -1 ·min -1 ) completed a 6-week REHIT programme consisting of eighteen 10-min unloaded cycling sessions with 1 (first session) or 2 (all other sessions) "all-out" 10-20-s sprints against a resistance of 5% of body mass. Maximal aerobic capacity and oral glucose tolerance test-derived insulin sensitivity were determined before and after training. REHIT was associated with an increase in maximal aerobic capacity (2.54 ± 0.65 vs. 2.78 ± 0.68 L·min -1 , main effect of time: p < 0.01), a trend toward reduced plasma insulin area-under-the-curve (AUC; 6.7 ± 4.8 vs. 6.1 ± 4.0 IU·min -1 ·mL -1 , p = 0.096), but no significant change in plasma glucose AUC or the Cederholm index of insulin sensitivity. Substantial interindividual variability in response to REHIT was observed for all variables, but there was no significant effect of sex. In conclusion, REHIT improves the key health marker of aerobic capacity within a minimal total training time-commitment. There is large interindividual variability in responses to REHIT, but sex differences in the responses are not apparent.

  5. Predicting risk in space: Genetic markers for differential vulnerability to sleep restriction

    NASA Astrophysics Data System (ADS)

    Goel, Namni; Dinges, David F.

    2012-08-01

    Several laboratories have found large, highly reliable individual differences in the magnitude of cognitive performance, fatigue and sleepiness, and sleep homeostatic vulnerability to acute total sleep deprivation and to chronic sleep restriction in healthy adults. Such individual differences in neurobehavioral performance are also observed in space flight as a result of sleep loss. The reasons for these stable phenotypic differential vulnerabilities are unknown: such differences are not yet accounted for by demographic factors, IQ or sleep need, and moreover, psychometric scales do not predict those individuals cognitively vulnerable to sleep loss. The stable, trait-like (phenotypic) inter-individual differences observed in response to sleep loss—with intraclass correlation coefficients accounting for 58-92% of the variance in neurobehavioral measures—point to an underlying genetic component. To this end, we utilized multi-day highly controlled laboratory studies to investigate the role of various common candidate gene variants—each independently—in relation to cumulative neurobehavioral and sleep homeostatic responses to sleep restriction. These data suggest that common genetic variations (polymorphisms) involved in sleep-wake, circadian, and cognitive regulation may serve as markers for prediction of inter-individual differences in sleep homeostatic and neurobehavioral vulnerability to sleep restriction in healthy adults. Identification of genetic predictors of differential vulnerability to sleep restriction—as determined from candidate gene studies—will help identify astronauts most in need of fatigue countermeasures in space flight and inform medical standards for obtaining adequate sleep in space. This review summarizes individual differences in neurobehavioral vulnerability to sleep deprivation and ongoing genetic efforts to identify markers of such differences.

  6. Characterizing the spectrum of right ventricular remodelling in response to chronic training.

    PubMed

    Sitges, Marta; Merino, Beatriz; Butakoff, Constatine; de la Garza, Maria Sanz; Paré, Carles; Montserrat, Silvia; Vidal, Barbara; Azqueta, Manel; Sarquella, Georgia; Gutierrez, Josep Antoni; Canal, Ramon; Brugada, Josep; Bijnens, Bart H

    2017-03-01

    The significance and spectrum of reduced right ventricular (RV) deformation, reported in endurance athletes, is unclear. To comprehensively analyze the cardiac performance at rest of athletes, especially focusing on integrating RV size and deformation to unravel the underlying triggers of this ventricular remodelling. Hundred professional male athletes and 50 sedentary healthy males of similar age were prospectively studied. Conventional echocardiographic parameters of all four chambers were obtained, as well as 2D echo-derived strain (2DSE) in the left (LV) and in the RV free wall with separate additional analysis of the RV basal and apical segments. Left and right-sided dimensions were larger in athletes than in controls, but with a disproportionate RA enlargement. RV global strain was lower in sportsmen (-26.8 ± 2.8% vs -28.5 ± 3.4%, p < 0.001) due to a decrease in the basal segment (-22.8 ± 3.5% vs -25.8 ± 4.0%, p < 0.001) resulting in a marked gradient of deformation from the RV inlet towards the apex. By integrating size, deformation and stroke volume, we observed that the LV working conditions were similar in all sportsmen while a wider variability existed in the RV. Cardiac remodelling in athletes is more pronounced in the right heart cavities with specific regional differences within the right ventricle, but with a wide variability among individuals. The large inter-individual differences, as well as its acute and chronic relevance warrant further investigation.

  7. Processing emotions: Effects of menstrual cycle phase and premenstrual symptoms on the startle reflex, facial EMG and heart rate.

    PubMed

    Armbruster, Diana; Grage, Tobias; Kirschbaum, Clemens; Strobel, Alexander

    2018-10-01

    Emotional reactivity varies across the menstrual cycle although physiological findings are not entirely consistent. We assessed facial EMG and heart rate (HR) changes in healthy free cycling women (N = 45) with an emotional startle paradigm both during the early follicular and the late luteal phase, verified by repeated salivary 17β-estradiol, progesterone and testosterone assessments. Cycle phase impacted startle responses with larger magnitudes during the luteal phase. Notably, this effect was only present when premenstrual symptoms and sequence of lab sessions were included as co-variates. At rest, participants showed a tendency towards higher HR and reduced high frequency (HF) power during the luteal phase indicating reduced parasympathetic tone. HF power was also negatively associated with startle magnitudes. HR changes in response to emotional images differed between the two cycle phases. Initial HR deceleration was more marked during the follicular phase particularly when viewing negative pictures. However, cycle phase did not significantly impact corrugator and zygomaticus activity in response to emotional pictures. Among the three gonadal steroids, correlation patterns were most consistent for testosterone. During the follicular phase, testosterone was associated with zygomaticus activity while viewing neutral or positive pictures and with less pronounced HR deceleration in response to negative images. During the luteal phase, testosterone was negatively associated with fear potentiated startle. The findings underscore the importance of considering menstrual cycle phase when investigating physiological indicators of emotion. However, the modulating effect of premenstrual symptoms also emphasizes potential inter-individual differences. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Precision, Reliability, and Effect Size of Slope Variance in Latent Growth Curve Models: Implications for Statistical Power Analysis

    PubMed Central

    Brandmaier, Andreas M.; von Oertzen, Timo; Ghisletta, Paolo; Lindenberger, Ulman; Hertzog, Christopher

    2018-01-01

    Latent Growth Curve Models (LGCM) have become a standard technique to model change over time. Prediction and explanation of inter-individual differences in change are major goals in lifespan research. The major determinants of statistical power to detect individual differences in change are the magnitude of true inter-individual differences in linear change (LGCM slope variance), design precision, alpha level, and sample size. Here, we show that design precision can be expressed as the inverse of effective error. Effective error is determined by instrument reliability and the temporal arrangement of measurement occasions. However, it also depends on another central LGCM component, the variance of the latent intercept and its covariance with the latent slope. We derive a new reliability index for LGCM slope variance—effective curve reliability (ECR)—by scaling slope variance against effective error. ECR is interpretable as a standardized effect size index. We demonstrate how effective error, ECR, and statistical power for a likelihood ratio test of zero slope variance formally relate to each other and how they function as indices of statistical power. We also provide a computational approach to derive ECR for arbitrary intercept-slope covariance. With practical use cases, we argue for the complementary utility of the proposed indices of a study's sensitivity to detect slope variance when making a priori longitudinal design decisions or communicating study designs. PMID:29755377

  9. Pharmacogenetic study of second-generation antipsychotic long-term treatment metabolic side effects (the SLiM Study): rationale, objectives, design and sample description.

    PubMed

    Pina-Camacho, Laura; Díaz-Caneja, Covadonga M; Saiz, Pilar A; Bobes, Julio; Corripio, Iluminada; Grasa, Eva; Rodriguez-Jimenez, Roberto; Fernández, Miryam; Sanjuán, Julio; García-López, Aurelio; Tapia-Casellas, Cecilia; Álvarez-Blázquez, María; Fraguas, David; Mitjans, Marina; Arias, Bárbara; Arango, Celso

    2014-01-01

    Weight gain is an important and common side effect of second generation antipsychotics (SGAs). Furthermore, these drugs can induce other side effects associated with higher cardiovascular morbidity and mortality, such as insulin resistance, diabetes or metabolic syndrome. Preliminary studies show that inter-individual genetic differences produce varying degrees of vulnerability to the different SGA-induced side effects. The Second-generation antipsychotic Long-term treatment Metabolic side effects (SLiM) study aims to identify clinical, environmental and genetic factors that explain inter-individual differences in weight gain and metabolic changes in drug-naïve patients after six months of treatment with SGAs. The SLIM study is a multicenter, observational, six-month pharmacogenetic study where a cohort of 307 drug-naïve paediatric and adult patients (age range 8.8-90.1 years) and a cohort of 150 age- and sex- matched healthy controls (7.8-73.2 years) were recruited. This paper describes the rationale, objectives and design of the study and provides a description of the sample at baseline. Results from the SLiM study will provide a better understanding of the clinical, environmental, and genetic factors involved in weight gain and metabolic disturbances associated with SGA treatment. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

  10. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress

    PubMed Central

    Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C.; van Wingen, Guido A.; Fernández, Guillén

    2016-01-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus–pituitary–adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. PMID:26668010

  11. A Neural Basis for Interindividual Differences in the McGurk Effect, a Multisensory Speech Illusion

    PubMed Central

    Nath, Audrey R.; Beauchamp, Michael S.

    2011-01-01

    The McGurk effect is a compelling illusion in which humans perceive mismatched audiovisual speech as a completely different syllable. However, some normal individuals do not experience the illusion, reporting that the stimulus sounds the same with or without visual input. Converging evidence suggests that the left superior temporal sulcus (STS) is critical for audiovisual integration during speech perception. We used blood-oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) to measure brain activity as McGurk perceivers and non-perceivers were presented with congruent audiovisual syllables, McGurk audiovisual syllables, and non-McGurk incongruent syllables. The inferior frontal gyrus showed an effect of stimulus condition (greater responses for incongruent stimuli) but not susceptibility group, while the left auditory cortex showed an effect of susceptibility group (greater response in susceptible individuals) but not stimulus condition. Only one brain region, the left STS, showed a significant effect of both susceptibility and stimulus condition. The amplitude of the response in the left STS was significantly correlated with the likelihood of perceiving the McGurk effect: a weak STS response meant that a subject was less likely to perceive the McGurk effect, while a strong response meant that a subject was more likely to perceive it. These results suggest that the left STS is a key locus for interindividual differences in speech perception. PMID:21787869

  12. Inter-individual differences in the initial 80 minutes of motor learning of handrim wheelchair propulsion.

    PubMed

    Vegter, Riemer J K; Lamoth, Claudine J; de Groot, Sonja; Veeger, Dirkjan H E J; van der Woude, Lucas H V

    2014-01-01

    Handrim wheelchair propulsion is a cyclic skill that needs to be learned during rehabilitation. Yet it is unclear how inter-individual differences in motor learning impact wheelchair propulsion practice. Therefore we studied how early-identified motor learning styles in novice able-bodied participants impact the outcome of a low-intensity wheelchair-practice intervention. Over a 12-minute pre-test, 39 participants were split in two groups based on a relative 10% increase in mechanical efficiency. Following the pretest the participants continued one of four different low-intensity wheelchair practice interventions, yet all performed in the same trial-setup with a total 80-minute dose at 1.11 m/s at 0.20 W/kg. Instead of focusing on the effect of the different interventions, we focused on differences in motor learning between participants over the intervention. Twenty-six participants started the pretest with a lower mechanical efficiency and a less optimal propulsion technique, but showed a fast improvement during the first 12 minutes and this effect continued over the 80 minutes of practice. Eventually these initially fast improvers benefitted more from the given practice indicated by a better propulsion technique (like reduced frequency and increased stroke angle) and a higher mechanical efficiency. The initially fast improvers also had a higher intra-individual variability in the pre and posttest, which possibly relates to the increased motor learning of the initially fast improvers. Further exploration of the common characteristics of different types of learners will help to better tailor rehabilitation to the needs of wheelchair-dependent persons and improve our understanding of cyclic motor learning processes.

  13. Comparison of weighed food record procedures for the reference methods in two validation studies of food frequency questionnaires.

    PubMed

    Ishii, Yuri; Ishihara, Junko; Takachi, Ribeka; Shinozawa, Yurie; Imaeda, Nahomi; Goto, Chiho; Wakai, Kenji; Takahashi, Toshiaki; Iso, Hiroyasu; Nakamura, Kazutoshi; Tanaka, Junta; Shimazu, Taichi; Yamaji, Taiki; Sasazuki, Shizuka; Sawada, Norie; Iwasaki, Motoki; Mikami, Haruo; Kuriki, Kiyonori; Naito, Mariko; Okamoto, Naoko; Kondo, Fumi; Hosono, Satoyo; Miyagawa, Naoko; Ozaki, Etsuko; Katsuura-Kamano, Sakurako; Ohnaka, Keizo; Nanri, Hinako; Tsunematsu-Nakahata, Noriko; Kayama, Takamasa; Kurihara, Ayako; Kojima, Shiomi; Tanaka, Hideo; Tsugane, Shoichiro

    2017-07-01

    Although open-ended dietary assessment methods, such as weighed food records (WFRs), are generally considered to be comparable, differences between procedures may influence outcome when WFRs are conducted independently. In this paper, we assess the procedures of WFRs in two studies to describe their dietary assessment procedures and compare the subsequent outcomes. WFRs of 12 days (3 days for four seasons) were conducted as reference methods for intake data, in accordance with the study protocol, among a subsample of participants of two large cohort studies. We compared the WFR procedures descriptively. We also compared some dietary intake variables, such as the frequency of foods and dishes and contributing foods, to determine whether there were differences in the portion size distribution and intra- and inter-individual variation in nutrient intakes caused by the difference in procedures. General procedures of the dietary records were conducted in accordance with the National Health and Nutrition Survey and were the same for both studies. Differences were seen in 1) selection of multiple days (non-consecutive days versus consecutive days); and 2) survey sheet recording method (individual versus family participation). However, the foods contributing to intake of energy and selected nutrients, the portion size distribution, and intra- and inter-individual variation in nutrient intakes were similar between the two studies. Our comparison of WFR procedures in two independent studies revealed several differences. Notwithstanding these procedural differences, however, the subsequent outcomes were similar. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  14. A possible structural correlate of learning performance on a colour discrimination task in the brain of the bumblebee

    PubMed Central

    Li, Li; MaBouDi, HaDi; Egertová, Michaela; Elphick, Maurice R.

    2017-01-01

    Synaptic plasticity is considered to be a basis for learning and memory. However, the relationship between synaptic arrangements and individual differences in learning and memory is poorly understood. Here, we explored how the density of microglomeruli (synaptic complexes) within specific regions of the bumblebee (Bombus terrestris) brain relates to both visual learning and inter-individual differences in learning and memory performance on a visual discrimination task. Using whole-brain immunolabelling, we measured the density of microglomeruli in the collar region (visual association areas) of the mushroom bodies of the bumblebee brain. We found that bumblebees which made fewer errors during training in a visual discrimination task had higher microglomerular density. Similarly, bumblebees that had better retention of the learned colour-reward associations two days after training had higher microglomerular density. Further experiments indicated experience-dependent changes in neural circuitry: learning a colour-reward contingency with 10 colours (but not two colours) does result, and exposure to many different colours may result, in changes to microglomerular density in the collar region of the mushroom bodies. These results reveal the varying roles that visual experience, visual learning and foraging activity have on neural structure. Although our study does not provide a causal link between microglomerular density and performance, the observed positive correlations provide new insights for future studies into how neural structure may relate to inter-individual differences in learning and memory. PMID:28978727

  15. A possible structural correlate of learning performance on a colour discrimination task in the brain of the bumblebee.

    PubMed

    Li, Li; MaBouDi, HaDi; Egertová, Michaela; Elphick, Maurice R; Chittka, Lars; Perry, Clint J

    2017-10-11

    Synaptic plasticity is considered to be a basis for learning and memory. However, the relationship between synaptic arrangements and individual differences in learning and memory is poorly understood. Here, we explored how the density of microglomeruli (synaptic complexes) within specific regions of the bumblebee ( Bombus terrestris ) brain relates to both visual learning and inter-individual differences in learning and memory performance on a visual discrimination task. Using whole-brain immunolabelling, we measured the density of microglomeruli in the collar region (visual association areas) of the mushroom bodies of the bumblebee brain. We found that bumblebees which made fewer errors during training in a visual discrimination task had higher microglomerular density. Similarly, bumblebees that had better retention of the learned colour-reward associations two days after training had higher microglomerular density. Further experiments indicated experience-dependent changes in neural circuitry: learning a colour-reward contingency with 10 colours (but not two colours) does result, and exposure to many different colours may result, in changes to microglomerular density in the collar region of the mushroom bodies. These results reveal the varying roles that visual experience, visual learning and foraging activity have on neural structure. Although our study does not provide a causal link between microglomerular density and performance, the observed positive correlations provide new insights for future studies into how neural structure may relate to inter-individual differences in learning and memory. © 2017 The Authors.

  16. Influence of Different Patellofemoral Design Variations Based on Genesis II Total Knee Endoprosthesis on Patellofemoral Pressure and Kinematics

    PubMed Central

    Lange, Barbara; Herzog, Yvonne; Schnauffer, Peter; Leichtle, Carmen I.; Wülker, Nikolaus

    2017-01-01

    In total knee arthroplasty (TKA), patellofemoral groove design varies greatly and likely has a distinct influence on patellofemoral biomechanics. To analyse the selective influence, five patellofemoral design variations were developed based on Genesis II total knee endoprosthesis (original design, being completely flat, being laterally elevated, being medially elevated, and both sides elevated) and made from polyamide using rapid prototyping. Muscle-loaded knee flexion was simulated on 10 human knee specimens using a custom-made knee simulator, measuring the patellofemoral pressure distribution and tibiofemoral and patellofemoral kinematics. The measurements were carried out in the native knee as well as after TKA with the 5 design prototypes. The overall influence of the different designs on the patellofemoral kinematics was small, but we found detectable effects for mediolateral tilt (p < 0.05 for 35°–80° flexion) and translation of the patella (p < 0.045 for 20°–65° and 75°–90°), especially for the completely flat design. Considering patellofemoral pressures, major interindividual differences were seen between the designs, which, on average, largely cancelled each other out. These results suggest that the elevation of the lateral margin of the patellofemoral groove is essential for providing mediolateral guidance, but smooth contouring as with original Genesis II design seems to be sufficient. The pronounced interindividual differences identify a need for more patellofemoral design options in TKA. PMID:28255225

  17. Dose–response effects of aerobic exercise on energy compensation in postmenopausal women: combined results from two randomized controlled trials

    PubMed Central

    McNeil, J; Brenner, D R; Courneya, K S; Friedenreich, C M

    2017-01-01

    Background/objectives: Despite the clear health benefits of exercise, exercised-induced weight loss is often less than expected. The term ‘exercise energy compensation’ is used to define the amount of weight loss below what is expected for the amount of exercise energy expenditure. We examined the dose–response effects of exercise volume on energy compensation in postmenopausal women. Participants/methods: Data from Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were combined for the present analysis. The ALPHA and BETA trials were two-centred, two-armed, 12-month randomized controlled trials. The ALPHA trial included 160 participants randomized to 225 min per week of aerobic exercise, and the BETA trial randomized 200 participants to each 150 and 300 min per week of aerobic exercise. All participants were aged 50–74 years, moderately inactive (<90 min per week of exercise), had no previous cancer diagnosis and a body mass index between 22 and 40 kg m−2. Energy compensation was based on changes in body composition (dual-energy X-ray absorptiometry scan) and estimated exercise energy expenditure from completed exercise volume. Associations between Δenergy intake, ΔVO2peak and Δphysical activity time with energy compensation were assessed. Results: No differences in energy compensation were noted between interventions. However, there were large inter-individual differences in energy compensation between participants; 9.4% experienced body composition changes that were greater than expected based on exercise energy expenditure, 64% experienced some degree of energy compensation and 26.6% experienced weight gain based on exercise energy expenditure. Increases in VO2peak were associated with reductions in energy compensation (β=−3.44 ml kg−1 min−1, 95% confidence interval for β=−4.71 to −2.17 ml kg−1 min−1; P=0.0001). Conclusions: Large inter-individual differences in energy compensation were noted, despite no differences between activity doses. In addition, increases in VO2peak were associated with lower energy compensation. Future studies are needed to identify behavioral and metabolic factors that may contribute to this large inter-individual variability in energy compensation. PMID:28360432

  18. Fear or greed? Oxytocin regulates inter-individual conflict by enhancing fear in men.

    PubMed

    Zheng, Huimin; Kendrick, Keith M; Yu, Rongjun

    2016-09-01

    People may choose non-cooperation in social dilemmas either out of fear (if others choose to defect) or out of greed (when others choose to cooperate). Previous studies have shown that exogenous oxytocin motivates a "tend and defend" pattern in inter-group conflict in which oxytocin stimulates in-group cooperation and out-group defense. Using a double-blind placebo-controlled design combined with a modified Prisoner's dilemma game (PDG), we examined the effect of oxytocin on social motivations in inter-individual conflict in men. Results showed that compared with the placebo group, oxytocin-exposed participants were less cooperative in general. Specifically, oxytocin amplified the effect of fear on defection but did not influence the effect of greed. Another non-social control study confirmed participants' decisions were sensitive to social factors. Our findings suggest that even when social group conflict is removed, oxytocin promotes distrust of strangers in "me and you" inter-individual conflict by elevating social fear in men. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Individual Variation in the Late Positive Complex to Semantic Anomalies

    PubMed Central

    Kos, Miriam; van den Brink, Danielle; Hagoort, Peter

    2012-01-01

    It is well-known that, within ERP paradigms of sentence processing, semantically anomalous words elicit N400 effects. Less clear, however, is what happens after the N400. In some cases N400 effects are followed by Late Positive Complexes (LPC), whereas in other cases such effects are lacking. We investigated several factors which could affect the LPC, such as contextual constraint, inter-individual variation, and working memory. Seventy-two participants read sentences containing a semantic manipulation (Whipped cream tastes sweet/anxious and creamy). Neither contextual constraint nor working memory correlated with the LPC. Inter-individual variation played a substantial role in the elicitation of the LPC with about half of the participants showing a negative response and the other half showing an LPC. This individual variation correlated with a syntactic ERP as well as an alternative semantic manipulation. In conclusion, our results show that inter-individual variation plays a large role in the elicitation of the LPC and this may account for the diversity in LPC findings in language research. PMID:22973249

  20. Individualism and nonindividualism in the application of nonhuman animal welfare to policy.

    PubMed

    Yeates, J W

    2013-01-01

    Science-based policy making and assessments are individualistic insofar as they are sensitive to interindividual differences, intraindividual connectivity, or both. Several scientists and policymakers have argued that nonhuman animal welfare should relate to individual animals, but there are reasons for both individualistic and nonindividualistic approaches. Opportunities to develop more individualistic approaches include employing concepts such as "quality-of-life," "welfare opportunities," and greater stockperson flexibility.

  1. 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.

  2. Reading and lexical-decision tasks generate different patterns of individual variability as a function of condition difficulty.

    PubMed

    Zoccolotti, Pierluigi; De Luca, Maria; Di Filippo, Gloria; Marinelli, Chiara Valeria; Spinelli, Donatella

    2018-06-01

    We reanalyzed previous experiments based on lexical-decision and reading-aloud tasks in children with dyslexia and control children and tested the prediction of the difference engine model (DEM) that mean condition reaction times (RTs) and standard deviations (SDs) would be linearly related (Myerson et al., 2003). Then we evaluated the slope and the intercept with the x-axis of these linear functions in comparison with previously reported values (i.e., slope of about 0.30 and intercept of about 300 ms). In the case of lexical decision, the parameters were close to these values; by contrast, in the case of reading aloud, a much steeper slope (0.66) and a greater intercept (482.6 ms) were found. Therefore, interindividual variability grows at a much faster rate as a function of condition difficulty for reading than for lexical-decision tasks (or for other tasks reported in the literature). According to the DEM, the slope of the regression that relates means and SDs indicates the degree of correlation among the durations of the stages of processing. We propose that the need for a close coupling between orthographic and phonological processing in reading is what drives the particularly strong relationship between performance and interindividual variability that we observed in reading tasks.

  3. Motility, ATP levels and metabolic enzyme activity of sperm from bluegill (Lepomis macrochirus).

    PubMed

    Burness, Gary; Moyes, Christopher D; Montgomerie, Robert

    2005-01-01

    Male bluegill displays one of two life history tactics. Some males (termed "parentals") delay reproduction until ca. 7 years of age, at which time they build nests and actively courts females. Others mature precociously (sneakers) and obtain fertilizations by cuckolding parental males. In the current study, we studied the relations among sperm motility, ATP levels, and metabolic enzyme activity in parental and sneaker bluegill. In both reproductive tactics, sperm swimming speed and ATP levels declined in parallel over the first 60 s of motility. Although sneaker sperm initially had higher ATP levels than parental sperm, by approximately 30 s postactivation, no differences existed between tactics. No differences were noted between tactics in swimming speed, percent motility, or the activities of key metabolic enzymes, although sperm from parentals had a higher ratio of creatine phosphokinase (CPK) to citrate synthase (CS). In both tactics, with increasing CPK and CS activity, sperm ATP levels increased at 20 s postactivation, suggesting that capacities for phosphocreatine hydrolysis and aerobic metabolism may influence interindividual variation in rates of ATP depletion. Nonetheless, there was no relation between sperm ATP levels and either swimming speed or percent of sperm that were motile. This suggests that interindividual variation in ATP levels may not be the primary determinant of variation in sperm swimming performance in bluegill.

  4. 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

  5. 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.

  6. 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.

  7. Influence of multiple injections of human chorionic gonadotropin (hCG) on urine and serum endogenous steroids concentrations.

    PubMed

    Strahm, Emmanuel; Marques-Vidal, Pedro; Pralong, François; Dvorak, Jiri; Saugy, Martial; Baume, Norbert

    2011-12-10

    Since it is established that human chorionic gonadotropin (hCG) affects testosterone production and release in the human body, the use of this hormone as a performance enhancing drug has been prohibited by the World Anti-Doping Agency. Nowadays, the only validated biomarker of a hCG doping is its direct quantification in urine. However, this specific parameter is subjected to large inter-individual variability and its determination is directly dependent on the reliability of hCG immunoassays used. In order to counteract these weaknesses, new biomarkers need to be evidenced. To address this issue, a pilot clinical study was performed on 10 volunteers submitted to 3 subsequent hCG injections. Blood and urine samples were collected during two weeks in order to follow the physiological effects on related compounds such as the steroid profile or hormones involved in the hypothalamo-pituitary axis. The hCG pharmacokinetic observed in all subjects was, as expected, prone to important inter-individual variations. Using ROC plots, level of testosterone and testosterone on luteinizing hormone ratio in both blood and urine were found to be the most relevant biomarker of a hCG abuse, regardless of inter-individual variations. In conclusion, this study showed the crucial importance of reliable quantification methods to assess low differences in hormonal patterns. In regard to these results and to anti-doping requirements and constraints, blood together with urine matrix should be included in the anti-doping testing program. Together with a longitudinal follow-up approach it could constitute a new strategy to detect a hCG abuse, applicable to further forms of steroid or other forbidden drug manipulation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. 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.

  9. [Interindividual variation of pharmacokinetic disposition of and clinical responses to opioid analgesics in cancer pain patients].

    PubMed

    Naito, Takafumi; Kawakami, Junichi

    2015-01-01

    Use of prescription opioids for cancer pain according to the World Health Organization analgesic ladder has been accepted in Japan. Although oxycodone and fentanyl are commonly used as first-line analgesics, a few clinical reports have been published on interindividual variations in their pharmacokinetics and clinical responses in cancer patients. (1) Some factors relating to CYP2D6, CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu 1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans. The relations between their genetic variations and clinical responses to oxycodone are being revealed in limited groups. In our study, the impact of genetic variants and pharmacokinetics on clinical responses to oxycodone were evaluated in Japanese populations. (2) Opioid switching improves the opioid tolerance related to the balance between analgesia and adverse effects. Some patients have difficulty in obtaining better opioid tolerance in recommended conversion ratios. The activities of CYP3A, ABCB1, and OPRM1 contribute to the interindividual variations in clinical responses to fentanyl in cancer patients. However, the variations in opioid switching remain to be clarified in clinical settings. In our study, genetic factors related to interindividual variations in clinical responses in opioid switching to fentanyl were revealed in Japanese populations. In this symposium review, the possibility of approaches to personalized palliative care using opioids based on genetic variants of CYP2D6, CYP3A5, ABCB1, and OPRM1 is discussed.

  10. 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

  11. 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.

  12. Fairness, fast and slow: A review of dual process models of fairness.

    PubMed

    Hallsson, Bjørn G; Siebner, Hartwig R; Hulme, Oliver J

    2018-06-01

    Fairness, the notion that people deserve or have rights to certain resources or kinds of treatment, is a fundamental dimension of moral cognition. Drawing on recent evidence from economics, psychology, and neuroscience, we ask whether self-interest is always intuitive, requiring self-control to override with reasoning-based fairness concerns, or whether fairness itself can be intuitive. While we find strong support for rejecting the notion that self-interest is always intuitive, the literature has reached conflicting conclusions about the neurocognitive systems underpinning fairness. We propose that this disagreement can largely be resolved in light of an extended Social Heuristics Hypothesis. Divergent findings may be attributed to the interpretation of behavioral effects of ego depletion or neurostimulation, reverse inference from brain activity to the underlying psychological process, and insensitivity to social context and inter-individual differences. To better dissect the neurobiological basis of fairness, we outline how future research should embrace cross-disciplinary methods that combine psychological manipulations with neuroimaging, and that can probe inter-individual, and cultural heterogeneities. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Adjustment of sleep and the circadian temperature rhythm after flights across nine time zones

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Myhre, Grete; Graeber, R. Curtis; Lauber, John K.; Andersen, Harald T.

    1989-01-01

    The adjustment of sleep-wake patterns and the circadian temperature rhythm was monitored in nine Royal Norwegian Airforce volunteers operating P-3 aircraft during a westward training deployment across nine time zones. Subjects recorded all sleep and nap times, rated nightly sleep quality, and completed personality inventories. Rectal temperature, heart rate, and wrist activity were continuously monitored. Adjustment was slower after the return eastward flight than after the outbound westward flight. The eastward flight produced slower readjustment of sleep timing to local time and greater interindividual variability in the patterns of adjustment of sleep and temperature. One subject apparently exhibited resynchronization by partition, with the temperature rhythm undergoing the reciprocal 15-h delay. In contrast, average heart rates during sleep were significantly elevated only after westward flight. Interindividual differences in adjustment of the temperature rhythm were correlated with some of the personality measures. Larger phase delays in the overall temperature waveform (as measured on the 5th day after westward flight) were exhibited by extraverts, and less consistently by evening types.

  14. 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.

  15. Pharmacogenetics and pharmacogenomics as tools in cancer therapy.

    PubMed

    Rodríguez-Vicente, Ana E; Lumbreras, Eva; Hernández, Jesus M; Martín, Miguel; Calles, Antonio; Otín, Carlos López; Algarra, Salvador Martín; Páez, David; Taron, Miquel

    2016-03-01

    Pharmacogenetics and pharmacogenomics (PGx) are rapidly growing fields that aim to elucidate the genetic basis for the interindividual differences in drug response. PGx approaches have been applied to many anticancer drugs in an effort to identify relevant inherited or acquired genetic variations that may predict patient response to chemotherapy and targeted therapies. In this article, we discuss the advances in the field of cancer pharmacogenetics and pharmacogenomics, driven by the recent technological advances and new revolutionary massive sequencing technologies and their application to elucidate the genetic bases for interindividual drug response and the development of biomarkers able to personalize drug treatments. Specifically, we present recent progress in breast cancer molecular classifiers, cell-free circulating DNA as a prognostic and predictive biomarker in cancer, patient-derived tumor xenograft models, chronic lymphocytic leukemia genomic landscape, and current pharmacogenetic advances in colorectal cancer. This review is based on the lectures presented by the speakers of the symposium "Pharmacogenetics and Pharmacogenomics as Tools in Cancer Therapy" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society (SEFF), held in Madrid (Spain) on April 21, 2015.

  16. Effects of Handling and Vehicle Injections on Adrenocorticotropic and Corticosterone Concentrations in Sprague–Dawley Compared with Lewis Rats

    PubMed Central

    Deutsch-Feldman, Molly; Picetti, Roberto; Seip-Cammack, Katharine; Zhou, Yan; Kreek, Mary Jeanne

    2015-01-01

    The hypothalamic–pituitary–adrenal (HPA) axis is a key factor in the trajectory of the addiction-like cycle (a pattern of behavior characterized by escalating drug use, withdrawal, and relapse) in preclinical and clinical studies. Concentrations of HPA hormones change in laboratory animals in response to standard experimental procedures, including handling and vehicle injections. We compared HPA activity in adult male Lewis (inbred) and Sprague–Dawley (outbred) rats, 2 common strains in rodent models of addiction, after different schedules of handling and saline injections, to explore the extent to which HPA responses differ by strain and whether interindividual differences underlie addiction vulnerability. The 4 treatment conditions were no, short, or long handling and saline injections. In handled groups, rats were handled for 1 to 2 min for 3 times daily and were euthanized after 7 d (short handling) or 14 d (long handling). The injection schedule in the saline injection group mimicked that in a model of binge-like cocaine exposure. Across all treatment groups, concentrations of adrenocorticotropic hormone were higher in Sprague–Dawley than in Lewis rats. In Sprague–Dawley rats, corticosterone concentrations decreased after continued handling but remained constant in Lewis rats. Interindividual variability in hormone levels was greater in Sprague–Dawley than Lewis rats, although corticosterone variability decreased after continued handling. Prolactin did not differ between groups of either Sprague–Dawley and Lewis rats before or after handling. This study underscores the importance of prolonged handling before experimenter-provided drug-administration paradigms and of strain-associated differences that may affect study outcomes. PMID:25651089

  17. Intraindividual differences in executive functions during childhood: the role of emotions.

    PubMed

    Pnevmatikos, Dimitris; Trikkaliotis, Ioannis

    2013-06-01

    Intraindividual differences in executive functions (EFs) have been rarely investigated. In this study, we addressed the question of whether the emotional fluctuations that schoolchildren experience in their classroom settings could generate substantial intraindividual differences in their EFs and, more specifically, in the fundamental unifying component of EFs, their inhibition function. We designed an experimental research with ecological validity within the school setting where schoolchildren of three age groups (8-, 10-, and 12-year-olds) were involved. We executed three experiments. In Experiment 1, using a between-participants design, we isolated a classroom episode that, compared with the other episodes, generated significant differences in inhibitory function in a consequent Go/NoGo task. This was an episode that induced frustration after the experience of anxiety due to the uncertainty. Experiment 2, using a within-participants design, confirmed both the induced emotions from the episode and the intraindividual variability in schoolchildren's inhibition accuracy in the consequent Go/NoGo task. Experiment 3, again using a within-participants design, examined whether the same episode could generate intraindividual differences in a more demanding inhibition task, namely the anti-saccade task. The experiment confirmed the previous evidence; the episode generated high variability that in some age groups accounted for more than 1.5 standard deviations from the interindividual variability between the schoolchildren of the same age. Results showed that, regardless of their sex and the developmental progression in their inhibition with age, the variability induced within participants from the experienced frustration was very high compared with the interindividual variability of the same age group. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Integrating Genomic Based Information into Clinical Warfarin (Coumadin®) Management: An Illustrative Case Report

    PubMed Central

    LaSala, Anthony; Bower, Bruce; Windemuth, Andreas; White, C. Michael; Kocherla, Mohan; Seip, Richard; Duconge, Jorge; Ruaño, Gualberto

    2013-01-01

    Warfarin is a well established oral anticoagulant for the treatment of thromboembolic disorders. Warfarin therapy is complicated by a narrow therapeutic index and marked inter-individual dose variability with therapeutic doses ranging from 1 mg to 10 mg/day.1 Recently genetic variation and resultant drug metabolizing polymorphisms have been found to contribute to warfarin dose variability with resultant hemorrhagic or thromboembolic complications. Cytochrome P450 2C9 alters the rate of warfarin metabolism and clearance. A second enzyme, vitamin K epoxide reductase comple (VKOR) binds and reduces vitamin K which is necessary for activation of clotting Factors II, VII, IX and X. The VKORC1 gene encodes for vitamin K epoxide reductase complex subunit 1, a key component of VKOR. The combination of physiologic factors (30%), CYP2C9 variations (20%) and VKORC1 variants (25%) accounts for approximately 75% of warfarin dose variability. This illustrative case report demonstrates the clinical importance of this new information. Clinicians need to incorporate these new genomic findings into appropriate management of warfarin dose anticoagulation. PMID:18763667

  19. Inter-Individual Differences in the Initial 80 Minutes of Motor Learning of Handrim Wheelchair Propulsion

    PubMed Central

    Vegter, Riemer J. K.; Lamoth, Claudine J.; de Groot, Sonja; Veeger, Dirkjan H. E. J.; van der Woude, Lucas H. V.

    2014-01-01

    Handrim wheelchair propulsion is a cyclic skill that needs to be learned during rehabilitation. Yet it is unclear how inter-individual differences in motor learning impact wheelchair propulsion practice. Therefore we studied how early-identified motor learning styles in novice able-bodied participants impact the outcome of a low-intensity wheelchair-practice intervention. Over a 12-minute pre-test, 39 participants were split in two groups based on a relative 10% increase in mechanical efficiency. Following the pretest the participants continued one of four different low-intensity wheelchair practice interventions, yet all performed in the same trial-setup with a total 80-minute dose at 1.11 m/s at 0.20 W/kg. Instead of focusing on the effect of the different interventions, we focused on differences in motor learning between participants over the intervention. Twenty-six participants started the pretest with a lower mechanical efficiency and a less optimal propulsion technique, but showed a fast improvement during the first 12 minutes and this effect continued over the 80 minutes of practice. Eventually these initially fast improvers benefitted more from the given practice indicated by a better propulsion technique (like reduced frequency and increased stroke angle) and a higher mechanical efficiency. The initially fast improvers also had a higher intra-individual variability in the pre and posttest, which possibly relates to the increased motor learning of the initially fast improvers. Further exploration of the common characteristics of different types of learners will help to better tailor rehabilitation to the needs of wheelchair-dependent persons and improve our understanding of cyclic motor learning processes. PMID:24586992

  20. Context Matters: Multiple Novelty Tests Reveal Different Aspects of Shyness-Boldness in Farmed American Mink (Neovison vison).

    PubMed

    Noer, Christina Lehmkuhl; Needham, Esther Kjær; Wiese, Ann-Sophie; Balsby, Thorsten Johannes Skovbjerg; Dabelsteen, Torben

    2015-01-01

    Animal personality research is receiving increasing interest from related fields, such as evolutionary personality psychology. By merging the conceptual understanding of personality, the contributions to both fields of research may be enhanced. In this study, we investigate animal personality based on the definition of personality traits as underlying dispositional factors, which are not directly measurable, but which predispose individuals to react through different behavioural patterns. We investigated the shyness-boldness continuum reflected in the consistency of inter-individual variation in behavioural responses towards novelty in 47 farmed American mink (Neovison vison), which were raised in identical housing conditions. Different stages of approach behaviour towards novelty, and how these related within and across contexts, were explored. Our experimental design contained four tests: two novel object tests (non-social contexts) and two novel animated stimuli tests (social contexts). Our results showed consistency in shyness measures across multiple tests, indicating the existence of personality in farmed American mink. It was found that consistency in shyness measures differs across non-social and social contexts, as well as across the various stages in the approach towards novel objects, revealing that different aspects of shyness exist in the farmed American mink. To our knowledge this is the first study to reveal aspects of the shyness-boldness continuum in the American mink. Since the mink were raised in identical housing conditions, inherited factors may have been important in shaping the consistent inter-individual variation. Body weight and sex had no effect on the personality of the mink. Altogether, our results suggest that the shyness-boldness continuum cannot be explained by a simple underlying dispositional factor, but instead encompasses a broader term of hesitating behaviour that might comprise several different personality traits.

  1. Differences in Early Cytokine Production Are Associated With Development of a Greater Number of Symptoms Following West Nile Virus Infection.

    PubMed

    Hoffman, Kevin W; Sachs, David; Bardina, Susana V; Michlmayr, Daniela; Rodriguez, Carlos A; Sum, Janet; Foster, Gregory A; Krysztof, David; Stramer, Susan L; Lim, Jean K

    2016-08-15

    West Nile virus (WNV) is an emerging cause of meningitis and encephalitis in the United States. Although severe neuroinvasive disease and death can occur in rare instances, the majority of infected individuals remain asymptomatic or present with a range of clinical manifestations associated with West Nile fever. To better understand the interindividual variability associated with the majority of WNV infections, we evaluated the association of cytokine/chemokine production and outcome of infection among 115 WNV-positive US blood donors identified in 2008-2011. All subjects self-reported symptoms as having occurred during the 2 weeks following blood donation, using a standardized questionnaire. We discovered that, prior to seroconversion, an early potent, largely type I interferon-mediated response correlated with development of a greater number of symptoms in WNV-infected individuals. Interestingly, individuals who developed fewer symptoms had not only a more modest type I interferon response initially, but also a protracted cytokine response after seroconversion, marked by the production of monocyte and T-cell-associated chemokines. Collectively, our data suggest that, although an early type I interferon response appears to be crucial to control WNV infection, successful immunity may require a modest early response that is maintained during the course of infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

    PubMed

    Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

    2016-04-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  3. Taxonomy of Individual Variations in Aesthetic Responses to Fractal Patterns

    PubMed Central

    Spehar, Branka; Walker, Nicholas; Taylor, Richard P.

    2016-01-01

    In two experiments, we investigate group and individual preferences in a range of different types of patterns with varying fractal-like scaling characteristics. In Experiment 1, we used 1/f filtered grayscale images as well as their thresholded (black and white) and edges only counterparts. Separate groups of observers viewed different types of images varying in slope of their amplitude spectra. Although with each image type, the groups exhibited the “universal” pattern of preference for intermediate amplitude spectrum slopes, we identified 4 distinct sub-groups in each case. Sub-group 1 exhibited a typical peak preference for intermediate amplitude spectrum slopes (“intermediate”; approx. 50%); sub-group 2 exhibited a linear increase in preference with increasing amplitude spectrum slope (“smooth”; approx. 20%), while sub-group 3 exhibited a linear decrease in preference as a function of the amplitude spectrum slope (“sharp”; approx. 20%). Sub-group 4 revealed no significant preference (“other”; approx. 10%). In Experiment 2, we extended the range of different image types and investigated preferences within the same observers. We replicate the results of our first experiment and show that individual participants exhibit stable patterns of preference across a wide range of image types. In both experiments, Q-mode factor analysis identified two principal factors that were able to explain more than 80% of interindividual variations in preference across all types of images, suggesting a highly similar dimensional structure of interindividual variations in preference for fractal-like scaling characteristics. PMID:27458365

  4. Integration of white matter network is associated with interindividual differences in psychologically mediated placebo response in migraine patients.

    PubMed

    Liu, Jixin; Ma, Shaohui; Mu, Junya; Chen, Tao; Xu, Qing; Dun, Wanghuan; Tian, Jie; Zhang, Ming

    2017-10-01

    Individual differences of brain changes of neural communication and integration in the modular architecture of the human brain network exist for the repeated migraine attack and physical or psychological stressors. However, whether the interindividual variability in the migraine brain connectome predicts placebo response to placebo treatment is still unclear. Using DTI and graph theory approaches, we systematically investigated the topological organization of white matter networks in 71 patients with migraine without aura (MO) and 50 matched healthy controls at three levels: global network measure, nodal efficiency, and nodal intramodule/intermodule efficiency. All patients participated in an 8-week sham acupuncture treatment to induce analgesia. In our results, 30% (n = 21) of patients had 50% change in migraine days from baseline after placebo treatment. At baseline, abnormal increased network integration was found in MO patients as compared with the HC group, and the increased global efficiency before starting clinical treatment was associated with their following placebo response. For nodal efficiency, significantly increased within-subnetwork nodal efficiency and intersubnetwork connectivity of the hippocampus and middle frontal gyrus in patients' white matter network were correlated with the responses of follow-up placebo treatment. Our findings suggested that the trait-like individual differences in pain-related maladaptive stress interfered with and diminished the capacity of chronic pain modulation differently, and the placebo response for treatment could be predicted from a prior white matter network modular structure in migraineurs. Hum Brain Mapp 38:5250-5259, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies

    PubMed Central

    Li, Lucia M.; Uehara, Kazumasa; Hanakawa, Takashi

    2015-01-01

    There has been an explosion of research using transcranial direct current stimulation (tDCS) for investigating and modulating human cognitive and motor function in healthy populations. It has also been used in many studies seeking to improve deficits in disease populations. With the slew of studies reporting “promising results” for everything from motor recovery after stroke to boosting memory function, one could be easily seduced by the idea of tDCS being the next panacea for all neurological ills. However, huge variability exists in the reported effects of tDCS, with great variability in the effect sizes and even contradictory results reported. In this review, we consider the interindividual factors that may contribute to this variability. In particular, we discuss the importance of baseline neuronal state and features, anatomy, age and the inherent variability in the injured brain. We additionally consider how interindividual variability affects the results of motor-evoked potential (MEP) testing with transcranial magnetic stimulation (TMS), which, in turn, can lead to apparent variability in response to tDCS in motor studies. PMID:26029052

  6. Variability of mammary blood flow in lactating Holstein-Friesian cows during the first twelve weeks of lactation.

    PubMed

    Götze, A; Honnens, A; Flachowsky, G; Bollwein, H

    2010-01-01

    The goals of the present study were to measure mammary blood flow volume (BFV) during the first 12 wk of lactation in dairy cows by using color Doppler sonography and to determine what affects the mammary blood flow. Forty cows were examined via color Doppler sonography on d 1, 7, 14, 28, 56, and 84 after parturition (d 0). The total BFV (BFV(total)) to the 4 mammary glands was calculated by measuring time-averaged maximum velocities (TAMV) and cross-sectional areas (A) of the left and right pudendoepigastric trunks via transrectal color Doppler sonography. Because there were no significant differences in A, TAMV, and BFV between the right and left pudendoepigastric trunks, the means of A and TAMV, and the BFV(total) of both trunks were used for calculations. The intraindividual and interindividual variability of repeated BFV measures quantified by intraclass correlation coefficients were 96 and 98%, respectively. The BFV(total) ranged from 19.9 to 27.9 L/min, with a mean of 22.3+/-4.9 L/min. Interindividual differences in BFV values were attributable to variations in A and TAMV. The interindividual variability of the BFV(total), which was determined using the coefficients of variation of the BFV(total) on individual days, ranged from 16 to 28%. All the cows had similar changes in the BFV(total) during the study. Changes in BFV(total) were not correlated with changes in the mean of A, but there was a good correlation between changes in BFV(total) and in the mean of TAMV (r=0.94). The BFV(total) was highest on d 1 of lactation, decreased 28% by d 7, and remained at this level until d 28. By d 56, the BFV(total) had increased by 15% compared with d 14 and by 10% compared with d 28. The BFV(total) on d 84 was significantly different from all other days except d 56. There were moderate correlations between daily milk yield and BFV on individual days (0.24

  7. Critical research issues in development of biomathematical models of fatigue and performance.

    PubMed

    Dinges, David F

    2004-03-01

    This article reviews the scientific research needed to ensure the continued development, validation, and operational transition of biomathematical models of fatigue and performance. These models originated from the need to ascertain the formal underlying relationships among sleep and circadian dynamics in the control of alertness and neurobehavioral performance capability. Priority should be given to research that further establishes their basic validity, including the accuracy of the core mathematical formulae and parameters that instantiate the interactions of sleep/wake and circadian processes. Since individuals can differ markedly and reliably in their responses to sleep loss and to countermeasures for it, models must incorporate estimates of these inter-individual differences, and research should identify predictors of them. To ensure models accurately predict recovery of function with sleep of varying durations, dose-response curves for recovery of performance as a function of prior sleep homeostatic load and the number of days of recovery are needed. It is also necessary to establish whether the accuracy of models is affected by using work/rest schedules as surrogates for sleep/wake inputs to models. Given the importance of light as both a circadian entraining agent and an alerting agent, research should determine the extent to which light input could incrementally improve model predictions of performance, especially in persons exposed to night work, jet lag, and prolonged work. Models seek to estimate behavioral capability and/or the relative risk of adverse events in a fatigued state. Research is needed on how best to scale and interpret metrics of behavioral capability, and incorporate factors that amplify or diminish the relationship between model predictions of performance and risk outcomes.

  8. Variation between the oral and faecal microbiota in a free-living passerine bird, the great tit (Parus major).

    PubMed

    Kropáčková, Lucie; Pechmanová, Hana; Vinkler, Michal; Svobodová, Jana; Velová, Hana; Těšičký, Martin; Martin, Jean-François; Kreisinger, Jakub

    2017-01-01

    The gastrointestinal tract of vertebrates is inhabited by diverse bacterial communities that induce marked effects on the host physiology and health status. The composition of the gastrointestinal microbiota is characterized by pronounced taxonomic and functional variability among different regions of the vertebrate gastrointestinal tract. Despite the relatively solid knowledge on the among-region variations of the gastrointestinal microbiota in model mammalian species, there are only a few studies concerning among-region variations of the gastrointestinal microbiota in free-living non-mammalian vertebrate taxa. We used Illumina MiSeq sequencing of bacterial 16S rRNA amplicons to compare the diversity as well as taxonomic composition of bacterial communities in proximal vs. distal parts of the gastrointestinal tract (represented by oral swabs and faecal samples, respectively) in a wild passerine bird, the great tit (Parus major). The diversity of the oral microbiota was significantly higher compared to the faecal microbiota, whereas interindividual variation was higher in faecal than in oral samples. We also observed a pronounced difference in taxonomic content between the oral and faecal microbiota. Bacteria belonging to the phyla Proteobacteria, Firmicutes and Actinobacteria typically dominated in both oral and faecal samples. A high abundance of bacteria belonging to Tenericutes was observed only in faecal samples. Surprisingly, we found only a slight correlation between the faecal and oral microbiota at the within-individual level, suggesting that the microbial composition in these body sites is shaped by independent regulatory processes. Given the independence of these two communities at the individual level, we propose that simultaneous sampling of the faecal and oral microbiota will extend our understanding of host vs. microbiota interactions in wild populations.

  9. Genome-wide map of quantified epigenetic changes during in vitro chondrogenic differentiation of primary human mesenchymal stem cells.

    PubMed

    Herlofsen, Sarah R; Bryne, Jan Christian; Høiby, Torill; Wang, Li; Issner, Robbyn; Zhang, Xiaolan; Coyne, Michael J; Boyle, Patrick; Gu, Hongcang; Meza-Zepeda, Leonardo A; Collas, Philippe; Mikkelsen, Tarjei S; Brinchmann, Jan E

    2013-02-15

    For safe clinical application of engineered cartilage made from mesenchymal stem cells (MSCs), molecular mechanisms for chondrogenic differentiation must be known in detail. Changes in gene expression and extracellular matrix synthesis have been extensively studied, but the epigenomic modifications underlying these changes have not been described. To this end we performed whole-genome chromatin immunoprecipitation and deep sequencing to quantify six histone modifications, reduced representation bisulphite sequencing to quantify DNA methylation and mRNA microarrays to quantify gene expression before and after 7 days of chondrogenic differentiation of MSCs in an alginate scaffold. To add to the clinical relevance of our observations, the study is based on primary bone marrow-derived MSCs from four donors, allowing us to investigate inter-individual variations. We see two levels of relationship between epigenetic marking and gene expression. First, a large number of genes ontogenetically linked to MSC properties and the musculoskeletal system are epigenetically prepatterned by moderate changes in H3K4me3 and H3K9ac near transcription start sites. Most of these genes remain transcriptionally unaltered. Second, transcriptionally upregulated genes, more closely associated with chondrogenesis, are marked by H3K36me3 in gene bodies, highly increased H3K4me3 and H3K9ac on promoters and 5' end of genes, and increased H3K27ac and H3K4me1 marking in at least one enhancer region per upregulated gene. Within the 7-day time frame, changes in promoter DNA methylation do not correlate significantly with changes in gene expression. Inter-donor variability analysis shows high level of similarity between the donors for this data set. Histone modifications, rather than DNA methylation, provide the primary epigenetic control of early differentiation of MSCs towards the chondrogenic lineage.

  10. 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.

  11. Association of speed of onset and speed of recovery of depressive episodes in patients with major depression.

    PubMed

    Strauss, Maria; Mergl, Roland; Sander, Christian; Schönknecht, Peter; Hegerl, Ulrich

    2015-01-01

    Depressive episodes show large interindividual differences concerning their speed of onset and speed of recovery, which might suggest differences in underlying pathophysiological processes. The aim of the present study was to assess whether there is a relationship between the speed of onset and the speed of recovery from depressive episodes. The speed of onset and the speed of recovery from depression were assessed using a structured patient interview, the Onset of Depression Inventory (ODI). In total, 28 patients with bipolar depression and 91 patients with unipolar depression were included. The mean speed of onset of depression was significantly faster than the mean speed of recovery from depression (35.25, range 0-360 days vs. 59.60, range 0.13-720 days; Z = -3.40; p = 0.001). The correlation between these variables was positive, but numerically low (ρ = 0.22; p = 0.016). The speed of onset of the previous episode and that of the present episode were significantly correlated (ρ = 0.45; p < 0.001). Data are based on retrospective patient reports within a naturalistic study. While the speed of onset of depressive episodes has been found to show large interindividual variability and some intraindividual stability, the data of this study do not indicate that the neurobiological processes involved in the onset of and in the recovery from depressive episodes are closely linked. © 2014 S. Karger AG, Basel.

  12. Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men.

    PubMed

    Shumay, Elena; Logan, Jean; Volkow, Nora D; Fowler, Joanna S

    2012-10-01

    Human brain function is mediated by biochemical processes, many of which can be visualized and quantified by positron emission tomography (PET). PET brain imaging of monoamine oxidase A (MAO A)-an enzyme metabolizing neurotransmitters-revealed that MAO A levels vary widely between healthy men and this variability was not explained by the common MAOA genotype (VNTR genotype), suggesting that environmental factors, through epigenetic modifications, may mediate it. Here, we analyzed MAOA methylation in white blood cells (by bisulphite conversion of genomic DNA and subsequent sequencing of cloned DNA products) and measured brain MAO A levels (using PET and [(11)C]clorgyline, a radiotracer with specificity for MAO A) in 34 healthy non-smoking male volunteers. We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. The VNTR genotype did not influence the methylation status of the gene or brain MAO A activity. In contrast, we found a robust association of the regional and CpG site-specific methylation of the core MAOA promoter with brain MAO A levels. These results suggest that the methylation status of the MAOA promoter (detected in white blood cells) can reliably predict the brain endophenotype. Therefore, the status of MAOA methylation observed in healthy males merits consideration as a variable contributing to interindividual differences in behavior.

  13. Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAOA enzyme in healthy men

    PubMed Central

    Shumay, Elena; Logan, Jean; Volkow, Nora D.; Fowler, Joanna S.

    2012-01-01

    Human brain function is mediated by biochemical processes, many of which can be visualized and quantified by positron emission tomography (PET). PET brain imaging of monoamine oxidase A (MAOA)—an enzyme metabolizing neurotransmitters—revealed that MAOA levels vary widely between healthy men and this variability was not explained by the common MAOA genotype (VNTR genotype), suggesting that environmental factors, through epigenetic modifications, may mediate it. Here, we analyzed MAOA methylation in white blood cells (by bisulphite conversion of genomic DNA and subsequent sequencing of cloned DNA products) and measured brain MAOA levels (using PET and [11C]clorgyline, a radiotracer with specificity for MAOA) in 34 healthy non-smoking male volunteers. We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. The VNTR genotype did not influence the methylation status of the gene or brain MAOA activity. In contrast, we found a robust association of the regional and CpG site-specific methylation of the core MAOA promoter with brain MAOA levels. These results suggest that the methylation status of the MAOA promoter (detected in white blood cells) can reliably predict the brain endophenotype. Therefore, the status of MAOA methylation observed in healthy males merits consideration as a variable contributing to interindividual differences in behavior. PMID:22948232

  14. Flexibility of Physiological Traits Underlying Inter-Individual Growth Differences in Intertidal and Subtidal Mussels Mytilusgalloprovincialis

    PubMed Central

    Fernández-Reiriz, María José; Irisarri, Jade; Labarta, Uxio

    2016-01-01

    Mussel seed (Mytilusgalloprovincialis) gathered from the intertidal and subtidal environments of a Galician embayment (NW, Spain) were maintained in the laboratory during five months to select fast (F) and slow (S) growing mussels. The physiological basis underlying inter-individual growth variations were compared for F and S mussels from both origins. Fast growing seemed to be a consequence of greater energy intake (20% higher clearance and ingestion rate) and higher food absorption rate coupled with low metabolic costs. The enhanced energy absorption (around 65% higher) resulted in 3 times higher Scope for Growth in F mussels (20.5±4.9 J h−1) than S individuals (7.3±1.1 J h−1). The higher clearance rate of F mussels appears to be linked with larger gill filtration surface compared to S mussels. Intertidal mussels showed higher food acquisition and absorption per mg of organic weight (i.e. mass-specific standardization) than subtidal mussels under the optimal feeding conditions of the laboratory. However, the enhanced feeding and digestive rates were not enough to compensate for the initial differences in tissue weight between mussels of similar shell length collected from the intertidal and subtidal environments. At the end of the experiment, subtidal individuals had higher gill efficiency, which probably lead to higher total feeding and absorption rates relative to intertidal individuals. PMID:26849372

  15. Metabolomic phenotyping of a cloned pig model

    PubMed Central

    2011-01-01

    Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5) was for the first time elucidated by nuclear magnetic resonance (NMR)-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n = 6) by multivariate data analysis, which revealed differences in the metabolic phenotypes. Plasma lactate was higher for cloned vs control pigs, while multiple metabolites were altered in the bile. However a lower inter-individual variability for cloned pigs compared with control pigs could not be established. Conclusions From the present study we conclude that cloned and normal outbred pigs are phenotypically different. However, it cannot be concluded that the use of cloned animals will reduce the inter-individual variation in intervention studies, though this is based on a limited number of animals. PMID:21859467

  16. Genetic and Environmental Influences on the Developmental Course of Attention-Deficit/Hyperactivity Disorder Symptoms From Childhood to Adolescence.

    PubMed

    Pingault, Jean-Baptiste; Viding, Essi; Galéra, Cédric; Greven, Corina U; Zheng, Yao; Plomin, Robert; Rijsdijk, Frühling

    2015-07-01

    Attention-deficit/hyperactivity disorder (ADHD) is conceptualized as a neurodevelopmental disorder that is strongly heritable. However, to our knowledge, no study to date has examined the genetic and environmental influences explaining interindividual differences in the developmental course of ADHD symptoms from childhood to adolescence (ie, systematic decreases or increases with age). The reason ADHD symptoms persist in some children but decline in others is an important concern, with implications for prognosis and interventions. To assess the proportional impact of genes and the environment on interindividual differences in the developmental course of ADHD symptom domains of hyperactivity/impulsivity and inattention between ages 8 and 16 years. A prospective sample of 8395 twin pairs from the Twins Early Development Study, recruited from population records of births in England and Wales between January 1, 1994, and December 31, 1996. Data collection at age 8 years took place between November 2002 and November 2004; data collection at age 16 years took place between February 2011 and January 2013. Both DSM-IV ADHD symptom subscales were rated 4 times by participants' mothers. Estimates from latent growth curve models indicated that the developmental course of hyperactivity/impulsivity symptoms followed a sharp linear decrease (mean score of 6.0 at age 8 years to 2.9 at age 16 years). Interindividual differences in the linear change in hyperactivity/impulsivity were under strong additive genetic influences (81%; 95% CI, 73%-88%). More than half of the genetic variation was specific to the developmental course and not shared with the baseline level of hyperactivity/impulsivity. The linear decrease in inattention symptoms was less pronounced (mean score of 5.8 at age 8 years to 4.9 at age 16 years). Nonadditive genetic influences accounted for a substantial amount of variation in the developmental course of inattention symptoms (54%; 95% CI, 8%-76%), with more than half being specific to the developmental course. The large genetic influences on the developmental course of ADHD symptoms are mostly specific and independent of those that account for variation in the baseline level of symptoms. Different sets of genes may be associated with the developmental course vs the baseline level of ADHD symptoms and explain why some children remit from ADHD, whereas others persist. Recent longitudinal imaging data indicate that the maintenance or increase in symptoms is underpinned by atypical trajectories of cortical development. This may reflect a specific genetic liability, distinct from that which contributes to baseline ADHD symptoms, and warrants closer follow-up.

  17. Age and motivation predict gaze behavior for facial expressions.

    PubMed

    Nikitin, Jana; Freund, Alexandra M

    2011-09-01

    This study investigated age-related differences between younger (M = 25.52 years) and older (M = 70.51 years) adults in avoidance motivation and the influence of avoidance motivation on gaze preferences for happy, neutral, and angry faces. In line with the hypothesis of reduced negativity effect later in life, older adults avoided angry faces and (to a lesser degree) preferred happy faces more than younger adults did. This effect cannot be explained by age-related changes in dispositional motivation. Irrespective of age, avoidance motivation predicted gaze behavior towards emotional faces. The study demonstrates the importance of interindividual differences beyond young adulthood.

  18. Pectoral fin contact as a mechanism for social bonding among dolphins

    USGS Publications Warehouse

    Dudzinski, Kathleen; Ribic, Christine

    2017-01-01

    Bottlenose dolphins are large-brained social mammals residing in a fission-fusion society with relationships that are established and maintained over decades. We examined a decade-long data set of inter-individual pectoral fin contact exchanges to better understand how dolphins share information via tactile contact. Sex and age are significant factors in pectoral fin contact within non-kin dolphin dyads. Adult females shared more pectoral fin contacts with other adult females, while younger females showed no pattern of contact. Males shared more pectoral fin contacts with other males as juveniles and as adults, but showed no difference in the number of touches versus rubs as pectoral fin contacts with other males. Whether in the role of initiator as rubber or initiator as rubbee, male dolphins again preferred other males. These results support the notion that dolphins, especially male dolphins, might use pectoral fin contact as one tool in their repertoire for social bonding to establish, maintain and manage their inter-individual relationships. Additionally, it is also likely that the exchange of pectoral fin contact is developed and refined as individuals age, mature socially, and establish their place within a fission-fusion society.

  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. Individual differences in visual motion perception and neurotransmitter concentrations in the human brain.

    PubMed

    Takeuchi, Tatsuto; Yoshimoto, Sanae; Shimada, Yasuhiro; Kochiyama, Takanori; Kondo, Hirohito M

    2017-02-19

    Recent studies have shown that interindividual variability can be a rich source of information regarding the mechanism of human visual perception. In this study, we examined the mechanisms underlying interindividual variability in the perception of visual motion, one of the fundamental components of visual scene analysis, by measuring neurotransmitter concentrations using magnetic resonance spectroscopy. First, by psychophysically examining two types of motion phenomena-motion assimilation and contrast-we found that, following the presentation of the same stimulus, some participants perceived motion assimilation, while others perceived motion contrast. Furthermore, we found that the concentration of the excitatory neurotransmitter glutamate-glutamine (Glx) in the dorsolateral prefrontal cortex (Brodmann area 46) was positively correlated with the participant's tendency to motion assimilation over motion contrast; however, this effect was not observed in the visual areas. The concentration of the inhibitory neurotransmitter γ-aminobutyric acid had only a weak effect compared with that of Glx. We conclude that excitatory process in the suprasensory area is important for an individual's tendency to determine antagonistically perceived visual motion phenomena.This article is part of the themed issue 'Auditory and visual scene analysis'. © 2017 The Author(s).

  1. Circadian rhythms of performance: new trends

    NASA Technical Reports Server (NTRS)

    Carrier, J.; Monk, T. H.

    2000-01-01

    This brief review is concerned with how human performance efficiency changes as a function of time of day. It presents an overview of some of the research paradigms and conceptual models that have been used to investigate circadian performance rhythms. The influence of homeostatic and circadian processes on performance regulation is discussed. The review also briefly presents recent mathematical models of alertness that have been used to predict cognitive performance. Related topics such as interindividual differences and the postlunch dip are presented.

  2. Interindividual Differences in Metabolism of Carcinogens as a Risk Factor for Breast Cancer

    DTIC Science & Technology

    2000-09-01

    development of primary congenital glaucoma , an autosomal recessive disease 10, 11), indicating that CYPIB1 has a physiological function in addition to...preleukemia cells in mice treated with 7,12-dimethylbenz[a] anthracene. Cancer Res. 60:3454-3460. 8. Hayes, C.L., Spink, D.C., Spink, B.C.,Cao, J.Q., Walker... glaucoma in Saudi Arabia. Am. J. Hum. Genet.62: 325-333. 11. Stoilov, I., Akarsu, A.N., Alozie, I., child, A., Barsoum-Homsy, M., Turacli, M. E., Or, M

  3. The development of interindividual sharing of knowledge and beliefs in 5- to 9-year-old children.

    PubMed

    Bradmetz, Joël; Gauthier, Cécile

    2005-03-01

    The authors studied the evolution of interindividual intentionality in children and showed that the sharing of knowledge and beliefs requires more complex operations than those involved in usual false-belief tasks. The authors conducted 3 experiments on 380 children (aged 5 years, 0 months to 9 years, 6 months). They assessed the children's ability to attribute to a character an intended action that was compatible with the belief held by another character interacting with that character. The observed lag in performances is explained both in terms of information processing and at the Piagetian concrete operational level.

  4. Intensity standardisation of 7T MR images for intensity-based segmentation of the human hypothalamus

    PubMed Central

    Schreiber, Jan; Bazin, Pierre-Louis; Trampel, Robert; Anwander, Alfred; Geyer, Stefan; Schönknecht, Peter

    2017-01-01

    The high spatial resolution of 7T MRI enables us to identify subtle volume changes in brain structures, providing potential biomarkers of mental disorders. Most volumetric approaches require that similar intensity values represent similar tissue types across different persons. By applying colour-coding to T1-weighted MP2RAGE images, we found that the high measurement accuracy achieved by high-resolution imaging may be compromised by inter-individual variations in the image intensity. To address this issue, we analysed the performance of five intensity standardisation techniques in high-resolution T1-weighted MP2RAGE images. Twenty images with extreme intensities in the GM and WM were standardised to a representative reference image. We performed a multi-level evaluation with a focus on the hypothalamic region—analysing the intensity histograms as well as the actual MR images, and requiring that the correlation between the whole-brain tissue volumes and subject age be preserved during standardisation. The results were compared with T1 maps. Linear standardisation using subcortical ROIs of GM and WM provided good results for all evaluation criteria: it improved the histogram alignment within the ROIs and the average image intensity within the ROIs and the whole-brain GM and WM areas. This method reduced the inter-individual intensity variation of the hypothalamic boundary by more than half, outperforming all other methods, and kept the original correlation between the GM volume and subject age intact. Mixed results were obtained for the other four methods, which sometimes came at the expense of unwarranted changes in the age-related pattern of the GM volume. The mapping of the T1 relaxation time with the MP2RAGE sequence is advertised as being especially robust to bias field inhomogeneity. We found little evidence that substantiated the T1 map’s theoretical superiority over the T1-weighted images regarding the inter-individual image intensity homogeneity. PMID:28253330

  5. [Personalized drug therapy-directed clinical pharmacology research based on genetic polymorphisms and pharmacokinetics analysis].

    PubMed

    Hayashi, Hideki

    2013-01-01

    In this decade, the field of pharmacogenomics (PGx), which is related to pharmacokinetics (PK) or pharmacodynamics (PD), has attracted much attention because it may provide a possible explanation for individual differences in the clinical efficacy of drugs. For the development of personalized drug therapy, it is important to accumulate evidence from PK/PD/PGx analysis in clinical trials. Warfarin (WF) is one of the most widely prescribed anticoagulants for the prevention and treatment of venous and arterial thromboembolism. However, large interindividual and interethnic differences have been observed in the WF dose required to elicit the anticoagulant effect. We investigated the factors influencing the WF maintenance dose in Japanese patients. Our study confirmed a large interindividual variability in the WF maintenance dose that was due to a VKORC1 1639 G>A polymorphism and differences in body weight, age, and serum albumin. In addition, we found that the CYP4F2 genotype affects the plasma concentration of menaquinone-4, and that this finding was correlated with the WF sensitivity index in Japanese pediatric patients. Methotrexate (MTX) is an antifolate that is widely used to treat rheumatoid arthritis (RA) and cancer. The response to low-dose MTX demonstrated wide interpatient variability; however, the contributing factors remain unclear. We found that the frequency of the RFC1 80A allele was higher in RA patients treated with MTX alone compared with patients who received biological disease-modifying antirheumatic drugs (bDMARDs). This finding may support the combined use of bDMARDs and MTX. Further large-scale prospective clinical trials are required to confirm these findings.

  6. Cytochrome P450s and molecular epidemiology

    NASA Astrophysics Data System (ADS)

    Gonzalez, Frank J.; Gelboin, Harry V.

    1993-03-01

    Cytochrome P450 (P450) represent a superfamily of heme-containing monooxygenases that are found throughout the animal and plant kingdoms and in many microorganisms. A number of these enzymes are involved in biosynthetic pathways of steroid synthesis but in mammals the vast majority of P450s function to metabolize foreign chemicals or xenobiotics. In the classical phase I reactions on the latter, a membrane-bound P450 will hydroxylate a compound, usually hydrophobic in nature, and the hydroxyl group will serve as a substrate for the various transferases or phase II enzymes that attach hydrophilic substituents such as glutathione, sulfate or glucuronic acid. Some chemicals, however, are metabolically-activated by P450s to electrophiles capable of reacting with cellular macromolecules. The cellular concentrations of the chemical and P450, reactivity of the active metabolite with nucleic acid and the repairability of the resultant adducts, in addition to the nature of the cell type, likely determines whether a chemical will be toxic and kill the cell or will transform the cell. Immunocorrelative and cDNA-directed expression have been used to define the substrate specificities of numerous human P450s. Levels of expression of different human P450 forms have been measured by both in vivo and in vitro methodologies leading to the realization that a large degree of interindividual differences occur in P450 expression. Reliable procedures for measuring P450 expression in healthy and diseased subjects will lead to prospective and case- cohort studies to determine whether interindividual differences in levels of P450 are associated with susceptibility or resistance to environmentally-based disease.

  7. Who gets afraid in the MRI-scanner? Neurogenetics of state-anxiety changes during an fMRI experiment.

    PubMed

    Mutschler, Isabella; Wieckhorst, Birgit; Meyer, Andrea H; Schweizer, Tina; Klarhöfer, Markus; Wilhelm, Frank H; Seifritz, Erich; Ball, Tonio

    2014-11-07

    Experiments using functional magnetic resonance imaging (fMRI) play a fundamental role in affective neuroscience. When placed in an MR scanner, some volunteers feel safe and relaxed in this situation, while others experience uneasiness and fear. Little is known about the basis and consequences of such inter-individually different responses to the general experimental fMRI setting. In this study emotional stimuli were presented during fMRI and subjects' state-anxiety was assessed at the onset and end of the experiment while they were within the scanner. We show that Val/Val but neither Met/Met nor Val/Met carriers of the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism-a prime candidate for anxiety vulnerability-became significantly more anxious during the fMRI experiment (N=97 females: 24 Val/Val, 51 Val/Met, and 22 Met/Met). Met carriers demonstrated brain responses with increased stability over time in the right parietal cortex and significantly better cognitive performances likely mediated by lower levels of anxiety. Val/Val, Val/Met and Met/Met did not significantly differ in state-anxiety at the beginning of the experiment. The exposure of a control group (N=56 females) to the same experiment outside the scanner did not cause a significant increase in state-anxiety, suggesting that the increase we observe in the fMRI experiment may be specific to the fMRI setting. Our findings reveal that genetics may play an important role in shaping inter-individual different emotional, cognitive and neuronal responses during fMRI experiments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Circadian preference modulates the neural substrate of conflict processing across the day.

    PubMed

    Schmidt, Christina; Peigneux, Philippe; Leclercq, Yves; Sterpenich, Virginie; Vandewalle, Gilles; Phillips, Christophe; Berthomier, Pierre; Berthomier, Christian; Tinguely, Gilberte; Gais, Steffen; Schabus, Manuel; Desseilles, Martin; Dang-Vu, Thanh; Salmon, Eric; Degueldre, Christian; Balteau, Evelyne; Luxen, André; Cajochen, Christian; Maquet, Pierre; Collette, Fabienne

    2012-01-01

    Human morning and evening chronotypes differ in their preferred timing for sleep and wakefulness, as well as in optimal daytime periods to cope with cognitive challenges. Recent evidence suggests that these preferences are not a simple by-product of socio-professional timing constraints, but can be driven by inter-individual differences in the expression of circadian and homeostatic sleep-wake promoting signals. Chronotypes thus constitute a unique tool to access the interplay between those processes under normally entrained day-night conditions, and to investigate how they impinge onto higher cognitive control processes. Using functional magnetic resonance imaging (fMRI), we assessed the influence of chronotype and time-of-day on conflict processing-related cerebral activity throughout a normal waking day. Sixteen morning and 15 evening types were recorded at two individually adapted time points (1.5 versus 10.5 hours spent awake) while performing the Stroop paradigm. Results show that interference-related hemodynamic responses are maintained or even increased in evening types from the subjective morning to the subjective evening in a set of brain areas playing a pivotal role in successful inhibitory functioning, whereas they decreased in morning types under the same conditions. Furthermore, during the evening hours, activity in a posterior hypothalamic region putatively involved in sleep-wake regulation correlated in a chronotype-specific manner with slow wave activity at the beginning of the night, an index of accumulated homeostatic sleep pressure. These results shed light into the cerebral mechanisms underlying inter-individual differences of higher-order cognitive state maintenance under normally entrained day-night conditions.

  9. Neurocognitive Function and State Cognitive Stress Appraisal Predict Cortisol Reactivity to an Acute Psychosocial Stressor in Adolescents

    PubMed Central

    Slattery, Marcia J.; Grieve, Adam J.; Ames, Michelle E.; Armstrong, Jeffrey M.; Essex, Marilyn J.

    2014-01-01

    Stress and associated alterations in hypothalamic-pituitary-adrenal (HPA) function have deleterious impacts on the development of multiple mental and physical health problems. Prior research has aimed to identify individuals most at risk for the development of these stress-related maladies by examining factors that may contribute to inter-individual differences in HPA responses to acute stress. The objectives of this study were to investigate, in adolescents, 1) whether differences in neurocognitive abilities influenced cortisol reactivity to an acute stressor, 2) whether internalizing psychiatric disorders influenced this relationship, and 3) whether acute cognitive stress-appraisal mechanisms mediated an association between neurocognitive function and cortisol reactivity. Subjects were 70 adolescents from a community sample who underwent standardized neurocognitive assessments of IQ, achievement, and declarative memory measures at mean age 14 and whose physiological and behavioral responses to a standardized psychosocial stress paradigm (Trier Social Stress Test, TSST) were assessed at mean age 18. Results showed that, among all adolescents, lower nonverbal memory performance predicted lower cortisol reactivity. In addition, internalizing disorders interacted with verbal memory such that the association with cortisol reactivity was strongest for adolescents with internalizing disorders. Finally, lower secondary cognitive appraisal of coping in anticipation of the TSST independently predicted lower cortisol reactivity but did not mediate the neurocognitive–cortisol relationship. Findings suggest that declarative memory may contribute to inter-individual differences in acute cortisol reactivity in adolescents, internalizing disorders may influence this relationship, and cognitive stress appraisal also predicts cortisol reactivity. Developmental, research, and clinical implications are discussed. PMID:23253895

  10. 1-Hydroxypyrene concentrations in first morning voids and 24-h composite urine: intra- and inter-individual comparisons.

    PubMed

    Han, In-Kyu; Duan, Xiaoli; Zhang, Lin; Yang, Hongbiao; Rhoads, George G; Wei, Fusheng; Zhang, Junfeng

    2008-09-01

    Urinary 1-hydroxypyrene (1-OHP) has been suggested as an exposure biomarker for polycyclic aromatic hydrocarbons (PAHs). However, it remains unknown whether a first morning urine sample can be used to reflect average exposure. In this paper, we examine intra-individual differences and inter-individual associations between first morning voids and 24-h composite urine samples. The analysis was performed using data collected from 100 adults who had a wide range of PAH exposure due to differences in their occupation, e.g., coke oven workers vs. non-coke oven workers. For each subject, all the urine voids within each of two 24-h measurement periods were collected. Results showed a significant (40% to 62%) intra-individual difference between first morning voids and 24-h urinary 1-OHP concentrations (in ng/ml urine). Creatinine adjustments of 1-OHP concentrations (in micromol/mol urinary creatinine) reduced the intra-individual difference by approximately 10%. Across all the subjects, a high overall correlation (r=0.76) was observed between first morning and 24-h average 1-OHP concentrations. Work environment and sampling season were found to significantly affect the relationship between first morning and 24-h 1-OHP concentrations. An increase of 1 ng/ml of first morning urinary 1-OHP predicted an increase of 0.5 and 0.25 ng/ml of 24-h urinary 1-OHP for coke oven workers and non-coke oven workers, respectively. Data collected in a winter season showed a higher correlation between first morning and 24-h concentrations than data collected in a fall season. Creatinine adjustments did not significantly improve overall correlations between first morning void and 24-h measurements, but increased total variances for 24-h urines explained by first morning urines in coke workers.

  11. Distinct Patterns of Cognitive Conflict Dynamics in Promise Keepers and Promise Breakers.

    PubMed

    Calluso, Cinzia; Saulin, Anne; Baumgartner, Thomas; Knoch, Daria

    2018-01-01

    On a daily basis, we see how different people can be in keeping or breaking a given promise. However, we know very little about the cognitive conflict dynamics that underlie the decision to keep or break a promise and whether this is shaped by inter-individual variability. In order to fill this gap, we applied an ecologically valid promise decision task with real monetary consequences for all involved interaction partners and used mouse tracking to identify the dynamic, on-line cognitive processes that underlie the decision to keep or break a promise. Our findings revealed that on average, the process of breaking a promise is associated with largely curved mouse trajectories, while the process of keeping a promise was not, indicating that breaking a promise is associated with a larger conflict. Interestingly, however, this conflict pattern was strongly shaped by individual differences. Individuals who always kept their promises did not show any signs of conflict (i.e., straight mouse trajectories), indicating that they were not tempted by the monetary benefits associated with breaking the promise. In contrast, individuals who did not always keep their promise exhibited a large conflict (i.e., curved mouse trajectories), irrespective of whether they broke or kept their promise. A possible interpretation of these findings is that these individuals were always tempted by the unchosen decision option - the desire to act in a fair manner when breaking the promise and the monetary benefits when keeping the promise. This study provides the first piece of evidence that there are substantial inter-individual differences in cognitive conflict dynamics that underlie the decision to keep or break promises and that mouse tracking is able to illuminate important insights into individual differences in complex human's decision processes.

  12. 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.

  13. 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.

  14. No effect of running and laboratory housing on adult hippocampal neurogenesis in wild caught long-tailed wood mouse

    PubMed Central

    Hauser, Thomas; Klaus, Fabienne; Lipp, Hans-Peter; Amrein, Irmgard

    2009-01-01

    Background Studies of adult hippocampal neurogenesis (AHN) in laboratory rodents have raised hopes for therapeutic interventions in neurodegenerative diseases and mood disorders, as AHN can be modulated by physical exercise, stress and environmental changes in these animals. Since it is not known whether cell proliferation and neurogenesis in wild living mice can be experimentally changed, this study investigates the responsiveness of AHN to voluntary running and to environmental change in wild caught long-tailed wood mice (Apodemus sylvaticus). Results Statistical analyses show that running had no impact on cell proliferation (p = 0.44), neurogenesis (p = 0.94) or survival of newly born neurons (p = 0.58). Likewise, housing in the laboratory has no effect on AHN. In addition, interindividual differences in the level of neurogenesis are not related to interindividual differences of running wheel performance (rs = -0.09, p = 0.79). There is a correlation between the number of proliferating cells and the number of cells of neuronal lineage (rs = 0.63, p < 0.001) and the number of pyknotic cells (rs = 0.5, p = 0.009), respectively. Conclusion Plasticity of adult neurogenesis is an established feature in strains of house mice and brown rats. Here, we demonstrate that voluntary running and environmental changes which are effective in house mice and brown rats cannot influence AHN in long-tailed wood mice. This indicates that in wild long-tailed wood mice different regulatory mechanisms act on cell proliferation and neurogenesis. If this difference reflects a species-specific adaptation or a broader adaptive strategy to a natural vs. domestic environment is unknown. PMID:19419549

  15. Determining the importance of fundamental hearing aid attributes.

    PubMed

    Meister, Hartmut; Lausberg, Isabel; Kiessling, Juergen; Walger, Martin; von Wedel, Hasso

    2002-07-01

    To determine the importance of fundamental hearing aid attributes and to elicit measures of satisfaction and dissatisfaction. A prospective study based on a survey using a decompositional approach of preference measurement (conjoint analysis). Ear, nose, and throat university hospitals in Cologne and Giessen; various branches of hearing aid dispensers. A random sample of 175 experienced hearing aid users aged 20 to 91 years (mean age, 61 yr) recruited at two different sites. Relative importance of different hearing aid attributes, satisfaction and dissatisfaction with hearing aid attributes. Of the six fundamental hearing aid attributes assessed by the hearing aid users, the two features concerning speech perception attained the highest relative importance (25% speech in quiet, 27% speech in noise). The remaining four attributes (sound quality, handling, feedback, localization) had significantly lower values in a narrow range of 10 to 12%. Comparison of different subgroups of hearing aid wearers based on sociodemographic and user-specific data revealed a large interindividual scatter of the preferences for the attributes. A similar examination with 25 clinicians revealed overestimation of the importance of the attributes commonly associated with problems. Moreover, examination of satisfaction showed that speech in noise was the most frequent source of dissatisfaction (30% of all statements), whereas the subjects were satisfied with speech in quiet. The results emphasize the high importance of attributes related to speech perception. Speech discrimination in noise was the most important but also the most frequent source of negative statements. This attribute will be the outstanding parameter of future developments. Appropriate handling becomes an important factor for elderly subjects. However, because of the large interindividual scatter of data, the preferences of different hearing aid users were hardly predictable, giving evidence of multifactorial influences.

  16. Genetic polymorphisms in the formaldehyde dehydrogenase gene and their biological significance.

    PubMed

    Just, Walter; Zeller, Jasmin; Riegert, Clarissa; Speit, Günter

    2011-11-30

    The GSH-dependent formaldehyde dehydrogenase (FDH) is the most important enzyme for the metabolic inactivation of formaldehyde. We studied three polymorphisms of this gene with the intention to elucidate their relevance for inter-individual differences in the protection against the (geno-)toxicity of FA. The first polymorphism (rs11568816) was investigated using real-time PCR and restriction fragment analysis in 150 subjects. However, we did not find the polymorphic sequence in any of the subjects. We studied a second polymorphism (rs17028487), representing a base exchange (c.*114A>G) in exon 9 of the FDH gene. We analyzed 70 subjects with the SNaPshot Primer Extension method and subsequent analysis in a ABI PRISM 3100, but no variant allele was identified. A third polymorphism, rs13832 in exon 9 (c.*493G>T), was studied in a group of 105 subjects by the SNaPshot Primer Extension method. 43 of the subjects were heterozygous for the polymorphism (G/T), 46 homozygous for the T allele, and 16 were homozygous for the G-allele. Real-time RT-PCR measurements of FDH mRNA did not indicate a significant difference in transcript levels between the heterozygous and the homozygous groups. The in vitro comet assay after FA exposure of blood samples obtained from 5 homozygous GG and 3 homozygous TT subjects did not lead to a significant difference between these two groups. Altogether, our study did not identify biologically relevant polymorphisms in transcribed regions of the FDH gene, which may lead to inter-individual differences in the metabolic inactivation of FA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. 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.

  18. Effects of the Brain-Derived Neurotrophic Factor Val66Met polymorphism and resting brain functional connectivity on individual differences in tactile cognitive performance in healthy young adults.

    PubMed

    Yang, Xuejuan; Xu, Ziliang; Liu, Lin; Liu, Peng; Sun, Jinbo; Jin, Lingmin; Zhu, Yuanqiang; Fei, Ningbo; Qin, Wei

    2017-07-28

    Cognitive processes involve input from multiple sensory modalities and obvious differences in the level of cognitive function can be observed between individuals. Evidence to date understanding the biological basis of tactile cognitive variability, however, is limited compared with other forms of sensory cognition. Data from auditory and visual cognition research suggest that variations in both genetics and intrinsic brain function might contribute to individual differences in tactile cognitive performance. In the present study, by using the tactual performance test (TPT), a widely used neuropsychological assessment tool, we investigated the effects of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and resting-state brain functional connectivity (FC) on interindividual variability in TPT performance in healthy, young Chinese adults. Our results showed that the BDNF genotypes and resting-state FC had significant effects on the variability in TPT performance, together accounting for 32.5% and 19.1% of the variance on TPT total score and Memory subitem score respectively. Having fewer Met alleles, stronger anticorrelations between left posterior superior temporal gyrus and somatosensory areas (right postcentral gyrus and right parietal operculum cortex), and greater positive correlation between left parietal operculum cortex and left central opercular cortex, all correspond with better performance of TPT task. And FC between left parietal operculum cortex and left central opercular cortex might be a mediator of the relationship between BDNF genotypes and Memory subitem score. These data demonstrate a novel contribution of intrinsic brain function to tactile cognitive capacity, and further confirm the genetic basis of tactile cognition. Our findings might also explain the interindividual differences in cognitive ability observed in those who are blind and/or deaf from a new perspective. Copyright © 2017. Published by Elsevier Ltd.

  19. Interindividual Responses of Appetite to Acute Exercise: A Replicated Crossover Study.

    PubMed

    Goltz, Fernanda R; Thackray, Alice E; King, James A; Dorling, James L; Atkinson, Greg; Stensel, David J

    2018-04-01

    Acute exercise transiently suppresses appetite, which coincides with alterations in appetite-regulatory hormone concentrations. Individual variability in these responses is suspected, but replicated trials are needed to quantify them robustly. We examined the reproducibility of appetite and appetite-regulatory hormone responses to acute exercise and quantified the individual differences in responses. Fifteen healthy, recreationally active men completed two control (60-min resting) and two exercise (60-min fasted treadmill running at 70% peak oxygen uptake) conditions in randomized sequences. Perceived appetite and circulating concentrations of acylated ghrelin and total peptide YY (PYY) were measured immediately before and after the interventions. Interindividual differences were explored by correlating the two sets of response differences between exercise and control conditions. Within-participant covariate-adjusted linear mixed models were used to quantify participant-condition interactions. Compared with control, exercise suppressed mean acylated ghrelin concentrations and appetite perceptions (all ES = 0.62-1.47, P < 0.001) and elevated total PYY concentrations (ES = 1.49, P < 0.001). For all variables, the standard deviation of the change scores was substantially greater in the exercise versus control conditions. Moderate-to-large positive correlations were observed between the two sets of control-adjusted exercise responses for all variables (r = 0.54-0.82, P ≤ 0.036). After adjusting for baseline measurements, participant-condition interactions were present for all variables (P ≤ 0.053). Our replicated crossover study allowed, for the first time, the interaction between participant and acute exercise response in appetite parameters to be quantified. Even after adjustment for individual baseline measurements, participants demonstrated individual differences in perceived appetite and hormone responses to acute exercise bouts beyond any random within-subject variability over time.

  20. Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary Hotspot Gene tan in Drosophila melanogaster

    PubMed Central

    Mouchel-Vielh, Emmanuèle; De Castro, Sandra; Peronnet, Frédérique

    2016-01-01

    Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotypic plasticity is a widespread phenomenon, its molecular mechanisms are only beginning to be unravelled. Environmental conditions can affect gene expression through modification of chromatin structure, mainly via histone modifications, nucleosome remodelling or DNA methylation, suggesting that phenotypic plasticity might partly be due to chromatin plasticity. As a model of phenotypic plasticity, we study abdominal pigmentation of Drosophila melanogaster females, which is temperature sensitive. Abdominal pigmentation is indeed darker in females grown at 18°C than at 29°C. This phenomenon is thought to be adaptive as the dark pigmentation produced at lower temperature increases body temperature. We show here that temperature modulates the expression of tan (t), a pigmentation gene involved in melanin production. t is expressed 7 times more at 18°C than at 29°C in female abdominal epidermis. Genetic experiments show that modulation of t expression by temperature is essential for female abdominal pigmentation plasticity. Temperature modulates the activity of an enhancer of t without modifying compaction of its chromatin or level of the active histone mark H3K27ac. By contrast, the active mark H3K4me3 on the t promoter is strongly modulated by temperature. The H3K4 methyl-transferase involved in this process is likely Trithorax, as we show that it regulates t expression and the H3K4me3 level on the t promoter and also participates in female pigmentation and its plasticity. Interestingly, t was previously shown to be involved in inter-individual variation of female abdominal pigmentation in Drosophila melanogaster, and in abdominal pigmentation divergence between Drosophila species. Sensitivity of t expression to environmental conditions might therefore give more substrate for selection, explaining why this gene has frequently been involved in evolution of pigmentation. PMID:27508387

  1. Creation of Mice Bearing a Partial Duplication of HPRT Gene Marked with a GFP Gene and Detection of Revertant Cells In Situ as GFP-Positive Somatic Cells.

    PubMed

    Noda, Asao; Suemori, Hirofumi; Hirai, Yuko; Hamasaki, Kanya; Kodama, Yoshiaki; Mitani, Hiroshi; Landes, Reid D; Nakamura, Nori

    2015-01-01

    It is becoming clear that apparently normal somatic cells accumulate mutations. Such accumulations or propagations of mutant cells are thought to be related to certain diseases such as cancer. To better understand the nature of somatic mutations, we developed a mouse model that enables in vivo detection of rare genetically altered cells via GFP positive cells. The mouse model carries a partial duplication of 3' portion of X-chromosomal HPRT gene and a GFP gene at the end of the last exon. In addition, although HPRT gene expression was thought ubiquitous, the expression level was found insufficient in vivo to make the revertant cells detectable by GFP positivity. To overcome the problem, we replaced the natural HPRT-gene promoter with a CAG promoter. In such animals, termed HPRT-dup-GFP mouse, losing one duplicated segment by crossover between the two sister chromatids or within a single molecule of DNA reactivates gene function, producing hybrid HPRT-GFP proteins which, in turn, cause the revertant cells to be detected as GFP-positive cells in various tissues. Frequencies of green mutant cells were measured using fixed and frozen sections (liver and pancreas), fixed whole mount (small intestine), or by means of flow cytometry (unfixed splenocytes). The results showed that the frequencies varied extensively among individuals as well as among tissues. X-ray exposure (3 Gy) increased the frequency moderately (~2 times) in the liver and small intestine. Further, in two animals out of 278 examined, some solid tissues showed too many GFP-positive cells to score (termed extreme jackpot mutation). Present results illustrated a complex nature of somatic mutations occurring in vivo. While the HPRT-dup-GFP mouse may have a potential for detecting tissue-specific environmental mutagens, large inter-individual variations of mutant cell frequency cause the results unstable and hence have to be reduced. This future challenge will likely involve lowering the background mutation frequency, thus reducing inter-individual variation.

  2. Changes to Serum Sample Tube and Processing Methodology Does Not Cause Inter-Individual Variation in Automated Whole Serum N-Glycan Profiling in Health and Disease

    PubMed Central

    Shubhakar, Archana; Kalla, Rahul; Nimmo, Elaine R.; Fernandes, Daryl L.; Satsangi, Jack; Spencer, Daniel I. R.

    2015-01-01

    Introduction Serum N-glycans have been identified as putative biomarkers for numerous diseases. The impact of different serum sample tubes and processing methods on N-glycan analysis has received relatively little attention. This study aimed to determine the effect of different sample tubes and processing methods on the whole serum N-glycan profile in both health and disease. A secondary objective was to describe a robot automated N-glycan release, labeling and cleanup process for use in a biomarker discovery system. Methods 25 patients with active and quiescent inflammatory bowel disease and controls had three different serum sample tubes taken at the same draw. Two different processing methods were used for three types of tube (with and without gel-separation medium). Samples were randomised and processed in a blinded fashion. Whole serum N-glycan release, 2-aminobenzamide labeling and cleanup was automated using a Hamilton Microlab STARlet Liquid Handling robot. Samples were analysed using a hydrophilic interaction liquid chromatography/ethylene bridged hybrid(BEH) column on an ultra-high performance liquid chromatography instrument. Data were analysed quantitatively by pairwise correlation and hierarchical clustering using the area under each chromatogram peak. Qualitatively, a blinded assessor attempted to match chromatograms to each individual. Results There was small intra-individual variation in serum N-glycan profiles from samples collected using different sample processing methods. Intra-individual correlation coefficients were between 0.99 and 1. Unsupervised hierarchical clustering and principal coordinate analyses accurately matched samples from the same individual. Qualitative analysis demonstrated good chromatogram overlay and a blinded assessor was able to accurately match individuals based on chromatogram profile, regardless of disease status. Conclusions The three different serum sample tubes processed using the described methods cause minimal inter-individual variation in serum whole N-glycan profile when processed using an automated workstream. This has important implications for N-glycan biomarker discovery studies using different serum processing standard operating procedures. PMID:25831126

  3. Can skills assessment on a virtual reality trainer predict a surgical trainee's talent in laparoscopic surgery?

    PubMed

    Rosenthal, R; Gantert, W A; Scheidegger, D; Oertli, D

    2006-08-01

    A number of studies have investigated several aspects of feasibility and validity of performance assessments with virtual reality surgical simulators. However, the validity of performance assessments is limited by the reliability of such measurements, and some issues of reliability still need to be addressed. This study aimed to evaluate the hypothesis that test subjects show logarithmic performance curves on repetitive trials for a component task of laparoscopic cholecystectomy on a virtual reality simulator, and that interindividual differences in performance after considerable training are significant. According to kinesiologic theory, logarithmic performance curves are expected and an individual's learning capacity for a specific task can be extrapolated, allowing quantification of a person's innate ability to develop task-specific skills. In this study, 20 medical students at the University of Basel Medical School performed five trials of a standardized task on the LS 500 virtual reality simulator for laparoscopic surgery. Task completion time, number of errors, economy of instrument movements, and maximum speed of instrument movements were measured. The hypothesis was confirmed by the fact that the performance curves for some of the simulator measurements were very close to logarithmic curves, and there were significant interindividual differences in performance at the end of the repetitive trials. Assessment of perceptual motor skills and the innate ability of an individual with no prior experience in laparoscopic surgery to develop such skills using the LS 500 VR surgical simulator is feasible and reliable.

  4. 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

  5. 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.

  6. Individual differences in verbal creative thinking are reflected in the precuneus.

    PubMed

    Chen, Qun-Lin; Xu, Ting; Yang, Wen-Jing; Li, Ya-Dan; Sun, Jiang-Zhou; Wang, Kang-Cheng; Beaty, Roger E; Zhang, Qing-Lin; Zuo, Xi-Nian; Qiu, Jiang

    2015-08-01

    There have been many structural and functional imaging studies of creative thinking, but combining structural and functional magnetic resonance imaging (MRI) investigations with respect to creative thinking is still lacking. Thus, the aim of the present study was to explore the associations among inter-individual verbal creative thinking and both regional homogeneity and cortical morphology of the brain surface. We related the local functional homogeneity of spontaneous brain activity to verbal creative thinking and its dimensions--fluency, originality, and flexibility--by examining these inter-individual differences in a large sample of 268 healthy college students. Results revealed that people with high verbal creative ability and high scores for the three dimensions of creativity exhibited lower regional functional homogeneity in the right precuneus. Both cortical volume and thickness of the right precuneus were positively associated with individual verbal creativity and its dimensions. Moreover, originality was negatively correlated with functional homogeneity in the left superior frontal gyrus and positively correlated with functional homogeneity in the right occipito-temporal gyrus. In contrast, flexibility was positively correlated with functional homogeneity in the left superior and middle occipital gyrus. These findings provide additional evidence of a link between verbal creative thinking and brain structure in the right precuneus--a region involved in internally--focused attention and effective semantic retrieval-and further suggest that local functional homogeneity of verbal creative thinking has neurobiological relevance that is likely based on anatomical substrates. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Glutamatergic model psychoses: prediction error, learning, and inference.

    PubMed

    Corlett, Philip R; Honey, Garry D; Krystal, John H; Fletcher, Paul C

    2011-01-01

    Modulating glutamatergic neurotransmission induces alterations in conscious experience that mimic the symptoms of early psychotic illness. We review studies that use intravenous administration of ketamine, focusing on interindividual variability in the profundity of the ketamine experience. We will consider this individual variability within a hypothetical model of brain and cognitive function centered upon learning and inference. Within this model, the brains, neural systems, and even single neurons specify expectations about their inputs and responding to violations of those expectations with new learning that renders future inputs more predictable. We argue that ketamine temporarily deranges this ability by perturbing both the ways in which prior expectations are specified and the ways in which expectancy violations are signaled. We suggest that the former effect is predominantly mediated by NMDA blockade and the latter by augmented and inappropriate feedforward glutamatergic signaling. We suggest that the observed interindividual variability emerges from individual differences in neural circuits that normally underpin the learning and inference processes described. The exact source for that variability is uncertain, although it is likely to arise not only from genetic variation but also from subjects' previous experiences and prior learning. Furthermore, we argue that chronic, unlike acute, NMDA blockade alters the specification of expectancies more profoundly and permanently. Scrutinizing individual differences in the effects of acute and chronic ketamine administration in the context of the Bayesian brain model may generate new insights about the symptoms of psychosis; their underlying cognitive processes and neurocircuitry.

  8. Temporal dynamics of physical activity and affect in depressed and nondepressed individuals.

    PubMed

    Stavrakakis, Nikolaos; Booij, Sanne H; Roest, Annelieke M; de Jonge, Peter; Oldehinkel, Albertine J; Bos, Elisabeth H

    2015-12-01

    The association between physical activity and affect found in longitudinal observational studies is generally small to moderate. It is unknown how this association generalizes to individuals. The aim of the present study was to investigate interindividual differences in the bidirectional dynamic relationship between physical activity and affect, in depressed and nondepressed individuals, using time-series analysis. A pair-matched sample of 10 depressed and 10 nondepressed participants (mean age = 36.6, SD = 8.9, 30% males) wore accelerometers and completed electronic questionnaires 3 times a day for 30 days. Physical activity was operationalized as the total energy expenditure (EE) per day segment (i.e., 6 hr). The multivariate time series (T = 90) of every individual were analyzed using vector autoregressive modeling (VAR), with the aim to assess direct as well as lagged (i.e., over 1 day) effects of EE on positive and negative affect, and vice versa. Large interindividual differences in the strength, direction and temporal aspects of the relationship between physical activity and positive and negative affect were observed. An exception was the direct (but not the lagged) effect of physical activity on positive affect, which was positive in nearly all individuals. This study showed that the association between physical activity and affect varied considerably across individuals. Thus, while at the group level the effect of physical activity on affect may be small, in some individuals the effect may be clinically relevant. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  9. Inter-individual differences in the impulsive/compulsive dimension: deciphering related dopaminergic and serotonergic metabolisms at rest.

    PubMed

    Dellu-Hagedorn, Françoise; Rivalan, Marion; Fitoussi, Aurélie; De Deurwaerdère, Philippe

    2018-04-19

    Several impulse control disorders such as ADHD, mania, personality disorders or substance abuse share common behavioural traits, like impulsiveness, risk-taking or inflexible behaviour. These disorders are treated with drugs targeting dopamine (DA) and/or serotonin (5-HT). However, the patient's monoamine imbalance that these neurotransmitters compensate is unclear. This study aims to investigate the patterns of DA and 5-HT metabolisms at rest within selected brain regions related to inter-individual variability in six main components of impulsivity/compulsivity (anticipatory hyperactivity, premature responses, delay discounting, risk-taking, perseveration, flexibility). Rats with adaptive and highly inadaptive behaviours were identified in each task and a sensitive biochemical approach allowed mapping of post-mortem endogenous monoamine tissue content in 20 brain areas. Distinct patterns of 5-HT and DA metabolisms were revealed according to the behavioural traits. Except for hyperactive responses, lower control of actions was mainly associated with a lower DA or 5-HT metabolism in prefrontal and/or subcortical areas (i.e. in orbitofrontal cortex (DA), amygdala and anterior cingulate cortex (5-HT) for inflexible and risk-prone rats). Our results reveal the complex nature of behavioural traits related to impulse control disorders through their associated monoaminergic networks at rest, paving the way for understanding the link between mental disorders and drug therapeutic actions.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'. © 2018 The Author(s).

  10. Clinical application of a systems model of apoptosis execution for the prediction of colorectal cancer therapy responses and personalisation of therapy.

    PubMed

    Hector, Suzanne; Rehm, Markus; Schmid, Jasmin; Kehoe, Joan; McCawley, Niamh; Dicker, Patrick; Murray, Frank; McNamara, Deborah; Kay, Elaine W; Concannon, Caoimhin G; Huber, Heinrich J; Prehn, Jochen H M

    2012-05-01

    Key to the clinical management of colorectal cancer is identifying tools which aid in assessing patient prognosis and determining more effective and personalised treatment strategies. We evaluated whether an experimental systems biology strategy which analyses the susceptibility of cancer cells to undergo caspase activation can be exploited to predict patient responses to 5-fluorouracil-based chemotherapy and to case-specifically identify potential alternative targeted treatments to reactivate apoptosis. We quantified five essential apoptosis-regulating proteins (Pro-Caspases 3 and 9, APAF-1, SMAC and XIAP) in samples of Stage II (n = 13) and III (n=17) tumour and normal colonic (n = 8) tissue using absolute quantitative immunoblotting and employed systems simulations of apoptosis signalling to predict the susceptibility of tumour cells to execute apoptosis. Additional systems analyses assessed the efficacy of novel apoptosis-inducing therapeutics such as XIAP antagonists, proteasome inhibitors and Pro-Caspase-3-activating compounds in restoring apoptosis execution in apoptosis-incompetent tumours. Comparisons of caspase activity profiles demonstrated that the likelihood of colorectal tumours to undergo apoptosis decreases with advancing disease stage. Systems-level analysis correctly predicted positive or negative outcome in 85% (p=0.004) of colorectal cancer patients receiving 5-fluorouracil based chemotherapy and significantly outperformed common uni- and multi-variate statistical approaches. Modelling of individual patient responses to novel apoptosis-inducing therapeutics revealed markedly different inter-individual responses. Our study represents the first proof-of-concept example demonstrating the significant clinical potential of systems biology-based approaches for predicting patient outcome and responsiveness to novel targeted treatment paradigms.

  11. The role of neurotrophins related to stress in saliva and salivary glands.

    PubMed

    Saruta, Juri; Sato, Sadao; Tsukinoki, Keiichi

    2010-10-01

    Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are well-studied neurotrophins involved in neurogenesis, differentiation, growth, and maintenance of selected peripheral and central populations of neuronal cells during development and adulthood. Neurotrophins, in concert with the hypothalamic-pituitary-adrenal (HPA) axis, play key roles in modulating brain plasticity and behavioral coping, especially during ontogenetic critical periods, when the developing brain is particularly sensitive to external stimuli. Early life events, such as psychophysical stress, affect NGF and BDNF levels and induce dysregulation of the HPA axis, thereby affecting brain development and contributing to inter-individual differences in vulnerability to stress or psychiatric disorders. Immobilization stress modifies BDNF mRNA expression in some organs. We studied the effect of immobilization stress on BDNF and its receptor tyrosine receptor kinase B (TrkB) in rat submandibular glands, and found increased BDNF expression in duct cells under immobilization stress. Upon further investigation on the influence of salivary glands on plasma BDNF using an acute immobilization stress model, we found that acute immobilization stress lasting 60 min significantly increases the plasma BDNF level. However, plasma BDNF elevation is markedly suppressed in bilaterally sialoadenectomized rats. This suggests that salivary glands may be the primary source of plasma BDNF under acute immobilization stress. This report reviews the structure of salivary glands, the role of neurotrophins in salivary glands, and the significance of BDNF in saliva and salivary glands, followed by a summary of the evidence that indicates the relationship between immobilization stress and BDNF expression within salivary glands.

  12. Effects of remifentanil on gastric tone.

    PubMed

    Walldén, Jakob; Thörn, Sven-Egron; Lindberg, Greger; Wattwil, Magnus

    2008-08-01

    Opioids are well known for impairing gastric motility. The mechanism is far from clear and there is wide interindividual variability. The purpose of this study was to evaluate the effect of remifentanil on proximal gastric tone. Healthy volunteers were studied on two occasions and proximal gastric tone was measured by a gastric barostat. On the first occasion (n=8), glucagon 1 mg IV was given as a reference for a maximal relaxation of the stomach. On the second occasion (n=9), remifentanil was given in incremental doses (0.1, 0.2 and 0.3 microg/kg/min) for 15 min each, followed by a washout period of 30 min. Thereafter, remifentanil was readministered, and 10 min later glucagon 1 mg was given. Mean intragastric bag volumes were calculated for each 5-min interval. Glucagon decreased gastric tone in all subjects. Remifentanil had a marked effect on gastric tone; we found two distinct patterns of reactions with both increases and decreases in gastric tone and, during the remifentanil infusion, glucagon did not affect gastric tone. Remifentanil induced changes in gastric tone with both increases and decreases. The effect of remifentanil on gastric tone is probably dependent on the current state of the systems involved.

  13. The relevance of the urinary concentration of ephedrines in anti-doping analysis: determination of pseudoephedrine, cathine, and ephedrine after administration of over-the-counter medicaments.

    PubMed

    Strano-Rossi, Sabina; Leone, Daniele; de la Torre, Xavier; Botrè, Francesco

    2009-08-01

    This article describes a method for the detection and quantitation of cathine, pseudoephedrine, ephedrine, and methylephedrine in urine, using their deuterated analogues as internal standards and derivatization to form the corresponding trimethylsilyl derivatives after a simple liquid-liquid extraction. The study was designed to evaluate whether the urinary cutoff values set by the World Anti-Doping Agency for the banned ephedrines (cathine >5 microg/mL, ephedrine and methylephedrine >10 microg/mL) can be exceeded after the normal self-administration of common over-the-counter medicaments containing nonbanned ephedrines. The present method, after validation, has been applied on real urine samples obtained from 9 healthy volunteers taking different doses of over-the-counter preparations containing ephedrines. Results obtained from excretion studies show high interindividual differences in the urinary concentrations of both pseudoephedrine and cathine, not dependent on body weight or sex nor, in some instances, on the administered dose. The same typical therapeutic dose of pseudoephedrine (60 mg) produced a urinary concentration of more than 5 microg/mL for cathine and of more than 100 microg/mL for pseudoephedrine in 2 of 9 subjects only. When a dose of 120 mg was administered, cathine concentration exceeded 5 microg/mL in 4 of 7 subject, and also concentrations of pseudoephedrine above 100 microg/mL. After administration of 5 x 120 mg of pseudoephedrine (120 mg administered every 7 days for 5 weeks) to one of the subjects exceeding the urinary threshold values, the urinary concentration of cathine and pseudoephedrine exceeded 5 microg/mL (peak concentration 14.8 microg/mL) and 100 microg/mL (peak concentration 275 microg/mL), respectively. When the same subject took 180 mg of pseudoephedrine, the urinary concentration values were below 5 microg/mL for ephedrine and 100 microg/mL for pseudoephedrine. In the case of ephedrine administration in a sustained-release formulation containing 12 mg of ephedrine, 2 of 3 subjects exceeded the urinary cutoff value of 10 microg/mL. The high interindividual variability is still significant even if the urinary concentration values are adjusted by specific gravity and/or creatinine. These results confirm a high interindividual variability in the urinary concentration of ephedrines after the administration of the same therapeutic dose of a preparation.

  14. Comparison of the Inhibitory Profiles of Itraconazole and Cimetidine in Cytochrome P450 3A4 Genetic Variants

    PubMed Central

    Akiyoshi, Takeshi; Saito, Takashi; Murase, Saori; Miyazaki, Mitsue; Murayama, Norie; Yamazaki, Hiroshi; Guengerich, F. Peter; Nakamura, Katsunori; Yamamoto, Koujirou

    2011-01-01

    CYP3A4, an important drug-metabolizing enzyme, is known to have genetic variants. We have previously reported that CYP3A4 variants such as CYP3A4.2, 7, 16, and 18 show different enzymatic kinetics from CYP3A4.1 (wild type). In this study, we quantitatively investigated the inhibition kinetics of two typical inhibitors, itraconazole (ITCZ) and cimetidine (CMD), on CYP3A4 variants and evaluated whether the genetic variation leads to interindividual differences in the extent of CYP3A4-mediated drug interactions. The inhibitory profiles of ITCZ and CMD on the metabolism of testosterone (TST) were analyzed by using recombinant CYP3A4 variants. The genetic variation of CYP3A4 significantly affected the inhibition profiles of the two inhibitors. In CYP3A4.7, the Ki value for ITCZ was 2.4-fold higher than that for the wild-type enzyme, whereas the Ki value for CMD was 0.64-fold lower. In CYP3A4.16, the Ki value for ITCZ was 0.54-fold lower than that for wild-type CYP3A4, whereas the Ki value for CMD was 3.2-fold higher. The influence of other genetic variations also differed between the two inhibitors. Docking simulations could explain the changes in the Ki values, based on the accessibility of TST and inhibitors to the heme moiety of the CYP3A4 molecule. In conclusion, the inhibitory effects of an inhibitor differ among CYP3A4 variants, suggesting that the genetic variation of CYP3A4 may contribute, at least in part, to interindividual differences in drug interactions mediated by CYP3A4 inhibition, and the pattern of the influences of genetic variation differs among inhibitors as well as substrates. PMID:21212239

  15. 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.

  16. Genetic Influence on Slope Variability in a Childhood Reflexive Attention Task.

    PubMed

    Lundwall, Rebecca A; Watkins, Jeffrey K

    2015-01-01

    Individuals are not perfectly consistent, and interindividual variability is a common feature in all varieties of human behavior. Some individuals respond more variably than others, however, and this difference may be important to understanding how the brain works. In this paper, we explore genetic contributions to response time (RT) slope variability on a reflexive attention task. We are interested in such variability because we believe it is an important part of the overall picture of attention that, if understood, has the potential to improve intervention for those with attentional deficits. Genetic association studies are valuable in discovering biological pathways of variability and several studies have found such associations with a sustained attention task. Here, we expand our knowledge to include a reflexive attention task. We ask whether specific candidate genes are associated with interindividual variability on a childhood reflexive attention task in 9-16 year olds. The genetic makers considered are on 11 genes: APOE, BDNF, CHRNA4, COMT, DRD4, HTR4, IGF2, MAOA, SLC5A7, SLC6A3, and SNAP25. We find significant associations with variability with markers on nine and we discuss the results in terms of neurotransmitters associated with each gene and the characteristics of the associated measures from the reflexive attention task.

  17. The future prospects of pharmacogenetics in oral anticoagulation therapy

    PubMed Central

    Kamali, Farhad; Pirmohamed, Munir

    2006-01-01

    Coumarins are the mainstay of oral anticoagulation for the treatment and prophylaxis of thromboembolic disorders. They have a narrow therapeutic index and regular monitoring is therefore required to avoid serious adverse effects. There is wide interindividual variability in dosage requirements, which makes anticoagulation response unpredictable. Current dosing titrations are haphazard and inconvenient and poor initial control leads to morbidity, and occasional mortality, because of bleeding and further thromboembolism. Recent discoveries have helped to characterize the factors that contribute to the interindividual variability in responses to coumarins. Patient and environmental factors that affect anticoagulation response to coumarins include age, body size, dietary vitamin K status, concurrent disease and drug interactions. More recently, single nucleotide polymorphisms in the 2C9 isoform of cytochrome P450 (CYP2C9) and vitamin K epoxide reductase (VKOR) have been shown to make significant contributions to the variability in coumarin dosage requirements. Polymorphisms in other genes that mediate the actions of coumarins may also contribute to this variability. Racial and cultural differences influence dosage requirements, which can be explained, at least in part, by genetic and dietary factors. Incorporation of genetic and environmental factors could help in the prediction of more individualized loading and maintenance doses for safer anticoagulation therapy. PMID:16722840

  18. 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.

  19. 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

  20. Testing all six person-oriented principles in dynamic factor analysis.

    PubMed

    Molenaar, Peter C M

    2010-05-01

    All six person-oriented principles identified by Sterba and Bauer's Keynote Article can be tested by means of dynamic factor analysis in its current form. In particular, it is shown how complex interactions and interindividual differences/intraindividual change can be tested in this way. In addition, the necessity to use single-subject methods in the analysis of developmental processes is emphasized, and attention is drawn to the possibility to optimally treat developmental psychopathology by means of new computational techniques that can be integrated with dynamic factor analysis.

  1. [Hard to accurately determine the age of children seeking asylum].

    PubMed

    Hjern, Anders; Ascher, Henry

    2015-10-12

    Many unaccompanied asylum seeking young people in Europe lack documents proving their age. X rays of the wrist and wisdom teeth are often used by European migration authorities to assess age in this situation. The large inter-individual differences in physical maturation during adolescence create such large margins of error for these methods that their informative value is very limited. The Swedish National Board of Health and Welfare should reconsider its previous position on these methods and examine the possibility to include psychosocial methods in these age assessment procedures.

  2. Night-rest urinary catecholamine excretion in relation to aspects of free time, work and background data in a teacher group.

    PubMed

    Kinnunen, U; Vihko, V

    1991-01-01

    Free time, work and background data were related to night-rest catecholamine excretion rates in a teacher group (n = 137) during an autumn term. The explained interindividual variance increased slightly towards the end of the term. Adrenaline excretion was predicted better than noradrenaline, notedly by coffee consumption, amount of physical activity, and subjective stress feelings which explained 16% of the variance in adrenaline excretion during night rest. However, the results indicated that the differences in catecholamine excretion during night rest remained mostly unpredictable.

  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. Time-on-task decrement in vigilance is modulated by inter-individual vulnerability to homeostatic sleep pressure manipulation

    PubMed Central

    Maire, Micheline; Reichert, Carolin F.; Gabel, Virginie; Viola, Antoine U.; Krebs, Julia; Strobel, Werner; Landolt, Hans-Peter; Bachmann, Valérie; Cajochen, Christian; Schmidt, Christina

    2014-01-01

    Under sleep loss, vigilance is reduced and attentional failures emerge progressively. It becomes difficult to maintain stable performance over time, leading to growing performance variability (i.e., state instability) in an individual and among subjects. Task duration plays a major role in the maintenance of stable vigilance levels, such that the longer the task, the more likely state instability will be observed. Vulnerability to sleep-loss-dependent performance decrements is highly individual and is also modulated by a polymorphism in the human clock gene PERIOD3 (PER3). By combining two different protocols, we manipulated sleep-wake history by once extending wakefulness for 40 h (high sleep pressure condition) and once by imposing a short sleep-wake cycle by alternating 160 min of wakefulness and 80 min naps (low sleep pressure condition) in a within-subject design. We observed that homozygous carriers of the long repeat allele of PER3 (PER35/5) experienced a greater time-on-task dependent performance decrement (i.e., a steeper increase in the number of lapses) in the Psychomotor Vigilance Task compared to the carriers of the short repeat allele (PER34/4). These genotype-dependent effects disappeared under low sleep pressure conditions, and neither motivation, nor perceived effort accounted for these differences. Our data thus suggest that greater sleep-loss related attentional vulnerability based on the PER3 polymorphism is mirrored by a greater state instability under extended wakefulness in the short compared to the long allele carriers. Our results undermine the importance of time-on-task related aspects when investigating inter-individual differences in sleep loss-induced behavioral vulnerability. PMID:24639634

  5. Heterogeneity of muscle recruitment pattern during pedaling in professional road cyclists: a magnetic resonance imaging and electromyography study.

    PubMed

    Hug, François; Bendahan, David; Le Fur, Yann; Cozzone, Patrick J; Grélot, Laurent

    2004-07-01

    Although a number of studies have been devoted to the analysis of the activity pattern of the muscles involved in pedaling in sedentary subjects and/or amateur cyclists, data on professional cyclists are scarce and the issue of inter-individual differences has never been addressed in detail. In the present series of experiments, we performed a non-invasive investigation using functional magnetic resonance imaging and surface electromyography to determine the pattern of activity of lower limb muscles during two different exhausting pedaling exercises in eight French professional cyclists. Each subject performed an incremental exercise during which electromyographic activity of eight lower limb muscles and respiratory variables were recorded. After a 3-h recovery period, transverse relaxation times (T2) were measured before and just after a standardized constant-load maximal exercise in order to quantify exercise-related T2 changes. The global EMG activity illustrated by the root mean square clearly showed a large inter-individual difference during the incremental exercise regardless of the investigated muscle (variation coefficient up to 81%). In addition, for most of the muscles investigated, the constant-load exercise induced T2 increases, which varied noticeably among the subjects. This high level of variation in the recruitment of lower limb muscles in professional cyclists during both incremental and constant-load exercises is surprising given the homogeneity related to maximal oxygen consumption and training volume. The high degree of expertise of these professional cyclists was not linked to the production of a common pattern of pedaling and our results provide an additional evidence that the nervous system has multiple ways of accomplishing a given motor task, as has been suggested previously by neural control theorists and experimentalists.

  6. Simulation of interindividual differences in inactivation of reactive para-benzoquinone imine metabolites of diclofenac by glutathione S-transferases in human liver cytosol.

    PubMed

    den Braver, Michiel W; Zhang, Yongjie; Venkataraman, Harini; Vermeulen, Nico P E; Commandeur, Jan N M

    2016-07-25

    Diclofenac is a widely prescribed NSAID that causes severe idiosyncratic drug induced liver injury (IDILI) in a small part of the patient population. Formation of protein-reactive metabolites is considered to play a role in the development of diclofenac-induced IDILI. Therefore, a high hepatic activity of enzymes involved in bioactivation of diclofenac is expected to increase the risk for liver injury. However, the extent of covalent protein binding may also be determined by activity of protective enzymes, such as glutathione S-transferases (GSTs). This is supported by an association study in which a correlation was found between NSAID-induced IDILI and the combined null genotypes of GSTM1 and GSTT1. In the present study, the activity of 10 different recombinant human GSTs in inactivation of protein-reactive quinoneimine (QI) metabolites of diclofenac was tested. Both at low and high GSH concentrations, high activities of GSTA1-1, A2-2, A3-3, M1-1, M3-3 and P1-1 in the inactivation of these QIs were found. By using the expression levels of GSTs in livers of 22 donors, a 6-fold variation in GST-dependent inactivation of reactive diclofenac metabolites was predicted. Moreover, it was shown in vitro that GSTs can strongly increase the efficiency of GSH to protect against the alkylation of the model thiol N-acetylcysteine by reactive diclofenac metabolites. The results of this study demonstrate that variability of GST expression may significantly contribute to the inter-individual differences in susceptibility to diclofenac-induced liver injury. In addition, expression levels of GSTs in in vitro models for hepatotoxicity may be important factors determining sensitivity to diclofenac cytotoxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Concepts in human biological rhythms

    PubMed Central

    Reinberg, Alain; Ashkenazi, Israel

    2003-01-01

    Biological rhythms and their temporal organization are adaptive phenomena to periodic changes in environmental factors linked to the earth's rotation on its axis and around the sun. Experimental data from the plant and animal kingdoms have led to many models and concepts related to biological clocks that help describe and understand the mechanisms of these changes. Many of the prevailing concepts apply to all organisms, but most of the experimental data are insufficient to explain the dynamics of human biological clocks. This review presents phenomena thai are mainly characteristic ofand unique to - human chronobiology, and which cannot be fully explained by concepts and models drawn from laboratory experiments. We deal with the functional advantages of the human temporal organization and the problem of desynchronization, with special reference to the period (τ) of the circadian rhythm and its interindividual and intraindividual variability. We describe the differences between right- and left-hand rhythms suggesting the existence of different biological clocks in the right and left cortices, Desynchronization of rhythms is rather frequent (one example is night shift workers). In some individuals, desynchronization causes no clinical symptoms and we propose the concept of “allochronism” to designate a variant of the human temporal organization with no pathological implications. We restrict the term “dyschronism” to changes or alterations in temporal organization associated with a set of symptoms similar to those observed in subjects intolerant to shift work, eg, persisting fatigue and mood and sleep alterations. Many diseases involve chronic deprivation of sleep at night and constitute conditions mimicking thai of night shift workers who are intolerant to desynchronization. We also present a genetic model (the dian-circadian model) to explain interindividual differences in the period of biological rhythms in certain conditions. PMID:22033796

  8. 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.

  9. Inter-individual differences in serotonin and glutamate co-transmission reflect differentiation in context-induced conditioned 50-kHz USVs response after morphine withdrawal.

    PubMed

    Hamed, Adam; Kursa, Miron Bartosz

    2018-05-17

    A growing body of research provides compelling evidence that in rats 50-kHz USVs are a form of expression of positive emotions. Context-induced 50-kHz USVs emission is variable among rats, indicating individual differences in contextual response bound up with pharmacological reward. The aims of this study were to: extract the most important neurotransmitters related to context-induced conditioned 50-kHz USVs response; find biological basis of existing inter-individual differences in context-induced conditioned 50-kHz USVs response; create a model of all-to-all neurotransmitters correlations. The data collected here confirms that re-exposure to the context of morphine administration after the withdrawal period increases the level of 50-kHz USVs and this contextual response is associated with elevated serotonin concentrations in amygdala, hippocampus and mPFC and with increased Glu/Gln ratio in nucleus accumbens. The concentration of serotonin increases simultaneously in amygdala, nucleus accumbens and hippocampus. Moreover, 5-HT concentration in amygdala is bound up with glutamate level in this structure as well as in hippocampus. Furthermore, Glu/Gln ratio in nucleus accumbens has strong associations with Glu/Gln ratio simultaneously in VTA, amygdala, striatum and hippocampus. All-to-all-analysis indicate that concentration of glutamate in hippocampus is proportional to glutamate in VTA and GABA concentration in the hippocampus. We have also demonstrated that Glu/GABA ratio in VTA and amygdala was elevated after post withdrawal re-exposure to the pharmacological reward paired context. Presented analysis indicates a strong correlation between serotonergic and glutamatergic systems in context-induced conditioned response. The strength of this co-transmission correlates with the number of 50-kHz USVs emitted in response to morphine-paired context.

  10. The role of digestive factors in determining glycemic response in a multiethnic Asian population.

    PubMed

    Tan, Verena Ming Hui; Ooi, Delicia Shu Qin; Kapur, Jeevesh; Wu, Ting; Chan, Yiong Huak; Henry, Christiani Jeyakumar; Lee, Yung Seng

    2016-06-01

    There are wide inter-individual differences in glycemic response (GR). We aimed to examine key digestive parameters that influence inter-individual and ethnic differences in GR in healthy Asian individuals. Seventy-five healthy male subjects (25 Chinese, 25 Malays, and 25 Asian-Indians) were served equivalent available carbohydrate amounts (50 g) of jasmine rice (JR) and basmati rice (BR) on separate occasions. Postprandial blood glucose concentrations were measured at fasting (-5 and 0 min) and at 15- to 30-min interval over 180 min. Mastication parameters (number of chews per mouth and chewing time per mouthful), saliva α-amylase activity, AMY1 gene copy numbers and gastric emptying rate were measured to investigate their relationships with GR. The GR for jasmine rice was significantly higher than for basmati rice (P < 0.001). The median number of AMY1 gene copies was 6, with a range of 2-15. There was a significant positive relationship between AMY1 copy number and α-amylase activity (P = 0.002). There were no significant ethnic differences in GR. For both rice varieties, the number of chews per mouthful was positively associated with the GR (JR, P = 0.011; BR, P = 0.005), while chewing time per mouthful showed a negative association (JR, P = 0.039; BR, P = 0.016). Ethnicity, salivary α-amylase activity, particle size distribution, gastric emptying rate and AMY1 gene copy numbers were not significant contributors to GR (P > 0.05). Mastication parameters contribute significantly to GR. Eating slowly and having larger food boluses before swallowing (less chewing), both potentially modifiable, may be beneficial in glycemic control.

  11. Sleep Consolidates Motor Learning of Complex Movement Sequences in Mice.

    PubMed

    Nagai, Hirotaka; de Vivo, Luisa; Bellesi, Michele; Ghilardi, Maria Felice; Tononi, Giulio; Cirelli, Chiara

    2017-02-01

    Sleep-dependent consolidation of motor learning has been extensively studied in humans, but it remains unclear why some, but not all, learned skills benefit from sleep. Here, we compared 2 different motor tasks, both requiring the mice to run on an accelerating device. In the rotarod task, mice learn to maintain balance while running on a small rod, while in the complex wheel task, mice run on an accelerating wheel with an irregular rung pattern. In the rotarod task, performance improved to the same extent after sleep or after sleep deprivation (SD). Overall, using 7 different experimental protocols (41 sleep deprived mice, 26 sleeping controls), we found large interindividual differences in the learning and consolidation of the rotarod task, but sleep before/after training did not account for this variability. By contrast, using the complex wheel, we found that sleep after training, relative to SD, led to better performance from the beginning of the retest session, and longer sleep was correlated with greater subsequent performance. As in humans, the effects of sleep showed large interindividual variability and varied between fast and slow learners, with sleep favoring the preservation of learned skills in fast learners and leading to a net offline gain in the performance in slow learners. Using Fos expression as a proxy for neuronal activation, we also found that complex wheel training engaged motor cortex and hippocampus more than the rotarod training. Sleep specifically consolidates a motor skill that requires complex movement sequences and strongly engages both motor cortex and hippocampus. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  12. Impulsive Approach Tendencies towards Physical Activity and Sedentary Behaviors, but Not Reflective Intentions, Prospectively Predict Non-Exercise Activity Thermogenesis

    PubMed Central

    Cheval, Boris; Sarrazin, Philippe; Pelletier, Luc

    2014-01-01

    Understanding the determinants of non-exercise activity thermogenesis (NEAT) is crucial, given its extensive health benefits. Some scholars have assumed that a proneness to react differently to environmental cues promoting sedentary versus active behaviors could be responsible for inter-individual differences in NEAT. In line with this reflection and grounded on the Reflective-Impulsive Model, we test the assumption that impulsive processes related to sedentary and physical activity behaviors can prospectively predict NEAT, operationalized as spontaneous effort exerted to maintain low intensity muscle contractions within the release phases of an intermittent maximal isometric contraction task. Participants (n = 91) completed a questionnaire assessing their intentions to adopt physical activity behaviors and a manikin task to assess impulsive approach tendencies towards physical activity behaviors (IAPA) and sedentary behaviors (IASB). Participants were then instructed to perform a maximal handgrip strength task and an intermittent maximal isometric contraction task. As hypothesized, multilevel regression analyses revealed that spontaneous effort was (a) positively predicted by IAPA, (b) negatively predicted by IASB, and (c) was not predicted by physical activity intentions, after controlling for some confounding variables such as age, sex, usual PA level and average force provided during the maximal-contraction phases of the task. These effects remained constant throughout all the phases of the task. This study demonstrated that impulsive processes may play a unique role in predicting spontaneous physical activity behaviors. Theoretically, this finding reinforces the utility of a motivational approach based on dual-process models to explain inter-individual differences in NEAT. Implications for health behavior theories and behavior change interventions are outlined. PMID:25526596

  13. Impulsive approach tendencies towards physical activity and sedentary behaviors, but not reflective intentions, prospectively predict non-exercise activity thermogenesis.

    PubMed

    Cheval, Boris; Sarrazin, Philippe; Pelletier, Luc

    2014-01-01

    Understanding the determinants of non-exercise activity thermogenesis (NEAT) is crucial, given its extensive health benefits. Some scholars have assumed that a proneness to react differently to environmental cues promoting sedentary versus active behaviors could be responsible for inter-individual differences in NEAT. In line with this reflection and grounded on the Reflective-Impulsive Model, we test the assumption that impulsive processes related to sedentary and physical activity behaviors can prospectively predict NEAT, operationalized as spontaneous effort exerted to maintain low intensity muscle contractions within the release phases of an intermittent maximal isometric contraction task. Participants (n = 91) completed a questionnaire assessing their intentions to adopt physical activity behaviors and a manikin task to assess impulsive approach tendencies towards physical activity behaviors (IAPA) and sedentary behaviors (IASB). Participants were then instructed to perform a maximal handgrip strength task and an intermittent maximal isometric contraction task. As hypothesized, multilevel regression analyses revealed that spontaneous effort was (a) positively predicted by IAPA, (b) negatively predicted by IASB, and (c) was not predicted by physical activity intentions, after controlling for some confounding variables such as age, sex, usual PA level and average force provided during the maximal-contraction phases of the task. These effects remained constant throughout all the phases of the task. This study demonstrated that impulsive processes may play a unique role in predicting spontaneous physical activity behaviors. Theoretically, this finding reinforces the utility of a motivational approach based on dual-process models to explain inter-individual differences in NEAT. Implications for health behavior theories and behavior change interventions are outlined.

  14. Dietary intake is independently associated with the maximal capacity for fat oxidation during exercise.

    PubMed

    Fletcher, Gareth; Eves, Frank F; Glover, Elisa I; Robinson, Scott L; Vernooij, Carlijn A; Thompson, Janice L; Wallis, Gareth A

    2017-04-01

    Background: Substantial interindividual variability exists in the maximal rate of fat oxidation (MFO) during exercise with potential implications for metabolic health. Although the diet can affect the metabolic response to exercise, the contribution of a self-selected diet to the interindividual variability in the MFO requires further clarification. Objective: We sought to identify whether recent, self-selected dietary intake independently predicts the MFO in healthy men and women. Design: The MFO and maximal oxygen uptake ([Formula: see text]O 2 max) were determined with the use of indirect calorimetry in 305 healthy volunteers [150 men and 155 women; mean ± SD age: 25 ± 6 y; body mass index (BMI; in kg/m 2 ): 23 ± 2]. Dual-energy X-ray absorptiometry was used to assess body composition with the self-reported physical activity level (SRPAL) and dietary intake determined in the 4 d before exercise testing. To minimize potential confounding with typically observed sex-related differences (e.g., body composition), predictor variables were mean-centered by sex. In the analyses, hierarchical multiple linear regressions were used to quantify each variable's influence on the MFO. Results: The mean absolute MFO was 0.55 ± 0.19 g/min (range: 0.19-1.13 g/min). A total of 44.4% of the interindividual variability in the MFO was explained by the [Formula: see text]O 2 max, sex, and SRPAL with dietary carbohydrate (carbohydrate; negative association with the MFO) and fat intake (positive association) associated with an additional 3.2% of the variance. When expressed relative to fat-free mass (FFM), the MFO was 10.8 ± 3.2 mg · kg FFM -1 · min -1 (range: 3.5-20.7 mg · kg FFM -1 · min -1 ) with 16.6% of the variability explained by the [Formula: see text]O 2 max, sex, and SRPAL; dietary carbohydrate and fat intakes together explained an additional 2.6% of the variability. Biological sex was an independent determinant of the MFO with women showing a higher MFO [men: 10.3 ± 3.1 mg · kg FFM -1 · min -1 (3.5-19.9 mg · kg FFM -1 · min -1 ); women: 11.2 ± 3.3 mg · kg FFM -1 · min -1 (4.6-20.7 mg · kg FFM -1 · min -1 ); P < 0.05]. Conclusion: Considered alongside other robust determinants, dietary carbohydrate and fat intake make modest but independent contributions to the interindividual variability in the capacity to oxidize fat during exercise. This trial was registered at clinicaltrials.gov as NCT02070055.

  15. Dietary intake is independently associated with the maximal capacity for fat oxidation during exercise12

    PubMed Central

    Eves, Frank F; Glover, Elisa I; Robinson, Scott L; Vernooij, Carlijn A

    2017-01-01

    Background: Substantial interindividual variability exists in the maximal rate of fat oxidation (MFO) during exercise with potential implications for metabolic health. Although the diet can affect the metabolic response to exercise, the contribution of a self-selected diet to the interindividual variability in the MFO requires further clarification. Objective: We sought to identify whether recent, self-selected dietary intake independently predicts the MFO in healthy men and women. Design: The MFO and maximal oxygen uptake (O2 max) were determined with the use of indirect calorimetry in 305 healthy volunteers [150 men and 155 women; mean ± SD age: 25 ± 6 y; body mass index (BMI; in kg/m2): 23 ± 2]. Dual-energy X-ray absorptiometry was used to assess body composition with the self-reported physical activity level (SRPAL) and dietary intake determined in the 4 d before exercise testing. To minimize potential confounding with typically observed sex-related differences (e.g., body composition), predictor variables were mean-centered by sex. In the analyses, hierarchical multiple linear regressions were used to quantify each variable’s influence on the MFO. Results: The mean absolute MFO was 0.55 ± 0.19 g/min (range: 0.19–1.13 g/min). A total of 44.4% of the interindividual variability in the MFO was explained by the O2 max, sex, and SRPAL with dietary carbohydrate (carbohydrate; negative association with the MFO) and fat intake (positive association) associated with an additional 3.2% of the variance. When expressed relative to fat-free mass (FFM), the MFO was 10.8 ± 3.2 mg · kg FFM−1 · min−1 (range: 3.5–20.7 mg · kg FFM−1 · min−1) with 16.6% of the variability explained by the O2 max, sex, and SRPAL; dietary carbohydrate and fat intakes together explained an additional 2.6% of the variability. Biological sex was an independent determinant of the MFO with women showing a higher MFO [men: 10.3 ± 3.1 mg · kg FFM−1 · min−1 (3.5–19.9 mg · kg FFM−1 · min−1); women: 11.2 ± 3.3 mg · kg FFM−1 · min−1 (4.6–20.7 mg · kg FFM−1 · min−1); P < 0.05]. Conclusion: Considered alongside other robust determinants, dietary carbohydrate and fat intake make modest but independent contributions to the interindividual variability in the capacity to oxidize fat during exercise. This trial was registered at clinicaltrials.gov as NCT02070055. PMID:28251936

  16. 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.

  17. Individual behavioral and neurochemical markers of unadapted decision-making processes in healthy inbred mice.

    PubMed

    Pittaras, Elsa; Callebert, Jacques; Chennaoui, Mounir; Rabat, Arnaud; Granon, Sylvie

    2016-12-01

    One of the hallmarks of decision-making processes is the inter-individual variability between healthy subjects. These behavioral patterns could constitute risk factors for the development of psychiatric disorders. Therefore, finding predictive markers of safe or risky decision-making is an important challenge for psychiatry research. We set up a mouse gambling task (MGT)-adapted from the human Iowa gambling task with uncertain contingencies between response and outcome that furthermore enables the emergence of inter-individual differences. Mice (n = 54) were further individually characterized for locomotive, emotional and cognitive behavior. Individual basal rates of monoamines and brain activation after the MGT were assessed in brain regions related to reward, emotion or cognition. In a large healthy mice population, 44 % showed a balanced strategy with limited risk-taking and flexible choices, 29 % showed a safe but rigid strategy, while 27 % adopted risky behavior. Risky mice took also more risks in other apparatus behavioral devices and were less sensitive to reward. No difference existed between groups regarding anxiety, working memory, locomotion and impulsivity. Safe/rigid mice exhibited a hypoactivation of prefrontal subareas, a high level of serotonin in the orbitofrontal cortex combined with a low level of dopamine in the putamen that predicted the emergence of rigid behavior. By contrast, high levels of dopamine, serotonin and noradrenalin in the hippocampus predicted the emergence of more exploratory and risky behaviors. The coping of C57bl/6J mice in MGT enables the determination of extreme patterns of choices either safe/rigid or risky/flexible, related to specific neurochemical and behavioral markers.

  18. Analysis of Inter-Individual Bacterial Variation in Gut of Cicada Meimuna mongolica (Hemiptera: Cicadidae)

    PubMed Central

    Zhou, Wenting; Nan, Xiaoning; Zheng, Zhou; Wei, Cong; He, Hong

    2015-01-01

    Intestinal bacterial community plays a crucial role in the nutrition, development, survival, and reproduction of insects. When compared with other insects with piercing-sucking mouthparts, the habitats of cicada nymphs and adults are totally different. However, little is known about the differences in the gut bacterial communities in the nymphs and adults within any cicada species. The diversity of bacteria in the gut of nymphs and adults of both genders of Meimuna mongolica (Distant) was studied using the denaturing gradient gel electrophoresis (DGGE) method. Few inter-individual variations among gut microbiota were observed, suggesting that M. mongolica typically harbors a limited and consistent suite of bacterial species. Bacteria in the genera Pseudomonas and Enterobacter were the predominant components of the gut microflora of M. mongolica at all life stages. Bacteria of Pantoea, Streptococcus, and Uruburuella were also widespread in the cicada samples but at relatively lower concentrations. The relative stability and similarity of the PCR-DGGE patterns indicate that all individuals of this cicada species harbor a characteristic bacterial community which is independent from developmental stages and genders. Related endosymbionts that could be harbored in bacteromes of cicadas were not detected in any gut samples, which could be related to the cicada species and the distribution of these endosymbionts in the cicada cavity, or due to some of the possible limitations of PCR-DGGE community profiling. It is worthwhile to further address if related cicada endosymbiont clades distribute in the alimentary canals and other internal organs through diagnostic PCR using group-specific primer sets. PMID:26411784

  19. 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

  20. Hypothalamus, sexual arousal and psychosexual identity in human males: a functional magnetic resonance imaging study.

    PubMed

    Brunetti, M; Babiloni, C; Ferretti, A; Del Gratta, C; Merla, A; Olivetti Belardinelli, M; Romani, G L

    2008-06-01

    In a recent functional magnetic resonance imaging study, a complex neural circuit was shown to be involved in human males during sexual arousal [A. Ferretti et al. (2005) Neuroimage, 26, 1086]. At group level, there was a specific correlation between penile erection and activations in anterior cingulate, insula, amygdala, hypothalamus and secondary somatosensory regions. However, it is well known that there are remarkable inter-individual differences in the psychological view and attitude to sex of human males. Therefore, a crucial issue is the relationship among cerebral responses, sexual arousal and psychosexual identity at individual level. To address this issue, 18 healthy male subjects were recruited. Their deep sexual identity (DSI) was assessed following the construct revalidation by M. Olivetti Belardinelli [(1994) Sci. Contrib. Gen. Psychol., 11, 131] of the Franck drawing completion test, a projective test providing, according to this revalidation, quantitative scores on 'accordance/non-accordance' between self-reported and psychological sexual identity. Cerebral activity was evaluated by means of functional magnetic resonance imaging during hard-core erotic movies and sport movies. Results showed a statistically significant positive correlation between the blood oxygen level-dependent signal in bilateral hypothalamus and the Franck drawing completion test score during erotic movies. The higher the blood oxygen level-dependent activation in bilateral hypothalamus, the higher the male DSI profile. These results suggest that, in male subjects, inter-individual differences in the DSI are strongly correlated with blood flow to the bilateral hypothalamus, a dimorphic brain region deeply implicated in instinctual drives including reproduction.

  1. 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

  2. Identifying ontogenetic, environmental and individual components of forest tree growth

    PubMed Central

    Chaubert-Pereira, Florence; Caraglio, Yves; Lavergne, Christian; Guédon, Yann

    2009-01-01

    Background and Aims This study aimed to identify and characterize the ontogenetic, environmental and individual components of forest tree growth. In the proposed approach, the tree growth data typically correspond to the retrospective measurement of annual shoot characteristics (e.g. length) along the trunk. Methods Dedicated statistical models (semi-Markov switching linear mixed models) were applied to data sets of Corsican pine and sessile oak. In the semi-Markov switching linear mixed models estimated from these data sets, the underlying semi-Markov chain represents both the succession of growth phases and their lengths, while the linear mixed models represent both the influence of climatic factors and the inter-individual heterogeneity within each growth phase. Key Results On the basis of these integrative statistical models, it is shown that growth phases are not only defined by average growth level but also by growth fluctuation amplitudes in response to climatic factors and inter-individual heterogeneity and that the individual tree status within the population may change between phases. Species plasticity affected the response to climatic factors while tree origin, sampling strategy and silvicultural interventions impacted inter-individual heterogeneity. Conclusions The transposition of the proposed integrative statistical modelling approach to cambial growth in relation to climatic factors and the study of the relationship between apical growth and cambial growth constitute the next steps in this research. PMID:19684021

  3. Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD

    PubMed Central

    Lee, Thomas; Clavel, Thomas; Smirnov, Kirill; Schmidt, Annemarie; Lagkouvardos, Ilias; Walker, Alesia; Lucio, Marianna; Michalke, Bernhard; Schmitt-Kopplin, Philippe; Fedorak, Richard; Haller, Dirk

    2017-01-01

    Objective Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open-labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT). Design The study population included patients with Crohn's disease (CD; N=31), UC (N=22) and control subjects with iron deficiency (non-inflamed, NI=19). After randomisation, participants received iron sulfate (PO) or iron sucrose (IV) over 3 months. Clinical parameters, faecal bacterial communities and metabolomes were assessed before and after intervention. Results Both PO and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV. Changes in disease activity were independent of iron treatment types. Faecal samples in IBD were characterised by marked interindividual differences, lower phylotype richness and proportions of Clostridiales. Metabolite analysis also showed separation of both UC and CD from control anaemic participants. Major shifts in bacterial diversity occurred in approximately half of all participants after IRT, but patients with CD were most susceptible. Despite individual-specific changes in phylotypes due to IRT, PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp. and Collinsella aerofaciens. Clear IV-specific and PO-specific fingerprints were evident at the level of metabolomes, with changes affecting cholesterol-derived host substrates. Conclusions Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy. Trial registration number clinicaltrial.gov (NCT01067547). PMID:26848182

  4. Sex and ESR1 genotype may influence the response to treatment with donepezil and rivastigmine in patients with Alzheimer's disease.

    PubMed

    Scacchi, Renato; Gambina, Giuseppe; Broggio, Elisabetta; Corbo, Rosa Maria

    2014-06-01

    Many factors could be responsible for the different response to treatment with the cholinesterase inhibitors (ChEIs) donepezil and rivastigmine in Alzheimer's disease (AD) patients. Sex and the variants of the estrogen receptor α (ESR1) gene are reported to modulate AD susceptibility or the course of the disease. The aim of the present study was to verify whether patient's sex and ESR1 genotype could influence the response to ChEI treatment, as there is evidence that estrogens affect cholinergic system functioning. Two ESR1 intronic polymorphisms (PvuII, rs2234693; XbaI, rs9340799) were examined in 184 AD patients: 157 were receiving treatment with donepezil or rivastigmine and 27 were receiving no treatment. Cognitive status was assessed using the mini mental state examination at four time points (1, 3, 9, and 15 months into therapy). Among the patients under treatment with either ChEI, the women responded more markedly than the men. As compared with the untreated patients, the effects of treatment were statistically significant for both donepezil and rivastigmine. A significant effect of ESR1 genotypes was observed for the donepezil-treated patients, among which those carrying at least one copy of P and X alleles showed a significantly lower cognitive decline than the noncarriers. The present data seem to confirm a sex-related influence on treatment, as the women seemed to be more sensitive to therapy and to have experienced less cognitive decline. ESR1 may be another gene contributing to interindividual variability in response to treatment with ChEIs. Copyright © 2013 John Wiley & Sons, Ltd.

  5. Parallel effects of processing fluency and positive affect on familiarity-based recognition decisions for faces.

    PubMed

    Duke, Devin; Fiacconi, Chris M; Köhler, Stefan

    2014-01-01

    According to attribution models of familiarity assessment, people can use a heuristic in recognition-memory decisions, in which they attribute the subjective ease of processing of a memory probe to a prior encounter with the stimulus in question. Research in social cognition suggests that experienced positive affect may be the proximal cue that signals fluency in various experimental contexts. In the present study, we compared the effects of positive affect and fluency on recognition-memory judgments for faces with neutral emotional expression. We predicted that if positive affect is indeed the critical cue that signals processing fluency at retrieval, then its manipulation should produce effects that closely mirror those produced by manipulations of processing fluency. In two experiments, we employed a masked-priming procedure in combination with a Remember-Know (RK) paradigm that aimed to separate familiarity- from recollection-based memory decisions. In addition, participants performed a prime-discrimination task that allowed us to take inter-individual differences in prime awareness into account. We found highly similar effects of our priming manipulations of processing fluency and of positive affect. In both cases, the critical effect was specific to familiarity-based recognition responses. Moreover, in both experiments it was reflected in a shift toward a more liberal response bias, rather than in changed discrimination. Finally, in both experiments, the effect was found to be related to prime awareness; it was present only in participants who reported a lack of such awareness on the prime-discrimination task. These findings add to a growing body of evidence that points not only to a role of fluency, but also of positive affect in familiarity assessment. As such they are consistent with the idea that fluency itself may be hedonically marked.

  6. Platelet cyclooxygenase expression in normal dogs.

    PubMed

    Thomason, J; Lunsford, K; Mullins, K; Stokes, J; Pinchuk, L; Wills, R; McLaughlin, R; Langston, C; Pruett, S; Mackin, A

    2011-01-01

    Human platelets express both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Variation in COX-2 expression could be a mechanism for variable response to aspirin. The hypotheses were that circulating canine platelets express COX-1 and COX-2, and that aspirin alters COX expression. The objective was to identify changes in platelet COX expression and in platelet function caused by aspirin administration to dogs. Eight female, intact hounds. A single population, repeated measures design was used to evaluate platelet COX-1 and COX-2 expression by flow cytometry before and after aspirin (10 mg/kg Q12h for 10 days). Platelet function was analyzed via PFA-100(®) (collagen/epinephrine), and urine 11-dehydro-thromboxane B(2) (11-dTXB(2)) was measured and normalized to urinary creatinine. Differences in COX expression, PFA-100(®) closure times, and urine 11-dTXB(2 ): creatinine ratio were analyzed before and after aspirin administration. Both COX-1 and COX-2 were expressed in canine platelets. COX-1 mean fluorescent intensity (MFI) increased in all dogs, by 250% (range 63-476%), while COX-2 expression did not change significantly (P = 0.124) after aspirin exposure, with large interindividual variation. PFA-100(®) closure times were prolonged and urine 11-dTXB(2) concentration decreased in all dogs after aspirin administration. Canine platelets express both COX isoforms. After aspirin exposure, COX-1 expression increased despite impairment of platelet function, while COX-2 expression varied markedly among dogs. Variability in platelet COX-2 expression should be explored as a potential mechanism for, or marker of, variable aspirin responsiveness. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  7. Aberrant Gene Expression in Humans

    PubMed Central

    Yang, Ence; Ji, Guoli; Brinkmeyer-Langford, Candice L.; Cai, James J.

    2015-01-01

    Gene expression as an intermediate molecular phenotype has been a focus of research interest. In particular, studies of expression quantitative trait loci (eQTL) have offered promise for understanding gene regulation through the discovery of genetic variants that explain variation in gene expression levels. Existing eQTL methods are designed for assessing the effects of common variants, but not rare variants. Here, we address the problem by establishing a novel analytical framework for evaluating the effects of rare or private variants on gene expression. Our method starts from the identification of outlier individuals that show markedly different gene expression from the majority of a population, and then reveals the contributions of private SNPs to the aberrant gene expression in these outliers. Using population-scale mRNA sequencing data, we identify outlier individuals using a multivariate approach. We find that outlier individuals are more readily detected with respect to gene sets that include genes involved in cellular regulation and signal transduction, and less likely to be detected with respect to the gene sets with genes involved in metabolic pathways and other fundamental molecular functions. Analysis of polymorphic data suggests that private SNPs of outlier individuals are enriched in the enhancer and promoter regions of corresponding aberrantly-expressed genes, suggesting a specific regulatory role of private SNPs, while the commonly-occurring regulatory genetic variants (i.e., eQTL SNPs) show little evidence of involvement. Additional data suggest that non-genetic factors may also underlie aberrant gene expression. Taken together, our findings advance a novel viewpoint relevant to situations wherein common eQTLs fail to predict gene expression when heritable, rare inter-individual variation exists. The analytical framework we describe, taking into consideration the reality of differential phenotypic robustness, may be valuable for investigating complex traits and conditions. PMID:25617623

  8. Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans.

    PubMed

    Böttiger, Y; Dostert, P; Benedetti, M S; Bani, M; Fiorentini, F; Casati, M; Poggesti, I; Alm, C; Alvan, G; Bertilsson, L

    1996-12-01

    1. Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia. 2. Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-alpha-methoxy-9,10-dihydrolysergol (MMDL), which is further N-demethylated to form 10-alpha-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms. 3. After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes. 4. The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL Cmax 59 nmol l-1 and AUC (0, th) 144 nmol l-1h, mean MDL Cmax 183 nmol l-1 and AUC 2627 nmol l-1h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL Cmax 356 nmol l-1 and AUC 10512 nmol l-1h, MDL concentrations below limit of quantitation). 5. We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism.

  9. Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans

    PubMed Central

    BÖTTIGER, Y.; DOSTERT, P.; STROLIN BENEDETTI, M.; BANI, M.; FIORENTINI, F.; CASATI, M.; POGGESTI, I.; ALM, C.; ALVAN, G.; BERTILSSON, L.

    1996-01-01

    1Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia. 2Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N-demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms. 3After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes. 4The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL Cmax 59 nmol l−1 and AUC (0, th) 144 nmol l−1h, mean MDL Cmax 183 nmol l−1 and AUC 2627 nmol l−1h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL Cmax 356 nmol l−1 and AUC 10512 nmol l−1h, MDL concentrations below limit of quantitation). 5We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism. PMID:8971425

  10. The complex liaison between cachexia and tumor burden (Review).

    PubMed

    De Lerma Barbaro, Andrea

    2015-10-01

    Cachexia is a wasting syndrome that afflicts end-stage cancer patients. Whereas a consensus statement for a definition of cachexia recently has been accomplished, a useful measurement for this condition at present is lacking. The aim of the present review is to discuss the advantage of introducing the measurement of tumor burden for a better overall evaluation of cachexia. Our suggestion ensues from a somewhat novel perspective in the field of infectious disease research where a careful measurement of the pathogen load, between i.e. different host genotypes, leads to the definition of the concept of tolerance to the infectious insult. Indeed tolerance concurs, together the more classical resistance, in maintaining the host reproductive fitness or health state. Noticeably a similar reasoning may apply to tumor biology as well. Whereas the extent of cachexia increases with tumor burden, the relationship between these two correlates of tumor progression fluctuates in a broad range. We have selected from the literature studies in the rodent model where significant variation in the course of the wasting illness during cancer was observed and quantitatively assessed comparing experimental groups marked by different genotype, drug treatment, diet or gender. These studies may be further classified in two categories: the former where the experimental condition associated to milder cachexia is accompanied to a lesser tumor burden, the latter where the inhibition of cachexia results disentangled from the tumor burden, that is the whole number of cancer cells results unchanged or even, paradoxically, is increased. In addition we survey, even in the context of human malignancy, the significance and feasibility of plotting quantitative estimates of cachexia against the whole tumor burden. Ultimately, the principal endeavor of introducing the measurement of tumor burden, in both experimental and clinical oncology, may be to achieve a better assessment of the inter-individual variation in the host vulnerability to cancer cachexia.

  11. Dietary fat acutely increases glucose concentrations and insulin requirements in patients with type 1 diabetes: implications for carbohydrate-based bolus dose calculation and intensive diabetes management.

    PubMed

    Wolpert, Howard A; Atakov-Castillo, Astrid; Smith, Stephanie A; Steil, Garry M

    2013-04-01

    Current guidelines for intensive treatment of type 1 diabetes base the mealtime insulin bolus calculation exclusively on carbohydrate counting. There is strong evidence that free fatty acids impair insulin sensitivity. We hypothesized that patients with type 1 diabetes would require more insulin coverage for higher-fat meals than lower-fat meals with identical carbohydrate content. We used a crossover design comparing two 18-h periods of closed-loop glucose control after high-fat (HF) dinner compared with low-fat (LF) dinner. Each dinner had identical carbohydrate and protein content, but different fat content (60 vs. 10 g). Seven patients with type 1 diabetes (age, 55 ± 12 years; A1C 7.2 ± 0.8%) successfully completed the protocol. HF dinner required more insulin than LF dinner (12.6 ± 1.9 units vs. 9.0 ± 1.3 units; P = 0.01) and, despite the additional insulin, caused more hyperglycemia (area under the curve >120 mg/dL = 16,967 ± 2,778 vs. 8,350 ± 1,907 mg/dL⋅min; P < 0001). Carbohydrate-to-insulin ratio for HF dinner was significantly lower (9 ± 2 vs. 13 ± 3 g/unit; P = 0.01). There were marked interindividual differences in the effect of dietary fat on insulin requirements (percent increase significantly correlated with daily insulin requirement; R(2) = 0.64; P = 0.03). This evidence that dietary fat increases glucose levels and insulin requirements highlights the limitations of the current carbohydrate-based approach to bolus dose calculation. These findings point to the need for alternative insulin dosing algorithms for higher-fat meals and suggest that dietary fat intake is an important nutritional consideration for glycemic control in individuals with type 1 diabetes.

  12. Antidepressants differentially affect striatal amphetamine-stimulated dopamine and serotonin release in rats with high and low novelty-oriented behaviour.

    PubMed

    O'Leary, Aet; Kõiv, Kadri; Raudkivi, Karita; Harro, Jaanus

    2016-11-01

    In the studies of depression pathogenesis and antidepressant action, the monoaminergic hypothesis of depression has mainly focused on the serotonergic and noradrenergic mechanisms. However, dopaminergic neurotransmission is also linked to both depressive symptomatology as well as antidepressant effects. We have previously shown that persistent inter-individual differences in the rat behavioural activity in novel environments is associated with differences in the striatal extracellular levels of dopamine and serotonin, depressive-like behaviour and the expression of several depression-related genes. The aim of the current study was to investigate the relative potency of the tricyclic antidepressant imipramine, the selective serotonin re-uptake inhibitor fluoxetine, and the selective noradrenaline re-uptake inhibitor reboxetine (all drugs administered in the dose of 10mg/kg, i.p.) to enhance amphetamine-stimulated dopamine and serotonin release in the striatum using in vivo microdialysis in awake, freely-moving rats, categorized into high explorers (HE) and low explorers (LE) based on their spontaneous novelty-oriented behaviour. The basal extracellular dopamine and serotonin concentration in the striatum did not differ between the LE- and HE-rats. None of the antidepressants alone were able to modify baseline striatal dopamine levels, but the amphetamine-stimulated dopamine release was significantly higher in the HE-rats after acute and chronic imipramine (but not fluoxetine or reboxetine). Acute imipramine and fluoxetine, but not reboxetine, increased both the basal and amphetamine-stimulated levels of serotonin in the striatum. Again, the HE-rats had higher amphetamine-stimulated serotonin release after fluoxetine administration. These findings suggest that rats with depressive-like phenotype are less sensitive to the neurochemical effects of antidepressants in the striatum. These results may have relevance in understanding the neurobiological bases for inter-individual differences in antidepressant treatment response in humans and development of novel medicines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. A new approach for deciphering between single and multiple accumulation events using intra-tooth isotopic variations: Application to the Middle Pleistocene bone bed of Schöningen 13 II-4.

    PubMed

    Julien, Marie-Anne; Rivals, Florent; Serangeli, Jordi; Bocherens, Hervé; Conard, Nicholas J

    2015-12-01

    It is often difficult to differentiate between archaeological bonebeds formed by one event such as a mass kill of a single herd, and those formed by multiple events that occurred over a longer period of time. The application of high temporal resolution studies such as intra-tooth isotopic profiles on archaeological mammal cohorts offers new possibilities for exploring this issue, allowing investigators to decipher between single and multiple accumulation events. We examined (18)O and (13)C isotopic variations from the enamel carbonate of 23 horse third molars from the Middle Pleistocene archaeological site of Schöningen. We employed a new approach to investigate processes of fossil accumulation that uses both bulk and intra-tooth isotopic variations and takes into account animal behavior, age at death and dental development to test the degree of isotopic affinity of animals from the same fossil assemblage. Oxygen and carbon isotope bulk values indicate that the horses from Schöningen 13 II-4 experienced relatively similar climatic and dietary regimes. Inter-individual differences of the bulk values of the horses sampled in the current study present nevertheless inter-individual variability similar to individuals from multi-layered localities. In addition, the intra-tooth isotopic variation of specimens of the same age at death seems to indicate that the studied cohort corresponds to a mix of individuals that recorded both similar and different isotopic histories. Finally, the conditions recorded in the isotopic signal shortly before death (i.e., for teeth not fully mineralized) varied between sampled individuals, suggesting possible differences in the seasonality of death. Considering those results, we discuss the possibility that the horses from Schöningen 13 II-4 correspond to an accumulation of different death events. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Decision Makers Use Norms, Not Cost-Benefit Analysis, When Choosing to Conceal or Reveal Unfair Rewards

    PubMed Central

    Heimann, Marco; Girotto, Vittorio; Legrenzi, Paolo; Bonnefon, Jean-François

    2013-01-01

    We introduce the Conceal or Reveal Dilemma, in which individuals receive unfair benefits, and must decide whether to conceal or to reveal this unfair advantage. This dilemma has two important characteristics: it does not lend itself easily to cost-benefit analysis, neither to the application of any strong universal norm. As a consequence, it is ideally suited to the study of interindividual and intercultural variations in moral-economic norms. In this paper we focus on interindividual variations, and we report four studies showing that individuals cannot be swayed by financial incentives to conceal or to reveal, and follow instead fixed, idiosyncratic strategies. We discuss how this result can be extended to individual and cultural variations in the tendency to display or to hide unfair rewards. PMID:24066040

  15. Decision makers use norms, not cost-benefit analysis, when choosing to conceal or reveal unfair rewards.

    PubMed

    Heimann, Marco; Girotto, Vittorio; Legrenzi, Paolo; Bonnefon, Jean-François

    2013-01-01

    We introduce the Conceal or Reveal Dilemma, in which individuals receive unfair benefits, and must decide whether to conceal or to reveal this unfair advantage. This dilemma has two important characteristics: it does not lend itself easily to cost-benefit analysis, neither to the application of any strong universal norm. As a consequence, it is ideally suited to the study of interindividual and intercultural variations in moral-economic norms. In this paper we focus on interindividual variations, and we report four studies showing that individuals cannot be swayed by financial incentives to conceal or to reveal, and follow instead fixed, idiosyncratic strategies. We discuss how this result can be extended to individual and cultural variations in the tendency to display or to hide unfair rewards.

  16. Exercise economy in skiing and running

    PubMed Central

    Losnegard, Thomas; Schäfer, Daniela; Hallén, Jostein

    2014-01-01

    Substantial inter-individual variations in exercise economy exist even in highly trained endurance athletes. The variation is believed to be determined partly by intrinsic factors. Therefore, in the present study, we compared exercise economy in V2-skating, double poling, and uphill running. Ten highly trained male cross-country skiers (23 ± 3 years, 180 ± 6 cm, 75 ± 8 kg, VO2peak running: 76.3 ± 5.6 mL·kg−1·min−1) participated in the study. Exercise economy and VO2peak during treadmill running, ski skating (V2 technique) and double poling were compared based on correlation analysis. There was a very large correlation in exercise economy between V2-skating and double poling (r = 0.81) and large correlations between V2-skating and running (r = 0.53) and double poling and running (r = 0.58). There were trivial to moderate correlations between exercise economy and the intrinsic factors VO2peak (r = 0.00–0.23), cycle rate (r = 0.03–0.46), body mass (r = −0.09–0.46) and body height (r = 0.11–0.36). In conclusion, the inter-individual variation in exercise economy could be explained only moderately by differences in VO2peak, body mass and body height. Apparently other intrinsic factors contribute to the variation in exercise economy between highly trained subjects. PMID:24478718

  17. Sleep variability in military-related PTSD: a comparison to primary insomnia and healthy controls.

    PubMed

    Straus, Laura D; Drummond, Sean P A; Nappi, Carla M; Jenkins, Melissa M; Norman, Sonya B

    2015-02-01

    Sleep disturbances are prevalent in posttraumatic stress disorder (PTSD) and are associated with a number of adverse health consequences. Few studies have used comprehensive assessment methods to characterize sleep in Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OEF/OIF/OND) veterans with PTSD. OEF/OIF/OND veterans with PTSD and sleep disturbance (n = 45) were compared to patients with primary insomnia (n = 25) and healthy control subjects (n = 27). Participants were assessed using questionnaire-based measures as well as daily subjective and objective measures of sleep. The 3 groups were compared with regard to (a) group means, (b) intraindividual (i.e., night-to-night) variability of sleep, and (c) interindividual (i.e., within-group) variability of sleep. In terms of group means, only objective sleep efficiency was significantly worse with PTSD than with primary insomnia (d = 0.54). Those with PTSD differed from those with primary insomnia on measures of intraindividual as well as interindividual variability (d = 0.48-0.73). These results suggested sleep symptoms in OEF/OIF/OND veterans with PTSD are more variable across nights and less consistent across patients relative to sleep symptoms in insomnia patients without PTSD. These findings have implications for research, as well as for personalizing treatment for individuals with PTSD. Published 2015. This article is a US Government work and is in the public domain in the USA.

  18. DEVELOPMENT OF A METHOD TO QUANTIFY THE IMPACT ...

    EPA Pesticide Factsheets

    Advances in human health risk assessment, especially for contaminants encountered by the inhalation route, have evolved so that the uncertainty factors (UF) used in the extrapolation of non-cancer effects across species (UFA) have been split into the respective pharmacodynamic (PD) and pharmacokinetic (PK) components. Present EPA default values for these components are divided into two half-logs (e.g., 10 to the 0.5 power or 3.16), so that their multiplication yields the 10-fold UF customarily seen in Agency risk assessments as UFA. The state of the science at present does not support a detailed evaluation of species-dependent and human interindividual variance of PD, but more data exist by which PK variance can be examined and quantified both across species and within the human species. Because metabolism accounts for much of the PK variance, we sought to examine the impact that differences in hepatic enzyme content exerts upon risk-relevant PK outcomes among humans. Because of the age and ethnic diversity expressed in the human organ donor population and the wide availability of tissues from these human organ donors, a program was developed to include information from those tissues in characterizing human interindividual PK variance. An Interagency Agreement with CDC/NIOSH Taft Laboratory, a Cooperative Agreement with CIIT Centers for Health Research, and a collaborative agreement with NHEERL/ETD were established to successfully complete the project. The di

  19. Assessing Variations in Areal Organization for the Intrinsic Brain: From Fingerprints to Reliability

    PubMed Central

    Xu, Ting; Opitz, Alexander; Craddock, R. Cameron; Wright, Margaret J.; Zuo, Xi-Nian; Milham, Michael P.

    2016-01-01

    Resting state fMRI (R-fMRI) is a powerful in-vivo tool for examining the functional architecture of the human brain. Recent studies have demonstrated the ability to characterize transitions between functionally distinct cortical areas through the mapping of gradients in intrinsic functional connectivity (iFC) profiles. To date, this novel approach has primarily been applied to iFC profiles averaged across groups of individuals, or in one case, a single individual scanned multiple times. Here, we used a publically available R-fMRI dataset, in which 30 healthy participants were scanned 10 times (10 min per session), to investigate differences in full-brain transition profiles (i.e., gradient maps, edge maps) across individuals, and their reliability. 10-min R-fMRI scans were sufficient to achieve high accuracies in efforts to “fingerprint” individuals based upon full-brain transition profiles. Regarding test–retest reliability, the image-wise intraclass correlation coefficient (ICC) was moderate, and vertex-level ICC varied depending on region; larger durations of data yielded higher reliability scores universally. Initial application of gradient-based methodologies to a recently published dataset obtained from twins suggested inter-individual variation in areal profiles might have genetic and familial origins. Overall, these results illustrate the utility of gradient-based iFC approaches for studying inter-individual variation in brain function. PMID:27600846

  20. 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.

  1. Spectral relative standard deviation: a practical benchmark in metabolomics.

    PubMed

    Parsons, Helen M; Ekman, Drew R; Collette, Timothy W; Viant, Mark R

    2009-03-01

    Metabolomics datasets, by definition, comprise of measurements of large numbers of metabolites. Both technical (analytical) and biological factors will induce variation within these measurements that is not consistent across all metabolites. Consequently, criteria are required to assess the reproducibility of metabolomics datasets that are derived from all the detected metabolites. Here we calculate spectrum-wide relative standard deviations (RSDs; also termed coefficient of variation, CV) for ten metabolomics datasets, spanning a variety of sample types from mammals, fish, invertebrates and a cell line, and display them succinctly as boxplots. We demonstrate multiple applications of spectral RSDs for characterising technical as well as inter-individual biological variation: for optimising metabolite extractions, comparing analytical techniques, investigating matrix effects, and comparing biofluids and tissue extracts from single and multiple species for optimising experimental design. Technical variation within metabolomics datasets, recorded using one- and two-dimensional NMR and mass spectrometry, ranges from 1.6 to 20.6% (reported as the median spectral RSD). Inter-individual biological variation is typically larger, ranging from as low as 7.2% for tissue extracts from laboratory-housed rats to 58.4% for fish plasma. In addition, for some of the datasets we confirm that the spectral RSD values are largely invariant across different spectral processing methods, such as baseline correction, normalisation and binning resolution. In conclusion, we propose spectral RSDs and their median values contained herein as practical benchmarks for metabolomics studies.

  2. Are body size and volatile blends honest signals in orchid bees?

    PubMed

    Arriaga-Osnaya, Brenda Jessica; Contreras-Garduño, Jorge; Espinosa-García, Francisco Javier; García-Rodríguez, Yolanda Magdalena; Moreno-García, Miguel; Lanz-Mendoza, Humberto; Godínez-Álvarez, Héctor; Cueva Del Castillo, Raúl

    2017-05-01

    Secondary sexual traits may convey reliable information about males' ability to resist pathogens and that females may prefer those traits because their genes for resistance would be passed on to their offspring. In many insect species, large males have high mating success and can canalize more resources to the immune function than smaller males. In other species, males use pheromones to identify and attract conspecific mates, and thus, they might function as an honest indicator of a male's condition. The males of orchid bees do not produce pheromones. They collect and store flower volatiles, which are mixed with the volatile blends from other sources, like fungi, sap and resins. These blends are displayed as perfumes during the courtship. In this study, we explored the relationship between inter-individual variation in body size and blend composition with the males' phenoloxidase (PO) content in Euglossa imperialis . PO content is a common measure of insect immune response because melanine, its derived molecule, encapsulates parasites and pathogens. Body size and blend composition were related to bees' phenolic PO content. The inter-individual variation in body size and tibial contents could indicate differences among males in their skills to gain access to some compounds. The females may evaluate their potential mates through these compounds because some of them are reliable indicators of the males' capacity to resist infections and parasites.

  3. The impact of eating methods on eating rate and glycemic response in healthy adults.

    PubMed

    Sun, Lijuan; Ranawana, Dinesh Viren; Tan, Wei Jie Kevin; Quek, Yu Chin Rina; Henry, Christiani Jeyakumar

    2015-02-01

    Singapore is an island state that is composed of three major ethnic groups, namely Chinese, Malay and Indian. Its inhabitants consume food either using chopsticks (Chinese), fingers (Malay and Indian) or spoon (Chinese, Malay and Indian). Previous work by our group showed that the degree of mastication significantly influenced the glycemic response. The degree of mastication in turn may depend on the eating method as the amount of food taken per mouthful and chewing time differs between eating methods. Eleven healthy volunteers came in on six non-consecutive days to the laboratory and evaluated three methods of eating white rice (spoon, chopsticks and fingers) once and the reference food (glucose solution) three times in a random order. Their glycemic response (GR) was measured for the subsequent 120 min. Mastication parameters were determined using surface electrode electromyography. The GR to white rice eating with chopsticks was significantly lower than spoon. The GI of eating rice with chopsticks was 68 which is significantly lower than eating with spoon (GI=81). However there were no differences between fingers and spoon, and between fingers and chopsticks either in GR 120 min or GI. The inter-individual number of mouthful, number of chews per mouthful, chewing time per mouthful and the total time taken to consume the whole portion of rice were significantly different between spoon and chopsticks groups. Significant correlations between the number of mouthful to take the entire portion of rice and amount of rice per mouthful during mastication and the GR were observed for eating rice with spoon and chopsticks, but not for fingers. The results suggest that individual differences in number of mouthful and amount of rice per mouthful may be two of the causes for inter-individual differences in the GR between spoon and chopsticks. The present study suggests that eating rice with different feeding tools has different chewing times and amount of food taken per mouthful and then alters the GI of the rice. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Pharmacogenetics and forensic toxicology.

    PubMed

    Musshoff, Frank; Stamer, Ulrike M; Madea, Burkhard

    2010-12-15

    Large inter-individual variability in drug response and toxicity, as well as in drug concentrations after application of the same dosage, can be of genetic, physiological, pathophysiological, or environmental origin. Absorption, distribution and metabolism of a drug and interactions with its target often are determined by genetic differences. Pharmacokinetic and pharmacodynamic variations can appear at the level of drug metabolizing enzymes (e.g., the cytochrome P450 system), drug transporters, drug targets or other biomarker genes. Pharmacogenetics or toxicogenetics can therefore be relevant in forensic toxicology. This review presents relevant aspects together with some examples from daily routines. Copyright © 2010. Published by Elsevier Ireland Ltd.

  5. Human knee joint anatomy revisited: morphometry in the light of sex-specific total knee arthroplasty.

    PubMed

    Dargel, Jens; Michael, Joern W P; Feiser, Janna; Ivo, Roland; Koebke, Juergen

    2011-04-01

    This study investigates differences in the anatomy of male and female knee joints to contribute to the current debate on sex-specific total knee implants. Morphometric data were obtained from 60 human cadaver knees, and sex differences were calculated. All data were corrected for height, and male and female specimens presenting with an identical length of the femur were analyzed as matched pairs. Male linear knee joint dimensions were significantly larger when compared with females. When corrected for differences in height, medial-lateral dimensions of male knees were significantly larger than female; however, matched paired analysis did not prove these differences to be consistent. Although implant design should focus interindividual variations in knee joint anatomy, our data do not support the concept of a female-specific implant design. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. [Application of the method of one-day learning in a Morris water maze to analyse the effects of sleep deprivation on memory trace recall 24 hours later, after learning].

    PubMed

    Dorokhov, V B; Kozhedub, R G; Arsenyev, G N; Bukhgolts, O I; Marchenko, V G; Puchkova, A N

    2014-01-01

    The proposed model of a one-day spatial learning is of interest in research of how sleep influences the hippocamp-dependent memory consolidation. We have studied the influence of a one-day total sleep deprivation on spatial memory consolidation in hooded rats after a one-day learning in the Morris water maze according to Feldman et al. [2010] protocol. According to it rats had to find a submerged platform that was alternatively marked by a flag or completely invisible to an animal. In a previous study [Dorokhov et al., 2011] we have used another one-day learning protocol [Frick et al., 2000] and Wistar rats and have demonstrated a large interindividual variance in learning parameters and sleep deprivation effects on memory consolidation. In this study we confirm previously acquired results on negative impact of sleep deprivation on spatial memory consolidation. To demonstrate the effects of sleep deprivation on the results of one-day learning we are using for the first time an evaluation of the time spent by an animal in the area of the platform placement and corresponding areas in the other quadrants of the water maze.

  7. Genetic determinants of drug responsiveness and drug interactions.

    PubMed

    Caraco, Y

    1998-10-01

    Six cytochrome P450 enzymes mediate the oxidative metabolism of most drugs in common use: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. These enzymes have selective substrate specificity, and their activity is characterized by marked interindividual variation. Some of these systems (CYP2C19, CYP2D6) are polymorphically distributed; thus, a subset of the population may be genetically deficient in enzyme activity. Phenotyping procedures designed to identify subjects with impaired metabolism who may be at increased risk for drug toxicity have been developed and validated. This has been supplemented in recent years by the availability of genetic analysis and the identification of specific alleles that are associated with altered (i.e., reduced, deficient, or increased) enzyme activity. The potential of genotyping to predict pharmacodynamics holds great promise for the future because it does not involve the administration of exogenous compound and is not confounded by drug therapy. Drug interactions caused by the inhibition or induction of oxidative drug metabolism may be of great clinical importance because they may result in drug toxicity or therapeutic failure. Further understanding of cytochrome P450 complexity may allow, through a combined in vitro-in vivo approach, the reliable prediction and possible prevention of deleterious drug interactions.

  8. How Non-nutritive Sweeteners Influence Hormones and Health.

    PubMed

    Rother, Kristina I; Conway, Ellen M; Sylvetsky, Allison C

    2018-07-01

    Non-nutritive sweeteners (NNSs) elicit a multitude of endocrine effects in vitro, in animal models, and in humans. The best-characterized consequences of NNS exposure are metabolic changes, which may be mediated by activation of sweet taste receptors in oral and extraoral tissues (e.g., intestine, pancreatic β cells, and brain), and alterations of the gut microbiome. These mechanisms are likely synergistic and may differ across species and chemically distinct NNSs. However, the extent to which these hormonal effects are clinically relevant in the context of human consumption is unclear. Further investigation following prolonged exposure is required to better understand the role of NNSs in human health, with careful consideration of genetic, dietary, anthropometric, and other interindividual differences. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Parenting and trajectories of children's maladaptive behaviors: a 12-year prospective community study.

    PubMed

    Luyckx, Koen; Tildesley, Elizabeth A; Soenens, Bart; Andrews, Judy A; Hampson, Sarah E; Peterson, Missy; Duriez, Bart

    2011-01-01

    This study investigated how parenting accounted for interindividual differences in developmental trajectories of different child behaviors across childhood and adolescence. In a cohort sequential community sample of 1,049 children, latent class growth analysis was applied to three parent-reported dimensions (monitoring, positive parenting, inconsistent discipline) across 12 annual assessments (ages 6-18). Four longitudinal parenting styles (authoritative, authoritarian, indulgent, uninvolved) were differentiated on the basis of levels and rates of change in the constituent parenting dimensions. Multigroup analyses demonstrated that these parenting styles were differentially related to changes in parent- and child-reported measures of children's alcohol and cigarette use, antisocial behavior, and internalizing symptoms, with the authoritative parenting class being related to the most optimal long-term development.

  10. Polymorphisms in the dopamine receptor 2 gene region influence improvements during working memory training in children and adolescents.

    PubMed

    Söderqvist, Stina; Matsson, Hans; Peyrard-Janvid, Myriam; Kere, Juha; Klingberg, Torkel

    2014-01-01

    Studying the effects of cognitive training can lead to finding better treatments, but it can also be a tool for investigating factors important for brain plasticity and acquisition of cognitive skills. In this study, we investigated how single-nucleotide polymorphisms (SNPs) and ratings of intrinsic motivation were associated to interindividual differences in improvement during working memory training. The study included 256 children aged 7-19 years who were genotyped for 13 SNPs within or near eight candidate genes previously implicated in learning: COMT, SLC6A3 (DAT1), DRD4, DRD2, PPP1R1B (DARPP32), MAOA, LMX1A, and BDNF. Ratings on the intrinsic motivation inventory were also available for 156 of these children. All participants performed at least 20 sessions of working memory training, and performance during the training was logged and used as the outcome variable. We found that two SNPs, rs1800497 and rs2283265, located near and within the dopamine receptor 2 (DRD2) gene, respectively, were significantly associated with improvements during training (p < .003 and p < .0004, respectively). Scores from a questionnaire regarding intrinsic motivation did not correlate with training outcome. However, we observed both the main effect of genotype at those two loci as well as the interaction between genotypes and ratings of intrinsic motivation (perceived competence). Both SNPs have previously been shown to affect DRD2 receptor density primarily in the BG. Our results suggest that genetic variation is accounting for some interindividual differences in how children acquire cognitive skills and that part of this effect is also seen on intrinsic motivation. Moreover, they suggest that dopamine D2 transmission in the BG is a key factor for cognitive plasticity.

  11. Event-related potentials reveal task-dependence and inter-individual differences in negation processing during silent listening and explicit truth-value evaluation.

    PubMed

    Herbert, C; Kissler, J

    2014-09-26

    In sentences such as dogs cannot fly/bark, evaluation of the truth-value of the sentence is assumed to appear after the negation has been integrated into the sentence structure. Moreover negation processing and truth-value processing are considered effortful processes, whereas processing of the semantic relatedness of the words within sentences is thought to occur automatically. In the present study, modulation of event-related brain potentials (N400 and late positive potential, LPP) was investigated during an implicit task (silent listening) and active truth-value evaluation to test these theoretical assumptions and determine if truth-value evaluation will be modulated by the way participants processed the negated information implicitly prior to truth-value verification. Participants first listened to negated sentences and then evaluated these sentences for their truth-value in an active evaluation task. During passive listening, the LPP was generally more pronounced for targets in false negative (FN) than true negative (TN) sentences, indicating enhanced attention allocation to semantically-related but false targets. N400 modulation by truth-value (FN>TN) was observed in 11 out of 24 participants. However, during active evaluation, processing of semantically-unrelated but true targets (TN) elicited larger N400 and LPP amplitudes as well as a pronounced frontal negativity. This pattern was particularly prominent in those 11 individuals, whose N400 modulation during silent listening indicated that they were more sensitive to violations of the truth-value than to semantic priming effects. The results provide evidence for implicit truth-value processing during silent listening of negated sentences and for task dependence related to inter-individual differences in implicit negation processing. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Epizoochorous dispersal by ungulates depends on fur, grooming and social interactions.

    PubMed

    Liehrmann, Océane; Jégoux, Flore; Guilbert, Marie-Alice; Isselin-Nondedeu, Francis; Saïd, Sonia; Locatelli, Yann; Baltzinger, Christophe

    2018-02-01

    The transport phase of the animal-mediated plant dispersal process is critical to dispersal effectiveness as it determines the spatial distribution of the diaspores released and their chance for further recruitment. Assessing this specific phase of the dispersal process generally requires combining diaspore retention times with the associated distances covered. Here, we specifically tested the effect of grooming behavior, interindividual contacts and ungulate fur on diaspore retention times and associated dispersal distances for the hooked diaspores of Xanthium strumarium L. experimentally attached to tamed individuals of three ungulate species. We used a comparative approach based on differing fur quality on different body zones of these three ungulates. During 6-hr sessions, we monitored for grooming and social interactions that may induce intended or inadvertent diaspore detachment. Additionally, we proposed innovative approaches to directly assessing diaspore dispersal distances by red deer in situ. Fat-tailed functions fitted diaspore retention time, highlighting the potential for long-distance dispersal events. The longer the hair, the higher the retention capacity of diaspores in the animal's fur. As predicted, donkey retained diaspores longer than red deer and dwarf goat; and we also confirmed that diaspores attached to the short hair of the head fell off more quickly than did those on the other body zones. Dwarf goat groomed more often than both red deer and donkey, but also when it carried diaspores. Up to 14% of the diaspores detached from animal fur after specific grooming behavior. We observed, in controlled conditions, for the first time and for each ungulate species, interindividual transfers of diaspores, representing 5% of the diaspores attached to animals' fur. Our results militate for incorporating animal behavior into plant dispersal modeling approaches.

  13. BCR-ABL1 expression, RT-qPCR and treatment decisions in chronic myeloid leukaemia.

    PubMed

    Latham, Susan; Bartley, Paul A; Budgen, Bradley; Ross, David M; Hughes, Elizabeth; Branford, Susan; White, Deborah; Hughes, Timothy P; Morley, Alexander A

    2016-09-01

    RT-qPCR is used to quantify minimal residual disease (MRD) in chronic myeloid leukaemia (CML) in order to make decisions on treatment, but its results depend on the level of BCR-ABL1 expression as well as leukaemic cell number. The aims of the study were to quantify inter-individual differences in expression level, to determine the relationship between expression level and response to treatment, and to investigate the effect of expression level on interpretation of the RT-qPCR result. BCR-ABL1 expression was studied in 248 samples from 65 patients with CML by determining the difference between MRD quantified by RT-qPCR and DNA-qPCR. The results were analysed statistically and by simple indicative modelling. Inter-individual levels of expression approximated a normal distribution with an SD of 0.36 log. Expression at diagnosis correlated with expression during treatment. Response to treatment, as measured by the number of leukaemic cells after 3, 6 or 12 months of treatment, was not related to the level of expression. Indicative modelling suggested that interpretation of RT-qPCR results in relation to treatment guidelines could be affected by variation in expression when MRD was around 10% at 3 months and by both expression variation and Poisson variation when MRD was around or below the limit of detection of RT-qPCR. Variation between individuals in expression of BCR-ABL1 can materially affect interpretation of the RT-qPCR when this test is used to make decisions on treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Steady-state pharmacokinetics of (R)- and (S)-methadone in methadone maintenance patients

    PubMed Central

    Foster, David J R; Somogyi, Andrew A; Dyer, Kyle R; White, Jason M; Bochner, Felix

    2000-01-01

    Aims To investigate the steady-state pharmacokinetics of (R)- and (S)-methadone in a methadone maintenance population. Methods Eighteen patients recruited from a public methadone maintenance program underwent an interdosing interval pharmacokinetic study. Plasma and urine samples were collected and analysed for methadone and its major metabolite (EDDP) using stereoselective h.p.l.c. Methadone plasma protein binding was examined using ultrafiltration, and plasma α1-acid glycoprotein concentrations were quantified by radial immunoassay. Results (R)-methadone had a significantly (P < 0.05) greater unbound fraction (mean 173%) and total renal clearance (182%) compared with (S)-methadone, while maximum measured plasma concentrations (83%) and apparent partial clearance of methadone to EDDP (76%) were significantly (P < 0.001) lower. When protein binding was considered (R)-methadone plasma clearance of the unbound fraction (59%) and apparent partial intrinsic clearance to EDDP (44%) were significantly (P < 0.01) lower than for (S)-methadone, while AUCτSS, (167%) was significantly (P < 0.001) greater. There were no significant (P > 0.2) differences between the methadone enantiomers for AUCτSS, steady-state plasma clearance, trough plasma concentrations and unbound renal clearance. Patients excreted significantly (P < 0.0001) more (R)-methadone and (S)-EDDP than the corresponding enantiomers. Considerable interindividual variability was observed for the pharmacokinetic parameters, with coefficients of variation of up to 70%. Conclusions Steady-state pharmacokinetics of unbound methadone are stereoselective, and there is large interindividual variability consistent with CYP3A4 mediated metabolism to the major metabolite EDDP; the variability did not obscure a significant dose-plasma concentration relationship. Stereoselective differences in the pharmacokinetics of methadone may have important implications for pharmacokinetic-pharmacodynamic modelling but is unlikely to be important for therapeutic drug monitoring of methadone, in the setting of opioid dependence. PMID:11069437

  15. Analysis of Inter-Individual Bacterial Variation in Gut of Cicada Meimuna mongolica (Hemiptera: Cicadidae).

    PubMed

    Zhou, Wenting; Nan, Xiaoning; Zheng, Zhou; Wei, Cong; He, Hong

    2015-01-01

    Intestinal bacterial community plays a crucial role in the nutrition, development, survival, and reproduction of insects. When compared with other insects with piercing-sucking mouthparts, the habitats of cicada nymphs and adults are totally different. However, little is known about the differences in the gut bacterial communities in the nymphs and adults within any cicada species. The diversity of bacteria in the gut of nymphs and adults of both genders of Meimuna mongolica (Distant) was studied using the denaturing gradient gel electrophoresis (DGGE) method. Few inter-individual variations among gut microbiota were observed, suggesting that M. mongolica typically harbors a limited and consistent suite of bacterial species. Bacteria in the genera Pseudomonas and Enterobacter were the predominant components of the gut microflora of M. mongolica at all life stages. Bacteria of Pantoea, Streptococcus, and Uruburuella were also widespread in the cicada samples but at relatively lower concentrations. The relative stability and similarity of the PCR-DGGE patterns indicate that all individuals of this cicada species harbor a characteristic bacterial community which is independent from developmental stages and genders. Related endosymbionts that could be harbored in bacteromes of cicadas were not detected in any gut samples, which could be related to the cicada species and the distribution of these endosymbionts in the cicada cavity, or due to some of the possible limitations of PCR-DGGE community profiling. It is worthwhile to further address if related cicada endosymbiont clades distribute in the alimentary canals and other internal organs through diagnostic PCR using group-specific primer sets. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

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

    PubMed

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

    2016-11-01

    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. 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. We observed significant 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 interindividual variability in the steepness of the initial APS change and in the APS plateau achieved and sustained between 20 and 40 hours. We found that participants who achieved the fastest APS plateau, showed the greatest transfer effects to untrained cognitive domains. 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 interindividual differences in neural plasticity and sensory system efficiency that characterize schizophrenia. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  17. Sequential isotopic signature along gladius highlights contrasted individual foraging strategies of jumbo squid (Dosidicus gigas).

    PubMed

    Lorrain, Anne; Argüelles, Juan; Alegre, Ana; Bertrand, Arnaud; Munaron, Jean-Marie; Richard, Pierre; Cherel, Yves

    2011-01-01

    Cephalopods play a major role in marine ecosystems, but knowledge of their feeding ecology is limited. In particular, intra- and inter-individual variations in their use of resources has not been adequatly explored, although there is growing evidence that individual organisms can vary considerably in the way they use their habitats and resources. Using δ(13)C and δ(15)N values of serially sampled gladius (an archival tissue), we examined high resolution variations in the trophic niche of five large (>60 cm mantle length) jumbo squids (Dosidicus gigas) that were collected off the coast of Peru. We report the first evidence of large inter-individual differences in jumbo squid foraging strategies with no systematic increase of trophic level with size. Overall, gladius δ(13)C values indicated one or several migrations through the squid's lifetime (∼8-9 months), during which δ(15)N values also fluctuated (range: 1 to 5‰). One individual showed an unexpected terminal 4.6‰ δ(15)N decrease (more than one trophic level), thus indicating a shift from higher- to lower-trophic level prey at that time. The data illustrate the high diversity of prey types and foraging histories of this species at the individual level. The isotopic signature of gladii proved to be a powerful tool to depict high resolution and ontogenic variations in individual foraging strategies of squids, thus complementing traditional information offered by stomach content analysis and stable isotopes on metabolically active tissues. The observed differences in life history strategies highlight the high degree of plasticity of the jumbo squid and its high potential to adapt to environmental changes.

  18. Sequential Isotopic Signature Along Gladius Highlights Contrasted Individual Foraging Strategies of Jumbo Squid (Dosidicus gigas)

    PubMed Central

    Lorrain, Anne; Argüelles, Juan; Alegre, Ana; Bertrand, Arnaud; Munaron, Jean-Marie; Richard, Pierre; Cherel, Yves

    2011-01-01

    Background Cephalopods play a major role in marine ecosystems, but knowledge of their feeding ecology is limited. In particular, intra- and inter-individual variations in their use of resources has not been adequatly explored, although there is growing evidence that individual organisms can vary considerably in the way they use their habitats and resources. Methodology/Principal Findings Using δ13C and δ15N values of serially sampled gladius (an archival tissue), we examined high resolution variations in the trophic niche of five large (>60 cm mantle length) jumbo squids (Dosidicus gigas) that were collected off the coast of Peru. We report the first evidence of large inter-individual differences in jumbo squid foraging strategies with no systematic increase of trophic level with size. Overall, gladius δ13C values indicated one or several migrations through the squid's lifetime (∼8–9 months), during which δ15N values also fluctuated (range: 1 to 5‰). One individual showed an unexpected terminal 4.6‰ δ15N decrease (more than one trophic level), thus indicating a shift from higher- to lower-trophic level prey at that time. The data illustrate the high diversity of prey types and foraging histories of this species at the individual level. Conclusions/Significance The isotopic signature of gladii proved to be a powerful tool to depict high resolution and ontogenic variations in individual foraging strategies of squids, thus complementing traditional information offered by stomach content analysis and stable isotopes on metabolically active tissues. The observed differences in life history strategies highlight the high degree of plasticity of the jumbo squid and its high potential to adapt to environmental changes. PMID:21779391

  19. In vivo maximal fascicle-shortening velocity during plantar flexion in humans.

    PubMed

    Hauraix, Hugo; Nordez, Antoine; Guilhem, Gaël; Rabita, Giuseppe; Dorel, Sylvain

    2015-12-01

    Interindividual variability in performance of fast movements is commonly explained by a difference in maximal muscle-shortening velocity due to differences in the proportion of fast-twitch fibers. To provide a better understanding of the capacity to generate fast motion, this study aimed to 1) measure for the first time in vivo the maximal fascicle-shortening velocity of human muscle; 2) evaluate the relationship between angular velocity and fascicle-shortening velocity from low to maximal angular velocities; and 3) investigate the influence of musculo-articular features (moment arm, tendinous tissues stiffness, and muscle architecture) on maximal angular velocity. Ultrafast ultrasound images of the gastrocnemius medialis were obtained from 31 participants during maximal isokinetic and light-loaded plantar flexions. A strong linear relationship between fascicle-shortening velocity and angular velocity was reported for all subjects (mean R(2) = 0.97). The maximal shortening velocity (V(Fmax)) obtained during the no-load condition (NLc) ranged between 18.8 and 43.3 cm/s. V(Fmax) values were very close to those of the maximal shortening velocity (V(max)), which was extrapolated from the F-V curve (the Hill model). Angular velocity reached during the NLc was significantly correlated with this V(Fmax) (r = 0.57; P < 0.001). This finding was in agreement with assumptions about the role of muscle fiber type, whereas interindividual comparisons clearly support the fact that other parameters may also contribute to performance during fast movements. Nevertheless, none of the biomechanical features considered in the present study were found to be directly related to the highest angular velocity, highlighting the complexity of the upstream mechanics that lead to maximal-velocity muscle contraction. Copyright © 2015 the American Physiological Society.

  20. Linking melanism to brain development: expression of a melanism-related gene in barn owl feather follicles covaries with sleep ontogeny

    PubMed Central

    2013-01-01

    Background Intra-specific variation in melanocyte pigmentation, common in the animal kingdom, has caught the eye of naturalists and biologists for centuries. In vertebrates, dark, eumelanin pigmentation is often genetically determined and associated with various behavioral and physiological traits, suggesting that the genes involved in melanism have far reaching pleiotropic effects. The mechanisms linking these traits remain poorly understood, and the potential involvement of developmental processes occurring in the brain early in life has not been investigated. We examined the ontogeny of rapid eye movement (REM) sleep, a state involved in brain development, in a wild population of barn owls (Tyto alba) exhibiting inter-individual variation in melanism and covarying traits. In addition to sleep, we measured melanistic feather spots and the expression of a gene in the feather follicles implicated in melanism (PCSK2). Results As in mammals, REM sleep declined with age across a period of brain development in owlets. In addition, inter-individual variation in REM sleep around this developmental trajectory was predicted by variation in PCSK2 expression in the feather follicles, with individuals expressing higher levels exhibiting a more precocial pattern characterized by less REM sleep. Finally, PCSK2 expression was positively correlated with feather spotting. Conclusions We demonstrate that the pace of brain development, as reflected in age-related changes in REM sleep, covaries with the peripheral activation of the melanocortin system. Given its role in brain development, variation in nestling REM sleep may lead to variation in adult brain organization, and thereby contribute to the behavioral and physiological differences observed between adults expressing different degrees of melanism. PMID:23886007

  1. 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

  2. Diurnal Rhythms in Blood Cell Populations and the Effect of Acute Sleep Deprivation in Healthy Young Men

    PubMed Central

    Ackermann, Katrin; Revell, Victoria L.; Lao, Oscar; Rombouts, Elwin J.; Skene, Debra J.; Kayser, Manfred

    2012-01-01

    Study Objectives: The sleep/wake cycle is accompanied by changes in circulating numbers of immune cells. The goal of this study was to provide an in-depth characterization of diurnal rhythms in different blood cell populations and to investigate the effect of acute sleep deprivation on the immune system, as an indicator of the body's acute stress response. Design: Observational within-subject design. Setting: Home environment and Clinical Research Centre. Participants: 15 healthy male participants aged 23.7 ± 5.4 (standard deviation) yr. Interventions: Total sleep deprivation. Measurements and Results: Diurnal rhythms of several blood cell populations were assessed under a normal sleep/wake cycle followed by 29 hr of extended wakefulness. The effect of condition (sleep versus sleep deprivation) on peak time and amplitude was investigated. Interindividual variation of, and the level of correlation between, the different cell populations was assessed. Comprehensive nonlinear curve fitting showed significant diurnal rhythms for all blood cell types investigated, with CD4 (naïve) cells exhibiting the most robust rhythms independent of condition. For those participants exhibiting significant diurnal rhythms in blood cell populations, only the amplitude of the granulocyte rhythm was significantly reduced by sleep deprivation. Granulocytes were the most diverse population, being most strongly affected by condition, and showed the lowest correlations with any other given cell type while exhibiting the largest interindividual variation in abundance. Conclusions: Granulocyte levels and diurnal rhythmicity are directly affected by acute sleep deprivation; these changes mirror the body's immediate immune response upon exposure to stress. Citation: Ackermann K; Revell VL; Lao O; Rombouts EJ; Skene DJ; Kayser M. Diurnal rhythms in blood cell populations and the effect of acute sleep deprivation in healthy young men. SLEEP 2012;35(7):933-940. PMID:22754039

  3. 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

  4. A Novel Framework for Characterizing Exposure-Related ...

    EPA Pesticide Factsheets

    Descriptions of where and how individuals spend their time are important for characterizing exposures to chemicals in consumer products and in indoor environments. Herein we create an agent-based model (ABM) that is able to simulate longitudinal patterns in behaviors. By basing our ABM upon a needs-based artificial intelligence (AI) system, we create agents that mimic human decisions on these exposure-relevant behaviors. In a case study of adults, we use the AI to predict the inter-individual variation in the start time and duration of four behaviors: sleeping, eating, commuting, and working. The results demonstrate that the ABM can capture both inter-individual variation and how decisions on one behavior can affect subsequent behaviors. Preset NERL's research on the use of agent based modeling in exposure assessments. To obtain feed back on the approach from the leading experts in the field.

  5. 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.

  6. The gravity of pollination: integrating at-site features into spatial analysis of contemporary pollen movement.

    PubMed

    DiLeo, Michelle F; Siu, Jenna C; Rhodes, Matthew K; López-Villalobos, Adriana; Redwine, Angela; Ksiazek, Kelly; Dyer, Rodney J

    2014-08-01

    Pollen-mediated gene flow is a major driver of spatial genetic structure in plant populations. Both individual plant characteristics and site-specific features of the landscape can modify the perceived attractiveness of plants to their pollinators and thus play an important role in shaping spatial genetic variation. Most studies of landscape-level genetic connectivity in plants have focused on the effects of interindividual distance using spatial and increasingly ecological separation, yet have not incorporated individual plant characteristics or other at-site ecological variables. Using spatially explicit simulations, we first tested the extent to which the inclusion of at-site variables influencing local pollination success improved the statistical characterization of genetic connectivity based upon examination of pollen pool genetic structure. The addition of at-site characteristics provided better models than those that only considered interindividual spatial distance (e.g. IBD). Models parameterized using conditional genetic covariance (e.g. population graphs) also outperformed those assuming panmixia. In a natural population of Cornus florida L. (Cornaceae), we showed that the addition of at-site characteristics (clumping of primary canopy opening above each maternal tree and maternal tree floral output) provided significantly better models describing gene flow than models including only between-site spatial (IBD) and ecological (isolation by resistance) variables. Overall, our results show that including interindividual and local ecological variation greatly aids in characterizing landscape-level measures of contemporary gene flow. © 2014 John Wiley & Sons Ltd.

  7. Increased energy intake following sleep restriction in men and women: A one-size-fits-all conclusion?

    PubMed

    McNeil, Jessica; St-Onge, Marie-Pierre

    2017-06-01

    This study assessed the degree of interindividual responses in energy intake (EI) to an imposed sleep restriction versus habitual sleep duration protocol. It also investigated participant (age, sex, ethnicity, and BMI) and study (study site and protocol order) characteristics as potential contributors to the variance in EI responses to sleep restriction between individuals. Data from two randomized crossover trials were combined. All participants (n = 43; age: 31 ± 7 years, BMI: 23 ± 2 kg/m 2 ) were free of medical/sleep conditions, were nonsmokers, reported not performing shift work, and had an average sleep duration of 7 to 9 hours per night. Ad libitum, 24-hour EI was objectively assessed following sleep restriction (3.5-4 hours in bed per night) and habitual sleep (7-9 hours in bed per night) conditions. Large interindividual variations in EI change (ΔEI) between restricted and habitual sleep conditions were noted (-813 to 1437 kcal/d). Only phase order was associated with ΔEI (β = -568 kcal/d, 95% confidence interval for β = -921 to -215 kcal/d; P = 0.002); participants randomized to the habitual sleep condition first had greater increases in EI when sleep was restricted (P = 0.01). Large interindividual variations in ΔEI following sleep restriction were noted, suggesting that not all participants were negatively impacted by the effects of sleep restriction. © 2017 The Obesity Society.

  8. [Comparison of bite marks and teeth features using 2D and 3D methods].

    PubMed

    Lorkiewicz-Muszyńska, Dorota; Glapiński, Mariusz; Zaba, Czesław; Łabecka, Marzena

    2011-01-01

    The nature of bite marks is complex. They are found at the scene of crime on different materials and surfaces - not only on human body and corpse, but also on food products and material objects. Human bites on skin are sometimes difficult to interpret and to analyze because of the specific character of skin--elastic and distortable--and because different areas of human body have different surfaces and curvatures. A bite mark left at the scene of crime can be a highly helpful way to lead investigators to criminals. The study was performed to establish: 1) whether bite marks exhibit variations in the accuracy of impressions on different materials, 2) whether it is possible to use the 3D method in the process of identifying an individual based on the comparison of bite marks revealed at the scene, and 3D scans of dental casts, 3) whether application of the 3D method allows for elimination of secondary photographic distortion of bite marks. The authors carried out experiments on simulated cases. Five volunteers bit various materials with different surfaces. Experimental bite marks were collected with emphasis on differentiations of materials. Subsequently, dental impressions were taken from five volunteers in order to prepare five sets of dental casts (the maxilla and mandible. The biting edges of teeth were impressed in wax to create an imprint. The samples of dental casts, corresponding wax bite impressions and bite marks from different materials were scanned with 2D and 3D scanners and photographs were taken. All of these were examined in detail and then compared using different methods (2D and 3D). 1) Bite marks exhibit variations in accuracy of impression on different materials. The most legible reproduction of bite marks was seen on cheese. 2) In comparison of bite marks, the 3D method and 3D scans of dental casts are highly accurate. 3) The 3D method helps to eliminate secondary photographic distortion of bite marks.

  9. Numerical Transcoding Proficiency in 10-Year-Old Schoolchildren is Associated with Gray Matter Inter-Individual Differences: A Voxel-Based Morphometry Study.

    PubMed

    Lubin, Amélie; Rossi, Sandrine; Simon, Grégory; Lanoë, Céline; Leroux, Gaëlle; Poirel, Nicolas; Pineau, Arlette; Houdé, Olivier

    2013-01-01

    Are individual differences in numerical performance sustained by variations in gray matter volume in schoolchildren? To our knowledge, this challenging question for neuroeducation has not yet been investigated in typical development. We used the Voxel-Based Morphometry method to search for possible structural brain differences between two groups of 10-year-old schoolchildren (N = 22) whose performance differed only in numerical transcoding between analog and symbolic systems. The results indicated that children with low numerical proficiency have less gray matter volume in the parietal (particularly in the left intraparietal sulcus and the bilateral angular gyri) and occipito-temporal areas. All the identified regions have previously been shown to be functionally involved in transcoding between analog and symbolic numerical systems. Our data contribute to a better understanding of the intertwined relationships between mathematics learning and brain structure in healthy schoolchildren.

  10. Is the social brain theory applicable to human individual differences? Relationship between sociability personality dimension and brain size.

    PubMed

    Horváth, Klára; Martos, János; Mihalik, Béla; Bódizs, Róbert

    2011-06-17

    Our study intends to examine whether the social brain theory is applicable to human individual differences. According to the social brain theory primates have larger brains as it could be expected from their body sizes due to the adaptation to a more complex social life. Regarding humans there were few studies about the relationship between theory of mind and frontal and temporal brain lobes. We hypothesized that these brain lobes, as well as the whole cerebrum and neocortex are in connection with the Sociability personality dimension that is associated with individuals' social lives. Our findings support this hypothesis as Sociability correlated positively with the examined brain structures if we control the effects of body size differences and age. These results suggest that the social brain theory can be extended to human interindividual differences and they have some implications to personality psychology too.

  11. Express yourself: bold individuals induce enhanced morphological defences

    PubMed Central

    Hulthén, Kaj; Chapman, Ben B.; Nilsson, P. Anders; Hollander, Johan; Brönmark, Christer

    2014-01-01

    Organisms display an impressive array of defence strategies in nature. Inducible defences (changes in morphology and/or behaviour within a prey's lifetime) allow prey to decrease vulnerability to predators and avoid unnecessary costs of expression. Many studies report considerable interindividual variation in the degree to which inducible defences are expressed, yet what underlies this variation is poorly understood. Here, we show that individuals differing in a key personality trait also differ in the magnitude of morphological defence expression. Crucian carp showing risky behaviours (bold individuals) expressed a significantly greater morphological defence response when exposed to a natural enemy when compared with shy individuals. Furthermore, we show that fish of different personality types differ in their behavioural plasticity, with shy fish exhibiting greater absolute plasticity than bold fish. Our data suggest that individuals with bold personalities may be able to compensate for their risk-prone behavioural type by expressing enhanced morphological defences. PMID:24335987

  12. A Modular Mind? A Test Using Individual Data from Seven Primate Species

    PubMed Central

    Amici, Federica; Barney, Bradley; Johnson, Valen E.; Call, Josep; Aureli, Filippo

    2012-01-01

    It has long been debated whether the mind consists of specialized and independently evolving modules, or whether and to what extent a general factor accounts for the variance in performance across different cognitive domains. In this study, we used a hierarchical Bayesian model to re-analyse individual level data collected on seven primate species (chimpanzees, bonobos, orangutans, gorillas, spider monkeys, brown capuchin monkeys and long-tailed macaques) across 17 tasks within four domains (inhibition, memory, transposition and support). Our modelling approach evidenced the existence of both a domain-specific factor and a species factor, each accounting for the same amount (17%) of the observed variance. In contrast, inter-individual differences played a minimal role. These results support the hypothesis that the mind of primates is (at least partially) modular, with domain-specific cognitive skills undergoing different evolutionary pressures in different species in response to specific ecological and social demands. PMID:23284816

  13. Numerical Transcoding Proficiency in 10-Year-Old Schoolchildren is Associated with Gray Matter Inter-Individual Differences: A Voxel-Based Morphometry Study

    PubMed Central

    Lubin, Amélie; Rossi, Sandrine; Simon, Grégory; Lanoë, Céline; Leroux, Gaëlle; Poirel, Nicolas; Pineau, Arlette; Houdé, Olivier

    2013-01-01

    Are individual differences in numerical performance sustained by variations in gray matter volume in schoolchildren? To our knowledge, this challenging question for neuroeducation has not yet been investigated in typical development. We used the Voxel-Based Morphometry method to search for possible structural brain differences between two groups of 10-year-old schoolchildren (N = 22) whose performance differed only in numerical transcoding between analog and symbolic systems. The results indicated that children with low numerical proficiency have less gray matter volume in the parietal (particularly in the left intraparietal sulcus and the bilateral angular gyri) and occipito-temporal areas. All the identified regions have previously been shown to be functionally involved in transcoding between analog and symbolic numerical systems. Our data contribute to a better understanding of the intertwined relationships between mathematics learning and brain structure in healthy schoolchildren. PMID:23630510

  14. Influence of the axial rotation angle on tool mark striations.

    PubMed

    Garcia, Derrel Louis; Pieterman, René; Baiker, Martin

    2017-10-01

    A tool's axial rotation influences the geometric properties of a tool mark. The larger the axial rotation angle, the larger the compression of structural details like striations. This complicates comparing tool marks at different axial rotations. Using chisels, tool marks were made from 0° to 75° axial rotation and compared using an automated approach Baiker et al. [10]. In addition, a 3D topographic surface of a chisel was obtained to generate virtual tool marks and to test whether the axial rotation angle of a mark could be predicted. After examination of the tool mark and chisel data-sets it was observed that marks lose information with increasing rotation due to the change in relative distance between geometrical details on the tool and the disappearance of smaller details. The similarity and repeatability were high for comparisons between marks with no difference in axial rotation, but decreasing with increased rotation angle from 0° to 75°. With an increasing difference in the rotation angles, the tool marks had to be corrected to account for the different compression factors between them. For compression up to 7.5%, this was obtained automatically by the tool mark alignment method. For larger compression, manually re-sizing the marks to the uncompressed widths at 0° rotation before the alignment was found suitable for successfully comparing even large differences in axial rotation. The similarity and repeatability were decreasing however, with increasing degree of re-sizing. The quality was assessed by determining the similarity at different detail levels within a tool mark. With an axial rotation up to 75°, tool marks were found to reliably represent structural details down to 100μm. The similarity of structural details below 100μm was dependent on the angle, with the highest similarity at small rotation angles and the lowest similarity at large rotation angles. Filtering to remove the details below 100μm lead to consistently higher similarity between tool marks at all angles and allowed for a comparison of marks up to 75° axial rotation. Finally, generated virtual tool mark profiles with an axial rotation were compared to experimental tool marks. The similarity between virtual and experimental tool marks remained high up to 60° rotation after which it decreased due to the loss in quality in both marks. Predicting the rotation angle is possible under certain conditions up to 45° rotation with an accuracy of 2.667±0.577° rotation. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Examination of emotion-induced changes in eating: A latent profile analysis of the Emotional Appetite Questionnaire.

    PubMed

    Bourdier, L; Morvan, Y; Kotbagi, G; Kern, L; Romo, L; Berthoz, S

    2018-04-01

    It is now recognized that emotions can influence food intake. While some people report eating less when distressed, others report either no change of eating or eating more in the same condition. The question whether this interindividual variability also occurs in response to positive emotions has been overlooked in most studies on Emotional Eating (EE). Using the Emotional Appetite Questionnaire (EMAQ) and Latent Profile Analysis, this study aimed to examine the existence of latent emotion-induced changes in eating profiles, and explore how these profiles differ by testing their relations with 1) age and sex, 2) BMI and risk for eating disorders (ED) and 3) factors that are known to be associated with EE such as perceived positive/negative feelings, depression, anxiety, stress symptoms and impulsivity. Among 401 university students (245 females) who completed the EMAQ, 3 profiles emerged (P1:11.2%, P2:60.1%, P3:28.7%), with distinct patterns of eating behaviors in response to negative emotions and situations but few differences regarding positive ones. Negative emotional overeaters (P1) and negative emotional undereaters (P3) reported similar levels of emotional distress and positive feelings, and were at greater risk for ED. However, the people in the former profile i) reported decreasing their food intake in a positive context, ii) were in majority females, iii) had higher BMI and iv) were more prone to report acting rashly when experiencing negative emotions. Our findings suggest that a person-centred analysis of the EMAQ scores offers a promising way to capture the inter-individual variability of emotionally-driven eating behaviors. These observations also add to the growing literature underscoring the importance of further investigating the role of different facets of impulsivity in triggering overeating and to develop more targeted interventions of EE. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. [Methods for detection of changes in muscle tonus].

    PubMed

    Kovac, C; Krapf, M; Ettlin, T; Mennet, P; Stratz, T; Müller, W

    1994-01-01

    Muscular spasm is a frequent symptom which is difficult to record precisely. On the basis of literature on the subject and of own studies, we undertook to describe various methods of examination which could be used to demonstrate such changes. Up to now, palpation is still the most important and most exact method for the experienced examiner. In this way local as well as extended muscular spasms can be made evident. The disadvantage however is the lack of objective proof. The easy-to-use Tissue-Compliance-Meter of Fischer, which measures the consistency of soft tissue, documents the intraindividual difference rather than the interindividual difference. This is due to the individually variable thickness of the subcutaneous fatty tissue. However, on the whole there is a good correlation to the findings of palpation. The pendulous-test and badismography allow especially the conclusion with regard to unilateral changes of tonus in the gluteal and upper leg muscles. This method also very well suits the intraindividual comparison, but less so the interindividual one. The continuous electromyogram is able to show the enhanced activity in spasmotic muscles also during sleep. The evaluation of enhanced muscle activity remains uncertain when using plain electromyogram. Recording of muscle tissue oxygen pressure is of little use to evaluate muscle spasm. Nonetheless, it provides interesting insights into pathogenetic questions. Thermography, measuring the blood circulation at the skin surface, is especially suited for perceiving intraindividual differences in case of muscle spasm. Nuclear magnetic resonance spectroscopy allows for noninvasive pH measurements in the muscle and therewith renders certain data concerning the degree of tension of this tissue. It is not yet suited for routine examination. The value of positron emission tomography for registering muscle spasm remains uncertain. Hopefully, this method, which documents the muscle energy metabolism, will enable us to more clearly evaluate muscle spasm than previous methods have done. Light and electron microscopic studies have provided contradictory results concerning histological changes in muscle biopsy in case of muscle spasm.

  17. Nature and Nurture of Human Pain

    PubMed Central

    2013-01-01

    Humans are very different when it comes to pain. Some get painful piercings and tattoos; others can not stand even a flu shot. Interindividual variability is one of the main characteristics of human pain on every level including the processing of nociceptive impulses at the periphery, modification of pain signal in the central nervous system, perception of pain, and response to analgesic strategies. As for many other complex behaviors, the sources of this variability come from both nurture (environment) and nature (genes). Here, I will discuss how these factors contribute to human pain separately and via interplay and how epigenetic mechanisms add to the complexity of their effects. PMID:24278778

  18. Hogan's framework for the study of behavior as applied to personality psychology.

    PubMed

    Ashton, Michael C

    2015-08-01

    Hogan's framework for the study of behavior can be used as a guide to the study of personality, considered here as interindividual differences in typical behavioral tendency. For any given dimension of personality variation, one can examine its development, its causal biological bases, its genetic and environmental origins, and its function and evolutionary history. These topics are discussed after a brief introduction to personality assessment and structure, and are followed by a brief review of personality research on non-human animals. This article is part of a Special Issue entitled: In Honor of Jerry Hogan. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Integrative Etiopathogenetic Models of Psychotic Disorders: Methods, Evidence and Concepts

    PubMed Central

    Gaebel, Wolfgang; Zielasek, Jürgen

    2011-01-01

    Integrative models of the etiopathogesnesis of psychotic disorders are needed since a wealth of information from such diverse fields as neurobiology, psychology, and the social sciences is currently changing the concepts of mental disorders. Several approaches to integrate these streams of information into coherent concepts of psychosis are feasible and will need to be assessed in future experimental studies. Common to these concepts are the notion of psychotic disorders as brain disorders and a polythetic approach in that it is increasingly realized that a multitude of interindividually partially different pathogenetic factors interact in individual persons in a complex fashion resulting in the clinical symptoms of psychosis. PMID:21860047

  20. Biomarkers in nutrition: new frontiers in research and application.

    PubMed

    Combs, Gerald F; Trumbo, Paula R; McKinley, Michelle C; Milner, John; Studenski, Stephanie; Kimura, Takeshi; Watkins, Steven M; Raiten, Daniel J

    2013-03-01

    Nutritional biomarkers--biochemical, functional, or clinical indices of nutrient intake, status, or functional effects--are needed to support evidence-based clinical guidance and effective health programs and policies related to food, nutrition, and health. Such indices can reveal information about biological or physiological responses to dietary behavior or pathogenic processes, and can be used to monitor responses to therapeutic interventions and to provide information on interindividual differences in response to diet and nutrition. Many nutritional biomarkers are available; yet there has been no formal mechanism to establish consensus regarding the optimal biomarkers for particular nutrients and applications. © 2013 New York Academy of Sciences.

  1. Age-related differences in the structural complexity of subcortical and ventricular structures.

    PubMed

    Madan, Christopher R; Kensinger, Elizabeth A

    2017-02-01

    It has been well established that the volume of several subcortical structures decreases in relation to age. Different metrics of cortical structure (e.g., volume, thickness, surface area, and gyrification) have been shown to index distinct characteristics of interindividual differences; thus, it is important to consider the relation of age to multiple structural measures. Here, we compare age-related differences in subcortical and ventricular volume to those differences revealed with a measure of structural complexity, quantified as fractal dimensionality. Across 3 large data sets, totaling nearly 900 individuals across the adult lifespan (aged 18-94 years), we found greater age-related differences in complexity than volume for the subcortical structures, particularly in the caudate and thalamus. The structural complexity of ventricular structures was not more strongly related to age than volume. These results demonstrate that considering shape-related characteristics improves sensitivity to detect age-related differences in subcortical structures. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Effect of pasture size on behavioural synchronization and spacing in German Blackface ewes (Ovis aries).

    PubMed

    Hauschildt, Verena; Gerken, Martina

    2016-03-01

    This study aims to assess plot size related changes in spacing and behavioural synchronization in a herd of 14 German Blackface ewes kept on three different pasture sizes: S (126m(2)), M (1100m(2)), and L (11,200m(2)). In direct field observations, behaviour and nearest neighbour distance were recorded individually. Additionally, interindividual and nearest neighbour distances were derived from aerial photographs of the herd taken on plot sizes S and M. Nearest neighbour distances <1m accounted for more than 60% of observations, and were more frequent on plot size L than on plot sizes S (Z=3.3; p<0.01) and M (Z=3.2; p<0.01). Average interindividual distances were significantly smaller on S (4.89±2.62m) than on M plots (5.99±3.06m; t=7.3; p<0.01). Synchronization tended to increase with plot size (K(S)=0.42; K(M)=0.52; K(L)=0.66), but was not accompanied by a concomitant increase in dispersion. Aerial photography proved a valuable tool in the analysis of spacing behaviour as intraindividual repeatability of the derived distances was highly significant (Kendall's W between 0.32 and 0.58; p<0.01). The sheep kept small distances on all plot sizes, thus the high degree of behavioural synchronization might be mainly attributed to the motivation for close proximity to any conspecific. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. 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

  4. 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 Central

    Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

    2014-01-01

    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. PMID:24647074

  5. Pylorus preserving loop duodeno-enterostomy with sleeve gastrectomy - preliminary results

    PubMed Central

    2014-01-01

    Background Bariatric operations mostly combine a restrictive gastric component with a rerouting of the intestinal passage. The pylorus can thereby be alternatively preserved or excluded. With the aim of performing a “pylorus-preserving gastric bypass”, we present early results of a proximal postpyloric loop duodeno-jejunostomy associated with a sleeve gastrectomy (LSG) compared to results of a parallel, but distal LSG with a loop duodeno-ileostomy as a two-step procedure. Methods 16 patients underwent either a two-step LSG with a distal loop duodeno-ileostomy (DIOS) as revisional bariatric surgery or a combined single step operation with a proximal duodeno-jejunostomy (DJOS). Total small intestinal length was determined to account for inter-individual differences. Results Mean operative time for the second-step of the DIOS operation was 121 min and 147 min for the combined DJOS operation. The overall intestinal length was 750.8 cm (range 600-900 cm) with a bypassed limb length of 235.7 cm in DJOS patients. The mean length of the common channel in DIOS patients measured 245.6 cm. Overall excess weight loss (%EWL) of the two-step DIOS procedure came to 38.31% and 49.60%, DJOS patients experienced an %EWL of 19.75% and 46.53% at 1 and 6 months, resp. No complication related to the duodeno-enterostomy occurred. Conclusions Loop duodeno-enterosomies with sleeve gastrectomy can be safely performed and may open new alternatives in bariatric surgery with the possibility for inter-individual adaptation. PMID:24725654

  6. Population nutrikinetics of green tea extract.

    PubMed

    Scholl, Catharina; Lepper, Anna; Lehr, Thorsten; Hanke, Nina; Schneider, Katharina Luise; Brockmöller, Jürgen; Seufferlein, Thomas; Stingl, Julia Carolin

    2018-01-01

    Green tea polyphenols may contribute to the prevention of cancer and other diseases. To learn more about the pharmacokinetics and interindividual variation of green tea polyphenols after oral intake in humans we performed a population nutrikinetic study of standardized green tea extract. 84 healthy participants took green tea extract capsules standardized to 150 mg epigallocatechin-gallate (EGCG) twice a day for 5 days. On day 5 catechin plasma concentrations were analyzed using non-compartmental and population pharmacokinetic methods. A strong between-subject variability in catechin pharmacokinetics was found with maximum plasma concentrations varying more than 6-fold. The AUCs of EGCG, EGC and ECG were 877.9 (360.8-1576.5), 35.1 (8.0-87.4), and 183.6 (55.5-364.6) h*μg/L respectively, and the elimination half lives were 2.6 (1.8-3.8), 3.9 (0.9-10.7) and 1.8 (0.8-2.9) h, respectively. Genetic polymorphisms in genes of the drug transporters MRP2 and OATP1B1 could at least partly explain the high variability in pharmacokinetic parameters. The observed variability in catechin plasma levels might contribute to interindividual variation in benefical and adverse effects of green tea polyphenols. Our data could help to gain a better understanding of the causes of variability of green tea effects and to improve the design of studies on the effects of green tea polyphenols in different health conditions. ClinicalTrials.gov: NCT01360320.

  7. Circulating intact and cleaved forms of the urokinase-type plasminogen activator receptor: biological variation, reference intervals and clinical useful cut-points.

    PubMed

    Thurison, Tine; Christensen, Ib J; Lund, Ida K; Nielsen, Hans J; Høyer-Hansen, Gunilla

    2015-01-15

    High levels of circulating forms of the urokinase-type plasminogen activator receptor (uPAR) are significantly associated to poor prognosis in cancer patients. Our aim was to determine biological variations and reference intervals of the uPAR forms in blood, and in addition, to test the clinical relevance of using these as cut-points in colorectal cancer (CRC) prognosis. uPAR forms were measured in citrated and EDTA plasma samples using time-resolved fluorescence immunoassays. Diurnal, intra- and inter-individual variations were assessed in plasma samples from cohorts of healthy individuals. Reference intervals were determined in plasma from healthy individuals randomly selected from a Danish multi-center cross-sectional study. A cohort of CRC patients was selected from the same cross-sectional study. The reference intervals showed a slight increase with age and women had ~20% higher levels. The intra- and inter-individual variations were ~10% and ~20-30%, respectively and the measured levels of the uPAR forms were within the determined 95% reference intervals. No diurnal variation was found. Applying the normal upper limit of the reference intervals as cut-point for dichotomizing CRC patients revealed significantly decreased overall survival of patients with levels above this cut-point of any uPAR form. The reference intervals for the different uPAR forms are valid and the upper normal limits are clinically relevant cut-points for CRC prognosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Sperm function and assisted reproduction technology

    PubMed Central

    MAAß, GESA; BÖDEKER, ROLF‐HASSO; SCHEIBELHUT, CHRISTINE; STALF, THOMAS; MEHNERT, CLAAS; SCHUPPE, HANS‐CHRISTIAN; JUNG, ANDREAS; SCHILL, WOLF‐BERNHARD

    2005-01-01

    The evaluation of different functional sperm parameters has become a tool in andrological diagnosis. These assays determine the sperm's capability to fertilize an oocyte. It also appears that sperm functions and semen parameters are interrelated and interdependent. Therefore, the question arose whether a given laboratory test or a battery of tests can predict the outcome in in vitro fertilization (IVF). One‐hundred and sixty‐one patients who underwent an IVF treatment were selected from a database of 4178 patients who had been examined for male infertility 3 months before or after IVF. Sperm concentration, motility, acrosin activity, acrosome reaction, sperm morphology, maternal age, number of transferred embryos, embryo score, fertilization rate and pregnancy rate were determined. In addition, logistic regression models to describe fertilization rate and pregnancy were developed. All the parameters in the models were dichotomized and intra‐ and interindividual variability of the parameters were assessed. Although the sperm parameters showed good correlations with IVF when correlated separately, the only essential parameter in the multivariate model was morphology. The enormous intra‐ and interindividual variability of the values was striking. In conclusion, our data indicate that the andrological status at the end of the respective treatment does not necessarily represent the status at the time of IVF. Despite a relatively low correlation coefficient in the logistic regression model, it appears that among the parameters tested, the most reliable parameter to predict fertilization is normal sperm morphology. (Reprod Med Biol 2005; 4: 7–30) PMID:29699207

  9. Individual epigenetic variation: When, why, and so what?

    USDA-ARS?s Scientific Manuscript database

    Epigenetics provides a potential explanation for how environmental factors modify the risk for common diseases among individuals. Interindividual variation in DNA methylation and epigenetic regulation has been reported at specific genomic regions including transposable elements, genomically imprinte...

  10. Could pharmacogenetic data explain part of the interindividual sensitivity to methadone-induced respiratory depression?

    PubMed Central

    Crettol, Séverine; Monnat, Martine; Eap, Chin B

    2007-01-01

    In this issue of Critical Care, Megarbane and colleagues present a case report of methadone-induced respiratory depression and conduct a toxicokinetic/toxicodynamic evaluation. An opioid-dependent patient receiving methadone maintenance treatment (daily dose 70 mg) was found unconscious after ingesting 240 mg methadone and 2 mg flunitrazepam. Significant improvement in consciousness was achieved after an intravenous bolus of 0.3 mg naloxone followed by a continuous infusion of naloxone at 0.3 mg/hour. In patients receiving methadone maintenance treatment, an occasional intake of two to four times the usual daily dose of methadone is not an exceptional occurrence. However, few such patients experience episodes of life-threatening respiratory depression. Here, we discuss whether recent pharmacogenetic data could help us to understand interindividual variability in sensitivity to respiratory depression and, ultimately, to predict which patients are most likely to be affected. PMID:17338832

  11. Individual musical tempo preference correlates with EEG beta rhythm.

    PubMed

    Bauer, Anna-Katharina R; Kreutz, Gunter; Herrmann, Christoph S

    2015-04-01

    Every individual has a preferred musical tempo, which peaks slightly above 120 beats per minute and is subject to interindividual variation. The preferred tempo is believed to be associated with rhythmic body movements as well as motor cortex activity. However, a long-standing question is whether preferred tempo is determined biologically. To uncover the neural correlates of preferred tempo, we first determined an individual's preferred tempo using a multistep procedure. Subsequently, we correlated the preferred tempo with a general EEG timing parameter as well as perceptual and motor EEG correlates-namely, individual alpha frequency, auditory evoked gamma band response, and motor beta activity. Results showed a significant relation between preferred tempo and the frequency of motor beta activity. These findings suggest that individual tempo preferences result from neural activity in the motor cortex, explaining the interindividual variation. Copyright © 2014 Society for Psychophysiological Research.

  12. Pharmacogenetics and outcome with antipsychotic drugs.

    PubMed

    Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

    2014-12-01

    Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

  13. Pharmacogenetics and outcome with antipsychotic drugs

    PubMed Central

    Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.

    2014-01-01

    Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959

  14. Laser marking as environment technology

    NASA Astrophysics Data System (ADS)

    Sobotova, Lydia; Badida, Miroslav

    2017-11-01

    The contribution deals with the laser marking as one of the progressive and environment friendly technologies with utilisation in many branches of industry. Engraving and other types of laser marking of different types of materials are very actual technologies these days. Laser marking decreases the waste creation in comparison with the other classical marking technologies, which use paintings or created chips. In this experimental investigation the laser marking surface texturing of material AL99,7 according to STN 42 4003:1993-08 (STN EN 573) has been conducted. The laser marking machine TruMark 6020 and software TruTops Mark were used. Laser surface texturing after laser marking has been realised under different combinations of process parameters: pulse frequency, pulse energy and laser beam scanning speed. The morphological characterization of engraving or annealing surfaces has been performed using scanning electron microscopy (SEM) technique. The evaluation of roughness of engraved surfaces has been realized according to STN EN ISO 4287 by using Surftest SJ 301. The aim of the contribution was to show how different laser parameters affect the surface texture and colour change of metallic materials while creating minimal waste.

  15. Genome-Wide Discovery of Drug-Dependent Human Liver Regulatory Elements

    PubMed Central

    Morrissey, Kari M.; Luizon, Marcelo R.; Hoffmann, Thomas J.; Sun, Xuefeng; Jones, Stacy L.; Force Aldred, Shelley; Ramamoorthy, Anuradha; Desta, Zeruesenay; Liu, Yunlong; Skaar, Todd C.; Trinklein, Nathan D.; Giacomini, Kathleen M.; Ahituv, Nadav

    2014-01-01

    Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR) and three active regulatory marks (p300, H3K4me1, H3K27ac) on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4%) that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements. PMID:25275310

  16. 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.

  17. The potential anticancer effect of beta-blockers and the genetic variations involved in the interindividual difference.

    PubMed

    He, Ruo-Hui; He, Yi-Jing; Tang, Yong-Jun; Zhou, Hong-Hao; McLeod, Howard L; Liu, Jie

    2016-01-01

    β-ARs are extensively spread in different tissues of our body, which could be activated by neurotransmitters norepinephrine and epinephrine to mediate physiological function and abnormal states including cancer. Recently, β-AR blockers could have significant implications in cancer therapy. But the precise molecular mechanisms are far from being fully understood. Through identifying the β-AR system signal pathways relevant to cancer, we can understand the mechanisms of β-blockers used for cancer treatment. What's more, retrospective clinical data made β-blockers jump out of the traditional field of cardiovascular disease and strengthened our confidence in cancer therapy. At last, genetic studies of β-adrenergic system offered crucial genes to analyze the effects of polymorphisms on cancer susceptibility, therapy response and prognosis of cancer patients.

  18. [Individual variation in the frequency of chromosome aberrations under the influence of chemical mutagens. I. Inter-cultural and inter-individual variations in the effect of mutagens on human lymphocytes].

    PubMed

    Iakovenko, K N; Tarusina, T O

    1976-01-01

    The study of the distribution law of human peripheral blood cultures for the sensitivity to thiophosphamide was performed. In the first experiment the blood from one person was used, in the second one the blood was used from different persons. "The percent of aberrant cells" and "the number of chromosome breaks per 100 cells" were scored. The distribution law of the cultures in all the experiments was found to be normal. Analysis of the variances on the percent of aberrant cells showed that the distribution law of the cultures received from one donor corresponded to the binomial one, and that of the cultures received from different donors--to the Poisson's one.

  19. [The scent marking of territory of gerbils: a comparative analysis exemplified by 4 species of the genus Meriones].

    PubMed

    Gromov, V S

    1997-01-01

    Sex-age and seasonal variability of the ventral glands and different stereotypes of scent marking behaviour in four Meriones species (M. unguiculatus, M. meridianus, M. libycus, M. tamariscinus) have been studied in nature and under semi-natural conditions. Two major ways of olfactory marking are considered: by secretion of the ventral glands and by "signal heaps" with urine and feces. Intraspecific and inter-species variability of marking activity is investigated. The ventral glands start to function at the period of preparation of a generative system to reproduction. The peak of secretary activity of gland and maximum of two types of marking activity is observed in spring and early summer, i.e. the period of active reproduction. The maximum of two types of the marking activity is observed during this period. In M. tamariscinus and M. meridianus the marking by the ventral gland is prevailing mode of the territory scent marking, while Mongolian gerbils (M. unguiculatus) prefer to use "signal heaps" Libyan gerbils (M. libycus) in this relation take an intermediate position. At the non-productive period a level of marking activity is on 10-20 times lower than at the reproductive season. Besides hormonal, social factors were also important for regulation of marking activity. By influence of these factors the differences in the level of marking activity in high-rank and low-rank individuals and differences in patterns of a spatial distribution of scent marks in individuals of different hierarchical rank is explained. Functional significance of various ways of territory scent marking is discussed.

  20. Multiple layer identification label using stacked identification symbols

    NASA Technical Reports Server (NTRS)

    Schramm, Harry F. (Inventor)

    2005-01-01

    An automatic identification system and method are provided which employ a machine readable multiple layer label. The label has a plurality of machine readable marking layers stacked one upon another. Each of the marking layers encodes an identification symbol detectable using one or more sensing technologies. The various marking layers may comprise the same marking material or each marking layer may comprise a different medium having characteristics detectable by a different sensing technology. These sensing technologies include x-ray, radar, capacitance, thermal, magnetic and ultrasonic. A complete symbol may be encoded within each marking layer or a symbol may be segmented into fragments which are then divided within a single marking layer or encoded across multiple marking layers.

  1. Role of post-mapping computed tomography in virtual-assisted lung mapping.

    PubMed

    Sato, Masaaki; Nagayama, Kazuhiro; Kuwano, Hideki; Nitadori, Jun-Ichi; Anraku, Masaki; Nakajima, Jun

    2017-02-01

    Background Virtual-assisted lung mapping is a novel bronchoscopic preoperative lung marking technique in which virtual bronchoscopy is used to predict the locations of multiple dye markings. Post-mapping computed tomography is performed to confirm the locations of the actual markings. This study aimed to examine the accuracy of marking locations predicted by virtual bronchoscopy and elucidate the role of post-mapping computed tomography. Methods Automated and manual virtual bronchoscopy was used to predict marking locations. After bronchoscopic dye marking under local anesthesia, computed tomography was performed to confirm the actual marking locations before surgery. Discrepancies between marking locations predicted by the different methods and the actual markings were examined on computed tomography images. Forty-three markings in 11 patients were analyzed. Results The average difference between the predicted and actual marking locations was 30 mm. There was no significant difference between the latest version of the automated virtual bronchoscopy system (30.7 ± 17.2 mm) and manual virtual bronchoscopy (29.8 ± 19.1 mm). The difference was significantly greater in the upper vs. lower lobes (37.1 ± 20.1 vs. 23.0 ± 6.8 mm, for automated virtual bronchoscopy; p < 0.01). Despite this discrepancy, all targeted lesions were successfully resected using 3-dimensional image guidance based on post-mapping computed tomography reflecting the actual marking locations. Conclusions Markings predicted by virtual bronchoscopy were dislocated from the actual markings by an average of 3 cm. However, surgery was accurately performed using post-mapping computed tomography guidance, demonstrating the indispensable role of post-mapping computed tomography in virtual-assisted lung mapping.

  2. Using eye tracking to test for individual differences in attention to attractive faces

    PubMed Central

    Valuch, Christian; Pflüger, Lena S.; Wallner, Bernard; Laeng, Bruno; Ansorge, Ulrich

    2015-01-01

    We assessed individual differences in visual attention toward faces in relation to their attractiveness via saccadic reaction times. Motivated by the aim to understand individual differences in attention to faces, we tested three hypotheses: (a) Attractive faces hold or capture attention more effectively than less attractive faces; (b) men show a stronger bias toward attractive opposite-sex faces than women; and (c) blue-eyed men show a stronger bias toward blue-eyed than brown-eyed feminine faces. The latter test was included because prior research suggested a high effect size. Our data supported hypotheses (a) and (b) but not (c). By conducting separate tests for disengagement of attention and attention capture, we found that individual differences exist at distinct stages of attentional processing but these differences are of varying robustness and importance. In our conclusion, we also advocate the use of linear mixed effects models as the most appropriate statistical approach for studying inter-individual differences in visual attention with naturalistic stimuli. PMID:25698993

  3. Using eye tracking to test for individual differences in attention to attractive faces.

    PubMed

    Valuch, Christian; Pflüger, Lena S; Wallner, Bernard; Laeng, Bruno; Ansorge, Ulrich

    2015-01-01

    We assessed individual differences in visual attention toward faces in relation to their attractiveness via saccadic reaction times. Motivated by the aim to understand individual differences in attention to faces, we tested three hypotheses: (a) Attractive faces hold or capture attention more effectively than less attractive faces; (b) men show a stronger bias toward attractive opposite-sex faces than women; and (c) blue-eyed men show a stronger bias toward blue-eyed than brown-eyed feminine faces. The latter test was included because prior research suggested a high effect size. Our data supported hypotheses (a) and (b) but not (c). By conducting separate tests for disengagement of attention and attention capture, we found that individual differences exist at distinct stages of attentional processing but these differences are of varying robustness and importance. In our conclusion, we also advocate the use of linear mixed effects models as the most appropriate statistical approach for studying inter-individual differences in visual attention with naturalistic stimuli.

  4. 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.

  5. High interindividual variability in dose-dependent reduction in speed of movement after exposing C. elegans to shock waves

    PubMed Central

    Angstman, Nicholas B.; Kiessling, Maren C.; Frank, Hans-Georg; Schmitz, Christoph

    2015-01-01

    In blast-related mild traumatic brain injury (br-mTBI) little is known about the connections between initial trauma and expression of individual clinical symptoms. Partly due to limitations of current in vitro and in vivo models of br-mTBI, reliable prediction of individual short- and long-term symptoms based on known blast input has not yet been possible. Here we demonstrate a dose-dependent effect of shock wave exposure on C. elegans using shock waves that share physical characteristics with those hypothesized to induce br-mTBI in humans. Increased exposure to shock waves resulted in decreased mean speed of movement while increasing the proportion of worms rendered paralyzed. Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods. Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions. Reduction of cavitation by exposing worms to shock waves in polyvinyl alcohol resulted in reduced effect, implicating primary blast effects as damaging components in shock wave induced trauma. Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures. Taken together, these data indicate that reliable prediction of individual clinical symptoms based on known blast input as well as drawing conclusions on blast input from individual clinical symptoms is not feasible in br-mTBI. PMID:25705183

  6. Trajectories of Evening Fatigue in Oncology Outpatients Receiving Chemotherapy

    PubMed Central

    Wright, Fay; Melkus, Gail D’Eramo; Hammer, Marilyn; Schmidt, Brian L.; Knobf, M. Tish; Paul, Steven M.; Cartwright, Frances; Mastick, Judy; Cooper, Bruce A.; Chen, Lee-May; Melisko, Michelle; Levine, Jon D.; Kober, Kord; Aouizerat, Bradley E.; Miaskowski, Christine

    2015-01-01

    Context Fatigue is a distressing, persistent sense of physical tiredness that is not proportional to a person’s recent activity. Fatigue impacts patients’ treatment decisions and can limit their self-care activities. While significant interindividual variability in fatigue severity has been noted, little is known about predictors of interindividual variability in initial levels and trajectories of evening fatigue severity in oncology patients receiving chemotherapy (CTX). Objectives To determine whether demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of evening fatigue. Methods A sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer (N=586) completed demographic and symptom questionnaires a total of six times over two cycles of CTX. Fatigue severity was evaluated using the Lee Fatigue Scale. Hierarchical linear modeling (HLM) was used to answer the study objectives. Results A large amount of interindividual variability was found in the evening fatigue trajectories. A piecewise model fit the data best. Patients who were White, diagnosed with breast, gynecological, or lung cancer, and who had more years of education, child care responsibilities, lower functional status, and higher levels of sleep disturbance and depression reported higher levels of evening fatigue at enrollment. Conclusion This study identified both non-modifiable (e.g., ethnicity) and modifiable (e.g., child care responsibilities, depressive symptoms, sleep disturbance) risk factors for more severe evening fatigue. Using this information, clinicians can identify patients at higher risk for more severe evening fatigue, provide individualized patient education, and tailor interventions to address the modifiable risk factors. PMID:25828560

  7. Differential Gene Expression in Normal Human Mammary Epithelial Cells Treated with Malathion Monitored by DNA Microarrays

    PubMed Central

    Gwinn, Maureen R.; Whipkey, Diana L.; Tennant, Lora B.; Weston, Ainsley

    2005-01-01

    Organophosphate pesticides are a major source of occupational exposure in the United States. Moreover, malathion has been sprayed over major urban populations in an effort to control mosquitoes carrying West Nile virus. Previous research, reviewed by the U.S. Environmental Protection Agency, on the genotoxicity and carcinogenicity of malathion has been inconclusive, although malathion is a known endocrine disruptor. Here, interindividual variations and commonality of gene expression signatures have been studied in normal human mammary epithelial cells from four women undergoing reduction mammoplasty. The cell strains were obtained from the discarded tissues through the Cooperative Human Tissue Network (sponsors: National Cancer Institute and National Disease Research Interchange). Interindividual variation of gene expression patterns in response to malathion was observed in various clustering patterns for the four cell strains. Further clustering identified three genes with increased expression after treatment in all four cell strains. These genes were two aldo–keto reductases (AKR1C1 and AKR1C2) and an estrogen-responsive gene (EBBP). Decreased expression of six RNA species was seen at various time points in all cell strains analyzed: plasminogen activator (PLAT), centromere protein F (CPF), replication factor C (RFC3), thymidylate synthetase (TYMS), a putative mitotic checkpoint kinase (BUB1), and a gene of unknown function (GenBank accession no. AI859865). Expression changes in all these genes, detected by DNA microarrays, have been verified by real-time polymerase chain reaction. Differential changes in expression of these genes may yield biomarkers that provide insight into interindividual variation in malathion toxicity. PMID:16079077

  8. Effect of acute dietary standardization on the urinary, plasma, and salivary metabolomic profiles of healthy humans.

    PubMed

    Walsh, Marianne C; Brennan, Lorraine; Malthouse, J Paul G; Roche, Helen M; Gibney, Michael J

    2006-09-01

    Metabolomics in human nutrition research is faced with the challenge that changes in metabolic profiles resulting from diet may be difficult to differentiate from normal physiologic variation. We assessed the extent of intra- and interindividual variation in normal human metabolic profiles and investigated the effect of standardizing diet on reducing variation. Urine, plasma, and saliva were collected from 30 healthy volunteers (23 females, 7 males) on 4 separate mornings. For visits 1 and 2, free food choice was permitted on the day before biofluid collection. Food choice on the day before visit 3 was intended to mimic that for visit 2, and all foods were standardized on the day before visit 4. Samples were analyzed by using 1H nuclear magnetic resonance spectroscopy followed by multivariate data analysis. Intra- and interindividual variations were considerable for each biofluid. Visual inspection of the principal components analysis scores plots indicated a reduction in interindividual variation in urine, but not in plasma or saliva, after the standard diet. Partial least-squares discriminant analysis indicated time-dependent changes in urinary and salivary samples, mainly resulting from creatinine in urine and acetate in saliva. The predictive power of each model to classify the samples as either night or morning was 85% for urine and 75% for saliva. Urine represented a sensitive metabolic profile that reflected acute dietary intake, whereas plasma and saliva did not. Future metabolomics studies should consider recent dietary intake and time of sample collection as a means of reducing normal physiologic variation.

  9. Estimating the actual subject-specific genetic correlations in behavior genetics.

    PubMed

    Molenaar, Peter C M

    2012-10-01

    Generalization of the standard behavior longitudinal genetic factor model for the analysis of interindividual phenotypic variation to a genetic state space model for the analysis of intraindividual variation enables the possibility to estimate subject-specific heritabilities.

  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. QIVIVE Approaches to Evaluate Interindividual Toxicokinetic Variability

    EPA Science Inventory

    Toxicokinetic (TK) variability across life-stages and populations can significantly impact the amount of chemical available systemically to elicit an effect despite similar external exposures. This variability is driven by physiologic (e.g., liver weights, blood flow rates, etc.)...

  12. 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.

  13. On how high performers keep cool brains in situations of cognitive overload.

    PubMed

    Jaeggi, Susanne M; Buschkuehl, Martin; Etienne, Alex; Ozdoba, Christoph; Perrig, Walter J; Nirkko, Arto C

    2007-06-01

    What happens in the brain when we reach or exceed our capacity limits? Are there individual differences for performance at capacity limits? We used functional magnetic resonance imaging (fMRI) to investigate the impact of increases in processing demand on selected cortical areas when participants performed a parametrically varied and challenging dual task. Low-performing participants respond with large and load-dependent activation increases in many cortical areas when exposed to excessive task requirements, accompanied by decreasing performance. It seems that these participants recruit additional attentional and strategy-related resources with increasing difficulty, which are either not relevant or even detrimental to performance. In contrast, the brains of the high-performing participants "keep cool" in terms of activation changes, despite continuous correct performance, reflecting different and more efficient processing. These findings shed light on the differential implications of performance on activation patterns and underline the importance of the interindividual-differences approach in neuroimaging research.

  14. Why contagious yawning does not (yet) equate to empathy.

    PubMed

    Massen, Jorg J M; Gallup, Andrew C

    2017-09-01

    Various studies and researchers have proposed a link between contagious yawning and empathy, yet the conceptual basis for the proposed connection is not clear and deserves critical evaluation. Therefore, we systematically examined the available empirical evidence addressing this association; i.e., a critical review of studies on inter-individual differences in contagion and self-reported values of empathy, differences in contagion based on familiarity or sex, and differences in contagion among individuals with psychological disorders, as well as developmental research, and brain imaging and neurophysiological studies. In doing so, we reveal a pattern of inconsistent and inconclusive evidence regarding the connection between contagious yawning and empathy. Furthermore, we identify study limitations and confounding variables, such as visual attention and social inhibition. Future research examining links between contagious yawning and empathy requires more rigorous investigation involving objective measurements to explicitly test for this connection. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence.

    PubMed

    Bou Sleiman, Maroun S; Osman, Dani; Massouras, Andreas; Hoffmann, Ary A; Lemaitre, Bruno; Deplancke, Bart

    2015-07-27

    Gut immunocompetence involves immune, stress and regenerative processes. To investigate the determinants underlying inter-individual variation in gut immunocompetence, we perform enteric infection of 140 Drosophila lines with the entomopathogenic bacterium Pseudomonas entomophila and observe extensive variation in survival. Using genome-wide association analysis, we identify several novel immune modulators. Transcriptional profiling further shows that the intestinal molecular state differs between resistant and susceptible lines, already before infection, with one transcriptional module involving genes linked to reactive oxygen species (ROS) metabolism contributing to this difference. This genetic and molecular variation is physiologically manifested in lower ROS activity, lower susceptibility to ROS-inducing agent, faster pathogen clearance and higher stem cell activity in resistant versus susceptible lines. This study provides novel insights into the determinants underlying population-level variability in gut immunocompetence, revealing how relatively minor, but systematic genetic and transcriptional variation can mediate overt physiological differences that determine enteric infection susceptibility.

  16. Observed differences in learning ability of heart rate self-regulation as a function of hypnotic susceptibility

    NASA Technical Reports Server (NTRS)

    Cowings, P. S.

    1977-01-01

    Three groups of eight male and female subjects (aged 20-27 yr) categorized by low and high hypnotic susceptibility were taught to control their heart rates by means of an appropriate autogenic therapy/biofeedback technique. The experimental groups were trained by autogenic therapy and biofeedback, while the control group received only biofeedback. Significant differences are observed in all psychological test scores between subjects of high and low hypnotic susceptibility. The results confirm that (1) there are qualitative and quantitative differences between the performance of individuals with high and low hypnotic susceptibility; (2) interindividual-variability tests yield data relevant to individual performance in visceral learning tasks; (3) the combined autogenic therapy/biofeedback/verbal feedback technique is suitable for conditioning large stable autonomic responses in humans; and (4) this kind of conditioning is effective in eliminating or alleviating physiological reactions to some environmental stressors.

  17. 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.

  18. Sex and age-specific differences in ultraviolet reflectance of scent marks of bank voles (Clethrionomys glareolus).

    PubMed

    Koivula, M; Koskela, E; Viitala, J

    1999-12-01

    Scent markings of voles are visible via their ultraviolet reflection. Kestrels, and possibly other diurnal raptors, may use this property when hunting. We performed a laboratory study on bank voles to determine whether UV-reflectance of scent marks differs in relation to sex, age and social status. When reflectance spectra of scent marks were measured with a spectro-radiometer, we found UV reflectance to be strongest in mature males. There were no differences between mature females and immature juveniles, nor between sexes in juveniles or mature and immature individuals in females. Moreover, we did not find any difference in UV reflectance between dominant and subordinate mature males. The results of this study support earlier findings that UV sensitive predators may use UV reflectance of scent marks as a prey cue. Consequently, studies on differing vulnerability of voles to avian predators should take into account not only their space use and behaviour but also the UV reflectance of their scent marks.

  19. A Morphological and Morphometric Study of Bite Marks Caused by Mice (Mus Musculus) on Different Baits for Forensic Purposes.

    PubMed

    Toledo, Víctor A; Fonseca, Gabriel M; González, Paula A; Ibarra, Luis; Torres, Francisco J; Sáez, Pedro L

    2017-03-01

    In animal bites, the dental attributes can be fundamental in identifying the marks made by various species on different matrices. Although rodent bite marks have been studied in the context of postmortem interference, little research has used different baits to analyze these marks linking not only specific behavior patterns but also the possibility of structural damage. Twenty mice (Mus musculus) were exposed to different baits to study their bite marks in a controlled model. The known pattern of parallel and multiple grooves has been seen in all baits, but polyvinyl chloride and fiber-optic cable were significantly different between each other and the other baits. Some baits showed patterns of anchorage of the upper incisors and space between the lower incisors when gnawing. This technical note represents a novel model of analysis where veterinarians and/or dentists may be asked to give an opinion on alleged animal bite marks. © 2016 American Academy of Forensic Sciences.

  20. 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

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