A cross-cultural convergent parallel mixed methods study of what makes a cancer-related symptom or functional health problem clinically important.

PubMed

Giesinger, Johannes M; Aaronson, Neil K; Arraras, Juan I; Efficace, Fabio; Groenvold, Mogens; Kieffer, Jacobien M; Loth, Fanny L; Petersen, Morten Aa; Ramage, John; Tomaszewski, Krzysztof A; Young, Teresa; Holzner, Bernhard

2018-02-01

In this study, we investigated what makes a symptom or functional impairment clinically important, that is, relevant for a patient to discuss with a health care professional (HCP). This is the first part of a European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group project focusing on the development of thresholds for clinical importance for the EORTC QLQ-C30 questionnaire and its corresponding computer-adaptive version. We conducted interviews with cancer patients and HCPs in 6 European countries. Participants were asked to name aspects of a symptom or problem that make it clinically important and to provide importance ratings for a predefined set of aspects (eg, need for help and limitations of daily functioning). We conducted interviews with 83 cancer patients (mean age, 60.3 y; 50.6% men) and 67 HCPs. Participants related clinical importance to limitations of everyday life (patients, 65.1%; HCPs, 77.6%), the emotional impact of a symptom/problem (patients, 53.0%; HCPs, 64.2%), and duration/frequency (patients, 51.8%; HCPs, 49.3%). In the patient sample, importance ratings were highest for worries by partner or family, limitations in everyday life, and need for help from the medical staff. Health care professionals rated limitations in everyday life and need for help from the medical staff to be most important. Limitations in everyday life, need for (medical) help, and emotional impact on the patient or family/partner were found to be relevant aspects of clinical importance. Based on these findings, we will define anchor items for the development of thresholds for clinical importance for the EORTC measures in a Europe-wide field study. Copyright © 2017 John Wiley & Sons, Ltd.

Threshold concepts in prosthetics.

PubMed

Hill, Sophie

2017-12-01

Curriculum documents identify key concepts within learning prosthetics. Threshold concepts provide an alternative way of viewing the curriculum, focussing on the ways of thinking and practicing within prosthetics. Threshold concepts can be described as an opening to a different way of viewing a concept. This article forms part of a larger study exploring what students and staff experience as difficult in learning about prosthetics. To explore possible threshold concepts within prosthetics. Qualitative, interpretative phenomenological analysis. Data from 18 students and 8 staff at two universities with undergraduate prosthetics and orthotics programmes were generated through interviews and questionnaires. The data were analysed using an interpretative phenomenological analysis approach. Three possible threshold concepts arose from the data: 'how we walk', 'learning to talk' and 'considering the person'. Three potential threshold concepts in prosthetics are suggested with possible implications for prosthetics education. These possible threshold concepts involve changes in both conceptual and ontological knowledge, integrating into the persona of the individual. This integration occurs through the development of memories associated with procedural concepts that combine with disciplinary concepts. Considering the prosthetics curriculum through the lens of threshold concepts enables a focus on how students learn to become prosthetists. Clinical relevance This study provides new insights into how prosthetists learn. This has implications for curriculum design in prosthetics education.

Treatment of osteoporosis in men

PubMed Central

Kaufman, J.-M.; Reginster, J.-Y.; Boonen, S.; Brandi, M. L.; Cooper, C.; Dere, W.; Devogelaer, J.-P.; Diez-Perez, A.; Kanis, J. A.; McCloskey, E.; Mitlak, B.; Orwoll, E.; Ringe, J.D.; Weryha, G.; Rizzoli, R.

2013-01-01

Summary Aspects of osteoporosis in men, such as screening and identification strategies, definitions of diagnosis and intervention thresholds, and treatment options (both approved and in the pipeline) are discussed. Introduction Awareness of osteoporosis in men is improving, although it remains under-diagnosed and under-treated. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) workshop was convened to discuss osteoporosis in men and to provide a report by a panel of experts (the authors). Methods A debate with an expert panel on preselected topics was conducted. Results and Conclusions Although additional fracture data are needed to endorse the clinical care of osteoporosis in men, consensus views were reached on diagnostic criteria and intervention thresholds. Empirical data in men display similarities with data acquired in women, despite pathophysiological differences, which may not be clinically relevant. Men should receive treatment at a similar 10-year fracture probability as in women. The design of mixed studies may reduce the lag between comparable treatments for osteoporosis in women becoming available in men. PMID:23201268

A threshold method for immunological correlates of protection

PubMed Central

2013-01-01

Background Immunological correlates of protection are biological markers such as disease-specific antibodies which correlate with protection against disease and which are measurable with immunological assays. It is common in vaccine research and in setting immunization policy to rely on threshold values for the correlate where the accepted threshold differentiates between individuals who are considered to be protected against disease and those who are susceptible. Examples where thresholds are used include development of a new generation 13-valent pneumococcal conjugate vaccine which was required in clinical trials to meet accepted thresholds for the older 7-valent vaccine, and public health decision making on vaccination policy based on long-term maintenance of protective thresholds for Hepatitis A, rubella, measles, Japanese encephalitis and others. Despite widespread use of such thresholds in vaccine policy and research, few statistical approaches have been formally developed which specifically incorporate a threshold parameter in order to estimate the value of the protective threshold from data. Methods We propose a 3-parameter statistical model called the a:b model which incorporates parameters for a threshold and constant but different infection probabilities below and above the threshold estimated using profile likelihood or least squares methods. Evaluation of the estimated threshold can be performed by a significance test for the existence of a threshold using a modified likelihood ratio test which follows a chi-squared distribution with 3 degrees of freedom, and confidence intervals for the threshold can be obtained by bootstrapping. The model also permits assessment of relative risk of infection in patients achieving the threshold or not. Goodness-of-fit of the a:b model may be assessed using the Hosmer-Lemeshow approach. The model is applied to 15 datasets from published clinical trials on pertussis, respiratory syncytial virus and varicella. Results Highly significant thresholds with p-values less than 0.01 were found for 13 of the 15 datasets. Considerable variability was seen in the widths of confidence intervals. Relative risks indicated around 70% or better protection in 11 datasets and relevance of the estimated threshold to imply strong protection. Goodness-of-fit was generally acceptable. Conclusions The a:b model offers a formal statistical method of estimation of thresholds differentiating susceptible from protected individuals which has previously depended on putative statements based on visual inspection of data. PMID:23448322

A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation.

PubMed

Kleikers, Pamela W M; Hooijmans, Carlijn; Göb, Eva; Langhauser, Friederike; Rewell, Sarah S J; Radermacher, Kim; Ritskes-Hoitinga, Merel; Howells, David W; Kleinschnitz, Christoph; Schmidt, Harald H H W

2015-08-27

Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX2 to be a major therapeutic target in stroke. Systematic review and MA of all available NOX2(-/y) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX2 as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.

Adaptive semantic tag mining from heterogeneous clinical research texts.

PubMed

Hao, T; Weng, C

2015-01-01

To develop an adaptive approach to mine frequent semantic tags (FSTs) from heterogeneous clinical research texts. We develop a "plug-n-play" framework that integrates replaceable unsupervised kernel algorithms with formatting, functional, and utility wrappers for FST mining. Temporal information identification and semantic equivalence detection were two example functional wrappers. We first compared this approach's recall and efficiency for mining FSTs from ClinicalTrials.gov to that of a recently published tag-mining algorithm. Then we assessed this approach's adaptability to two other types of clinical research texts: clinical data requests and clinical trial protocols, by comparing the prevalence trends of FSTs across three texts. Our approach increased the average recall and speed by 12.8% and 47.02% respectively upon the baseline when mining FSTs from ClinicalTrials.gov, and maintained an overlap in relevant FSTs with the base- line ranging between 76.9% and 100% for varying FST frequency thresholds. The FSTs saturated when the data size reached 200 documents. Consistent trends in the prevalence of FST were observed across the three texts as the data size or frequency threshold changed. This paper contributes an adaptive tag-mining framework that is scalable and adaptable without sacrificing its recall. This component-based architectural design can be potentially generalizable to improve the adaptability of other clinical text mining methods.

Old and in pain: Enduring and situational effects of cultural aging stereotypes on older people's pain experiences.

PubMed

Bernardes, S F; Marques, S; Matos, M

2015-08-01

This study aimed to investigate the interplay between enduring and situational aging stereotype (AS) effects in older adults' self-reports of clinical and experimentally induced pain. We expected that, as compared with the situational activation of positive AS or a neutral condition, the activation of negative AS would lead to more severe self-reports of clinical pain (H1, hypothesis 1), higher cold pressor task (CPT) pain threshold (H2) and lower CPT pain tolerance (H3), especially among older adults who more strongly endorsed AS. This was a prospective study across two moments in time. At time 1 (T1), 52 older adults (Mage  = 74.7; 51.9% women) filled out measures of cultural AS endorsement, clinical pain severity and interference. Three months afterwards (T2), some of these participants collaborated in an experimental study on the effects of AS activation on reported clinical pain (n = 40) and experimentally induced (using CPT) pain threshold and tolerance (n = 35). Our results supported H2, i.e., as compared with the activation of positive AS or a neutral condition, when negative AS were activated older adults showed higher CPT pain thresholds, but this effect was more salient among those who more strongly endorsed AS at T1. This study stresses the influence of cultural AS in older adults' pain experiences showing that the situational activation of negative AS greatly increases experimentally induced pain thresholds of elders who more strongly endorse those stereotypes. It also highlights the relevance of interventions at the level of the physical and/or social environments surrounding elders in pain. © 2014 European Pain Federation - EFIC®

Effect, Feasibility, and Clinical Relevance of Cell Enrichment in Large Volume Fat Grafting: A Systematic Review.

PubMed

Rasmussen, Bo Sonnich; Lykke Sørensen, Celine; Vester-Glowinski, Peter Viktor; Herly, Mikkel; Trojahn Kølle, Stig-Frederik; Fischer-Nielsen, Anne; Drzewiecki, Krzysztof Tadeusz

2017-07-01

Large volume fat grafting is limited by unpredictable volume loss; therefore, methods of improving graft retention have been developed. Fat graft enrichment with either stromal vascular fraction (SVF) cells or adipose tissue-derived stem/stromal cells (ASCs) has been investigated in several animal and human studies, and significantly improved graft retention has been reported. Improvement of graft retention and the feasibility of these techniques are equally important in evaluating the clinical relevance of cell enrichment. We conducted a systematic search of PubMed to identify studies on fat graft enrichment that used either SVF cells or ASCs, and only studies reporting volume assessment were included. A total of 38 articles (15 human and 23 animal) were included to investigate the effects of cell enrichment on graft retention as well as the feasibility and clinical relevance of cell-enriched fat grafting. Improvements in graft retention, the SVF to fat (SVF:fat) ratio, and the ASC concentration used for enrichment were emphasized. We proposed an increased retention rate greater than 1.5-fold relative to nonenriched grafts and a maximum SVF:fat ratio of 1:1 as the thresholds for clinical relevance and feasibility, respectively. Nine studies fulfilled these criteria, whereof 6 used ASCs for enrichment. We found no convincing evidence of a clinically relevant effect of SVF enrichment in humans. ASC enrichment has shown promising results in enhancing graft retention, but additional clinical trials are needed to substantiate this claim and also determine the optimal concentration of SVF cells/ASCs for enrichment. 4. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Recognition of speech in noise after application of time-frequency masks: Dependence on frequency and threshold parameters

PubMed Central

Sinex, Donal G.

2013-01-01

Binary time-frequency (TF) masks can be applied to separate speech from noise. Previous studies have shown that with appropriate parameters, ideal TF masks can extract highly intelligible speech even at very low speech-to-noise ratios (SNRs). Two psychophysical experiments provided additional information about the dependence of intelligibility on the frequency resolution and threshold criteria that define the ideal TF mask. Listeners identified AzBio Sentences in noise, before and after application of TF masks. Masks generated with 8 or 16 frequency bands per octave supported nearly-perfect identification. Word recognition accuracy was slightly lower and more variable with 4 bands per octave. When TF masks were generated with a local threshold criterion of 0 dB SNR, the mean speech reception threshold was −9.5 dB SNR, compared to −5.7 dB for unprocessed sentences in noise. Speech reception thresholds decreased by about 1 dB per dB of additional decrease in the local threshold criterion. Information reported here about the dependence of speech intelligibility on frequency and level parameters has relevance for the development of non-ideal TF masks for clinical applications such as speech processing for hearing aids. PMID:23556604

Opposite optimal current flow directions for induction of neuroplasticity and excitation threshold in the human motor cortex.

PubMed

Sommer, Martin; Norden, Christoph; Schmack, Lars; Rothkegel, Holger; Lang, Nicolas; Paulus, Walter

2013-05-01

Directional sensitivity is relevant for the excitability threshold of the human primary motor cortex, but its importance for externally induced plasticity is unknown. To study the influence of current direction on two paradigms inducing neuroplasticity by repetitive transcranial magnetic stimulation (rTMS). We studied short-lasting after-effects induced in the human primary motor cortex of 8 healthy subjects, using 5 Hz rTMS applied in six blocks of 200 pulses each, at 90% active motor threshold. We controlled for intensity, frequency, waveform and spinal effects. Only biphasic pulses with the effective component delivered in an anterioposterior direction (henceforth posteriorly directed) in the brain yielded an increase of motor-evoked potential (MEP) amplitudes outlasting rTMS. MEP latencies and F-wave amplitudes remained unchanged. Biphasic pulses directed posteroanterior (i.e. anteriorly) were ineffective, as were monophasic pulses from either direction. A 1 Hz study in a group of 12 healthy subjects confirmed facilitation after posteriorly directed biphasic pulses only. The anisotropy of the human primary motor cortex is relevant for induction of plasticity by subtreshold rTMS, with a current flow opposite to that providing lowest excitability thresholds. This is consistent with the idea of TMS primarily targeting cortical columns of the phylogenetically new M1 in the anterior bank of the central sulcus. For these, anteriorly directed currents are soma-depolarizing, therefore optimal for low thresholds, whereas posteriorly directed currents are soma-hyperpolarizing, likely dendrite-depolarizing and bested suited for induction of plasticity. Our findings should help focus and enhance rTMS effects in experimental and clinical settings. Copyright © 2013 Elsevier Inc. All rights reserved.

At-risk and intervention thresholds of occupational stress using a visual analogue scale

PubMed Central

Pereira, Bruno; Moustafa, Farès; Naughton, Geraldine; Lesage, François-Xavier; Lambert, Céline

2017-01-01

Background The visual analogue scale (VAS) is widely used in clinical practice by occupational physicians to assess perceived stress in workers. However, a single cut-off (black-or-white decision) inadequately discriminates between workers with and without stress. We explored an innovative statistical approach to distinguish an at-risk population among stressed workers, and to establish a threshold over which an action is urgently required, via the use of two cut-offs. Methods Participants were recruited during annual work medical examinations by a random sample of workers from five occupational health centres. We previously proposed a single cut-off of VAS stress in comparison with the Perceived Stress Scale (PSS14). Similar methodology was used in the current study, along with a gray zone approach. The lower limit of the gray zone supports sensitivity (“at-risk” threshold; interpreted as requiring closer surveillance) and the upper limit supports specificity (i.e. “intervention” threshold–emergency action required). Results We included 500 workers (49.6% males), aged 40±11 years, with a PSS14 score of 3.8±1.4 and a VAS score of 4.0±2.4. Using a receiver operating characteristic curve and the PSS cut-off score of 7.2, the optimal VAS threshold was 6.8 (sensitivity = 0.89, specificity = 0.87). The lower and upper thresholds of the gray zone were 5 and 8.2, respectively. Conclusions We identified two clinically relevant cut-offs on the VAS of stress: a first cut-off of 5.0 for an at-risk population, and a second cut-off of 8.2 over which an action is urgently required. Future investigations into the relationships between this upper threshold and deleterious events are required. PMID:28586383

[Does the Youth Psychopathic Traits Inventory (YPI) identify a clinically relevant subgroup among young offenders?].

PubMed

Mingers, Daniel; Köhler, Denis; Huchzermeier, Christian; Hinrichs, Günter

2017-01-01

Does the Youth Psychopathic Traits Inventory identify one or more high-risk subgroups among young offenders? Which recommendations for possible courses of action can be derived for individual clinical or forensic cases? Method: Model-based cluster analysis (Raftery, 1995) was conducted on a sample of young offenders (N = 445, age 14–22 years, M = 18.5, SD = 1.65). The resulting model was then tested for differences between clusters with relevant context variables of psychopathy. The variables included measures of intelligence, social competence, drug use, and antisocial behavior. Results: Three clusters were found (Low Trait, Impulsive/Irresponsible, Psychopathy) that differ highly significantly concerning YPI scores and the variables mentioned above. The YPI Scores Δ Low = 4.28 (Low Trait – Impulsive/Irresponsible) and Δ High = 6.86 (Impulsive/Irresponsible – Psychopathy) were determined to be thresholds between the clusters. The allocation of a person to be assessed within the calculated clusters allows for an orientation of consequent tests beyond the diagnosis of psychopathy. We conclude that the YPI is a valuable instrument for the assessment of young offenders, as it yields clinically and forensically relevant information concerning the cause and expected development of psychopathological behavior.

Montreal Cognitive Assessment for the diagnosis of Alzheimer's disease and other dementias.

PubMed

Davis, Daniel H J; Creavin, Sam T; Yip, Jennifer L Y; Noel-Storr, Anna H; Brayne, Carol; Cullum, Sarah

2015-10-29

Dementia is a progressive syndrome of global cognitive impairment with significant health and social care costs. Global prevalence is projected to increase, particularly in resource-limited settings. Recent policy changes in Western countries to increase detection mandates a careful examination of the diagnostic accuracy of neuropsychological tests for dementia. To determine the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) at various thresholds for dementia and its subtypes. We searched MEDLINE, EMBASE, BIOSIS Previews, Science Citation Index, PsycINFO and LILACS databases to August 2012. In addition, we searched specialised sources containing diagnostic studies and reviews, including MEDION (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence-based Laboratory Medicine) databases. We also searched ALOIS (Cochrane Dementia and Cognitive Improvement Group specialized register of diagnostic and intervention studies). We identified further relevant studies from the PubMed 'related articles' feature and by tracking key studies in Science Citation Index and Scopus. We also searched for relevant grey literature from the Web of Science Core Collection, including Science Citation Index and Conference Proceedings Citation Index (Thomson Reuters Web of Science), PhD theses and contacted researchers with potential relevant data. Cross-sectional designs where all participants were recruited from the same sample were sought; case-control studies were excluded due to high chance of bias. We searched for studies from memory clinics, hospital clinics, primary care and community populations. We excluded studies of early onset dementia, dementia from a secondary cause, or studies where participants were selected on the basis of a specific disease type such as Parkinson's disease or specific settings such as nursing homes. We extracted dementia study prevalence and dichotomised test positive/test negative results with thresholds used to diagnose dementia. This allowed calculation of sensitivity and specificity if not already reported in the study. Study authors were contacted where there was insufficient information to complete the 2x2 tables. We performed quality assessment according to the QUADAS-2 criteria.Methodological variation in selected studies precluded quantitative meta-analysis, therefore results from individual studies were presented with a narrative synthesis. Seven studies were selected: three in memory clinics, two in hospital clinics, none in primary care and two in population-derived samples. There were 9422 participants in total, but most of studies recruited only small samples, with only one having more than 350 participants. The prevalence of dementia was 22% to 54% in the clinic-based studies, and 5% to 10% in population samples. In the four studies that used the recommended threshold score of 26 or over indicating normal cognition, the MoCA had high sensitivity of 0.94 or more but low specificity of 0.60 or less. The overall quality and quantity of information is insufficient to make recommendations on the clinical utility of MoCA for detecting dementia in different settings. Further studies that do not recruit participants based on diagnoses already present (case-control design) but apply diagnostic tests and reference standards prospectively are required. Methodological clarity could be improved in subsequent DTA studies of MoCA by reporting findings using recommended guidelines (e.g. STARDdem). Thresholds lower than 26 are likely to be more useful for optimal diagnostic accuracy of MoCA in dementia, but this requires confirmation in further studies.

Demoralization in Patients With Substance Use and Co-Occurring Psychiatric Disorders.

PubMed

De Weert, Gerdien H; Markus, Wiebren; Kissane, David W; De Jong, Cornelis A J

2017-01-01

In recent years, treatment of substance use disorder has rekindled emphasis on recovery which, being a gradual process, starts with remoralization. In this study, we examine the level of demoralization throughout the treatment process for patients with comorbid substance dependence and psychiatric disorders. 217 patients with co-occurring disorders and 179 community-based individuals participated in this study. Demoralization was measured twice over one month as inpatient treatment happened. In contrast with the community sample, we found high levels of demoralization in the clinical cohort, with 86% of patients having demoralization scores above threshold. During the first month there was a statistically significant reduction in demoralization scores. However, clinically relevant change appeared limited, with only 3% of patients moving from dysfunctional to functional status in this naturalistic setting without targeted intervention aimed at remoralization. Although the level of demoralization is significantly improved during the first month of treatment, patients still remain strongly demoralized. Clinically relevant improvement is limited. It could be worthwhile to set up targeted interventions aimed at remoralization. Furthermore, we advocate for the assessment of demoralization in the clinical setting to monitor patients' treatment outcomes.

Cost-effectiveness of different strategies for selecting and treating individuals at increased risk of osteoporosis or osteopenia: a systematic review.

PubMed

Müller, Dirk; Pulm, Jannis; Gandjour, Afschin

2012-01-01

To compare cost-effectiveness modeling analyses of strategies to prevent osteoporotic and osteopenic fractures either based on fixed thresholds using bone mineral density or based on variable thresholds including bone mineral density and clinical risk factors. A systematic review was performed by using the MEDLINE database and reference lists from previous reviews. On the basis of predefined inclusion/exclusion criteria, we identified relevant studies published since January 2006. Articles included for the review were assessed for their methodological quality and results. The literature search resulted in 24 analyses, 14 of them using a fixed-threshold approach and 10 using a variable-threshold approach. On average, 70% of the criteria for methodological quality were fulfilled, but almost half of the analyses did not include medication adherence in the base case. The results of variable-threshold strategies were more homogeneous and showed more favorable incremental cost-effectiveness ratios compared with those based on a fixed threshold with bone mineral density. For analyses with fixed thresholds, incremental cost-effectiveness ratios varied from €80,000 per quality-adjusted life-year in women aged 55 years to cost saving in women aged 80 years. For analyses with variable thresholds, the range was €47,000 to cost savings. Risk assessment using variable thresholds appears to be more cost-effective than selecting high-risk individuals by fixed thresholds. Although the overall quality of the studies was fairly good, future economic analyses should further improve their methods, particularly in terms of including more fracture types, incorporating medication adherence, and including or discussing unrelated costs during added life-years. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Frontal plane hip and ankle sensorimotor function, not age, predicts unipedal stance time

PubMed Central

Allet, Lara; Kim, Hogene; Ashton-Miller, James; De Mott, Trina; Richardson, James K.

2011-01-01

Introduction Changes occur in muscles and nerves with aging. This study aimed to explore the relationship between unipedal stance time (UST) and frontal plane hip and ankle sensorimotor function in subjects with diabetic neuropathy. Methods UST, quantitative measures of frontal plane ankle proprioceptive thresholds, and ankle and hip motor function were tested in forty-one persons with a spectrum of lower limb sensorimotor function, ranging from healthy to moderately severe diabetic neuropathy. Results Frontal plane hip and ankle sensorimotor function demonstrated significant relationships with UST. Multivariate analysis identified only composite hip strength, composite ankle proprioceptive threshold, and age to be significant predictors of UST (R2=0.73); they explained 46%, 24% and 3% of the variance, respectively. Discussion/Conclusions Frontal plane hip strength was the single best predictor of UST and appeared to compensate for less precise ankle proprioceptive thresholds. This finding is clinically relevant given the possibility of strengthening the hip, even in patients with significant PN. . PMID:22431092

Frontal plane hip and ankle sensorimotor function, not age, predicts unipedal stance time.

PubMed

Allet, Lara; Kim, Hogene; Ashton-Miller, James; De Mott, Trina; Richardson, James K

2012-04-01

Changes occur in muscles and nerves with aging. In this study we explore the relationship between unipedal stance time (UST) and frontal plane hip and ankle sensorimotor function in subjects with diabetic neuropathy. UST, quantitative measures of frontal plane ankle proprioceptive thresholds, and ankle and hip motor function were tested in 41 subjects with a spectrum of lower limb sensorimotor function ranging from healthy to moderately severe diabetic neuropathy. Frontal plane hip and ankle sensorimotor function demonstrated significant relationships with UST. Multivariate analysis identified only composite hip strength, ankle proprioceptive threshold, and age to be significant predictors of UST (R(2) = 0.73), explaining 46%, 24%, and 3% of the variance, respectively. Frontal plane hip strength was the single best predictor of UST and appeared to compensate for less precise ankle proprioceptive thresholds. This finding is clinically relevant given the possibility of strengthening the hip, even in patients with significant peripheral neuropathy. Copyright © 2011 Wiley Periodicals, Inc.

Hot of Not: Physiological versus Meteorological Heatwaves—Support for a Mean Temperature Threshold

PubMed Central

Luther, Matt; Gardiner, Fergus W.; Hansen, Claire; Caldicott, David

2016-01-01

The aim of this study was to determine whether a revised heat warning threshold provides an enhanced predictive tool for increases in Emergency Department heat-related presentations in Canberra, Australia. All Emergency Department triage records containing the word “heat”, as well as those diagnosing a heat related illness for the summer periods 2013/2014, 2014/2015, and 2015/2016 were searched. Then a medical record review was conducted to confirm that the patient’s presentation was related to environmental heat, which was defined by the final clinical diagnosis, presentation complaint and details of the patient’s treatment. Researchers then compared this presentation data, to a mean threshold formula. The mean threshold formula included the past three consecutive daily mean temperatures and the last measured temperature upon presentation. This formula was designed to take into account the variance of night-time lows, with concurrent daily ambient temperatures, and was used to determine whether there was a correlation between heat-related presentations and increasing mean temperatures. Heat-related presentations appeared to occur when the mean threshold temperature reached 25 °C (77 °F), with significant increases when the mean threshold reached 30 °C (86 °F). These results confirm that a mean temperature of 30 °C corresponds to a relevant local public health heat-related threat. PMID:27472348

Thinking individuation forward.

PubMed

Tresan, David

2007-02-01

This paper extends Jung's theory of individuation as faithfully elaborated by Joseph L. Henderson in his authoritative book Thresholds of Initiation. It addresses analyses that continue over very many years with analysands said to be individuated and proposes psychodynamics that explain and support such work that is otherwise beyond formal theoretical justification. In so doing, the paper addresses both Jung's and Henderson's refusal to explore the relevance of metaphysics for psychology and offers both a theoretical corrective for this shortcoming and a clinical illustration in support of an expanded point of view. In the course of the paper, personal material from interviews with Dr. Henderson, aged 101, serve as a substrate, both to support the above considerations and to shed new light on the development of his thought that led to Thresholds of Initiation.

Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects.

PubMed

Le Prell, Colleen G; Dell, Shawna; Hensley, Brittany; Hall, James W; Campbell, Kathleen C M; Antonelli, Patrick J; Green, Glenn E; Miller, James M; Guire, Kenneth

2012-01-01

One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects. Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later. Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure. These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values.

Reliability, standard error, and minimum detectable change of clinical pressure pain threshold testing in people with and without acute neck pain.

PubMed

Walton, David M; Macdermid, Joy C; Nielson, Warren; Teasell, Robert W; Chiasson, Marco; Brown, Lauren

2011-09-01

Clinical measurement. To evaluate the intrarater, interrater, and test-retest reliability of an accessible digital algometer, and to determine the minimum detectable change in normal healthy individuals and a clinical population with neck pain. Pressure pain threshold testing may be a valuable assessment and prognostic indicator for people with neck pain. To date, most of this research has been completed using algometers that are too resource intensive for routine clinical use. Novice raters (physiotherapy students or clinical physiotherapists) were trained to perform algometry testing over 2 clinically relevant sites: the angle of the upper trapezius and the belly of the tibialis anterior. A convenience sample of normal healthy individuals and a clinical sample of people with neck pain were tested by 2 different raters (all participants) and on 2 different days (healthy participants only). Intraclass correlation coefficient (ICC), standard error of measurement, and minimum detectable change were calculated. A total of 60 healthy volunteers and 40 people with neck pain were recruited. Intrarater reliability was almost perfect (ICC = 0.94-0.97), interrater reliability was substantial to near perfect (ICC = 0.79-0.90), and test-retest reliability was substantial (ICC = 0.76-0.79). Smaller change was detectable in the trapezius compared to the tibialis anterior. This study provides evidence that novice raters can perform digital algometry with adequate reliability for research and clinical use in people with and without neck pain.

Is the diagnostic threshold for bulimia nervosa clinically meaningful?

PubMed

Chapa, Danielle A N; Bohrer, Brittany K; Forbush, Kelsie T

2018-01-01

The DSM-5 differentiates full- and sub-threshold bulimia nervosa (BN) according to average weekly frequencies of binge eating and inappropriate compensatory behaviors. This study was the first to evaluate the modified frequency criterion for BN published in the DSM-5. The purpose of this study was to test whether community-recruited adults (N=125; 83.2% women) with current full-threshold (n=77) or sub-threshold BN (n=48) differed in comorbid psychopathology and eating disorder (ED) illness duration, symptom severity, and clinical impairment. Participants completed the Clinical Impairment Assessment and participated in semi-structured clinical interviews of ED- and non-ED psychopathology. Differences between the sub- and full-threshold BN groups were assessed using MANOVA and Chi-square analyses. ED illness duration, age-of-onset, body mass index (BMI), alcohol and drug misuse, and the presence of current and lifetime mood or anxiety disorders did not differ between participants with sub- and full-threshold BN. Participants with full-threshold BN had higher levels of clinical impairment and weight concern than those with sub-threshold BN. However, minimal clinically important difference analyses suggested that statistically significant differences between participants with sub- and full-threshold BN on clinical impairment and weight concern were not clinically significant. In conclusion, sub-threshold BN did not differ from full-threshold BN in clinically meaningful ways. Future studies are needed to identify an improved frequency criterion for BN that better distinguishes individuals in ways that will more validly inform prognosis and effective treatment planning for BN. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioengineering Spin-Offs from Dynamical Systems Theory

NASA Astrophysics Data System (ADS)

Collins, J. J.

1997-03-01

Recently, there has been considerable interest in applying concepts and techniques from dynamical systems and statistical physics to physiological systems. In this talk, we present work dealing which two active topics in this area: stochastic resonance and (2) chaos control. Stochastic resonance is a phenomenon wherein the response of nonlinear system to a weak input signal is optimally enhanced by the presence of a particular level of noise. Here we demonstrate that noise-based techniques can be used to lower sensory detection thresholds in humans. We discuss how from a bioengineering and clinical standpoint, these developments may be particularly relevant for individuals with elevated sensory thresholds, such as older adults and patients with peripheral neuropathy. Chaos control techniques have been applied to a wide range of experimental systems, including biological preparations. The application of chaos control to biological systems has led to speculations that these methods may be clinically useful. Here we demonstrate that the principles of chaos control can be utilized to stabilize underlying unstable periodic orbits in non-chaotic biological systems. We discuss how from a bioengineering and clinical standpoint, these developments may be important for suppressing or eliminating certain types of cardiac arrhythmias.

Clinical trial considerations on male contraception and collection of pregnancy information from female partner: update.

PubMed

Banholzer, Maria Longauer; Wandel, Christoph; Barrow, Paul; Mannino, Marie; Schmitt, Georg; Guérard, Melanie; Müller, Lutz; Greig, Gerard; Amemiya, Kenjie; Peck, Richard; Singer, Thomas; Doessegger, Lucette

2016-12-01

This is an update to our 2012 publication on clinical trial considerations on male contraception and collection of pregnancy information from female partner, after critical review of recent (draft) guidances released by the International Council for Harmonisation [ICH] the Clinical Trial Facilitation Group [CTFG] and the US Food & Drug Administration [FDA]. Relevant aspects of the new guidance documents are discussed in the context of male contraception and pregnancy reporting from female partner in clinical trials and the approach is updated accordingly. Genotoxicity The concept of a threshold is introduced using acceptable daily intake/permissible daily exposure to define genotoxicity requirements, hence highly effective contraception in order to avoid conception. The duration for highly effective contraception has been extended from 74 to 90 days from the end of relevant systemic exposure. Teratogenicity Pharmacokinetic considerations to estimate safety margins have been contextualized with regard to over- and underestimation of the risk of teratogenicity transmitted by a vaginal dose. The duration of male contraception after the last dose takes into account the end of relevant systemic exposure if measured, or a default period of five half-lives after last dose for small molecules and two half-lives for immunoglobulins (mAbs). Measures to prevent exposure of the conceptus via a vaginal dose apply to reproductively competent or vasectomized men, unless measurements fail to detect the compound in seminal fluid. Critical review of new guidance documents provides a comparison across approaches and resulted in an update of our previous publication. Separate algorithms for small molecules and monoclonal antibodies are proposed to guide the recommendations for contraception for male trial participants and pregnancy reporting from female partners. No male contraception is required if the dose is below a defined threshold for genotoxic concern applicable to small molecules. For men treated with teratogenic mAbs, condom use to prevent exposure of a potentially pregnant partner is unlikely to be recommended because of the minimal female exposure anticipated following a vaginal dose. The proposed safety margins for teratogenicity may evolve with further knowledge.

Collection of annotated data in a clinical validation study for alarm algorithms in intensive care--a methodologic framework.

PubMed

Siebig, Sylvia; Kuhls, Silvia; Imhoff, Michael; Langgartner, Julia; Reng, Michael; Schölmerich, Jürgen; Gather, Ursula; Wrede, Christian E

2010-03-01

Monitoring of physiologic parameters in critically ill patients is currently performed by threshold alarm systems with high sensitivity but low specificity. As a consequence, a multitude of alarms are generated, leading to an impaired clinical value of these alarms due to reduced alertness of the intensive care unit (ICU) staff. To evaluate a new alarm procedure, we currently generate a database of physiologic data and clinical alarm annotations. Data collection is taking place at a 12-bed medical ICU. Patients with monitoring of at least heart rate, invasive arterial blood pressure, and oxygen saturation are included in the study. Numerical physiologic data at 1-second intervals, monitor alarms, and alarm settings are extracted from the surveillance network. Bedside video recordings are performed with network surveillance cameras. Based on the extracted data and the video recordings, alarms are clinically annotated by an experienced physician. The alarms are categorized according to their technical validity and clinical relevance by a taxonomy system that can be broadly applicable. Preliminary results showed that only 17% of the alarms were classified as relevant, and 44% were technically false. The presented system for collecting real-time bedside monitoring data in conjunction with video-assisted annotations of clinically relevant events is the first allowing the assessment of 24-hour periods and reduces the bias usually created by bedside observers in comparable studies. It constitutes the basis for the development and evaluation of "smart" alarm algorithms, which may help to reduce the number of alarms at the ICU, thereby improving patient safety. Copyright 2010 Elsevier Inc. All rights reserved.

Molindone hydrochloride: a review of laboratory and clinical findings.

PubMed

Owen, R R; Cole, J O

1989-08-01

Molindone hydrochloride, a dihydroindolone neuroleptic, is structurally distinct from other classes of neuroleptics. Molindone exhibits many similarities to other neuroleptics, including dopamine receptor blockade, antipsychotic efficacy, and extrapyramidal side effects. Despite these similarities, molindone also has atypical properties and inhibits the enzyme monoamine oxidase in vitro and in vivo. Several studies have shown that molindone causes less dopamine receptor supersensitivity than other neuroleptics and thus may be less likely to cause tardive dyskinesia. It also appears to have a greater effect on mesolimbic and mesocortical dopamine neurons than on those in the nigrostriatal dopamine system. Clinically, molindone has a tendency to cause weight loss and may have less effect on seizure threshold than conventional antipsychotic agents. The authors review the laboratory and clinical data on molindone and discuss the relevance of atypical research findings to the clinical characteristics of this antipsychotic agent.

Regulation of non-relevant metabolites of plant protection products in drinking and groundwater in the EU: Current status and way forward.

PubMed

Laabs, V; Leake, C; Botham, P; Melching-Kollmuß, S

2015-10-01

Non-relevant metabolites are defined in the EU regulation for plant protection product authorization and a detailed definition of non-relevant metabolites is given in an EU Commission DG Sanco (now DG SANTE - Health and Food Safety) guidance document. However, in water legislation at EU and member state level non-relevant metabolites of pesticides are either not specifically regulated or diverse threshold values are applied. Based on their inherent properties, non-relevant metabolites should be regulated based on substance-specific and toxicity-based limit values in drinking and groundwater like other anthropogenic chemicals. Yet, if a general limit value for non-relevant metabolites in drinking and groundwater is favored, an application of a Threshold of Toxicological Concern (TTC) concept for Cramer class III compounds leads to a threshold value of 4.5 μg L(-1). This general value is exemplarily shown to be protective for non-relevant metabolites, based on individual drinking water limit values derived for a set of 56 non-relevant metabolites. A consistent definition of non-relevant metabolites of plant protection products, as well as their uniform regulation in drinking and groundwater in the EU, is important to achieve legal clarity for all stakeholders and to establish planning security for development of plant protection products for the European market. Copyright © 2015 Elsevier Inc. All rights reserved.

Minimum clinically important differences in chronic pain vary considerable by baseline pain and methodological factors: systematic review of empirical studies.

PubMed

Frahm Olsen, Mette; Bjerre, Eik; Hansen, Maria Damkjær; Tendal, Britta; Hilden, Jørgen; Hróbjartsson, Asbjørn

2018-05-21

The minimum clinically important difference (MCID) is used to interpret the relevance of treatment effects, e.g., when developing clinical guidelines, evaluating trial results or planning sample sizes. There is currently no agreement on an appropriate MCID in chronic pain and little is known about which contextual factors cause variation. This is a systematic review. We searched PubMed, EMBASE, and Cochrane Library. Eligible studies determined MCID for chronic pain based on a one-dimensional pain scale, a patient-reported transition scale of perceived improvement, and either a mean change analysis (mean difference in pain among minimally improved patients) or a threshold analysis (pain reduction associated with best sensitivity and specificity for identifying minimally improved patients). Main results were descriptively summarized due to considerable heterogeneity, which were quantified using meta-analyses and explored using subgroup analyses and metaregression. We included 66 studies (31.254 patients). Median absolute MCID was 23 mm on a 0-100 mm scale (interquartile range [IQR] 12-39) and median relative MCID was 34% (IQR 22-45) among studies using the mean change approach. In both cases, heterogeneity was very high: absolute MCID I 2  = 99% and relative MCID I 2  = 96%. High variation was also seen among studies using the threshold approach: median absolute MCID was 20 mm (IQR 15-30) and relative MCID was 32% (IQR 15-41). Absolute MCID was strongly associated with baseline pain, explaining approximately two-thirds of the variation, and to a lesser degree with the operational definition of minimum pain relief and clinical condition. A total of 15 clinical and methodological factors were assessed as possible causes for variation in MCID. MCID for chronic pain relief vary considerably. Baseline pain is strongly associated with absolute, but not relative, measures. To a much lesser degree, MCID is also influenced by the operational definition of relevant pain relief and possibly by clinical condition. Explicit and conscientious reflections on the choice of an MCID are required when classifying effect sizes as clinically important or trivial. Copyright © 2018 Elsevier Inc. All rights reserved.

Cumulative effects of HIV illness and caring for children orphaned by AIDS on anxiety symptoms among adults caring for children in HIV-endemic South Africa.

PubMed

Kuo, Caroline; Cluver, Lucie; Casale, Marisa; Lane, Tyler

2014-06-01

Adults caring for children in HIV-endemic communities are at risk for poor psychological outcomes. However, we still have a limited understanding of how various HIV impacts--including caregiver's own HIV illness, responsibilities of caring for a child orphaned by AIDS, or both--affect psychological outcomes among caregivers. Furthermore, few studies have explored the relationship between stigma, HIV, and psychological outcomes among caregivers of children in HIV-endemic communities. A cross-sectional survey conducted from 2009 to 2010 assessed anxiety among 2477 caregivers of children in HIV-endemic South Africa. Chi-square tested differences in anxiety among caregivers living with HIV, caregivers of a child orphaned by AIDS, and caregivers affected with both conditions. Multivariate logistic regressions identified whether the relationship between HIV impacts and anxiety remained after controlling for socio-demographic co-factors. Mediation analysis tested the relationship between stigma, HIV, and anxiety. The odds of meeting threshold criteria for clinically relevant anxiety symptoms were two and a half times greater among caregivers living with HIV compared to nonaffected caregivers. The odds of meeting threshold criteria for clinically relevant anxiety symptoms were greatest among caregivers living with HIV and caring for a child orphaned by AIDS. Exposure to AIDS-related stigma partially mediated the relationship between HIV and anxiety. Interventions are needed to address caregiver psychological health, particularly among caregivers affected with both conditions of living with HIV and caring for a child orphaned by AIDS.

Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review.

PubMed

Daru, J; Allotey, J; Peña-Rosas, J P; Khan, K S

2017-06-01

The aim of this review was to understand the landscape of serum ferritin in diagnosing iron deficiency in the aetiology of anaemia in pregnancy. Iron deficiency in pregnancy is a major public health problem leading to the development of anaemia. Reducing the global prevalence of anaemia in women of reproductive age is a 2025 global nutrition target. Bone marrow aspiration is the gold standard test for iron deficiency but requires an invasive procedure; therefore, serum ferritin is the most clinically useful test. We undertook a systematic search of electronic databases and trial registers from inception to January 2016. Studies of iron or micronutrient supplementation in pregnancy with pre-defined serum ferritin thresholds were included. Two independent reviewers selected studies, extracted data and assessed quality. There were 76 relevant studies mainly of observational study design (57%). The most commonly used thresholds of serum ferritin for the diagnosis of iron deficiency were <12 and <15 ng mL -1 (68%). Most primary studies provided no justification for the choice of serum ferritin threshold used, but 25 studies (33%) used thresholds defined by expert consensus in a guideline development process. There were five studies (7%) using a serum ferritin threshold defining iron deficiency derived from primary studies of bone marrow aspiration. Unified international thresholds of iron deficiency for women throughout pregnancy are required for accurate assessments of the global disease burden and for evaluating effectiveness of interventions addressing this problem. © 2017 World Health Organization licensed by Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.

Quantitative Ultrasound for Measuring Obstructive Severity in Children with Hydronephrosis.

PubMed

Cerrolaza, Juan J; Peters, Craig A; Martin, Aaron D; Myers, Emmarie; Safdar, Nabile; Linguraru, Marius George

2016-04-01

We define sonographic biomarkers for hydronephrotic renal units that can predict the necessity of diuretic nuclear renography. We selected a cohort of 50 consecutive patients with hydronephrosis of varying severity in whom 2-dimensional sonography and diuretic mercaptoacetyltriglycine renography had been performed. A total of 131 morphological parameters were computed using quantitative image analysis algorithms. Machine learning techniques were then applied to identify ultrasound based safety thresholds that agreed with the t½ for washout. A best fit model was then derived for each threshold level of t½ that would be clinically relevant at 20, 30 and 40 minutes. Receiver operating characteristic curve analysis was performed. Sensitivity, specificity and area under the receiver operating characteristic curve were determined. Improvement obtained by the quantitative imaging method compared to the Society for Fetal Urology grading system and the hydronephrosis index was statistically verified. For the 3 thresholds considered and at 100% sensitivity the specificities of the quantitative imaging method were 94%, 70% and 74%, respectively. Corresponding area under the receiver operating characteristic curve values were 0.98, 0.94 and 0.94, respectively. Improvement obtained by the quantitative imaging method over the Society for Fetal Urology grade and hydronephrosis index was statistically significant (p <0.05 in all cases). Quantitative imaging analysis of renal sonograms in children with hydronephrosis can identify thresholds of clinically significant washout times with 100% sensitivity to decrease the number of diuretic renograms in up to 62% of children. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Evaluation of quantification methods for real-time PCR minor groove binding hybridization probe assays.

PubMed

Durtschi, Jacob D; Stevenson, Jeffery; Hymas, Weston; Voelkerding, Karl V

2007-02-01

Real-time PCR data analysis for quantification has been the subject of many studies aimed at the identification of new and improved quantification methods. Several analysis methods have been proposed as superior alternatives to the common variations of the threshold crossing method. Notably, sigmoidal and exponential curve fit methods have been proposed. However, these studies have primarily analyzed real-time PCR with intercalating dyes such as SYBR Green. Clinical real-time PCR assays, in contrast, often employ fluorescent probes whose real-time amplification fluorescence curves differ from those of intercalating dyes. In the current study, we compared four analysis methods related to recent literature: two versions of the threshold crossing method, a second derivative maximum method, and a sigmoidal curve fit method. These methods were applied to a clinically relevant real-time human herpes virus type 6 (HHV6) PCR assay that used a minor groove binding (MGB) Eclipse hybridization probe as well as an Epstein-Barr virus (EBV) PCR assay that used an MGB Pleiades hybridization probe. We found that the crossing threshold method yielded more precise results when analyzing the HHV6 assay, which was characterized by lower signal/noise and less developed amplification curve plateaus. In contrast, the EBV assay, characterized by greater signal/noise and amplification curves with plateau regions similar to those observed with intercalating dyes, gave results with statistically similar precision by all four analysis methods.

Effects of programming threshold and maplaw settings on acoustic thresholds and speech discrimination with the MED-EL COMBI 40+ cochlear implant.

PubMed

Boyd, Paul J

2006-12-01

The principal task in the programming of a cochlear implant (CI) speech processor is the setting of the electrical dynamic range (output) for each electrode, to ensure that a comfortable loudness percept is obtained for a range of input levels. This typically involves separate psychophysical measurement of electrical threshold ([theta] e) and upper tolerance levels using short current bursts generated by the fitting software. Anecdotal clinical experience and some experimental studies suggest that the measurement of [theta]e is relatively unimportant and that the setting of upper tolerance limits is more critical for processor programming. The present study aims to test this hypothesis and examines in detail how acoustic thresholds and speech recognition are affected by setting of the lower limit of the output ("Programming threshold" or "PT") to understand better the influence of this parameter and how it interacts with certain other programming parameters. Test programs (maps) were generated with PT set to artificially high and low values and tested on users of the MED-EL COMBI 40+ CI system. Acoustic thresholds and speech recognition scores (sentence tests) were measured for each of the test maps. Acoustic thresholds were also measured using maps with a range of output compression functions ("maplaws"). In addition, subjective reports were recorded regarding the presence of "background threshold stimulation" which is occasionally reported by CI users if PT is set to relatively high values when using the CIS strategy. Manipulation of PT was found to have very little effect. Setting PT to minimum produced a mean 5 dB (S.D. = 6.25) increase in acoustic thresholds, relative to thresholds with PT set normally, and had no statistically significant effect on speech recognition scores on a sentence test. On the other hand, maplaw setting was found to have a significant effect on acoustic thresholds (raised as maplaw is made more linear), which provides some theoretical explanation as to why PT has little effect when using the default maplaw of c = 500. Subjective reports of background threshold stimulation showed that most users could perceive a relatively loud auditory percept, in the absence of microphone input, when PT was set to double the behaviorally measured electrical thresholds ([theta]e), but that this produced little intrusion when microphone input was present. The results of these investigations have direct clinical relevance, showing that setting of PT is indeed relatively unimportant in terms of speech discrimination, but that it is worth ensuring that PT is not set excessively high, as this can produce distracting background stimulation. Indeed, it may even be set to minimum values without deleterious effect.

Differentiation of low-attenuation intracranial hemorrhage and calcification using dual-energy computed tomography in a phantom system

PubMed Central

Nute, Jessica L.; Roux, Lucia Le; Chandler, Adam G.; Baladandayuthapani, Veera; Schellingerhout, Dawid; Cody, Dianna D.

2015-01-01

Objectives Calcific and hemorrhagic intracranial lesions with attenuation levels of <100 Hounsfield Units (HU) cannot currently be reliably differentiated by single-energy computed tomography (SECT). The proper differentiation of these lesion types would have a multitude of clinical applications. A phantom model was used to test the ability of dual-energy CT (DECT) to differentiate such lesions. Materials and Methods Agar gel-bound ferric oxide and hydroxyapatite were used to model hemorrhage and calcification, respectively. Gel models were scanned using SECT and DECT and organized into SECT attenuation-matched pairs at 16 attenuation levels between 0 and 100 HU. DECT data were analyzed using 3D Gaussian mixture models (GMMs), as well as a simplified threshold plane metric derived from the 3D GMM, to assign voxels to hemorrhagic or calcific categories. Accuracy was calculated by comparing predicted voxel assignments with actual voxel identities. Results We measured 6,032 voxels from each gel model, for a total of 193,024 data points (16 matched model pairs). Both the 3D GMM and its more clinically implementable threshold plane derivative yielded similar results, with >90% accuracy at matched SECT attenuation levels ≥50 HU. Conclusions Hemorrhagic and calcific lesions with attenuation levels between 50 and 100 HU were differentiable using DECT in a clinically relevant phantom system with >90% accuracy. This method warrants further testing for potential clinical applications. PMID:25162534

Digital music exposure reliably induces temporary threshold shift (TTS) in normal hearing human subjects

PubMed Central

Le Prell, C. G.; Dell, S.; Hensley, B.; Hall, J. W.; Campbell, K. C. M.; Antonelli, P. J.; Green, G. E.; Miller, J. M.; Guire, K.

2012-01-01

Objectives One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is availability of an established clinical paradigm with real world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal hearing human subjects. Design Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93–95 (n=10), 98–100 (n=11), or 100–102 (n=12) dBA in-ear exposure level for a period of four hours. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured prior to and after music exposure. Post-music tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and one week later. Results Changes in thresholds after the lowest level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a “notch” configuration, with the largest changes observed at 4 kHz (mean=6.3±3.9dB; range=0–13 dB). Recovery was largely complete within the first 4 hours post-exposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1-week post-exposure. Conclusions These data provide insight into the variability of TTS induced by music player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function following digital music player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values. PMID:22885407

Rare Variation in TET2 Is Associated with Clinically Relevant Prostate Carcinoma in African-Americans

PubMed Central

Koboldt, Daniel C.; Kanchi, Krishna L.; Gui, Bin; Larson, David E.; Fulton, Robert S.; Isaacs, William B.; Kraja, Aldi; Borecki, Ingrid B.; Jia, Li; Wilson, Richard K.; Mardis, Elaine R.; Kibel, Adam S.

2016-01-01

Background Common variants have been associated with prostate cancer risk. Unfortunately, few are reproducibly linked to aggressive disease, the phenotype of greatest clinical relevance. One possible explanation is that rare genetic variants underlie a significant proportion of the risk for aggressive disease. Method To identify such variants, we performed a two staged approach using whole exome sequencing followed by targeted sequencing of 800 genes in 652 aggressive prostate cancer patients and 752 disease-free controls in both African and European Americans. In each population, we tested rare variants for association using two gene-based aggregation tests. We established a study-wide significance threshold of 3.125 × 10−5 to correct for multiple testing. Results TET2 in African-Americans was associated with aggressive disease with 24.4% of cases harboring a rare deleterious variant compared to 9.6% of controls (FET p = 1.84×10−5, OR=3.0; SKAT-O p= 2.74×10−5). We report 8 additional genes with suggestive evidence of association, including the DNA repair genes PARP2 and MSH6. Finally, we observed an excess of rare truncation variants in 5 genes including the DNA repair genes MSH6, BRCA1 and BRCA2. This adds to the growing body of evidence that DNA repair pathway defects may influence susceptibility to aggressive prostate cancer. Conclusion Our findings suggest that rare variants influence risk of clinically relevant prostate cancer and, if validated, could serve to identify men for screening, prophylaxis and treatment. Impact This study provides evidence that rare variants in TET2 may help identify African-American men at increased risk for clinically relevant prostate cancer. PMID:27486019

Visual Field Defects and Retinal Ganglion Cell Losses in Human Glaucoma Patients

PubMed Central

Harwerth, Ronald S.; Quigley, Harry A.

2007-01-01

Objective The depth of visual field defects are correlated with retinal ganglion cell densities in experimental glaucoma. This study was to determine whether a similar structure-function relationship holds for human glaucoma. Methods The study was based on retinal ganglion cell densities and visual thresholds of patients with documented glaucoma (Kerrigan-Baumrind, et al.) The data were analyzed by a model that predicted ganglion cell densities from standard clinical perimetry, which were then compared to histologic cell counts. Results The model, without free parameters, produced accurate and relatively precise quantification of ganglion cell densities associated with visual field defects. For 437 sets of data, the unity correlation for predicted vs. measured cell densities had a coefficient of determination of 0.39. The mean absolute deviation of the predicted vs. measured values was 2.59 dB, the mean and SD of the distribution of residual errors of prediction was -0.26 ± 3.22 dB. Conclusions Visual field defects by standard clinical perimetry are proportional to neural losses caused by glaucoma. Clinical Relevance The evidence for quantitative structure-function relationships provides a scientific basis of interpreting glaucomatous neuropathy from visual thresholds and supports the application of standard perimetry to establish the stage of the disease. PMID:16769839

Technical evaluation of the novel preanalytical module on instrumentation laboratory ACL TOP: advancing automation in hemostasis testing.

PubMed

Lippi, Giuseppe; Ippolito, Luigi; Favaloro, Emmanuel J

2013-10-01

Automation in hemostasis testing is entering an exciting and unprecedented phase. This study was planned to assess the performance of the new preanalytical module on the hemostasis testing system Instrumentation Laboratory ACL TOP. The evaluation included interference studies to define reliable thresholds for rejecting samples with significant concentrations of interfering substances; within-run imprecision studies of plasma indices on four different interference degrees for each index; comparison studies with reference measures of hemolysis index, bilirubin, and triglycerides on clinical chemistry analyzers; and calculation of turnaround time with and without automatic performance of preanalytical check. The upper limits for sample rejection according to our interference studies were 3.6 g/L for hemoglobin, 13.6 mg/dL for bilirubin, and 1454 mg/dL for triglycerides. We found optimal precision for all indices (0.6% to 3.1% at clinically relevant thresholds) and highly significant correlations with reference measures on clinical chemistry analyzers (from 0.985 to 0.998). The limited increase of turnaround time (i.e., +3% and +5% with or without cap-piercing), coupled with no adjunctive costs over performance of normal coagulation assays, contribute to make the automatic check of plasma indices on ACL TOP a reliable and practical approach for improving testing quality and safeguarding patient safety.

Thermal quantitative sensory testing to assess the sensory effects of three local anesthetic solutions in a randomized trial of interscalene blockade for shoulder surgery.

PubMed

Sermeus, Luc A; Hans, Guy H; Schepens, Tom; Bosserez, Nathalie M-L; Breebaart, Margaretha B; Smitz, Carine J; Vercauteren, Marcel P

2016-01-01

This study investigated whether quantitative sensory testing (QST) with thermal stimulations can quantitatively measure the characteristics of an ultrasound-guided interscalene brachial plexus block (US-ISB). This was a prospective randomized trial in patients scheduled for arthroscopic shoulder surgery under general anesthesia and US-ISB. Participants and observers were blinded for the study. We assigned the study participants to one of three groups: 0.5% levobupivacaine 15 mL, 0.5% levobupivacaine 15 mL with 1:200,000 epinephrine, and 0.75% ropivacaine 15 mL. We performed thermal QST within dermatomes C4, C5, C6, and C7 before infiltration and 30 min, six hours, ten hours, and 24 hr after performing the US-ISB. In addition, we used QST, a semi-objective quantitative testing method, to measure the onset, intensity, duration, extent, and functional recovery of the sensory block. We also measured detection thresholds for cold/warm sensations and cold/heat pain. Detection thresholds for all thermal sensations within the ipsilateral C4, C5, C6, and C7 dermatomes increased rapidly (indicating the development of a hypoesthetic state) and reached a steady state after 30 min. This lasted for approximately ten hours and returned to normal detection thresholds by 24 hr. There were no differences detected between the three groups at 24 hr when we compared warm sensation thresholds on one dermatome. Visual inspection of the pooled results per dermatome suggests the ability of QST to detect clinically relevant differences in block intensity per dermatome. Quantitative sensory testing can be useful as a method for detecting the presence and characteristics of regional anesthesia-induced sensory block and may be used for the evaluation of clinical protocols. The three local anesthetic solutions exhibited a similar anesthetic effect. The results support the use of QST to assess block characteristics quantitatively under clinical research conditions. This trial was registered at Clinicaltrals.gov, NCT02271867.

Physiologic basis for understanding quantitative dehydration assessment.

PubMed

Cheuvront, Samuel N; Kenefick, Robert W; Charkoudian, Nisha; Sawka, Michael N

2013-03-01

Dehydration (body water deficit) is a physiologic state that can have profound implications for human health and performance. Unfortunately, dehydration can be difficult to assess, and there is no single, universal gold standard for decision making. In this article, we review the physiologic basis for understanding quantitative dehydration assessment. We highlight how phenomenologic interpretations of dehydration depend critically on the type (dehydration compared with volume depletion) and magnitude (moderate compared with severe) of dehydration, which in turn influence the osmotic (plasma osmolality) and blood volume-dependent compensatory thresholds for antidiuretic and thirst responses. In particular, we review new findings regarding the biological variation in osmotic responses to dehydration and discuss how this variation can help provide a quantitative and clinically relevant link between the physiology and phenomenology of dehydration. Practical measures with empirical thresholds are provided as a starting point for improving the practice of dehydration assessment.

Estimation of pulse rate from ambulatory PPG using ensemble empirical mode decomposition and adaptive thresholding.

PubMed

Pittara, Melpo; Theocharides, Theocharis; Orphanidou, Christina

2017-07-01

A new method for deriving pulse rate from PPG obtained from ambulatory patients is presented. The method employs Ensemble Empirical Mode Decomposition to identify the pulsatile component from noise-corrupted PPG, and then uses a set of physiologically-relevant rules followed by adaptive thresholding, in order to estimate the pulse rate in the presence of noise. The method was optimized and validated using 63 hours of data obtained from ambulatory hospital patients. The F1 score obtained with respect to expertly annotated data was 0.857 and the mean absolute errors of estimated pulse rates with respect to heart rates obtained from ECG collected in parallel were 1.72 bpm for "good" quality PPG and 4.49 bpm for "bad" quality PPG. Both errors are within the clinically acceptable margin-of-error for pulse rate/heart rate measurements, showing the promise of the proposed approach for inclusion in next generation wearable sensors.

Smartphone threshold audiometry in underserved primary health-care contexts.

PubMed

Sandström, Josefin; Swanepoel, De Wet; Carel Myburgh, Hermanus; Laurent, Claude

2016-01-01

To validate a calibrated smartphone-based hearing test in a sound booth environment and in primary health-care clinics. A repeated-measure within-subject study design was employed whereby air-conduction hearing thresholds determined by smartphone-based audiometry was compared to conventional audiometry in a sound booth and a primary health-care clinic environment. A total of 94 subjects (mean age 41 years ± 17.6 SD and range 18-88; 64% female) were assessed of whom 64 were tested in the sound booth and 30 within primary health-care clinics without a booth. In the sound booth 63.4% of conventional and smartphone thresholds indicated normal hearing (≤15 dBHL). Conventional thresholds exceeding 15 dB HL corresponded to smartphone thresholds within ≤10 dB in 80.6% of cases with an average threshold difference of -1.6 dB ± 9.9 SD. In primary health-care clinics 13.7% of conventional and smartphone thresholds indicated normal hearing (≤15 dBHL). Conventional thresholds exceeding 15 dBHL corresponded to smartphone thresholds within ≤10 dB in 92.9% of cases with an average threshold difference of -1.0 dB ± 7.1 SD. Accurate air-conduction audiometry can be conducted in a sound booth and without a sound booth in an underserved community health-care clinic using a smartphone.

Sensitivity of frozen section histology for identifying Propionibacterium acnes infections in revision shoulder arthroplasty.

PubMed

Grosso, Matthew J; Frangiamore, Salvatore J; Ricchetti, Eric T; Bauer, Thomas W; Iannotti, Joseph P

2014-03-19

Propionibacterium acnes is a clinically relevant pathogen with total shoulder arthroplasty. The purpose of this study was to determine the sensitivity of frozen section histology in identifying patients with Propionibacterium acnes infection during revision total shoulder arthroplasty and investigate various diagnostic thresholds of acute inflammation that may improve frozen section performance. We reviewed the results of forty-five patients who underwent revision total shoulder arthroplasty. Patients were divided into the non-infection group (n = 15), the Propionibacterium acnes infection group (n = 18), and the other infection group (n = 12). Routine preoperative testing was performed and intraoperative tissue culture and frozen section histology were collected for each patient. The histologic diagnosis was determined by one pathologist for each of the four different thresholds. The absolute maximum polymorphonuclear leukocyte concentration was used to construct a receiver operating characteristics curve to determine a new potential optimal threshold. Using the current thresholds for grading frozen section histology, the sensitivity was lower for the Propionibacterium acnes infection group (50%) compared with the other infection group (67%). The specificity of frozen section was 100%. Using a receiver operating characteristics curve, an optimized threshold was found at a total of ten polymorphonuclear leukocytes in five high-power fields (400×). Using this threshold, the sensitivity of frozen section for Propionibacterium acnes was increased to 72%, and the specificity remained at 100%. Using current histopathology grading systems, frozen sections were specific but showed low sensitivity with respect to the Propionibacterium acnes infection. A new threshold value of a total of ten or more polymorphonuclear leukocytes in five high-power fields may increase the sensitivity of frozen section, with minimal impact on specificity.

Insights from internet-based remote intrathoracic impedance monitoring as part of a heart failure disease management program.

PubMed

Mullens, Wilfried; Oliveira, Leonardo P J; Verga, Tanya; Wilkoff, Bruce L; Tang, Wai Hong Wilson

2010-01-01

Changes in intrathoracic impedance (Z) leading to crossing of a derived fluid index (FI) threshold has been associated with heart failure (HF) hospitalization. The authors developed a remote monitoring program as part of HF disease management and prospectively examined the feasibility and resource utilization of monitoring individuals with an implanted device capable of measuring Z. An HF nurse analyzed all transmitted data daily, as they were routinely uploaded as part of quarterly remote device monitoring, and called the patient if the FI crossed the threshold (arbitrarily defined at 60 Omega) to identify clinically relevant events (CREs) that occurred during this period (eg, worsening dyspnea or increase in edema or weight). A total of 400 uploads were completed during the 4-month study period. During this period, 34 patients (18%) had an FI threshold crossing, averaging 0.52 FI threshold crossings per patient-year. Thirty-two of 34 patients contacted by telephone (94%) with FI threshold crossing had evidence of CREs during this period. However, only 6 (18%) had HF hospitalizations, 19 (56%) had reported changes in HF therapy, and 13 (38%) reported drug and/or dietary plan nonadherence. The average data analysis time required was 30 min daily when focusing on those with FI threshold crossing, averaging 8 uploads for review per working day and 5 telephone follow-ups per week. Our pilot observations suggested that Internet-based remote monitoring of Z trends from existing device interrogation uploads is feasible as part of a daily routine of HF disease management. 2010 Wiley Periodicals, Inc.

Do we need a threshold conception of competence?

PubMed

den Hartogh, Govert

2016-03-01

On the standard view we assess a person's competence by considering her relevant abilities without reference to the actual decision she is about to make. If she is deemed to satisfy certain threshold conditions of competence, it is still an open question whether her decision could ever be overruled on account of its harmful consequences for her ('hard paternalism'). In practice, however, one normally uses a variable, risk dependent conception of competence, which really means that in considering whether or not to respect a person's decision-making authority we weigh her decision on several relevant dimensions at the same time: its harmful consequences, its importance in terms of the person's own relevant values, the infringement of her autonomy involved in overruling it, and her decision-making abilities. I argue that we should openly recognize the multi-dimensional nature of this judgment. This implies rejecting both the threshold conception of competence and the categorical distinction between hard and soft paternalism.

Muscle Weakness Thresholds for Prediction of Diabetes in Adults

PubMed Central

Peterson, Mark D.; Zhang, Peng; Choksi, Palak; Markides, Kyriakos S.; Al Snih, Soham

2016-01-01

Background Despite the known links between weakness and early mortality, what remains to be fully understood is the extent to which strength preservation is associated with protection from cardiometabolic diseases such as diabetes. Purpose The purposes of this study were to determine the association between muscle strength and diabetes among adults, and to identify age- and sex-specific thresholds of low strength for detection of risk. Methods A population-representative sample of 4,066 individuals, aged 20–85 years, was included from the combined 2011–2012 National Health and Nutrition Examination Survey datasets. Strength was assessed using a hand-held dynamometer, and the single largest reading from either hand was normalized to body mass. A logistic regression model was used to assess the association between normalized grip strength and risk of diabetes, as determined by hemoglobin A1c (HbA1c) levels (≥6.5% [≥48 mmol/mol]), while controlling for sociodemographic characteristics, anthropometric measures, and television viewing time. Results For every 0.05 decrement in normalized strength, there was a 1.26 times increased adjusted odds for diabetes in men and women. Women were at lower odds of having diabetes (OR: 0.49; 95% CI: 0.29–0.82), whereas age, waist circumference and lower income were inversely associated. Optimal sex- and age-specific weakness thresholds to detect diabetes were 0.56, 0.50, and 0.45 for men, and 0.42, 0.38, and 0.33 for women, for ages 20–39 years, 40–59 years, and 60–80 years. Conclusions and Clinical Relevance We present thresholds of strength that can be incorporated into a clinical setting for identifying adults that are at risk for developing diabetes, and that might benefit from lifestyle interventions to reduce risk. PMID:26744337

Development and validation of a whole-exome sequencing test for simultaneous detection of point mutations, indels and copy-number alterations for precision cancer care

PubMed Central

Rennert, Hanna; Eng, Kenneth; Zhang, Tuo; Tan, Adrian; Xiang, Jenny; Romanel, Alessandro; Kim, Robert; Tam, Wayne; Liu, Yen-Chun; Bhinder, Bhavneet; Cyrta, Joanna; Beltran, Himisha; Robinson, Brian; Mosquera, Juan Miguel; Fernandes, Helen; Demichelis, Francesca; Sboner, Andrea; Kluk, Michael; Rubin, Mark A; Elemento, Olivier

2016-01-01

We describe Exome Cancer Test v1.0 (EXaCT-1), the first New York State-Department of Health-approved whole-exome sequencing (WES)-based test for precision cancer care. EXaCT-1 uses HaloPlex (Agilent) target enrichment followed by next-generation sequencing (Illumina) of tumour and matched constitutional control DNA. We present a detailed clinical development and validation pipeline suitable for simultaneous detection of somatic point/indel mutations and copy-number alterations (CNAs). A computational framework for data analysis, reporting and sign-out is also presented. For the validation, we tested EXaCT-1 on 57 tumours covering five distinct clinically relevant mutations. Results demonstrated elevated and uniform coverage compatible with clinical testing as well as complete concordance in variant quality metrics between formalin-fixed paraffin embedded and fresh-frozen tumours. Extensive sensitivity studies identified limits of detection threshold for point/indel mutations and CNAs. Prospective analysis of 337 cancer cases revealed mutations in clinically relevant genes in 82% of tumours, demonstrating that EXaCT-1 is an accurate and sensitive method for identifying actionable mutations, with reasonable costs and time, greatly expanding its utility for advanced cancer care. PMID:28781886

Cumulative Effects of HIV Illness and Caring for Children Orphaned by AIDS on Anxiety Symptoms Among Adults Caring for Children in HIV-Endemic South Africa

PubMed Central

Cluver, Lucie; Casale, Marisa; Lane, Tyler

2014-01-01

Abstract Adults caring for children in HIV-endemic communities are at risk for poor psychological outcomes. However, we still have a limited understanding of how various HIV impacts—including caregiver's own HIV illness, responsibilities of caring for a child orphaned by AIDS, or both—affect psychological outcomes among caregivers. Furthermore, few studies have explored the relationship between stigma, HIV, and psychological outcomes among caregivers of children in HIV-endemic communities. A cross-sectional survey conducted from 2009 to 2010 assessed anxiety among 2477 caregivers of children in HIV-endemic South Africa. Chi-square tested differences in anxiety among caregivers living with HIV, caregivers of a child orphaned by AIDS, and caregivers affected with both conditions. Multivariate logistic regressions identified whether the relationship between HIV impacts and anxiety remained after controlling for socio-demographic co-factors. Mediation analysis tested the relationship between stigma, HIV, and anxiety. The odds of meeting threshold criteria for clinically relevant anxiety symptoms were two and a half times greater among caregivers living with HIV compared to nonaffected caregivers. The odds of meeting threshold criteria for clinically relevant anxiety symptoms were greatest among caregivers living with HIV and caring for a child orphaned by AIDS. Exposure to AIDS-related stigma partially mediated the relationship between HIV and anxiety. Interventions are needed to address caregiver psychological health, particularly among caregivers affected with both conditions of living with HIV and caring for a child orphaned by AIDS. PMID:24901465

Clinical research in small genomically stratified patient populations.

PubMed

Martin-Liberal, J; Rodon, J

2017-07-01

The paradigm of early drug development in cancer is shifting from 'histology-oriented' to 'molecularly oriented' clinical trials. This change can be attributed to the vast amount of tumour biology knowledge generated by large international research initiatives such as The Cancer Genome Atlas (TCGA) and the use of next generation sequencing (NGS) techniques developed in recent years. However, targeting infrequent molecular alterations entails a series of special challenges. The optimal molecular profiling method, the lack of standardised biological thresholds, inter- and intra-tumor heterogeneity, availability of enough tumour material, correct clinical trials design, attrition rate, logistics or costs are only some of the issues that need to be taken into consideration in clinical research in small genomically stratified patient populations. This article examines the most relevant challenges inherent to clinical research in these populations. Moreover, perspectives from the Academia point of view are reviewed as well as initiatives to be taken in forthcoming years. Copyright © 2017 Elsevier Ltd. All rights reserved.

Si-strip photon counting detectors for contrast-enhanced spectral mammography

NASA Astrophysics Data System (ADS)

Chen, Buxin; Reiser, Ingrid; Wessel, Jan C.; Malakhov, Nail; Wawrzyniak, Gregor; Hartsough, Neal E.; Gandhi, Thulasi; Chen, Chin-Tu; Iwanczyk, Jan S.; Barber, William C.

2015-08-01

We report on the development of silicon strip detectors for energy-resolved clinical mammography. Typically, X-ray integrating detectors based on scintillating cesium iodide CsI(Tl) or amorphous selenium (a-Se) are used in most commercial systems. Recently, mammography instrumentation has been introduced based on photon counting Si strip detectors. The required performance for mammography in terms of the output count rate, spatial resolution, and dynamic range must be obtained with sufficient field of view for the application, thus requiring the tiling of pixel arrays and particular scanning techniques. Room temperature Si strip detector, operating as direct conversion x-ray sensors, can provide the required speed when connected to application specific integrated circuits (ASICs) operating at fast peaking times with multiple fixed thresholds per pixel, provided that the sensors are designed for rapid signal formation across the X-ray energy ranges of the application. We present our methods and results from the optimization of Si-strip detectors for contrast enhanced spectral mammography. We describe the method being developed for quantifying iodine contrast using the energy-resolved detector with fixed thresholds. We demonstrate the feasibility of the method by scanning an iodine phantom with clinically relevant contrast levels.

Does exercise pulmonary hypertension exist?

PubMed

Lau, Edmund M; Chemla, Denis; Whyte, Kenneth; Kovacs, Gabor; Olschewski, Horst; Herve, Philippe

2016-09-01

The exercise definition of pulmonary hypertension using a mean pulmonary artery pressure threshold of greater than 30 mmHg was abandoned following the 4th World Pulmonary Hypertension Symposium in 2008, as this definition was not supported by evidence and healthy individuals frequently exceed this threshold. Meanwhile, the clinical value of exercise pulmonary hemodynamic testing has also been questioned. Recent data support the notion that an abnormal pulmonary hemodynamic response during exercise (or exercise pulmonary hypertension) is associated with symptoms and exercise limitation. Pathophysiologic mechanisms accounting for the development of exercise pulmonary hypertension include increased vascular resistance, excessive elevation in left atrial pressure and/or increased volume of trapped air during exercise, resulting in a steep rise in pulmonary artery pressure relative to cardiac output. Recent evidence suggests that exercise pulmonary hypertension may be defined by a mean pulmonary artery pressure surpassing 30 mmHg together with a simultaneous total pulmonary resistance exceeding 3 WU. Exercise pulmonary hypertension is a clinically relevant entity and an improved definition has been suggested based on new evidence. Exercise pulmonary hemodynamics may help unmask early or latent disease, particularly in populations that are at high risk for the development of pulmonary hypertension.

The regional effect of spinal manipulation on the pressure pain threshold in asymptomatic subjects: a systematic literature review.

PubMed

Honoré, Margaux; Leboeuf-Yde, Charlotte; Gagey, Olivier

2018-01-01

Spinal manipulation (SM) has been shown to have an effect on pain perception. More knowledge is needed on this phenomenon and it would be relevant to study its effect in asymptomatic subjects. To compare regional effect of SM on pressure pain threshold (PPT) vs. sham, inactive control, mobilisation, another SM, and some type of physical therapy. In addition, we reported the results for the three different spinal regions. A systematic search of literature was done using PubMed, Embase and Cochrane. Search terms were ((spinal manipulation) AND (experimental pain)); ((spinal manipulative therapy OR spinal manipulation) AND ((experimental pain OR quantitative sensory testing OR pressure pain threshold OR pain threshold)) (Final search: June 13th 2017). The inclusion criteria were SM performed anywhere in the spine; the use of PPT, PPT tested in an asymptomatic region and on the same day as the SM. Studies had to be experimental with at least one external or internal control group. Studies on only spinal motion or tenderness, other reviews, case reports, and less than 15 invited participants in each group were excluded. Evidence tables were constructed with information relevant to each research question and by spinal region. Results were reported in relation to statistical significance and were interpreted taking into account their quality. Only 12 articles of 946 were accepted. The quality of studies was generally good. In 8 sham controlled studies, a psychologically and physiologically "credible" sham was found in only 2 studies. A significant difference was noted between SM vs. Sham, and between SM and an inactive control. No significant difference in PPT was found between SM and another SM, mobilisation or some type of physical therapy. The cervical region more often obtained significant findings as compared to studies in the thoracic or lumbar regions. SM has an effect regionally on pressure pain threshold in asymptomatic subjects. The clinical significance of this must be quantified. More knowledge is needed in relation to the comparison of different spinal regions and different types of interventions.

Identification of men with low-risk biopsy-confirmed prostate cancer as candidates for active surveillance.

PubMed

Lin, Daniel W; Crawford, E David; Keane, Thomas; Evans, Brent; Reid, Julia; Rajamani, Saradha; Brown, Krystal; Gutin, Alexander; Tward, Jonathan; Scardino, Peter; Brawer, Michael; Stone, Steven; Cuzick, Jack

2018-06-01

A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS. The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort. In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10 -5 ). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively). The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS. Copyright © 2018 Elsevier Inc. All rights reserved.

A critical evaluation of the PTW 2D‐ARRAY seven29 and OCTAVIUS II phantom for IMRT and VMAT verification

PubMed Central

Adams, Elizabeth J.; Jordan, Thomas J.; Clark, Catharine H.; Nisbet, Andrew

2013-01-01

Quality assurance (QA) for intensity‐ and volumetric‐modulated radiotherapy (IMRT and VMAT) has evolved substantially. In recent years, various commercial 2D and 3D ionization chamber or diode detector arrays have become available, allowing for absolute verification with near real time results, allowing for streamlined QA. However, detector arrays are limited by their resolution, giving rise to concerns about their sensitivity to errors. Understanding the limitations of these devices is therefore critical. In this study, the sensitivity and resolution of the PTW 2D‐ARRAY seven29 and OCTAVIUS II phantom combination was comprehensively characterized for use in dynamic sliding window IMRT and RapidArc verification. Measurement comparisons were made between single acquisition and a multiple merged acquisition techniques to improve the effective resolution of the 2D‐ARRAY, as well as comparisons against GAFCHROMIC EBT2 film and electronic portal imaging dosimetry (EPID). The sensitivity and resolution of the 2D‐ARRAY was tested using two gantry angle 0° modulated test fields. Deliberate multileaf collimator (MLC) errors of 1, 2, and 5 mm and collimator rotation errors were inserted into IMRT and RapidArc plans for pelvis and head & neck sites, to test sensitivity to errors. The radiobiological impact of these errors was assessed to determine the gamma index passing criteria to be used with the 2D‐ARRAY to detect clinically relevant errors. For gamma index distributions, it was found that the 2D‐ARRAY in single acquisition mode was comparable to multiple acquisition modes, as well as film and EPID. It was found that the commonly used gamma index criteria of 3% dose difference or 3 mm distance to agreement may potentially mask clinically relevant errors. Gamma index criteria of 3%/2 mm with a passing threshold of 98%, or 2%/2 mm with a passing threshold of 95%, were found to be more sensitive. We suggest that the gamma index passing thresholds may be used for guidance, but also should be combined with a visual inspection of the gamma index distribution and calculation of the dose difference to assess whether there may be a clinical impact in failed regions. PACS numbers: 87.55.Qr, 87.56.Fc PMID:24257288

Prevalence scaling: applications to an intelligent workstation for the diagnosis of breast cancer.

PubMed

Horsch, Karla; Giger, Maryellen L; Metz, Charles E

2008-11-01

Our goal was to investigate the effects of changes that the prevalence of cancer in a population have on the probability of malignancy (PM) output and an optimal combination of a true-positive fraction (TPF) and a false-positive fraction (FPF) of a mammographic and sonographic automatic classifier for the diagnosis of breast cancer. We investigate how a prevalence-scaling transformation that is used to change the prevalence inherent in the computer estimates of the PM affects the numerical and histographic output of a previously developed multimodality intelligent workstation. Using Bayes' rule and the binormal model, we study how changes in the prevalence of cancer in the diagnostic breast population affect our computer classifiers' optimal operating points, as defined by maximizing the expected utility. Prevalence scaling affects the threshold at which a particular TPF and FPF pair is achieved. Tables giving the thresholds on the scaled PM estimates that result in particular pairs of TPF and FPF are presented. Histograms of PMs scaled to reflect clinically relevant prevalence values differ greatly from histograms of laboratory-designed PMs. The optimal pair (TPF, FPF) of our lower performing mammographic classifier is more sensitive to changes in clinical prevalence than that of our higher performing sonographic classifier. Prevalence scaling can be used to change computer PM output to reflect clinically more appropriate prevalence. Relatively small changes in clinical prevalence can have large effects on the computer classifier's optimal operating point.

Threshold concepts: implications for the management of natural resources

USGS Publications Warehouse

Guntenspergen, Glenn R.; Gross, John

2014-01-01

Threshold concepts can have broad relevance in natural resource management. However, the concept of ecological thresholds has not been widely incorporated or adopted in management goals. This largely stems from the uncertainty revolving around threshold levels and the post hoc analyses that have generally been used to identify them. Natural resource managers have a need for new tools and approaches that will help them assess the existence and detection of conditions that demand management actions. Recognition of additional threshold concepts include: utility thresholds (which are based on human values about ecological systems) and decision thresholds (which reflect management objectives and values and include ecological knowledge about a system) as well as ecological thresholds. All of these concepts provide a framework for considering the use of threshold concepts in natural resource decision making.

Perceived Pain Extent is Not Associated With Widespread Pressure Pain Sensitivity, Clinical Features, Related Disability, Anxiety, or Depression in Women With Episodic Migraine.

PubMed

Fernández-de-Las-Peñas, Cesar; Falla, Deborah; Palacios-Ceña, María; Fuensalida-Novo, Stella; Arias-Buría, Jose L; Schneebeli, Alessandro; Arend-Nielsen, Lars; Barbero, Marco

2018-03-01

People with migraine present with varying pain extent and an expanded distribution of perceived pain may reflect central sensitization. The relationship between pain extent and clinical features, psychological outcomes, related disability, and pressure pain sensitivity in migraine has been poorly investigated. Our aim was to investigate whether the perceived pain extent, assessed from pain drawings, relates to measures of pressure pain sensitivity, clinical, psychological outcomes, and related disability in women with episodic migraine. A total of 72 women with episodic migraine completed pain drawings, which were subsequently digitized allowing pain extent to be calculated utilising novel software. Pressure pain thresholds were assessed bilaterally over the temporalis muscle (trigeminal area), the cervical spine (extratrigeminal area), and tibialis anterior muscle (distant pain-free area). Clinical features of migraine, migraine-related disability (migraine disability assessment questionnaire [MIDAS]), and anxiety and depression (Hospital Anxiety-Depression Scale [HADS]) were also assessed. Spearman ρ correlation coefficients were computed to reveal correlations between pain extent and the remaining outcomes. No significant associations were observed between pain extent and pressure pain thresholds in trigeminal, extratrigeminal or distant pain-free areas, migraine pain features, or psychological variables including anxiety or depression, and migraine-related disability. Pain extent within the trigeminocervical area was not associated with any of the measured clinical outcomes and not related to the degree of pressure pain sensitization in women with episodic migraine. Further research is needed to determine if the presence of expanded pain areas outside of the trigeminal area can play a relevant role in the sensitization processes in migraine.

Challenges in the Clinical Application of the American Society of Clinical Oncology Value Framework: A Medicare Cost-Benefit Analysis in Chronic Lymphocytic Leukemia.

PubMed

Seymour, Erlene K; Schiffer, Charles A; de Souza, Jonas A

2017-12-01

The ASCO Value Framework calculates the value of cancer therapies. Given costly novel therapeutics for chronic lymphocytic leukemia, we used the framework to compare net health benefit (NHB) and cost within Medicare of all regimens listed in the National Comprehensive Cancer Network (NCCN) guidelines. The current NCCN guidelines for chronic lymphocytic leukemia were reviewed. All referenced studies were screened, and only randomized controlled prospective trials were included. The revised ASCO Value Framework was used to calculate NHB. Medicare drug pricing was used to calculate the cost of therapies. Forty-nine studies were screened. The following observations were made: only 10 studies (20%) could be evaluated; when comparing regimens studied against the same control arm, ranking NHB scores were comparable to their preference in guidelines; NHB scores varied depending on which variables were used, and there were no clinically validated thresholds for low or high values; treatment-related deaths were not weighted in the toxicity scores; and six of the 10 studies used less potent control arms, ranked as the least-preferred NCCN-recommended regimens. The ASCO Value Framework is an important initial step to quantify value of therapies. Essential limitations include the lack of clinically relevant validated thresholds for NHB scores and lack of incorporation of grade 5 toxicities/treatment-related mortality into its methodology. To optimize its application for clinical practice, we urge investigators/sponsors to incorporate and report the required variables to calculate the NHB of regimens and encourage trials with stronger comparator arms to properly quantify the relative value of therapies.

Divergent sensory phenotypes in nonspecific arm pain: comparisons with cervical radiculopathy.

PubMed

Moloney, Niamh; Hall, Toby; Doody, Catherine

2015-02-01

To investigate whether distinct sensory phenotypes were identifiable in individuals with nonspecific arm pain (NSAP) and whether these differed from those in people with cervical radiculopathy. A secondary question considered whether the frequency of features of neuropathic pain, kinesiophobia, high pain ratings, hyperalgesia, and allodynia differed according to subgroups of sensory phenotypes. Cross-sectional study. Higher education institution. Forty office workers with NSAP, 17 people with cervical radiculopathy, and 40 age- and sex-matched healthy controls (N=97). Not applicable. Participants were assessed using quantitative sensory testing (QST) comprising thermal and vibration detection thresholds and thermal and pressure pain thresholds; clinical examination; and relevant questionnaires. Sensory phenotypes were identified for each individual in the patient groups using z-score transformation of the QST data. Individuals with NSAP and cervical radiculopathy present with a spectrum of sensory abnormalities; a dominant sensory phenotype was not identifiable in individuals with NSAP. No distinct pattern between clinical features and questionnaire results across sensory phenotypes was identified in either group. When considering sensory phenotypes, neither individuals with NSAP nor individuals with cervical radiculopathy should be considered homogeneous. Therefore, people with either condition may warrant different intervention approaches according to their individual sensory phenotype. Issues relating to the clinical identification of sensory hypersensitivity and the validity of QST are highlighted. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Perspective: Uses and misuses of thresholds in diagnostic decision making.

PubMed

Warner, Jeremy L; Najarian, Robert M; Tierney, Lawrence M

2010-03-01

The concept of thresholds plays a vital role in decisions involving the initiation, continuation, and completion of diagnostic testing. Much research has focused on the development of explicit thresholds, in the form of practice guidelines and decision analyses. However, these tools are used infrequently; most medical decisions are made at the bedside, using implicit thresholds. Study of these thresholds can lead to a deeper understanding of clinical decision making. The authors examine some factors constituting individual clinicians' implicit thresholds. They propose a model for static thresholds using the concept of situational gravity to explain why some thresholds are high, and some low. Next, they consider the hypothetical effects of incorrect placement of thresholds (miscalibration) and changes to thresholds during diagnosis (manipulation). They demonstrate these concepts using common clinical scenarios. Through analysis of miscalibration of thresholds, the authors demonstrate some common maladaptive clinical behaviors, which are nevertheless internally consistent. They then explain how manipulation of thresholds gives rise to common cognitive heuristics including premature closure and anchoring. They also discuss the case where no threshold has been exceeded despite exhaustive collection of data, which commonly leads to application of the availability or representativeness heuristics. Awareness of implicit thresholds allows for a more effective understanding of the processes of medical decision making and, possibly, to the avoidance of detrimental heuristics and their associated medical errors. Research toward accurately defining these thresholds for individual physicians and toward determining their dynamic properties during the diagnostic process may yield valuable insights.

Prioritizing CD4 Count Monitoring in Response to ART in Resource-Constrained Settings: A Retrospective Application of Prediction-Based Classification

PubMed Central

Liu, Yan; Li, Xiaohong; Johnson, Margaret; Smith, Collette; Kamarulzaman, Adeeba bte; Montaner, Julio; Mounzer, Karam; Saag, Michael; Cahn, Pedro; Cesar, Carina; Krolewiecki, Alejandro; Sanne, Ian; Montaner, Luis J.

2012-01-01

Background Global programs of anti-HIV treatment depend on sustained laboratory capacity to assess treatment initiation thresholds and treatment response over time. Currently, there is no valid alternative to CD4 count testing for monitoring immunologic responses to treatment, but laboratory cost and capacity limit access to CD4 testing in resource-constrained settings. Thus, methods to prioritize patients for CD4 count testing could improve treatment monitoring by optimizing resource allocation. Methods and Findings Using a prospective cohort of HIV-infected patients (n = 1,956) monitored upon antiretroviral therapy initiation in seven clinical sites with distinct geographical and socio-economic settings, we retrospectively apply a novel prediction-based classification (PBC) modeling method. The model uses repeatedly measured biomarkers (white blood cell count and lymphocyte percent) to predict CD4+ T cell outcome through first-stage modeling and subsequent classification based on clinically relevant thresholds (CD4+ T cell count of 200 or 350 cells/µl). The algorithm correctly classified 90% (cross-validation estimate = 91.5%, standard deviation [SD] = 4.5%) of CD4 count measurements <200 cells/µl in the first year of follow-up; if laboratory testing is applied only to patients predicted to be below the 200-cells/µl threshold, we estimate a potential savings of 54.3% (SD = 4.2%) in CD4 testing capacity. A capacity savings of 34% (SD = 3.9%) is predicted using a CD4 threshold of 350 cells/µl. Similar results were obtained over the 3 y of follow-up available (n = 619). Limitations include a need for future economic healthcare outcome analysis, a need for assessment of extensibility beyond the 3-y observation time, and the need to assign a false positive threshold. Conclusions Our results support the use of PBC modeling as a triage point at the laboratory, lessening the need for laboratory-based CD4+ T cell count testing; implementation of this tool could help optimize the use of laboratory resources, directing CD4 testing towards higher-risk patients. However, further prospective studies and economic analyses are needed to demonstrate that the PBC model can be effectively applied in clinical settings. Please see later in the article for the Editors' Summary PMID:22529752

Predicting Vasovagal Syncope from Heart Rate and Blood Pressure: A Prospective Study in 140 Subjects.

PubMed

Virag, Nathalie; Erickson, Mark; Taraborrelli, Patricia; Vetter, Rolf; Lim, Phang Boon; Sutton, Richard

2018-04-28

We developed a vasovagal syncope (VVS) prediction algorithm for use during head-up tilt with simultaneous analysis of heart rate (HR) and systolic blood pressure (SBP). We previously tested this algorithm retrospectively in 1155 subjects, showing sensitivity 95%, specificity 93% and median prediction time of 59s. This study was prospective, single center, on 140 subjects to evaluate this VVS prediction algorithm and assess if retrospective results were reproduced and clinically relevant. Primary endpoint was VVS prediction: sensitivity and specificity >80%. In subjects, referred for 60° head-up tilt (Italian protocol), non-invasive HR and SBP were supplied to the VVS prediction algorithm: simultaneous analysis of RR intervals, SBP trends and their variability represented by low-frequency power generated cumulative risk which was compared with a predetermined VVS risk threshold. When cumulative risk exceeded threshold, an alert was generated. Prediction time was duration between first alert and syncope. Of 140 subjects enrolled, data was usable for 134. Of 83 tilt+ve (61.9%), 81 VVS events were correctly predicted and of 51 tilt-ve subjects (38.1%), 45 were correctly identified as negative by the algorithm. Resulting algorithm performance was sensitivity 97.6%, specificity 88.2%, meeting primary endpoint. Mean VVS prediction time was 2min 26s±3min16s with median 1min 25s. Using only HR and HR variability (without SBP) the mean prediction time reduced to 1min34s±1min45s with median 1min13s. The VVS prediction algorithm, is clinically-relevant tool and could offer applications including providing a patient alarm, shortening tilt-test time, or triggering pacing intervention in implantable devices. Copyright © 2018. Published by Elsevier Inc.

Prevalence and correlates of cognitive impairment in euthymic adults with bipolar disorder: A systematic review.

PubMed

Cullen, Breda; Ward, Joey; Graham, Nicholas A; Deary, Ian J; Pell, Jill P; Smith, Daniel J; Evans, Jonathan J

2016-11-15

Previous reviews have identified medium-large group differences in cognitive performance in adults with bipolar disorder (BD) compared to healthy peers, but the proportion with clinically relevant cognitive impairment has not yet been established. This review aimed to quantify the prevalence of cognitive impairment in euthymic adults with BD, and to describe sociodemographic, clinical and other factors that are significantly associated with cognitive impairment. Systematic literature review. The population was euthymic community-dwelling adults with BD, aged 18-70 years, and recruited consecutively or randomly. The outcome was cognitive impairment, relative to healthy population norms. Electronic databases and reference lists of relevant articles were searched, and authors were contacted. Original cross-sectional studies published in peer-reviewed English-language journals from January 1994 to February 2015 were included. Methodological bias and reporting bias were assessed using standard tools. A narrative synthesis is presented together with tables and forest plots. Thirty articles were included, of which 15 contributed prevalence data. At the 5th percentile impairment threshold, prevalence ranges were: executive function 5.3-57.7%; attention/working memory 9.6-51.9%; speed/reaction time 23.3-44.2%; verbal memory 8.2-42.1%; visual memory 11.5-32.9%. More severe or longstanding illness and antipsychotic medication were associated with greater cognitive impairment. The synthesis was limited by heterogeneity in cognitive measures and impairment thresholds, precluding meta-analysis. Cognitive impairment affects a substantial proportion of euthymic adults with BD. Future research with more consistent measurement and reporting will facilitate an improved understanding of cognitive impairment burden in BD. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessing the prevalence and clinical relevance of positive abdominal and pelvic CT findings in senior patients presenting to the emergency department.

PubMed

Alabousi, Abdullah; Patlas, Michael N; Meshki, Malek; Monteiro, Sandra; Katz, Douglas S

2016-04-01

The purpose of our study was to retrospectively evaluate the prevalence and clinical relevance of positive abdominal and pelvic CT findings for patients 65 years of age and older, when compared with all other scanned adult Emergency Department (ED) patients, at a single tertiary care hospital. Our hypothesis was that there is an increased prevalence and clinical relevance of positive abdominal/pelvic CT findings in senior patients. A research ethics board-approved retrospective review of all adult patients who underwent an emergency CT of the abdomen and pelvis for acute nontraumatic abdominal and/or pelvic signs and symptoms was performed. Two thousand one hundred two patients between October 1, 2011, and September 30, 2013, were reviewed. Six hundred thirty-one patients were included in the <65 group (298 men and 333 women; mean age 46, age range 18-64), and 462 were included in the >65 group (209 men and 253 women; mean age 77.6, age range 65-99). Overall, there were more positive CT findings for patients <65 (389 positive cases, 61.6 %) compared with the >65 group (257 positive cases, 55.6 %), which was a statistically significant difference (p < 0.03). Moreover, with the exception of complicated appendicitis cases, which were more common in the >65 group, there were no statistically significant differences in the clinical/surgical relevance of the positive CT findings between the two groups. The findings of our retrospective study therefore refute our hypothesis that there is an increased prevalence of positive abdominal CT findings in patients >65. This may be related to ED physicians at our institution being more hesitant to order CT examinations for the younger population, presumably due to radiation concerns. However, older patients in our series were more likely to present with complicated appendicitis, and a lower threshold for ordering CT examinations of the abdomen and pelvis in this patient population should therefore be considered.

An investigation of mechanical nociceptive thresholds in dogs with hind limb joint pain compared to healthy control dogs.

PubMed

Harris, L K; Whay, H R; Murrell, J C

2018-04-01

This study investigated the effects of osteoarthritis (OA) on somatosensory processing in dogs using mechanical threshold testing. A pressure algometer was used to measure mechanical thresholds in 27 dogs with presumed hind limb osteoarthritis and 28 healthy dogs. Mechanical thresholds were measured at the stifles, radii and sternum, and were correlated with scores from an owner questionnaire and a clinical checklist, a scoring system that quantified clinical signs of osteoarthritis. The effects of age and bodyweight on mechanical thresholds were also investigated. Multiple regression models indicated that, when bodyweight was taken into account, dogs with presumed osteoarthritis had lower mechanical thresholds at the stifles than control dogs, but not at other sites. Non-parametric correlations showed that clinical checklist scores and questionnaire scores were negatively correlated with mechanical thresholds at the stifles. The results suggest that mechanical threshold testing using a pressure algometer can detect primary, and possibly secondary, hyperalgesia in dogs with presumed osteoarthritis. This suggests that the mechanical threshold testing protocol used in this study might facilitate assessment of somatosensory changes associated with disease progression or response to treatment. Copyright © 2017. Published by Elsevier Ltd.

Inter- and intra-observer reliability of clinical movement-control tests for marines

PubMed Central

2012-01-01

Background Musculoskeletal disorders particularly in the back and lower extremities are common among marines. Here, movement-control tests are considered clinically useful for screening and follow-up evaluation. However, few studies have addressed the reliability of clinical tests, and no such published data exists for marines. The present aim was therefore to determine the inter- and intra-observer reliability of clinically convenient tests emphasizing movement control of the back and hip among marines. A secondary aim was to investigate the sensitivity and specificity of these clinical tests for discriminating musculoskeletal pain disorders in this group of military personnel. Methods This inter- and intra-observer reliability study used a test-retest approach with six standardized clinical tests focusing on movement control for back and hip. Thirty-three marines (age 28.7 yrs, SD 5.9) on active duty volunteered and were recruited. They followed an in-vivo observation test procedure that covered both low- and high-load (threshold) tasks relevant for marines on operational duty. Two independent observers simultaneously rated performance as “correct” or “incorrect” following a standardized assessment protocol. Re-testing followed 7–10 days thereafter. Reliability was analysed using kappa (κ) coefficients, while discriminative power of the best-fitting tests for back- and lower-extremity pain was assessed using a multiple-variable regression model. Results Inter-observer reliability for the six tests was moderate to almost perfect with κ-coefficients ranging between 0.56-0.95. Three tests reached almost perfect inter-observer reliability with mean κ-coefficients > 0.81. However, intra-observer reliability was fair-to-moderate with mean κ-coefficients between 0.22-0.58. Three tests achieved moderate intra-observer reliability with κ-coefficients > 0.41. Combinations of one low- and one high-threshold test best discriminated prior back pain, but results were inconsistent for lower-extremity pain. Conclusions Our results suggest that clinical tests of movement control of back and hip are reliable for use in screening protocols using several observers with marines. However, test-retest reproducibility was less accurate, which should be considered in follow-up evaluations. The results also indicate that combinations of low- and high-threshold tests have discriminative validity for prior back pain, but were inconclusive for lower-extremity pain. PMID:23273285

PP087. Multicenter external validation and recalibration of a model for preconceptional prediction of recurrent early-onset preeclampsia.

PubMed

van Kuijk, Sander; Delahaije, Denise; Dirksen, Carmen; Scheepers, Hubertina C J; Spaanderman, Marc; Ganzevoort, W; Duvekot, Hans; Oudijk, M A; van Pampus, M G; Dadelszen, Peter von; Peeters, Louis L; Smiths, Luc

2013-04-01

In an earlier paper we reported on the development of a model aimed at the prediction of preeclampsia recurrence, based on variables obtained before the next pregnancy (fasting glucose, BMI, previous birth of a small-for-gestational-age infant, duration of the previous pregnancy, and the presence of hypertension). To externally validate and recalibrate the prediction model for the risk of recurrence of early-onset preeclampsia. We collected data about course and outcome of the next ongoing pregnancy in 229 women with a history of early-onset preeclampsia. Recurrence was defined as preeclampsia requiring delivery before 34 weeks. We computed risk of recurrence and assessed model performance. In addition, we constructed a table comparing sensitivity, specificity, and predictive values for different suggested risk-thresholds. Early-onset preeclampsia recurred in 6.6% of women. The model systematically underestimated recurrence risk. The model's discriminative ability was modest, the area under the receiver operating characteristic curve was 58.9% (95% CI: 45.1 - 72.7). Using relevant risk-thresholds, the model created groups that were only moderately different in terms of their average risk of recurrent preeclampsia (Table 1). Compared to an AUC of 65% in the development cohort, the discriminate ability of the model was diminished. It had inadequate performance to classify women into clinically relevant risk groups. Copyright © 2013. Published by Elsevier B.V.

Speech-in-Noise Tests and Supra-threshold Auditory Evoked Potentials as Metrics for Noise Damage and Clinical Trial Outcome Measures.

PubMed

Le Prell, Colleen G; Brungart, Douglas S

2016-09-01

In humans, the accepted clinical standards for detecting hearing loss are the behavioral audiogram, based on the absolute detection threshold of pure-tones, and the threshold auditory brainstem response (ABR). The audiogram and the threshold ABR are reliable and sensitive measures of hearing thresholds in human listeners. However, recent results from noise-exposed animals demonstrate that noise exposure can cause substantial neurodegeneration in the peripheral auditory system without degrading pure-tone audiometric thresholds. It has been suggested that clinical measures of auditory performance conducted with stimuli presented above the detection threshold may be more sensitive than the behavioral audiogram in detecting early-stage noise-induced hearing loss in listeners with audiometric thresholds within normal limits. Supra-threshold speech-in-noise testing and supra-threshold ABR responses are reviewed here, given that they may be useful supplements to the behavioral audiogram for assessment of possible neurodegeneration in noise-exposed listeners. Supra-threshold tests may be useful for assessing the effects of noise on the human inner ear, and the effectiveness of interventions designed to prevent noise trauma. The current state of the science does not necessarily allow us to define a single set of best practice protocols. Nonetheless, we encourage investigators to incorporate these metrics into test batteries when feasible, with an effort to standardize procedures to the greatest extent possible as new reports emerge.

Assessing conservation relevance of organism-environment relations using predicted changes in response variables

USGS Publications Warehouse

Gutzwiller, Kevin J.; Barrow, Wylie C.; White, Joseph D.; Johnson-Randall, Lori; Cade, Brian S.; Zygo, Lisa M.

2010-01-01

1. Organism–environment models are used widely in conservation. The degree to which they are useful for informing conservation decisions – the conservation relevance of these relations – is important because lack of relevance may lead to misapplication of scarce conservation resources or failure to resolve important conservation dilemmas. Even when models perform well based on model fit and predictive ability, conservation relevance of associations may not be clear without also knowing the magnitude and variability of predicted changes in response variables. 2. We introduce a method for evaluating the conservation relevance of organism–environment relations that employs confidence intervals for predicted changes in response variables. The confidence intervals are compared to a preselected magnitude of change that marks a threshold (trigger) for conservation action. To demonstrate the approach, we used a case study from the Chihuahuan Desert involving relations between avian richness and broad-scale patterns of shrubland. We considered relations for three winters and two spatial extents (1- and 2-km-radius areas) and compared predicted changes in richness to three thresholds (10%, 20% and 30% change). For each threshold, we examined 48 relations. 3. The method identified seven, four and zero conservation-relevant changes in mean richness for the 10%, 20% and 30% thresholds respectively. These changes were associated with major (20%) changes in shrubland cover, mean patch size, the coefficient of variation for patch size, or edge density but not with major changes in shrubland patch density. The relative rarity of conservation-relevant changes indicated that, overall, the relations had little practical value for informing conservation decisions about avian richness. 4. The approach we illustrate is appropriate for various response and predictor variables measured at any temporal or spatial scale. The method is broadly applicable across ecological environments, conservation objectives, types of statistical predictive models and levels of biological organization. By focusing on magnitudes of change that have practical significance, and by using the span of confidence intervals to incorporate uncertainty of predicted changes, the method can be used to help improve the effectiveness of conservation efforts.

Exercise increases pressure pain tolerance but not pressure and heat pain thresholds in healthy young men.

PubMed

Vaegter, H B; Hoeger Bement, M; Madsen, A B; Fridriksson, J; Dasa, M; Graven-Nielsen, T

2017-01-01

Exercise causes an acute decrease in the pain sensitivity known as exercise-induced hypoalgesia (EIH), but the specificity to certain pain modalities remains unknown. This study aimed to compare the effect of isometric exercise on the heat and pressure pain sensitivity. On three different days, 20 healthy young men performed two submaximal isometric knee extensions (30% maximal voluntary contraction in 3 min) and a control condition (quiet rest). Before and immediately after exercise and rest, the sensitivity to heat pain and pressure pain was assessed in randomized and counterbalanced order. Cuff pressure pain threshold (cPPT) and pain tolerance (cPTT) were assessed on the ipsilateral lower leg by computer-controlled cuff algometry. Heat pain threshold (HPT) was recorded on the ipsilateral foot by a computer-controlled thermal stimulator. Cuff pressure pain tolerance was significantly increased after exercise compared with baseline and rest (p < 0.05). Compared with rest, cPPT and HPT were not significantly increased by exercise. No significant correlation between exercise-induced changes in HPT and cPPT was found. Test-retest reliability before and after the rest condition was better for cPPT and CPTT (intraclass correlation > 0.77) compared with HPT (intraclass correlation = 0.54). The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. The effect of isometric exercise on pain tolerance may be relevant for patients in chronic musculoskeletal pain as a pain-coping strategy. WHAT DOES THIS STUDY ADD?: The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the heat and pressure pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. © 2016 European Pain Federation - EFIC®.

Clinical multiple sclerosis occurs at one end of a spectrum of CNS pathology: a modified threshold liability model leads to new ways of thinking about the cause of clinical multiple sclerosis.

PubMed

Haegert, David G

2005-01-01

Multiple sclerosis (MS) is a complex trait, the causes of which are elusive. A threshold liability model influences thinking about the causes of this disorder. According to this model, a population has a normal distribution of genetic liability to MS. In addition, a threshold exists, so that MS begins when an individual's liability exceeds the MS threshold; environmental and other causative factors may increase or decrease an individual's MS liability. It is argued here, however, that this model is misleading, as it is based on the incorrect assumption that MS is a disorder that one either has or does not have. This paper hypothesizes, instead, that patients with a diagnosis of MS share identical CNS pathology, termed MS pathology, with some individuals who have a diagnosis of possible MS and with some apparently healthy individuals, who may never have a diagnosis of MS. In order to accommodate this hypothesis, the current threshold liability model is modified as follows. (1) In addition to a normal distribution of MS liability within a population, a spectrum of MS pathology occurs in some who have a high MS liability. (2) A clinical MS threshold exists at a point on this liability distribution, where the burden and distribution of MS pathology permits a diagnosis of clinical MS. (3) Additional thresholds exist that correspond to a lower MS liability and a lesser burden of MS pathology than occur at the clinical MS threshold. This modified threshold model leads to the postulate that causes act at various time points to increase MS liability and induce MS pathology. The accumulation of MS pathology sometimes leads to a diagnosis of clinical MS. One implication of this model is that the MS pathology in clinical MS and in some with possible MS differs only in the extent but not in the type of CNS injury. Thus, it may be possible to obtain insight into the causative environmental factors that increase MS liability and induce MS pathology by focusing on patients who have clinical MS; some environmental factors that induce new lesions in patients with clinical MS may be identical to those that induce MS pathology in genetically susceptible individuals who do not have clinical MS. Identification of these causative factors has importance, as specific treatment may prevent the accumulation of MS pathology that leads to the significant CNS damage associated with clinical MS.

Accurate and robust genomic prediction of celiac disease using statistical learning.

PubMed

Abraham, Gad; Tye-Din, Jason A; Bhalala, Oneil G; Kowalczyk, Adam; Zobel, Justin; Inouye, Michael

2014-02-01

Practical application of genomic-based risk stratification to clinical diagnosis is appealing yet performance varies widely depending on the disease and genomic risk score (GRS) method. Celiac disease (CD), a common immune-mediated illness, is strongly genetically determined and requires specific HLA haplotypes. HLA testing can exclude diagnosis but has low specificity, providing little information suitable for clinical risk stratification. Using six European cohorts, we provide a proof-of-concept that statistical learning approaches which simultaneously model all SNPs can generate robust and highly accurate predictive models of CD based on genome-wide SNP profiles. The high predictive capacity replicated both in cross-validation within each cohort (AUC of 0.87-0.89) and in independent replication across cohorts (AUC of 0.86-0.9), despite differences in ethnicity. The models explained 30-35% of disease variance and up to ∼43% of heritability. The GRS's utility was assessed in different clinically relevant settings. Comparable to HLA typing, the GRS can be used to identify individuals without CD with ≥99.6% negative predictive value however, unlike HLA typing, fine-scale stratification of individuals into categories of higher-risk for CD can identify those that would benefit from more invasive and costly definitive testing. The GRS is flexible and its performance can be adapted to the clinical situation by adjusting the threshold cut-off. Despite explaining a minority of disease heritability, our findings indicate a genomic risk score provides clinically relevant information to improve upon current diagnostic pathways for CD and support further studies evaluating the clinical utility of this approach in CD and other complex diseases.

State of the Art in HIV Drug Resistance: Science and Technology Knowledge Gap.

PubMed

Boucher, Charles A; Bobkova, Marina R; Geretti, Anna Maria; Hung, Chien-Ching; Kaiser, Rolf; Marcelin, Anne-Geneviève; Streinu-Cercel, Adrian; van Wyk, Jean; Dorr, Pat; Vandamme, Anne-Mieke

2018-01-01

Resistance to antiretroviral therapy (ART) threatens the efficacy of human immunodeficiency virus type 1 (HIV-1) treatment. We present a review of knowledge gaps in the science and technologies of acquired HIV-1 drug resistance (HIVDR) in an effort to facilitate research, scientific exchange, and progress in clinical management. The expert authorship of this review convened to identify data gaps that exist in the field of HIVDR and discuss their clinical implications. A subsequent literature review of trials and current practices was carried out to provide supporting evidence. Several gaps were identified across HIVDR science and technology. A summary of the major gaps is presented, with an expert discussion of their implications within the context of the wider field. Crucial to optimizing the use of ART will be improved understanding of protease inhibitors and, in particular, integrase strand transfer inhibitors (INSTI) in the context of HIVDR. Limited experience with INSTI represents an important knowledge gap in HIV resistance science. Utilizing such knowledge in a clinical setting relies on accurate testing and analysis of resistance-associated mutations. As next-generation sequencing becomes more widely available, a gap in the interpretation of data is the lack of a defined, clinically relevant threshold of minority variants. Further research will provide evidence on where such thresholds lie and how they can be most effectively applied. Expert discussion identified a series of gaps in our knowledge of HIVDR. Addressing prefsuch gaps through further research and characterization will facilitate the optimal use of ART therapies and technologies.

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

PubMed

Del Paggio, J C; Azariah, B; Sullivan, R; Hopman, W M; James, F V; Roshni, S; Tannock, I F; Booth, C M

2017-01-01

The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit. RCTs evaluating systemic therapy for breast cancer, nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011-2015 were reviewed. Data were abstracted regarding trial characteristics and outcomes, and these were applied to the ESMO-MCBS. We also determined whether RCTs were designed to detect an effect that would meet clinical benefit as defined by the ESMO-MCBS. About 277 eligible RCTs were included (40% breast, 31% NSCLC, 22% CRC, 6% pancreas). Median sample size was 532 and 83% were funded by industry. Among all 277 RCTs, the experimental therapy was statistically superior to the control arm in 138 (50%) trials: results of only 31% (43/138) of these trials met the ESMO-MCBS clinical benefit threshold. RCTs with curative intent were more likely to meet clinically meaningful thresholds than those with palliative intent [61% (19/31) versus 22% (24/107), P < 0.001]. Among the 226 RCTs for which the ESMO-MCBS could be applied, 31% (70/226) were designed to detect an effect size that could meet ESMO-MCBS thresholds. Less than one-third of contemporary RCTs with statistically significant results meet ESMO thresholds for meaningful clinical benefit, and this represents only 15% of all published trials. Investigators, funding agencies, regulatory agencies, and industry should adopt more stringent thresholds for meaningful benefit in the design of future RCTs. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bicarbonate in diabetic ketoacidosis - a systematic review

PubMed Central

2011-01-01

Objective This study was designed to examine the efficacy and risk of bicarbonate administration in the emergent treatment of severe acidemia in diabetic ketoacidosis (DKA). Methods PUBMED database was used to identify potentially relevant articles in the pediatric and adult DKA populations. DKA intervention studies on bicarbonate administration versus no bicarbonate in the emergent therapy, acid-base studies, studies on risk association with cerebral edema, and related case reports, were selected for review. Two reviewers independently conducted data extraction and assessed the citation relevance for inclusion. Results From 508 potentially relevant articles, 44 were included in the systematic review, including three adult randomized controlled trials (RCT) on bicarbonate administration versus no bicarbonate in DKA. We observed a marked heterogeneity in pH threshold, concentration, amount, and timing for bicarbonate administration in various studies. Two RCTs demonstrated transient improvement in metabolic acidosis with bicarbonate treatment within the initial 2 hours. There was no evidence of improved glycemic control or clinical efficacy. There was retrospective evidence of increased risk for cerebral edema and prolonged hospitalization in children who received bicarbonate, and weak evidence of transient paradoxical worsening of ketosis, and increased need for potassium supplementation. No studies involved patients with an initial pH < 6.85. Conclusions The evidence to date does not justify the administration of bicarbonate for the emergent treatment of DKA, especially in the pediatric population, in view of possible clinical harm and lack of sustained benefits. PMID:21906367

Ambrisentan response in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) - A subgroup analysis of the ARIES-E clinical trial.

PubMed

Fischer, Aryeh; Denton, Christopher P; Matucci-Cerinic, Marco; Gillies, Hunter; Blair, Christiana; Tislow, James; Nathan, Steven D

2016-08-01

Pulmonary arterial hypertension (PAH) is a condition which may lead to right ventricular failure and early mortality and is an important complication in patients with connective tissue disease (CTD). Previously, the endothelin A selective receptor antagonist, ambrisentan, demonstrated efficacy and safety in treating patients with PAH due to WHO Group I etiologies. These analyses describe the 3-year efficacy and safety of ambrisentan in patients specifically with CTD associated PAH (CTD-PAH). Patients with CTD-PAH participating in the ARIES-1 and -2 clinical trials and their long-term extension were evaluated. Efficacy evaluations including 6-min walk distance (6MWD), clinical worsening, and survival were collected at routine study visits. Additional analyses of 6MWD categorical (30 m) breakpoints were conducted to determine any relationship between 6MWD and a prognostic threshold for survival. 124 patients with CTD-PAH were evaluated. 62.6%, 57.3%, and 58.2% of CTD-PAH patients treated with ambrisentan exhibited increases in 6MWD at 1-, 2-, and 3- years respectively. At 3 years, 64% of patients were free from clinical worsening and 76% of patients were still alive (Kaplan-Meier estimates). Identified factors holding prognostic relevance for survival include: baseline functional class, CTD-PAH subgroup, patient sex, improvement in 6MWD ≥30 m over the first 12 weeks of treatment, the most recent 6MWD, and a 6MWD absolute threshold of 222 m. These first analyses of the 3-year treatment of CTD-PAH patients with ambrisentan revealed fewer clinical worsening events and improved survival compared to historical controls. Key exercise parameters were also identified which appear important in guiding treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hidden Hearing Injury: The Emerging Science and Military Relevance of Cochlear Synaptopathy.

PubMed

Tepe, Victoria; Smalt, Christopher; Nelson, Jeremy; Quatieri, Thomas; Pitts, Kenneth

2017-09-01

The phenomenon recently described as "hidden hearing loss" was the subject of a meeting co-hosted by the Department of Defense Hearing Center of Excellence and MIT Lincoln Laboratory to consider the potential relevance of noise-related synaptopathic injury to military settings and performance, service-related injury scenarios, and military medical priorities. Participants included approximately 50 researchers and subject matter experts from academic, federal, and military laboratories. Here we present a synthesis of discussion topics and concerns, as well as specific research objectives identified to develop militarily relevant knowledge. We consider findings from studies to date that have demonstrated cochlear synaptopathy and neurodegenerative processes apparently linked to noise exposure in animal models. We explore the potential relevance of these findings to the prediction and prevention of military hearing injuries, and to comorbid injuries in the neurological domain. Noise-induced cochlear synaptopathic injury is not detected by conventional audiometric assessment of threshold sensitivity. Animal studies suggest there may be a generous window of opportunity for intervention to mitigate or prevent cochlear neurodegenerative processes, e.g., by administration of neurotrophins or antioxidants. However, it is not yet known if the mechanisms that underlie "hidden hearing loss" also occur in human beings or, if so, how to identify them early, and how and when to intervene. Neurological injuries resulting from noise exposures via the auditory system have potentially significant implications for military Service Member performance, long-term Veteran health, and noise exposure standards. Mediated via auditory pathways, such injuries have possible relationship to clinical impairments including speech perception, and may be a largely overlooked contributor to cognitive symptoms associated with other military service-related injuries such as blast exposure and brain trauma. The potential health and performance consequences of noise-induced cochlear synaptopathic injury are easily overlooked, especially if it is assumed that hearing threshold sensitivity loss is the major concern. There should be a renewed impetus to further characterize and model synaptopathic mechanisms of auditory injury; study its potential impact on human auditory function, cognition, and performance metrics of military relevance; and develop solutions for auditory protection (including noise dosimetry) and treatment if appropriate following noise or blast exposure in military scenarios. We identify specific problems, solution objectives, and research objectives. Recommended research calls for a multidisciplinary approach to address cochlear nerve synaptopathy, central (brain) dysfunction, noise exposure measurement and metrics, and clinical assessment. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Systematic review and cost-effectiveness evaluation of 'pill-in-the-pocket' strategy for paroxysmal atrial fibrillation compared to episodic in-hospital treatment or continuous antiarrhythmic drug therapy.

PubMed

Saborido, C Martin; Hockenhull, J; Bagust, A; Boland, A; Dickson, R; Todd, D

2010-06-01

Atrial fibrillation (AF) is a tachyarrhythmia characterised by uncoordinated atrial activation with consequent deterioration of impairment of atrial function and a rapid, irregular heartbeat. The annual incidence rate of paroxysmal AF (PAF) has been estimated at 1.0 per 1000 person-years (95% confidence interval 0.9 to 1.1), and reported prevalence rates show wide variations depending on age and country. Conventional treatment strategies for PAF focus on the suppression of paroxysms of AF and return to normal sinus rhythm. To summarise the results of the rapid reviews of the clinical effectiveness and cost-effectiveness literature describing the pill-in-the-pocket (PiP) approach for the treatment of patients with PAF; and to develop an economic model to assess the cost-effectiveness of PiP compared with in-hospital treatment (IHT) or continuous antiarrhythmic drugs (AADs) for the treatment of patients with PAF. Ovid MEDLINE and Ovid OLDMEDLINE 1950 to present with Daily Update were searched. The following electronic databases were searched for ongoing trials: Health Services Research Projects in Progress, ClinicalTrials.gov, metaRegister of Current Controlled Trials, BioMed Central, World Health Organization International Clinical Trials Registry Platform, ClinicalStudyResults.org and the National Library of Medicine Gateway. Inclusion criteria, which included patients suffering from PAF, were independently applied to all identified references by two reviewers (JH and CMS). Electronic searches were conducted to identify clinical effectiveness and cost-effectiveness evidence describing the use of a PiP strategy for the treatment of PAF, published since the release of the Royal College of Physicians' national guidelines on AF in June 2006. A Markov model was constructed to examine differences between three PAF strategies (PiP, AAD and IHT) in terms of cost per quality-adjusted life-year (QALY). A Markov model structure was chosen because it is assumed that PAF is a condition that causes patients to move between a limited number of relevant health states during their lives. The search strategies for clinical studies identified 201 randomised controlled trials (RCTs). Of the 201 RCTs identified, 12 were deemed to be relevant to the decision problem as they included drugs used to treat PAF; summary data were abstracted from these studies in order to inform the development of the economic model only. The model results indicate that the PiP strategy is slightly less effective than the other two strategies, but also less costly (incremental cost-effectiveness ratio of 45,916 pounds per QALY when compared to AAD, and 12,424 pounds per QALY when compared to IHT). The one-way sensitivity analyses performed do not show substantial changes in relative cost-effectiveness except in relation to the age of patients, where PiP dominates AAD in men over 65 years and in women over 70 years. At a threshold of 25,000 pounds per QALY, IHT has the maximum probability of being cost-effective at this threshold. For threshold values between 0 pounds and 9266 pounds per QALY, PiP is the option exhibiting the maximum probability of being cost-effective. The AAD strategy has a very poor probability of being cost-effective under any threshold. However, none of the strategies considered has more than a 40% probability of being cost-effective at a threshold of 25,000 pounds per QALY at any threshold level. This demonstrates the uncertainty around the parameters and its effect on the decision to choose any one strategy over the others. Most of the data used to populate the model have been taken from studies with populations that do not match the patient population specified in the decision problem. Populating the model in this way was unavoidable as there was a paucity of published clinical effectiveness and cost-effectiveness data describing a PiP strategy for this highly specific group of patients. Overall, a PiP strategy seems to be slightly less effective (i.e. fewer QALYs gained) than AAD and IHT, but is associated with cost savings. A PiP strategy seems to be more efficacious and cost-effective than an AAD strategy in men over 65 years and women over 70 years, but this is principally due to a very slight difference in QALY gained by the PiP strategy. A change in clinical practice that includes the introduction of PiP may save costs, but also involves a reduction in clinical effectiveness compared to existing approaches used to treat patients with PAF. Uncertainty in the available clinical data means there was insufficient evidence to support a recommendation for the use of PiP strategy in patients with PAF. Further research should identify outcomes of interest such as adverse events and recurrent AF episodes in an RCT setting because the only clinical study addressing these issues, even partially, is not an RCT but a descriptive analysis. Patient preferences also need to be considered in any future research designs.

Monitoring of Tumor Growth with [(18)F]-FET PET in a Mouse Model of Glioblastoma: SUV Measurements and Volumetric Approaches.

PubMed

Holzgreve, Adrien; Brendel, Matthias; Gu, Song; Carlsen, Janette; Mille, Erik; Böning, Guido; Mastrella, Giorgia; Unterrainer, Marcus; Gildehaus, Franz J; Rominger, Axel; Bartenstein, Peter; Kälin, Roland E; Glass, Rainer; Albert, Nathalie L

2016-01-01

Noninvasive tumor growth monitoring is of particular interest for the evaluation of experimental glioma therapies. This study investigates the potential of positron emission tomography (PET) using O-(2-(18)F-fluoroethyl)-L-tyrosine ([(18)F]-FET) to determine tumor growth in a murine glioblastoma (GBM) model-including estimation of the biological tumor volume (BTV), which has hitherto not been investigated in the pre-clinical context. Fifteen GBM-bearing mice (GL261) and six control mice (shams) were investigated during 5 weeks by PET followed by autoradiographic and histological assessments. [(18)F]-FET PET was quantitated by calculation of maximum and mean standardized uptake values within a universal volume-of-interest (VOI) corrected for healthy background (SUVmax/BG, SUVmean/BG). A partial volume effect correction (PVEC) was applied in comparison to ex vivo autoradiography. BTVs obtained by predefined thresholds for VOI definition (SUV/BG: ≥1.4; ≥1.6; ≥1.8; ≥2.0) were compared to the histologically assessed tumor volume (n = 8). Finally, individual "optimal" thresholds for BTV definition best reflecting the histology were determined. In GBM mice SUVmax/BG and SUVmean/BG clearly increased with time, however at high inter-animal variability. No relevant [(18)F]-FET uptake was observed in shams. PVEC recovered signal loss of SUVmean/BG assessment in relation to autoradiography. BTV as estimated by predefined thresholds strongly differed from the histology volume. Strikingly, the individual "optimal" thresholds for BTV assessment correlated highly with SUVmax/BG (ρ = 0.97, p < 0.001), allowing SUVmax/BG-based calculation of individual thresholds. The method was verified by a subsequent validation study (n = 15, ρ = 0.88, p < 0.01) leading to extensively higher agreement of BTV estimations when compared to histology in contrast to predefined thresholds. [(18)F]-FET PET with standard SUV measurements is feasible for glioma imaging in the GBM mouse model. PVEC is beneficial to improve accuracy of [(18)F]-FET PET SUV quantification. Although SUVmax/BG and SUVmean/BG increase during the disease course, these parameters do not correlate with the respective tumor size. For the first time, we propose a histology-verified method allowing appropriate individual BTV estimation for volumetric in vivo monitoring of tumor growth with [(18)F]-FET PET and show that standardized thresholds from routine clinical practice seem to be inappropriate for BTV estimation in the GBM mouse model.

Oxytocin administration selectively improves olfactory detection thresholds for lyral in patients with schizophrenia

PubMed Central

Woolley, J.D.; Lam, O.; Chuang, B.; Ford, J.M.; Mathalon, D.H.; Vinogradov, S.

2015-01-01

Summary Background Olfaction plays an important role in mammalian social behavior. Olfactory deficits are common in schizophrenia and correlate with negative symptoms and low social drive. Despite their prominence and possible clinical relevance, little is understood about the pathological mechanisms underlying olfactory deficits in schizophrenia and there are currently no effective treatments for these deficits. The prosocial neuropeptide oxytocin may affect the olfactory system when administered intranasally to humans and there is growing interest in its therapeutic potential in schizophrenia. Methods To examine this model, we administered 40 IU of oxytocin and placebo intranasally to 31 patients with a schizophrenia spectrum illness and 34 age-matched healthy control participants in a randomized, double-blind, placebo-controlled, cross-over study. On each test day, participants completed an olfactory detection threshold test for two different odors: (1) lyral, a synthetic fragrance compound for which patients with schizophrenia have specific olfactory detection threshold deficits, possibly related to decreased cyclic adenosine 3′,5′-monophosphate (cAMP) signaling; and (2) anise, a compound for which olfactory detection thresholds change with menstrual cycle phase in women. Results On the placebo test day, patients with schizophrenia did not significantly differ from healthy controls in detection of either odor. We found that oxytocin administration significantly and selectively improved olfactory detection thresholds for lyral but not for anise in patients with schizophrenia. In contrast, oxytocin had no effect on detection of either odor in healthy controls. Discussion Our data indicate that oxytocin administration may ameliorate olfactory deficits in schizophrenia and suggest the effects of intranasal oxytocin may extend to influencing the olfactory system. Given that oxytocin has been found to increase cAMP signaling in vitro a possible mechanism for these effects is discussed. PMID:25637811

Oxytocin administration selectively improves olfactory detection thresholds for lyral in patients with schizophrenia.

PubMed

Woolley, J D; Lam, O; Chuang, B; Ford, J M; Mathalon, D H; Vinogradov, S

2015-03-01

Olfaction plays an important role in mammalian social behavior. Olfactory deficits are common in schizophrenia and correlate with negative symptoms and low social drive. Despite their prominence and possible clinical relevance, little is understood about the pathological mechanisms underlying olfactory deficits in schizophrenia and there are currently no effective treatments for these deficits. The prosocial neuropeptide oxytocin may affect the olfactory system when administered intranasally to humans and there is growing interest in its therapeutic potential in schizophrenia. To examine this model, we administered 40IU of oxytocin and placebo intranasally to 31 patients with a schizophrenia spectrum illness and 34 age-matched healthy control participants in a randomized, double-blind, placebo-controlled, cross-over study. On each test day, participants completed an olfactory detection threshold test for two different odors: (1) lyral, a synthetic fragrance compound for which patients with schizophrenia have specific olfactory detection threshold deficits, possibly related to decreased cyclic adenosine 3',5'-monophosphate (cAMP) signaling; and (2) anise, a compound for which olfactory detection thresholds change with menstrual cycle phase in women. On the placebo test day, patients with schizophrenia did not significantly differ from healthy controls in detection of either odor. We found that oxytocin administration significantly and selectively improved olfactory detection thresholds for lyral but not for anise in patients with schizophrenia. In contrast, oxytocin had no effect on detection of either odor in healthy controls. Our data indicate that oxytocin administration may ameliorate olfactory deficits in schizophrenia and suggest the effects of intranasal oxytocin may extend to influencing the olfactory system. Given that oxytocin has been found to increase cAMP signaling in vitro a possible mechanism for these effects is discussed. Published by Elsevier Ltd.

Comparison of clinical probability-adjusted D-dimer and age-adjusted D-dimer interpretation to exclude venous thromboembolism.

PubMed

Takach Lapner, Sarah; Julian, Jim A; Linkins, Lori-Ann; Bates, Shannon; Kearon, Clive

2017-10-05

Two new strategies for interpreting D-dimer results have been proposed: i) using a progressively higher D-dimer threshold with increasing age (age-adjusted strategy) and ii) using a D-dimer threshold in patients with low clinical probability that is twice the threshold used in patients with moderate clinical probability (clinical probability-adjusted strategy). Our objective was to compare the diagnostic accuracy of age-adjusted and clinical probability-adjusted D-dimer interpretation in patients with a low or moderate clinical probability of venous thromboembolism (VTE). We performed a retrospective analysis of clinical data and blood samples from two prospective studies. We compared the negative predictive value (NPV) for VTE, and the proportion of patients with a negative D-dimer result, using two D-dimer interpretation strategies: the age-adjusted strategy, which uses a progressively higher D-dimer threshold with increasing age over 50 years (age in years × 10 µg/L FEU); and the clinical probability-adjusted strategy which uses a D-dimer threshold of 1000 µg/L FEU in patients with low clinical probability and 500 µg/L FEU in patients with moderate clinical probability. A total of 1649 outpatients with low or moderate clinical probability for a first suspected deep vein thrombosis or pulmonary embolism were included. The NPV of both the clinical probability-adjusted strategy (99.7 %) and the age-adjusted strategy (99.6 %) were similar. However, the proportion of patients with a negative result was greater with the clinical probability-adjusted strategy (56.1 % vs, 50.9 %; difference 5.2 %; 95 % CI 3.5 % to 6.8 %). These findings suggest that clinical probability-adjusted D-dimer interpretation is a better way of interpreting D-dimer results compared to age-adjusted interpretation.

Cortical and Sensory Causes of Individual Differences in Selective Attention Ability among Listeners with Normal Hearing Thresholds

ERIC Educational Resources Information Center

Shinn-Cunningham, Barbara

2017-01-01

Purpose: This review provides clinicians with an overview of recent findings relevant to understanding why listeners with normal hearing thresholds (NHTs) sometimes suffer from communication difficulties in noisy settings. Method: The results from neuroscience and psychoacoustics are reviewed. Results: In noisy settings, listeners focus their…

Noise reduction in Lidar signal using correlation-based EMD combined with soft thresholding and roughness penalty

NASA Astrophysics Data System (ADS)

Chang, Jianhua; Zhu, Lingyan; Li, Hongxu; Xu, Fan; Liu, Binggang; Yang, Zhenbo

2018-01-01

Empirical mode decomposition (EMD) is widely used to analyze the non-linear and non-stationary signals for noise reduction. In this study, a novel EMD-based denoising method, referred to as EMD with soft thresholding and roughness penalty (EMD-STRP), is proposed for the Lidar signal denoising. With the proposed method, the relevant and irrelevant intrinsic mode functions are first distinguished via a correlation coefficient. Then, the soft thresholding technique is applied to the irrelevant modes, and the roughness penalty technique is applied to the relevant modes to extract as much information as possible. The effectiveness of the proposed method was evaluated using three typical signals contaminated by white Gaussian noise. The denoising performance was then compared to the denoising capabilities of other techniques, such as correlation-based EMD partial reconstruction, correlation-based EMD hard thresholding, and wavelet transform. The use of EMD-STRP on the measured Lidar signal resulted in the noise being efficiently suppressed, with an improved signal to noise ratio of 22.25 dB and an extended detection range of 11 km.

Interplay of threshold resummation and hadron mass corrections in deep inelastic processes

DOE PAGES

Accardi, Alberto; Anderle, Daniele P.; Ringer, Felix

2015-02-01

We discuss hadron mass corrections and threshold resummation for deep-inelastic scattering lN-->l'X and semi-inclusive annihilation e +e - → hX processes, and provide a prescription how to consistently combine these two corrections respecting all kinematic thresholds. We find an interesting interplay between threshold resummation and target mass corrections for deep-inelastic scattering at large values of Bjorken x B. In semi-inclusive annihilation, on the contrary, the two considered corrections are relevant in different kinematic regions and do not affect each other. A detailed analysis is nonetheless of interest in the light of recent high precision data from BaBar and Belle onmore » pion and kaon production, with which we compare our calculations. For both deep inelastic scattering and single inclusive annihilation, the size of the combined corrections compared to the precision of world data is shown to be large. Therefore, we conclude that these theoretical corrections are relevant for global QCD fits in order to extract precise parton distributions at large Bjorken x B, and fragmentation functions over the whole kinematic range.« less

A novel approach to estimation of the time to biomarker threshold: applications to HIV.

PubMed

Reddy, Tarylee; Molenberghs, Geert; Njagi, Edmund Njeru; Aerts, Marc

2016-11-01

In longitudinal studies of biomarkers, an outcome of interest is the time at which a biomarker reaches a particular threshold. The CD4 count is a widely used marker of human immunodeficiency virus progression. Because of the inherent variability of this marker, a single CD4 count below a relevant threshold should be interpreted with caution. Several studies have applied persistence criteria, designating the outcome as the time to the occurrence of two consecutive measurements less than the threshold. In this paper, we propose a method to estimate the time to attainment of two consecutive CD4 counts less than a meaningful threshold, which takes into account the patient-specific trajectory and measurement error. An expression for the expected time to threshold is presented, which is a function of the fixed effects, random effects and residual variance. We present an application to human immunodeficiency virus-positive individuals from a seroprevalent cohort in Durban, South Africa. Two thresholds are examined, and 95% bootstrap confidence intervals are presented for the estimated time to threshold. Sensitivity analysis revealed that results are robust to truncation of the series and variation in the number of visits considered for most patients. Caution should be exercised when interpreting the estimated times for patients who exhibit very slow rates of decline and patients who have less than three measurements. We also discuss the relevance of the methodology to the study of other diseases and present such applications. We demonstrate that the method proposed is computationally efficient and offers more flexibility than existing frameworks. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

How much is enough? Examining frequency criteria for NSSI disorder in adolescent inpatients.

PubMed

Muehlenkamp, Jennifer J; Brausch, Amy M; Washburn, Jason J

2017-06-01

To empirically evaluate the diagnostic relevance of the proposed Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5 ; APA, 2013) Criterion-A frequency threshold for nonsuicidal self-injury (NSSI) disorder. Archival, de-identified, self-reported clinical assessment data from 746 adolescent psychiatric patients (Mage = 14.97; 88% female; 76% White) were used. The sample was randomly split into 2 unique samples for data analyses. Measures included assessments of NSSI, proposed DSM-5 NSSI-disorder criteria, psychopathology, dysfunction, distress, functional impairment, and suicidality. Discriminant-function analyses run with Sample A identified a significant differentiation of groups based on a frequency of NSSI at 25 or more days in the past year, Λ = .814, χ2(54) = 72.59, p < .05, canonical R2 = .36. This cutoff was replicated in the second sample. All patients were coded into 1 of 3 empirically derived NSSI-frequency cutoff groups: high (>25 days), moderate (5-24 days), and low (1-4 days) and compared. The high-NSSI group scored higher on most NSSI features, including DSM-5 -proposed Criterion-B and -C symptoms, depression, psychotic symptoms, substance abuse, borderline personality-disorder features, suicidal ideation, and suicide plans, than the moderate- and low-NSSI groups, who did not differ from each other on many of the variables. The currently proposed DSM-5 Criterion-A frequency threshold for NSSI disorder lacks validity and clinical utility. The field needs to consider raising the frequency threshold to ensure that a meaningful and valid set of diagnostic criteria are established, and to avoid overpathologizing individuals who infrequently engage in NSSI. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Repeatability of quantitative sensory testing in healthy cats in a clinical setting with comparison to cats with osteoarthritis.

PubMed

Addison, Elena S; Clements, Dylan N

2017-12-01

Objectives The aim of this study was to evaluate the repeatability of quantitative sensory tests (QSTs) in a group of healthy untrained cats (n = 14) and to compare the results with those from cats with osteoarthritis (n = 7). Methods Peak vertical force (PVF) and vertical impulse were measured on a pressure plate system. Thermal sensitivity was assessed using a temperature-controlled plate at 7°C and 40°C. Individual paw lifts and overall duration of paw lifts were counted and measured for each limb. Paw withdrawal thresholds were measured using manual and electronic von Frey monofilaments (MVF and EVF, respectively) applied to the metacarpal or metatarsal pads. All measurements were repeated twice to assess repeatability of the tests. Results In healthy cats all tests were moderately repeatable. When compared with cats with osteoarthritis the PVF was significantly higher in healthy hindlimbs in repeat 1 but not in repeat 2. Cats with osteoarthritis of the forelimbs showed a decrease in the frequency of paw lifts on the 7°C plate compared with cats with healthy forelimbs, and the duration of paw lifts was significantly less than healthy forelimbs in the first repeat but not in the second repeat. Osteoarthritic limbs had significantly lower paw withdrawal thresholds with both MVF and EVF than healthy limbs. Conclusions and relevance QSTs are moderately repeatable in untrained cats. Kinetic gait analysis did not permit differentiation between healthy limbs and those with osteoarthritis, but thermal sensitivity testing (cold) does. Sensory threshold testing can differentiate osteoarthritic and healthy limbs, and may be useful in the diagnosis and monitoring of this condition in cats in the clinical setting.

Topological dimension tunes activity patterns in hierarchical modular networks

NASA Astrophysics Data System (ADS)

Safari, Ali; Moretti, Paolo; Muñoz, Miguel A.

2017-11-01

Connectivity patterns of relevance in neuroscience and systems biology can be encoded in hierarchical modular networks (HMNs). Recent studies highlight the role of hierarchical modular organization in shaping brain activity patterns, providing an excellent substrate to promote both segregation and integration of neural information. Here, we propose an extensive analysis of the critical spreading rate (or ‘epidemic’ threshold)—separating a phase with endemic persistent activity from one in which activity ceases—on diverse HMNs. By employing analytical and computational techniques we determine the nature of such a threshold and scrutinize how it depends on general structural features of the underlying HMN. We critically discuss the extent to which current graph-spectral methods can be applied to predict the onset of spreading in HMNs and, most importantly, we elucidate the role played by the network topological dimension as a relevant and unifying structural parameter, controlling the epidemic threshold.

Short-term changes in neck pain, widespread pressure pain sensitivity, and cervical range of motion after the application of trigger point dry needling in patients with acute mechanical neck pain: a randomized clinical trial.

PubMed

Mejuto-Vázquez, María J; Salom-Moreno, Jaime; Ortega-Santiago, Ricardo; Truyols-Domínguez, Sebastián; Fernández-de-Las-Peñas, César

2014-04-01

Randomized clinical trial. To determine the effects of trigger point dry needling (TrPDN) on neck pain, widespread pressure pain sensitivity, and cervical range of motion in patients with acute mechanical neck pain and active trigger points in the upper trapezius muscle. TrPDN seems to be effective for decreasing pain in individuals with upper-quadrant pain syndromes. Potential effects of TrPDN for decreasing pain and sensitization in individuals with acute mechanical neck pain are needed. Methods Seventeen patients (53% female) were randomly assigned to 1 of 2 groups: a single session of TrPDN or no intervention (waiting list). Pressure pain thresholds over the C5-6 zygapophyseal joint, second metacarpal, and tibialis anterior muscle; neck pain intensity; and cervical spine range-of-motion data were collected at baseline (pretreatment) and 10 minutes and 1 week after the intervention by an assessor blinded to the treatment allocation of the patient. Mixed-model analyses of variance were used to examine the effects of treatment on each outcome variable. Patients treated with 1 session of TrPDN experienced greater decreases in neck pain, greater increases in pressure pain threshold, and higher increases in cervical range of motion than those who did not receive an intervention at both 10 minutes and 1 week after the intervention (P<.01 for all comparisons). Between-group effect sizes were medium to large immediately after the TrPDN session (standardized mean score differences greater than 0.56) and large at the 1-week follow-up (standardized mean score differences greater than 1.34). The results of the current randomized clinical trial suggest that a single session of TrPDN may decrease neck pain intensity and widespread pressure pain sensitivity, and also increase active cervical range of motion, in patients with acute mechanical neck pain. Changes in pain, pressure pain threshold, and cervical range of motion surpassed their respective minimal detectable change values, supporting clinically relevant treatment effects. Level of Evidence Therapy, level 1b-.

Current role of cryotherapy in retinopathy of prematurity: a report by the American Academy of Ophthalmology.

PubMed

Simpson, Jennifer L; Melia, Michele; Yang, Michael B; Buffenn, Angela N; Chiang, Michael F; Lambert, Scott R

2012-04-01

To evaluate the role of cryotherapy in the current treatment of retinopathy of prematurity (ROP). Literature searches of PubMed and the Cochrane Library were conducted on December 2, 2009, for articles published after 1984. The searches included all languages and retrieved 187 relevant citations. Thirteen articles were deemed relevant to the assessment question and were rated according to the strength of evidence. Four articles reported results from 2 large multicenter randomized clinical trials, and the remaining 9 articles reported results of 3 small randomized trials that directly compared cryotherapy and laser. Neither of the multicenter randomized clinical trials was a direct comparison of cryotherapy with laser. These studies were used to evaluate the comparative trials based on treatment criteria, study populations, and clinical results. Higher percentages of poor structural and functional outcomes generally were seen in eyes treated with cryotherapy compared with eyes undergoing laser treatment. Higher rates of systemic complications and myopia also were identified after treatment with cryotherapy. Despite a relative paucity of level I evidence directly comparing cryotherapy and laser treatment for threshold ROP, the literature suggests that neonatal facilities should gain access to laser technology and laser-trained ophthalmic staff to achieve better outcomes for treatment of the disease. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The dynamics of learning about a climate threshold

NASA Astrophysics Data System (ADS)

Keller, Klaus; McInerney, David

2008-02-01

Anthropogenic greenhouse gas emissions may trigger threshold responses of the climate system. One relevant example of such a potential threshold response is a shutdown of the North Atlantic meridional overturning circulation (MOC). Numerous studies have analyzed the problem of early MOC change detection (i.e., detection before the forcing has committed the system to a threshold response). Here we analyze the early MOC prediction problem. To this end, we virtually deploy an MOC observation system into a simple model that mimics potential future MOC responses and analyze the timing of confident detection and prediction. Our analysis suggests that a confident prediction of a potential threshold response can require century time scales, considerably longer that the time required for confident detection. The signal enabling early prediction of an approaching MOC threshold in our model study is associated with the rate at which the MOC intensity decreases for a given forcing. A faster MOC weakening implies a higher MOC sensitivity to forcing. An MOC sensitivity exceeding a critical level results in a threshold response. Determining whether an observed MOC trend in our model differs in a statistically significant way from an unforced scenario (the detection problem) imposes lower requirements on an observation system than the determination whether the MOC will shut down in the future (the prediction problem). As a result, the virtual observation systems designed in our model for early detection of MOC changes might well fail at the task of early and confident prediction. Transferring this conclusion to the real world requires a considerably refined MOC model, as well as a more complete consideration of relevant observational constraints.

Domestic violence and mental health: a cross-sectional survey of women seeking help from domestic violence support services.

PubMed

Ferrari, Giulia; Agnew-Davies, Roxane; Bailey, Jayne; Howard, Louise; Howarth, Emma; Peters, Tim J; Sardinha, Lynnmarie; Feder, Gene

2014-01-01

Domestic violence and abuse (DVA) are associated with an increased risk of mental illness, but we know little about the mental health of female DVA survivors seeking support from domestic violence services. Domestic violence and abuse (DVA) are associated with an increased risk of mental illness, but we know little about the mental health of female DVA survivors seeking support from domestic violence services. Baseline data on 260 women enrolled in a randomized controlled trial of a psychological intervention for DVA survivors was analyzed. We report prevalence of and associations between mental health status and severity of abuse at the time of recruitment. We used logistic and normal regression models for binary and continuous outcomes, respectively. Mental health measures used were: Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), Patient Health Questionnaire, Generalized Anxiety Disorder Assessment, and the Posttraumatic Diagnostic Scale (PDS) to measure posttraumatic stress disorder. The Composite Abuse Scale (CAS) measured abuse. Exposure to DVA was high, with a mean CAS score of 56 (SD 34). The mean CORE-OM score was 18 (SD 8) with 76% above the clinical threshold (95% confidence interval: 70-81%). Depression and anxiety levels were high, with means close to clinical thresholds, and all respondents recorded PTSD scores above the clinical threshold. Symptoms of mental illness increased stepwise with increasing severity of DVA. Exposure to DVA was high, with a mean CAS score of 56 (SD 34). The mean CORE-OM score was 18 (SD 8) with 76% above the clinical threshold (95% confidence interval: 70-81%). Depression and anxiety levels were high, with means close to clinical thresholds, and all respondents recorded PTSD scores above the clinical threshold. Symptoms of mental illness increased stepwise with increasing severity of DVA.

Agreeable Smellers and Sensitive Neurotics – Correlations among Personality Traits and Sensory Thresholds

PubMed Central

Croy, Ilona; Springborn, Maria; Lötsch, Jörn; Johnston, Amy N. B.; Hummel, Thomas

2011-01-01

Correlations between personality traits and a wide range of sensory thresholds were examined. Participants (N = 124) completed a personality inventory (NEO-FFI) and underwent assessment of olfactory, trigeminal, tactile and gustatory detection thresholds, as well as examination of trigeminal and tactile pain thresholds. Significantly enhanced odor sensitivity in socially agreeable people, significantly enhanced trigeminal sensitivity in neurotic subjects, and a tendency for enhanced pain tolerance in highly conscientious participants was revealed. It is postulated that varied sensory processing may influence an individual's perception of the environment; particularly their perception of socially relevant or potentially dangerous stimuli and thus, varied with personality. PMID:21556139

Agreeable smellers and sensitive neurotics--correlations among personality traits and sensory thresholds.

PubMed

Croy, Ilona; Springborn, Maria; Lötsch, Jörn; Johnston, Amy N B; Hummel, Thomas

2011-04-27

Correlations between personality traits and a wide range of sensory thresholds were examined. Participants (N = 124) completed a personality inventory (NEO-FFI) and underwent assessment of olfactory, trigeminal, tactile and gustatory detection thresholds, as well as examination of trigeminal and tactile pain thresholds. Significantly enhanced odor sensitivity in socially agreeable people, significantly enhanced trigeminal sensitivity in neurotic subjects, and a tendency for enhanced pain tolerance in highly conscientious participants was revealed. It is postulated that varied sensory processing may influence an individual's perception of the environment; particularly their perception of socially relevant or potentially dangerous stimuli and thus, varied with personality.

Customization of Advia 120 thresholds for canine erythrocyte volume and hemoglobin concentration, and effects on morphology flagging results.

PubMed

Grimes, Carolyn N; Fry, Michael M

2014-12-01

This study sought to develop customized morphology flagging thresholds for canine erythrocyte volume and hemoglobin concentration [Hgb] on the ADVIA 120 hematology analyzer; compare automated morphology flagging with results of microscopic blood smear evaluation; and examine effects of customized thresholds on morphology flagging results. Customized thresholds were determined using data from 52 clinically healthy dogs. Blood smear evaluation and automated morphology flagging results were correlated with mean cell volume (MCV) and cellular hemoglobin concentration mean (CHCM) in 26 dogs. Customized thresholds were applied retroactively to complete blood (cell) count (CBC) data from 5 groups of dogs, including a reference sample group, clinical cases, and animals with experimentally induced iron deficiency anemia. Automated morphology flagging correlated more highly with MCV or CHCM than did blood smear evaluation; correlation with MCV was highest using customized thresholds. Customized morphology flagging thresholds resulted in more sensitive detection of microcytosis, macrocytosis, and hypochromasia than default thresholds.

Reliability, Validity, and Clinical Utility of the Dominic Interactive for Adolescents-RevisedA DSM-5-Based Self-Report Screen for Mental Disorders, Borderline Personality Traits, and Suicidality.

PubMed

Bergeron, Lise; Smolla, Nicole; Berthiaume, Claude; Renaud, Johanne; Breton, Jean-Jacques; St-Georges, Marie; Morin, Pauline; Zavaglia, Elissa; Labelle, Réal

2017-03-01

The Dominic Interactive for Adolescents-Revised (DIA-R) is a multimedia self-report screen for 9 mental disorders, borderline personality traits, and suicidality defined by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders ( DSM-5). This study aimed to examine the reliability and the validity of this instrument. French- and English-speaking adolescents aged 12 to 15 years ( N = 447) were recruited from schools and clinical settings in Montreal and were evaluated twice. The internal consistency was estimated by Cronbach alpha coefficients and the test-retest reliability by intraclass correlation coefficients. Cutoff points on the DIA-R scales were determined by using clinically relevant measures for defining external validation criteria: the Schedule for Affective Disorders and Schizophrenia for School-Aged Children, the Beck Hopelessness Scale, and the Abbreviated-Diagnostic Interview for Borderlines. Receiver operating characteristic (ROC) analyses provided accuracy estimates (area under the ROC curve, sensitivity, specificity, likelihood ratio) to evaluate the ability of the DIA-R scales to predict external criteria. For most of the DIA-R scales, reliability coefficients were excellent or moderate. High or moderate accuracy estimates from ROC analyses demonstrated the ability of the DIA-R thresholds to predict psychopathological conditions. These thresholds were generally capable to discriminate between clinical and school subsamples. However, the validity of the obsessions/compulsions scale was too low. Findings clearly support the reliability and the validity of the DIA-R. This instrument may be useful to assess a wide range of adolescents' mental health problems in the continuum of services. This conclusion applies to all scales, except the obsessions/compulsions one.

GREAT: a gradient-based color-sampling scheme for Retinex.

PubMed

Lecca, Michela; Rizzi, Alessandro; Serapioni, Raul Paolo

2017-04-01

Modeling the local color spatial distribution is a crucial step for the algorithms of the Milano Retinex family. Here we present GREAT, a novel, noise-free Milano Retinex implementation based on an image-aware spatial color sampling. For each channel of a color input image, GREAT computes a 2D set of edges whose magnitude exceeds a pre-defined threshold. Then GREAT re-scales the channel intensity of each image pixel, called target, by the average of the intensities of the selected edges weighted by a function of their positions, gradient magnitudes, and intensities relative to the target. In this way, GREAT enhances the input image, adjusting its brightness, contrast and dynamic range. The use of the edges as pixels relevant to color filtering is justified by the importance that edges play in human color sensation. The name GREAT comes from the expression "Gradient RElevAnce for ReTinex," which refers to the threshold-based definition of a gradient relevance map for edge selection and thus for image color filtering.

Semi-automatic assessment of pediatric hydronephrosis severity in 3D ultrasound

NASA Astrophysics Data System (ADS)

Cerrolaza, Juan J.; Otero, Hansel; Yao, Peter; Biggs, Elijah; Mansoor, Awais; Ardon, Roberto; Jago, James; Peters, Craig A.; Linguraru, Marius George

2016-03-01

Hydronephrosis is the most common abnormal finding in pediatric urology. Thanks to its non-ionizing nature, ultrasound (US) imaging is the preferred diagnostic modality for the evaluation of the kidney and the urinary track. However, due to the lack of correlation of US with renal function, further invasive and/or ionizing studies might be required (e.g., diuretic renograms). This paper presents a computer-aided diagnosis (CAD) tool for the accurate and objective assessment of pediatric hydronephrosis based on morphological analysis of kidney from 3DUS scans. The integration of specific segmentation tools in the system, allows to delineate the relevant renal structures from 3DUS scans of the patients with minimal user interaction, and the automatic computation of 90 anatomical features. Using the washout half time (T1/2) as indicative of renal obstruction, an optimal subset of predictive features is selected to differentiate, with maximum sensitivity, those severe cases where further attention is required (e.g., in the form of diuretic renograms), from the noncritical ones. The performance of this new 3DUS-based CAD system is studied for two clinically relevant T1/2 thresholds, 20 and 30 min. Using a dataset of 20 hydronephrotic cases, pilot experiments show how the system outperforms previous 2D implementations by successfully identifying all the critical cases (100% of sensitivity), and detecting up to 100% (T1/2 = 20 min) and 67% (T1/2 = 30 min) of non-critical ones for T1/2 thresholds of 20 and 30 min, respectively.

Influence of surgical gloves on haptic perception thresholds.

PubMed

Hatzfeld, Christian; Dorsch, Sarah; Neupert, Carsten; Kupnik, Mario

2018-02-01

Impairment of haptic perception by surgical gloves could reduce requirements on haptic systems for surgery. While grip forces and manipulation capabilities were not impaired in previous studies, no data is available for perception thresholds. Absolute and differential thresholds (20 dB above threshold) of 24 subjects were measured for frequencies of 25 and 250 Hz with a Ψ-method. Effects of wearing a surgical glove, moisture on the contact surface and subject's experience with gloves were incorporated in a full-factorial experimental design. Absolute thresholds of 12.8 dB and -29.6 dB (means for 25 and 250 Hz, respectively) and differential thresholds of -12.6 dB and -9.5 dB agree with previous studies. A relevant effect of the frequency on absolute thresholds was found. Comparisons of glove- and no-glove-conditions did not reveal a significant mean difference. Wearing a single surgical glove does not affect absolute and differential haptic perception thresholds. Copyright © 2017 John Wiley & Sons, Ltd.

78 FR 71566 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to a...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-29

... species or stock(s) for subsistence uses (where relevant). Further, the permissible methods of taking and... Thresholds During Pile Installation Distance Area (sq. Pile type Method Threshold (m)\\1\\ km)\\2\\ Steel (sheet... methods of taking pursuant to such activity, and other means of effecting the least practicable impact on...

Is skin penetration a determining factor in skin sensitization potential and potency? Refuting the notion of a LogKow threshold for Skin Sensitization

EPA Science Inventory

Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW < 500, are assumed and widely accepted as self-evident truths. Objective...

Newly postulated neurodevelopmental risks of pediatric anesthesia: theories that could rock our world.

PubMed

Hays, Stephen Robert; Deshpande, Jayant K

2013-04-01

General anesthetics can induce apoptotic neurodegeneration and subsequent maladaptive behaviors in animals. Retrospective human studies suggest associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes. The relevance of animal data to clinical practice is unclear and to our knowledge the causality underlying observed associations in humans is unknown. We reviewed newly postulated neurodevelopmental risks of pediatric anesthesia and discuss implications for the surgical care of children. We queried the MEDLINE®/PubMed® and EMBASE® databases for citations in English on pediatric anesthetic neurotoxicity with the focus on references from the last decade. Animal studies in rodents and primates demonstrate apoptotic neuropathology and subsequent maladaptive behaviors after exposure to all currently available general anesthetics with the possible exception of α2-adrenergic agonists. Similar adverse pathological and clinical effects occur after untreated pain. Anesthetic neurotoxicity in animals develops only after exposure above threshold doses and durations during a critical neurodevelopmental window of maximal synaptogenesis in the absence of concomitant painful stimuli. Anesthetic exposure outside this window or below threshold doses and durations shows no apparent neurotoxicity, while exposure in the context of concomitant painful stimuli is neuroprotective. Retrospective human studies suggest associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes, particularly after multiple exposures. The causality underlying the associations is unknown. Ongoing investigations may clarify the risks associated with current practice. Surgical care of all patients mandates appropriate anesthesia. Neurotoxic doses and the duration of anesthetic exposure in animals may have little relevance to clinical practice, particularly surgical anesthesia for perioperative pain. The causality underlying the observed associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes is unknown. Anesthetic exposure may be a marker of increased risk. Especially in young children, procedures requiring general anesthesia should be performed only as necessary and general anesthesia duration should be minimized. Alternatives to general anesthesia and the deferral of elective procedures beyond the first few years of life should be considered, as appropriate. Participation in ongoing efforts should be encouraged to generate further data. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

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

Yamada, Shigeyuki; Zhang Xiuquan; Kadono, Toshie

Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca{sup 2+}]{sub i} was measured by flow cytometry using fluo-3. Mitochondrial [Ca{sup 2+}] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified bymore » dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca{sup 2+} uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca{sup 2+}]{sub i} in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca{sup 2+}]{sub i} during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [Ca{sup 2+}]{sub i} during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold.« less

AutoNR: an automated system that measures ECAP thresholds with the Nucleus Freedom cochlear implant via machine intelligence.

PubMed

Botros, Andrew; van Dijk, Bas; Killian, Matthijs

2007-05-01

AutoNRT is an automated system that measures electrically evoked compound action potential (ECAP) thresholds from the auditory nerve with the Nucleus Freedom cochlear implant. ECAP thresholds along the electrode array are useful in objectively fitting cochlear implant systems for individual use. This paper provides the first detailed description of the AutoNRT algorithm and its expert systems, and reports the clinical success of AutoNRT to date. AutoNRT determines thresholds by visual detection, using two decision tree expert systems that automatically recognise ECAPs. The expert systems are guided by a dataset of 5393 neural response measurements. The algorithm approaches threshold from lower stimulus levels, ensuring recipient safety during postoperative measurements. Intraoperative measurements use the same algorithm but proceed faster by beginning at stimulus levels much closer to threshold. When searching for ECAPs, AutoNRT uses a highly specific expert system (specificity of 99% during training, 96% during testing; sensitivity of 91% during training, 89% during testing). Once ECAPs are established, AutoNRT uses an unbiased expert system to determine an accurate threshold. Throughout the execution of the algorithm, recording parameters (such as implant amplifier gain) are automatically optimised when needed. In a study that included 29 intraoperative and 29 postoperative subjects (a total of 418 electrodes), AutoNRT determined a threshold in 93% of cases where a human expert also determined a threshold. When compared to the median threshold of multiple human observers on 77 randomly selected electrodes, AutoNRT performed as accurately as the 'average' clinician. AutoNRT has demonstrated a high success rate and a level of performance that is comparable with human experts. It has been used in many clinics worldwide throughout the clinical trial and commercial launch of Nucleus Custom Sound Suite, significantly streamlining the clinical procedures associated with cochlear implant use.

A durable gain in motor and non-motor symptoms of Parkinson's Disease following repeated caloric vestibular stimulation: A single-case study.

PubMed

Wilkinson, David; Podlewska, Aleksandra; Sakel, Mohamed

2016-01-01

To gain 'first-in-man' evidence that repeated caloric vestibular stimulation (CVS), a non-invasive form of neuro-modulation, can induce a lasting and clinically-relevant reduction in Parkinson's Disease (PD) symptoms. A 70  yr old male, diagnosed with PD 7 years prior to study enrolment, self-administered CVS at home 2×20 minutes per day for three months using a solid-state portable device. Standardised neuropsychological assessments of motor, cognitive, affective and independent function were carried out prior to stimulation, at the start and end of the sham (month 1) and active (months 2-3) phases, and 5 months post-stimulation. Relative to the pre-stimulation baseline, behavioural improvements that exceeded the minimal detectable change were observed on the EQ5D, Unified Parkinson's Disease Rating Scale, Schwab and England scale, 2 minute walk, Timed up and go, Non-motor symptom assessment scale for PD, Montreal cognitive assessment, Hospital depression scale and Epworth sleepiness scale. The level of change exceeded the threshold for a minimal clinically important difference on all scales for which a threshold has been published. By contrast, little improvement was seen during the sham (i.e., placebo) phase. Caloric vestibular stimulation may offer a novel, home-based method of relieving everyday symptoms of PD, and merits further evaluative study.

Temporal characteristics of decisions in hospital encounters: a threshold for shared decision making? A qualitative study.

PubMed

Ofstad, Eirik H; Frich, Jan C; Schei, Edvin; Frankel, Richard M; Gulbrandsen, Pål

2014-11-01

To identify and characterize physicians' statements that contained evidence of clinically relevant decisions in encounters with patients in different hospital settings. Qualitative analysis of 50 videotaped encounters from wards, the emergency room (ER) and outpatient clinics in a department of internal medicine at a Norwegian university hospital. Clinical decisions could be grouped in a temporal order: decisions which had already been made, and were brought into the encounter by the physician (preformed decisions), decisions made in the present (here-and-now decisions), and decisions prescribing future actions given a certain course of events (conditional decisions). Preformed decisions were a hallmark in the ward and conditional decisions a main feature of ER encounters. Clinical decisions related to a patient-physician encounter spanned a time frame exceeding the duration of the encounter. While a distribution of decisions over time and space fosters sharing and dilution of responsibility between providers, it makes the decision making process hard to access for patients. In order to plan when and how to involve patients in decisions, physicians need increased awareness of when clinical decisions are made, who usually makes them, and who should make them. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Blood Pressure Response to Exercise and Cardiovascular Disease.

PubMed

Schultz, Martin G; La Gerche, Andre; Sharman, James E

2017-10-18

This review aimed to provide a clinical update on exercise blood pressure (BP) and its relationship to cardiovascular disease (CVD), outlining key determinants of abnormal exercise BP responses. We also highlight current evidence gaps that need addressing in order to optimise the relevance of exercise BP as clinical CVD risk factor. Abnormal exercise BP manifests as either exercise hypotension (low BP response) or as exaggerated exercise BP (high BP response). Exercise hypotension is an established sign of existing and likely severe CVD, but exaggerated exercise BP also carries elevated CVD risk due to its association with sub-clinical hypertension. Although exaggerated exercise BP is related to heightened CVD risk at any exercise intensity, recent data suggest that the BP response to submaximal intensity exercise holds greater prognostic and clinical significance than BP achieved at peak/maximal intensity exercise. Cardiorespiratory fitness is a strong modifier of the exercise BP response, and should be taken into consideration when assessing the association with CVD. Both exercise hypotension and exaggerated exercise BP serve as markers that should prompt evaluation for potential underlying CVD. However, the clinical utility of these markers is currently inhibited by the lack of consensus informing the definitions and thresholds for abnormalities in exercise BP.

Proposal for defining the relevance of drug accumulation derived from single dose study data for modified release dosage forms

PubMed Central

Scheerans, Christian; Heinig, Roland; Mueck, Wolfgang

2015-01-01

Recently, the European Medicines Agency (EMA) published the new draft guideline on the pharmacokinetic and clinical evaluation of modified release (MR) formulations. The draft guideline contains the new requirement of performing multiple dose (MD) bioequivalence studies, in the case when the MR formulation is expected to show ‘relevant’ drug accumulation at steady state (SS). This new requirement reveals three fundamental issues, which are discussed in the current work: first, measurement for the extent of drug accumulation (MEDA) predicted from single dose (SD) study data; second, its relationship with the percentage residual area under the plasma concentration–time curve (AUC) outside the dosing interval (τ) after SD administration, %AUC(τ-∞)SD; and third, the rationale for a threshold of %AUC(τ-∞)SD that predicts ‘relevant’ drug accumulation at SS. This work revealed that the accumulation ratio RA,AUC, derived from the ratio of the time-averaged plasma concentrations during τ at SS and after SD administration, respectively, is the ‘preferred’ MEDA for MR formulations. A causal relationship was derived between %AUC(τ-∞)SD and RA,AUC, which is valid for any drug (product) that shows (dose- and time-) linear pharmacokinetics regardless of the shape of the plasma concentration–time curve. Considering AUC thresholds from other guidelines together with the causal relationship between %AUC(τ-∞)SD and RA,AUC indicates that values of %AUC(τ-∞)SD ≤ 20%, resulting in RA,AUC ≤ 1.25, can be considered as leading to non-relevant drug accumulation. Hence, the authors suggest that 20% for %AUC(τ-∞)SD is a reasonable threshold and selection criterion between SD or MD study designs for bioequivalence studies of new MR formulations. © 2014 The Authors Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd. PMID:25327367

Extended high-frequency thresholds in college students: effects of music player use and other recreational noise.

PubMed

Le Prell, Colleen G; Spankovich, Christopher; Lobariñas, Edward; Griffiths, Scott K

2013-09-01

Human hearing is sensitive to sounds from as low as 20 Hz to as high as 20,000 Hz in normal ears. However, clinical tests of human hearing rarely include extended high-frequency (EHF) threshold assessments, at frequencies extending beyond 8000 Hz. EHF thresholds have been suggested for use monitoring the earliest effects of noise on the inner ear, although the clinical usefulness of EHF threshold testing is not well established for this purpose. The primary objective of this study was to determine if EHF thresholds in healthy, young adult college students vary as a function of recreational noise exposure. A retrospective analysis of a laboratory database was conducted; all participants with both EHF threshold testing and noise history data were included. The potential for "preclinical" EHF deficits was assessed based on the measured thresholds, with the noise surveys used to estimate recreational noise exposure. EHF thresholds measured during participation in other ongoing studies were available from 87 participants (34 male and 53 female); all participants had hearing within normal clinical limits (≤25 HL) at conventional frequencies (0.25-8 kHz). EHF thresholds closely matched standard reference thresholds [ANSI S3.6 (1996) Annex C]. There were statistically reliable threshold differences in participants who used music players, with 3-6 dB worse thresholds at the highest test frequencies (10-16 kHz) in participants who reported long-term use of music player devices (>5 yr), or higher listening levels during music player use. It should be possible to detect small changes in high-frequency hearing for patients or participants who undergo repeated testing at periodic intervals. However, the increased population-level variability in thresholds at the highest frequencies will make it difficult to identify the presence of small but potentially important deficits in otherwise normal-hearing individuals who do not have previously established baseline data. American Academy of Audiology.

Stratified cost-utility analysis of C-Leg versus mechanical knees: Findings from an Italian sample of transfemoral amputees.

PubMed

Cutti, Andrea Giovanni; Lettieri, Emanuele; Del Maestro, Martina; Radaelli, Giovanni; Luchetti, Martina; Verni, Gennero; Masella, Cristina

2017-06-01

The fitting rate of the C-Leg electronic knee (Otto-Bock, D) has increased steadily over the last 15 years. Current cost-utility studies, however, have not considered the patients' characteristics. To complete a cost-utility analysis involving C-Leg and mechanical knee users; "age at the time of enrollment," "age at the time of first prosthesis," and "experience with the current type of prosthesis" are assumed as non-nested stratification parameters. Cohort retrospective. In all, 70 C-Leg and 57 mechanical knee users were selected. For each stratification criteria, we evaluated the cost-utility of C-Leg versus mechanical knees by computing the incremental cost-utility ratio, that is, the ratio of the "difference in cost" and the "difference in utility" of the two technologies. Cost consisted of acquisition, maintenance, transportation, and lodging expenses. Utility was measured in terms of quality-adjusted life years, computed on the basis of participants' answers to the EQ-5D questionnaire. Patients over 40 years at the time of first prosthesis were the only group featuring an incremental cost-utility ratio (88,779 €/quality-adjusted life year) above the National Institute for Health and Care Excellence practical cost-utility threshold (54,120 €/quality-adjusted live year): C-Leg users experience a significant improvement of "mobility," but limited outcomes on "usual activities," "self-care," "depression/anxiety," and reduction of "pain/discomfort." The stratified cost-utility results have relevant clinical implications and provide useful information for practitioners in tailoring interventions. Clinical relevance A cost-utility analysis that considered patients characteristics provided insights on the "affordability" of C-Leg compared to mechanical knees. In particular, results suggest that C-Leg has a significant impact on "mobility" for first-time prosthetic users over 40 years, but implementation of specific low-cost physical/psychosocial interventions is required to retun within cost-utility thresholds.

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…

Statistical evaluation of the Local Lymph Node Assay.

PubMed

Hothorn, Ludwig A; Vohr, Hans-Werner

2010-04-01

In the Local Lymph Node Assay measured endpoints for each animal, such as cell proliferation, cell counts and/or lymph node weight should be evaluated separately. The primary criterion for a positive response is when the estimated stimulation index is larger than a specified relative threshold that is endpoint- and strain-specific. When the lower confidence limit for ratio-to-control comparisons is larger than a relevance threshold, a biologically relevant increase can be concluded according to the proof of hazard. Alternatively, when the upper confidence limit for ratio-to-control comparisons is smaller than a tolerable margin, harmlessness can be concluded according to a proof of safety. Copyright 2009 Elsevier Inc. All rights reserved.

Determination of the anaerobic threshold in the pre-operative assessment clinic: inter-observer measurement error.

PubMed

Sinclair, R C F; Danjoux, G R; Goodridge, V; Batterham, A M

2009-11-01

The variability between observers in the interpretation of cardiopulmonary exercise tests may impact upon clinical decision making and affect the risk stratification and peri-operative management of a patient. The purpose of this study was to quantify the inter-reader variability in the determination of the anaerobic threshold (V-slope method). A series of 21 cardiopulmonary exercise tests from patients attending a surgical pre-operative assessment clinic were read independently by nine experienced clinicians regularly involved in clinical decision making. The grand mean for the anaerobic threshold was 10.5 ml O(2).kg body mass(-1).min(-1). The technical error of measurement was 8.1% (circa 0.9 ml.kg(-1).min(-1); 90% confidence interval, 7.4-8.9%). The mean absolute difference between readers was 4.5% with a typical random error of 6.5% (6.0-7.2%). We conclude that the inter-observer variability for experienced clinicians determining the anaerobic threshold from cardiopulmonary exercise tests is acceptable.

Rapid Whole-Genome Sequencing for Investigation of a Neonatal MRSA Outbreak

PubMed Central

Köser, Claudio U.; Holden, Matthew T.G.; Ellington, Matthew J.; Cartwright, Edward J.P.; Brown, Nicholas M.; Ogilvy-Stuart, Amanda L.; Hsu, Li Yang; Chewapreecha, Claire; Croucher, Nicholas J.; Harris, Simon R.; Sanders, Mandy; Enright, Mark C.; Dougan, Gordon; Bentley, Stephen D.; Parkhill, Julian; Fraser, Louise J.; Betley, Jason R.; Schulz-Trieglaff, Ole B.; Smith, Geoffrey P.; Peacock, Sharon J.

2013-01-01

Background Isolates of methicillin-resistant Staphylococcus aureus (MRSA) belonging to a single lineage are often indistinguishable by means of current typing techniques. Whole-genome sequencing may provide improved resolution to define transmission pathways and characterize outbreaks. Methods We investigated a putative MRSA outbreak in a neonatal intensive care unit. By using rapid high-throughput sequencing technology with a clinically relevant turnaround time, we retrospectively sequenced the DNA from seven isolates associated with the outbreak and another seven MRSA isolates associated with carriage of MRSA or bacteremia in the same hospital. Results We constructed a phylogenetic tree by comparing single-nucleotide polymorphisms (SNPs) in the core genome to a reference genome (an epidemic MRSA clone, EMRSA-15 [sequence type 22]). This revealed a distinct cluster of outbreak isolates and clear separation between these and the nonoutbreak isolates. A previously missed transmission event was detected between two patients with bacteremia who were not part of the outbreak. We created an artificial “resistome” of antibiotic-resistance genes and demonstrated concordance between it and the results of phenotypic susceptibility testing; we also created a “toxome” consisting of toxin genes. One outbreak isolate had a hypermutator phenotype with a higher number of SNPs than the other outbreak isolates, highlighting the difficulty of imposing a simple threshold for the number of SNPs between isolates to decide whether they are part of a recent transmission chain. Conclusions Whole-genome sequencing can provide clinically relevant data within a time frame that can influence patient care. The need for automated data interpretation and the provision of clinically meaningful reports represent hurdles to clinical implementation. (Funded by the U.K. Clinical Research Collaboration Translational Infection Research Initiative and others.) PMID:22693998

In vivo relevance of two critical levels for NAD(P)H:quinone oxidoreductase (NQO1)-mediated cellular protection against electrophile toxicity found in vitro.

PubMed

de Haan, Laura H J; Pot, Gerda K; Aarts, Jac M M J G; Rietjens, Ivonne M C M; Alink, Gerrit M

2006-08-01

NAD(P)H:quinone oxidoreductase (NQO1)-mediated detoxification of quinones is suggested to be involved in cancer prevention. In the present study, using transfected CHO cells, it was demonstrated that the relation between NQO1 activity and the resulting protection against the cytotoxicity of menadione shows a steep dose-response curve revealing a 'lower protection threshold' of 0.5mumol DCPIP/min/mg protein and an 'upper protection threshold' at 1mumol DCPIP/min/mg protein. In an additional in vivo experiment it was investigated how both in vitro critical activity levels of NQO1, relate to NQO1 activities in mice and man, either without or upon induction of the enzyme by butylated hydroxyanisol (BHA) or indole-3-carbinol (I(3)C). Data from an experiment with CD1 mice revealed that base-line NQO1 levels in liver, kidney, small intestine, colon and lung are generally below the observed 'lower protection threshold' in vitro, this also holds for most human tissue S-9 samples. To achieve NQO1 levels above this 'lower protection threshold' will require 5-20 fold NQO1 induction. Discussion focuses on the relevance of the in vitro NQO1 activity thresholds for the in vivo situation. We conclude that increased protection against menadione toxicity can probably not be achieved by NQO1 induction but should be achieved by other mechanisms. Whether this conclusion also holds for other electrophiles and the in vivo situation awaits further definition of their NQO1 protection thresholds.

Effect of two doses of carbamylated allergoid extract of dust mite on nasal reactivity.

PubMed

Scalone, G; Compalati, E; Bruno, M E; Mistrello, G

2013-11-01

Background and Objective. Single SLIT studies with native allergen extracts support a dose-response effect for clinical and immunological outcomes. Conversely for carbamylated allergoids this dose-response effects is less evident, likely because the threshold for efficacy is more easily reached through the enhanced bioavailability of the extract consequent to the selective chemical modification. Thus this pilot study investigates the dose-response effect on nasal specific reactivity and safety of two unusual doses of carbamylated allergoid in patients mono-sensitized to house dust mites. Methods. A prospective open randomized study involved 6-65 year-old Italian patients with clinically relevant sensitization to house dust mites and positive response to nasal provocation challenge. Monomeric carbamylated allergoid was delivered once daily at the dose of 1000 AU or 2000 AU from June to September 2009, during the lowest level of mites exposure. Primary outcomes were the change of the threshold of allergen concentration for a positive nasal provocation test (NPT) before and after the treatment and the product safety. Secondary outcome was the change  in the mean percentage fall of peak nasal inspiratory flow (PNIF) following nasal challenge. Results. Thirty-four patients were enrolled. Fifteen in group 1 and 14 in group 2 concluded the study. After 12 weeks all patients treated in group 1 and all but one in group 2 showed an increase in the threshold dose provoking a positive NPT. Those with no symptoms onset with the highest dose delivered were 80% in group 1 and 78.6% in group 2 (p=0.92). From first to second challenge, the mean percentage fall of PNIF  was reduced with no statistical difference between groups (p=0.95), and with no difference between the final mean percentage falls (p=0.65). No serious adverse reactions occurred and the frequency of events, all mild, was similar in the two groups. Conclusions. Twelve weeks of carbamylated sublingual allergoid delivered at 1000AU or 2000AU once daily appear equally safe and show comparable effect in increasing  the threshold of allergen concentration for a positive nasal provocation test, confirming the apparent absence of a dose response effect for the used doses.

Prevalence of subclinical ketosis and relationships with postpartum diseases in European dairy cows.

PubMed

Suthar, V S; Canelas-Raposo, J; Deniz, A; Heuwieser, W

2013-05-01

Subclinical ketosis (SCK) is defined as concentrations of β-hydroxybutyrate (BHBA) ≥ 1.2 to 1.4 mmol/L and it is considered a gateway condition for other metabolic and infectious disorders such as metritis, mastitis, clinical ketosis, and displaced abomasum. Reported prevalence rates range from 6.9 to 43% in the first 2 mo of lactation. However, there is a dearth of information on prevalence rates considering the diversity of European dairy farms. The objectives of this study were to (1) determine prevalence of SCK, (2) identify thresholds of BHBA, and (3) study their relationships with postpartum metritis, clinical ketosis, displaced abomasum, lameness, and mastitis in European dairy farms. From May to October 2011, a convenience sample of 528 dairy herds from Croatia, Germany, Hungary, Italy, Poland, Portugal, Serbia, Slovenia, Spain, and Turkey was studied. β-Hydroxybutyrate levels were measured in 5,884 cows with a handheld meter within 2 to 15 d in milk (DIM). On average, 11 cows were enrolled per farm and relevant information (e.g., DIM, postpartum diseases, herd size) was recorded. Using receiver operator characteristic curve analyses, blood BHBA thresholds were determined for the occurrence of metritis, mastitis, clinical ketosis, displaced abomasum, and lameness. Multivariate binary logistic regression models were built for each disease, considering cow as the experimental unit and herd as a random effect. Overall prevalence of SCK (i.e., blood BHBA ≥ 1.2 mmol/L) within 10 countries was 21.8%, ranging from 11.2 to 36.6%. Cows with SCK had 1.5, 9.5, and 5.0 times greater odds of developing metritis, clinical ketosis, and displaced abomasum, respectively. Multivariate binary logistic regression models demonstrated that cows with blood BHBA levels of ≥ 1.4, ≥ 1.1 and ≥ 1.7 mmol/L during 2 to 15 DIM had 1.7, 10.5, and 6.9 times greater odds of developing metritis, clinical ketosis, and displaced abomasum, respectively, compared with cows with lower BHBA blood levels. Interestingly, a postpartum blood BHBA threshold ≥ 1.1 mmol/L increased the odds for lameness in dairy cows 1.8 (95% confidence interval: 1.3 to 2.5) times. Overall, prevalence of SCK was high between 2 to 15 DIM and SCK increased the odds of metritis, clinical ketosis, lameness, and displaced abomasum in European dairy herds. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Jackknife variance of the partial area under the empirical receiver operating characteristic curve.

PubMed

Bandos, Andriy I; Guo, Ben; Gur, David

2017-04-01

Receiver operating characteristic analysis provides an important methodology for assessing traditional (e.g., imaging technologies and clinical practices) and new (e.g., genomic studies, biomarker development) diagnostic problems. The area under the clinically/practically relevant part of the receiver operating characteristic curve (partial area or partial area under the receiver operating characteristic curve) is an important performance index summarizing diagnostic accuracy at multiple operating points (decision thresholds) that are relevant to actual clinical practice. A robust estimate of the partial area under the receiver operating characteristic curve is provided by the area under the corresponding part of the empirical receiver operating characteristic curve. We derive a closed-form expression for the jackknife variance of the partial area under the empirical receiver operating characteristic curve. Using the derived analytical expression, we investigate the differences between the jackknife variance and a conventional variance estimator. The relative properties in finite samples are demonstrated in a simulation study. The developed formula enables an easy way to estimate the variance of the empirical partial area under the receiver operating characteristic curve, thereby substantially reducing the computation burden, and provides important insight into the structure of the variability. We demonstrate that when compared with the conventional approach, the jackknife variance has substantially smaller bias, and leads to a more appropriate type I error rate of the Wald-type test. The use of the jackknife variance is illustrated in the analysis of a data set from a diagnostic imaging study.

Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics

PubMed Central

Hanemaaijer, Nicolien M; Sikkema-Raddatz, Birgit; van der Vries, Gerben; Dijkhuizen, Trijnie; Hordijk, Roel; van Essen, Anthonie J; Veenstra-Knol, Hermine E; Kerstjens-Frederikse, Wilhelmina S; Herkert, Johanna C; Gerkes, Erica H; Leegte, Lamberta K; Kok, Klaas; Sinke, Richard J; van Ravenswaaij-Arts, Conny M A

2012-01-01

The correct interpretation of copy number gains in patients with developmental delay and multiple congenital anomalies is hampered by the large number of copy number variations (CNVs) encountered in healthy individuals. The variable phenotype associated with copy number gains makes interpretation even more difficult. Literature shows that inheritence, size and presence in healthy individuals are commonly used to decide whether a certain copy number gain is pathogenic, but no general consensus has been established. We aimed to develop guidelines for interpreting gains detected by array analysis using array CGH data of 300 patients analysed with the 105K Agilent oligo array in a diagnostic setting. We evaluated the guidelines in a second, independent, cohort of 300 patients. In the first 300 patients 797 gains of four or more adjacent oligonucleotides were observed. Of these, 45.4% were de novo and 54.6% were familial. In total, 94.8% of all de novo gains and 87.1% of all familial gains were concluded to be benign CNVs. Clinically relevant gains ranged from 288 to 7912 kb in size, and were significantly larger than benign gains and gains of unknown clinical relevance (P<0.001). Our study showed that a threshold of 200 kb is acceptable in a clinical setting, whereas heritability does not exclude a pathogenic nature of a gain. Evaluation of the guidelines in the second cohort of 300 patients revealed that the interpretation guidelines were clear, easy to follow and efficient. PMID:21934709

Single photons from a gain medium below threshold

NASA Astrophysics Data System (ADS)

Ghosh, Sanjib; Liew, Timothy C. H.

2018-06-01

The emission from a nonlinear photonic mode coupled weakly to a gain medium operating below threshold is predicted to exhibit antibunching. In the steady state regime, analytical solutions for the relevant observable quantities are found in accurate agreement with exact numerical results. Under pulsed excitation, the unequal time second-order correlation function demonstrates the triggered probabilistic generation of single photons well separated in time.

Surrogate pregnancy: a guide for Canadian prenatal health care providers

PubMed Central

Reilly, Dan R.

2007-01-01

Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is limited evidence about the medical and psychological risks ofsurrogacy. Whether theoretical concerns about these risks are clinically relevant remains unknown. In the face of these uncertainties, the prenatal health care provider should have a low threshold for seeking obstetrical, social work, ethical and legal support. PMID:17296962

Surrogate pregnancy: a guide for Canadian prenatal health care providers.

PubMed

Reilly, Dan R

2007-02-13

Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is limited evidence about the medical and psychological risks of surrogacy. Whether theoretical concerns about these risks are clinically relevant remains unknown. In the face of these uncertainties, the prenatal health care provider should have a low threshold for seeking obstetrical, social work, ethical and legal support.

A low dose of three local anesthetic solutions for interscalene blockade tested by thermal quantitative sensory testing: a randomized controlled trial.

PubMed

Sermeus, Luc A; Schepens, Tom; Hans, Guy H; Morrison, Stuart G; Wouters, Kristien; Breebaart, Margaretha B; Smitz, Carine J; Vercauteren, Marcel P

2018-05-03

This randomized double-blind controlled trial compared the block characteristics of three low-dose local anesthetics at different roots in an ultrasound-guided interscalene block, using thermal quantitative sensory testing for assessing the functioning of cutaneous small nerve fibres. A total of 37 adults scheduled to undergo shoulder arthroscopy were randomized to receive 5 mL of either 0.5% levobupivacaine with and without epinephrine 1/200,000 or 0.75% ropivacaine in a single-shot interscalene block. Thermal quantitative sensory testing was performed in the C4, C5, C6 and C7 dermatomes. Detection thresholds for cold/warm sensation and cold/heat pain were measured before and at 30 min, 6, 10 and 24 h after infiltration around C5. The need for rescue medication was recorded. No significant differences between groups were found for any sensation (lowest P = 0.28). At 6 h, the largest differences in sensory thresholds were observed for the C5 dermatome. The increase in thresholds were less in C4 and C6 and minimal in C7 for all sensations. The analgesic effect lasted the longest in C5 (time × location mixed model P < 0.001 for all sensory tests). The time to rescue analgesia was significantly shorter with 0.75% ropivacaine (P = 0.02). The quantitative sensory findings showed no difference in intensity between the local anesthetics tested. A decrease in block intensity, with minimal changes in pain detection thresholds, was observed in the roots adjacent to C5, with the lowest block intensity in C7. A clinically relevant shorter duration was found with 0.75% ropivacaine compared to the other groups. Trial registration NCT 02691442.

Defining a Hospital Volume Threshold for Minimally Invasive Pancreaticoduodenectomy in the United States

PubMed Central

Adam, Mohamed Abdelgadir; Thomas, Samantha; Youngwirth, Linda; Pappas, Theodore; Roman, Sanziana A.

2016-01-01

Importance There is increasing interest in expanding use of minimally invasive pancreaticoduodenectomy (MIPD). This procedure is complex, with data suggesting a significant association between hospital volume and outcomes. Objective To determine whether there is an MIPD hospital volume threshold for which patient outcomes could be optimized. Design, Setting, and Participants Adult patients undergoing MIPD were identified from the Healthcare Cost and Utilization Project National Inpatient Sample from 2000 to 2012. Multivariable models with restricted cubic splines were used to identify a hospital volume threshold by plotting annual hospital volume against the adjusted odds of postoperative complications. The current analysis was conducted on August 16, 2016. Main Outcomes and Measures Incidence of any complication. Results Of the 865 patients who underwent MIPD, 474 (55%) were male and the median patient age was 67 years (interquartile range, 59-74 years). Among the patients, 747 (86%) had cancer and 91 (11%) had benign conditions/pancreatitis. Overall, 410 patients (47%) had postoperative complications and 31 (4%) died in-hospital. After adjustment for demographic and clinical characteristics, increasing hospital volume was associated with reduced complications (overall association P < .001); the likelihood of experiencing a complication declined as hospital volume increased up to 22 cases per year (95% CI, 21-23). Median hospital volume was 6 cases per year (range, 1-60). Most patients (n = 717; 83%) underwent the procedure at low-volume (≤22 cases per year) hospitals. After adjustment for patient mix, undergoing MIPD at low- vs high-volume hospitals was significantly associated with increased odds for postoperative complications (odds ratio, 1.74; 95% CI, 1.03-2.94; P = .04). Conclusions and Relevance Hospital volume is significantly associated with improved outcomes from MIPD, with a threshold of 22 cases per year. Most patients undergo MIPD at low-volume hospitals. Protocols outlining minimum procedural volume thresholds should be considered to facilitate safer dissemination of MIPD. PMID:28030713

Deficits in the Sensitivity to Pitch Sweeps by School-Aged Children Wearing Cochlear Implants

PubMed Central

Deroche, Mickael L. D.; Kulkarni, Aditya M.; Christensen, Julie A.; Limb, Charles J.; Chatterjee, Monita

2016-01-01

Sensitivity to static changes in pitch has been shown to be poorer in school-aged children wearing cochlear implants (CIs) than children with normal hearing (NH), but it is unclear whether this is also the case for dynamic changes in pitch. Yet, dynamically changing pitch has considerable ecological relevance in terms of natural speech, particularly aspects such as intonation, emotion, or lexical tone information. Twenty one children with NH and 23 children wearing a CI participated in this study, along with 18 NH adults and 6 CI adults for comparison. Listeners with CIs used their clinically assigned settings with envelope-based coding strategies. Percent correct was measured in one- or three-interval two-alternative forced choice tasks, for the direction or discrimination of harmonic complexes based on a linearly rising or falling fundamental frequency. Sweep rates were adjusted per subject, in a logarithmic scale, so as to cover the full extent of the psychometric function. Data for up- and down-sweeps were fitted separately, using a maximum-likelihood technique. Fits were similar for up- and down-sweeps in the discrimination task, but diverged in the direction task because psychometric functions for down-sweeps were very shallow. Hits and false alarms were then converted into d′ and beta values, from which a threshold was extracted at a d′ of 0.77. Thresholds were very consistent between the two tasks and considerably higher (worse) for CI listeners than for their NH peers. Thresholds were also higher for children than adults. Factors such as age at implantation, age at profound hearing loss, and duration of CI experience did not play any major role in this sensitivity. Thresholds of dynamic pitch sensitivity (in either task) also correlated with thresholds for static pitch sensitivity and with performance in tasks related to speech prosody. PMID:26973451

Remote Patient Management in Automated Peritoneal Dialysis: A Promising New Tool.

PubMed

Drepper, Valérie Jotterand; Martin, Pierre-Yves; Chopard, Catherine Stoermann; Sloand, James A

2018-01-01

Remote patient management (RPM) has the potential to help clinicians detect early issues, allowing intervention prior to development of more significant problems. A 23-year-old end-stage kidney disease patient required urgent start of renal replacement therapy. A newly available automated peritoneal dialysis (APD) RPM system with cloud-based connectivity was implemented in her care. Pre-defined RPM threshold parameters were set to identify clinically relevant issues. Red flag dashboard alerts heralded prolonged drain times leading to clinical evaluation with subsequent diagnosis of and surgical repositioning for catheter displacement, although it took several days for newly-RPM-exposed staff to recognize this issue. Post-PD catheter repositioning, drain times were again normal as indicated by disappearance of flag alerts and unremarkable cycle volume profiles. Identification of < 90% adherence to prescribed PD therapy was then documented with the RPM system, alerting the clinical staff to address this important issue given its association with significant negative clinical outcomes. Healthcare providers face a "learning curve" to effect optimal utilization of the RPM tool. Larger scale observational studies will determine the impact of RPM on APD technique survival and resource utilization. Copyright © 2018 International Society for Peritoneal Dialysis.

Thresholds in chemical respiratory sensitisation.

PubMed

Cochrane, Stella A; Arts, Josje H E; Ehnes, Colin; Hindle, Stuart; Hollnagel, Heli M; Poole, Alan; Suto, Hidenori; Kimber, Ian

2015-07-03

There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the acquisition of sensitisation to chemical respiratory allergens is a dose-related phenomenon, and that thresholds exist, it is frequently difficult to define accurate numerical values for threshold exposure levels. Nevertheless, based on occupational exposure data it may sometimes be possible to derive levels of exposure in the workplace, which are safe. An additional observation is the lack currently of suitable experimental methods for both routine hazard characterisation and the measurement of thresholds, and that such methods are still some way off. Given the current trajectory of toxicology, and the move towards the use of non-animal in vitro and/or in silico) methods, there is a need to consider the development of alternative approaches for the identification and characterisation of respiratory sensitisation hazards, and for risk assessment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficacy of scheduled return visits for emergency department patients with non-specific abdominal pain.

PubMed

Boendermaker, Annemieke E; Coolsma, Constant W; Emous, Marloes; Ter Avest, Ewoud

2018-06-02

Many patients presenting with abdominal pain to emergency departments (EDs) are discharged without a definitive diagnosis. For these patients, often designated as having non-specific abdominal pain, re-evaluation is often advocated. We aimed to investigate how often re-evaluation changes the diagnosis and clinical management and discern factors that could help identify patients likely to benefit from re-evaluation. This was a retrospective study conducted in the Netherlands between 1 January 2014 and 31 December 2015 of patients asked to return to the ED after an initial presentation with acute non-traumatic abdominal pain. The primary outcome was a clinically relevant change in treatment (surgery, endoscopy during admission and/or hospitalisation) and diagnosis at ED re-evaluation within 30 hours. During the 2-year study period, 358 ED patients with non-specific abdominal pain were scheduled for re-evaluation. Of these, 14% (11%-18%)) did not present for re-evaluation. Re-evaluation resulted in a clinically relevant change in diagnosis and treatment in, respectively, 21.3% (17%-29%)) and 22.3% (18%-27%)) of the subjects. Of the clinical, biochemical and radiological factors available at the index visit, C reactive protein (CRP) at the index visit predicted a change in treatment (CRP >27 mg/L likelihood ratio (LR)+ 1.69 (1.21-2.36)), while an increase in CRP of >25 mg/L between index and re-evaluation visit (LR+ 2.85 (1.88-4.32)) and the conduct of radiological studies at the re-evaluation visit were associated with changes in treatment (LR+ 3.05 (2.41-3.86)). Re-evaluation within 30 hours for ED patients discharged with non-specific abdominal pain resulted in a clinically relevant change in diagnosis and therapy in almost one-quarter of patients. Elevated CRP at the index visit might assist in correctly identifying patients with a greater likelihood of needing treatment in follow-up, and a low threshold for radiological studies should be considered during re-evaluation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The anaerobic threshold: over-valued or under-utilized? A novel concept to enhance lipid optimization!

PubMed

Connolly, Declan A J

2012-09-01

The purpose of this article is to assess the value of the anaerobic threshold for use in clinical populations with the intent to improve exercise adaptations and outcomes. The anaerobic threshold is generally poorly understood, improperly used, and poorly measured. It is rarely used in clinical settings and often reserved for athletic performance testing. Increased exercise participation within both clinical and other less healthy populations has increased our attention to optimizing exercise outcomes. Of particular interest is the optimization of lipid metabolism during exercise in order to improve numerous conditions such as blood lipid profile, insulin sensitivity and secretion, and weight loss. Numerous authors report on the benefits of appropriate exercise intensity in optimizing outcomes even though regulation of intensity has proved difficult for many. Despite limited use, selected exercise physiology markers have considerable merit in exercise-intensity regulation. The anaerobic threshold, and other markers such as heart rate, may well provide a simple and valuable mechanism for regulating exercising intensity. The use of the anaerobic threshold and accurate target heart rate to regulate exercise intensity is a valuable approach that is under-utilized across populations. The measurement of the anaerobic threshold can be simplified to allow clients to use nonlaboratory measures, for example heart rate, in order to self-regulate exercise intensity and improve outcomes.

Genetic architecture of threshold reaction norms for male alternative reproductive tactics in Atlantic salmon (Salmo salar L.)

PubMed Central

Lepais, Olivier; Manicki, Aurélie; Glise, Stéphane; Buoro, Mathieu; Bardonnet, Agnès

2017-01-01

Alternative mating tactics have important ecological and evolutionary implications and are determined by complex interactions between environmental and genetic factors. Here, we study the genetic effect and architecture of the variability in reproductive tactics among Atlantic salmon males which can either mature sexually early in life in freshwater or more commonly only after completing a migration at sea. We applied the latent environmental threshold model (LETM), which provides a conceptual framework linking individual status to a threshold controlling the decision to develop alternative traits, in an innovative experimental design using a semi-natural river which allowed for ecologically relevant phenotypic expression. Early male parr maturation rates varied greatly across families (10 to 93%) which translated into 90% [64–100%] of the phenotypic variation explained by genetic variation. Three significant QTLs were found for the maturation status, however only one collocated with a highly significant QTL explaining 20.6% of the variability of the maturation threshold located on chromosome 25 and encompassing a locus previously shown to be linked to sea age at maturity in anadromous Atlantic salmon. These results provide new empirical illustration of the relevance of the LETM for a better understanding of alternative mating tactics evolution in natural populations. PMID:28281522

Bumblebees are not deterred by ecologically relevant concentrations of nectar toxins.

PubMed

Tiedeken, Erin Jo; Stout, Jane C; Stevenson, Philip C; Wright, Geraldine A

2014-05-01

Bees visit flowers to collect nectar and pollen that contain nutrients and simultaneously facilitate plant sexual reproduction. Paradoxically, nectar produced to attract pollinators often contains deterrent or toxic plant compounds associated with herbivore defence. The functional significance of these nectar toxins is not fully understood, but they may have a negative impact on pollinator behaviour and health, and, ultimately, plant pollination. This study investigates whether a generalist bumblebee, Bombus terrestris, can detect naturally occurring concentrations of nectar toxins. Using paired-choice experiments, we identified deterrence thresholds for five compounds found in the nectar of bee-pollinated plants: quinine, caffeine, nicotine, amygdalin and grayanotoxin. The deterrence threshold was determined when bumblebees significantly preferred a sucrose solution over a sucrose solution containing the compound. Bumblebees had the lowest deterrence threshold for the alkaloid quinine (0.01 mmol l(-1)); all other compounds had higher deterrence thresholds, above the natural concentration range in floral nectar. Our data, combined with previous work using honeybees, suggest that generalist bee species have poor acuity for the detection of nectar toxins. The fact that bees do not avoid nectar-relevant concentrations of these compounds likely indicates that it is difficult for them to learn to associate floral traits with the presence of toxins, thus maintaining this trait in plant populations.

Bumblebees are not deterred by ecologically relevant concentrations of nectar toxins

PubMed Central

Tiedeken, Erin Jo; Stout, Jane C.; Stevenson, Philip C.; Wright, Geraldine A.

2014-01-01

Bees visit flowers to collect nectar and pollen that contain nutrients and simultaneously facilitate plant sexual reproduction. Paradoxically, nectar produced to attract pollinators often contains deterrent or toxic plant compounds associated with herbivore defence. The functional significance of these nectar toxins is not fully understood, but they may have a negative impact on pollinator behaviour and health, and, ultimately, plant pollination. This study investigates whether a generalist bumblebee, Bombus terrestris, can detect naturally occurring concentrations of nectar toxins. Using paired-choice experiments, we identified deterrence thresholds for five compounds found in the nectar of bee-pollinated plants: quinine, caffeine, nicotine, amygdalin and grayanotoxin. The deterrence threshold was determined when bumblebees significantly preferred a sucrose solution over a sucrose solution containing the compound. Bumblebees had the lowest deterrence threshold for the alkaloid quinine (0.01 mmol l−1); all other compounds had higher deterrence thresholds, above the natural concentration range in floral nectar. Our data, combined with previous work using honeybees, suggest that generalist bee species have poor acuity for the detection of nectar toxins. The fact that bees do not avoid nectar-relevant concentrations of these compounds likely indicates that it is difficult for them to learn to associate floral traits with the presence of toxins, thus maintaining this trait in plant populations. PMID:24526720

Threshold response using modulated continuous wave illumination for multilayer 3D optical data storage

NASA Astrophysics Data System (ADS)

Saini, A.; Christenson, C. W.; Khattab, T. A.; Wang, R.; Twieg, R. J.; Singer, K. D.

2017-01-01

In order to achieve a high capacity 3D optical data storage medium, a nonlinear or threshold writing process is necessary to localize data in the axial dimension. To this end, commercial multilayer discs use thermal ablation of metal films or phase change materials to realize such a threshold process. This paper addresses a threshold writing mechanism relevant to recently reported fluorescence-based data storage in dye-doped co-extruded multilayer films. To gain understanding of the essential physics, single layer spun coat films were used so that the data is easily accessible by analytical techniques. Data were written by attenuating the fluorescence using nanosecond-range exposure times from a 488 nm continuous wave laser overlapping with the single photon absorption spectrum. The threshold writing process was studied over a range of exposure times and intensities, and with different fluorescent dyes. It was found that all of the dyes have a common temperature threshold where fluorescence begins to attenuate, and the physical nature of the thermal process was investigated.

Threshold concepts in finance: conceptualizing the curriculum

NASA Astrophysics Data System (ADS)

Hoadley, Susan; Tickle, Leonie; Wood, Leigh N.; Kyng, Tim

2015-08-01

Graduates with well-developed capabilities in finance are invaluable to our society and in increasing demand. Universities face the challenge of designing finance programmes to develop these capabilities and the essential knowledge that underpins them. Our research responds to this challenge by identifying threshold concepts that are central to the mastery of finance and by exploring their potential for informing curriculum design and pedagogical practices to improve student outcomes. In this paper, we report the results of an online survey of finance academics at multiple institutions in Australia, Canada, New Zealand, South Africa and the United Kingdom. The outcomes of our research are recommendations for threshold concepts in finance endorsed by quantitative evidence, as well as a model of the finance curriculum incorporating finance, modelling and statistics threshold concepts. In addition, we draw conclusions about the application of threshold concept theory supported by both quantitative and qualitative evidence. Our methodology and findings have general relevance to the application of threshold concept theory as a means to investigate and inform curriculum design and delivery in higher education.

Application of the "threshold of toxicological concern" to derive tolerable concentrations of "non-relevant metabolites" formed from plant protection products in ground and drinking water.

PubMed

Melching-Kollmuss, Stephanie; Dekant, Wolfgang; Kalberlah, Fritz

2010-03-01

Limits for tolerable concentrations of ground water metabolites ("non-relevant metabolites" without targeted toxicities and specific classification and labeling) derived from active ingredients (AI) of plant protection products (PPPs) are discussed in the European Union. Risk assessments for "non-relevant metabolites" need to be performed when concentrations are above 0.75 microg/L. Since oral uptake is the only relevant exposure pathway for "non-relevant metabolites", risk assessment approaches as used for other chemicals with predominantly oral exposure in humans are applicable. The concept of "thresholds of toxicological concern" (TTC) defines tolerable dietary intakes for chemicals without toxicity data and is widely applied to chemicals present in food in low concentrations such as flavorings. Based on a statistical evaluation of the results of many toxicity studies and considerations of chemical structures, the TTC concept derives a maximum daily oral intake without concern of 90 microg/person/day for non-genotoxic chemicals, even for those with appreciable toxicity. When using the typical exposure assessment for drinking water contaminants (consumption of 2L of drinking water/person/day, allocation of 10% of the tolerable daily intake to drinking water), a TTC-based upper concentration limit of 4.5 microg/L for "non-relevant metabolites" in ground/drinking water is delineated. In the present publication it has been evaluated, whether this value would cover all relevant toxicities (repeated dose, reproductive and developmental, and immune effects). Taking into account, that after evaluation of specific reproduction toxicity data from chemicals and pharmaceuticals, a value of 1 microg/kgbw/day has been assessed as to cover developmental and reproduction toxicity, a TTC value of 60 microg/person/day was assessed as to represent a safe value. Based on these reasonable worst case assumptions, a TTC-derived threshold of 3 microg/L in drinking water is derived. When a non-relevant metabolite is present in concentration below 3 microg/L, animal testing for toxicity is not considered necessary for a compound-specific risk assessment since the application of the TTC covers all relevant toxicities to be considered in such assessment and any health risk resulting from these exposures is very low. (c) 2009 Elsevier Inc. All rights reserved.

Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1.

PubMed

Schiroli, Giulia; Ferrari, Samuele; Conway, Anthony; Jacob, Aurelien; Capo, Valentina; Albano, Luisa; Plati, Tiziana; Castiello, Maria C; Sanvito, Francesca; Gennery, Andrew R; Bovolenta, Chiara; Palchaudhuri, Rahul; Scadden, David T; Holmes, Michael C; Villa, Anna; Sitia, Giovanni; Lombardo, Angelo; Genovese, Pietro; Naldini, Luigi

2017-10-11

Targeted genome editing in hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematological diseases. However, the limited efficiency of homology-directed editing in primitive HSPCs constrains the yield of corrected cells and might affect the feasibility and safety of clinical translation. These concerns need to be addressed in stringent preclinical models and overcome by developing more efficient editing methods. We generated a humanized X-linked severe combined immunodeficiency (SCID-X1) mouse model and evaluated the efficacy and safety of hematopoietic reconstitution from limited input of functional HSPCs, establishing thresholds for full correction upon different types of conditioning. Unexpectedly, conditioning before HSPC infusion was required to protect the mice from lymphoma developing when transplanting small numbers of progenitors. We then designed a one-size-fits-all IL2RG (interleukin-2 receptor common γ-chain) gene correction strategy and, using the same reagents suitable for correction of human HSPC, validated the edited human gene in the disease model in vivo, providing evidence of targeted gene editing in mouse HSPCs and demonstrating the functionality of the IL2RG -edited lymphoid progeny. Finally, we optimized editing reagents and protocol for human HSPCs and attained the threshold of IL2RG editing in long-term repopulating cells predicted to safely rescue the disease, using clinically relevant HSPC sources and highly specific zinc finger nucleases or CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9). Overall, our work establishes the rationale and guiding principles for clinical translation of SCID-X1 gene editing and provides a framework for developing gene correction for other diseases. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Consensus Recommendations on Initiating Prescription Therapies for Opioid‐Induced Constipation

PubMed Central

Argoff, Charles E.; Brennan, Michael J.; Camilleri, Michael; Davies, Andrew; Fudin, Jeffrey; Galluzzi, Katherine E.; Gudin, Jeffrey; Lembo, Anthony; Stanos, Steven P.

2015-01-01

Abstract Objective Aims of this consensus panel were to determine (1) an optimal symptom‐based method for assessing opioid‐induced constipation in clinical practice and (2) a threshold of symptom severity to prompt consideration of prescription therapy. Methods A multidisciplinary panel of 10 experts with extensive knowledge/experience with opioid‐associated adverse events convened to discuss the literature on assessment methods used for opioid‐induced constipation and reach consensus on each objective using the nominal group technique. Results Five validated assessment tools were evaluated: the Patient Assessment of Constipation–Symptoms (PAC‐SYM), Patient Assessment of Constipation–Quality of Life (PAC‐QOL), Stool Symptom Screener (SSS), Bowel Function Index (BFI), and Bowel Function Diary (BF‐Diary). The 3‐item BFI and 4‐item SSS, both clinician administered, are the shortest tools. In published trials, the BFI and 12‐item PAC‐SYM are most commonly used. The 11‐item BF‐Diary is highly relevant in opioid‐induced constipation and was developed and validated in accordance with US Food and Drug Administration guidelines. However, the panel believes that the complex scoring for this tool and the SSS, PAC‐SYM, and 28‐item PAC‐QOL may be unfeasible for clinical practice. The BFI is psychometrically validated and responsive to changes in symptom severity; scores range from 0 to 100, with higher scores indicating greater severity and scores >28.8 points indicating constipation. Conclusions The BFI is a simple assessment tool with a validated threshold of clinically significant constipation. Prescription treatments for opioid‐induced constipation should be considered for patients who have a BFI score of ≥30 points and an inadequate response to first‐line interventions. PMID:26582720

Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

PubMed

Banelli, Barbara; Merlo, Domenico Franco; Allemanni, Giorgio; Forlani, Alessandra; Romani, Massimo

2013-01-01

Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma) that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months). Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

Effectiveness of high-frequency transcutaneous electrical nerve stimulation at tender points as adjuvant therapy for patients with fibromyalgia.

PubMed

Carbonario, F; Matsutani, L A; Yuan, S L K; Marques, A P

2013-04-01

Fibromyalgia is a chronic pain syndrome associated with sleep disorders, fatigue and psychological symptoms. Combinations therapies, such as electrotherapy and therapeutic exercises have been used in the clinical practice. To assess the efficacy of high-frequency transcutaneous electrical nerve stimulation (TENS) as an adjuvant therapy to aerobic and stretching exercises, for the treatment of fibromyalgia. Controlled clinical trial. Unit of rehabilitation of a public hospital. Twenty-eight women aged 52.4±7.5 years, with fibromyalgia. A visual analogue scale measured pain intensity; tender points pain threshold, by dolorimetry; and quality of life, by the Fibromyalgia Impact Questionnaire. All subjects participated in an eight-week program consisting of aerobic exercises, followed by static stretching of muscle chains. In TENS group, high-frequency (150 Hz) was applied on bilateral tender points of trapezium and supraspinatus. TENS group had a greater pain reduction (mean change score=-2.0±2.9 cm) compared to Without TENS group (-0.7±3.7 cm). There was a difference between mean change scores of each group for pain threshold (right trapezium: 0.2±1 kg/cm² in TENS group and -0.2±1.2 kg/cm² in Without TENS group). In the evaluation of clinically important changes, patients receiving TENS had relevant improvement of pain, work performance, fatigue, stiffness, anxiety and depression compared to those not receiving TENS. It has suggested that high-frequency TENS as an adjuvant therapy is effective in relieving pain, anxiety, fatigue, stiffness, and in improving ability to work of patients with fibromyalgia. High-frequency TENS may be used as a short-term complementary treatment of fibromyalgia.

78 FR 69825 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to a...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-21

... availability of the species or stock(s) for subsistence uses (where relevant). Further, the permissible methods... (ITA) under section 101(a)(5)(D) of the MMPA, we must set forth the permissible methods of taking... basis of predicted distances to relevant thresholds in post-processing of observational and acoustic...

47 CFR 1.774 - Pricing flexibility.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the non-MSA parts of a study area, must show that the price cap LEC has met the relevant thresholds... or non-MSA parts of a study area, as described in § 69.707 of this chapter; (ii) The number and location of the wire centers in which competitors have collocated in the relevant MSA or non-MSA parts of a...

Threshold factorization redux

NASA Astrophysics Data System (ADS)

Chay, Junegone; Kim, Chul

2018-05-01

We reanalyze the factorization theorems for the Drell-Yan process and for deep inelastic scattering near threshold, as constructed in the framework of the soft-collinear effective theory (SCET), from a new, consistent perspective. In order to formulate the factorization near threshold in SCET, we should include an additional degree of freedom with small energy, collinear to the beam direction. The corresponding collinear-soft mode is included to describe the parton distribution function (PDF) near threshold. The soft function is modified by subtracting the contribution of the collinear-soft modes in order to avoid double counting on the overlap region. As a result, the proper soft function becomes infrared finite, and all the factorized parts are free of rapidity divergence. Furthermore, the separation of the relevant scales in each factorized part becomes manifest. We apply the same idea to the dihadron production in e+e- annihilation near threshold, and show that the resultant soft function is also free of infrared and rapidity divergences.

Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

PubMed

Eickenscheidt, Max; Zeck, Günther

2014-06-01

The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

Using Smartphones to Monitor Bipolar Disorder Symptoms: A Pilot Study.

PubMed

Beiwinkel, Till; Kindermann, Sally; Maier, Andreas; Kerl, Christopher; Moock, Jörn; Barbian, Guido; Rössler, Wulf

2016-01-06

Relapse prevention in bipolar disorder can be improved by monitoring symptoms in patients' daily life. Smartphone apps are easy-to-use, low-cost tools that can be used to assess this information. To date, few studies have examined the usefulness of smartphone data for monitoring symptoms in bipolar disorder. We present results from a pilot test of a smartphone-based monitoring system, Social Information Monitoring for Patients with Bipolar Affective Disorder (SIMBA), that tracked daily mood, physical activity, and social communication in 13 patients. The objective of this study was to investigate whether smartphone measurements predicted clinical symptoms levels and clinical symptom change. The hypotheses that smartphone measurements are (1) negatively related to clinical depressive symptoms and (2) positively related to clinical manic symptoms were tested. Clinical rating scales were administered to assess clinical depressive and manic symptoms. Patients used a smartphone with the monitoring app for up to 12 months. Random-coefficient multilevel models were computed to analyze the relationship between smartphone data and externally rated manic and depressive symptoms. Overall clinical symptom levels and clinical symptom changes were predicted by separating between-patient and within-patient effects. Using established clinical thresholds from the literature, marginal effect plots displayed clinical relevance of smartphone data. Overall symptom levels and change in clinical symptoms were related to smartphone measures. Higher overall levels of clinical depressive symptoms were predicted by lower self-reported mood measured by the smartphone (beta=-.56, P<.001). An increase in clinical depressive symptoms was predicted by a decline in social communication (ie, outgoing text messages: beta=-.28, P<.001) and a decline in physical activity as measured by the smartphone (ie, cell tower movements: beta=-.11, P=.03). Higher overall levels of clinical manic symptoms were predicted by lower physical activity on the smartphone (ie, distance travelled: beta=-.37, P<.001), and higher social communication (beta=.48, P=.03). An increase in clinical manic symptoms was predicted by a decrease in physical activity on the smartphone (beta=-.17, P<.001). Clinical symptoms were related to some objective and subjective smartphone measurements, but not all smartphone measures predicted the occurrence of bipolar symptoms above clinical thresholds. Thus, smartphones have the potential to monitor bipolar disorder symptoms in patients' daily life. Further validation of monitoring tools in a larger sample is needed. Conclusions are limited by the low prevalence of manic and depressive symptoms in the study sample. International Standard Randomized Controlled Trial Number (ISRCTN): 05663421; http://www.controlled-trials.com/ISRCTN05663421 (Archived by WebCite at http://www.webcitation.org/6d9wsibJB).

[Depression and epilepsy : Two clinical pictures with common causes?].

PubMed

Borgmann, M; Holtkamp, M; Adli, M; Behr, J

2016-07-01

Epilepsy and depressive disorders show a high rate of comorbidity. Thus, neurobiological similarities and a bidirectional relationship in terms of pathogenesis have been suggested. The aim of this article is to present the common neurobiological features of both disorders, to characterize the bidirectional relationship and to provide an overview of therapeutic consequences. A review of the current literature and evaluation of studies on the topics of depression and epilepsy are presented. Epilepsy and depression share common neurobiological features. In epileptic patients depression should be diagnosed early and reliably as the successful treatment has a great influence on the prognosis, quality of life and suicide risk in these individuals. In therapeutic doses, antidepressive medication with noradrenergic and specific serotonergic antidepressants (NaSSA) or selective serotonin reuptake inhibitors (SSRI) imparts no clinically relevant epileptogenic potential; however, it increases the quality of life and could have anticonvulsant effects in patients with epilepsy. Clomipramine, bupropion and maprotiline, however, should not be administered to patients with epilepsy as they are known to lower the seizure threshold.

How large must a treatment effect be before it matters to practitioners? An estimation method and demonstration.

PubMed

Miller, William R; Manuel, Jennifer Knapp

2008-09-01

Treatment research is sometimes criticised as lacking in clinical relevance, and one potential source of this friction is a disconnection between statistical significance and what clinicians regard to be a meaningful difference in outcomes. This report demonstrates a novel methodology for estimating what substance abuse practitioners regard to be clinically important differences. To illustrate the estimation method, we surveyed 50 substance abuse treatment providers participating in the National Institute on Drug Abuse (NIDA) Clinical Trials Network. Practitioners identified thresholds for clinically meaningful differences on nine common outcome variables, indicated the size of effect that would justify their learning a new treatment method and estimated current outcomes from their services. Clinicians judged a difference between two treatments to be meaningful if outcomes were improved by about 10 - 12 points on the percentage of patients totally abstaining, arrested for driving while intoxicated, employed or having abnormal liver enzymes. A 5 percentage-point reduction in patient mortality was regarded as clinically significant. On continuous outcome measures (such as percentage of days abstinent or drinks per drinking day), practitioners judged an outcome to be significant when it doubled or halved the base rate. When a new treatment meets such criteria, practitioners were interested in learning it. Effects that are statistically significant in clinical trials may be unimpressive to practitioners. Clinicians' judgements of meaningful differences can inform the powering of clinical trials.

When is rational to order a diagnostic test, or prescribe treatment: the threshold model as an explanation of practice variation.

PubMed

Djulbegovic, Benjamin; van den Ende, Jef; Hamm, Robert M; Mayrhofer, Thomas; Hozo, Iztok; Pauker, Stephen G

2015-05-01

The threshold model represents an important advance in the field of medical decision-making. It is a linchpin between evidence (which exists on the continuum of credibility) and decision-making (which is a categorical exercise - we decide to act or not act). The threshold concept is closely related to the question of rational decision-making. When should the physician act, that is order a diagnostic test, or prescribe treatment? The threshold model embodies the decision theoretic rationality that says the most rational decision is to prescribe treatment when the expected treatment benefit outweighs its expected harms. However, the well-documented large variation in the way physicians order diagnostic tests or decide to administer treatments is consistent with a notion that physicians' individual action thresholds vary. We present a narrative review summarizing the existing literature on physicians' use of a threshold strategy for decision-making. We found that the observed variation in decision action thresholds is partially due to the way people integrate benefits and harms. That is, explanation of variation in clinical practice can be reduced to a consideration of thresholds. Limited evidence suggests that non-expected utility threshold (non-EUT) models, such as regret-based and dual-processing models, may explain current medical practice better. However, inclusion of costs and recognition of risk attitudes towards uncertain treatment effects and comorbidities may improve the explanatory and predictive value of the EUT-based threshold models. The decision when to act is closely related to the question of rational choice. We conclude that the medical community has not yet fully defined criteria for rational clinical decision-making. The traditional notion of rationality rooted in EUT may need to be supplemented by reflective rationality, which strives to integrate all aspects of medical practice - medical, humanistic and socio-economic - within a coherent reasoning system. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Diuretics and diabetes incidence--an appeal against the reluctance to prescribe a medication that is safe and proven.

PubMed

Siebenhofer, A; Jeitler, K; Rakovac, I; Horvath, K

2010-02-01

The publication of the scientific report of the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany on the 'Comparative evaluation of the benefits and harms of different antihypertensive drug classes [diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers and angiotensin II (AT-II) blockers] as first-choice therapy for patients with essential hypertension' raised an enormous public debate, particularly as diabetes incidence was not judged to be a patient-relevant outcome. In this assessment, the overall view of the patient-relevant results was that diuretics can be used as first-line antihypertensive treatment. Diabetes incidence is highest with diuretics, but minimal differences in fasting plasma glucose of approximately 0.28 mmol/l are magnified by the transformation of continuous blood glucose values into categorical data: with the establishment of thresholds, the diagnosis of diabetes depends on being above a certain blood glucose value. The protective cardiovascular effects of diuretics do not seem to be reduced in hypertensive patients who develop new-onset diabetes during treatment. Since blood pressure control is often worse, detection, treatment and control should be urgently improved. The debate on antihypertensive agents is mainly of scientific interest and has only minor clinical relevance for everyday patient care.

Interpreting the biological relevance of bioinformatic analyses with T-DNA sequence for protein allergenicity.

PubMed

Harper, B; McClain, S; Ganko, E W

2012-08-01

Global regulatory agencies require bioinformatic sequence analysis as part of their safety evaluation for transgenic crops. Analysis typically focuses on encoded proteins and adjacent endogenous flanking sequences. Recently, regulatory expectations have expanded to include all reading frames of the inserted DNA. The intent is to provide biologically relevant results that can be used in the overall assessment of safety. This paper evaluates the relevance of assessing the allergenic potential of all DNA reading frames found in common food genes using methods considered for the analysis of T-DNA sequences used in transgenic crops. FASTA and BLASTX algorithms were used to compare genes from maize, rice, soybean, cucumber, melon, watermelon, and tomato using international regulatory guidance. Results show that BLASTX for maize yielded 7254 alignments that exceeded allergen similarity thresholds and 210,772 alignments that matched eight or more consecutive amino acids with an allergen; other crops produced similar results. This analysis suggests that each nontransgenic crop has a much greater potential for allergenic risk than what has been observed clinically. We demonstrate that a meaningful safety assessment is unlikely to be provided by using methods with inherently high frequencies of false positive alignments when broadly applied to all reading frames of DNA sequence. Copyright © 2012 Elsevier Inc. All rights reserved.

Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Valdes, Gilmer; Solberg, Timothy D.; Heskel, Marina; Ungar, Lyle; Simone, Charles B., II

2016-08-01

To develop a patient-specific ‘big data’ clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm.

Reducing depression during the menopausal transition with health coaching: Results from the healthy menopausal transition randomised controlled trial.

PubMed

Almeida, Osvaldo P; Marsh, Kylie; Murray, Karen; Hickey, Martha; Sim, Moira; Ford, Andrew; Flicker, Leon

2016-10-01

To determine if health coaching (HC) decreases the incidence of depression, reduces the severity of symptoms, and increases quality of life during the menopausal transition (MT). Parallel, single-blinded, randomised controlled trial of 6 sessions of phone-delivered HC compared with usual care. Participants were 351 community-dwelling women free of major depression going through the MT, of whom 180 were assigned the intervention and 171 usual care. The primary outcome of interest was the incidence of clinically significant depressive symptoms over 52 weeks. Other study measures included the Hospital Anxiety and Depression Scale, quality of life (SF-12), the Menopause Rating Scale (MRS), diet, body mass index, alcohol use, smoking and physical activity. We considered that women with Patient Health Questionnaire (PHQ-9) scores between 5 and 14 (inclusive) had sub-threshold depressive symptoms. Nine women developed clinically significant symptoms of depression during the study-2 had been assigned HC (odds ratio, OR=0.26, 95%CI=0.05, 1.29; p=0.099). Intention-to-treat showed that, compared with usual care, the intervention led to a greater decline in depressive scores, most markedly for participants with sub-threshold depressive symptoms. Similar, but less pronounced, benefits were noticed for anxiety scores and the mental component summary of the SF-12. The intervention led to a decline in MRS scores by week 26 and subtle improvements in body mass, consumption of vegetables and smoking. HC addressing relevant risk factors for depression during the MT improves mental health measures. Our findings indicate that women with sub-threshold depressive symptoms may benefit the most from such interventions, and suggest that HC could play a useful role in minimizing mental health disturbance for women going through the MT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

"Long-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves".

PubMed

Christie, Breanne P; Freeberg, Max; Memberg, William D; Pinault, Gilles J C; Hoyen, Harry A; Tyler, Dustin J; Triolo, Ronald J

2017-07-11

Electrical stimulation of the peripheral nerves has been shown to be effective in restoring sensory and motor functions in the lower and upper extremities. This neural stimulation can be applied via non-penetrating spiral nerve cuff electrodes, though minimal information has been published regarding their long-term performance for multiple years after implantation. Since 2005, 14 human volunteers with cervical or thoracic spinal cord injuries, or upper limb amputation, were chronically implanted with a total of 50 spiral nerve cuff electrodes on 10 different nerves (mean time post-implant 6.7 ± 3.1 years). The primary outcome measures utilized in this study were muscle recruitment curves, charge thresholds, and percent overlap of recruited motor unit populations. In the eight recipients still actively involved in research studies, 44/45 of the spiral contacts were still functional. In four participants regularly studied over the course of 1 month to 10.4 years, the charge thresholds of the majority of individual contacts remained stable over time. The four participants with spiral cuffs on their femoral nerves were all able to generate sufficient moment to keep the knees locked during standing after 2-4.5 years. The dorsiflexion moment produced by all four fibular nerve cuffs in the active participants exceeded the value required to prevent foot drop, but no tibial nerve cuffs were able to meet the plantarflexion moment that occurs during push-off at a normal walking speed. The selectivity of two multi-contact spiral cuffs was examined and both were still highly selective for different motor unit populations for up to 6.3 years after implantation. The spiral nerve cuffs examined remain functional in motor and sensory neuroprostheses for 2-11 years after implantation. They exhibit stable charge thresholds, clinically relevant recruitment properties, and functional muscle selectivity. Non-penetrating spiral nerve cuff electrodes appear to be a suitable option for long-term clinical use on human peripheral nerves in implanted neuroprostheses.

The Impact of Clinical History on the Threshold Estimation of Auditory Brainstem Response Results for Infants

ERIC Educational Resources Information Center

Zaitoun, Maha; Cumming, Steven; Purcell, Alison; O'Brien, Katie

2017-01-01

Purpose: This study assesses the impact of patient clinical history on audiologists' performance when interpreting auditory brainstem response (ABR) results. Method: Fourteen audiologists' accuracy in estimating hearing threshold for 16 infants through interpretation of ABR traces was compared on 2 occasions at least 5 months apart. On the 1st…

Detecting fatigue thresholds from electromyographic signals: A systematic review on approaches and methodologies.

PubMed

Ertl, Peter; Kruse, Annika; Tilp, Markus

2016-10-01

The aim of the current paper was to systematically review the relevant existing electromyographic threshold concepts within the literature. The electronic databases MEDLINE and SCOPUS were screened for papers published between January 1980 and April 2015 including the keywords: neuromuscular fatigue threshold, anaerobic threshold, electromyographic threshold, muscular fatigue, aerobic-anaerobictransition, ventilatory threshold, exercise testing, and cycle-ergometer. 32 articles were assessed with regard to their electromyographic methodologies, description of results, statistical analysis and test protocols. Only one article was of very good quality. 21 were of good quality and two articles were of very low quality. The review process revealed that: (i) there is consistent evidence of one or two non-linear increases of EMG that might reflect the additional recruitment of motor units (MU) or different fiber types during fatiguing cycle ergometer exercise, (ii) most studies reported no statistically significant difference between electromyographic and metabolic thresholds, (iii) one minute protocols with increments between 10 and 25W appear most appropriate to detect muscular threshold, (iv) threshold detection from the vastus medialis, vastus lateralis, and rectus femoris is recommended, and (v) there is a great variety in study protocols, measurement techniques, and data processing. Therefore, we recommend further research and standardization in the detection of EMGTs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Threshold resummation for top-pair hadroproduction to next-to-next-to-leading log

NASA Astrophysics Data System (ADS)

Czakon, Michal; Mitov, Alexander; Sterman, George

2009-10-01

We derive the threshold-resummed total cross section for heavy quark production in hadronic collisions accurate to next-to-next-to-leading logarithm, employing recent advances on soft anomalous dimension matrices for massive pair production in the relevant kinematic limit. We also derive the relation between heavy quark threshold resummations for fixed pair kinematics and the inclusive cross section. As a check of our results, we have verified that they reproduce all poles of the color-averaged qq¯→tt¯ amplitudes at two loops, noting that the latter are insensitive to the color-antisymmetric terms of the soft anomalous dimension.

No Clinically Significant Difference Between Adult and Pediatric IKDC Subjective Knee Evaluation Scores in Adults

PubMed Central

Stegmeier, Nicole; Oak, Sameer R.; O’Rourke, Colin; Strnad, Greg; Spindler, Kurt P.; Jones, Morgan; Farrow, Lutul D.; Andrish, Jack; Saluan, Paul

2017-01-01

Background: Two versions of the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form currently exist: the original version (1999) and a recently modified pediatric-specific version (2011). Comparison of the pediatric IKDC with the adult version in the adult population may reveal that either version could be used longitudinally. Hypothesis: We hypothesize that the scores for the adult IKDC and pediatric IKDC will not be clinically different among adult patients aged 18 to 50 years. Study Design: Randomized crossover study design. Level of Evidence: Level 2. Methods: The study consisted of 100 participants, aged 18 to 50 years, who presented to orthopaedic outpatient clinics with knee problems. All participants completed both adult and pediatric versions of the IKDC in random order with a 10-minute break in between. We used a paired t test to test for a difference between the scores and a Welch’s 2-sample t test to test for equivalence. A least-squares regression model was used to model adult scores as a function of pediatric scores, and vice versa. Results: A paired t test revealed a statistically significant 1.6-point difference between the mean adult and pediatric scores. However, the 95% confidence interval (0.54-2.66) for this difference did not exceed our a priori threshold of 5 points, indicating that this difference was not clinically important. Equivalence testing with an equivalence region of 5 points further supported this finding. The adult and pediatric scores had a linear relationship and were highly correlated with an R2 of 92.6%. Conclusion: There is no clinically relevant difference between the scores of the adult and pediatric IKDC forms in adults, aged 18 to 50 years, with knee conditions. Clinical Relevance: Either form, adult or pediatric, of the IKDC can be used in this population for longitudinal studies. If the pediatric version is administered in adolescence, it can be used for follow-up into adulthood. PMID:28080306

Parameters of metabolic quantification in clinical practice. Is it now time to include them in reports?

PubMed

Mucientes, J; Calles, L; Rodríguez, B; Mitjavila, M

2018-01-18

Qualitative techniques have traditionally been the standard for the diagnostic assessment with 18 F-FDG PET studies. Since the introduction of the technique, quantitative parameters have been sought, more accurate and with better diagnostic precision, that may offer relevant information of the behavior, aggressiveness or prognosis of tumors. Nowadays, more and more studies with high quality evidence show the utility of other metabolic parameters different from the SUV maximum, which despite being widely used in clinical practice is controversial and many physicians still do not know its real meaning. The objective of this paper has been to review the key concepts of these metabolic parameters that could be relevant in normal practice in the future. It has been seen that there is more evidence in the complete evaluation of the metabolism of a lesion, through volumetric parameters that more adequately reflect the patient's tumor burden. Basically, these parameters calculate the volume of tumor that fulfills certain characteristics. A software available in the majority of the workstations has been used for this purpose and it has allowed to calculate these volumes using more or less complex criteria. The simplest threshold-based segmentation methods are available in most equipments, they are easy to calculate and they have been shown in many studies to have an important prognostic significance. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.

PubMed

Vidriales, María-Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José-Juan; Chandía, Mauricio; Díaz-Mediavilla, Joaquín; Rayón, Consuelo; de Las Heras, Natalia; Fernández-Abellán, Pascual; Cabezudo, Miguel; de Coca, Alfonso García; Alonso, Jose M; Olivier, Carmen; Hernández-Rivas, Jesús M; Montesinos, Pau; Fernández, Rosa; García-Suárez, Julio; García, Magdalena; Sayas, María-José; Paiva, Bruno; González, Marcos; Orfao, Alberto; San Miguel, Jesús F

2016-01-01

The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tissue viability monitoring: a multi-sensor wearable platform approach

NASA Astrophysics Data System (ADS)

Mathur, Neha; Davidson, Alan; Buis, Arjan; Glesk, Ivan

2016-12-01

Health services worldwide are seeking ways to improve patient care for amputees suffering from diabetes, and at the same time reduce costs. The monitoring of residual limb temperature, interface pressure and gait can be a useful indicator of tissue viability in lower limb amputees especially to predict the occurrence of pressure ulcers. This is further exacerbated by elevated temperatures and humid micro environment within the prosthesis which encourages the growth of bacteria and skin breakdown. Wearable systems for prosthetic users have to be designed such that the sensors are minimally obtrusive and reliable enough to faithfully record movement and physiological signals. A mobile sensor platform has been developed for use with the lower limb prosthetic users. This system uses an Arduino board that includes sensors for temperature, gait, orientation and pressure measurements. The platform transmits sensor data to a central health authority database server infrastructure through the Bluetooth protocol at a suitable sampling rate. The data-sets recorded using these systems are then processed using machine learning algorithms to extract clinically relevant information from the data. Where a sensor threshold is reached a warning signal can be sent wirelessly together with the relevant data to the patient and appropriate medical personnel. This knowledge is also useful in establishing biomarkers related to a possible deterioration in a patient's health or for assessing the impact of clinical interventions.

Major Depressive Disorder with Sub-threshold Bipolarity in the National Comorbidity Survey Replication

PubMed Central

Angst, Jules; Cui, Lihong; Swendsen, J. Joel; Rothen, S.; Cravchik, Anibal; Kessler, Ronald; Merikangas, Kathleen

2011-01-01

Objectives There is growing clinical and epidemiologic evidence indicating that major mood disorders form a spectrum from Major Depressive Disorder (MDD) to pure mania. The present investigation examined the prevalence and clinical correlates of MDD with sub-threshold bipolarity vs. pure MDD in the National Comorbidity Survey Replication (NCS-R). Methods The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February, 2001 and April, 2003. Lifetime history of mood disorders, symptoms and clinical indicators of severity were collected using version 3.0 of the WHO Composite International Diagnostic Interview, a fully structured lay-administered diagnostic interview. Results Nearly 40% of study participants with a history of major depressive disorder had a history of sub-threshold hypomania. This subgroup had a younger age of disorder onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania, and lower levels of clinical severity than those with bipolar II disorder. Conclusions The findings demonstrate heterogeneity of major depressive disorder and support the validity of inclusion of sub-threshold mania in the diagnostic classification. The broadening of criteria for bipolar disorder would have important implications for research and clinical practice. PMID:20713498

Long-term thresholds of nonsteroidal permanent pacing leads: a 5-year study.

PubMed

Gumbrielle, T P; Bourke, J P; Sinkovic, M; Tynan, M; Kittpawong, P; Gold, R G

1996-05-01

The present commercial market supports many nonsteroidal endocardial pacing leads of differing construction. In order to compare the performance of these configurations, we studied the long-term pacing properties of three representative lead types by randomized clinical trial in 99 patients undergoing a first elective VVI implant. Thirty-one patients received sintered platinum leads, 36 activated pyrolytic carbon leads, and 32 vitreous carbon leads. All received generators capable of noninvasive threshold testing. Acute sensing parameters were R wave amplitude and ST segment elevation measured from the endocardial electrogram. Noninvasive voltage thresholds were measured at implantation, 2 days, 1, 3, and 6 months, and yearly thereafter for 5 years. There were no significant differences between leads in pacing or sensing capabilities at implantation. All three demonstrated similar increases in thresholds, peaking at 1 month, then falling to a plateau by 6 months and did not vary significantly thereafter. There were no significant differences in thresholds between leads during 5 years of follow-up. The lowest mean threshold at 5 years was 0.93 V at 0.5 ms. This study suggests that: (1) although these lead types all perform well, none offers any particular clinical advantage over another; (2) the degree of early threshold peaking precludes immediate postimplant output reduction, but later thresholds are sufficiently low to enable reductions in pacing output; (3) safe low energy pacing requires greater attention to the lead-generator combinations; (4) data obtained at subsequent annual follow-up provided no additional useful clinical information to that obtained at 1 year; and (5) in the absence of other differences, cost can be the deciding factor in lead selection.

Modern concepts of caries measurement.

PubMed

Pitts, N B

2004-01-01

Following the consideration of several recent systematic and other reviews, there is a growing professional and scientific consensus that caries measurement methodology in caries clinical trials (CCT) should be updated to reflect progress made elsewhere in cariology. In this paper, therefore, "modern" means accepted in contemporary dental research and dental practice on the basis of sound research evidence--not necessarily new or requiring the use of new technology. Caries measurement should be seen in the context of the objectives of modern clinical caries management and the continuum of disease states, ranging from sub-surface carious changes through to more advanced lesions. Measurement concepts can be applied to at least three levels: the tooth surface, the individual, or the group/population. All are relevant to CCTs. Modern clinical caries management can be seen as comprised of seven discrete but linked steps (Steps 2, 3, and 4 are directly concerned with measurement.): (1) 'Caries detection' represents a yes/no decision as to whether caries is present; (2) lesion measurement assesses defined stages of the caries process, taking into account the histopatholgical morphology and appearance of different sizes and types of lesion and the diagnostic threshold(s) being used; (3) lesion monitoring by repeated measures at a series of examinations is used when lesions are less advanced than the stage judged to require operative intervention (A comparison of serial measurements permits the efficacy of preventive care aiming either to arrest or to reverse the lesion to be assessed.); (4) caries activity measures would be very valuable, but are relatively poorly developed and tested at present; (5) diagnosis, prognosis, and clinical decision-making are the important human processes in which all the information obtained from steps 1 to 4 is synthesised; (6) interventions/treatments, both preventive and operative, are now routinely used for caries management; and (7) outcome of caries control/management assesses caries management by examining evidence on the long-term outcomes. A challenge for the future is to define a range of optimal caries measurement methods--in use or in development in recent trials, in clinical practice, and/or in caries epidemiology--that will best contribute to more efficient, modern caries clinical trials.

Proton threshold states in the Na22(p,γ)Mg23 reaction and astrophysical implications

NASA Astrophysics Data System (ADS)

Comisel, H.; Hategan, C.; Graw, G.; Wolter, H. H.

2007-04-01

Proton threshold states in Mg23 are important for the astrophysically relevant proton capture reaction Na22(p,γ)Mg23. In the indirect determination of the resonance strength of the lowest states, which were not accessible by direct methods, some of the spin-parity-assignments remained experimentally uncertain. We have investigated these states with shell model, Coulomb displacement, and Thomas-Ehrman shift calculations. From the comparison of calculated and observed properties, we relate the lowest relevant resonance state at Ex=7643 keV to an excited 3/2+ state in accordance with a recent experimental determination by Jenkins From this we deduce significantly improved values for the Na22(p,γ)Mg23 reaction rate at stellar temperatures below T9=0.1 K.

p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women

PubMed Central

Fetterman, Barbara; Castle, Philip E.; Schiffman, Mark; Wood, Shannon N.; Stiemerling, Eric; Tokugawa, Diane; Bodelon, Clara; Poitras, Nancy; Lorey, Thomas; Kinney, Walter

2015-01-01

Background: Human papillomavirus (HPV)–based cervical cancer screening requires triage markers to decide who should be referred to colposcopy. p16/Ki-67 dual stain cytology has been proposed as a biomarker for cervical precancers. We evaluated the dual stain in a large population of HPV-positive women. Methods: One thousand five hundred and nine HPV-positive women screened with HPV/cytology cotesting at Kaiser Permanente California were enrolled into a prospective observational study in 2012. Dual stain cytology was performed on residual Surepath material, and slides were evaluated for dual stain–positive cells. Disease endpoints were ascertained from the clinical database at KPNC. We evaluated the clinical performance of the assay among all HPV-positive women and among HPV-positive, cytology-negative women. We used internal benchmarks for clinical management to evaluate the clinical relevance of the dual stain assay. We evaluated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the dual stain compared with Pap cytology. All statistical tests were two-sided. Results: The dual stain had lower positivity (45.9%) compared with cytology at an ASC-US threshold (53.4%). For detection of CIN2+, the dual stain had similar sensitivity (83.4% vs 76.6%, P = .1), and statistically higher specificity (58.9% vs 49.6%, P < .001), PPV (21.0% vs 16.6%, P < .001), and NPV (96.4% vs 94.2%, P = .01) compared with cytology. Similar patterns were observed for CIN3+. Women with a positive test had high enough risk for referral to colposcopy, while the risk for women with negative tests was below a one-year return threshold based on current US management guidelines. Conclusion: Dual stain cytology showed good risk stratification for all HPV-positive women and for HPV-positive women with normal cytology. Additional follow-up is needed to determine how long dual stain negative women remain at low risk of precancer. PMID:26376685

Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage.

PubMed

Carson, Jeffrey L; Guyatt, Gordon; Heddle, Nancy M; Grossman, Brenda J; Cohn, Claudia S; Fung, Mark K; Gernsheimer, Terry; Holcomb, John B; Kaplan, Lewis J; Katz, Louis M; Peterson, Nikki; Ramsey, Glenn; Rao, Sunil V; Roback, John D; Shander, Aryeh; Tobian, Aaron A R

2016-11-15

More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence). Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.

Even High Doses of Oral Cannabidiol Do Not Cause THC-Like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research 2016;1(1):102–112; DOI: 10.1089/can.2015.0004

PubMed Central

Grotenhermen, Franjo; Russo, Ethan; Zuardi, Antonio Waldo

2017-01-01

Abstract This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that “the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response.” They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses. PMID:28861499

Even High Doses of Oral Cannabidol Do Not Cause THC-Like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research 2016;1(1):102-112; DOI: 10.1089/can.2015.0004.

PubMed

Grotenhermen, Franjo; Russo, Ethan; Zuardi, Antonio Waldo

2017-01-01

This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that "the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response." They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses.

Resected Brain Tissue, Seizure Onset Zone and Quantitative EEG Measures: Towards Prediction of Post-Surgical Seizure Control

PubMed Central

Andrzejak, Ralph G.; Hauf, Martinus; Pollo, Claudio; Müller, Markus; Weisstanner, Christian; Wiest, Roland; Schindler, Kaspar

2015-01-01

Background Epilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure. Methods Despite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels. Results In patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied. Conclusions We conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent with growing evidence that spatially extended networks might be more relevant for seizure generation, evolution and termination than a single highly localized brain region (i.e. a “focus”) where seizures start. PMID:26513359

Clinical disorders and pressure-pain threshold of the forearm and hand among automobile assembly line workers.

PubMed

Byström, S; Hall, C; Welander, T; Kilbom, A

1995-12-01

The prevalence of forearm and hand disorders was examined by questionnaire and clinical examination in 199 automobile assembly line workers and in 186 controls. The pressure-pain threshold, hand grip force and hand anthropometry were also studied. There was an increased prevalence of de Quervain's disease for male automobile assembly line workers, and of carpal tunnel syndrome in female workers. The prevalence of symptoms in the forearm and hand during the last 7 days were twice as high among automobile assembly line workers than controls for both men and women. The occurrence of symptoms in the last 7 days was associated with de Quervain's disease, carpal tunnel syndrome and sick-leave due to forearm or hand problems, and it also influenced activities of daily living. Hand grip strength and anthropometrics were not associated with findings in the clinical examination or the occurrence of symptoms in the last 7 days. Low pressure-pain threshold was not associated with findings in the clinical examination, except for reported occurrence of symptoms in the last 7 days for women. Pressure-pain threshold as an indicator of tissue damage is discussed.

Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons.

PubMed

Weissman-Fogel, Irit; Sprecher, Elliot; Granovsky, Yelena; Yarnitsky, David

2003-08-01

Recent clinical studies showed that acute migraine attacks are accompanied by increased periorbital and bodily skin sensitivity to touch, heat and cold. Parallel pre-clinical studies showed that the underlying mechanism is sensitization of primary nociceptors and central trigeminovascular neurons. The present study investigates the sensory state of neuronal pathways that mediate skin pain sensation in migraine patients in between attacks. The assessments of sensory perception included (a) mechanical and thermal pain thresholds of the periorbital area, electrical pain threshold of forearm skin, (b) pain scores to phasic supra-threshold stimuli in the same modalities and areas as above, and (c) temporal summation of pain induced by applying noxious tonic heat pain and brief trains of noxious mechanical and electrical pulses to the above skin areas. Thirty-four pain-free migraine patients and 28 age- and gender-matched controls were studied. Patients did not differ from controls in their pain thresholds for heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6 mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for all modalities. They did, however, differ in their pain threshold for mechanical stimulation, just by one von Frey filament (P=0.01) and in their pain scores of the temporal summation tests. Increased summation of pain was found in migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS) +2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased summation corresponded with more severe clinical parameters of migraine and tended to depend on interval since last migraine attack. The absence of clinically or overt laboratory expressed allodynia suggests that pain pathways are not sensitized in the pain-free migraine patients. Nevertheless, the increased temporal summation, and the slight decrease in mechanical pain thresholds, suggest that central nociceptive neurons do express activation-dependent plasticity. These findings may point to an important pathophysiological change in membrane properties of nociceptive neurons of migraine patients; a change that may hold a key to more effective prophylactic treatment.

Thwarting science by protecting the received wisdom on tobacco addiction from the scientific method.

PubMed

Difranza, Joseph R

2010-11-04

In their commentary, Dar and Frenk call into question the validity of all published data that describe the onset of nicotine addiction. They argue that the data that describe the early onset of nicotine addiction is so different from the conventional wisdom that it is irrelevant. In this rebuttal, the author argues that the conventional wisdom cannot withstand an application of the scientific method that requires that theories be tested and discarded when they are contradicted by data. The author examines the origins of the threshold theory that has represented the conventional wisdom concerning the onset of nicotine addiction for 4 decades. The major tenets of the threshold theory are presented as hypotheses followed by an examination of the relevant literature. Every tenet of the threshold theory is contradicted by all available relevant data and yet it remains the conventional wisdom. The author provides an evidence-based account of the natural history of nicotine addiction, including its onset and development as revealed by case histories, focus groups, and surveys involving tens of thousands of smokers. These peer-reviewed and replicated studies are the work of independent researchers from around the world using a variety of measures, and they provide a consistent and coherent clinical picture. The author argues that the scientific method demands that the fanciful conventional wisdom be discarded and replaced with the evidence-based description of nicotine addiction that is backed by data. The author charges that in their attempt to defend the conventional wisdom in the face of overwhelming data to the contrary, Dar and Frenk attempt to destroy the credibility of all who have produced these data. Dar and Frenk accuse other researchers of committing methodological errors and showing bias in the analysis of data when in fact Dar and Frenk commit several errors and reveal their bias by using a few outlying data points to misrepresent an entire body of research, and by grossly and consistently mischaracterizing the claims of those whose research they attack.

Should Malaria Treatment Be Guided by a Point of Care Rapid Test? A Threshold Approach to Malaria Management in Rural Burkina Faso

PubMed Central

Bisoffi, Zeno; Tinto, Halidou; Sirima, Bienvenu Sodiomon; Gobbi, Federico; Angheben, Andrea; Buonfrate, Dora; Van den Ende, Jef

2013-01-01

Background In Burkina Faso, rapid diagnostic tests for malaria have been made recently available. Previously, malaria was managed clinically. This study aims at assessing which is the best management option of a febrile patient in a hyperendemic setting. Three alternatives are: treating presumptively, testing, or refraining from both test and treatment. The test threshold is the tradeoff between refraining and testing, the test-treatment threshold is the tradeoff between testing and treating. Only if the disease probability lies between the two should the test be used. Methods and Findings Data for this analysis was obtained from previous studies on malaria rapid tests, involving 5220 patients. The thresholds were calculated, based on disease risk, treatment risk and cost, test accuracy and cost. The thresholds were then matched against the disease probability. For a febrile child under 5 in the dry season, the pre-test probability of clinical malaria (3.2%), was just above the test/treatment threshold. In the rainy season, that probability was 63%, largely above the test/treatment threshold. For febrile children >5 years and adults in the dry season, the probability was 1.7%, below the test threshold, while in the rainy season it was higher (25.1%), and situated between the two thresholds (3% and 60.9%), only if costs were not considered. If they were, neither testing nor treating with artemisinin combination treatments (ACT) would be recommended. Conclusions A febrile child under 5 should be treated presumptively. In the dry season, the probability of clinical malaria in adults is so low, that neither testing nor treating with any regimen should be recommended. In the rainy season, if costs are considered, a febrile adult should not be tested, nor treated with ACT, but a possible alternative would be a presumptive treatment with amodiaquine plus sulfadoxine-pyrimethamine. If costs were not considered, testing would be recommended. PMID:23472129

Controversies in the physiological basis of the 'anaerobic threshold' and their implications for clinical cardiopulmonary exercise testing.

PubMed

Hopker, J G; Jobson, S A; Pandit, J J

2011-02-01

This article reviews the notion of the 'anaerobic threshold' in the context of cardiopulmonary exercise testing. Primarily, this is a review of the proposed mechanisms underlying the ventilatory and lactate response to incremental exercise, which is important to the clinical interpretation of an exercise test. Since such tests are often conducted for risk stratification before major surgery, a failure to locate or justify the existence of an anaerobic threshold will have some implications for clinical practice. We also consider alternative endpoints within the exercise response that might be better used to indicate a patient's capacity to cope with the metabolic demands encountered both during and following major surgery. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

Detailed statistical assessment of the characteristics of the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) threshold rules.

PubMed

Dafni, Urania; Karlis, Dimitris; Pedeli, Xanthi; Bogaerts, Jan; Pentheroudakis, George; Tabernero, Josep; Zielinski, Christoph C; Piccart, Martine J; de Vries, Elisabeth G E; Latino, Nicola Jane; Douillard, Jean-Yves; Cherny, Nathan I

2017-01-01

The European Society for Medical Oncology (ESMO) has developed the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS), a tool to assess the magnitude of clinical benefit from new cancer therapies. Grading is guided by a dual rule comparing the relative benefit (RB) and the absolute benefit (AB) achieved by the therapy to prespecified threshold values. The ESMO-MCBS v1.0 dual rule evaluates the RB of an experimental treatment based on the lower limit of the 95%CI (LL95%CI) for the hazard ratio (HR) along with an AB threshold. This dual rule addresses two goals: inclusiveness: not unfairly penalising experimental treatments from trials designed with adequate power targeting clinically meaningful relative benefit; and discernment: penalising trials designed to detect a small inconsequential benefit. Based on 50 000 simulations of plausible trial scenarios, the sensitivity and specificity of the LL95%CI rule and the ESMO-MCBS dual rule, the robustness of their characteristics for reasonable power and range of targeted and true HRs, are examined. The per cent acceptance of maximal preliminary grade is compared with other dual rules based on point estimate (PE) thresholds for RB. For particularly small or particularly large studies, the observed benefit needs to be relatively big for the ESMO-MCBS dual rule to be satisfied and the maximal grade awarded. Compared with approaches that evaluate RB using the PE thresholds, simulations demonstrate that the MCBS approach better exhibits the desired behaviour achieving the goals of both inclusiveness and discernment. RB assessment using the LL95%CI for HR rather than a PE threshold has two advantages: it diminishes the probability of excluding big benefit positive studies from achieving due credit and, when combined with the AB assessment, it increases the probability of downgrading a trial with a statistically significant but clinically insignificant observed benefit.

Detailed statistical assessment of the characteristics of the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) threshold rules

PubMed Central

Dafni, Urania; Karlis, Dimitris; Pedeli, Xanthi; Bogaerts, Jan; Pentheroudakis, George; Tabernero, Josep; Zielinski, Christoph C; Piccart, Martine J; de Vries, Elisabeth G E; Latino, Nicola Jane; Douillard, Jean-Yves; Cherny, Nathan I

2017-01-01

Background The European Society for Medical Oncology (ESMO) has developed the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS), a tool to assess the magnitude of clinical benefit from new cancer therapies. Grading is guided by a dual rule comparing the relative benefit (RB) and the absolute benefit (AB) achieved by the therapy to prespecified threshold values. The ESMO-MCBS v1.0 dual rule evaluates the RB of an experimental treatment based on the lower limit of the 95%CI (LL95%CI) for the hazard ratio (HR) along with an AB threshold. This dual rule addresses two goals: inclusiveness: not unfairly penalising experimental treatments from trials designed with adequate power targeting clinically meaningful relative benefit; and discernment: penalising trials designed to detect a small inconsequential benefit. Methods Based on 50 000 simulations of plausible trial scenarios, the sensitivity and specificity of the LL95%CI rule and the ESMO-MCBS dual rule, the robustness of their characteristics for reasonable power and range of targeted and true HRs, are examined. The per cent acceptance of maximal preliminary grade is compared with other dual rules based on point estimate (PE) thresholds for RB. Results For particularly small or particularly large studies, the observed benefit needs to be relatively big for the ESMO-MCBS dual rule to be satisfied and the maximal grade awarded. Compared with approaches that evaluate RB using the PE thresholds, simulations demonstrate that the MCBS approach better exhibits the desired behaviour achieving the goals of both inclusiveness and discernment. Conclusions RB assessment using the LL95%CI for HR rather than a PE threshold has two advantages: it diminishes the probability of excluding big benefit positive studies from achieving due credit and, when combined with the AB assessment, it increases the probability of downgrading a trial with a statistically significant but clinically insignificant observed benefit. PMID:29067214

Perspectives on the relevance of the circadian time structure to workplace threshold limit values and employee biological monitoring.

PubMed

Smolensky, Michael H; Reinberg, Alain E; Sackett-Lundeen, Linda

2017-01-01

The circadian time structure (CTS) and its disruption by rotating and nightshift schedules relative to work performance, accident risk, and health/wellbeing have long been areas of occupational medicine research. Yet, there has been little exploration of the relevance of the CTS to setting short-term, time-weighted, and ceiling threshold limit values (TLVs); conducting employee biological monitoring (BM); and establishing normative reference biological exposure indices (BEIs). Numerous publications during the past six decades document the CTS substantially affects the disposition - absorption, distribution, metabolism, and elimination - and effects of medications. Additionally, laboratory animal and human studies verify the tolerance to chemical, biological (contagious), and physical agents can differ extensively according to the circadian time of exposure. Because of slow and usually incomplete CTS adjustment by rotating and permanent nightshift workers, occupational chemical and other contaminant encounters occur during a different circadian stage than for dayshift workers. Thus, the intended protection of some TLVs when working the nightshift compared to dayshift might be insufficient, especially in high-risk settings. The CTS is germane to employee BM in that large-amplitude predictable-in-time 24h variation can occur in the concentration of urine, blood, and saliva of monitored chemical contaminants and their metabolites plus biomarkers indicative of adverse xenobiotic exposure. The concept of biological time-qualified (for rhythms) reference values, currently of interest to clinical laboratory pathology practice, is seemingly applicable to industrial medicine as circadian time and workshift-specific BEIs to improve surveillance of night workers, in particular. Furthermore, BM as serial assessments performed frequently both during and off work, exemplified by employee self-measurement of lung function using a small portable peak expiratory flow meter, can easily identify intolerance before induction of pathology.

Risk assessment for job burnout with a mobile health web application using questionnaire data: a proof of concept study.

PubMed

von Känel, Roland; van Nuffel, Marc; Fuchs, Walther J

2016-01-01

Job burnout has become a rampant epidemic in working societies, causing high productivity loss and healthcare costs. An easy accessible tool to detect clinically relevant risk may bear the potential to timely avert the dire sequelae of burnout. As a start, we performed a proof of concept study to test the utilization of a mobile health web application for a free and anonymous burnout risk assessment with established questionnaires. We designed a client-side javascript web application for users who filled out demographic and psychometric data forms over the internet. Users were recruited through social media, back links from hospital websites, and search engine optimization. Similar to population-based studies, we used the Maslach Burnout Inventory-General Survey (MBI-GS) to calculate a burnout risk index (BRIX). As additional mental health burden indices, users filled out the Perceived Stress Scale, Insomina Severity Index, and Profile of Mood States. Within six months, the MBI-GS was completed by 11,311 users (median age 33 years, 85 % women) of whom 20.0 % had no clinically relevant burnout risk, 54.7 % had mild-to-moderate risk, and 25.3 % had high risk. In the 2947 users completing all questionnaires, female sex ( B  = -0.03), cohabiting ( B  = -0.03), negative affect ( B  = 0.46), positive affect ( B  = -0.20), perceived stress ( B  = 0.18), and insomnia symptoms ( B  = 0.04) explained 56.2 % of the variance in the continuously scaled BRIX. The reliability was good to excellent for all psychometric scales. The weighting of the BRIX with mental health burden indices primarily modified the risk in users with mild-to-moderate burnout risk. A low-threshold web application can reliably assess the risk of job burnout. As the bulk of users had clinically relevant burnout scores, a web application may be useful to target employees at risk. The clinical value of the BRIX and its modification with coexistent/absent mental health burden awaits evaluation with work and health outcomes.

High performance dental resin composites with hydrolytically stable monomers.

PubMed

Wang, Xiaohong; Huyang, George; Palagummi, Sri Vikram; Liu, Xiaohui; Skrtic, Drago; Beauchamp, Carlos; Bowen, Rafael; Sun, Jirun

2018-02-01

The objectives of this project were to: 1) develop strong and durable dental resin composites by employing new monomers that are hydrolytically stable, and 2) demonstrate that resin composites based on these monomers perform superiorly to the traditional bisphenol A glycidyl dimethacrylate/triethylene glycol dimethacrylate (Bis-GMA/TEGDMA) composites under testing conditions relevant to clinical applications. New resins comprising hydrolytically stable, ether-based monomer, i.e., triethylene glycol divinylbenzyl ether (TEG-DVBE), and urethane dimethacrylate (UDMA) were produced via composition-controlled photo-polymerization. Their composites contained 67.5wt% of micro and 7.5wt% of nano-sized filler. The performances of both copolymers and composites were evaluated by a battery of clinically-relevant assessments: degree of vinyl conversion (DC: FTIR and NIR spectroscopy); refractive index (n: optical microscopy); elastic modulus (E), flexural strength (F) and fracture toughness (K IC ) (universal mechanical testing); Knoop hardness (HK; indentation); water sorption (W sp ) and solubility (W su ) (gravimetry); polymerization shrinkage (S v ; mercury dilatometry) and polymerization stress (tensometer). The experimental UDMA/TEG-DVBE composites were compared with the Bis-GMA/TEGDMA composites containing the identical filler contents, and with the commercial micro hybrid flowable composite. UDMA/TEG-DBVE composites exhibited n, E, W sp , W su and S v equivalent to the controls. They outperformed the controls with respect to F (up to 26.8% increase), K IC (up to 27.7% increase), modulus recovery upon water sorption (full recovery vs. 91.9% recovery), and stress formation (up to 52.7% reduction). In addition, new composites showed up to 27.7% increase in attainable DC compared to the traditional composites. Bis-GMA/TEGDMA controls exceeded the experimental composites with respect to only one property, the composite hardness. Significantly, up to 18.1% lower HK values in the experimental series (0.458GPa) were still above the clinically required threshold of approx. 0.4GPa. Hydrolytic stability, composition-controlled polymerization and the overall enhancement in clinically-relevant properties of the new resin composites make them viable candidates to replace traditional resin composites as a new generation of strong and durable dental restoratives. Copyright © 2017 The Academy of Dental Materials. All rights reserved.

Clinical relevance vs. statistical significance: Using neck outcomes in patients with temporomandibular disorders as an example.

PubMed

Armijo-Olivo, Susan; Warren, Sharon; Fuentes, Jorge; Magee, David J

2011-12-01

Statistical significance has been used extensively to evaluate the results of research studies. Nevertheless, it offers only limited information to clinicians. The assessment of clinical relevance can facilitate the interpretation of the research results into clinical practice. The objective of this study was to explore different methods to evaluate the clinical relevance of the results using a cross-sectional study as an example comparing different neck outcomes between subjects with temporomandibular disorders and healthy controls. Subjects were compared for head and cervical posture, maximal cervical muscle strength, endurance of the cervical flexor and extensor muscles, and electromyographic activity of the cervical flexor muscles during the CranioCervical Flexion Test (CCFT). The evaluation of clinical relevance of the results was performed based on the effect size (ES), minimal important difference (MID), and clinical judgement. The results of this study show that it is possible to have statistical significance without having clinical relevance, to have both statistical significance and clinical relevance, to have clinical relevance without having statistical significance, or to have neither statistical significance nor clinical relevance. The evaluation of clinical relevance in clinical research is crucial to simplify the transfer of knowledge from research into practice. Clinical researchers should present the clinical relevance of their results. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Natural history of occupational hearing loss induced by noise].

PubMed

de Almeida, S I; Albernaz, P L; Zaia, P A; Xavier, O G; Karazawa, E H

2000-01-01

To evaluate the clinical and audiometric characteristics of occupational hearing loss induced by noise, according to age and time of exposition in years. 222 patients with occupational sensorineural hearing loss induced by noise were studied retrospectively, correlating the auditive clinical claims, alterations of audiometric thresholds at frequencies of 250 Hz to 8000 Hz, speech discrimination indicator with age and time of exposure. As a control group were used the audiometric threshold of a population of same medium age, without morbid antecedents of hearing illness, as preconized by ISO 1999 (1990). The group were divided into subgroups and three decades of exposure were analyzed. It was verified that the clinical claims of hipoacusia increases according to the age and time of exposure. The frequency of tinnitus is constant. The audiometric thresholds in the second decade of exposure present variations that depend on the age. The several audiometric curves are parallel, but they are not horizontal. The worst thresholds were found in the high frequencies from 3000 Hz to 8000 Hz, as a clinical and physiopathological consequences of the commitment of basal areas of cochlea. The speech discrimination showed to be worst according to the increase of age and time of exposure. Patients with hearing loss disacusia induced by occupational noise present characteristic audiometric thresholds that vary according to age and time of exposure to noise. These characteristics defined and resumed in audiometric curves can constitute a standard of comparison, evaluation and control for exposed populations.

Cochlear neuropathy and the coding of supra-threshold sound.

PubMed

Bharadwaj, Hari M; Verhulst, Sarah; Shaheen, Luke; Liberman, M Charles; Shinn-Cunningham, Barbara G

2014-01-01

Many listeners with hearing thresholds within the clinically normal range nonetheless complain of difficulty hearing in everyday settings and understanding speech in noise. Converging evidence from human and animal studies points to one potential source of such difficulties: differences in the fidelity with which supra-threshold sound is encoded in the early portions of the auditory pathway. Measures of auditory subcortical steady-state responses (SSSRs) in humans and animals support the idea that the temporal precision of the early auditory representation can be poor even when hearing thresholds are normal. In humans with normal hearing thresholds (NHTs), paradigms that require listeners to make use of the detailed spectro-temporal structure of supra-threshold sound, such as selective attention and discrimination of frequency modulation (FM), reveal individual differences that correlate with subcortical temporal coding precision. Animal studies show that noise exposure and aging can cause a loss of a large percentage of auditory nerve fibers (ANFs) without any significant change in measured audiograms. Here, we argue that cochlear neuropathy may reduce encoding precision of supra-threshold sound, and that this manifests both behaviorally and in SSSRs in humans. Furthermore, recent studies suggest that noise-induced neuropathy may be selective for higher-threshold, lower-spontaneous-rate nerve fibers. Based on our hypothesis, we suggest some approaches that may yield particularly sensitive, objective measures of supra-threshold coding deficits that arise due to neuropathy. Finally, we comment on the potential clinical significance of these ideas and identify areas for future investigation.

Advances in clinical studies of cardiopulmonary resuscitation

PubMed Central

Chen, Shou-quan

2015-01-01

BACKGROUND: The survival rate of patients after cardiac arrest (CA) remains lower since 2010 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) was published. In clinical trials, the methods and techniques for CPR have been overly described. This article gives an overview of the progress in methods and techniques for CPR in the past years. DATA SOURCES: Original articles about cardiac arrest and CPR from MEDLINE (PubMed) and relevant journals were searched, and most of them were clinical randomized controlled trials (RCTs). RESULTS: Forty-two articles on methods and techniques of CPR were reviewed, including chest compression and conventional CPR, chest compression depth and speed, defibrillation strategies and priority, mechanical and manual chest compression, advanced airway management, impedance threshold device (ITD) and active compression-decompression (ACD) CPR, epinephrine use, and therapeutic hypothermia. The results of studies and related issues described in the international guidelines had been testified. CONCLUSIONS: Although large multicenter studies on CPR are still difficult to carry out, progress has been made in the past 4 years in the methods and techniques of CPR. The results of this review provide evidences for updating the 2015 international guidelines. PMID:26056537

Optimal threshold estimator of a prognostic marker by maximizing a time-dependent expected utility function for a patient-centered stratified medicine.

PubMed

Dantan, Etienne; Foucher, Yohann; Lorent, Marine; Giral, Magali; Tessier, Philippe

2018-06-01

Defining thresholds of prognostic markers is essential for stratified medicine. Such thresholds are mostly estimated from purely statistical measures regardless of patient preferences potentially leading to unacceptable medical decisions. Quality-Adjusted Life-Years are a widely used preferences-based measure of health outcomes. We develop a time-dependent Quality-Adjusted Life-Years-based expected utility function for censored data that should be maximized to estimate an optimal threshold. We performed a simulation study to compare estimated thresholds when using the proposed expected utility approach and purely statistical estimators. Two applications illustrate the usefulness of the proposed methodology which was implemented in the R package ROCt ( www.divat.fr ). First, by reanalysing data of a randomized clinical trial comparing the efficacy of prednisone vs. placebo in patients with chronic liver cirrhosis, we demonstrate the utility of treating patients with a prothrombin level higher than 89%. Second, we reanalyze the data of an observational cohort of kidney transplant recipients: we conclude to the uselessness of the Kidney Transplant Failure Score to adapt the frequency of clinical visits. Applying such a patient-centered methodology may improve future transfer of novel prognostic scoring systems or markers in clinical practice.

Computer simulation of fibrillation threshold measurements and electrophysiologic testing procedures

NASA Technical Reports Server (NTRS)

Grumbach, M. P.; Saxberg, B. E.; Cohen, R. J.

1987-01-01

A finite element model of cardiac conduction was used to simulate two experimental protocols: 1) fibrillation threshold measurements and 2) clinical electrophysiologic (EP) testing procedures. The model consisted of a cylindrical lattice whose properties were determined by four parameters: element length, conduction velocity, mean refractory period, and standard deviation of refractory periods. Different stimulation patterns were applied to the lattice under a given set of lattice parameter values and the response of the model was observed through a simulated electrocardiogram. The studies confirm that the model can account for observations made in experimental fibrillation threshold measurements and in clinical EP testing protocols.

Subthalamic deep brain stimulation modulates conscious perception of sensory function in Parkinson's disease.

PubMed

Cury, Rubens G; Galhardoni, Ricardo; Teixeira, Manoel J; Dos Santos Ghilardi, Maria G; Silva, Valquiria; Myczkowski, Martin L; Marcolin, Marco A; Barbosa, Egberto R; Fonoff, Erich T; Ciampi de Andrade, Daniel

2016-12-01

Subthalamic deep brain stimulation (STN-DBS) is used to treat refractory motor complications in Parkinson disease (PD), but its effects on nonmotor symptoms remain uncertain. Up to 80% of patients with PD may have pain relief after STN-DBS, but it is unknown whether its analgesic properties are related to potential effects on sensory thresholds or secondary to motor improvement. We have previously reported significant and long-lasting pain relief after DBS, which did not correlate with motor symptomatic control. Here we present secondary data exploring the effects of DBS on sensory thresholds in a controlled way and have explored the relationship between these changes and clinical pain and motor improvement after surgery. Thirty-seven patients were prospectively evaluated before STN-DBS and 12 months after the procedure compared with healthy controls. Compared with baseline, patients with PD showed lower thermal and mechanical detection and higher cold pain thresholds after surgery. There were no changes in heat and mechanical pain thresholds. Compared with baseline values in healthy controls, patients with PD had higher thermal and mechanical detection thresholds, which decreased after surgery toward normalization. These sensory changes had no correlation with motor or clinical pain improvement after surgery. These data confirm the existence of sensory abnormalities in PD and suggest that STN-DBS mainly influenced the detection thresholds rather than painful sensations. However, these changes may depend on the specific effects of DBS on somatosensory loops with no correlation to motor or clinical pain improvement.

Diagnostic Performance of a Rapid Magnetic Resonance Imaging Method of Measuring Hepatic Steatosis

PubMed Central

House, Michael J.; Gan, Eng K.; Adams, Leon A.; Ayonrinde, Oyekoya T.; Bangma, Sander J.; Bhathal, Prithi S.; Olynyk, John K.; St. Pierre, Tim G.

2013-01-01

Objectives Hepatic steatosis is associated with an increased risk of developing serious liver disease and other clinical sequelae of the metabolic syndrome. However, visual estimates of steatosis from histological sections of biopsy samples are subjective and reliant on an invasive procedure with associated risks. The aim of this study was to test the ability of a rapid, routinely available, magnetic resonance imaging (MRI) method to diagnose clinically relevant grades of hepatic steatosis in a cohort of patients with diverse liver diseases. Materials and Methods Fifty-nine patients with a range of liver diseases underwent liver biopsy and MRI. Hepatic steatosis was quantified firstly using an opposed-phase, in-phase gradient echo, single breath-hold MRI methodology and secondly, using liver biopsy with visual estimation by a histopathologist and by computer-assisted morphometric image analysis. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of the MRI method against the biopsy observations. Results The MRI approach had high sensitivity and specificity at all hepatic steatosis thresholds. Areas under ROC curves were 0.962, 0.993, and 0.972 at thresholds of 5%, 33%, and 66% liver fat, respectively. MRI measurements were strongly associated with visual (r2 = 0.83) and computer-assisted morphometric (r2 = 0.84) estimates of hepatic steatosis from histological specimens. Conclusions This MRI approach, using a conventional, rapid, gradient echo method, has high sensitivity and specificity for diagnosing liver fat at all grades of steatosis in a cohort with a range of liver diseases. PMID:23555650

Validation of a Behavioral Ethogram for Assessing Postoperative Pain in Guinea Pigs (Cavia porcellus)

PubMed Central

Dunbar, Misha L; David, Emily M; Aline, Marian R; Lofgren, Jennifer L

2016-01-01

Although guinea pigs (Cavia porcellus) have been used in research for more than a century and remain the most prevalent USDA-covered species, little has been elucidated regarding the recognition of clinical pain or analgesic efficacy in this species. We sought to assess pain in guinea pigs by using newer, clinically relevant methods that have been validated in other rodent species: the behavioral ethogram and cageside proxy indicator. In this study, 10 male guinea pigs underwent electronic von Frey testing of nociception, remote videorecording of behavior, and cageside assessment by using time-to-consumption (TTC) of a preferred treat test. These assessments were performed across 2 conditions (anesthesia only and castration surgery under anesthesia) at 3 time points (2, 8, and 24 h after the event). The anesthesia only condition served to control for the nonpainful but potentially distressing components of the surgical experience. Compared with those after anesthesia only conditions, subtle body movements were increased and nociceptive thresholds were decreased at 2 and 8 h after surgery. At 24 h, neither subtle body movement behaviors nor nociceptive thresholds differed between the 2 conditions. In contrast, TTC scores did not differ between the anesthesia only and surgery conditions at any time point, underscoring the challenge of identifying pain in this species through cageside evaluation. By comparing ethogram scores with measures of nociception, we validated select behaviors as pain-specific. Therefore, our novel ethogram allowed us to assess postoperative pain and may further serve as a platform for future analgesia efficacy studies in guinea pigs. PMID:26817977

Delivery of nicotine in an extract of a smokeless tobacco product reduces its reinforcement-attenuating and discriminative stimulus effects in rats

PubMed Central

Harris, Andrew C.; Stepanov, Irina; Pentel, Paul R.; LeSage, Mark G.

2012-01-01

Rationale Animal models of tobacco addiction rely on administration of nicotine alone or nicotine combined with isolated constituents. Models using tobacco extracts derived from tobacco products and containing a range of tobacco constituents might more accurately simulate tobacco exposure in humans. Objective To compare the effects of nicotine alone and an aqueous smokeless tobacco extract in several addiction-related animal behavioral models. Methods Nicotine alone and nicotine dose-equivalent concentrations of extract were compared in terms of their acute effects on intracranial self-stimulation (ICSS) thresholds, discriminative stimulus effects, and effects on locomotor activity. Results Similar levels of nicotine and minor alkaloids were achieved using either artificial saliva or saline for extraction, supporting the clinical relevance of the saline extracts used in these studies. Extract produced reinforcement-enhancing (ICSS threshold-decreasing) effects similar to those of nicotine alone at low to moderate nicotine doses, but reduced reinforcement-attenuating (ICSS threshold-increasing) effects at a high nicotine dose. In rats trained to discriminate nicotine alone from saline, intermediate extract doses did not substitute for the training dose as well as nicotine alone. Locomotor stimulant effects and nicotine distribution to brain were similar following administration of extract or nicotine alone. Conclusions The reinforcement-attenuating and discriminative stimulus effects of nicotine delivered in an extract of a commercial smokeless tobacco product differed from those of nicotine alone. Extracts of tobacco products may be useful for evaluating the abuse liability of those products and understanding the role of non-nicotine constituents in tobacco addiction. PMID:21960181

Delivery of nicotine in an extract of a smokeless tobacco product reduces its reinforcement-attenuating and discriminative stimulus effects in rats.

PubMed

Harris, Andrew C; Stepanov, Irina; Pentel, Paul R; Lesage, Mark G

2012-04-01

Animal models of tobacco addiction rely on administration of nicotine alone or nicotine combined with isolated constituents. Models using tobacco extracts derived from tobacco products and containing a range of tobacco constituents might more accurately simulate tobacco exposure in humans. To compare the effects of nicotine alone and an aqueous smokeless tobacco extract in several addiction-related animal behavioral models. Nicotine alone and nicotine dose-equivalent concentrations of extract were compared in terms of their acute effects on intracranial self-stimulation (ICSS) thresholds, discriminative stimulus effects, and effects on locomotor activity. Similar levels of nicotine and minor alkaloids were achieved using either artificial saliva or saline for extraction, supporting the clinical relevance of the saline extracts used in these studies. Extract produced reinforcement-enhancing (ICSS threshold-decreasing) effects similar to those of nicotine alone at low to moderate nicotine doses, but reduced reinforcement-attenuating (ICSS threshold-increasing) effects at a high nicotine dose. In rats trained to discriminate nicotine alone from saline, intermediate extract doses did not substitute for the training dose as well as nicotine alone. Locomotor stimulant effects and nicotine distribution to brain were similar following administration of extract or nicotine alone. The reinforcement-attenuating and discriminative stimulus effects of nicotine delivered in an extract of a commercial smokeless tobacco product differed from those of nicotine alone. Extracts of tobacco products may be useful for evaluating the abuse liability of those products and understanding the role of non-nicotine constituents in tobacco addiction.

In vitro characterization of perfluorocarbon droplets for focused ultrasound therapy

NASA Astrophysics Data System (ADS)

Schad, Kelly C.; Hynynen, Kullervo

2010-09-01

Focused ultrasound therapy can be enhanced with microbubbles by thermal and cavitation effects. However, localization of treatment is difficult as bioeffects can occur outside of the target region. Spatial control of bubbles can be achieved by ultrasound-induced conversion of liquid perfluorocarbon droplets to gas bubbles. This study was undertaken to determine the acoustic parameters for bubble production by droplet conversion and how it depends on the acoustic conditions and droplet physical parameters. Lipid-encapsulated droplets containing dodecafluoropentane were manufactured with sizes ranging from 1.9 to 7.2 µm in diameter and diluted to a concentration of 8 × 106 droplets mL-1. The droplets were sonicated in vitro with a focused ultrasound transducer and varying frequency and exposure under flow conditions through an acoustically transparent vessel. The sonications were 10 ms in duration at frequencies of 0.578, 1.736 and 2.855 MHz. The pressure threshold for droplet conversion was measured with an active transducer operating in pulse-echo mode and simultaneous measurements of broadband acoustic emissions were performed with passive acoustic detection. The results show that droplets cannot be converted at low frequency without broadband emissions occurring. However, the pressure threshold for droplet conversion decreased with increasing frequency, exposure and droplet size. The pressure threshold for broadband emissions was independent of the droplet size and was 2.9, 4.4 and 5.3 MPa for 0.578, 1736 and 2.855 MHz, respectively. In summary, we have demonstrated that droplet conversion is feasible for clinically relevant sized droplets and acoustic exposures.

Temporal Sensitivity Measured Shortly After Cochlear Implantation Predicts 6-Month Speech Recognition Outcome.

PubMed

Erb, Julia; Ludwig, Alexandra Annemarie; Kunke, Dunja; Fuchs, Michael; Obleser, Jonas

2018-04-24

Psychoacoustic tests assessed shortly after cochlear implantation are useful predictors of the rehabilitative speech outcome. While largely independent, both spectral and temporal resolution tests are important to provide an accurate prediction of speech recognition. However, rapid tests of temporal sensitivity are currently lacking. Here, we propose a simple amplitude modulation rate discrimination (AMRD) paradigm that is validated by predicting future speech recognition in adult cochlear implant (CI) patients. In 34 newly implanted patients, we used an adaptive AMRD paradigm, where broadband noise was modulated at the speech-relevant rate of ~4 Hz. In a longitudinal study, speech recognition in quiet was assessed using the closed-set Freiburger number test shortly after cochlear implantation (t0) as well as the open-set Freiburger monosyllabic word test 6 months later (t6). Both AMRD thresholds at t0 (r = -0.51) and speech recognition scores at t0 (r = 0.56) predicted speech recognition scores at t6. However, AMRD and speech recognition at t0 were uncorrelated, suggesting that those measures capture partially distinct perceptual abilities. A multiple regression model predicting 6-month speech recognition outcome with deafness duration and speech recognition at t0 improved from adjusted R = 0.30 to adjusted R = 0.44 when AMRD threshold was added as a predictor. These findings identify AMRD thresholds as a reliable, nonredundant predictor above and beyond established speech tests for CI outcome. This AMRD test could potentially be developed into a rapid clinical temporal-resolution test to be integrated into the postoperative test battery to improve the reliability of speech outcome prognosis.

A systematic review of the Diagnostic and Statistical Manual diagnostic criteria for nicotine dependence.

PubMed

DiFranza, Joseph; Ursprung, W W Sanouri; Lauzon, Béatrice; Bancej, Christina; Wellman, Robert J; Ziedonis, Douglas; Kim, Sun S; Gervais, André; Meltzer, Bruce; McKay, Colleen E; O'Loughlin, Jennifer; Okoli, Chizimuzo T C; Fortuna, Lisa R; Tremblay, Michèle

2010-05-01

The Diagnostic and Statistical Manual diagnostic criteria for nicotine dependence (DSM-ND) are based on the proposition that dependence is a syndrome that can be diagnosed only when a minimum of 3 of the 7 proscribed features are present. The DSM-ND criteria are an accepted research measure, but the validity of these criteria has not been subjected to a systematic evaluation. To systematically review evidence of validity and reliability for the DSM-ND criteria, a literature search was conducted of 16 national and international databases. Each article with original data was independently reviewed by two or more reviewers. In total, 380 potentially relevant articles were examined and 169 were reviewed in depth. The DSM-ND criteria have seen wide use in research settings, but sensitivity and specificity are well below the accepted standards for clinical applications. Predictive validity is generally poor. The 7 DSM-ND criteria are regarded as having face validity, but no data support a 3-symptom ND diagnostic threshold, or a 4-symptom withdrawal syndrome threshold. The DSM incorrectly states that daily smoking is a prerequisite for withdrawal symptoms. The DSM shows poor to modest concurrence with all other measures of nicotine dependence, smoking behaviors and biological measures of tobacco use. The data support the DSM-ND criteria as a valid measure of nicotine dependence severity for research applications. However, the data do not support the central premise of a 3-symptom diagnostic threshold, and no data establish that the DSM-ND criteria provide an accurate diagnosis of nicotine dependence. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Effects of 20 mg oral Δ9-tetrahydrocannabinol on the olfactory function of healthy volunteers*

PubMed Central

Walter, Carmen; Oertel, Bruno G; Ludyga, Dagmar; Ultsch, Alfred; Hummel, Thomas; Lötsch, Jörn

2014-01-01

Aims Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ9-tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the olfactory effects of THC to be expected during analgesic treatment. Methods The effects of 20 mg oral THC on olfaction were assessed in a placebo-controlled, randomized cross-over study in healthy volunteers. Using an established olfactory test (Sniffin' Sticks), olfactory thresholds, odour discrimination and odour identification were assessed in 15 subjects at baseline and 2 h after THC administration. Results Δ9-Tetrahydrocannabinol impaired the performance of subjects (n = 15) in the olfactory test. Specifically, olfactory thresholds were increased and odour discrimination performance was reduced. This resulted in a significant drop in composite threshold, discrimination, identification (TDI) olfactory score by 5.5 points (from 37.7 ± 4.2 to 32.2 ± 5.6, 95% confidence interval for differences THC vs. placebo, −7.8 to −2.0, P = 0.003), which is known to be a subjectively perceptible impairment of olfactory function. Conclusions Considering the resurgence of THC in medical use for several pathological conditions, the present results indicate that THC-based analgesics may be accompanied by subjectively noticeable reductions in olfactory acuity. In particular, for patients relying on their sense of smell, this might be relevant information for personalized therapy strategies. PMID:24802974

Effects of 20 mg oral Δ(9) -tetrahydrocannabinol on the olfactory function of healthy volunteers.

PubMed

Walter, Carmen; Oertel, Bruno G; Ludyga, Dagmar; Ultsch, Alfred; Hummel, Thomas; Lötsch, Jörn

2014-11-01

Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ(9) -tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the olfactory effects of THC to be expected during analgesic treatment. The effects of 20 mg oral THC on olfaction were assessed in a placebo-controlled, randomized cross-over study in healthy volunteers. Using an established olfactory test (Sniffin' Sticks), olfactory thresholds, odour discrimination and odour identification were assessed in 15 subjects at baseline and 2 h after THC administration. Δ(9) -Tetrahydrocannabinol impaired the performance of subjects (n = 15) in the olfactory test. Specifically, olfactory thresholds were increased and odour discrimination performance was reduced. This resulted in a significant drop in composite threshold, discrimination, identification (TDI) olfactory score by 5.5 points (from 37.7 ± 4.2 to 32.2 ± 5.6, 95% confidence interval for differences THC vs. placebo, -7.8 to -2.0, P = 0.003), which is known to be a subjectively perceptible impairment of olfactory function. Considering the resurgence of THC in medical use for several pathological conditions, the present results indicate that THC-based analgesics may be accompanied by subjectively noticeable reductions in olfactory acuity. In particular, for patients relying on their sense of smell, this might be relevant information for personalized therapy strategies. © 2014 The British Pharmacological Society.

In vitro characterization of perfluorocarbon droplets for focused ultrasound therapy.

PubMed

Schad, Kelly C; Hynynen, Kullervo

2010-09-07

Focused ultrasound therapy can be enhanced with microbubbles by thermal and cavitation effects. However, localization of treatment is difficult as bioeffects can occur outside of the target region. Spatial control of bubbles can be achieved by ultrasound-induced conversion of liquid perfluorocarbon droplets to gas bubbles. This study was undertaken to determine the acoustic parameters for bubble production by droplet conversion and how it depends on the acoustic conditions and droplet physical parameters. Lipid-encapsulated droplets containing dodecafluoropentane were manufactured with sizes ranging from 1.9 to 7.2 microm in diameter and diluted to a concentration of 8 x 10(6) droplets mL(-1). The droplets were sonicated in vitro with a focused ultrasound transducer and varying frequency and exposure under flow conditions through an acoustically transparent vessel. The sonications were 10 ms in duration at frequencies of 0.578, 1.736 and 2.855 MHz. The pressure threshold for droplet conversion was measured with an active transducer operating in pulse-echo mode and simultaneous measurements of broadband acoustic emissions were performed with passive acoustic detection. The results show that droplets cannot be converted at low frequency without broadband emissions occurring. However, the pressure threshold for droplet conversion decreased with increasing frequency, exposure and droplet size. The pressure threshold for broadband emissions was independent of the droplet size and was 2.9, 4.4 and 5.3 MPa for 0.578, 1736 and 2.855 MHz, respectively. In summary, we have demonstrated that droplet conversion is feasible for clinically relevant sized droplets and acoustic exposures.

A partial hearing animal model for chronic electro-acoustic stimulation

NASA Astrophysics Data System (ADS)

Irving, S.; Wise, A. K.; Millard, R. E.; Shepherd, R. K.; Fallon, J. B.

2014-08-01

Objective. Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This paper outlines such a model that has been successfully used in our laboratory. Approach. This paper outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. Main results. Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. Significance. This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual hearing following cochlear implantation. The ability to record CAPs via the CI has clinical direct relevance for obtaining objective measures of residual hearing.

Acoustic Reflexes in Normal-Hearing Adults, Typically Developing Children, and Children with Suspected Auditory Processing Disorder: Thresholds, Real-Ear Corrections, and the Role of Static Compliance on Estimates.

PubMed

Saxena, Udit; Allan, Chris; Allen, Prudence

2017-06-01

Previous studies have suggested elevated reflex thresholds in children with auditory processing disorders (APDs). However, some aspects of the child's ear such as ear canal volume and static compliance of the middle ear could possibly affect the measurements of reflex thresholds and thus impact its interpretation. Sound levels used to elicit reflexes in a child's ear may be higher than predicted by calibration in a standard 2-cc coupler, and lower static compliance could make visualization of very small changes in impedance at threshold difficult. For this purpose, it is important to evaluate threshold data with consideration of differences between children and adults. A set of studies were conducted. The first compared reflex thresholds obtained using standard clinical procedures in children with suspected APD to that of typically developing children and adults to test the replicability of previous studies. The second study examined the impact of ear canal volume on estimates of reflex thresholds by applying real-ear corrections. Lastly, the relationship between static compliance and reflex threshold estimates was explored. The research is a set of case-control studies with a repeated measures design. The first study included data from 20 normal-hearing adults, 28 typically developing children, and 66 children suspected of having an APD. The second study included 28 normal-hearing adults and 30 typically developing children. In the first study, crossed and uncrossed reflex thresholds were measured in 5-dB step size. Reflex thresholds were analyzed using repeated measures analysis of variance (RM-ANOVA). In the second study, uncrossed reflex thresholds, real-ear correction, ear canal volume, and static compliance were measured. Reflex thresholds were measured using a 1-dB step size. The effect of real-ear correction and static compliance on reflex threshold was examined using RM-ANOVA and Pearson correlation coefficient, respectively. Study 1 replicated previous studies showing elevated reflex thresholds in many children with suspected APD when compared to data from adults using standard clinical procedures, especially in the crossed condition. The thresholds measured in children with suspected APD tended to be higher than those measured in the typically developing children. There were no significant differences between the typically developing children and adults. However, when real-ear calibrated stimulus levels were used, it was found that children's thresholds were elicited at higher levels than in the adults. A significant relationship between reflex thresholds and static compliance was found in the adult data, showing a trend for higher thresholds in ears with lower static compliance, but no such relationship was found in the data from the children. This study suggests that reflex measures in children should be adjusted for real-ear-to-coupler differences before interpretation. The data in children with suspected APD support previous studies suggesting abnormalities in reflex thresholds. The lack of correlation between threshold and static compliance estimates in children as was observed in the adults may suggest a nonmechanical explanation for age and clinically related effects. American Academy of Audiology

A review of the physics and response models for burnout of semiconductor devices

NASA Astrophysics Data System (ADS)

Orvis, W. J.; Khanaka, G. H.; Yee, J. H.

1984-12-01

Physical mechanisms that cause semiconductor devices to fail from electrical overstress--particularly, EMP-induced electrical stress--are described in light of the current literature and the authors' own research. A major concern is the cause and effects of second breakdown phenomena in p-n junction devices. Models of failure thresholds are evaluated for their inherent errors and for their ability to represent the relevant physics. Finally, the response models that relate electromagnetic stress parameters to appropriate failure-threshold parameters are discussed.

Preliminay Investigation of Variation in Some Dark Adaptation Aspects fo Possible Relevance to Military Helicopter Aircrew.

DTIC Science & Technology

1983-06-01

Niven, J.I., McFarland, R.A., and Roughton, F.J. Variations in Visual Thresholds During Carbon Monoxide and Hypoxic Anoxia (abstract). Fed. Proc...and Niven, J.I. Visual Thresholds as an Index of the Modification of the Effects of Anoxia by Glucose. Am. J. Physiol. 144:378-88. 1945. 71... Diphosphoglycerate and Night Vision. Aviat. Space Environ. Med. 52(1):41-44. 1981. 100. Sexton, M., Malone, F. and Farnsworth, D. The Effect of Ultra- violet

Photodetachment cross sections of negative ions - The range of validity of the Wigner threshold law

NASA Technical Reports Server (NTRS)

Farley, John W.

1989-01-01

The threshold behavior of the photodetachment cross section of negative ions as a function of photon frequency is usually described by the Wigner law. This paper reports the results of a model calculation using the zero-core-contribution (ZCC) approximation. Theoretical expressions for the leading correction to the Wigner law are developed, giving the range of validity of the Wigner law and the expected accuracy. The results are relevant to extraction of electron affinities from experimental photodetachment data.

Monopolar Detection Thresholds Predict Spatial Selectivity of Neural Excitation in Cochlear Implants: Implications for Speech Recognition

PubMed Central

2016-01-01

The objectives of the study were to (1) investigate the potential of using monopolar psychophysical detection thresholds for estimating spatial selectivity of neural excitation with cochlear implants and to (2) examine the effect of site removal on speech recognition based on the threshold measure. Detection thresholds were measured in Cochlear Nucleus® device users using monopolar stimulation for pulse trains that were of (a) low rate and long duration, (b) high rate and short duration, and (c) high rate and long duration. Spatial selectivity of neural excitation was estimated by a forward-masking paradigm, where the probe threshold elevation in the presence of a forward masker was measured as a function of masker-probe separation. The strength of the correlation between the monopolar thresholds and the slopes of the masking patterns systematically reduced as neural response of the threshold stimulus involved interpulse interactions (refractoriness and sub-threshold adaptation), and spike-rate adaptation. Detection threshold for the low-rate stimulus most strongly correlated with the spread of forward masking patterns and the correlation reduced for long and high rate pulse trains. The low-rate thresholds were then measured for all electrodes across the array for each subject. Subsequently, speech recognition was tested with experimental maps that deactivated five stimulation sites with the highest thresholds and five randomly chosen ones. Performance with deactivating the high-threshold sites was better than performance with the subjects’ clinical map used every day with all electrodes active, in both quiet and background noise. Performance with random deactivation was on average poorer than that with the clinical map but the difference was not significant. These results suggested that the monopolar low-rate thresholds are related to the spatial neural excitation patterns in cochlear implant users and can be used to select sites for more optimal speech recognition performance. PMID:27798658

Acupuncture for peripheral joint osteoarthritis

PubMed Central

Manheimer, Eric; Cheng, Ke; Linde, Klaus; Lao, Lixing; Yoo, Junghee; Wieland, Susan; van der Windt, Daniëlle AWM; Berman, Brian M; Bouter, Lex M

2011-01-01

Background Peripheral joint osteoarthritis is a major cause of pain and functional limitation. Few treatments are safe and effective. Objectives To assess the effects of acupuncture for treating peripheral joint osteoarthritis. Search strategy We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 1), MEDLINE, and EMBASE (both through December 2007), and scanned reference lists of articles. Selection criteria Randomized controlled trials (RCTs) comparing needle acupuncture with a sham, another active treatment, or a waiting list control group in people with osteoarthritis of the knee, hip, or hand. Data collection and analysis Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We calculated standardized mean differences using the differences in improvements between groups. Main results Sixteen trials involving 3498 people were included. Twelve of the RCTs included only people with OA of the knee, 3 only OA of the hip, and 1 a mix of people with OA of the hip and/or knee. In comparison with a sham control, acupuncture showed statistically significant, short-term improvements in osteoarthritis pain (standardized mean difference -0.28, 95% confidence interval -0.45 to -0.11; 0.9 point greater improvement than sham on 20 point scale; absolute percent change 4.59%; relative percent change 10.32%; 9 trials; 1835 participants) and function (-0.28, -0.46 to -0.09; 2.7 point greater improvement on 68 point scale; absolute percent change 3.97%; relative percent change 8.63%); however, these pooled short-term benefits did not meet our predefined thresholds for clinical relevance (i.e. 1.3 points for pain; 3.57 points for function) and there was substantial statistical heterogeneity. Additionally, restriction to sham-controlled trials using shams judged most likely to adequately blind participants to treatment assignment (which were also the same shams judged most likely to have physiological activity), reduced heterogeneity and resulted in pooled short-term benefits of acupuncture that were smaller and non-significant. In comparison with sham acupuncture at the six-month follow-up, acupuncture showed borderline statistically significant, clinically irrelevant improvements in osteoarthritis pain (-0.10, -0.21 to 0.01; 0.4 point greater improvement than sham on 20 point scale; absolute percent change 1.81%; relative percent change 4.06%; 4 trials;1399 participants) and function (-0.11, -0.22 to 0.00; 1.2 point greater improvement than sham on 68 point scale; absolute percent change 1.79%; relative percent change 3.89%). In a secondary analysis versus a waiting list control, acupuncture was associated with statistically significant, clinically relevant short-term improvements in osteoarthritis pain (-0.96, -1.19 to -0.72; 14.5 point greater improvement than sham on 100 point scale; absolute percent change 14.5%; relative percent change 29.14%; 4 trials; 884 participants) and function (-0.89, -1.18 to -0.60; 13.0 point greater improvement than sham on 100 point scale; absolute percent change 13.0%; relative percent change 25.21%). In the head-on comparisons of acupuncture with the ‘supervised osteoarthritis education’ and the ‘physician consultation’ control groups, acupuncture was associated with clinically relevant short- and long-term improvements in pain and function. In the head on comparisons of acupuncture with ‘home exercises/advice leaflet’ and ‘supervised exercise’, acupuncture was associated with similar treatment effects as the controls. Acupuncture as an adjuvant to an exercise based physiotherapy program did not result in any greater improvements than the exercise program alone. Information on safety was reported in only 8 trials and even in these trials there was limited reporting and heterogeneous methods. Authors' conclusions Sham-controlled trials show statistically significant benefits; however, these benefits are small, do not meet our pre-defined thresholds for clinical relevance, and are probably due at least partially to placebo effects from incomplete blinding. Waiting list-controlled trials of acupuncture for peripheral joint osteoarthritis suggest statistically significant and clinically relevant benefits, much of which may be due to expectation or placebo effects. PMID:20091527

Computational Study of Collisions Between O(3P) and NO(2Pi) at Temperatures Relevant to the Hypersonic Flight Regime

DTIC Science & Technology

2014-10-29

hypersonic flight regime. For this reason, the thermal rate coefficients for reactive processes involving O(3P) and NO(2_) are relevant over a wide...hypersonic flight regime. For this reason, the thermal rate coefficients for reactive processes involving O(3P) and NO(2) are relevant over a wide...N) is of particular interest since the thermal dissociation threshold for O2 is lower than that for N2 in air. A central question is how

Amylase in drain fluid for the diagnosis of pancreatic leak in post-pancreatic resection.

PubMed

Davidson, Tsetsegdemberel Bat-Ulzii; Yaghoobi, Mohammad; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-07

The treatment of people with clinically significant postoperative pancreatic leaks is different from those without clinically significant pancreatic leaks. It is important to know the diagnostic accuracy of drain fluid amylase as a triage test for the detection of clinically significant pancreatic leaks, so that an informed decision can be made as to whether the patient with a suspected pancreatic leak needs further investigations and treatment. There is currently no systematic review of the diagnostic test accuracy of drain fluid amylase for the diagnosis of clinically relevant pancreatic leak. To determine the diagnostic accuracy of amylase in drain fluid at 48 hours or more for the diagnosis of pancreatic leak in people who had undergone pancreatic resection. We searched MEDLINE, Embase, the Science Citation Index Expanded, and the National Institute for Health Research Health Technology Assessment (NIHR HTA) websites up to 20 February 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase. We included all studies that evaluated the diagnostic test accuracy of amylase in the drain fluid at 48 hours or more for the diagnosis of pancreatic leak in people who had undergone pancreatic resection excluding total pancreatectomy. We planned to exclude case-control studies because these studies are prone to bias, but did not find any. At least two authors independently searched and screened the references produced by the search to identify relevant studies. Two review authors independently extracted data from the included studies. The included studies reported drain fluid amylase on different postoperative days and measured at different cut-off levels, so it was not possible to perform a meta-analysis using the bivariate model as planned. We have reported the sensitivity, specificity, post-test probability of a positive and negative drain fluid amylase along with 95% confidence interval (CI) on each of the different postoperative days and measured at different cut-off levels. A total of five studies including 868 participants met the inclusion criteria for this review. The five studies included in this review reported the value of drain fluid amylase at different thresholds and different postoperative days. The sensitivities and specificities were variable; the sensitivities ranged between 0.72 and 1.00 while the specificities ranged between 0.73 and 0.99 for different thresholds on different postoperative days. At the median prevalence (pre-test probability) of 15.9%, the post-test probabilities for pancreatic leak ranged between 35.9% and 95.4% for a positive drain fluid amylase test and ranged between 0% and 5.5% for a negative drain fluid amylase test.None of the studies used the reference standard of confirmation by surgery or by a combination of surgery and clinical follow-up, but used the International Study Group on Pancreatic Fistula (ISGPF) grade B and C as the reference standard. The overall methodological quality was unclear or high in all the studies. Because of the paucity of data and methodological deficiencies in the studies, we are uncertain whether drain fluid amylase should be used as a method for testing for pancreatic leak in an unselected population after pancreatic resection; and we judge that the optimal cut-off of drain fluid amylase for making the diagnosis of pancreatic leak is also not clear. Further well-designed diagnostic test accuracy studies with pre-specified index test threshold of drain fluid amylase (at three times more on postoperative day 5 or another suitable pre-specified threshold), appropriate follow-up (for at least six to eight weeks to ensure that there are no pancreatic leaks), and clearly defined reference standards (of surgical, clinical, and radiological confirmation of pancreatic leak) are important to reliably determine the diagnostic accuracy of drain fluid amylase in the diagnosis of pancreatic leak.

Using Smartphones to Monitor Bipolar Disorder Symptoms: A Pilot Study

PubMed Central

Kindermann, Sally; Maier, Andreas; Kerl, Christopher; Moock, Jörn; Barbian, Guido; Rössler, Wulf

2016-01-01

Background Relapse prevention in bipolar disorder can be improved by monitoring symptoms in patients' daily life. Smartphone apps are easy-to-use, low-cost tools that can be used to assess this information. To date, few studies have examined the usefulness of smartphone data for monitoring symptoms in bipolar disorder. Objective We present results from a pilot test of a smartphone-based monitoring system, Social Information Monitoring for Patients with Bipolar Affective Disorder (SIMBA), that tracked daily mood, physical activity, and social communication in 13 patients. The objective of this study was to investigate whether smartphone measurements predicted clinical symptoms levels and clinical symptom change. The hypotheses that smartphone measurements are (1) negatively related to clinical depressive symptoms and (2) positively related to clinical manic symptoms were tested. Methods Clinical rating scales were administered to assess clinical depressive and manic symptoms. Patients used a smartphone with the monitoring app for up to 12 months. Random-coefficient multilevel models were computed to analyze the relationship between smartphone data and externally rated manic and depressive symptoms. Overall clinical symptom levels and clinical symptom changes were predicted by separating between-patient and within-patient effects. Using established clinical thresholds from the literature, marginal effect plots displayed clinical relevance of smartphone data. Results Overall symptom levels and change in clinical symptoms were related to smartphone measures. Higher overall levels of clinical depressive symptoms were predicted by lower self-reported mood measured by the smartphone (beta=-.56, P<.001). An increase in clinical depressive symptoms was predicted by a decline in social communication (ie, outgoing text messages: beta=-.28, P<.001) and a decline in physical activity as measured by the smartphone (ie, cell tower movements: beta=-.11, P=.03). Higher overall levels of clinical manic symptoms were predicted by lower physical activity on the smartphone (ie, distance travelled: beta=-.37, P<.001), and higher social communication (beta=.48, P=.03). An increase in clinical manic symptoms was predicted by a decrease in physical activity on the smartphone (beta=-.17, P<.001). Conclusions Clinical symptoms were related to some objective and subjective smartphone measurements, but not all smartphone measures predicted the occurrence of bipolar symptoms above clinical thresholds. Thus, smartphones have the potential to monitor bipolar disorder symptoms in patients’ daily life. Further validation of monitoring tools in a larger sample is needed. Conclusions are limited by the low prevalence of manic and depressive symptoms in the study sample. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 05663421; http://www.controlled-trials.com/ISRCTN05663421 (Archived by WebCite at http://www.webcitation.org/6d9wsibJB) PMID:26740354

Children with developmental dyslexia showed greater sleep disturbances than controls, including problems initiating and maintaining sleep.

PubMed

Carotenuto, M; Esposito, M; Cortese, S; Laino, D; Verrotti, A

2016-09-01

Although there have been frequent clinical reports about sleep disturbances in children with learning disabilities, no data are available about the prevalence of sleep disturbances in children with developmental dyslexia (DD). This study evaluated sleep disturbances in children with DD referred to a hospital clinic and compared their scores with healthy controls. We consecutively enrolled 147 children (66% male) aged 10.26 ± 2.63 years who were referred by clinical paediatricians to the Clinic for Child and Adolescent Neuropsychiatry at the Second University of Naples with DD and 766 children without DD (60% male) aged 10.49 ± 2.39 years recruited from schools in the same urban area. Sleep disturbances were assessed with the Sleep Disturbances Scale for Children (SDSC), which was filled out by the children's main carers. Compared with the controls, the children with DD showed significantly higher rates of above threshold scores on the total SDSC score (p < 0.001) and on the subscales for disorders in initiating and maintaining sleep (p < 0.001), sleep breathing disorders (p < 0.001) and disorders of arousal (p < 0.001). Sleep disorders were significantly more frequent in children with DD than in healthy controls. A possible relationship between dyslexia and sleep disorders may have relevant clinical implications. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Motor excitability measurements: the influence of gender, body mass index, age and temperature in healthy controls.

PubMed

Casanova, I; Diaz, A; Pinto, S; de Carvalho, M

2014-04-01

The technique of threshold tracking to test axonal excitability gives information about nodal and internodal ion channel function. We aimed to investigate variability of the motor excitability measurements in healthy controls, taking into account age, gender, body mass index (BMI) and small changes in skin temperature. We examined the left median nerve of 47 healthy controls using the automated threshold-tacking program, QTRAC. Statistical multiple regression analysis was applied to test relationship between nerve excitability measurements and subject variables. Comparisons between genders did not find any significant difference (P>0.2 for all comparisons). Multiple regression analysis showed that motor amplitude decreases with age and temperature, stimulus-response slope decreases with age and BMI, and that accommodation half-time decrease with age and temperature. The changes related to demographic features on TRONDE protocol parameters are small and less important than in conventional nerve conduction studies. Nonetheless, our results underscore the relevance of careful temperature control, and indicate that interpretation of stimulus-response slope and accommodation half-time should take into account age and BMI. In contrast, gender is not of major relevance to axonal threshold findings in motor nerves. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Analysis of the Spatial Organization of Pastures as a Contact Network, Implications for Potential Disease Spread and Biosecurity in Livestock, France, 2010.

PubMed

Palisson, Aurore; Courcoul, Aurélie; Durand, Benoit

2017-01-01

The use of pastures is part of common herd management practices for livestock animals, but contagion between animals located on neighbouring pastures is one of the major modes of infectious disease transmission between herds. At the population level, this transmission is strongly constrained by the spatial organization of pastures. The aim of this study was to answer two questions: (i) is the spatial configuration of pastures favourable to the spread of infectious diseases in France? (ii) would biosecurity measures allow decreasing this vulnerability? Based on GIS data, the spatial organization of pastures was represented using networks. Nodes were the 3,159,787 pastures reported in 2010 by the French breeders to claim the Common Agricultural Policy subsidies. Links connected pastures when the distance between them was below a predefined threshold. Premises networks were obtained by aggregating into a single node all the pastures under the same ownership. Although the pastures network was very fragmented when the distance threshold was short (1.5 meters, relevant for a directly-transmitted disease), it was not the case when the distance threshold was larger (500 m, relevant for a vector-borne disease: 97% of the nodes in the largest connected component). The premises network was highly connected as the largest connected component always included more than 83% of the nodes, whatever the distance threshold. Percolation analyses were performed to model the population-level efficacy of biosecurity measures. Percolation thresholds varied according to the modelled biosecurity measures and to the distance threshold. They were globally high (e.g. >17% of nodes had to be removed, mimicking the confinement of animals inside farm buildings, to obtain the disappearance of the large connected component). The network of pastures thus appeared vulnerable to the spread of diseases in France. Only a large acceptance of biosecurity measures by breeders would allow reducing this structural risk.

Analysis of the Spatial Organization of Pastures as a Contact Network, Implications for Potential Disease Spread and Biosecurity in Livestock, France, 2010

PubMed Central

Palisson, Aurore; Courcoul, Aurélie; Durand, Benoit

2017-01-01

The use of pastures is part of common herd management practices for livestock animals, but contagion between animals located on neighbouring pastures is one of the major modes of infectious disease transmission between herds. At the population level, this transmission is strongly constrained by the spatial organization of pastures. The aim of this study was to answer two questions: (i) is the spatial configuration of pastures favourable to the spread of infectious diseases in France? (ii) would biosecurity measures allow decreasing this vulnerability? Based on GIS data, the spatial organization of pastures was represented using networks. Nodes were the 3,159,787 pastures reported in 2010 by the French breeders to claim the Common Agricultural Policy subsidies. Links connected pastures when the distance between them was below a predefined threshold. Premises networks were obtained by aggregating into a single node all the pastures under the same ownership. Although the pastures network was very fragmented when the distance threshold was short (1.5 meters, relevant for a directly-transmitted disease), it was not the case when the distance threshold was larger (500 m, relevant for a vector-borne disease: 97% of the nodes in the largest connected component). The premises network was highly connected as the largest connected component always included more than 83% of the nodes, whatever the distance threshold. Percolation analyses were performed to model the population-level efficacy of biosecurity measures. Percolation thresholds varied according to the modelled biosecurity measures and to the distance threshold. They were globally high (e.g. >17% of nodes had to be removed, mimicking the confinement of animals inside farm buildings, to obtain the disappearance of the large connected component). The network of pastures thus appeared vulnerable to the spread of diseases in France. Only a large acceptance of biosecurity measures by breeders would allow reducing this structural risk. PMID:28060913

Clinical evaluation of an inspiratory impedance threshold device during standard cardiopulmonary resuscitation in patients with out-of-hospital cardiac arrest.

PubMed

Aufderheide, Tom P; Pirrallo, Ronald G; Provo, Terry A; Lurie, Keith G

2005-04-01

To determine whether an impedance threshold device, designed to enhance circulation, would increase acute resuscitation rates for patients in cardiac arrest receiving conventional manual cardiopulmonary resuscitation. Prospective, randomized, double-blind, intention-to-treat. Out-of-hospital trial conducted in the Milwaukee, WI, emergency medical services system. Adults in cardiac arrest of presumed cardiac etiology. On arrival of advanced life support, patients were treated with standard cardiopulmonary resuscitation combined with either an active or a sham impedance threshold device. We measured safety and efficacy of the impedance threshold device; the primary end point was intensive care unit admission. Statistical analyses performed included the chi-square test and multivariate regression analysis. One hundred sixteen patients were treated with a sham impedance threshold device, and 114 patients were treated with an active impedance threshold device. Overall intensive care unit admission rates were 17% with the sham device vs. 25% in the active impedance threshold device (p = .13; odds ratio, 1.64; 95% confidence interval, 0.87, 3.10). Patients in the subgroup presenting with pulseless electrical activity had intensive care unit admission and 24-hr survival rates of 20% and 12% in sham (n = 25) vs. 52% and 30% in active impedance threshold device groups (n = 27) (p = .018, odds ratio, 4.31; 95% confidence interval, 1.28, 14.5, and p = .12, odds ratio, 3.09; 95% confidence interval, 0.74, 13.0, respectively). A post hoc analysis of patients with pulseless electrical activity at any time during the cardiac arrest revealed that intensive care unit and 24-hr survival rates were 20% and 11% in the sham (n = 56) vs. 41% and 27% in the active impedance threshold device groups (n = 49) (p = .018, odds ratio, 2.82; 95% confidence interval, 1.19, 6.67, and p = .037, odds ratio, 3.01; 95% confidence interval, 1.07, 8.96, respectively). There were no statistically significant differences in outcomes for patients presenting in ventricular fibrillation and asystole. Adverse event and complication rates were also similar. During this first clinical trial of the impedance threshold device during standard cardiopulmonary resuscitation, use of the new device more than doubled short-term survival rates in patients presenting with pulseless electrical activity. A larger clinical trial is underway to determine the potential longer term benefits of the impedance threshold device in cardiac arrest.

The volume threshold of 300 versus 100 ml/day for chest tube removal after pulmonary lobectomy: a meta-analysis.

PubMed

Zhang, Tian-Xiang; Zhang, Ye; Liu, Zhi-Dong; Zhou, Shi-Jie; Xu, Shao-Fa

2018-05-07

In this meta-analysis, we conducted a pooled analysis of clinical studies comparing the efficacy of a volume threshold of 300 ml/day before removing a chest tube (CT) versus 100 ml/day after a lobectomy. According to the recommendations of the Cochrane Collaboration, we established a rigorous study protocol. We performed a systematic electronic search of PubMed, Embase, Cochrane Library, Web of Science databases, CNKI, the Wanfang database, CBMdisc and Google Scholar to identify articles to include in our meta-analysis. A literature search was performed using relevant keywords. A meta-analysis was performed using RevMan© software. Five studies, published between 2014 and 2015, including 615 patients (314 patients who had the CT removed when daily drainage was <300 ml and 301 patients who had the CT removed when daily drainage was <100 ml) met the selection criteria. From the available data, the patients using the volume threshold of 300 ml/day had a significantly decreased duration of drainage [MD = -44.07; 95% confidence interval (CI) -64.45 to -23.68; P < 0.0001] and hospital stay after operation (MD = -2.25; 95% CI -3.52 to -0.97; P = 0.0006) compared with patients using a volume threshold of 100 ml/day after a pulmonary lobectomy. However, no significant differences were observed in postoperative complications, such as pleural fluid reaccumulation [Odds ratio (OR) = 1.73; 95% CI = 0.74-4.07; P = 0.21] and atelectasis (OR = 0.97; 95% CI = 0.52-1.81; P = 0.93). Thoracentesis rates after removing the CT also showed no significant difference (OR = 1.53; 95% CI 0.55-4.22; P = 0.41). Our results showed that a higher volume threshold, up to 300 ml/day, is effective in reducing hospitalization times and duration of drainage in patients who undergo a lobectomy. Moreover, the volume threshold of 300 ml/day does not increase the occurrence of postoperative atelectasis, pleural fluid reaccumulation and thoracentesis rates. However, this review is limited by the methodological quality of the included trials, and additional studies according to the recommendations of Cochrane Library are appreciated.

Effect of threshold disorder on the quorum percolation model

NASA Astrophysics Data System (ADS)

Monceau, Pascal; Renault, Renaud; Métens, Stéphane; Bottani, Samuel

2016-07-01

We study the modifications induced in the behavior of the quorum percolation model on neural networks with Gaussian in-degree by taking into account an uncorrelated Gaussian thresholds variability. We derive a mean-field approach and show its relevance by carrying out explicit Monte Carlo simulations. It turns out that such a disorder shifts the position of the percolation transition, impacts the size of the giant cluster, and can even destroy the transition. Moreover, we highlight the occurrence of disorder independent fixed points above the quorum critical value. The mean-field approach enables us to interpret these effects in terms of activation probability. A finite-size analysis enables us to show that the order parameter is weakly self-averaging with an exponent independent on the thresholds disorder. Last, we show that the effects of the thresholds and connectivity disorders cannot be easily discriminated from the measured averaged physical quantities.

Integrating physiological threshold experiments with climate modeling to project mangrove range limits

NASA Astrophysics Data System (ADS)

Cavanaugh, K. C.; Kellner, J.; Cook-Patton, S.; Williams, P.; Feller, I. C.; Parker, J.

2014-12-01

Due to limitations of purely correlative species distribution models, there is a need for more integration of experimental approaches when studying impacts of climate change on species distributions. Here we used controlled experiments to identify physiological thresholds that control poleward range limits of three species of mangroves found in North America. We found that all three species exhibited a threshold response to extreme cold, but freeze tolerance thresholds varied among species. From these experiments we developed a climate metric, freeze degree days (FDD), which incorporates both the intensity and frequency of freezes. When included in distribution models, FDD was a better predictor of mangrove presence/absence than other temperature-based metrics. Using 27 years of satellite imagery, we linked FDD to past changes in mangrove abundance in Florida, further supporting the relevance of FDD. We then used downscaled climate projections of FDD to project poleward migration of these range limits over the next 50 years.

Cortical and Sensory Causes of Individual Differences in Selective Attention Ability Among Listeners With Normal Hearing Thresholds.

PubMed

Shinn-Cunningham, Barbara

2017-10-17

This review provides clinicians with an overview of recent findings relevant to understanding why listeners with normal hearing thresholds (NHTs) sometimes suffer from communication difficulties in noisy settings. The results from neuroscience and psychoacoustics are reviewed. In noisy settings, listeners focus their attention by engaging cortical brain networks to suppress unimportant sounds; they then can analyze and understand an important sound, such as speech, amidst competing sounds. Differences in the efficacy of top-down control of attention can affect communication abilities. In addition, subclinical deficits in sensory fidelity can disrupt the ability to perceptually segregate sound sources, interfering with selective attention, even in listeners with NHTs. Studies of variability in control of attention and in sensory coding fidelity may help to isolate and identify some of the causes of communication disorders in individuals presenting at the clinic with "normal hearing." How well an individual with NHTs can understand speech amidst competing sounds depends not only on the sound being audible but also on the integrity of cortical control networks and the fidelity of the representation of suprathreshold sound. Understanding the root cause of difficulties experienced by listeners with NHTs ultimately can lead to new, targeted interventions that address specific deficits affecting communication in noise. http://cred.pubs.asha.org/article.aspx?articleid=2601617.

Understanding Phenotypes of Obstructive Sleep Apnea: Applications in Anesthesia, Surgery, and Perioperative Medicine

PubMed Central

Subramani, Yamini; Singh, Mandeep; Wong, Jean; Kushida, Clete A.; Malhotra, Atul; Chung, Frances

2017-01-01

Obstructive sleep apnea (OSA) is a prevalent sleep-disordered breathing with potential long-term major neurocognitive and cardiovascular sequelae. The pathophysiology of OSA varies between individuals and is composed of different underlying mechanisms. Several components including the upper airway anatomy, effectiveness of the upper airway dilator muscles such as the genioglossus, arousal threshold of the individual, and inherent stability of the respiratory control system determine the pathogenesis of OSA. Their recognition may have implications for the perioperative health care team. For example, OSA patients with a high arousal threshold are likely to be sensitive to sedatives and narcotics with a higher risk of respiratory arrest in the perioperative period. Supplemental oxygen therapy can help to stabilize breathing in OSA patients with inherent respiratory instability. Avoidance of supine position can minimize airway obstruction in patients with a predisposition to upper airway collapse in this posture. In this review, the clinically relevant endotypes and phenotypes of OSA are described. Continuous positive airway pressure (CPAP) therapy is the treatment of choice for most patients with OSA but tolerance and adherence can be a problem. Patient-centered individualized approaches to OSA management will be the focus of future research into developing potential treatment options that will help decrease the disease burden and improve treatment effectiveness. PMID:27861433

Emerging issues in radiogenic cataracts and cardiovascular disease.

PubMed

Hamada, Nobuyuki; Fujimichi, Yuki; Iwasaki, Toshiyasu; Fujii, Noriko; Furuhashi, Masato; Kubo, Eri; Minamino, Tohru; Nomura, Takaharu; Sato, Hitoshi

2014-09-01

In 2011, the International Commission on Radiological Protection issued a statement on tissue reactions (formerly termed non-stochastic or deterministic effects) to recommend lowering the threshold for cataracts and the occupational equivalent dose limit for the crystalline lens of the eye. Furthermore, this statement was the first to list circulatory disease (cardiovascular and cerebrovascular disease) as a health hazard of radiation exposure and to assign its threshold for the heart and brain. These changes have stimulated various discussions and may have impacts on some radiation workers, such as those in the medical sector. This paper considers emerging issues associated with cataracts and cardiovascular disease. For cataracts, topics dealt with herein include (i) the progressive nature, stochastic nature, target cells and trigger events of lens opacification, (ii) roles of lens protein denaturation, oxidative stress, calcium ions, tumor suppressors and DNA repair factors in cataractogenesis, (iii) dose rate effect, radiation weighting factor, and classification systems for cataracts, and (iv) estimation of the lens dose in clinical settings. Topics for cardiovascular disease include experimental animal models, relevant surrogate markers, latency period, target tissues, and roles of inflammation and cellular senescence. Future research needs are also discussed. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Animal model of cochlear third window in the scala vestibuli or scala tympani.

PubMed

Attias, Joseph; Preis, Michal; Shemesh, Rafi; Hadar, Tuvia; Nageris, Ben I

2010-08-01

The auditory impact of a cochlear third window differs by its location in the scala vestibuli or scala tympani. Pathologic third window has been investigated primarily in the vestibular apparatus of animals and humans. Dehiscence of the superior semicircular canal is the clinical model. Fat sand rats (n = 11) have a unique inner-ear anatomy that allows easy surgical access. A window was drilled in the bony labyrinth over the scala vestibuli in 1 group (12 ears) and over the scala tympani in another (7 ears) while preserving the membranous labyrinth. Auditory brain stem responses to high- and low-frequency stimuli delivered by air and bone conduction were recorded before and after the procedure. Scala vestibuli group: preoperative air-conduction thresholds to clicks and tone-bursts averaged 8.3 and 9.6 dB, respectively, and bone-conduction thresholds, 4.6 and 3.3 dB, respectively; after fenestration, air-conduction thresholds averaged 40.4 and 41.8 dB, respectively, and bone-conduction thresholds, -1 and 5.6 dB, respectively. Scala tympani group: preoperative air-conduction thresholds to clicks and tone-bursts averaged 8.6 dB each, and bone-conduction thresholds, 7.9 dB and 7.1 dB, respectively; after fenestration, air-conduction thresholds averaged 11.4 and 9.3 dB, respectively, and bone-conduction thresholds, 9.3 and 4.2 dB, respectively. The changes in air- (p = 0.0001) and bone-conduction (p = 0.04) thresholds were statistically significant only in the scala vestibuli group. The presence of a cochlear third window over the scala vestibuli, but not over the scala tympani, causes a significant increase in air-conduction auditory thresholds. These results agree with the theoretic model and clinical findings and contribute to our understanding of vestibular dehiscence.

Sarcopenic Obesity in Adults With Spinal Cord Injury: A Cross-Sectional Study.

PubMed

Pelletier, Chelsea A; Miyatani, Masae; Giangregorio, Lora; Craven, B Catharine

2016-11-01

To describe (1) the frequency and utility of clinically relevant spinal cord injury (SCI)-specific and general population thresholds for obesity and sarcopenic obesity; and (2) the fat and lean soft tissue distributions based on the neurologic level of injury and the American Spinal Injury Association Impairment Scale. Cross-sectional. Tertiary SCI rehabilitation hospital. Persons (N=136; men, n=100; women, n=36) with chronic (mean ± SD: 15.6±11.3y postinjury) tetraplegia (n=66) or paraplegia (n=70). Not applicable. Body composition was assessed with anthropometrics and whole-body dual-energy x-ray absorptiometry. Muscle atrophy was quantified using a sarcopenia threshold of appendicular lean mass index (ALMI) (men, ≤7.26kg/m 2 ; women, ≤5.5kg/m 2 ). Obesity was defined by percentage body fat (men, ≥25%; women, ≥35%), visceral adipose tissue (≥130cm 2 ), and SCI-specific obesity thresholds (body mass index [BMI] ≥22kg/m 2 ; waist circumference ≥94cm). Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Groups were compared based on impairment characteristics using an analysis of covariance. Sarcopenic obesity was prevalent in 41.9% of the sample. ALMI was lower among participants with motor-complete (6.2±1.3kg/m 2 ) versus motor-incomplete (7.5±1.6kg/m 2 ) injuries (P<.01). Whole-body fat was greater among participants with tetraplegia (28.8±11.2kg) versus paraplegia (24.1±8.7kg; P<.05). Compared with general population guidelines (20.6%), SCI-specific BMI thresholds identified all the participants with obesity (77.9%) based on percentage body fat (72.1%). The observed frequency of sarcopenic obesity in this sample of individuals with chronic SCI is very high, and identification of obesity is dissimilar when using SCI-specific versus general population criteria. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Cytogenomics of hexavalent chromium (Cr6+) exposed cells: A comprehensive review

PubMed Central

Nigam, Akanksha; Priya, Shivam; Bajpai, Preeti; Kumar, Sushil

2014-01-01

The altered cellular gene expression profile is being hypothesized as the possible molecular basis navigating the onset or progress of various morbidities. This hypothesis has been evaluated here in respect of Cr6+ induced toxicity. Several studies using gene microarray show selective and strategic dysregulations of cellular genes and pathways induced by Cr6+. Relevant literature has been reviewed to unravel these changes in different test systems after exposure to Cr6+ and also to elucidate association if any, of the altered cytogenomics with Cr6+ induced toxicity or carcinogenicity. The aim was to verify the hypothesis for critical role of altered cytogenomics in onset of Cr6+ induced biological / clinical effects by identifying genes modulated commonly by the toxicant irrespective of test system or test concentrations / doses, and by scrutinizing their importance in regulation of the flow of mechanistically linked events crucial for resultant morbidities. Their probability as biomarkers to monitor the toxicant induced biological changes is speculative. The modulated genes have been found to cluster under the pathways that manage onset of oxidative stress, DNA damage, apoptosis, cell-cycle regulation, cytoskeleton, morphological changes, energy metabolism, biosynthesis, oncogenes, bioenergetics, and immune system critical for toxicity. In these studies, the identity of genes has been found to differ remarkably; albeit the trend of pathways’ dysregulation has been found to remain similar. We conclude that the intensity of dysregulation of genes or pathways involved in mechanistic events forms a sub-threshold or threshold level depending upon the dose and type (including speciation) of the toxicant, duration of exposure, type of target cells, and niche microenvironment of cells, and the intensity of sub-threshold or threshold level of the altered cytogenomics paves way in toxicant exposed cells eventually either to opt for reversal to differentiation and growth, or to result in toxicity like dedifferentiation and apoptosis, respectively. PMID:24820829

Effect of Cigarette Smoking and Passive Smoking on Hearing Impairment: Data from a Population–Based Study

PubMed Central

Chang, Jiwon; Ryou, Namhyung; Jun, Hyung Jin; Hwang, Soon Young; Song, Jae-Jun; Chae, Sung Won

2016-01-01

Objectives In the present study, we aimed to determine the effect of both active and passive smoking on the prevalence of the hearing impairment and the hearing thresholds in different age groups through the analysis of data collected from the Korea National Health and Nutrition Examination Survey (KNHANES). Study Design Cross-sectional epidemiological study. Methods The KNHANES is an ongoing population study that started in 1998. We included a total of 12,935 participants aged ≥19 years in the KNHANES, from 2010 to 2012, in the present study. Pure-tone audiometric (PTA) testing was conducted and the frequencies tested were 0.5, 1, 2, 3, 4, and 6 kHz. Smoking status was categorized into three groups; current smoking group, passive smoking group and non-smoking group. Results In the current smoking group, the prevalence of speech-frequency bilateral hearing impairment was increased in ages of 40−69, and the rate of high frequency bilateral hearing impairment was elevated in ages of 30−79. When we investigated the impact of smoking on hearing thresholds, we found that the current smoking group had significantly increased hearing thresholds compared to the passive smoking group and non-smoking groups, across all ages in both speech-relevant and high frequencies. The passive smoking group did not have an elevated prevalence of either speech-frequency bilateral hearing impairment or high frequency bilateral hearing impairment, except in ages of 40s. However, the passive smoking group had higher hearing thresholds than the non-smoking group in the 30s and 40s age groups. Conclusion Current smoking was associated with hearing impairment in both speech-relevant frequency and high frequency across all ages. However, except in the ages of 40s, passive smoking was not related to hearing impairment in either speech-relevant or high frequencies. PMID:26756932

Threshold level or not for low-density lipoprotein cholesterol.

PubMed

Barter, P J; Sacks, F M

2001-05-01

As drugs, such as the statins, and other therapies demonstrate the ability to significantly lower levels of low-density lipoprotein cholesterol (LDL-C), one issue is whether there is a lower threshold below which no further decline in coronary heart disease occurs. Those who evaluate the data from multiple trials and conclude that no significant decrease in coronary event rates occurs at or below 125 mg/dL suggest using this level as a guideline for clinical application of cholesterol-lowering therapy. On the other hand, analysis of the results of the same population and primary prevention studies concludes that no such threshold exists. The issues affected by the decision of whether to use a threshold include costs to the healthcare system for additional physician time, tests, and medication; unknown clinical events and safety related to very low LDL-C; and resource prioritization to an unestablished therapeutic approach.

Lubiprostone does not Influence Visceral Pain Thresholds in Patients with Irritable Bowel Syndrome

PubMed Central

Whitehead, William E.; Palsson, Olafur S.; Gangarosa, Lisa; Turner, Marsha; Tucker, Jane

2011-01-01

Background In clinical trials, lubiprostone reduced the severity of abdominal pain. Aims The primary aim was to determine whether lubiprostone raises the threshold for abdominal pain induced by intraluminal balloon distention. A secondary aim was to determine whether changes in pain sensitivity influence clinical pain independently of changes in transit time. Methods Sixty-two patients with irritable bowel syndrome with constipation (IBS-C) participated in an 8-week crossover study. All subjects completed a 14-day baseline ending with a barostat test of pain and urge sensory thresholds. Half, randomly selected, then received 48 ug/day of lubiprostone for 14 days ending with a pain sensitivity test and a Sitzmark test of transit time. This was followed by a 14-day washout and then a crossover to 14 days of placebo with tests of pain sensitivity and transit time. The other half of the subjects received placebo before lubiprostone. All kept symptom diaries. Results Stools were significantly softer when taking lubiprostone compared to placebo (Bristol Stool scores 4.20 vs. 3.44, p<0.001). However, thresholds for pain (17.36 vs. 17.83 mmHg, lubiprostone vs. placebo) and urgency to defecate (14.14 vs. 14.53 mmHg) were not affected by lubiprostone. Transit time was not significantly different between lubiprostone and placebo (51.27 vs. 51.81 hours), and neither pain sensitivity nor transit time was a significant predictor of clinical pain. Conclusions Lubiprostone has no effect on visceral sensory thresholds. The reductions in clinical pain that occur while taking lubiprostone appear to be secondary to changes in stool consistency. PMID:21914041

Early identification of ‘acute-onset’ chronic inflammatory demyelinating polyneuropathy

PubMed Central

Sung, Jia-Ying; Tani, Jowy; Park, Susanna B.; Kiernan, Matthew C.

2014-01-01

Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased threshold change in threshold electrotonus in both hyperpolarizing and depolarizing directions [depolarizing threshold electrotonus (90–100 ms) P < 0.005, hyperpolarizing threshold electrotonus (10–20 ms), P < 0.01, hyperpolarizing threshold electrotonus (90–100 ms), P < 0.05], perhaps suggesting early hyperpolarization. In addition, using excitability parameters superexcitability, subexcitability and hyperpolarizing threshold electrotonus (10–20 ms), the patients with acute inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to differentiate acute from acute-onset chronic inflammatory demyelinating polyneuropathy at an early stage. Characteristic nerve excitability parameter changes occur in early acute-onset chronic inflammatory demyelinating polyneuropathy, to match the clinical phenotype. Importantly, this pattern of change was strikingly different to that shown by patients with acute inflammatory demyelinating polyneuropathy, suggesting that nerve excitability techniques may be useful in distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy at the initial stage. PMID:24983276

Nanosecond laser pulses for mimicking thermal effects on nanostructured tungsten-based materials

NASA Astrophysics Data System (ADS)

Besozzi, E.; Maffini, A.; Dellasega, D.; Russo, V.; Facibeni, A.; Pazzaglia, A.; Beghi, M. G.; Passoni, M.

2018-03-01

In this work, we exploit nanosecond laser irradiation as a compact solution for investigating the thermomechanical behavior of tungsten materials under extreme thermal loads at the laboratory scale. Heat flux factor thresholds for various thermal effects, such as melting, cracking and recrystallization, are determined under both single and multishot experiments. The use of nanosecond lasers for mimicking thermal effects induced on W by fusion-relevant thermal loads is thus validated by direct comparison of the thresholds obtained in this work and the ones reported in the literature for electron beams and millisecond laser irradiation. Numerical simulations of temperature and thermal stress performed on a 2D thermomechanical code are used to predict the heat flux factor thresholds of the different thermal effects. We also investigate the thermal effect thresholds of various nanostructured W coatings. These coatings are produced by pulsed laser deposition, mimicking W coatings in tokamaks and W redeposited layers. All the coatings show lower damage thresholds with respect to bulk W. In general, thresholds decrease as the porosity degree of the materials increases. We thus propose a model to predict these thresholds for coatings with various morphologies, simply based on their porosity degree, which can be directly estimated by measuring the variation of the coating mass density with respect to that of the bulk.

Upper stimulation threshold for retinal ganglion cell activation.

PubMed

Meng, Kevin; Fellner, Andreas; Rattay, Frank; Ghezzi, Diego; Meffin, Hamish; Ibbotson, Michael R; Kameneva, Tatiana

2018-08-01

The existence of an upper threshold in electrically stimulated retinal ganglion cells (RGCs) is of interest because of its relevance to the development of visual prosthetic devices, which are designed to restore partial sight to blind patients. The upper threshold is defined as the stimulation level above which no action potentials (direct spikes) can be elicited in electrically stimulated retina. We collected and analyzed in vitro recordings from rat RGCs in response to extracellular biphasic (anodic-cathodic) pulse stimulation of varying amplitudes and pulse durations. Such responses were also simulated using a multicompartment model. We identified the individual cell variability in response to stimulation and the phenomenon known as upper threshold in all but one of the recorded cells (n  =  20/21). We found that the latencies of spike responses relative to stimulus amplitude had a characteristic U-shape. In silico, we showed that the upper threshold phenomenon was observed only in the soma. For all tested biphasic pulse durations, electrode positions, and pulse amplitudes above lower threshold, a propagating action potential was observed in the distal axon. For amplitudes above the somatic upper threshold, the axonal action potential back-propagated in the direction of the soma, but the soma's low level of hyperpolarization prevented action potential generation in the soma itself. An upper threshold observed in the soma does not prevent spike conductance in the axon.

The safe volume threshold for chest drain removal following pulmonary resection.

PubMed

Yap, Kok Hooi; Soon, Jia Lin; Ong, Boon Hean; Loh, Yee Jim

2017-11-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients undergoing pulmonary resection, is there a safe drainage volume threshold for chest drain removal?' Altogether 1054 papers were found, of which 5 papers represented the best evidence. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Chest drainage threshold, where used, ranged from 250 to 500 ml/day. Both randomized controlled trials showed no significant difference in reintervention rates with a higher chest drainage volume threshold. Four studies that performed analysis on other complications showed no statistical significant difference with a higher chest drainage volume threshold. Four studies evaluating length of hospital stay showed reduced or no difference in the length of stay with a higher chest drainage volume threshold. Two cohort studies reported the mortality rate of 0-0.01% with a higher chest drainage volume threshold. We conclude that early chest drain removal after pulmonary resection, accepting a higher chest drainage volume threshold of 250-500 ml/day is safe, and may result in shorter hospital stay without increasing reintervention, morbidity or mortality. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

"Diagnostic shift" from eating disorder not otherwise specified to bulimia nervosa using DSM-5 criteria: a clinical comparison with DSM-IV bulimia.

PubMed

MacDonald, Danielle E; McFarlane, Traci L; Olmsted, Marion P

2014-01-01

In the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the diagnostic threshold for binging and compensation in bulimia nervosa (BN) decreased from twice to once weekly for 3 months. This study investigates the validity of this change by examining whether BN patients and those whose diagnoses "shift" to BN with DSM-5 are similar in their psychological functioning. EDNOS patients whose symptoms met DSM-5 BN criteria (n=25) were compared to DSM-IV BN patients (n=146) on clinically relevant variables. No differences were found on: BMI; weight-based self-evaluation; perfectionism; depression and anxiety symptoms; or readiness for change. Differences were found on one Eating Disorder Inventory subscale (i.e., bulimia), with the BN group reporting higher scores, consistent with group definitions. These findings support the modified criteria, suggesting that psychopathology both directly and indirectly related to eating disorders is comparable between those with once weekly versus more frequent bulimic episodes. © 2013.

Can Preoperative Patient-reported Outcome Measures Be Used to Predict Meaningful Improvement in Function After TKA?

PubMed

Berliner, Jonathan L; Brodke, Dane J; Chan, Vanessa; SooHoo, Nelson F; Bozic, Kevin J

2017-01-01

Despite the overall effectiveness of total knee arthroplasty (TKA), a subset of patients do not experience expected improvements in pain, physical function, and quality of life as documented by patient-reported outcome measures (PROMs), which assess a patient's physical and emotional health and pain. It is therefore important to develop preoperative tools capable of identifying patients unlikely to improve by a clinically important margin after surgery. The purpose of this study was to determine if an association exists between preoperative PROM scores and patients' likelihood of experiencing a clinically meaningful change in function 1 year after TKA. A retrospective study design was used to evaluate preoperative and 1-year postoperative Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-12 version 2 (SF12v2) scores from 562 patients who underwent primary unilateral TKA. This cohort represented 75% of the 750 patients who underwent surgery during that time period; a total of 188 others (25%) either did not complete PROM scores at the designated times or were lost to follow-up. Minimum clinically important differences (MCIDs) were calculated for each PROM using a distribution-based method and were used to define meaningful clinical improvement. MCID values for KOOS and SF12v2 physical component summary (PCS) scores were calculated to be 10 and 5, respectively. A receiver operating characteristic analysis was used to determine threshold values for preoperative KOOS and SF12v2 PCS scores and their respective predictive abilities. Threshold values defined the point after which the likelihood of clinically meaningful improvement began to diminish. Multivariate regression was used to control for the effect of preoperative mental and emotional health, patient attributes quantified by SF12v2 mental component summary (MCS) scores, on patients' likelihood of experiencing meaningful improvement in function after surgery. Threshold values for preoperative KOOS and SF12v2 PCS scores were a maximum of 58 (area under the curve [AUC], 0.76; p < 0.001) and 34 (AUC, 0.65; p < 0.001), respectively. Patients scoring above these thresholds, indicating better preoperative function, were less likely to experience a clinically meaningful improvement in function after TKA. When accounting for mental and emotional health with a multivariate analysis, the predictive ability of both KOOS and SF12v2 PCS threshold values improved (AUCs increased to 0.80 and 0.71, respectively). Better preoperative mental and emotional health, as reflected by a higher MCS score, resulted in higher threshold values for KOOS and SF12v2 PCS. We identified preoperative PROM threshold values that are associated with clinically meaningful improvements in functional outcome after TKA. Patients with preoperative KOOS or SF12v2 PCS scores above the defined threshold values have a diminishing probability of experiencing clinically meaningful improvement after TKA. Patients with worse baseline mental and emotional health (as defined by SF12v2 MCS score) have a lower probability of experiencing clinically important levels of functional improvement after surgery. The results of this study are directly applicable to patient-centered informed decision-making tools and may be used to facilitate discussions with patients regarding the expected benefit after TKA. Level III, prognostic study.

Threshold Evaluation of Emergency Risk Communication for Health Risks Related to Hazardous Ambient Temperature.

PubMed

Liu, Yang; Hoppe, Brenda O; Convertino, Matteo

2018-04-10

Emergency risk communication (ERC) programs that activate when the ambient temperature is expected to cross certain extreme thresholds are widely used to manage relevant public health risks. In practice, however, the effectiveness of these thresholds has rarely been examined. The goal of this study is to test if the activation criteria based on extreme temperature thresholds, both cold and heat, capture elevated health risks for all-cause and cause-specific mortality and morbidity in the Minneapolis-St. Paul Metropolitan Area. A distributed lag nonlinear model (DLNM) combined with a quasi-Poisson generalized linear model is used to derive the exposure-response functions between daily maximum heat index and mortality (1998-2014) and morbidity (emergency department visits; 2007-2014). Specific causes considered include cardiovascular, respiratory, renal diseases, and diabetes. Six extreme temperature thresholds, corresponding to 1st-3rd and 97th-99th percentiles of local exposure history, are examined. All six extreme temperature thresholds capture significantly increased relative risks for all-cause mortality and morbidity. However, the cause-specific analyses reveal heterogeneity. Extreme cold thresholds capture increased mortality and morbidity risks for cardiovascular and respiratory diseases and extreme heat thresholds for renal disease. Percentile-based extreme temperature thresholds are appropriate for initiating ERC targeting the general population. Tailoring ERC by specific causes may protect some but not all individuals with health conditions exacerbated by hazardous ambient temperature exposure. © 2018 Society for Risk Analysis.

From individual to population level effects of toxicants in the tubicifid Branchiura sowerbyi using threshold effect models in a Bayesian framework.

PubMed

Ducrot, Virginie; Billoir, Elise; Péry, Alexandre R R; Garric, Jeanne; Charles, Sandrine

2010-05-01

Effects of zinc were studied in the freshwater worm Branchiura sowerbyi using partial and full life-cycle tests. Only newborn and juveniles were sensitive to zinc, displaying effects on survival, growth, and age at first brood at environmentally relevant concentrations. Threshold effect models were proposed to assess toxic effects on individuals. They were fitted to life-cycle test data using Bayesian inference and adequately described life-history trait data in exposed organisms. The daily asymptotic growth rate of theoretical populations was then simulated with a matrix population model, based upon individual-level outputs. Population-level outputs were in accordance with existing literature for controls. Working in a Bayesian framework allowed incorporating parameter uncertainty in the simulation of the population-level response to zinc exposure, thus increasing the relevance of test results in the context of ecological risk assessment.

Proton threshold states in the {sup 22}Na(p,{gamma}){sup 23}Mg reaction and astrophysical implications

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

Comisel, H.; Hategan, C.; Graw, G.

Proton threshold states in {sup 23}Mg are important for the astrophysically relevant proton capture reaction {sup 22}Na(p,{gamma}){sup 23}Mg. In the indirect determination of the resonance strength of the lowest states, which were not accessible by direct methods, some of the spin-parity-assignments remained experimentally uncertain. We have investigated these states with shell model, Coulomb displacement, and Thomas-Ehrman shift calculations. From the comparison of calculated and observed properties, we relate the lowest relevant resonance state at E{sub x}=7643 keV to an excited 3/2{sup +} state in accordance with a recent experimental determination by Jenkins et al. From this we deduce significantly improvedmore » values for the {sup 22}Na(p,{gamma}){sup 23}Mg reaction rate at stellar temperatures below T{sub 9}=0.1 K.« less

Theory of Auditory Thresholds in Primates

NASA Astrophysics Data System (ADS)

Harrison, Michael J.

2001-03-01

The influence of thermal pressure fluctuations at the tympanic membrane has been previously investigated as a possible determinant of the threshold of hearing in humans (L.J. Sivian and S.D. White, J. Acoust. Soc. Am. IV, 4;288(1933).). More recent work has focussed more precisely on the relation between statistical mechanics and sensory signal processing by biological means in creatures' brains (W. Bialek, in ``Physics of Biological Systems: from molecules to species'', H. Flyvberg et al, (Eds), p. 252; Springer 1997.). Clinical data on the frequency dependence of hearing thresholds in humans and other primates (W.C. Stebbins, ``The Acoustic Sense of Animals'', Harvard 1983.) has long been available. I have derived an expression for the frequency dependence of hearing thresholds in primates, including humans, by first calculating the frequency dependence of thermal pressure fluctuations at eardrums from damped normal modes excited in model ear canals of given simple geometry. I then show that most of the features of the clinical data are directly related to the frequency dependence of the ratio of thermal noise pressure arising from without to that arising from within the masking bandwidth which signals must dominate in order to be sensed. The higher intensity of threshold signals in primates smaller than humans, which is clinically observed over much but not all of the human auditory spectrum is shown to arise from their smaller meatus dimensions. note

Normative behavioral thresholds for short tone-bursts.

PubMed

Beattie, R C; Rochverger, I

2001-10-01

Although tone-bursts have been commonly used in auditory brainstem response (ABR) evaluations for many years, national standards describing normal calibration values have not been established. This study was designed to gather normative threshold data to establish a physical reference for tone-burst stimuli that can be reproduced across clinics and laboratories. More specifically, we obtained norms for 3-msec tone-bursts presented at two repetition rates (9.3/sec and 39/sec), two gating functions (Trapezoid and Blackman), and four frequencies (500, 1000, 2000, and 4000 Hz). Our results are specified using three physical references: dB peak sound pressure level, dB peak-to-peak equivalent sound pressure level, and dB SPL (fast meter response, rate = 50 stimuli/sec). These data are offered for consideration when calibrating ABR equipment. The 39/sec stimulus rate yielded tone-burst thresholds that were approximately 3 dB lower than the 9.3/sec rate. The improvement in threshold with increasing stimulus rate may reflect the ability of the auditory system to integrate energy that occurs within a time interval of 200 to 500 msec (temporal integration). The Trapezoid gating function yielded thresholds that averaged 1.4 dB lower than the Blackman function. Although these differences are small and of little clinical importance, the cumulative effects of several instrument and/or procedural variables may yield clinically important differences.

Value of information and pricing new healthcare interventions.

PubMed

Willan, Andrew R; Eckermann, Simon

2012-06-01

Previous application of value-of-information methods to optimal clinical trial design have predominantly taken a societal decision-making perspective, implicitly assuming that healthcare costs are covered through public expenditure and trial research is funded by government or donation-based philanthropic agencies. In this paper, we consider the interaction between interrelated perspectives of a societal decision maker (e.g. the National Institute for Health and Clinical Excellence [NICE] in the UK) charged with the responsibility for approving new health interventions for reimbursement and the company that holds the patent for a new intervention. We establish optimal decision making from societal and company perspectives, allowing for trade-offs between the value and cost of research and the price of the new intervention. Given the current level of evidence, there exists a maximum (threshold) price acceptable to the decision maker. Submission for approval with prices above this threshold will be refused. Given the current level of evidence and the decision maker's threshold price, there exists a minimum (threshold) price acceptable to the company. If the decision maker's threshold price exceeds the company's, then current evidence is sufficient since any price between the thresholds is acceptable to both. On the other hand, if the decision maker's threshold price is lower than the company's, then no price is acceptable to both and the company's optimal strategy is to commission additional research. The methods are illustrated using a recent example from the literature.

Experimental Investigation on Minimum Frame Rate Requirements of High-Speed Videoendoscopy for Clinical Voice Assessment

PubMed Central

Deliyski, Dimitar D; Powell, Maria EG; Zacharias, Stephanie RC; Gerlach, Terri Treman; de Alarcon, Alessandro

2015-01-01

This study investigated the impact of high-speed videoendoscopy (HSV) frame rates on the assessment of nine clinically-relevant vocal-fold vibratory features. Fourteen adult patients with voice disorder and 14 adult normal controls were recorded using monochromatic rigid HSV at a rate of 16000 frames per second (fps) and spatial resolution of 639×639 pixels. The 16000-fps data were downsampled to 16 other rate denominations. Using paired comparisons design, nine common clinical vibratory features were visually compared between the downsampled and the original images. Three raters reported the thresholds at which: (1) a detectable difference between the two videos was first noticed, and (2) differences between the two videos would result in a change of clinical rating. Results indicated that glottal edge, mucosal wave magnitude and extent, aperiodicity, contact and loss of contact of the vocal folds were the vibratory features most sensitive to frame rate. Of these vibratory features, the glottal edge was selected for further analysis, due to its higher rating reliability, universal prevalence and consistent definition. Rates of 8000 fps were found to be free from visually-perceivable feature degradation, and for rates of 5333 fps, degradation was minimal. For rates of 4000 fps and higher, clinical assessments of glottal edge were not affected. Rates of 2000 fps changed the clinical ratings in over 16% of the samples, which could lead to inaccurate functional assessment. PMID:28989342

Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density

PubMed Central

Edwards, D. L.; Saleh, A. A.; Greenspan, S. L.

2015-01-01

Summary We performed a systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for DXA-determined osteoporosis or low bone density. Commonly evaluated risk instruments showed high sensitivity approaching or exceeding 90 % at particular thresholds within various populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. Introduction The purpose of the study is to systematically review the performance of clinical risk assessment instruments for screening for dual-energy X-ray absorptiometry (DXA)-determined osteoporosis or low bone density. Methods Systematic review and meta-analysis were performed. Multiple literature sources were searched, and data extracted and analyzed from included references. Results One hundred eight references met inclusion criteria. Studies assessed many instruments in 34 countries, most commonly the Osteoporosis Self-Assessment Tool (OST), the Simple Calculated Osteoporosis Risk Estimation (SCORE) instrument, the Osteoporosis Self-Assessment Tool for Asians (OSTA), the Osteoporosis Risk Assessment Instrument (ORAI), and body weight criteria. Meta-analyses of studies evaluating OST using a cutoff threshold of <1 to identify US postmenopausal women with osteoporosis at the femoral neck provided summary sensitivity and specificity estimates of 89 % (95%CI 82–96 %) and 41 % (95%CI 23–59 %), respectively. Meta-analyses of studies evaluating OST using a cutoff threshold of 3 to identify US men with osteoporosis at the femoral neck, total hip, or lumbar spine provided summary sensitivity and specificity estimates of 88 % (95%CI 79–97 %) and 55 % (95%CI 42–68 %), respectively. Frequently evaluated instruments each had thresholds and populations for which sensitivity for osteoporosis or low bone mass detection approached or exceeded 90 % but always with a trade-off of relatively low specificity. Conclusions Commonly evaluated clinical risk assessment instruments each showed high sensitivity approaching or exceeding 90 % for identifying individuals with DXA-determined osteoporosis or low BMD at certain thresholds in different populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. PMID:25644147

Correlations among within-channel and between-channel auditory gap-detection thresholds in normal listeners.

PubMed

Phillips, Dennis P; Smith, Jennifer C

2004-01-01

We obtained data on within-channel and between-channel auditory temporal gap-detection acuity in the normal population. Ninety-five normal listeners were tested for gap-detection thresholds, for conditions in which the gap was bounded by spectrally identical, and by spectrally different, acoustic markers. Separate thresholds were obtained with the use of an adaptive tracking method, for gaps delimited by narrowband noise bursts centred on 1.0 kHz, noise bursts centred on 4.0 kHz, and for gaps bounded by a leading marker of 4.0 kHz noise and a trailing marker of 1.0 kHz noise. Gap thresholds were lowest for silent periods bounded by identical markers--'within-channel' stimuli. Gap thresholds were significantly longer for the between-channel stimulus--silent periods bounded by unidentical markers (p < 0.0001). Thresholds for the two within-channel tasks were highly correlated (R = 0.76). Thresholds for the between-channel stimulus were weakly correlated with thresholds for the within-channel stimuli (1.0 kHz, R = 0.39; and 4.0 kHz, R = 0.46). The relatively poor predictability of between-channel thresholds from the within-channel thresholds is new evidence on the separability of the mechanisms that mediate performance of the two tasks. The data confirm that the acuity difference for the tasks, which has previously been demonstrated in only small numbers of highly trained listeners, extends to a population of untrained listeners. The acuity of the between-channel mechanism may be relevant to the formation of voice-onset time-category boundaries in speech perception.

Thorough statistical comparison of machine learning regression models and their ensembles for sub-pixel imperviousness and imperviousness change mapping

NASA Astrophysics Data System (ADS)

Drzewiecki, Wojciech

2017-12-01

We evaluated the performance of nine machine learning regression algorithms and their ensembles for sub-pixel estimation of impervious areas coverages from Landsat imagery. The accuracy of imperviousness mapping in individual time points was assessed based on RMSE, MAE and R2. These measures were also used for the assessment of imperviousness change intensity estimations. The applicability for detection of relevant changes in impervious areas coverages at sub-pixel level was evaluated using overall accuracy, F-measure and ROC Area Under Curve. The results proved that Cubist algorithm may be advised for Landsat-based mapping of imperviousness for single dates. Stochastic gradient boosting of regression trees (GBM) may be also considered for this purpose. However, Random Forest algorithm is endorsed for both imperviousness change detection and mapping of its intensity. In all applications the heterogeneous model ensembles performed at least as well as the best individual models or better. They may be recommended for improving the quality of sub-pixel imperviousness and imperviousness change mapping. The study revealed also limitations of the investigated methodology for detection of subtle changes of imperviousness inside the pixel. None of the tested approaches was able to reliably classify changed and non-changed pixels if the relevant change threshold was set as one or three percent. Also for fi ve percent change threshold most of algorithms did not ensure that the accuracy of change map is higher than the accuracy of random classifi er. For the threshold of relevant change set as ten percent all approaches performed satisfactory.

Comparison of three versions of Partin tables to predict final pathologic stage in a Chinese cohort: a decision curve analysis.

PubMed

Xiao, Wen-Jun; Ye, Ding-Wei; Yao, Xu-Dong; Zhang, Shi-Lin; Dai, Bo

2013-01-01

To compare Partin tables (PTs) 1997, 2001, and 2007 for their clinical applicability in a Chinese cohort based upon a decision curve analysis (DCA). Clinical and pathologic data of 264 consecutive Chinese patients with clinically localized prostate cancer were used. These patients underwent open radical prostatectomy between 2005 and 2011. DCA quantified the net benefit of different PT versions relating to specific threshold probabilities of established capsular penetration (ECP), seminal vesicle involvement (SVI), and lymph node involvement (LNI). Overall, ECP, SVI, and LNI were recorded in 23.1, 10.2, and 6.1%, respectively. When the threshold probability was below the prevalence for LNI and ECP predictions, the DCA favored the 2007 version versus the 1997 version for SVI. DCA indicates that for low threshold probability, decision models are useful to discriminate the performance differences of three PT versions, although net benefit differences were not apparent. For high threshold probability, there may not be an important benefit from the use of PTs and the current analysis cannot translate into meaningful net gains differences. Copyright © 2013 S. Karger AG, Basel.

The S factor--a new derived hemodynamic oxygenation parameter--a useful tool for simplified mathematical modeling of global problems of oxygen transport.

PubMed

Farrell, K; Wasser, T

1997-01-01

We describe a new derived hemodynamic oxygenation parameter, the S factor (S). The factor is based on oxygen delivery and oxygen consumption and can range from -3 to 1. It allows simplified mathematical modeling of clinical problems of oxygen transport and can be applied to many clinical situations. A new hemodynamic oxygenation parameter, the S factor (S), is introduced as an aid to mathematical modeling. It is defined as follows: [formula: see text] (DO2 = oxygen delivery, VO2 = oxygen consumption) S can theoretically vary from -3 (DO2 = VO2) to +1 (VO2 = 0). When DO2/VO2 = 4 (ie. OER = 0.25), S = 0. An S < 0 implies utilization of reserve oxygen transport capacity. An S > 0 implies increased oxygen delivery in relation to oxygen consumption (ie. "shunted oxygen delivery"). By algebraic manipulation and substitution of the components of DO2 into Equation 1: DO2 = Q x Ca x 10 DO2 = Q [(Hb)(Sat)(1.36) + PaO2(.0031)] 10 (2) the following equations can be derived: [formula: see text] [formula: see text] Ca - Cv (Ca = arterial content, Cv = venous content) can be determined by substituting components of oxygen consumption: VO2 = Q (Ca - Cv) x 10 (5) into equation 1 and solving for Ca - Cv. [formula: see text] Equation 6 can be simplified to: [formula: see text] A previously defined relationship between mixed venous PO2 (PvO2) and DO2/VO2 (where calculated P50 is 26.6 +/- 1.0) can be used to modify S in a clinically relevant manner. PvO2 = 5.44D O2/VO2 + 18.16 (8) The relationship between S and PvO2 can be defined by substituting Equation 4 into Equation 1 and solving for PvO2 PvO2 = [21.76/(1-S)] + 18.16 (9) As an example, at a PvO2 of 28 torr (anaerobic threshold), S = -1.2. The relationship between PvO2 and S is shown in Figure 1. S, which can also be defined as 1-4(VO2/DO2) or 1-4(OER), is a useful tool for mathematical modeling of global problems of oxygen transport because the previously derived equations with the S value allow the components of oxygen transport to be interrelated in a clinically relevant manner. Additional advantages of using S in mathematical modeling are: 1. Conceptually it 'fits' in that in regards to the sign (+ or -), as a -S implies utilization of reserve oxygen transport capacity and a +S implies wasted or excess oxygen delivery (shunted). 2. These concepts are easily quantified using the S factor. 3. It 'spreads out' the difference between values for parameters (OER or S) integrating components of oxygen transport, ie. in the 'normal state' regarding oxygen transport, OER = 0.25 and S = 0. At the anaerobic threshold (PvO2 = 28 torr), OER = 0.55 and S = -1.2. Thus, the change in OER from 'normal state' to anaerobic threshold is 0.3 (0.55-0.25) and the change in S is 1.2. This represents a four-fold increase. Four examples of mathematical modeling of global problems of oxygen transport using the S factor are described below.

Generation of cyclotron harmonic waves in the ionospheric modification experiments

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

Janabi, A.H.A.; Kumar, A.; Sharma, R.P.

1994-02-01

In the present paper, the parametric decay instability of the pump X-mode into electron Bernstein wave (EBW) near second harmonics of electron cyclotron frequency and IBW at different harmonics ([omega] < n[omega][sub ci];n = 2, 3, 4) is examined. Expressions are derived for homogeneous threshold, growth rate and convective threshold for this instability. Applications and relevances of the present investigation to ionospheric modification experiment in the F-layer of the ionosphere as well as during intense electron cyclotron resonance heating in the upcoming MTX tokamak have been given.

Incorporating ecologically relevant habitat and demographic data in assessment of contaminant risk to wildlife

EPA Science Inventory

Evaluating population-level effects of contamination on wildlife requires specific information on habitat quality, species distribution, and contaminant concentration. Establishing broadly applicable thresholds for risk assessment involves an understanding of the applicability o...

Preliminary findings on the safety of 1.5 and 3 Tesla magnetic resonance imaging in cardiac pacemaker patients.

PubMed

van Dijk, Vincent F; Delnoy, Peter Paul H M; Smit, Jaap Jan J; Ramdat Misier, R Anand; Elvan, Arif; van Es, H Wouter; Rensing, Benno J W M; Raciti, Giovanni; Boersma, Lucas V A

2017-07-01

Modern pacemakers are designed to allow patients to undergo magnetic resonance imaging (MRI) under a set of specific conditions. Aim of this study is to provide confirmatory evidence of safety and performance of a new pacing system (ImageReady™, Boston Scientific) in patients undergoing 1.5 and 3T MRI. Two prospective, nonrandomized, single-arm studies were designed to provide confirmatory data of no impact of MRI on device function, lead parameters, and patient conditions in subjects implanted with the system undergoing a clinically non-indicated 1.5T and 3T MRI, respectively. Device measurements were done within 1 hour before and after the scan and at 1 month follow-up. Thirty-two subjects underwent MRI visit (17 subjects with 1.5T MRI and 15 subjects with 3T MRI). There were no unanticipated adverse effects related to the pacemaker. Device measurements taken pre- and post-MRI scan did not show any clinical relevant change that could indicate an effect of the MRI on the device or at the lead-tissue interface (RV threshold change: 0.01 ± 0.13 V, P = 0.60; RA threshold change: 0.01 ± 0.11 V, P = 0.53; R wave change: -0.44 ± 1.73 mV, P = 0.36; R wave change: 0.12 ± 1.67 mV, P = 0.73), with data confirmed at 1-month follow-up visit. The study documented safety of the pacing system in the 1.5T and 3T MRI environment by showing no adverse events related to device or MRI scan. Additional data are required to cover the more complex scenarios involving different diagnostic needs, conditions of use, clinical conditions, and new emerging technologies. © 2017 Wiley Periodicals, Inc.

Effect of Pain Neuroscience Education Combined With Cognition-Targeted Motor Control Training on Chronic Spinal Pain: A Randomized Clinical Trial.

PubMed

Malfliet, Anneleen; Kregel, Jeroen; Coppieters, Iris; De Pauw, Robby; Meeus, Mira; Roussel, Nathalie; Cagnie, Barbara; Danneels, Lieven; Nijs, Jo

2018-04-16

Effective treatments for chronic spinal pain are essential to reduce the related high personal and socioeconomic costs. To compare pain neuroscience education combined with cognition-targeted motor control training with current best-evidence physiotherapy for reducing pain and improving functionality, gray matter morphologic features, and pain cognitions in individuals with chronic spinal pain. Multicenter randomized clinical trial conducted from January 1, 2014, to January 30, 2017, among 120 patients with chronic nonspecific spinal pain in 2 outpatient hospitals with follow-up at 3, 6, and 12 months. Participants were randomized into an experimental group (combined pain neuroscience education and cognition-targeted motor control training) and a control group (combining education on back and neck pain and general exercise therapy). Primary outcomes were pain (pressure pain thresholds, numeric rating scale, and central sensitization inventory) and function (pain disability index and mental health and physical health). There were 22 men and 38 women in the experimental group (mean [SD] age, 39.9 [12.0] years) and 25 men and 35 women in the control group (mean [SD] age, 40.5 [12.9] years). Participants in the experimental group experienced reduced pain (small to medium effect sizes): higher pressure pain thresholds at primary test site at 3 months (estimated marginal [EM] mean, 0.971; 95% CI, -0.028 to 1.970) and reduced central sensitization inventory scores at 6 months (EM mean, -5.684; 95% CI, -10.589 to -0.780) and 12 months (EM mean, -6.053; 95% CI, -10.781 to -1.324). They also experienced improved function (small to medium effect sizes): significant and clinically relevant reduction of disability at 3 months (EM mean, -5.113; 95% CI, -9.994 to -0.232), 6 months (EM mean, -6.351; 95% CI, -11.153 to -1.550), and 12 months (EM mean, -5.779; 95% CI, -10.340 to -1.217); better mental health at 6 months (EM mean, 36.496; 95% CI, 7.998-64.995); and better physical health at 3 months (EM mean, 39.263; 95% CI, 9.644-66.882), 6 months (EM mean, 53.007; 95% CI, 23.805-82.209), and 12 months (EM mean, 32.208; 95% CI, 2.402-62.014). Pain neuroscience education combined with cognition-targeted motor control training appears to be more effective than current best-evidence physiotherapy for improving pain, symptoms of central sensitization, disability, mental and physical functioning, and pain cognitions in individuals with chronic spinal pain. Significant clinical improvements without detectable changes in brain gray matter morphologic features calls into question the relevance of brain gray matter alterations in this population. clinicaltrials.gov Identifier: NCT02098005.

Sub-threshold Post Traumatic Stress Disorder in the WHO World Mental Health Surveys

PubMed Central

McLaughlin, Katie A.; Koenen, Karestan C.; Friedman, Matthew J.; Ruscio, Ayelet Meron; Karam, Elie G.; Shahly, Victoria; Stein, Dan J.; Hill, Eric D.; Petukhova, Maria; Alonso, Jordi; Andrade, Laura Helena; Angermeyer, Matthias C.; Borges, Guilherme; de Girolamo, Giovanni; de Graaf, Ron; Demyttenaere, Koen; Florescu, Silvia E.; Mladenova, Maya; Posada-Villa, Jose; Scott, Kate M.; Takeshima, Tadashi; Kessler, Ronald C.

2014-01-01

Background Although only a minority of people exposed to a traumatic event (TE) develops PTSD, symptoms not meeting full PTSD criteria are common and often clinically significant. Individuals with these symptoms have sometimes been characterized as having sub-threshold PTSD, but no consensus exists on the optimal definition of this term. Data from a large cross-national epidemiological survey are used to provide a principled basis for such a definition. Methods The WHO World Mental Health (WMH) Surveys administered fully-structured psychiatric diagnostic interviews to community samples in 13 countries containing assessments of PTSD associated with randomly selected TEs. Focusing on the 23,936 respondents reporting lifetime TE exposure, associations of approximated DSM-5 PTSD symptom profiles with six outcomes (distress-impairment, suicidality, comorbid fear-distress disorders, PTSD symptom duration) were examined to investigate implications of different sub-threshold definitions. Results Although consistently highest distress-impairment, suicidality, comorbidity, and symptom duration were observed among the 3.0% of respondents with DSM-5 PTSD than other symptom profiles, the additional 3.6% of respondents meeting two or three of DSM-5 Criteria BE also had significantly elevated scores for most outcomes. The proportion of cases with threshold versus sub-threshold PTSD varied depending on TE type, with threshold PTSD more common following interpersonal violence and sub-threshold PTSD more common following events happening to loved ones. Conclusions Sub-threshold DSM-5 PTSD is most usefully defined as meeting two or three of the DSM-5 Criteria B-E. Use of a consistent definition is critical to advance understanding of the prevalence, predictors, and clinical significance of sub-threshold PTSD. PMID:24842116

On the optimal z-score threshold for SISCOM analysis to localize the ictal onset zone.

PubMed

De Coster, Liesbeth; Van Laere, Koen; Cleeren, Evy; Baete, Kristof; Dupont, Patrick; Van Paesschen, Wim; Goffin, Karolien E

2018-04-17

In epilepsy patients, SISCOM or subtraction ictal single photon emission computed tomography co-registered to magnetic resonance imaging has become a routinely used, non-invasive technique to localize the ictal onset zone (IOZ). Thresholding of clusters with a predefined number of standard deviations from normality (z-score) is generally accepted to localize the IOZ. In this study, we aimed to assess the robustness of this parameter in a group of patients with well-characterized drug-resistant epilepsy in whom the exact location of the IOZ was known after successful epilepsy surgery. Eighty patients underwent preoperative SISCOM and were seizure free in a postoperative period of minimum 1 year. SISCOMs with z-threshold 2 and 1.5 were analyzed by two experienced readers separately, blinded from the clinical ground truth data. Their reported location of the IOZ was compared with the operative resection zone. Furthermore, confidence scores of the SISCOM IOZ were compared for the two thresholds. Visual reporting with a z-score threshold of 1.5 and 2 showed no statistically significant difference in localizing correspondence with the ground truth (70 vs. 72% respectively, p = 0.17). Interrater agreement was moderate (κ = 0.65) at the threshold of 1.5, but high (κ = 0.84) at a threshold of 2, where also reviewers were significantly more confident (p < 0.01). SISCOM is a clinically useful, routinely used modality in the preoperative work-up in many epilepsy surgery centers. We found no significant differences in localizing value of the IOZ using a threshold of 1.5 or 2, but interrater agreement and reader confidence were higher using a z-score threshold of 2.

Clinical relevance in anesthesia journals.

PubMed

Lauritsen, Jakob; Møller, Ann M

2006-04-01

The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles. In the last few years, more attention has been paid to evidence-based medicine in anesthesia. Several articles on the subject have focused on the need to base clinical decisions on sound research employing both methodological rigor and clinically relevant outcomes. The number of systematic reviews in anesthesia literature is increasing as well as the focus on diminishing the number of surrogate outcomes. It has been shown that the impact factor is not a valid measure of establishing the level of clinical relevance to a journal. This review presents definitions of clinically relevant anesthesia articles. A clinically relevant article employs both methodological rigor and a clinically relevant outcome. The terms methodological rigor and clinical outcomes are fully discussed in the review as well as problems with journal impact factors.

Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens.

PubMed

Sauter, Guido; Steurer, Stefan; Clauditz, Till Sebastian; Krech, Till; Wittmer, Corinna; Lutz, Florian; Lennartz, Maximilian; Janssen, Tim; Hakimi, Nayira; Simon, Ronald; von Petersdorff-Campen, Mareike; Jacobsen, Frank; von Loga, Katharina; Wilczak, Waldemar; Minner, Sarah; Tsourlakis, Maria Christina; Chirico, Viktoria; Haese, Alexander; Heinzer, Hans; Beyer, Burkhard; Graefen, Markus; Michl, Uwe; Salomon, Georg; Steuber, Thomas; Budäus, Lars Henrik; Hekeler, Elena; Malsy-Mink, Julia; Kutzera, Sven; Fraune, Christoph; Göbel, Cosima; Huland, Hartwig; Schlomm, Thorsten

2016-04-01

Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤ 6, 3 + 4, 4 + 3, 8, and 9-10, but there is variability within these subgroups. For example, Gleason 4 components may range from 5-45% in a Gleason 3 + 4 = 7 cancer. To assess the clinical relevance of the fractions of Gleason patterns. Prostatectomy specimens from 12823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database. To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence. Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed. Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens. Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories ≤ 3 + 3, 3 + 4, 4 + 3, 8, 9 -1 0. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Lubiprostone does not influence visceral pain thresholds in patients with irritable bowel syndrome.

PubMed

Whitehead, W E; Palsson, O S; Gangarosa, L; Turner, M; Tucker, J

2011-10-01

In clinical trials, lubiprostone reduced the severity of abdominal pain. The primary aim was to determine whether lubiprostone raises the threshold for abdominal pain induced by intraluminal balloon distention. A secondary aim was to determine whether changes in pain sensitivity influence clinical pain independently of changes in transit time. Sixty-two patients with irritable bowel syndrome with constipation (IBS-C) participated in an 8-week cross-over study. All subjects completed a 14-day baseline ending with a barostat test of pain and urge sensory thresholds. Half, randomly selected, then received 48 μg day(-1) of lubiprostone for 14 days ending with a pain sensitivity test and a Sitzmark test of transit time. This was followed by a 14-day washout and then a crossover to 14 days of placebo with tests of pain sensitivity and transit time. The other half of the subjects received placebo before lubiprostone. All kept symptom diaries. Stools were significantly softer when taking lubiprostone compared to placebo (Bristol Stool scores 4.20 vs 3.44, P < 0.001). However, thresholds for pain (17.36 vs 17.83 mmHg, lubiprostone vs placebo) and urgency to defecate (14.14 vs 14.53 mmHg) were not affected by lubiprostone. Transit time was not significantly different between lubiprostone and placebo (51.27 vs 51.81 h), and neither pain sensitivity nor transit time was a significant predictor of clinical pain. Lubiprostone has no effect on visceral sensory thresholds. The reductions in clinical pain that occur while taking lubiprostone appear to be secondary to changes in stool consistency. © 2011 Blackwell Publishing Ltd.

High-resolution audiometry: an automated method for hearing threshold acquisition with quality control.

PubMed

Bian, Lin

2012-01-01

In clinical practice, hearing thresholds are measured at only five to six frequencies at octave intervals. Thus, the audiometric configuration cannot closely reflect the actual status of the auditory structures. In addition, differential diagnosis requires quantitative comparison of behavioral thresholds with physiological measures, such as otoacoustic emissions (OAEs) that are usually measured in higher resolution. The purpose of this research was to develop a method to improve the frequency resolution of the audiogram. A repeated-measure design was used in the study to evaluate the reliability of the threshold measurements. A total of 16 participants with clinically normal hearing and mild hearing loss were recruited from a population of university students. No intervention was involved in the study. Custom developed system and software were used for threshold acquisition with quality control (QC). With real-ear calibration and monitoring of test signals, the system provided accurate and individualized measure of hearing thresholds that were determined by an analysis based on signal detection theory (SDT). The reliability of the threshold measure was assessed by correlation and differences between the repeated measures. The audiometric configurations were diverse and unique to each individual ear. The accuracy, within-subject reliability, and between-test repeatability are relatively high. With QC, the high-resolution audiograms can be reliably and accurately measured. Hearing thresholds measured as ear canal sound pressures with higher frequency resolution can provide more customized hearing-aid fitting. The test system may be integrated with other physiological measures, such as OAEs, into a comprehensive evaluative tool. American Academy of Audiology.

Psychological differences between children with and without chronic encopresis.

PubMed

Cox, Daniel J; Morris, James B; Borowitz, Stephen M; Sutphen, James L

2002-01-01

To validate a theoretical model of encopresis in terms of psychological factors that differentiates children with and without chronic encopresis and to identify scales that demonstrate these differences. Eighty-six children with encopresis were compared to 62 nonsymptomatic children on five psychometric instruments. Differences in the mean scores and the percentages of children falling beyond preselected clinical thresholds were compared across the patient-control groups. Children with encopresis were found to have more anxiety/depression symptoms, family environments with less expressiveness and poorer organization, more attention difficulties, greater social problems, more disruptive behavior, and poorer school performance (ps =.01 < or =.001 on 15/20 subscales). There were no differences in self-esteem. On those subscales where proportionately more encopretic children exceeded clinical thresholds, approximately 20% more of the encopretic children exceeded thresholds than control children. As a group, children with encopresis differ from children without encopresis on a variety of psychological parameters. However, only a minority of children with encopresis demonstrated clinically significant elevations in these parameters. Identification and treatment of such clinical issues may enhance treatment efficacy.

Percutaneous biliary drainage effectively lowers serum bilirubin to permit chemotherapy treatment.

PubMed

Levy, Jennifer L; Sudheendra, Deepak; Dagli, Mandeep; Mondschein, Jeffrey I; Stavropoulos, S William; Shlansky-Goldberg, Richard D; Trerotola, Scott O; Teitelbaum, Ursina; Mick, Rosemarie; Soulen, Michael C

2016-02-01

For digestive tract cancers, the bilirubin threshold for administration of systemic chemotherapy can be 5 or 2 mg/dL (85.5 or 34.2 μmol/L) depending upon the regimen. We examined the ability of percutaneous biliary drainage (PBD) in patients with malignant biliary obstruction to achieve these clinically relevant endpoints. 106 consecutive patients with malignant biliary obstruction and a baseline serum bilirubin >2 mg/dL underwent PBD. Time to achieve a bilirubin of 5 mg/dL (85.5 μmol/L), 2 mg/dL (34.2 μmol/L), and survival was estimated by Kaplan-Meier analysis. Potential technical and clinical prognostic factors were subjected to univariate and multivariate analysis. Categorical variables were analyzed by the log rank test. Hazard ratios were calculated for continuous variables. Median survival was 100 days (range 1-3771 days). Among 88 patients with a pre-drainage bilirubin >5 mg/dL, 62% achieved a serum bilirubin ≤5 mg/dL within 30 days and 84% within 60 days, median 21 days. Among 106 patients with a pre-drainage bilirubin >2 mg/dL, 37% achieved a serum bilirubin ≤2 mg/dL by 30 days and 70% within 60 days, median 43 days. None of the technical or clinical factors evaluated, including pre-drainage bilirubin, were significant predictors of time to achieve a bilirubin ≤2 mg/dL (p = 0.51). Size and type of biliary device were the only technical variables found to affect time to bilirubin of 5 mg/dL (p = 0.016). PBD of malignant obstruction achieves clinically relevant reduction in serum bilirubin in the majority of patients within 1-2 months, irrespective of the pre-drainage serum bilirubin, sufficient to allow administration of systemic chemotherapy. However, the decision to undergo this procedure for this indication alone must be considered in the context of patients' prognosis and treatment goals.

Crystalline glucosamine sulfate in the management of knee osteoarthritis: efficacy, safety, and pharmacokinetic properties

PubMed Central

Girolami, Federica; Persiani, Stefano

2012-01-01

Glucosamine is an amino monosaccharide and a natural constituent of glycosaminoglycans in articular cartilage. When administered exogenously, it is used for the treatment of osteoarthritis as a prescription drug or a dietary supplement. The latter use is mainly supported by its perception as a cartilage building block, but it actually exerts specific pharmacologic effects, mainly decreasing interleukin 1-induced gene expression by inhibiting the cytokine intracellular signaling cascade in general and nuclear factor-kappa B (NF-kB) activation in particular. As a whole, the use of glucosamine in the management of osteoarthritis is supported by the clinical trials performed with the original prescription product, that is, crystalline glucosamine sulfate. This is the stabilized form of glucosamine sulfate, while other formulations or different glucosamine salts (e.g. hydrochloride) have never been shown to be effective. In particular, long-term pivotal trials of crystalline glucosamine sulfate 1500 mg once daily have shown significant and clinically relevant improvement of pain and function limitation (symptom-modifying effect) in knee osteoarthritis. Continuous administration for up to 3 years resulted in significant reduction in the progression of joint structure changes compared with placebo as assessed by measuring radiologic joint space narrowing (structure-modifying effect). The two effects combined may suggest a disease-modifying effect that was postulated based on an observed decrease in the risk of undergoing total joint replacement in the follow up of patients receiving the product for at least 12 months in the pivotal trials. The safety of the drug was good in clinical trials and in the postmarketing surveillance. Crystalline glucosamine sulfate 1500 mg once daily is therefore recommended in the majority of clinical practice guidelines and was found to be cost effective in pharmacoeconomic analyses. Compared with other glucosamine formulations, salts, or dosage forms, the prescription product achieves higher plasma and synovial fluid concentrations that are above the threshold for a pharmacologically relevant effect, and may therefore justify its distinct therapeutic characteristics. PMID:22850875

Effectiveness of home-based cupping massage compared to progressive muscle relaxation in patients with chronic neck pain--a randomized controlled trial.

PubMed

Lauche, Romy; Materdey, Svitlana; Cramer, Holger; Haller, Heidemarie; Stange, Rainer; Dobos, Gustav; Rampp, Thomas

2013-01-01

Chronic neck pain is a major public health problem with very few evidence-based complementary treatment options. This study aimed to test the efficacy of 12 weeks of a partner-delivered home-based cupping massage, compared to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain. Patients were randomly assigned to self-directed cupping massage or progressive muscle relaxation. They were trained and asked to undertake the assigned treatment twice weekly for 12 weeks. Primary outcome measure was the current neck pain intensity (0-100 mm visual analog scale; VAS) after 12 weeks. Secondary outcome measures included pain on motion, affective pain perception, functional disability, psychological distress, wellbeing, health-related quality of life, pressure pain thresholds and adverse events. Sixty one patients (54.1±12.7 years; 73.8%female) were randomized to cupping massage (n = 30) or progressive muscle relaxation (n = 31). After treatment, both groups showed significantly less pain compared to baseline however without significant group differences. Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds. In conclusion, cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain. Both therapies can be easily used at home and can reduce pain to a minimal clinically relevant extent. Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger samples and longer follow-up periods are needed to confirm these results. ClinicalTrials.gov NCT01500330.

Effectiveness of Home-Based Cupping Massage Compared to Progressive Muscle Relaxation in Patients with Chronic Neck Pain—A Randomized Controlled Trial

PubMed Central

Lauche, Romy; Materdey, Svitlana; Cramer, Holger; Haller, Heidemarie; Stange, Rainer; Dobos, Gustav; Rampp, Thomas

2013-01-01

Chronic neck pain is a major public health problem with very few evidence-based complementary treatment options. This study aimed to test the efficacy of 12 weeks of a partner-delivered home-based cupping massage, compared to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain. Patients were randomly assigned to self-directed cupping massage or progressive muscle relaxation. They were trained and asked to undertake the assigned treatment twice weekly for 12 weeks. Primary outcome measure was the current neck pain intensity (0–100 mm visual analog scale; VAS) after 12 weeks. Secondary outcome measures included pain on motion, affective pain perception, functional disability, psychological distress, wellbeing, health-related quality of life, pressure pain thresholds and adverse events. Sixty one patients (54.1±12.7 years; 73.8%female) were randomized to cupping massage (n = 30) or progressive muscle relaxation (n = 31). After treatment, both groups showed significantly less pain compared to baseline however without significant group differences. Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds. In conclusion, cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain. Both therapies can be easily used at home and can reduce pain to a minimal clinically relevant extent. Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger samples and longer follow-up periods are needed to confirm these results. Trial Registration ClinicalTrials.gov NCT01500330 PMID:23762355

Genetic correlates of insight in schizophrenia.

PubMed

Xavier, Rose Mary; Vorderstrasse, Allison; Keefe, Richard S E; Dungan, Jennifer R

2018-05-01

Insight in schizophrenia is clinically important as it is associated with several adverse outcomes. Genetic contributions to insight are unknown. We examined genetic contributions to insight by investigating if polygenic risk scores (PRS) and candidate regions were associated with insight. Schizophrenia case-only analysis of the Clinical Antipsychotics Trials of Intervention Effectiveness trial. Schizophrenia PRS was constructed using Psychiatric Genomics Consortium (PGC) leave-one out GWAS as discovery data set. For candidate regions, we selected 105 schizophrenia-associated autosomal loci and 11 schizophrenia-related oligodendrocyte genes. We used regressions to examine PRS associations and set-based testing for candidate analysis. We examined data from 730 subjects. Best-fit PRS at p-threshold of 1e-07 was associated with total insight (R 2 =0.005, P=0.05, empirical P=0.054) and treatment insight (R 2 =0.005, P=0.048, empirical P=0.048). For models that controlled for neurocognition, PRS significantly predicted treatment insight but at higher p-thresholds (0.1 to 0.5) but did not survive correction. Patients with highest polygenic burden had 5.9 times increased risk for poor insight compared to patients with lowest burden. PRS explained 3.2% (P=0.002, empirical P=0.011) of variance in poor insight. Set-based analyses identified two variants associated with poor insight- rs320703, an intergenic variant (within-set P=6e-04, FDR P=0.046) and rs1479165 in SOX2-OT (within-set P=9e-04, FDR P=0.046). To the best of our knowledge, this is the first study examining genetic basis of insight. We provide evidence for genetic contributions to impaired insight. Relevance of findings and necessity for replication are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

The cost-effectiveness of temozolomide in the adjuvant treatment of newly diagnosed glioblastoma in the United States

PubMed Central

Messali, Andrew; Hay, Joel W.; Villacorta, Reginald

2013-01-01

Background The objective of this work was to determine the cost-effectiveness of temozolomide compared with that of radiotherapy alone in the adjuvant treatment of newly diagnosed glioblastoma. Temozolomide is the only chemotherapeutic agent to have demonstrated a significant survival benefit in a randomized clinical trial. Our analysis builds on earlier work by incorporating caregiver time costs and generic temozolomide availability. It is also the first analysis applicable to the US context. Methods A systematic literature review was conducted to collect relevant data. Transition probabilities were calculated from randomized controlled trial data comparing temozolomide plus radiotherapy with radiotherapy alone. Direct costs were calculated from charges reported by the Mayo Clinic. Utilities were obtained from a previous cost-utility analysis. Using these data, a Markov model with a 1-month cycle length and 5-year time horizon was constructed. Results The addition of brand Temodar and generic temozolomide to the standard radiotherapy regimen was associated with base-case incremental cost-effectiveness ratios of $102 364 and $8875, respectively, per quality-adjusted life-year. The model was most sensitive to the progression-free survival associated with the use of only radiotherapy. Conclusions Both the brand and generic base-case estimates are cost-effective under a willingness-to-pay threshold of $150 000 per quality-adjusted life-year. All 1-way sensitivity analyses produced incremental cost-effectiveness ratios below this threshold. We conclude that both the brand Temodar and generic temozolomide are cost-effective treatments for newly diagnosed glioblastoma within the US context. However, assuming that the generic product produces equivalent quality of life and survival benefits, it would be significantly more cost-effective than the brand option. PMID:23935155

Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

PubMed

Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

2016-05-01

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

T1- Thresholds in Black Holes Increase Clinical-Radiological Correlation in Multiple Sclerosis Patients.

PubMed

Thaler, Christian; Faizy, Tobias; Sedlacik, Jan; Holst, Brigitte; Stellmann, Jan-Patrick; Young, Kim Lea; Heesen, Christoph; Fiehler, Jens; Siemonsen, Susanne

2015-01-01

Magnetic Resonance Imaging (MRI) is an established tool in diagnosing and evaluating disease activity in Multiple Sclerosis (MS). While clinical-radiological correlations are limited in general, hypointense T1 lesions (also known as Black Holes (BH)) have shown some promising results. The definition of BHs is very heterogeneous and depends on subjective visual evaluation. We aimed to improve clinical-radiological correlations by defining BHs using T1 relaxation time (T1-RT) thresholds to achieve best possible correlation between BH lesion volume and clinical disability. 40 patients with mainly relapsing-remitting MS underwent MRI including 3-dimensional fluid attenuated inversion recovery (FLAIR), magnetization-prepared rapid gradient echo (MPRAGE) before and after Gadolinium (GD) injection and double inversion-contrast magnetization-prepared rapid gradient echo (MP2RAGE) sequences. BHs (BHvis) were marked by two raters on native T1-weighted (T1w)-MPRAGE, contrast-enhancing lesions (CE lesions) on T1w-MPRAGE after GD and FLAIR lesions (total-FLAIR lesions) were detected separately. BHvis and total-FLAIR lesion maps were registered to MP2RAGE images, and the mean T1-RT were calculated for all lesion ROIs. Mean T1 values of the cortex (CTX) were calculated for each patient. Subsequently, Spearman rank correlations between clinical scores (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite) and lesion volume were determined for different T1-RT thresholds. Significant differences in T1-RT were obtained between all different lesion types with highest T1 values in visually marked BHs (BHvis: 1453.3±213.4 ms, total-FLAIR lesions: 1394.33±187.38 ms, CTX: 1305.6±35.8 ms; p<0.05). Significant correlations between BHvis/total-FLAIR lesion volume and clinical disability were obtained for a wide range of T1-RT thresholds. The highest correlation for BHvis and total-FLAIR lesion masks were found at T1-RT>1500 ms (Expanded Disability Status Scale vs. lesion volume: rBHvis = 0.442 and rtotal-FLAIR = 0.497, p<0.05; Multiple Sclerosis Functional Composite vs. lesion volume: rBHvis = -0.53 and rtotal-FLAIR = -0.627, p<0.05). Clinical-radiological correlations in MS patients are increased by application of T1-RT thresholds. With the short acquisition time of the MP2RAGE sequences, quantitative T1 maps could be easily established in clinical studies.

Use of anti-TNF drug levels to optimise patient management

PubMed Central

Papamichael, Konstantinos; Cheifetz, Adam S

2016-01-01

Anti-tumour necrosis factor (TNF) therapies, such as infliximab, adalimumab, certolizumab pegol and golimumab, have been proven to be effective for the treatment of patients with Crohn's disease and ulcerative colitis. However, 10%–30% of patients with inflammatory bowel disease (IBD) show no initial clinical benefit to anti-TNF therapy (primary non-response), and over 50% after an initial favourable outcome will lose response over time (secondary loss of response (SLR)). Numerous recent studies in IBD have revealed an exposure–response relationship suggesting a positive correlation between high serum anti-TNF concentrations and favourable therapeutic outcomes including clinical, biomarker and endoscopic remission, whereas antidrug antibodies have been associated with SLR and infusion reactions. Currently, therapeutic drug monitoring (TDM) is typically performed when treatment failure occurs either for SLR, drug intolerance (potential immune-mediated reaction) or infusion reaction (reactive TDM). Nevertheless, recent data demonstrate that proactive TDM and a treat-to-target (trough) therapeutic approach may more effectively optimise anti-TNF therapy efficacy, safety and cost. However, implementing TDM in real-life clinical practice is currently limited by the diversity in study design, therapeutic outcomes and assays used, which have hindered the identification of robust clinically relevant concentration thresholds. This review will focus mainly on the pharmacodynamic properties of anti-TNF therapy and the role of TDM in guiding therapeutic decisions in IBD. PMID:28839870

Appearance of bony lesions on 3-D CT reconstructions: a case study in variable renderings

NASA Astrophysics Data System (ADS)

Mankovich, Nicholas J.; White, Stuart C.

1992-05-01

This paper discusses conventional 3-D reconstruction for bone visualization and presents a case study to demonstrate the dangers of performing 3-D reconstructions without careful selection of the bone threshold. The visualization of midface bone lesions directly from axial CT images is difficult because of the complex anatomic relationships. Three-dimensional reconstructions made from the CT to provide graphic images showing lesions in relation to adjacent facial bones. Most commercially available 3-D image reconstruction requires that the radiologist or technologist identify a threshold image intensity value that can be used to distinguish bone from other tissues. Much has been made of the many disadvantages of this technique, but it continues as the predominant method in producing 3-D pictures for clinical use. This paper is intended to provide a clear demonstration for the physician of the caveats that should accompany 3-D reconstructions. We present a case of recurrent odontogenic keratocyst in the anterior maxilla where the 3-D reconstructions, made with different bone thresholds (windows), are compared to the resected specimen. A DMI 3200 computer was used to convert the scan data from a GE 9800 CT into a 3-D shaded surface image. Threshold values were assigned to (1) generate the most clinically pleasing image, (2) produce maximum theoretical fidelity (using the midpoint image intensity between average cortical bone and average soft tissue), and (3) cover stepped threshold intensities between these two methods. We compared the computer lesions with the resected specimen and noted measurement errors of up to 44 percent introduced by inappropriate bone threshold levels. We suggest clinically applicable standardization techniques in the 3-D reconstruction as well as cautionary language that should accompany the 3-D images.

An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis.

PubMed

Kamath, Vidyulata; Moberg, Paul J; Calkins, Monica E; Borgmann-Winter, Karin; Conroy, Catherine G; Gur, Raquel E; Kohler, Christian G; Turetsky, Bruce I

2012-07-01

While olfactory deficits have been reported in schizophrenia and youths at-risk for psychosis, few studies have linked these deficits to current pathophysiological models of the illness. There is evidence that disrupted cyclic adenosine 3',5'-monophosphate (cAMP) signaling may contribute to schizophrenia pathology. As cAMP mediates olfactory signal transduction, the degree to which this disruption could manifest in olfactory impairment was ascertained. Odor-detection thresholds to two odorants that differ in the degree to which they activate intracellular cAMP were assessed in clinical risk and low-risk participants. Birhinal assessments of odor-detection threshold sensitivity to lyral and citralva were acquired in youths experiencing prodromal symptoms (n=17) and controls at low risk for developing psychosis (n=15). Citralva and lyral are odorants that differ in cAMP activation; citralva is a strong cAMP activator and lyral is a weak cAMP activator. The overall group-by-odor interaction was statistically significant. At-risk youths showed significantly reduced odor detection thresholds for lyral, but showed intact detection thresholds for citralva. This odor-specific threshold deficit was uncorrelated with deficits in odor identification or discrimination, which were also present. ROC curve analysis revealed that olfactory performance correctly classified at-risk and low-risk youths with greater than 97% accuracy. This study extends prior findings of an odor-specific hyposmia implicating cAMP-mediated signal transduction in schizophrenia and unaffected first-degree relatives to include youths at clinical risk for developing the disorder. These results suggest that dysregulation of cAMP signaling may be present during the psychosis prodrome. Copyright © 2012 Elsevier B.V. All rights reserved.

An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis

PubMed Central

Kamath, Vidyulata; Moberg, Paul J.; Calkins, Monica E.; Borgmann-Winter, Karin; Conroy, Catherine G.; Gur, Raquel E.; Kohler, Christian G.; Turetsky, Bruce I.

2012-01-01

Background While olfactory deficits have been reported in schizophrenia and youths at-risk for psychosis, few studies have linked these deficits to current pathophysiological models of the illness. There is evidence that disrupted cyclic adenosine 3’,5’-monophosphate (cAMP) signaling may contribute to schizophrenia pathology. As cAMP mediates olfactory signal transduction, the degree to which this disruption could manifest in olfactory impairment was ascertained. Odor-detection thresholds to two odorants that differ in the degree to which they activate intracellular cAMP were assessed in clinical risk and low-risk participants. Method Birhinal assessments of odor-detection threshold sensitivity to lyral and citralva were acquired in youths experiencing prodromal symptoms (n = 17) and controls at low risk for developing psychosis (n = 15). Citralva and lyral are odorants that differ in cAMP activation; citralva is a strong cAMP activator and lyral is a weak cAMP activator. Results The overall group-by-odor interaction was statistically significant. At-risk youths showed significantly reduced odor detection thresholds for lyral, but showed intact detection thresholds for citralva. This odor-specific threshold deficit was uncorrelated with deficits in odor identification or discrimination, which were also present. ROC curve analysis revealed that olfactory performance correctly classified at-risk and low-risk youths with greater than 97% accuracy. Conclusions This study extends prior findings of an odor-specific hyposmia implicating cAMP-mediated signal transduction in schizophrenia and unaffected first-degree relatives to include youths at clinical risk for developing the disorder. These results suggest that dysregulation of cAMP signaling may be present during the psychosis prodrome. PMID:22537567

The influence of informational masking in reverberant, multi-talker environments.

PubMed

Westermann, Adam; Buchholz, Jörg M

2015-08-01

The relevance of informational masking (IM) in real-world listening is not well understood. In literature, IM effects of up to 10 dB in measured speech reception thresholds (SRTs) are reported. However, these experiments typically employed simplified spatial configurations and speech corpora that magnified confusions. In this study, SRTs were measured with normal hearing subjects in a simulated cafeteria environment. The environment was reproduced by a 41-channel 3D-loudspeaker array. The target talker was 2 m in front of the listener and masking talkers were either spread throughout the room or colocated with the target. Three types of maskers were realized: one with the same talker as the target (maximum IM), one with talkers different from the target, and one with unintelligible, noise-vocoded talkers (minimal IM). Overall, SRTs improved for the spatially distributed conditions compared to the colocated conditions. Within the spatially distributed conditions, there was no significant difference between thresholds with the different- and vocoded-talker maskers. Conditions with the same-talker masker were the only conditions with substantially higher thresholds, especially in the colocated conditions. These results suggest that IM related to target-masker confusions, at least for normal-hearing listeners, is of low relevance in real-life listening.

Cluster-based analysis improves predictive validity of spike-triggered receptive field estimates

PubMed Central

Malone, Brian J.

2017-01-01

Spectrotemporal receptive field (STRF) characterization is a central goal of auditory physiology. STRFs are often approximated by the spike-triggered average (STA), which reflects the average stimulus preceding a spike. In many cases, the raw STA is subjected to a threshold defined by gain values expected by chance. However, such correction methods have not been universally adopted, and the consequences of specific gain-thresholding approaches have not been investigated systematically. Here, we evaluate two classes of statistical correction techniques, using the resulting STRF estimates to predict responses to a novel validation stimulus. The first, more traditional technique eliminated STRF pixels (time-frequency bins) with gain values expected by chance. This correction method yielded significant increases in prediction accuracy, including when the threshold setting was optimized for each unit. The second technique was a two-step thresholding procedure wherein clusters of contiguous pixels surviving an initial gain threshold were then subjected to a cluster mass threshold based on summed pixel values. This approach significantly improved upon even the best gain-thresholding techniques. Additional analyses suggested that allowing threshold settings to vary independently for excitatory and inhibitory subfields of the STRF resulted in only marginal additional gains, at best. In summary, augmenting reverse correlation techniques with principled statistical correction choices increased prediction accuracy by over 80% for multi-unit STRFs and by over 40% for single-unit STRFs, furthering the interpretational relevance of the recovered spectrotemporal filters for auditory systems analysis. PMID:28877194

Higgs-stoponium mixing near the stop-antistop threshold

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

Bodwin, Geoffrey T.; Chung, Hee Sok; Wagner, Carlos E. M.

Supersymmetric extensions of the standard model contain additional heavy neutral Higgs bosons that are coupled to heavy scalar top quarks (stops). This system exhibits interesting field theoretic phenomena when the Higgs mass is close to the stop-antistop production threshold. Existing work in the literature has examined the digluon-to-diphoton cross section near threshold and has focused on enhancements in the cross section that might arise either from the perturbative contributions to the Higgs-to-digluon and Higgs-to-diphoton form factors or from mixing of the Higgs boson with stoponium states. Near threshold, enhancements in the relevant amplitudes that go as inverse powers of themore » stop-antistop relative velocity require resummations of perturbation theory and/or nonperturbative treatments. We present a complete formulation of threshold effects at leading order in the stop-antistop relative velocity in terms of nonrelativistic effective field theory. We give detailed numerical calculations for the case in which the stop-antistop Green’s function is modeled with a Coulomb-Schr¨odinger Green’s function. We find several general effects that do not appear in a purely perturbative treatment. Higgs-stop-antistop mixing effects displace physical masses from the threshold region, thereby rendering the perturbative threshold enhancements inoperative. In the case of large Higgs-stop-antistop couplings, the displacement of a physical state above threshold substantially increases its width, owing to its decay width to a stop-antistop pair, and greatly reduces its contribution to the cross section.« less

PT-symmetry breaking with divergent potentials: Lattice and continuum cases

NASA Astrophysics Data System (ADS)

Joglekar, Yogesh N.; Scott, Derek D.; Saxena, Avadh

2014-09-01

We investigate the parity- and time-reversal (PT-) symmetry breaking in lattice models in the presence of long-ranged, non-Hermitian, PT-symmetric potentials that remain finite or become divergent in the continuum limit. By scaling analysis of the fragile PT threshold for an open finite lattice, we show that continuum loss-gain potentials Vα(x)∝i|x|αsgn(x) have a positive PT-breaking threshold for α >-2, and a zero threshold for α ≤-2. When α <0 localized states with complex (conjugate) energies in the continuum energy band occur at higher loss-gain strengths. We investigate the signatures of PT-symmetry breaking in coupled waveguides, and show that the emergence of localized states dramatically shortens the relevant time scale in the PT-symmetry broken region.

Prolactin receptor in regulation of neuronal excitability and channels

PubMed Central

Patil, Mayur J; Henry, Michael A; Akopian, Armen N

2014-01-01

Prolactin (PRL) activates PRL receptor isoforms to exert regulation of specific neuronal circuitries, and to control numerous physiological and clinically-relevant functions including; maternal behavior, energy balance and food intake, stress and trauma responses, anxiety, neurogenesis, migraine and pain. PRL controls these critical functions by regulating receptor potential thresholds, neuronal excitability and/or neurotransmission efficiency. PRL also influences neuronal functions via activation of certain neurons, resulting in Ca2+ influx and/or electrical firing with subsequent release of neurotransmitters. Although PRL was identified almost a century ago, very little specific information is known about how PRL regulates neuronal functions. Nevertheless, important initial steps have recently been made including the identification of PRL-induced transient signaling pathways in neurons and the modulation of neuronal transient receptor potential (TRP) and Ca2+-dependent K+ channels by PRL. In this review, we summarize current knowledge and recent progress in understanding the regulation of neuronal excitability and channels by PRL. PMID:24758841

Survey of Cooling Options for Application in a Low-TC Squid System for Fetal Magnetocardiography

NASA Astrophysics Data System (ADS)

Rijpma, A. P.; Uzunbajakau, S.; ter Brake, H. J. M.; Peters, M. J.; Rogalla, H.

2004-06-01

As part of the development of a low-Tc SQUID-based magnetometer system for measuring fetal heart activity, the means of cooling is evaluated. To lower the threshold for the clinical application of this fetal heart monitor, it should be simple to operate. It is, therefore, deemed necessary to replace the liquid helium by a closed-cycle refrigerator. In this paper, the requirements with respect to the cryogenic system are defined. These include operating temperature (4 K), temperature stability (<0.2 K), cooling power (>0.1 W) and requirements on magnetic and mechanical interference. The paper also reviews the most relevant options for the realization of the cryogenic system. After comparison, we selected a 4-K mechanical cooler. To reduce the interference, it is placed at several meters from the magnetometer. The cooling power is to be transferred by circulation of helium.

The association of pain and depression in preadolescent girls: moderation by race and pubertal stage.

PubMed

Keenan, Kate; Hipwell, Alison E; Hinze, Amanda E; Babinski, Dara E

2009-08-01

To test whether an association between pain response and depression in females is present during preadolescence using a controlled pain stimulus and a clinically relevant assessment of depressive symptoms. In a sample of 232 girls, pain threshold and tolerance were assessed at age 10 years using the cold pressor task, and a diagnostic interview was used to assess depression symptoms at 10 and 11 years of age. Response to pain at age 10 was associated with depressive symptoms at ages 10 and 11; race and pubertal stage moderated the association. Pain response and depression were more strongly associated among girls who had reached advanced stages of pubertal development and among European American girls. The results add to the existing literature on the co-occurrence of depression and pain by demonstrating modest but consistent concurrent and prospective associations between response to pain and depression among girls during preadolescence.

Wearable ear EEG for brain interfacing

NASA Astrophysics Data System (ADS)

Schroeder, Eric D.; Walker, Nicholas; Danko, Amanda S.

2017-02-01

Brain-computer interfaces (BCIs) measuring electrical activity via electroencephalogram (EEG) have evolved beyond clinical applications to become wireless consumer products. Typically marketed for meditation and neu- rotherapy, these devices are limited in scope and currently too obtrusive to be a ubiquitous wearable. Stemming from recent advancements made in hearing aid technology, wearables have been shrinking to the point that the necessary sensors, circuitry, and batteries can be fit into a small in-ear wearable device. In this work, an ear-EEG device is created with a novel system for artifact removal and signal interpretation. The small, compact, cost-effective, and discreet device is demonstrated against existing consumer electronics in this space for its signal quality, comfort, and usability. A custom mobile application is developed to process raw EEG from each device and display interpreted data to the user. Artifact removal and signal classification is accomplished via a combination of support matrix machines (SMMs) and soft thresholding of relevant statistical properties.

Low-Cost Optical Mapping Systems for Panoramic Imaging of Complex Arrhythmias and Drug-Action in Translational Heart Models

NASA Astrophysics Data System (ADS)

Lee, Peter; Calvo, Conrado J.; Alfonso-Almazán, José M.; Quintanilla, Jorge G.; Chorro, Francisco J.; Yan, Ping; Loew, Leslie M.; Filgueiras-Rama, David; Millet, José

2017-02-01

Panoramic optical mapping is the primary method for imaging electrophysiological activity from the entire outer surface of Langendorff-perfused hearts. To date, it is the only method of simultaneously measuring multiple key electrophysiological parameters, such as transmembrane voltage and intracellular free calcium, at high spatial and temporal resolution. Despite the impact it has already had on the fields of cardiac arrhythmias and whole-heart computational modeling, present-day system designs precludes its adoption by the broader cardiovascular research community because of their high costs. Taking advantage of recent technological advances, we developed and validated low-cost optical mapping systems for panoramic imaging using Langendorff-perfused pig hearts, a clinically-relevant model in basic research and bioengineering. By significantly lowering financial thresholds, this powerful cardiac electrophysiology imaging modality may gain wider use in research and, even, teaching laboratories, which we substantiated using the lower-cost Langendorff-perfused rabbit heart model.

Low-Cost Optical Mapping Systems for Panoramic Imaging of Complex Arrhythmias and Drug-Action in Translational Heart Models.

PubMed

Lee, Peter; Calvo, Conrado J; Alfonso-Almazán, José M; Quintanilla, Jorge G; Chorro, Francisco J; Yan, Ping; Loew, Leslie M; Filgueiras-Rama, David; Millet, José

2017-02-27

Panoramic optical mapping is the primary method for imaging electrophysiological activity from the entire outer surface of Langendorff-perfused hearts. To date, it is the only method of simultaneously measuring multiple key electrophysiological parameters, such as transmembrane voltage and intracellular free calcium, at high spatial and temporal resolution. Despite the impact it has already had on the fields of cardiac arrhythmias and whole-heart computational modeling, present-day system designs precludes its adoption by the broader cardiovascular research community because of their high costs. Taking advantage of recent technological advances, we developed and validated low-cost optical mapping systems for panoramic imaging using Langendorff-perfused pig hearts, a clinically-relevant model in basic research and bioengineering. By significantly lowering financial thresholds, this powerful cardiac electrophysiology imaging modality may gain wider use in research and, even, teaching laboratories, which we substantiated using the lower-cost Langendorff-perfused rabbit heart model.

The principle of equivalence reconsidered: assessing the relevance of the principle of equivalence in prison medicine.

PubMed

Jotterand, Fabrice; Wangmo, Tenzin

2014-01-01

In this article we critically examine the principle of equivalence of care in prison medicine. First, we provide an overview of how the principle of equivalence is utilized in various national and international guidelines on health care provision to prisoners. Second, we outline some of the problems associated with its applications, and argue that the principle of equivalence should go beyond equivalence to access and include equivalence of outcomes. However, because of the particular context of the prison environment, third, we contend that the concept of "health" in equivalence of health outcomes needs conceptual clarity; otherwise, it fails to provide a threshold for healthy states among inmates. We accomplish this by examining common understandings of the concepts of health and disease. We conclude our article by showing why the conceptualization of diseases as clinical problems provides a helpful approach in the delivery of health care in prison.

Vitamin B supplementation for diabetic peripheral neuropathy

PubMed Central

Jayabalan, Bhavani; Low, Lian Leng

2016-01-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. PMID:26892473

A pilot analytic study of a research-level, lower-cost human papillomavirus 16, 18, and 45 test.

PubMed

Yang, Hannah P; Walmer, David K; Merisier, Delson; Gage, Julia C; Bell, Laura; Rangwala, Sameera; Shrestha, Niwashin; Kobayashi, Lori; Eder, Paul S; Castle, Philip E

2011-09-01

The analytic performance of a low-cost, research-stage DNA test for the most carcinogenic human papillomavirus (HPV) genotypes (HPV16, HPV18, and HPV45) in aggregate was evaluated among carcinogenic HPV-positive women, which might be used to decide who needs immediate colposcopy in low-resource settings ("triage test"). We found that HPV16/18/45 test agreed well with two DNA tests, a GP5+/6+ genotyping assay (Kappa = 0.77) and a quantitative PCR assay (at a cutpoint of 5000 viral copies) (Kappa = 0.87). DNA sequencing on a subset of 16 HPV16/18/45 positive and 16 HPV16/18/45 negative verified the analytic specificity of the research test. It is concluded that the HPV16/18/45 assay is a promising triage test with a minimum detection of approximately 5000 viral copies, the clinically relevant threshold. Published by Elsevier B.V.

Outcome-driven thresholds for home blood pressure measurement: international database of home blood pressure in relation to cardiovascular outcome.

PubMed

Niiranen, Teemu J; Asayama, Kei; Thijs, Lutgarde; Johansson, Jouni K; Ohkubo, Takayoshi; Kikuya, Masahiro; Boggia, José; Hozawa, Atsushi; Sandoya, Edgardo; Stergiou, George S; Tsuji, Ichiro; Jula, Antti M; Imai, Yutaka; Staessen, Jan A

2013-01-01

The lack of outcome-driven operational thresholds limits the clinical application of home blood pressure (BP) measurement. Our objective was to determine an outcome-driven reference frame for home BP measurement. We measured home and clinic BP in 6470 participants (mean age, 59.3 years; 56.9% women; 22.4% on antihypertensive treatment) recruited in Ohasama, Japan (n=2520); Montevideo, Uruguay (n=399); Tsurugaya, Japan (n=811); Didima, Greece (n=665); and nationwide in Finland (n=2075). In multivariable-adjusted analyses of individual subject data, we determined home BP thresholds, which yielded 10-year cardiovascular risks similar to those associated with stages 1 (120/80 mm Hg) and 2 (130/85 mm Hg) prehypertension, and stages 1 (140/90 mm Hg) and 2 (160/100 mm Hg) hypertension on clinic measurement. During 8.3 years of follow-up (median), 716 cardiovascular end points, 294 cardiovascular deaths, 393 strokes, and 336 cardiac events occurred in the whole cohort; in untreated participants these numbers were 414, 158, 225, and 194, respectively. In the whole cohort, outcome-driven systolic/diastolic thresholds for the home BP corresponding with stages 1 and 2 prehypertension and stages 1 and 2 hypertension were 121.4/77.7, 127.4/79.9, 133.4/82.2, and 145.4/86.8 mm Hg; in 5018 untreated participants, these thresholds were 118.5/76.9, 125.2/79.7, 131.9/82.4, and 145.3/87.9 mm Hg, respectively. Rounded thresholds for stages 1 and 2 prehypertension and stages 1 and 2 hypertension amounted to 120/75, 125/80, 130/85, and 145/90 mm Hg, respectively. Population-based outcome-driven thresholds for home BP are slightly lower than those currently proposed in hypertension guidelines. Our current findings could inform guidelines and help clinicians in diagnosing and managing patients.

Response of algal metrics to nutrients and physical factors and identification of nutrient thresholds in agricultural streams

USGS Publications Warehouse

Black, R.W.; Moran, P.W.; Frankforter, J.D.

2011-01-01

Many streams within the United States are impaired due to nutrient enrichment, particularly in agricultural settings. The present study examines the response of benthic algal communities in agricultural and minimally disturbed sites from across the western United States to a suite of environmental factors, including nutrients, collected at multiple scales. The first objective was to identify the relative importance of nutrients, habitat and watershed features, and macroinvertebrate trophic structure to explain algal metrics derived from deposition and erosion habitats. The second objective was to determine if thresholds in total nitrogen (TN) and total phosphorus (TP) related to algal metrics could be identified and how these thresholds varied across metrics and habitats. Nutrient concentrations within the agricultural areas were elevated and greater than published threshold values. All algal metrics examined responded to nutrients as hypothesized. Although nutrients typically were the most important variables in explaining the variation in each of the algal metrics, environmental factors operating at multiple scales also were important. Calculated thresholds for TN or TP based on the algal metrics generated from samples collected from erosion and deposition habitats were not significantly different. Little variability in threshold values for each metric for TN and TP was observed. The consistency of the threshold values measured across multiple metrics and habitats suggest that the thresholds identified in this study are ecologically relevant. Additional work to characterize the relationship between algal metrics, physical and chemical features, and nuisance algal growth would be of benefit to the development of nutrient thresholds and criteria. ?? 2010 The Author(s).

Response of algal metrics to nutrients and physical factors and identification of nutrient thresholds in agricultural streams.

PubMed

Black, Robert W; Moran, Patrick W; Frankforter, Jill D

2011-04-01

Many streams within the United States are impaired due to nutrient enrichment, particularly in agricultural settings. The present study examines the response of benthic algal communities in agricultural and minimally disturbed sites from across the western United States to a suite of environmental factors, including nutrients, collected at multiple scales. The first objective was to identify the relative importance of nutrients, habitat and watershed features, and macroinvertebrate trophic structure to explain algal metrics derived from deposition and erosion habitats. The second objective was to determine if thresholds in total nitrogen (TN) and total phosphorus (TP) related to algal metrics could be identified and how these thresholds varied across metrics and habitats. Nutrient concentrations within the agricultural areas were elevated and greater than published threshold values. All algal metrics examined responded to nutrients as hypothesized. Although nutrients typically were the most important variables in explaining the variation in each of the algal metrics, environmental factors operating at multiple scales also were important. Calculated thresholds for TN or TP based on the algal metrics generated from samples collected from erosion and deposition habitats were not significantly different. Little variability in threshold values for each metric for TN and TP was observed. The consistency of the threshold values measured across multiple metrics and habitats suggest that the thresholds identified in this study are ecologically relevant. Additional work to characterize the relationship between algal metrics, physical and chemical features, and nuisance algal growth would be of benefit to the development of nutrient thresholds and criteria.

Publications in anesthesia journals: quality and clinical relevance.

PubMed

Lauritsen, Jakob; Moller, Ann M

2004-11-01

Clinicians performing evidence-based anesthesia rely on anesthesia journals for clinically relevant information. The objective of this study was to analyze the proportion of clinically relevant articles in five high impact anesthesia journals. We evaluated all articles published in Anesthesiology, Anesthesia & Analgesia, British Journal of Anesthesia, Anesthesia, and Acta Anaesthesiologica Scandinavica from January to June, 2000. Articles were assessed and classified according to type, outcome, and design; 1379 articles consisting of 5468 pages were evaluated and categorized. The most common types of article were animal and laboratory research (31.2%) and randomized clinical trial (20.4%). A clinically relevant article was defined as an article that used a statistically valid method and had a clinically relevant end-point. Altogether 18.6% of the pages had as their subject matter clinically relevant trials. We compared the Journal Impact Factor (a measure of the number of citations per article in a journal) and the proportion of clinically relevant pages and found that they were inversely proportional to each other.

The PM2.5 threshold for aerosol extinction in the Beijing megacity

NASA Astrophysics Data System (ADS)

Kong, Lingbin; Xin, Jinyuan; Liu, Zirui; Zhang, Kequan; Tang, Guiqian; Zhang, Wenyu; Wang, Yuesi

2017-10-01

Particulate pollution has remained at a high level in the megacity of Beijing in the past decade. The PM2.5, PM10, aerosol optical depth (AOD), Angstrom exponent(α), and PM2.5/PM10 ratio (the proportion of PM2.5 in PM10) in Beijing were 70±6 μg m-3, 128±6 μg m-3, 0.57 ± 0.05, 1.10 ± 0.08, 45 ± 4%, respectively, from 2005 to 2014. The annual means of PM concentration, AOD, α, and PM2.5/PM10 ratio decreased slightly during this decade, meanwhile PM concentration increased in the winter. Furthermore, we found there were thresholds of PM2.5 concentration for aerosol extinction. When the PM concentration was lower than a certain threshold, AOD decreased quickly with the decline of PM concentration. To make the improvement of the particle pollution more noticeable, the PM concentration should be controlled under the threshold. The annual averaged threshold is 63 μg m-3, and the threshold values reached the maximum of 74 μg m-3 in spring, ranged from 54 to 56 μg m-3 in the three other seasons. The threshold values ranged from 55 to 77 μg m-3 under other relevant factors, including air masses directions and relative humidity.

p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women.

PubMed

Wentzensen, Nicolas; Fetterman, Barbara; Castle, Philip E; Schiffman, Mark; Wood, Shannon N; Stiemerling, Eric; Tokugawa, Diane; Bodelon, Clara; Poitras, Nancy; Lorey, Thomas; Kinney, Walter

2015-12-01

Human papillomavirus (HPV)-based cervical cancer screening requires triage markers to decide who should be referred to colposcopy. p16/Ki-67 dual stain cytology has been proposed as a biomarker for cervical precancers. We evaluated the dual stain in a large population of HPV-positive women. One thousand five hundred and nine HPV-positive women screened with HPV/cytology cotesting at Kaiser Permanente California were enrolled into a prospective observational study in 2012. Dual stain cytology was performed on residual Surepath material, and slides were evaluated for dual stain-positive cells. Disease endpoints were ascertained from the clinical database at KPNC. We evaluated the clinical performance of the assay among all HPV-positive women and among HPV-positive, cytology-negative women. We used internal benchmarks for clinical management to evaluate the clinical relevance of the dual stain assay. We evaluated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the dual stain compared with Pap cytology. All statistical tests were two-sided. The dual stain had lower positivity (45.9%) compared with cytology at an ASC-US threshold (53.4%). For detection of CIN2+, the dual stain had similar sensitivity (83.4% vs 76.6%, P = .1), and statistically higher specificity (58.9% vs 49.6%, P < .001), PPV (21.0% vs 16.6%, P < .001), and NPV (96.4% vs 94.2%, P = .01) compared with cytology. Similar patterns were observed for CIN3+. Women with a positive test had high enough risk for referral to colposcopy, while the risk for women with negative tests was below a one-year return threshold based on current US management guidelines. Dual stain cytology showed good risk stratification for all HPV-positive women and for HPV-positive women with normal cytology. Additional follow-up is needed to determine how long dual stain negative women remain at low risk of precancer. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Neurosensory findings among electricians with self-reported remaining symptoms after an electrical injury: A case series.

PubMed

Rådman, Lisa; Gunnarsson, Lars-Gunnar; Nilsagård, Ylva; Nilsson, Tohr

2016-12-01

Symptoms described in previous studies indicate that electrical injury can cause longstanding injuries to the neurosensory nerves. The aim of the present case series was to objectively assess the profile of neurosensory dysfunction in electricians in relation to high voltage or low voltage electrical injury and the "no-let-go phenomenon". Twenty-three Swedish male electricians exposed to electrical injury were studied by using a battery of clinical instruments, including quantitative sensory testing (QST). The clinical test followed a predetermined order of assessments: thermal perceptions thresholds, vibration perception thresholds, tactile gnosis (the Shape and Texture Identification test), manual dexterity (Purdue Pegboard Test), and grip strength. In addition, pain was studied by means of a questionnaire, and a colour chart was used for estimation of white fingers. The main findings in the present case series were reduced thermal perceptions thresholds, where half of the group showed abnormal values for warm thermal perception and/or cold thermal perception. Also, the tactile gnosis and manual dexterity were reduced. High voltage injury was associated with more reduced sensibility compared to those with low voltage. Neurosensory injury can be objectively assessed after an electrical injury by using QST with thermal perception thresholds. The findings are consistent with injuries to small nerve fibres. In the clinical setting thermal perception threshold is therefore recommended, in addition to tests of tactile gnosis and manual dexterity (Purdue Pegboard). Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Altered quantitative sensory testing outcome in subjects with opioid therapy.

PubMed

Chen, Lucy; Malarick, Charlene; Seefeld, Lindsey; Wang, Shuxing; Houghton, Mary; Mao, Jianren

2009-05-01

Preclinical studies have suggested that opioid exposure may induce a paradoxical decrease in the nociceptive threshold, commonly referred as opioid-induced hyperalgesia (OIH). While OIH may have implications in acute and chronic pain management, its clinical features remain unclear. Using an office-based quantitative sensory testing (QST) method, we compared pain threshold, pain tolerance, and the degree of temporal summation of the second pain in response to thermal stimulation among three groups of subjects: those with neither pain nor opioid therapy (group 1), with chronic pain but without opioid therapy (group 2), and with both chronic pain and opioid therapy (group 3). We also examined the possible correlation between QST responses to thermal stimulation and opioid dose, opioid treatment duration, opioid analgesic type, pain duration, or gender in group 3 subjects. As compared with both group 1 (n=41) and group 2 (n=41) subjects, group 3 subjects (n=58) displayed a decreased heat pain threshold and exacerbated temporal summation of the second pain to thermal stimulation. In contrast, there were no differences in cold or warm sensation among three groups. Among clinical factors, daily opioid dose consistently correlated with the decreased heat pain threshold and exacerbated temporal summation of the second pain in group 3 subjects. These results indicate that decreased heat pain threshold and exacerbated temporal summation of the second pain may be characteristic QST changes in subjects with opioid therapy. The data suggest that QST may be a useful tool in the clinical assessment of OIH.

Vitamin D and solar ultraviolet radiation in the risk and treatment of tuberculosis.

PubMed

Ralph, Anna P; Ralph, Anna R; Lucas, Robyn M; Norval, Mary

2013-01-01

Improved understanding of the association between tuberculosis and vitamin D is needed to inform clinical practice. Vitamin D has both immunostimulatory and immunosuppressive effects relevant to human antimycobacterial responses. Ultraviolet radiation, the main source of vitamin D, also induces immunomodulation and could affect the relation between vitamin D and tuberculosis. Clinical trials of vitamin D supplementation in patients with tuberculosis have produced largely negative results, prompting the review of dosing regimens-an explanation for low 25-hydroxyvitamin D status in patients with active tuberculosis is also needed. The reporting of vitamin D deficiency needs to address assay inaccuracies, rising thresholds to define sufficiency, and scarce knowledge of the concentrations needed for optimum immune responses. Future research to measure the effect of the inflammatory setting on serum concentrations of 25-hydroxyvitamin D, at tuberculosis diagnosis and during recovery, could help to account for 25-hydroxyvitamin D changes in these concentrations in patients with tuberculosis. Studies into the role of vitamin D supplementation in latent tuberculosis justify clinical trials in this population, but pose methodological challenges. Vitamin D trials in patients with active tuberculosis should be done in well selected populations using adequate vitamin D doses, although such doses remain undefined. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mixed states in bipolar disorder - changes in DSM-5 and current treatment recommendations.

PubMed

Betzler, Felix; Stöver, Laura Apollonia; Sterzer, Philipp; Köhler, Stephan

2017-11-01

Mixed states in affective disorders represent a particular challenge in clinical routine, characterized by a complicated course of treatment and a worse treatment response. Clinical features of mixed states and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria are presented and critical discussed. We then performed a systematic review using the terms 'bipolar', 'mixed' and 'randomized' to evaluate current treatment options. For pharmacological treatment of mixed states in total, there is still insufficient data from RCTs. However, there is some evidence for efficacy in mixed states from RCTs for atypical antipsychotics, especially olanzapine, aripiprazole and asenapine as well as mood stabilizers as valproate and carbamazepine. Mixed states are of a high clinical relevance and the DSM-5 criteria substantially reduced the diagnostic threshold. Besides advantages of a better characterization of patients with former DSM-IV-defined mixed episodes, disadvantages arise for example differential diagnoses with a substantial overlap in symptoms such as borderline personality disorders. Atypical antipsychotics, valproate and carbamazepine demonstrated efficacy in a limited sample of RCTs. The number of RCTs in the treatment of mixed states is highly limited. Furthermore, nearly all studies were funded by pharmaceutical companies which may lead to an underestimation of classical mood stabilizers such as lithium.

Primary and persistent negative symptoms: Concepts, assessments and neurobiological bases.

PubMed

Mucci, Armida; Merlotti, Eleonora; Üçok, Alp; Aleman, André; Galderisi, Silvana

2017-08-01

Primary and persistent negative symptoms (PPNS) represent an unmet need in the care of people with schizophrenia. They have an unfavourable impact on real-life functioning and do not respond to available treatments. Underlying etiopathogenetic mechanisms of PPNS are still unknown. The presence of primary and enduring negative symptoms characterizes deficit schizophrenia (DS), proposed as a separate disease entity with respect to non-deficit schizophrenia (NDS). More recently, to reduce the heterogeneity of negative symptoms by using criteria easily applicable in the context of clinical trials, the concept of persistent negative symptoms (PNS) was developed. Both PNS and DS constructs include enduring negative symptoms (at least 6months for PNS and 12months for DS) that do not respond to available treatments. PNS exclude secondary negative symptoms based on a cross-sectional evaluation of severity thresholds on commonly used rating scales for positive symptoms, depression and extrapyramidal side effects; the DS diagnosis, instead, excludes all potential sources of secondary negative symptoms based on a clinical longitudinal assessment. In this paper we review the evolution of concepts and assessment modalities relevant to PPNS, data on prevalence of DS and PNS, as well as studies on clinical, neuropsychological, brain imaging electrophysiological and psychosocial functioning aspects of DS and PNS. Copyright © 2016 Elsevier B.V. All rights reserved.

A Bottom-up Vulnerability Analysis of Water Systems with Decentralized Decision Making and Demographic Shifts- the Case of Jordan.

NASA Astrophysics Data System (ADS)

Lachaut, T.; Yoon, J.; Klassert, C. J. A.; Talozi, S.; Mustafa, D.; Knox, S.; Selby, P. D.; Haddad, Y.; Gorelick, S.; Tilmant, A.

2016-12-01

Probabilistic approaches to uncertainty in water systems management can face challenges of several types: non stationary climate, sudden shocks such as conflict-driven migrations, or the internal complexity and dynamics of large systems. There has been a rising trend in the development of bottom-up methods that place focus on the decision side instead of probability distributions and climate scenarios. These approaches are based on defining acceptability thresholds for the decision makers and considering the entire range of possibilities over which such thresholds are crossed. We aim at improving the knowledge on the applicability and relevance of this approach by enlarging its scope beyond climate uncertainty and single decision makers; thus including demographic shifts, internal system dynamics, and multiple stakeholders at different scales. This vulnerability analysis is part of the Jordan Water Project and makes use of an ambitious multi-agent model developed by its teams with the extensive cooperation of the Ministry of Water and Irrigation of Jordan. The case of Jordan is a relevant example for migration spikes, rapid social changes, resource depletion and climate change impacts. The multi-agent modeling framework used provides a consistent structure to assess the vulnerability of complex water resources systems with distributed acceptability thresholds and stakeholder interaction. A proof of concept and preliminary results are presented for a non-probabilistic vulnerability analysis that involves different types of stakeholders, uncertainties other than climatic and the integration of threshold-based indicators. For each stakeholder (agent) a vulnerability matrix is constructed over a multi-dimensional domain, which includes various hydrologic and/or demographic variables.

Selenium bioaccumulation in fish exposed to coal ash at the Tennessee Valley Authority Kingston spill site.

PubMed

Mathews, Teresa J; Fortner, Allison M; Jett, R Trent; Morris, Jesse; Gable, Jennifer; Peterson, Mark J; Carriker, Neil

2014-10-01

In December 2008, 4.1 million cubic meters of coal ash were released into the Emory and Clinch Rivers by the Tennessee Valley Authority Kingston Fossil Plant. Coal ash contains several contaminants, including the bioaccumulative metalloid selenium (Se). Because Se is predominantly accumulated in aquatic organisms through dietary rather than aqueous exposure, tissue-based toxicity thresholds for Se are currently being considered. The proposed threshold concentrations range between 4 μg/g and 9 μg/g Se (dry wt.) in whole body fish, with a proposed fillet threshold of 11.8 μg/g. In the present study, the authors examined the spatial and temporal trends in Se bioaccumulation and examined the relationship between the Se content in fillets and in whole bodies of fish collected around the Kingston spill site to determine whether Se bioaccumulation was a significant concern at the ash spill site. Whereas Se concentrations in fish (whole bodies and fillets) were elevated at sampling locations affected by the Kingston ash spill relative to reference locations, concentrations do not appear to be above risk thresholds and have not been increasing over the 5-yr period since the spill. These findings are not only relevant to guiding the human health and ecological risk assessments at the Kingston ash spill site, but because of current national discussions on appropriate guidelines for Se in fish as well for the disposal of coal combustion wastes, the results are also relevant to the general understanding of Se bioaccumulation in contaminated water bodies. © 2014 SETAC.

Relationship between selenium body burdens and tissue concentrations in fish exposed to coal ash at the Tennessee Valley Authority Kingston spill site

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

Mathews, Teresa J; Fortner, Allison M; Jett, Robert T

2014-01-01

In December 2008, 4.1 million m3 of coal ash were released into the Emory and Clinch Rivers by the Tennessee Valley Authority (TVA) Kingston Fossil Plant. Coal ash contains several contaminants, including the bioaccumulative metalloid selenium (Se). Because Se is predominantly accumulated in aquatic organisms through dietary, rather than aqueous exposure, tissue-based toxicity thresholds for Se are currently being considered. The proposed threshold concentrations range between 4-9 g/g Se (dry wt.) in whole body fish, with a proposed fillet threshold of 11.8 g/g. In the present study we examined the spatial and temporal trends in Se bioaccumulation and examined themore » relationship between the Se content in fillets and in whole bodies of fish collected around the Kingston spill site to determine whether Se bioaccumulation was a significant concern at the ash spill site. While Se concentrations in fish (whole bodies and fillets) were elevated at sampling locations affected by the Kingston ash spill relative to reference locations, concentrations do not appear to be above risk thresholds and have not been increasing over the five year period since the spill. Our results are not only relevant to guiding the human health and ecological risk assessments at the Kingston ash spill site, but because of current national discussions on appropriate guidelines for Se in fish as well for the disposal of coal combustion wastes, our results are also relevant to the general understanding of Se bioaccumulation in contaminated water bodies.« less

Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

PubMed

Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

2014-08-01

Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased threshold change in threshold electrotonus in both hyperpolarizing and depolarizing directions [depolarizing threshold electrotonus (90-100 ms) P < 0.005, hyperpolarizing threshold electrotonus (10-20 ms), P < 0.01, hyperpolarizing threshold electrotonus (90-100 ms), P < 0.05], perhaps suggesting early hyperpolarization. In addition, using excitability parameters superexcitability, subexcitability and hyperpolarizing threshold electrotonus (10-20 ms), the patients with acute inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to differentiate acute from acute-onset chronic inflammatory demyelinating polyneuropathy at an early stage. Characteristic nerve excitability parameter changes occur in early acute-onset chronic inflammatory demyelinating polyneuropathy, to match the clinical phenotype. Importantly, this pattern of change was strikingly different to that shown by patients with acute inflammatory demyelinating polyneuropathy, suggesting that nerve excitability techniques may be useful in distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy at the initial stage. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Relationship between loss of echogenicity and cavitation emissions from echogenic liposomes insonified by spectral Doppler ultrasound

NASA Astrophysics Data System (ADS)

Radhakrishnan, Kirthi

Cardiovascular disease is the leading cause of death and disability in the United States and worldwide. Echogenic liposomes (ELIP) are theragonistic ultrasound contrast agents (UCAs) being developed for the early detection and treatment of cardiovascular disease. Stability of the echogenicity of ELIP in physiologic conditions is crucial to their successful translation to clinical use. The stability of ELIP echogenicity was determined in vitro under physiologic conditions of total dissolved gas concentration, temperature, and hydrodynamic pressure in porcine plasma and whole blood. Ultrasound contrast agents (UCAs) have the potential to nucleate cavitation and promote both beneficial and deleterious bioeffects in vivo. Previous studies have elucidated the pressure amplitude threshold for rapid loss of echogenicity due to UCA fragmentation as a function of pulse duration and pulse repetition frequency (PRF). Previous studies have also demonstrated that UCA fragmentation was concomitant with inertial cavitation. The purpose of this study was to evaluate the relationship between stable and inertial cavitation thresholds and loss of echogenicity of ELIP as a function of pulse duration and pulse repetition frequency. Determining the relationship between cavitation thresholds and loss of echogenicity of ELIP would enable monitoring of cavitation based upon the on-screen echogenicity in clinical applications. ELIP were insonified by a clinical ultrasound scanner in duplex spectral Doppler mode at four pulse durations and four PRFs in a static fluid and in a flow system. Cavitation emissions from the UCAs insonified by Doppler pulses were recorded using a single-element passive cavitation detection (PCD) system and a passive cavitation imaging (PCI) system. Stable and inertial cavitation thresholds were ascertained. Loss of echogenicity from ELIP was assessed within regions of interest on B-mode images. Stable cavitation thresholds were found to be lower than inertial cavitation thresholds. Stable and inertial cavitation thresholds of ELIP were found to have a weak dependence on pulse duration. However, the stable cavitation threshold of ELIP had no dependence on PRF. The inertial cavitation threshold of ELIP had a weak dependence on PRF. Cavitation thresholds ascertained using a PCI agreed with the thresholds ascertained using a single-element PCD. The azimuthal beamwidth of the cavitation emissions detected by the PCI system agreed with the calibrated beamwidth of the insonation Doppler pressure exceeding the cavitation threshold. The power of cavitation emissions was an exponential function of the loss of echogenicity over the investigated range of acoustic pressures. ELIP lost more than 80% echogenicity before the onset of stable or inertial cavitation. Once this level of echogenicity loss occurred, both stable and inertial cavitation emissions were detected in the physiologic flow phantom. These results indicate that 80% loss of echogenicity may be used as a qualitative metric to gauge the onset of stable and inertial cavitation from ELIP.

Analytic Results for e+e- --> tt-bar and gammagamma --> tt-bar Observables near the Threshold up to the Next-to-Next-to-Leading Order of NRQCD

NASA Astrophysics Data System (ADS)

Penin, A. A.; Pivovarov, A. A.

2001-02-01

We present an analytical description of top-antitop pair production near the threshold in $e^+e^-$ annihilation and $\\g\\g$ collisions. A set of basic observables considered includes the total cross sections, forward-backward asymmetry and top quark polarization. The threshold effects relevant for the basic observables are described by three universal functions related to S wave production, P wave production and S-P interference. These functions are computed analytically up to the next-to-next-to-leading order of NRQCD. The total $e^+e^-\\to t\\bar t$ cross section near the threshold is obtained in the next-to-next-to-leading order in the closed form including the contribution due to the axial coupling of top quark and mediated by the Z-boson. The effects of the running of the strong coupling constant and of the finite top quark width are taken into account analytically for the P wave production and S-P wave interference.

Pollutant threshold concentration determination in marine ecosystems using an ecological interaction endpoint.

PubMed

Wang, Changyou; Liang, Shengkang; Guo, Wenting; Yu, Hua; Xing, Wenhui

2015-09-01

The threshold concentrations of pollutants are determined by extrapolating single-species effect data to community-level effects. This assumes the most sensitive endpoint of the life cycle of individuals and the species sensitivity distribution from single-species toxic effect tests, thus, ignoring the ecological interactions. The uncertainties due to this extrapolation can be partially overcome using the equilibrium point of a customized ecosystem. This method incorporates ecological interactions and integrates the effects on growth, survival, and ingestion into a single effect measure, the equilibrium point excursion in the customized ecosystem, in order to describe the toxic effects on plankton. A case study showed that the threshold concentration of copper calculated with the endpoint of the equilibrium point was 10 μg L(-1), which is significantly different from the threshold calculated with a single-species endpoint. The endpoint calculated using this method provides a more relevant measure of the ecological impact than any single individual-level endpoint. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optical potential approach to the electron-atom impact ionization threshold problem

NASA Technical Reports Server (NTRS)

Temkin, A.; Hahn, Y.

1973-01-01

The problem of the threshold law for electron-atom impact ionization is reconsidered as an extrapolation of inelastic cross sections through the ionization threshold. The cross sections are evaluated from a distorted wave matrix element, the final state of which describes the scattering from the Nth excited state of the target atom. The actual calculation is carried for the e-H system, and a model is introduced which is shown to preserve the essential properties of the problem while at the same time reducing the dimensionability of the Schrodinger equation. Nevertheless, the scattering equation is still very complex. It is dominated by the optical potential which is expanded in terms of eigen-spectrum of QHQ. It is shown by actual calculation that the lower eigenvalues of this spectrum descend below the relevant inelastic thresholds; it follows rigorously that the optical potential contains repulsive terms. Analytical solutions of the final state wave function are obtained with several approximations of the optical potential.

Pitfalls in interpretation of CT-values of RT-PCR in children with acute respiratory tract infections.

PubMed

Wishaupt, Jérôme O; Ploeg, Tjeerd van der; Smeets, Leo C; Groot, Ronald de; Versteegh, Florens G A; Hartwig, Nico G

2017-05-01

The relation between viral load and disease severity in childhood acute respiratory tract infections (ARI) is not fully understood. To assess the clinical relevance of the relation between viral load, determined by cycle threshold (CT) value of real-time reverse transcription-polymerase chain reaction assays and disease severity in children with single- and multiple viral ARI. 582 children with ARI were prospectively followed and tested for 15 viruses. Correlations were calculated between CT values and clinical parameters. In single viral ARI, statistically significant correlations were found between viral loads of Respiratory Syncytial Virus (RSV) and hospitalization and between viral loads of Human Coronavirus (HCoV) and a disease severity score. In multiple-viral ARI, statistically significant correlations between viral load and clinical parameters were found. In RSV-Rhinovirus (RV) multiple infections, a low viral load of RV was correlated with a high length of hospital stay and a high duration of extra oxygen use. The mean CT value for RV, HCoV and Parainfluenza virus was significantly lower in single- versus multiple infections. Although correlations between CT values and clinical parameters in patients with single and multiple viral infection were found, the clinical importance of these findings is limited because individual differences in host-, viral and laboratory factors complicate the interpretation of statistically significant findings. In multiple infections, viral load cannot be used to differentiate between disease causing virus and innocent bystanders. Copyright © 2017 Elsevier B.V. All rights reserved.

The Incremental Value of Subjective and Quantitative Assessment of 18F-FDG PET for the Prediction of Pathologic Complete Response to Preoperative Chemoradiotherapy in Esophageal Cancer.

PubMed

van Rossum, Peter S N; Fried, David V; Zhang, Lifei; Hofstetter, Wayne L; van Vulpen, Marco; Meijer, Gert J; Court, Laurence E; Lin, Steven H

2016-05-01

A reliable prediction of a pathologic complete response (pathCR) to chemoradiotherapy before surgery for esophageal cancer would enable investigators to study the feasibility and outcome of an organ-preserving strategy after chemoradiotherapy. So far no clinical parameters or diagnostic studies are able to accurately predict which patients will achieve a pathCR. The aim of this study was to determine whether subjective and quantitative assessment of baseline and postchemoradiation (18)F-FDG PET can improve the accuracy of predicting pathCR to preoperative chemoradiotherapy in esophageal cancer beyond clinical predictors. This retrospective study was approved by the institutional review board, and the need for written informed consent was waived. Clinical parameters along with subjective and quantitative parameters from baseline and postchemoradiation (18)F-FDG PET were derived from 217 esophageal adenocarcinoma patients who underwent chemoradiotherapy followed by surgery. The associations between these parameters and pathCR were studied in univariable and multivariable logistic regression analysis. Four prediction models were constructed and internally validated using bootstrapping to study the incremental predictive values of subjective assessment of (18)F-FDG PET, conventional quantitative metabolic features, and comprehensive (18)F-FDG PET texture/geometry features, respectively. The clinical benefit of (18)F-FDG PET was determined using decision-curve analysis. A pathCR was found in 59 (27%) patients. A clinical prediction model (corrected c-index, 0.67) was improved by adding (18)F-FDG PET-based subjective assessment of response (corrected c-index, 0.72). This latter model was slightly improved by the addition of 1 conventional quantitative metabolic feature only (i.e., postchemoradiation total lesion glycolysis; corrected c-index, 0.73), and even more by subsequently adding 4 comprehensive (18)F-FDG PET texture/geometry features (corrected c-index, 0.77). However, at a decision threshold of 0.9 or higher, representing a clinically relevant predictive value for pathCR at which one may be willing to omit surgery, there was no clear incremental value. Subjective and quantitative assessment of (18)F-FDG PET provides statistical incremental value for predicting pathCR after preoperative chemoradiotherapy in esophageal cancer. However, the discriminatory improvement beyond clinical predictors does not translate into a clinically relevant benefit that could change decision making. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Dynamics of infant cortical auditory evoked potentials (CAEPs) for tone and speech tokens.

PubMed

Cone, Barbara; Whitaker, Richard

2013-07-01

Cortical auditory evoked potentials (CAEPs) to tones and speech sounds were obtained in infants to: (1) further knowledge of auditory development above the level of the brainstem during the first year of life; (2) establish CAEP input-output functions for tonal and speech stimuli as a function of stimulus level and (3) elaborate the data-base that establishes CAEP in infants tested while awake using clinically relevant stimuli, thus providing methodology that would have translation to pediatric audiological assessment. Hypotheses concerning CAEP development were that the latency and amplitude input-output functions would reflect immaturity in encoding stimulus level. In a second experiment, infants were tested with the same stimuli used to evoke the CAEPs. Thresholds for these stimuli were determined using observer-based psychophysical techniques. The hypothesis was that the behavioral thresholds would be correlated with CAEP input-output functions because of shared cortical response areas known to be active in sound detection. 36 infants, between the ages of 4 and 12 months (mean=8 months, s.d.=1.8 months) and 9 young adults (mean age 21 years) with normal hearing were tested. First, CAEPs amplitude and latency input-output functions were obtained for 4 tone bursts and 7 speech tokens. The tone bursts stimuli were 50 ms tokens of pure tones at 0.5, 1.0, 2.0 and 4.0 kHz. The speech sound tokens, /a/, /i/, /o/, /u/, /m/, /s/, and /∫/, were created from natural speech samples and were also 50 ms in duration. CAEPs were obtained for tone burst and speech token stimuli at 10 dB level decrements in descending order from 70 dB SPL. All CAEP tests were completed while the infants were awake and engaged in quiet play. For the second experiment, observer-based psychophysical methods were used to establish perceptual threshold for the same speech sound and tone tokens. Infant CAEP component latencies were prolonged by 100-150 ms in comparison to adults. CAEP latency-intensity input output functions were steeper in infants compared to adults. CAEP amplitude growth functions with respect to stimulus SPL are adult-like at this age, particularly for the earliest component, P1-N1. Infant perceptual thresholds were elevated with respect to those found in adults. Furthermore, perceptual thresholds were higher, on average, than levels at which CAEPs could be obtained. When CAEP amplitudes were plotted with respect to perceptual threshold (dB SL), the infant CAEP amplitude growth slopes were steeper than in adults. Although CAEP latencies indicate immaturity in neural transmission at the level of the cortex, amplitude growth with respect to stimulus SPL is adult-like at this age, particularly for the earliest component, P1-N1. The latency and amplitude input-output functions may provide additional information as to how infants perceive stimulus level. The reasons for the discrepancy between electrophysiologic and perceptual threshold may be due to immaturity in perceptual temporal resolution abilities and the broad-band listening strategy employed by infants. The findings from the current study can be translated to the clinical setting. It is possible to use tonal or speech sound tokens to evoke CAEPs in an awake, passively alert infant, and thus determine whether these sounds activate the auditory cortex. This could be beneficial in the verification of hearing aid or cochlear implant benefit. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Flagging threshold optimization for manual blood smear review in primary care laboratory.

PubMed

Bihl, Pierre-Adrien

2018-04-01

Manual blood smear review is required when an anomaly detected by the automated hematologic analyzer triggers a flag. Our will through this study is to optimize these flagging thresholds for manual slide review in order to limit workload, while insuring clinical care through no extra false-negative. Flagging causes of 4,373 samples were investigated by manual slide review, after having been run on ADVIA 2120i. A set of 6 user-adjustments is proposed. By implementing all recommendations that we made, false-positive rate falls from 81.8% to 58.6%, while PPV increases from 18.2% to 23.7%. Hence, use of such optimized thresholds enables us to maximize efficiency without altering clinical care, but each laboratory should establish its own criteria to take into consideration local distinctive features.

Manual vs. automatic capture management in implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators.

PubMed

Murgatroyd, Francis D; Helmling, Erhard; Lemke, Bernd; Eber, Bernd; Mewis, Christian; van der Meer-Hensgens, Judith; Chang, Yanping; Khalameizer, Vladimir; Katz, Amos

2010-06-01

The Secura ICD and Consulta CRT-D are the first defibrillators to have automatic right atrial (RA), right ventricular (RV), and left ventricular (LV) capture management (CM). Complete CM was evaluated in an implantable cardioverter defibrillator (ICD) population. Two prospective clinical studies were conducted in 28 centres in Europe and Israel. Automatic CM data were compared with manual threshold measurements, the CM applicability was determined, and adjustments to pacing outputs were analysed. In total, 160 patients [age 64.6 +/- 10.4 years, 77% male, 80 ICD and 80 cardiac resynchronization therapy defibrillator (CRT-D)] were included. The differences between automatic and manual measurements were 2.5 V) due to raised RA threshold in seven (4.4%), high RV threshold in nine (5.6%), and high LV threshold in three patients (3.8%). All high threshold detections and all automatic modulations of pacing output were adjudicated appropriate. Complete CM adjusts pacing output appropriately, permitting a reduction in office visits while it may maximize device longevity. The study was registered at ClinicalTrials.gov identifiers: NCT00526227 and NCT00526162.

A comparison of the ability of a 4:1 ketogenic diet and a 6.3:1 ketogenic diet to elevate seizure thresholds in adult and young rats.

PubMed

Nylen, Kirk; Likhodii, Sergei; Abdelmalik, Peter A; Clarke, Jasper; Burnham, W McIntyre

2005-08-01

The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically. Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and beta-hydroxybutyrate (beta-OHB) levels were measured. Neither KD elevated absolute "latencies to seizure" in young or adult rats. Similarly, neither KD elevated "threshold doses" in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats. "Threshold doses" and "latency to seizure" data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.

Cortical and Sensory Causes of Individual Differences in Selective Attention Ability Among Listeners With Normal Hearing Thresholds

PubMed Central

2017-01-01

Purpose This review provides clinicians with an overview of recent findings relevant to understanding why listeners with normal hearing thresholds (NHTs) sometimes suffer from communication difficulties in noisy settings. Method The results from neuroscience and psychoacoustics are reviewed. Results In noisy settings, listeners focus their attention by engaging cortical brain networks to suppress unimportant sounds; they then can analyze and understand an important sound, such as speech, amidst competing sounds. Differences in the efficacy of top-down control of attention can affect communication abilities. In addition, subclinical deficits in sensory fidelity can disrupt the ability to perceptually segregate sound sources, interfering with selective attention, even in listeners with NHTs. Studies of variability in control of attention and in sensory coding fidelity may help to isolate and identify some of the causes of communication disorders in individuals presenting at the clinic with “normal hearing.” Conclusions How well an individual with NHTs can understand speech amidst competing sounds depends not only on the sound being audible but also on the integrity of cortical control networks and the fidelity of the representation of suprathreshold sound. Understanding the root cause of difficulties experienced by listeners with NHTs ultimately can lead to new, targeted interventions that address specific deficits affecting communication in noise. Presentation Video http://cred.pubs.asha.org/article.aspx?articleid=2601617 PMID:29049598

Longitudinal risk factors for suicidal thoughts in depressed and non-depressed young adolescents.

PubMed

Pan, Yi-Ju; Juang, Kai-Dih; Lu, Shiang-Ru; Chen, Shih-Pin; Wang, Yen-Feng; Fuh, Jong-Ling; Wang, Shuu-Jiun

2017-09-01

Evidence regarding the role of risk factors in the longitudinal course of suicidal ideation among young adolescents is lacking. We aimed to assess the effects of a range of risk factors, including obesity, academic performance, child-parent relationship, physical maltreatment, and depressive symptoms, on the development of suicidal ideation in young adolescents. A school cohort of seventh and eighth graders was followed for 1 year and differences in the risk factors distributions were examined between depressed and non-depressed adolescents. We further examined risk factors for newly developed suicidal ideation and persistent suicidal ideation in the groups of adolescents based on the presence of suicidal ideation at baseline. A total of 1710 young adolescents were recruited, among whom 8.2% were categorised as having clinically significant depression. For depressed adolescents, being obese was associated with a three-fold increased risk of having suicidal ideation. For non-depressed adolescents, physical maltreatment, a feeling of not being cared about and sub-threshold depressive symptoms were the risk factors. The latter two remained robust in predicting newly developed suicidal ideation. The current study may shed light on the differential strategies to address suicidal thoughts in depressed and non-depressed adolescents. We emphasise the importance of recognition and management of sub-threshold depressive symptoms and the relevance of obesity, physical maltreatment and a feeling of not being cared about to suicide prevention programmes in early adolescence.

Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation.

PubMed

Hellmuth, Joanna; Colby, Donn; Valcour, Victor; Suttichom, Duanghathai; Spudich, Serena; Ananworanich, Jintanat; Prueksakaew, Peeriya; Sailasuta, Napapon; Allen, Isabel; Jagodzinski, Linda L; Slike, Bonnie; Ochi, Derek; Paul, Robert

2017-11-01

This observational study of 123 Thai participants sought to determine the rate and severity of affective symptoms during acute HIV infection (AHI) and possible associations to disease mechanisms. At diagnosis, just prior to starting combination antiretroviral therapy (cART), AHI participants completed assessments of depression and anxiety symptoms that were repeated at 4, 12, and 24 weeks. Blood markers of HIV infection and immune activation were measured at study entry, with optional cerebrospinal fluid measures. A high frequency of participants reported symptoms that exceeded published thresholds supportive of depression (55.0%) and anxiety (65.8%) at diagnosis, with significant reductions after starting cART. Meeting a threshold for clinically relevant depressive symptoms at study entry was associated with higher baseline plasma HIV RNA (5.98 vs. 5.50, t = 2.46, p = 0.015), lower CD4 counts (328 vs. 436 cells/mm 3 , t = 3.46, p = 0.001), and higher plasma neopterin, a marker of macrophage activation (2694 vs. 1730 pg/mL, Mann-Whitney U = 152.5, p = 0.011). Controlling for plasma HIV RNA and CD4 count, higher baseline plasma neopterin correlated with worse initial depression and anxiety scores. Depression and anxiety symptoms are frequent in acute HIV infection, associate with plasma immune activation, and can improve concurrent with cART.

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

Liu, Jianfei; Wang, Shijun; Turkbey, Evrim B.

Purpose: Renal calculi are common extracolonic incidental findings on computed tomographic colonography (CTC). This work aims to develop a fully automated computer-aided diagnosis system to accurately detect renal calculi on CTC images. Methods: The authors developed a total variation (TV) flow method to reduce image noise within the kidneys while maintaining the characteristic appearance of renal calculi. Maximally stable extremal region (MSER) features were then calculated to robustly identify calculi candidates. Finally, the authors computed texture and shape features that were imported to support vector machines for calculus classification. The method was validated on a dataset of 192 patients andmore » compared to a baseline approach that detects calculi by thresholding. The authors also compared their method with the detection approaches using anisotropic diffusion and nonsmoothing. Results: At a false positive rate of 8 per patient, the sensitivities of the new method and the baseline thresholding approach were 69% and 35% (p < 1e − 3) on all calculi from 1 to 433 mm{sup 3} in the testing dataset. The sensitivities of the detection methods using anisotropic diffusion and nonsmoothing were 36% and 0%, respectively. The sensitivity of the new method increased to 90% if only larger and more clinically relevant calculi were considered. Conclusions: Experimental results demonstrated that TV-flow and MSER features are efficient means to robustly and accurately detect renal calculi on low-dose, high noise CTC images. Thus, the proposed method can potentially improve diagnosis.« less

Healthcare professionals' agreement on clinical relevance of drug-related problems among elderly patients.

PubMed

Bech, Christine Flagstad; Frederiksen, Tine; Villesen, Christine Tilsted; Højsted, Jette; Nielsen, Per Rotbøll; Kjeldsen, Lene Juel; Nørgaard, Lotte Stig; Christrup, Lona Louring

2018-02-01

Background Disagreement among healthcare professionals on the clinical relevance of drug-related problems can lead to suboptimal treatment and increased healthcare costs. Elderly patients with chronic non-cancer pain and comorbidity are at increased risk of drug related problems compared to other patient groups due to complex medication regimes and transition of care. Objective To investigate the agreement among healthcare professionals on their classification of clinical relevance of drug-related problems in elderly patients with chronic non-cancer pain and comorbidity. Setting Multidisciplinary Pain Centre, Rigshospitalet, Copenhagen, Denmark. Method A pharmacist performed medication review on elderly patients with chronic non-cancer pain and comorbidity, identified their drug-related problems and classified these problems in accordance with an existing categorization system. A five-member clinical panel rated the drug-related problems' clinical relevance in accordance with a five-level rating scale, and their agreement was compared using Fleiss' κ. Main outcome measure Healthcare professionals' agreement on clinical relevance of drug related problems, using Fleiss' κ. Results Thirty patients were included in the study. A total of 162 drug related problems were identified, out of which 54% were of lower clinical relevance (level 0-2) and 46% of higher clinical relevance (level 3-4). Only slight agreement (κ = 0.12) was found between the panellists' classifications of clinical relevance using a five-level rating scale. Conclusion The clinical pharmacist identified drug related problems of lower and higher clinical relevance. Poor overall agreement on the severity of the drug related problems was found among the panelists.

Threshold and Jet Radius Joint Resummation for Single-Inclusive Jet Production

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

Liu, Xiaohui; Moch, Sven -Olaf; Ringer, Felix

Here, we present the first threshold and jet radius jointly resummed cross section for single-inclusive hadronic jet production. We work at next-to-leading logarithmic accuracy and our framework allows for a systematic extension beyond the currently achieved precision. Long-standing numerical issues are overcome by performing the resummation directly in momentum space within soft collinear effective theory. We present the first numerical results for the LHC and observe an improved description of the available data. Our results are of immediate relevance for LHC precision phenomenology including the extraction of parton distribution functions and the QCD strong coupling constant.

Measurement of the reaction 2H(e,e') at 180 degrees close to the deuteron breakup threshold.

PubMed

Ryezayeva, N; Arenhövel, H; Burda, O; Byelikov, A; Chernykh, M; Enders, J; Griesshammer, H W; Kalmykov, Y; von Neumann-Cosel, P; Ozel, B; Poltoratska, I; Pysmenetska, I; Rangacharyulu, C; Rathi, S; Richter, A; Schrieder, G; Shevchenko, A; Yevetska, O

2008-05-02

Inclusive inelastic electron scattering off the deuteron under 180 degrees has been studied at the S-DALINAC close to the breakup threshold at momentum transfers q=0.27 fm;{-1} and 0.74 fm;{-1} with good energy resolution sufficient to map in detail the spin flip M1 response, which governs the starting reaction pn-->dgamma of big-bang nucleosynthesis over most of the relevant temperature region. Results from potential model calculations and (for q=0.27 fm;{-1}) from pionless nuclear effective field theory are in excellent agreement with the data.

High-Pressure Oxygen Test Evaluations

NASA Technical Reports Server (NTRS)

Schwinghamer, R. J.; Key, C. F.

1974-01-01

The relevance of impact sensitivity testing to the development of the space shuttle main engine is discussed in the light of the special requirements for the engine. The background and history of the evolution of liquid and gaseous oxygen testing techniques and philosophy is discussed also. The parameters critical to reliable testing are treated in considerable detail, and test apparatus and procedures are described and discussed. Materials threshold sensitivity determination procedures are considered and a decision logic diagram for sensitivity threshold determination was plotted. Finally, high-pressure materials sensitivity test data are given for selected metallic and nonmetallic materials.

Threshold and Jet Radius Joint Resummation for Single-Inclusive Jet Production

DOE PAGES

Liu, Xiaohui; Moch, Sven -Olaf; Ringer, Felix

2017-11-20

Here, we present the first threshold and jet radius jointly resummed cross section for single-inclusive hadronic jet production. We work at next-to-leading logarithmic accuracy and our framework allows for a systematic extension beyond the currently achieved precision. Long-standing numerical issues are overcome by performing the resummation directly in momentum space within soft collinear effective theory. We present the first numerical results for the LHC and observe an improved description of the available data. Our results are of immediate relevance for LHC precision phenomenology including the extraction of parton distribution functions and the QCD strong coupling constant.

Approaches for estimating minimal clinically important differences in systemic lupus erythematosus.

PubMed

Rai, Sharan K; Yazdany, Jinoos; Fortin, Paul R; Aviña-Zubieta, J Antonio

2015-06-03

A minimal clinically important difference (MCID) is an important concept used to determine whether a medical intervention improves perceived outcomes in patients. Prior to the introduction of the concept in 1989, studies focused primarily on statistical significance. As most recent clinical trials in systemic lupus erythematosus (SLE) have failed to show significant effects, determining a clinically relevant threshold for outcome scores (that is, the MCID) of existing instruments may be critical for conducting and interpreting meaningful clinical trials as well as for facilitating the establishment of treatment recommendations for patients. To that effect, methods to determine the MCID can be divided into two well-defined categories: distribution-based and anchor-based approaches. Distribution-based approaches are based on statistical characteristics of the obtained samples. There are various methods within the distribution-based approach, including the standard error of measurement, the standard deviation, the effect size, the minimal detectable change, the reliable change index, and the standardized response mean. Anchor-based approaches compare the change in a patient-reported outcome to a second, external measure of change (that is, one that is more clearly understood, such as a global assessment), which serves as the anchor. Finally, the Delphi technique can be applied as an adjunct to defining a clinically important difference. Despite an abundance of methods reported in the literature, little work in MCID estimation has been done in the context of SLE. As the MCID can help determine the effect of a given therapy on a patient and add meaning to statistical inferences made in clinical research, we believe there ought to be renewed focus on this area. Here, we provide an update on the use of MCIDs in clinical research, review some of the work done in this area in SLE, and propose an agenda for future research.

Pollen derived low molecular compounds enhance the human allergen specific immune response in vivo.

PubMed

Gilles-Stein, S; Beck, I; Chaker, A; Bas, M; McIntyre, M; Cifuentes, L; Petersen, A; Gutermuth, J; Schmidt-Weber, C; Behrendt, H; Traidl-Hoffmann, C

2016-10-01

Besides allergens, pollen release bioactive, low molecular weight compounds that modulate and stimulate allergic reactions. Clinical relevance of these substances has not been investigated to date. To elucidate the effect of a non-allergenic, low molecular weight factors from aqueous birch pollen extracts (Bet-APE < 3 kDa) on the human allergic immune response in vivo. Birch and grass pollen allergic individuals underwent skin prick testing with allergen alone, allergen plus Bet-APE < 3 kDa, or allergen plus pre-identified candidate substances from low molecular pollen fraction. Nasal allergen challenges were performed in non-atopic and pollen allergic individuals using a 3 day repeated threshold challenge battery. Subjects were either exposed to allergen alone or to allergen plus Bet-APE< 3 kDa. Local cytokine levels, nasal secretion weights, nasal congestion and symptom scores were determined. Skin prick test reactions to pollen elicited larger weals when allergens were tested together with the low molecular weight compounds from pollen. Similar results were obtained with candidate pollen-associated lipid mediators. In nasal lining fluids of allergic patients challenged with allergen plus Bet-APE < 3 kDa, IL-8 and IgE was significantly increased as compared to allergen-only challenged patients. These patients also produced increased amounts of total nasal secretion and reported more severe rhinorrhea than the allergen-only challenged group. Low molecular compounds from pollen enhance the allergen specific immune response in the skin and nose. They are therefore of potential clinical relevance in allergic patients. © 2016 John Wiley & Sons Ltd.

Laser patterning of platinum electrodes for safe neurostimulation

NASA Astrophysics Data System (ADS)

Green, R. A.; Matteucci, P. B.; Dodds, C. W. D.; Palmer, J.; Dueck, W. F.; Hassarati, R. T.; Byrnes-Preston, P. J.; Lovell, N. H.; Suaning, G. J.

2014-10-01

Objective. Laser surface modification of platinum (Pt) electrodes was investigated for use in neuroprosthetics. Surface modification was applied to increase the surface area of the electrode and improve its ability to transfer charge within safe electrochemical stimulation limits. Approach. Electrode arrays were laser micromachined to produce Pt electrodes with smooth surfaces, which were then modified with four laser patterning techniques to produce surface structures which were nanosecond patterned, square profile, triangular profile and roughened on the micron scale through structured laser interference patterning (SLIP). Improvements in charge transfer were shown through electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and biphasic stimulation at clinically relevant levels. A new method was investigated and validated which enabled the assessment of in vivo electrochemically safe charge injection limits. Main results. All of the modified surfaces provided electrical advantage over the smooth Pt. The SLIP surface provided the greatest benefit both in vitro and in vivo, and this surface was the only type which had injection limits above the threshold for neural stimulation, at a level shown to produce a response in the feline visual cortex when using an electrode array implanted in the suprachoroidal space of the eye. This surface was found to be stable when stimulated with more than 150 million clinically relevant pulses in physiological saline. Significance. Critical to the assessment of implant devices is accurate determination of safe usage limits in an in vivo environment. Laser patterning, in particular SLIP, is a superior technique for improving the performance of implant electrodes without altering the interfacial electrode chemistry through coating. Future work will require chronic in vivo assessment of these electrode patterns.

Excitable Neurons, Firing Threshold Manifolds and Canards

PubMed Central

2013-01-01

We investigate firing threshold manifolds in a mathematical model of an excitable neuron. The model analyzed investigates the phenomenon of post-inhibitory rebound spiking due to propofol anesthesia and is adapted from McCarthy et al. (SIAM J. Appl. Dyn. Syst. 11(4):1674–1697, [2012]). Propofol modulates the decay time-scale of an inhibitory GABAa synaptic current. Interestingly, this system gives rise to rebound spiking within a specific range of propofol doses. Using techniques from geometric singular perturbation theory, we identify geometric structures, known as canards of folded saddle-type, which form the firing threshold manifolds. We find that the position and orientation of the canard separatrix is propofol dependent. Thus, the speeds of relevant slow synaptic processes are encoded within this geometric structure. We show that this behavior cannot be understood using a static, inhibitory current step protocol, which can provide a single threshold for rebound spiking but cannot explain the observed cessation of spiking for higher propofol doses. We then compare the analyses of dynamic and static synaptic inhibition, showing how the firing threshold manifolds of each relate, and why a current step approach is unable to fully capture the behavior of this model. PMID:23945278

Assessment of Minimum Important Difference and Substantial Clinical Benefit with the Vascular Quality of Life Questionnaire-6 when Evaluating Revascularisation Procedures in Peripheral Arterial Disease.

PubMed

Nordanstig, J; Pettersson, M; Morgan, M; Falkenberg, M; Kumlien, C

2017-09-01

Patient reported outcomes are increasingly used to assess outcomes after peripheral arterial disease (PAD) interventions. VascuQoL-6 (VQ-6) is a PAD specific health-related quality of life (HRQoL) instrument for routine clinical practice and clinical research. This study assessed the minimum important difference for the VQ-6 and determined thresholds for the minimum important difference and substantial clinical benefit following PAD revascularisation. This was a population-based observational cohort study. VQ-6 data from the Swedvasc Registry (January 2014 to September 2016) was analysed for revascularised PAD patients. The minimum important difference was determined using a combination of a distribution based and an anchor-based method, while receiver operating characteristic curve analysis (ROC) was used to determine optimal thresholds for a substantial clinical benefit following revascularisation. A total of 3194 revascularised PAD patients with complete VQ-6 baseline recordings (intermittent claudication (IC) n = 1622 and critical limb ischaemia (CLI) n = 1572) were studied, of which 2996 had complete VQ-6 recordings 30 days and 1092 a year after the vascular intervention. The minimum important difference 1 year after revascularisation for IC patients ranged from 1.7 to 2.2 scale steps, depending on the method of analysis. Among CLI patients, the minimum important difference after 1 year was 1.9 scale steps. ROC analyses demonstrated that the VQ-6 discriminative properties for a substantial clinical benefit was excellent for IC patients (area under curve (AUC) 0.87, sensitivity 0.81, specificity 0.76) and acceptable in CLI (AUC 0.736, sensitivity 0.63, specificity 0.72). An optimal VQ-6 threshold for a substantial clinical benefit was determined at 3.5 scale steps among IC patients and 4.5 in CLI patients. The suggested thresholds for minimum important difference and substantial clinical benefit could be used when evaluating VQ-6 outcomes following different interventions in PAD and in the design of clinical trials. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Structured decision making as a conceptual framework to identify thresholds for conservation and management

USGS Publications Warehouse

Martin, J.; Runge, M.C.; Nichols, J.D.; Lubow, B.C.; Kendall, W.L.

2009-01-01

Thresholds and their relevance to conservation have become a major topic of discussion in the ecological literature. Unfortunately, in many cases the lack of a clear conceptual framework for thinking about thresholds may have led to confusion in attempts to apply the concept of thresholds to conservation decisions. Here, we advocate a framework for thinking about thresholds in terms of a structured decision making process. The purpose of this framework is to promote a logical and transparent process for making informed decisions for conservation. Specification of such a framework leads naturally to consideration of definitions and roles of different kinds of thresholds in the process. We distinguish among three categories of thresholds. Ecological thresholds are values of system state variables at which small changes bring about substantial changes in system dynamics. Utility thresholds are components of management objectives (determined by human values) and are values of state or performance variables at which small changes yield substantial changes in the value of the management outcome. Decision thresholds are values of system state variables at which small changes prompt changes in management actions in order to reach specified management objectives. The approach that we present focuses directly on the objectives of management, with an aim to providing decisions that are optimal with respect to those objectives. This approach clearly distinguishes the components of the decision process that are inherently subjective (management objectives, potential management actions) from those that are more objective (system models, estimates of system state). Optimization based on these components then leads to decision matrices specifying optimal actions to be taken at various values of system state variables. Values of state variables separating different actions in such matrices are viewed as decision thresholds. Utility thresholds are included in the objectives component, and ecological thresholds may be embedded in models projecting consequences of management actions. Decision thresholds are determined by the above-listed components of a structured decision process. These components may themselves vary over time, inducing variation in the decision thresholds inherited from them. These dynamic decision thresholds can then be determined using adaptive management. We provide numerical examples (that are based on patch occupancy models) of structured decision processes that include all three kinds of thresholds. ?? 2009 by the Ecological Society of America.

Pressure and cold pain threshold reference values in a large, young adult, pain-free population.

PubMed

Waller, Robert; Smith, Anne Julia; O'Sullivan, Peter Bruce; Slater, Helen; Sterling, Michele; McVeigh, Joanne Alexandra; Straker, Leon Melville

2016-10-01

Currently there is a lack of large population studies that have investigated pain sensitivity distributions in healthy pain free people. The aims of this study were: (1) to provide sex-specific reference values of pressure and cold pain thresholds in young pain-free adults; (2) to examine the association of potential correlates of pain sensitivity with pain threshold values. This study investigated sex specific pressure and cold pain threshold estimates for young pain free adults aged 21-24 years. A cross-sectional design was utilised using participants (n=617) from the Western Australian Pregnancy Cohort (Raine) Study at the 22-year follow-up. The association of site, sex, height, weight, smoking, health related quality of life, psychological measures and activity with pain threshold values was examined. Pressure pain threshold (lumbar spine, tibialis anterior, neck and dorsal wrist) and cold pain threshold (dorsal wrist) were assessed using standardised quantitative sensory testing protocols. Reference values for pressure pain threshold (four body sites) stratified by sex and site, and cold pain threshold (dorsal wrist) stratified by sex are provided. Statistically significant, independent correlates of increased pressure pain sensitivity measures were site (neck, dorsal wrist), sex (female), higher waist-hip ratio and poorer mental health. Statistically significant, independent correlates of increased cold pain sensitivity measures were, sex (female), poorer mental health and smoking. These data provide the most comprehensive and robust sex specific reference values for pressure pain threshold specific to four body sites and cold pain threshold at the dorsal wrist for young adults aged 21-24 years. Establishing normative values in this young age group is important given that the transition from adolescence to adulthood is a critical temporal period during which trajectories for persistent pain can be established. These data will provide an important research resource to enable more accurate profiling and interpretation of pain sensitivity in clinical pain disorders in young adults. The robust and comprehensive data can assist interpretation of future clinical pain studies and provide further insight into the complex associations of pain sensitivity that can be used in future research. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Shock ignition targets: gain and robustness vs ignition threshold factor

NASA Astrophysics Data System (ADS)

Atzeni, Stefano; Antonelli, Luca; Schiavi, Angelo; Picone, Silvia; Volponi, Gian Marco; Marocchino, Alberto

2017-10-01

Shock ignition is a laser direct-drive inertial confinement fusion scheme, in which the stages of compression and hot spot formation are partly separated. The hot spot is created at the end of the implosion by a converging shock driven by a final ``spike'' of the laser pulse. Several shock-ignition target concepts have been proposed and relevant gain curves computed (see, e.g.). Here, we consider both pure-DT targets and more facility-relevant targets with plastic ablator. The investigation is conducted with 1D and 2D hydrodynamic simulations. We determine ignition threshold factors ITF's (and their dependence on laser pulse parameters) by means of 1D simulations. 2D simulations indicate that robustness to long-scale perturbations increases with ITF. Gain curves (gain vs laser energy), for different ITF's, are generated using 1D simulations. Work partially supported by Sapienza Project C26A15YTMA, Sapienza 2016 (n. 257584), Eurofusion Project AWP17-ENR-IFE-CEA-01.

Plasma facing materials performance under ITER-relevant mitigated disruption photonic heat loads

NASA Astrophysics Data System (ADS)

Klimov, N. S.; Putrik, A. B.; Linke, J.; Pitts, R. A.; Zhitlukhin, A. M.; Kuprianov, I. B.; Spitsyn, A. V.; Ogorodnikova, O. V.; Podkovyrov, V. L.; Muzichenko, A. D.; Ivanov, B. V.; Sergeecheva, Ya. V.; Lesina, I. G.; Kovalenko, D. V.; Barsuk, V. A.; Danilina, N. A.; Bazylev, B. N.; Giniyatulin, R. N.

2015-08-01

PFMs (Plasma-facing materials: ITER grade stainless steel, beryllium, and ferritic-martensitic steels) as well as deposited erosion products of PFCs (Be-like, tungsten, and carbon based) were tested in QSPA under photonic heat loads relevant to those expected from photon radiation during disruptions mitigated by massive gas injection in ITER. Repeated pulses slightly above the melting threshold on the bulk materials eventually lead to a regular, "corrugated" surface, with hills and valleys spaced by 0.2-2 mm. The results indicate that hill growth (growth rate of ∼1 μm per pulse) and sample thinning in the valleys is a result of melt-layer redistribution. The measurements on the 316L(N)-IG indicate that the amount of tritium absorbed by the sample from the gas phase significantly increases with pulse number as well as the modified layer thickness. Repeated pulses significantly below the melting threshold on the deposited erosion products lead to a decrease of hydrogen isotopes trapped during the deposition of the eroded material.

What is the optimal rate of caesarean section at population level? A systematic review of ecologic studies.

PubMed

Betran, Ana Pilar; Torloni, Maria Regina; Zhang, Jun; Ye, Jiangfeng; Mikolajczyk, Rafael; Deneux-Tharaux, Catherine; Oladapo, Olufemi Taiwo; Souza, João Paulo; Tunçalp, Özge; Vogel, Joshua Peter; Gülmezoglu, Ahmet Metin

2015-06-21

In 1985, WHO stated that there was no justification for caesarean section (CS) rates higher than 10-15% at population-level. While the CS rates worldwide have continued to increase in an unprecedented manner over the subsequent three decades, concern has been raised about the validity of the 1985 landmark statement. We conducted a systematic review to identify, critically appraise and synthesize the analyses of the ecologic association between CS rates and maternal, neonatal and infant outcomes. Four electronic databases were searched for ecologic studies published between 2000 and 2014 that analysed the possible association between CS rates and maternal, neonatal or infant mortality or morbidity. Two reviewers performed study selection, data extraction and quality assessment independently. We identified 11,832 unique citations and eight studies were included in the review. Seven studies correlated CS rates with maternal mortality, five with neonatal mortality, four with infant mortality, two with LBW and one with stillbirths. Except for one, all studies were cross-sectional in design and five were global analyses of national-level CS rates versus mortality outcomes. Although the overall quality of the studies was acceptable; only two studies controlled for socio-economic factors and none controlled for clinical or demographic characteristics of the population. In unadjusted analyses, authors found a strong inverse relationship between CS rates and the mortality outcomes so that maternal, neonatal and infant mortality decrease as CS rates increase up to a certain threshold. In the eight studies included in this review, this threshold was at CS rates between 9 and 16%. However, in the two studies that adjusted for socio-economic factors, this relationship was either weakened or disappeared after controlling for these confounders. CS rates above the threshold of 9-16% were not associated with decreases in mortality outcomes regardless of adjustments. Our findings could be interpreted to mean that at CS rates below this threshold, socio-economic development may be driving the ecologic association between CS rates and mortality. On the other hand, at rates higher than this threshold, there is no association between CS and mortality outcomes regardless of adjustment. The ecological association between CS rates and relevant morbidity outcomes needs to be evaluated before drawing more definite conclusions at population level.

Percolation of binary disk systems: Modeling and theory

DOE PAGES

Meeks, Kelsey; Tencer, John; Pantoya, Michelle L.

2017-01-12

The dispersion and connectivity of particles with a high degree of polydispersity is relevant to problems involving composite material properties and reaction decomposition prediction and has been the subject of much study in the literature. This paper utilizes Monte Carlo models to predict percolation thresholds for a two-dimensional systems containing disks of two different radii. Monte Carlo simulations and spanning probability are used to extend prior models into regions of higher polydispersity than those previously considered. A correlation to predict the percolation threshold for binary disk systems is proposed based on the extended dataset presented in this work and comparedmore » to previously published correlations. Finally, a set of boundary conditions necessary for a good fit is presented, and a condition for maximizing percolation threshold for binary disk systems is suggested.« less

Critical dynamics on a large human Open Connectome network

NASA Astrophysics Data System (ADS)

Ódor, Géza

2016-12-01

Extended numerical simulations of threshold models have been performed on a human brain network with N =836 733 connected nodes available from the Open Connectome Project. While in the case of simple threshold models a sharp discontinuous phase transition without any critical dynamics arises, variable threshold models exhibit extended power-law scaling regions. This is attributed to fact that Griffiths effects, stemming from the topological or interaction heterogeneity of the network, can become relevant if the input sensitivity of nodes is equalized. I have studied the effects of link directness, as well as the consequence of inhibitory connections. Nonuniversal power-law avalanche size and time distributions have been found with exponents agreeing with the values obtained in electrode experiments of the human brain. The dynamical critical region occurs in an extended control parameter space without the assumption of self-organized criticality.

Incidental findings in multislice computed tomography prior to transcatheter aortic valve implantation: frequency, clinical relevance and outcome.

PubMed

Trenkwalder, Teresa; Lahmann, Anna Lena; Nowicka, Magdalena; Pellegrini, Costanza; Rheude, Tobias; Mayr, N Patrick; Voss, Stephanie; Bleiziffer, Sabine; Lange, Rüdiger; Joner, Michael; Kasel, Albert M; Kastrati, Adnan; Schunkert, Heribert; Husser, Oliver; Hadamitzky, Martin; Hengstenberg, Christian

2018-02-21

Multislice computed tomography (MSCT) has emerged as the mainstay in patients planned for transcatheter aortic valve implantation (TAVI). Incidental findings (IF) in MSCT are common. However, the exact incidence, clinical relevance and further consequences of IF are unclear and it is controversial whether IF adversely affect patients' outcome. We analyzed MSCT data of 1050 patients screened for TAVI between January 2011 and December 2014. Median follow-up of patients was 20 months. In total, 3194 IF were identified, which were classified into clinically non-relevant IF (2872, 90%) and clinically relevant IF (322, 10%). In 25% of patients (258/1050) at least one clinically relevant IF was present. Age (80 ± 7 vs. 80 ± 7 years; p = 0.198) and EuroSCORE II (3.6% [2.1-5.7] vs. 3.6% [2.1-5.9]; p = 0.874) was similar between patients with and without a clinically relevant IF. TAVI was performed less frequently in patients with a clinically relevant IF (76% vs. 85%; p < 0.001), with more patients receiving surgical aortic valve replacement in that group (14% vs. 11%; p = 0.042), possibly due to the high rate of incidental aneurysms of the ascending aorta (n = 48). If TAVI was performed mortality did not differ (30-days: 4% vs. 3%; p = 0.339, 1-year: 11% vs. 14%; p = 0.226) between patients with and without a clinically relevant IF. Our study is the largest study to analyze prevalence, clinical relevance and therapeutic consequences of IF during screening for TAVI. IF in pre-procedural MSCT are common and clinically relevant in one-quarter of patients. However, these findings had no impact on overall mortality.

Estimation of Nasal Tip Support Using Computer-Aided Design and 3-Dimensional Printed Models

PubMed Central

Gray, Eric; Maducdoc, Marlon; Manuel, Cyrus; Wong, Brian J. F.

2016-01-01

IMPORTANCE Palpation of the nasal tip is an essential component of the preoperative rhinoplasty examination. Measuring tip support is challenging, and the forces that correspond to ideal tip support are unknown. OBJECTIVE To identify the integrated reaction force and the minimum and ideal mechanical properties associated with nasal tip support. DESIGN, SETTING, AND PARTICIPANTS Three-dimensional (3-D) printed anatomic silicone nasal models were created using a computed tomographic scan and computer-aided design software. From this model, 3-D printing and casting methods were used to create 5 anatomically correct nasal models of varying constitutive Young moduli (0.042, 0.086, 0.098, 0.252, and 0.302 MPa) from silicone. Thirty rhinoplasty surgeons who attended a regional rhinoplasty course evaluated the reaction force (nasal tip recoil) of each model by palpation and selected the model that satisfied their requirements for minimum and ideal tip support. Data were collected from May 3 to 4, 2014. RESULTS Of the 30 respondents, 4 surgeons had been in practice for 1 to 5 years; 9 surgeons, 6 to 15 years; 7 surgeons, 16 to 25 years; and 10 surgeons, 26 or more years. Seventeen surgeons considered themselves in the advanced to expert skill competency levels. Logistic regression estimated the minimum threshold for the Young moduli for adequate and ideal tip support to be 0.096 and 0.154 MPa, respectively. Logistic regression estimated the thresholds for the reaction force associated with the absolute minimum and ideal requirements for good tip recoil to be 0.26 to 4.74 N and 0.37 to 7.19 N during 1- to 8-mm displacement, respectively. CONCLUSIONS AND RELEVANCE This study presents a method to estimate clinically relevant nasal tip reaction forces, which serve as a proxy for nasal tip support. This information will become increasingly important in computational modeling of nasal tip mechanics and ultimately will enhance surgical planning for rhinoplasty. LEVEL OF EVIDENCE NA. PMID:27124818

Model for Estimating the Threshold Mechanical Stability of Structural Cartilage Grafts Used in Rhinoplasty

PubMed Central

Zemek, Allison; Garg, Rohit; Wong, Brian J. F.

2014-01-01

Objectives/Hypothesis Characterizing the mechanical properties of structural cartilage grafts used in rhinoplasty is valuable because softer engineered tissues are more time- and cost-efficient to manufacture. The aim of this study is to quantitatively identify the threshold mechanical stability (e.g., Young’s modulus) of columellar, L-strut, and alar cartilage replacement grafts. Study Design Descriptive, focus group survey. Methods Ten mechanical phantoms of identical size (5 × 20 × 2.3 mm) and varying stiffness (0.360 to 0.85 MPa in 0.05 MPa increments) were made from urethane. A focus group of experienced rhinoplasty surgeons (n = 25, 5 to 30 years in practice) were asked to arrange the phantoms in order of increasing stiffness. Then, they were asked to identify the minimum acceptable stiffness that would still result in favorable surgical outcomes for three clinical applications: columellar, L-strut, and lateral crural replacement grafts. Available surgeons were tested again after 1 week to evaluate intra-rater consistency. Results For each surgeon, the threshold stiffness for each clinical application differed from the threshold values derived by logistic regression by no more than 0.05 MPa (accuracy to within 10%). Specific thresholds were 0.56, 0.59, and 0.49 MPa for columellar, L-strut, and alar grafts, respectively. For comparison, human nasal septal cartilage is approximately 0.8 MPa. Conclusions There was little inter- and intra-rater variation of the identified threshold values for adequate graft stiffness. The identified threshold values will be useful for the design of tissue-engineered or semisynthetic cartilage grafts for use in structural nasal surgery. PMID:20513022

An evidence- and risk-based approach to a harmonized laboratory alert list in Australia and New Zealand.

PubMed

Campbell, Craig A; Lam, Que; Horvath, Andrea R

2018-04-19

Individual laboratories are required to compose an alert list for identifying critical and significant risk results. The high-risk result working party of the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists (AACB) has developed a risk-based approach for a harmonized alert list for laboratories throughout Australia and New Zealand. The six-step process for alert threshold identification and assessment involves reviewing the literature, rating the available evidence, performing a risk analysis, assessing method transferability, considering workload implications and seeking endorsement from stakeholders. To demonstrate this approach, a worked example for deciding the upper alert threshold for potassium is described. The findings of the worked example are for infants aged 0-6 months, a recommended upper potassium alert threshold of >7.0 mmol/L in serum and >6.5 mmol/L in plasma, and for individuals older than 6 months, a threshold of >6.2 mmol/L in both serum and plasma. Limitations in defining alert thresholds include the lack of well-designed studies that measure the relationship between high-risk results and patient outcomes or the benefits of treatment to prevent harm, and the existence of a wide range of clinical practice guidelines with conflicting decision points at which treatment is required. The risk-based approach described presents a transparent, evidence- and consensus-based methodology that can be used by any laboratory when designing an alert list for local use. The RCPA-AACB harmonized alert list serves as a starter set for further local adaptation or adoption after consultation with clinical users.

Evaluation of clinical risk factors for osteoporosis and applicability of the FRAX tool in Joinville City, Southern Brazil.

PubMed

Silva, Dalisbor Marcelo Weber; Borba, Victoria Zeghbi Cochenski; Kanis, John A

2017-12-09

Clinical risk factors for fracture in Southern Brazil are similar to those used in Fracture Risk Assessment Tool (FRAX®). Age-dependent intervention thresholds had higher accuracy than a fixed cut-off point. Access to bone mineral density testing is wanted for a large part of the Brazilian population. The FRAX® has an option to calculate the risk of fracture without this costly evaluation but relies on the clinical risk factors (CRFs) identified in the source cohorts used to generate FRAX. The aims of this study were to determine whether the CRFs used in FRAX are also risk indicators for individuals in Southern Brazil and to evaluate possible intervention thresholds for treatment in Brazil. We determined the CRFs for hip fractures in women and men aged 50 years and more with a hip fracture and controls in Joinville, Southern Brazil (April 1, 2010, and March 31, 2012). For intervention thresholds, we determined the accuracy of using the fixed thresholds of National Osteoporosis Foundation (NOF), USA, compared with the age-dependent thresholds of the National Osteoporosis Guideline Group (NOGG), UK. CRFs that were significant for hip fracture were very similar to FRAX, apart from chronic obstructive pulmonary disease and malabsorptive intestinal disease. FRAX based on the NOGG and NOF models had an accuracy of 64.2 and 58.7%, respectively. CRFs used in FRAX® were similar to those in the Southern Brazil. The NOGG model seems to be more accurate to discriminate patients with increased fracture risk in this population compared to the NOF model, but not significantly.

The effect of condoms on penile vibrotactile sensitivity thresholds in young, heterosexual men

PubMed Central

Hill, Brandon J.; Janssen, Erick; Kvam, Peter; Amick, Erick E.; Sanders, Stephanie A.

2013-01-01

Introduction Investigating the ways in which barrier methods such as condoms may affect penile sensory thresholds has potential relevance to the development of interventions in men who experience negative effects of condoms on sexual response and sensation. A quantitative, psychophysiological investigation examining the degree to which sensations are altered by condoms has, to date, not been conducted. Aim The objective of this study was to examine penile vibrotactile sensitivity thresholds in both flaccid and erect penises with and without a condom, while comparing men who do and those who do not report condom-associated erection problems (CAEP). Methods Penile vibrotactile sensitivity thresholds were assessed among a total of 141 young, heterosexual men using biothesiometry. An incremental two-step staircase method was used and repeated three times for each of four conditions. Intra-class correlation coefficients (ICC) were calculated for all vibratory assessments. Penile vibratory thresholds were compared using a mixed-model Analysis of Variance (ANOVA). Main Outcome Measures Penile vibrotactile sensitivity thresholds with and without a condom, erectile function measured by International Index of Erectile Function Questionnaire (IIEF), and self-reported degree of erection. Results Significant main effects of condoms (yes/no) and erection (yes/no) were found. No main or interaction effects of CAEP were found. Condoms were associated with higher penile vibrotactile sensitivity thresholds (F(1, 124)=17.11, p<.001). Penile vibrotactile thresholds were higher with an erect than with a flaccid penis (F(1, 124)=4.21, p=.042). Conclusion The current study demonstrates the feasibility of measuring penile vibratory thresholds with and without a condom in both erect and flaccid experimental conditions. As might be expected, condoms increased penile vibrotactile sensitivity thresholds. Interestingly, erections were associated with the highest thresholds. Thus, this study was the first to document that erect penises are less sensitive to vibrotactile stimulation than flaccid penises. PMID:24168347

Occupation and its relationship with health and wellbeing: the threshold concept for occupational therapy.

PubMed

Fortune, Tracy; Kennedy-Jones, Mary

2014-10-01

We introduce the educational framework of 'threshold concepts' and discuss its utility in understanding the fundamental difficulties learners have in understanding ways of thinking and practising as occupational therapists. We propose that the relationship between occupation and health is a threshold concept for occupational therapy because of students' trouble in achieving lasting conceptual change in relation to their understanding of it. The authors present and discuss key ideas drawn from educational writings on threshold concepts, review the emerging literature on threshold concepts in occupational therapy, and pose a series of questions in order to prompt consideration of the pedagogical issues requiring action by academic and fieldwork educators. Threshold concepts in occupational therapy have been considered in a primarily cross-disciplinary sense, that is, the understandings that occupational therapy learners grapple with are relevant to learners in other disciplines. In contrast, we present a more narrowly defined conception that emphasises the 'bounded-ness' of the concept to the discipline. A threshold concept that captures the essential nature of occupational therapy is likely to be (highly) troublesome in terms of a learner's acquisition of it. Rather than simplifying these learning 'jewels' educators are encouraged to sit with the discomfort that they and the learner may experience as the learner struggles to grasp them. Moreover, they should reshape their curricula to provoke such struggles if transformative learning is to be the outcome. © 2014 Occupational Therapy Australia.

Interactions between auditory 'what' and 'where' pathways revealed by enhanced near-threshold discrimination of frequency and position.

PubMed

Tardif, Eric; Spierer, Lucas; Clarke, Stephanie; Murray, Micah M

2008-03-07

Partially segregated neuronal pathways ("what" and "where" pathways, respectively) are thought to mediate sound recognition and localization. Less studied are interactions between these pathways. In two experiments, we investigated whether near-threshold pitch discrimination sensitivity (d') is altered by supra-threshold task-irrelevant position differences and likewise whether near-threshold position discrimination sensitivity is altered by supra-threshold task-irrelevant pitch differences. Each experiment followed a 2 x 2 within-subjects design regarding changes/no change in the task-relevant and task-irrelevant stimulus dimensions. In Experiment 1, subjects discriminated between 750 Hz and 752 Hz pure tones, and d' for this near-threshold pitch change significantly increased by a factor of 1.09 when accompanied by a task-irrelevant position change of 65 micros interaural time difference (ITD). No response bias was induced by the task-irrelevant position change. In Experiment 2, subjects discriminated between 385 micros and 431 micros ITDs, and d' for this near-threshold position change significantly increased by a factor of 0.73 when accompanied by task-irrelevant pitch changes (6 Hz). In contrast to Experiment 1, task-irrelevant pitch changes induced a response criterion bias toward responding that the two stimuli differed. The collective results are indicative of facilitative interactions between "what" and "where" pathways. By demonstrating how these pathways may cooperate under impoverished listening conditions, our results bear implications for possible neuro-rehabilitation strategies. We discuss our results in terms of the dual-pathway model of auditory processing.

Lowering of acoustic droplet vaporization threshold via aggregation

NASA Astrophysics Data System (ADS)

Guo, Shifang; Shi, Aiwei; Xu, Shanshan; Du, Xuan; Wang, Xin; Zong, Yujin; Bouakaz, Ayache; Wan, Mingxi

2017-12-01

Acoustically sensitive emulsion nanodroplets composed of perfluorocarbon have shown great potential for advanced medical diagnosis and therapy but are limited by the required high acoustic droplet vaporization (ADV) threshold for clinical applications. This study investigates the use of an ultrasonic standing wave to lower the ADV threshold while maintaining the generated bubble size in the required size range, ensuring the generation of inertial cavitation and corresponding physical effects. The results showed that disperse nanodroplets were manipulated to form micron-sized aggregations, and the required ADV threshold was significantly lowered, while a similar size range of the microbubbles generated by disperse nanodroplets was maintained. The threshold could be further regulated by adjusting the aggregation size via controlling the concentration of the disperse nanodroplets. Furthermore, the internal pressures in the aggregations with different sizes were calculated to determine their ADV thresholds theoretically, which were shown to be in good agreement with the experimental results.

Cost-effectiveness analysis of total ankle arthroplasty.

PubMed

SooHoo, Nelson F; Kominski, Gerald

2004-11-01

There is renewed interest in total ankle arthroplasty as an alternative to ankle fusion in the treatment of end-stage ankle arthritis. Despite a lack of long-term data on the clinical outcomes associated with these implants, the use of ankle arthroplasty is expanding. The purpose of this cost-effectiveness analysis was to evaluate whether the currently available literature justifies the emerging use of total ankle arthroplasty. This study also identifies thresholds for the durability and function of ankle prostheses that, if met, would support more widespread dissemination of this new technology. A decision model was created for the treatment of ankle arthritis. The literature was reviewed to identify possible outcomes and their probabilities following ankle fusion and ankle arthroplasty. Each outcome was weighted for quality of life with use of a utility factor, and effectiveness was expressed in units of quality-adjusted life years. Gross costs were estimated from Medicare charge and reimbursement data for the relevant codes. The effect of the uncertainty of estimates of costs and effectiveness was assessed with sensitivity analysis. The reference case of our model assumed a ten-year duration of survival of the prosthesis, resulting in an incremental cost-effectiveness ratio for ankle arthroplasty of $18,419 per quality-adjusted life year gained. This reflects a gain of 0.52 quality-adjusted life years at a cost of $9578 when ankle arthroplasty is chosen over fusion. This ratio compares favorably with the cost-effectiveness of other medical and surgical interventions. Sensitivity analysis determined that the cost per quality-adjusted life year gained with ankle arthroplasty rises above $50,000 if the prosthesis is assumed to fail before seven years. Treatment options with ratios above $50,000 per quality-adjusted life year are commonly considered to have limited cost-effectiveness. This threshold is also crossed when the theoretical functional advantages of ankle arthroplasty are eliminated in sensitivity analysis. The currently available literature has not yet shown that total ankle arthroplasty predictably results in levels of durability and function that make it cost-effective at this time. However, the reference case of this analysis does demonstrate that total ankle arthroplasty has the potential to be a cost-effective alternative to ankle fusion. This reference case assumes that the theoretical functional advantages of ankle arthroplasty over ankle fusion will be borne out in future clinical studies. Performance of total ankle replacement will be better justified if these thresholds are met in published long-term clinical trials.

Preoperative cow-side lactatemia measurement predicts negative outcome in Holstein dairy cattle with right abomasal disorders.

PubMed

Boulay, G; Francoz, D; Doré, E; Dufour, S; Veillette, M; Badillo, M; Bélanger, A-M; Buczinski, S

2014-01-01

The objectives of the current study were (1) to determine the gain in prognostic accuracy of preoperative l-lactate concentration (LAC) measured on farm on cows with right displaced abomasum (RDA) or abomasal volvulus (AV) for predicting negative outcome; and (2) to suggest clinically relevant thresholds for such use. A cohort of 102 cows with on-farm surgical diagnostic of RDA or AV was obtained from June 2009 through December 2011. Blood was drawn from coccygeal vessels before surgery and plasma LAC was immediately measured by using a portable clinical analyzer. Dairy producers were interviewed by phone 30 d following surgery and the outcome was determined: a positive outcome if the owner was satisfied of the overall evolution 30 d postoperatively, and a negative outcome if the cow was culled, died, or if the owner reported being unsatisfied 30 d postoperatively. The area under the curve of the receiver operating characteristic curve for LAC was 0.92 and was significantly greater than the area under the curve of the receiver operating characteristic curve of heart rate (HR; 0.77), indicating that LAC, in general, performed better than HR to predict a negative outcome. Furthermore, the ability to predict a negative outcome was significantly improved when LAC measurement was considered in addition to the already available HR data (area under the curve: 0.93 and 95% confidence interval: 0.87, 0.99). Important inflection points of the misclassification cost term function were noted at thresholds of 2 and 6 mmol/L, suggesting the potential utility of these cut-points. The 2 and 6 mmol/L thresholds had a sensitivity, specificity, positive predictive value, and negative predictive value for predicting a negative outcome of 76.2, 82.7, 53.3, and 93.1%, and of 28.6, 97.5, 75, and 84%, respectively. In terms of clinical interpretation, LAC ≤2 mmol/L appeared to be a good indicator of positive outcome and could be used to support a surgical treatment decision. The treatment decision for cows with LAC between 2 and 6 mmol/L, however, would depend on the economic context and the owner's attitude to risk in regard to potential return on its investment. Finally, performing a surgical correction on commercial cows with RDA or AV and a LAC ≥6 mmol/L appeared to be unjustified and these animals should be culled based on their high probability of negative outcome. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The thresholds for statistical and clinical significance – a five-step procedure for evaluation of intervention effects in randomised clinical trials

PubMed Central

2014-01-01

Background Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore, assessment of intervention effects in randomised clinical trials deserves more rigour in order to become more valid. Methods Several methodologies for assessing the statistical and clinical significance of intervention effects in randomised clinical trials were considered. Balancing simplicity and comprehensiveness, a simple five-step procedure was developed. Results For a more valid assessment of results from a randomised clinical trial we propose the following five-steps: (1) report the confidence intervals and the exact P-values; (2) report Bayes factor for the primary outcome, being the ratio of the probability that a given trial result is compatible with a ‘null’ effect (corresponding to the P-value) divided by the probability that the trial result is compatible with the intervention effect hypothesised in the sample size calculation; (3) adjust the confidence intervals and the statistical significance threshold if the trial is stopped early or if interim analyses have been conducted; (4) adjust the confidence intervals and the P-values for multiplicity due to number of outcome comparisons; and (5) assess clinical significance of the trial results. Conclusions If the proposed five-step procedure is followed, this may increase the validity of assessments of intervention effects in randomised clinical trials. PMID:24588900

Systematic review of effects of current transtibial prosthetic socket designs--Part 2: Quantitative outcomes.

PubMed

Safari, Mohammad Reza; Meier, Margrit Regula

2015-01-01

This review is an attempt to untangle the complexity of transtibial prosthetic socket fit and perhaps find some indication of whether a particular prosthetic socket type might be best for a given situation. In addition, we identified knowledge gaps, thus providing direction for possible future research. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using medical subject headings and standard key words to search for articles in relevant databases. No restrictions were made on study design and type of outcome measure used. From the obtained search results (n = 1,863), 35 articles were included. The relevant data were entered into a predefined data form that included the Downs and Black risk of bias assessment checklist. This article presents the results from the systematic review of the quantitative outcomes (n = 27 articles). Trends indicate that vacuum-assisted suction sockets improve gait symmetry, volume control, and residual limb health more than other socket designs. Hydrostatic sockets seem to create less inconsistent socket fittings, reducing a problem that greatly influences outcome measures. Knowledge gaps exist in the understanding of clinically meaningful changes in socket fit and its effect on biomechanical outcomes. Further, safe and comfortable pressure thresholds under various conditions should be determined through a systematic approach.

The Ling 6(HL) test: typical pediatric performance data and clinical use evaluation.

PubMed

Glista, Danielle; Scollie, Susan; Moodie, Sheila; Easwar, Vijayalakshmi

2014-01-01

The Ling 6(HL) test offers a calibrated version of naturally produced speech sounds in dB HL for evaluation of detection thresholds. Aided performance has been previously characterized in adults. The purpose of this work was to evaluate and refine the Ling 6(HL) test for use in pediatric hearing aid outcome measurement. This work is presented across two studies incorporating an integrated knowledge translation approach in the characterization of normative and typical performance, and in the evaluation of clinical feasibility, utility, acceptability, and implementation. A total of 57 children, 28 normally hearing and 29 with binaural sensorineural hearing loss, were included in Study 1. Children wore their own hearing aids fitted using Desired Sensation Level v5.0. Nine clinicians from The Network of Pediatric Audiologists participated in Study 2. A CD-based test format was used in the collection of unaided and aided detection thresholds in laboratory and clinical settings; thresholds were measured clinically as part of routine clinical care. Confidence intervals were derived to characterize normal performance and typical aided performance according to hearing loss severity. Unaided-aided performance was analyzed using a repeated-measures analysis of variance. The audiologists completed an online questionnaire evaluating the quality, feasibility/executability, utility/comparative value/relative advantage, acceptability/applicability, and interpretability, in addition to recommendation and general comments sections. Ling 6(HL) thresholds were reliably measured with children 3-18 yr old. Normative and typical performance ranges were translated into a scoring tool for use in pediatric outcome measurement. In general, questionnaire respondents generally agreed that the Ling 6(HL) test was a high-quality outcome evaluation tool that can be implemented successfully in clinical settings. By actively collaborating with pediatric audiologists and using an integrated knowledge translation framework, this work supported the creation of an evidence-based clinical tool that has the potential to be implemented in, and useful to, clinical practice. More research is needed to characterize performance in alternative listening conditions to facilitate use with infants, for example. Future efforts focused on monitoring the use of the Ling 6(HL) test in daily clinical practice may help describe whether clinical use has been maintained across time and if any additional adaptations are necessary to facilitate clinical uptake. American Academy of Audiology.

Differential activation of stress-response signaling in load-induced cardiac hypertrophy and failure

PubMed Central

Rothermel, Beverly A.; Berenji, Kambeez; Tannous, Paul; Kutschke, William; Dey, Asim; Nolan, Bridgid; Yoo, Ki-Dong; Demetroulis, Elaine; Gimbel, Michael; Cabuay, Barry; Karimi, Mohsen; Hill, Joseph A.

2014-01-01

Hypertrophic growth of the myocardium occurs in most forms of heart failure and may contribute to the pathogenesis of the failure state. Little is known about the regulatory mechanisms governing the often-coexisting phenotypes of hypertrophy, systolic failure, and diastolic stiffness that characterize clinical disease. We hypothesized that intracellular signaling pathways are differentially activated by graded degrees of hemodynamic stress. To test this, we developed models of graded pressure stress in mice and used them to directly compare compensated hypertrophy and pressure-overload heart failure. Surgical interventions were designed to be similar, on either side of a threshold separating compensated from decompensated responses. Our findings revealed two dramatically different hypertrophic phenotypes with only modest differences in the activation of relevant intracellular signaling pathways. Furthermore, we uncovered a functional requirement of calcineurin signaling in each model such that calcineurin suppression blunted hypertrophic growth. Remarkably, in each case, suppression of calcineurin signaling was not associated with clinical deterioration or increased mortality. Profiles of stress-response signaling and Ca2+ handling differ between the steady-state, maintenance phases of load-induced cardiac hypertrophy and failure. This information may be useful in identifying novel targets of therapy in chronic disease. PMID:16033866

Differential activation of stress-response signaling in load-induced cardiac hypertrophy and failure.

PubMed

Rothermel, Beverly A; Berenji, Kambeez; Tannous, Paul; Kutschke, William; Dey, Asim; Nolan, Bridgid; Yoo, Ki-Dong; Demetroulis, Elaine; Gimbel, Michael; Cabuay, Barry; Karimi, Mohsen; Hill, Joseph A

2005-09-21

Hypertrophic growth of the myocardium occurs in most forms of heart failure and may contribute to the pathogenesis of the failure state. Little is known about the regulatory mechanisms governing the often-coexisting phenotypes of hypertrophy, systolic failure, and diastolic stiffness that characterize clinical disease. We hypothesized that intracellular signaling pathways are differentially activated by graded degrees of hemodynamic stress. To test this, we developed models of graded pressure stress in mice and used them to directly compare compensated hypertrophy and pressure-overload heart failure. Surgical interventions were designed to be similar, on either side of a threshold separating compensated from decompensated responses. Our findings revealed two dramatically different hypertrophic phenotypes with only modest differences in the activation of relevant intracellular signaling pathways. Furthermore, we uncovered a functional requirement of calcineurin signaling in each model such that calcineurin suppression blunted hypertrophic growth. Remarkably, in each case, suppression of calcineurin signaling was not associated with clinical deterioration or increased mortality. Profiles of stress-response signaling and Ca2+ handling differ between the steady-state, maintenance phases of load-induced cardiac hypertrophy and failure. This information may be useful in identifying novel targets of therapy in chronic disease.

Using species sensitivity distribution approach to assess the risks of commonly detected agricultural pesticides to Australia's tropical freshwater ecosystems.

PubMed

Pathiratne, Asoka; Kroon, Frederieke J

2016-02-01

To assess the potential impacts of agricultural pesticides on tropical freshwater ecosystems, the present study developed temperature-specific, freshwater species protection concentrations (i.e., ecotoxicity threshold values) for 8 pesticides commonly detected in Australia's tropical freshwaters. Because relevant toxicity data for native tropical freshwater species to assess the ecological risks were mostly absent, scientifically robust toxicity data obtained at ≥20 °C were used for ecologically relevant taxonomic groups representing primary producers and consumers. Species sensitivity distribution (SSD) curves were subsequently generated for predicted chronic exposure using Burrlioz 2.0 software with mixed chronic and converted acute data relevant to exposure conditions at ≥20 °C. Ecotoxicity threshold values for tropical freshwater ecosystem protection were generated for ametryn, atrazine, diuron, metolachlor, and imidacloprid (all moderate reliability), as well as simazine, hexazinone, and tebuthiuron (all low reliability). Using these SSD curves, the retrospective risk assessments for recently reported pesticide concentrations highlight that the herbicides ametryn, atrazine, and diuron are of major concern for ecological health in Australia's tropical freshwater ecosystems. The insecticide imidacloprid also appears to pose an emerging threat to the most sensitive species in tropical freshwater ecosystems. The exposed temperature-specific approach may be applied to develop water quality guideline values for other environmental contaminants detected in tropical freshwater ecosystems until reliable and relevant toxicity data are generated using representative native species. © 2015 SETAC.

Implications of the concept of minimal risk in research on informed choice in clinical practice

PubMed Central

Wada, Kyoko; Nisker, Jeff

2015-01-01

The concept of a minimal risk threshold in research, beneath which exception to informed consent and ethics review processes may occur, has been codified for over 30 years in many national research regulations and by the Council for International Organizations of Medical Sciences. Although minimal risk in research constitutes one of the criteria for allowing waiver of informed consent or modification to the consent process and a large body of literature exists, discussion of a minimal risk threshold in clinical practice has not occurred. One reason for lack of discussion may be that implicit consent is accepted for a wide range of routine clinical practices. Extending the role of minimal risk in research to clinical practice might assist clinicians in identifying circumstances for which implicit consent is indeed sufficient and circumstances in which it is not. Further, concepts from minimal risk in research might assist clinicians regarding when information provision in health promotion is required. We begin by reviewing concepts in both minimal risk in research and informed choice in clinical practice. We then explore how a clinical minimal risk concept may clarify recommendations for information provision in clinical practice and support the patient's informed choice regarding therapeutic and diagnostic procedures and also health promotion. Given that clinical practice involves a broad scope of health information, professional practice guidelines on information provision based on the application of the minimal risk threshold in research could be developed to guide clinicians in what information must be provided to their patients. PMID:26108215

Information transmission and detection thresholds in the vestibular nuclei: single neurons vs. population encoding

PubMed Central

Massot, Corentin; Chacron, Maurice J.

2011-01-01

Understanding how sensory neurons transmit information about relevant stimuli remains a major goal in neuroscience. Of particular relevance are the roles of neural variability and spike timing in neural coding. Peripheral vestibular afferents display differential variability that is correlated with the importance of spike timing; regular afferents display little variability and use a timing code to transmit information about sensory input. Irregular afferents, conversely, display greater variability and instead use a rate code. We studied how central neurons within the vestibular nuclei integrate information from both afferent classes by recording from a group of neurons termed vestibular only (VO) that are known to make contributions to vestibulospinal reflexes and project to higher-order centers. We found that, although individual central neurons had sensitivities that were greater than or equal to those of individual afferents, they transmitted less information. In addition, their velocity detection thresholds were significantly greater than those of individual afferents. This is because VO neurons display greater variability, which is detrimental to information transmission and signal detection. Combining activities from multiple VO neurons increased information transmission. However, the information rates were still much lower than those of equivalent afferent populations. Furthermore, combining responses from multiple VO neurons led to lower velocity detection threshold values approaching those measured from behavior (∼2.5 vs. 0.5–1°/s). Our results suggest that the detailed time course of vestibular stimuli encoded by afferents is not transmitted by VO neurons. Instead, they suggest that higher vestibular pathways must integrate information from central vestibular neuron populations to give rise to behaviorally observed detection thresholds. PMID:21307329

Clinical assessment of ossicular mobility by a ceramic vibrator designed for implantable hearing aids.

PubMed

Gyo, K; Yanagihara, N

1986-01-01

Ossicular mobility was assessed by direct coupling of a piezoelectric ceramic vibrator to the ossicles during middle ear surgery. The sites excited were body of the incus, head of the stapes, and footplate of the stapes through a hydroxyapatite ceramic strut. The threshold of the vibratory hearing was determined by the patient's response as a minimum audition, and the vibration threshold was obtained by subtracting the preoperative bone conduction threshold from the vibratory hearing threshold. The results were analyzed by the state of hearing after the operation, which revealed that a patient with a good vibration threshold during the operation had a tendency to get good postoperative hearing. This may mean that postoperative hearing can be predicted to some extent during the operation by the measurement of ossicular mobility.

Considerations for automated machine learning in clinical metabolic profiling: Altered homocysteine plasma concentration associated with metformin exposure.

PubMed

Orlenko, Alena; Moore, Jason H; Orzechowski, Patryk; Olson, Randal S; Cairns, Junmei; Caraballo, Pedro J; Weinshilboum, Richard M; Wang, Liewei; Breitenstein, Matthew K

2018-01-01

With the maturation of metabolomics science and proliferation of biobanks, clinical metabolic profiling is an increasingly opportunistic frontier for advancing translational clinical research. Automated Machine Learning (AutoML) approaches provide exciting opportunity to guide feature selection in agnostic metabolic profiling endeavors, where potentially thousands of independent data points must be evaluated. In previous research, AutoML using high-dimensional data of varying types has been demonstrably robust, outperforming traditional approaches. However, considerations for application in clinical metabolic profiling remain to be evaluated. Particularly, regarding the robustness of AutoML to identify and adjust for common clinical confounders. In this study, we present a focused case study regarding AutoML considerations for using the Tree-Based Optimization Tool (TPOT) in metabolic profiling of exposure to metformin in a biobank cohort. First, we propose a tandem rank-accuracy measure to guide agnostic feature selection and corresponding threshold determination in clinical metabolic profiling endeavors. Second, while AutoML, using default parameters, demonstrated potential to lack sensitivity to low-effect confounding clinical covariates, we demonstrated residual training and adjustment of metabolite features as an easily applicable approach to ensure AutoML adjustment for potential confounding characteristics. Finally, we present increased homocysteine with long-term exposure to metformin as a potentially novel, non-replicated metabolite association suggested by TPOT; an association not identified in parallel clinical metabolic profiling endeavors. While warranting independent replication, our tandem rank-accuracy measure suggests homocysteine to be the metabolite feature with largest effect, and corresponding priority for further translational clinical research. Residual training and adjustment for a potential confounding effect by BMI only slightly modified the suggested association. Increased homocysteine is thought to be associated with vitamin B12 deficiency - evaluation for potential clinical relevance is suggested. While considerations for clinical metabolic profiling are recommended, including adjustment approaches for clinical confounders, AutoML presents an exciting tool to enhance clinical metabolic profiling and advance translational research endeavors.

Rationality, practice variation and person-centred health policy: a threshold hypothesis.

PubMed

Djulbegovic, Benjamin; Hamm, Robert M; Mayrhofer, Thomas; Hozo, Iztok; Van den Ende, Jef

2015-12-01

Variation in practice of medicine is one of the major health policy issues of today. Ultimately, it is related to physicians' decision making. Similar patients with similar likelihood of having disease are often managed by different doctors differently: some doctors may elect to observe the patient, others decide to act based on diagnostic testing and yet others may elect to treat without testing. We explain these differences in practice by differences in disease probability thresholds at which physicians decide to act: contextual social and clinical factors and emotions such as regret affect the threshold by influencing the way doctors integrate objective data related to treatment and testing. However, depending on a theoretical construct each of the physician's behaviour can be considered rational. In fact, we showed that the current regulatory policies lead to predictably low thresholds for most decisions in contemporary practice. As a result, we may expect continuing motivation for overuse of treatment and diagnostic tests. We argue that rationality should take into account both formal principles of rationality and human intuitions about good decisions along the lines of Rawls' 'reflective equilibrium/considered judgment'. In turn, this can help define a threshold model that is empirically testable. © 2015 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

Preparatory neural activity predicts performance on a conflict task.

PubMed

Stern, Emily R; Wager, Tor D; Egner, Tobias; Hirsch, Joy; Mangels, Jennifer A

2007-10-24

Advance preparation has been shown to improve the efficiency of conflict resolution. Yet, with little empirical work directly linking preparatory neural activity to the performance benefits of advance cueing, it is not clear whether this relationship results from preparatory activation of task-specific networks, or from activity associated with general alerting processes. Here, fMRI data were acquired during a spatial Stroop task in which advance cues either informed subjects of the upcoming relevant feature of conflict stimuli (spatial or semantic) or were neutral. Informative cues decreased reaction time (RT) relative to neutral cues, and cues indicating that spatial information would be task-relevant elicited greater activity than neutral cues in multiple areas, including right anterior prefrontal and bilateral parietal cortex. Additionally, preparatory activation in bilateral parietal cortex and right dorsolateral prefrontal cortex predicted faster RT when subjects responded to spatial location. No regions were found to be specific to semantic cues at conventional thresholds, and lowering the threshold further revealed little overlap between activity associated with spatial and semantic cueing effects, thereby demonstrating a single dissociation between activations related to preparing a spatial versus semantic task-set. This relationship between preparatory activation of spatial processing networks and efficient conflict resolution suggests that advance information can benefit performance by leading to domain-specific biasing of task-relevant information.

[Loss of capture by myocardial ischemia: A case report].

PubMed

Sonou, A; Adjagba, P M; Hounkponou, M; Codjo, L; Houéhanou-Sonou, C; Assani, S; Yessoufou, T; Sacca, J; Houénassi, M

2017-02-01

We report the case of a patient with pacemaker who presented chest pain during exercise followed by fainting. He has a history of arterial hypertension and diabetes. The initial examination was normal; the ventricular stimulation threshold was 1.125 volts (V) and cardiac enzymes were normal. Stress test has reproduced chest pain followed by loss of pacemaker capture and asystole. Coronary angiography showed a tight stenosis of the proximal anterior interventricular artery dilated by a drug-eluting stent. The control of stress test was normal. A stent thrombosis eight days later led to an acute coronary syndrome with recurrent syncope due to the loss of ventricular capture. The ventricular pacing threshold was then 2.25V. After revascularization and stabilization of the patient's clinical status, this threshold returned to 1.125V. This clinic case has confirmed that coronary artery disease could increase pacing threshold. It also highlights the usefulness of automatic capture algorithms in coronary patients. The stress test cannot only help to detect coronary artery disease but also allows the optimization of programming the pacemaker. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Method for Assessing Contrast Performance under Lighting Conditions such as Entering a Tunnel on Sunny Day.

PubMed

Huang, Y; Menozzi, M

2015-04-01

Clinical assessment of dark adaptation is time consuming and requires a specialised instrumentation such as a nyktometer. It is therefore not surprising that dark adaptation is rarely tested in practice. As for the case of testing fitness of a driver, demands on adaptation in daily driving tasks mostly depart from settings in a nyktometer. In daily driving, adaptation is stressed by high and fast transitions of light levels, and the period of time which is relevant to safe driving starts right after a transition and ends several seconds later. In the nyktometer dark adaptation is tested after completion of the adaptation process. RESULTS of a nyktometer test may therefore deliver little information about adaptation shortly after light transitions. In an attempt to develop a clinical test aiming to fulfill both a short measurement time and offering test conditions comparable to conditions in driving, we conducted a preliminary study in which contrast sensitivity thresholds were recorded for light transitions as found in daily driving tasks and for various times after transition onsets. Contrast sensitivity performance is compared to dark adaptation performance as assessed by a myktometer. Contrast sensitivity thresholds were recorded in 17 participants by means of a twin projection apparatus. The apparatus enabled the projection of an adapting field and of a Landolt ring both with a variable luminance. Five different stepwise transitions in levels of adapting luminance were tested. All transitions occurred from bright to dark. The Landolt ring was flashed 100 or 500 ms after the transition had occurred. Participants were instructed to report the orientation of the Landolt ring. A Rodenstock Nyktometer, Plate 501, was used to record dark adaptation threshold. Experimental data from the proposed test revealed a noticeably increasing contrast detection threshold measured in dark adaptation in the stronger transition from 14 000 to 8 cd/m2 than in the weaker transition from 2000 to 8 cd/m2. By raising the dark adaption luminance level from 8 to 60 cd/m2 in the stronger transition case, the contrast detection threshold was then improved by a factor of four. Another main finding showed that for the adaptation process from strong glare stimuli to the dark adaptation, a peak deterioration in contrast sensitivity occurred at the light adaptation level of 6000 cd/m2. Comparing the contrast performance assessed by the proposed test with that of the nyktometer test, there was no clear correlation between the two methods. Our suggested method to assess dark adaptation performance proved to be practical in use and, since the patient does not have to spend a long time to attain complete dark adaptation, the method required a short time for measurement. Our negative experience in the use of the myktometer was in agreement with reported experience in the literature. Georg Thieme Verlag KG Stuttgart · New York.

Rational use of Xpert testing in patients with presumptive TB: clinicians should be encouraged to use the test-treat threshold.

PubMed

Decroo, Tom; Henríquez-Trujillo, Aquiles R; De Weggheleire, Anja; Lynen, Lutgarde

2017-10-11

A recently published Ugandan study on tuberculosis (TB) diagnosis in HIV-positive patients with presumptive smear-negative TB, which showed that out of 90 patients who started TB treatment, 20% (18/90) had a positive Xpert MTB/RIF (Xpert) test, 24% (22/90) had a negative Xpert test, and 56% (50/90) were started without Xpert testing. Although Xpert testing was available, clinicians did not use it systematically. Here we aim to show more objectively the process of clinical decision-making. First, we estimated that pre-test probability of TB, or the prevalence of TB in smear-negative HIV infected patients with signs of presumptive TB in Uganda, was 17%. Second, we argue that the treatment threshold, the probability of disease at which the utility of treating and not treating is the same, and above which treatment should be started, should be determined. In Uganda, the treatment threshold was not yet formally established. In Rwanda, the calculated treatment threshold was 12%. Hence, one could argue that the threshold was reached without even considering additional tests. Still, Xpert testing can be useful when the probability of disease is above the treatment threshold, but only when a negative Xpert result can lower the probability of disease enough to cross the treatment threshold. This occurs when the pre-test probability is lower than the test-treat threshold, the probability of disease at which the utility of testing and the utility of treating without testing is the same. We estimated that the test-treatment threshold was 28%. Finally, to show the effect of the presence or absence of arguments on the probability of TB, we use confirming and excluding power, and a log10 odds scale to combine arguments. If the pre-test probability is above the test-treat threshold, empirical treatment is justified, because even a negative Xpert will not lower the post-test probability below the treatment threshold. However, Xpert testing for the diagnosis of TB should be performed in patients for whom the probability of TB was lower than the test-treat threshold. Especially in resource constrained settings clinicians should be encouraged to take clinical decisions and use scarce resources rationally.

Altitude training causes haematological fluctuations with relevance for the Athlete Biological Passport.

PubMed

Bonne, Thomas Christian; Lundby, Carsten; Lundby, Anne Kristine; Sander, Mikael; Bejder, Jacob; Nordsborg, Nikolai Baastrup

2015-08-01

The impact of altitude training on haematological parameters and the Athlete Biological Passport (ABP) was evaluated in international-level elite athletes. One group of swimmers lived high and trained high (LHTH, n = 10) for three to four weeks at 2130 m or higher whereas a control group (n = 10) completed a three-week training camp at sea-level. Haematological parameters were determined weekly three times before and four times after the training camps. ABP thresholds for haemoglobin concentration ([Hb]), reticulocyte percentage (RET%), OFF score and the abnormal blood profile score (ABPS) were calculated using the Bayesian model. After altitude training, six swimmers exceeded the 99% ABP thresholds: two swimmers exceeded the OFF score thresholds at day +7; one swimmer exceeded the OFF score threshold at day +28; one swimmer exceeded the threshold for RET% at day +14; and one swimmer surpassed the ABPS threshold at day +14. In the control group, no values exceeded the individual ABP reference range. In conclusion, LHTH induces haematological changes in Olympic-level elite athletes which can exceed the individually generated references in the ABP. Training at altitude should be considered a confounding factor for ABP interpretation for up to four weeks after altitude exposure but does not consistently cause abnormal values in the ABP. Copyright © 2014 John Wiley & Sons, Ltd.

Perfect Detection of Spikes in the Linear Sub-threshold Dynamics of Point Neurons

PubMed Central

Krishnan, Jeyashree; Porta Mana, PierGianLuca; Helias, Moritz; Diesmann, Markus; Di Napoli, Edoardo

2018-01-01

Spiking neuronal networks are usually simulated with one of three main schemes: the classical time-driven and event-driven schemes, and the more recent hybrid scheme. All three schemes evolve the state of a neuron through a series of checkpoints: equally spaced in the first scheme and determined neuron-wise by spike events in the latter two. The time-driven and the hybrid scheme determine whether the membrane potential of a neuron crosses a threshold at the end of the time interval between consecutive checkpoints. Threshold crossing can, however, occur within the interval even if this test is negative. Spikes can therefore be missed. The present work offers an alternative geometric point of view on neuronal dynamics, and derives, implements, and benchmarks a method for perfect retrospective spike detection. This method can be applied to neuron models with affine or linear subthreshold dynamics. The idea behind the method is to propagate the threshold with a time-inverted dynamics, testing whether the threshold crosses the neuron state to be evolved, rather than vice versa. Algebraically this translates into a set of inequalities necessary and sufficient for threshold crossing. This test is slower than the imperfect one, but can be optimized in several ways. Comparison confirms earlier results that the imperfect tests rarely miss spikes (less than a fraction 1/108 of missed spikes) in biologically relevant settings. PMID:29379430

Conditioned Pain Modulation Is Associated with Common Polymorphisms in the Serotonin Transporter Gene

PubMed Central

Lindstedt, Fredrik; Berrebi, Jonathan; Greayer, Erik; Lonsdorf, Tina B.; Schalling, Martin; Ingvar, Martin; Kosek, Eva

2011-01-01

Background Variation in the serotonin transporter (5-HTT) gene (SLC6A4) has been shown to influence a wide range of affective processes. Low 5-HTT gene-expression has also been suggested to increase the risk of chronic pain. Conditioned pain modulation (CPM) - i.e. ‘pain inhibits pain’ - is impaired in chronic pain states and, reciprocally, aberrations of CPM may predict the development of chronic pain. Therefore we hypothesized that a common variation in the SLC6A4 is associated with inter-individual variation in CPM. Forty-five healthy subjects recruited on the basis of tri-allelic 5-HTTLPR genotype, with inferred high or low 5-HTT-expression, were included in a double-blind study. A submaximal-effort tourniquet test was used to provide a standardized degree of conditioning ischemic pain. Individualized noxious heat and pressure pain thresholds (PPTs) were used as subjective test-modalities and the nociceptive flexion reflex (NFR) was used to provide an objective neurophysiological window into spinal processing. Results The low, as compared to the high, 5-HTT-expressing group exhibited significantly reduced CPM-mediated pain inhibition for PPTs (p = 0.02) and heat-pain (p = 0.02). The CPM-mediated inhibition of the NFR, gauged by increases in NFR-threshold, did not differ significantly between groups (p = 0.75). Inhibition of PPTs and heat-pain were correlated (Spearman’s rho = 0.35, p = 0.02), whereas the NFR-threshold increase was not significantly correlated with degree of inhibition of these subjectively reported modalities. Conclusions Our results demonstrate the involvement of the tri-allelic 5-HTTLPR genotype in explaining clinically relevant inter-individual differences in pain perception and regulation. Our results also illustrate that shifts in NFR-thresholds do not necessarily correlate to the modulation of experienced pain. We discuss various possible mechanisms underlying these findings and suggest a role of regulation of 5-HT receptors along the neuraxis as a function of differential 5-HTT-expression. PMID:21464942

Maximizing coupling strength of magnetically anchored surgical instruments: how thick can we go?

PubMed

Best, Sara L; Bergs, Richard; Gedeon, Makram; Paramo, Juan; Fernandez, Raul; Cadeddu, Jeffrey A; Scott, Daniel J

2011-01-01

The Magnetic Anchoring and Guidance System (MAGS) includes an external magnet that controls intra-abdominal surgical instruments via magnetic attraction forces. We have performed NOTES (Natural Orifice Transluminal Endoscopic Surgery) and LESS (Laparoendoscopic Single Site) procedures using MAGS instruments in porcine models with up to 2.5-cm-thick abdominal walls, but this distance may not be sufficient in some humans. The purpose of this study was to determine the maximal abdominal wall thickness for which the current MAGS platform is suitable. Successive iterations of prototype instruments were developed; those evaluated in this study include external (134-583 g, 38-61 mm diameter) and internal (8-39 g, 10-22 mm diameter) components using various grades, diameters, thicknesses, and stacking/shielding/focusing configurations of permanent Neodymium-iron-boron (NdFeB) magnets. Nine configurations were tested for coupling strength across distances of 0.1-10 cm. The force-distance tests across an air medium were conducted at 0.5-mm increments using a robotic arm fitted with a force sensor. A minimum theoretical instrument drop-off (decoupling) threshold was defined as the separation distance at which force decreased below the weight of the heaviest internal component (39 g). Magnetic attraction forces decreased exponentially over distance. For the nine configurations tested, the average forces were 3,334 ± 1,239 gf at 0.1 cm, 158 ± 98 gf at 2.5 cm, and 8.7 ± 12 gf at 5 cm; the drop-off threshold was 3.64 ± 0.8 cm. The larger stacking configurations and magnets yielded up to a 592% increase in attraction force at 2.5 cm and extended the drop-off threshold distance by up to 107% over single-stack anchors. For the strongest configuration, coupling force ranged from 5,337 gf at 0.1 cm to 0 gf at 6.95 cm and yielded a drop-off threshold distance of 4.78 cm. This study suggests that the strongest configuration of currently available MAGS instruments is suitable for clinically relevant abdominal wall thicknesses. Further platform development and optimization are warranted.

Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis.

PubMed

Pawade, Tania; Clavel, Marie-Annick; Tribouilloy, Christophe; Dreyfus, Julien; Mathieu, Tiffany; Tastet, Lionel; Renard, Cedric; Gun, Mesut; Jenkins, William Steven Arthur; Macron, Laurent; Sechrist, Jacob W; Lacomis, Joan M; Nguyen, Virginia; Galian Gay, Laura; Cuéllar Calabria, Hug; Ntalas, Ioannis; Cartlidge, Timothy Robert Graham; Prendergast, Bernard; Rajani, Ronak; Evangelista, Arturo; Cavalcante, João L; Newby, David E; Pibarot, Philippe; Messika Zeitoun, David; Dweck, Marc R

2018-03-01

Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an international multicenter cohort of patients. Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 [126-2251] days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 [95% confidence interval, 2.19-6.78]; P <0.001) after adjustment for age, sex, peak velocity, and aortic valve area. Among 210 (23%) patients with discordant echocardiographic assessments, there was considerable heterogeneity in CT-AVC scores, which again were an independent predictor of clinical outcomes (hazard ratio, 3.67 [95% confidence interval, 1.39-9.73]; P =0.010). Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431. © 2018 American Heart Association, Inc.

Diagnostic performance of BMI percentiles to identify adolescents with metabolic syndrome.

PubMed

Laurson, Kelly R; Welk, Gregory J; Eisenmann, Joey C

2014-02-01

To compare the diagnostic performance of the Centers for Disease Control and Prevention (CDC) and FITNESSGRAM (FGram) BMI standards for quantifying metabolic risk in youth. Adolescents in the NHANES (n = 3385) were measured for anthropometric variables and metabolic risk factors. BMI percentiles were calculated, and youth were categorized by weight status (using CDC and FGram thresholds). Participants were also categorized by presence or absence of metabolic syndrome. The CDC and FGram standards were compared by prevalence of metabolic abnormalities, various diagnostic criteria, and odds of metabolic syndrome. Receiver operating characteristic curves were also created to identify optimal BMI percentiles to detect metabolic syndrome. The prevalence of metabolic syndrome in obese youth was 19% to 35%, compared with <2% in the normal-weight groups. The odds of metabolic syndrome for obese boys and girls were 46 to 67 and 19 to 22 times greater, respectively, than for normal-weight youth. The receiver operating characteristic analyses identified optimal thresholds similar to the CDC standards for boys and the FGram standards for girls. Overall, BMI thresholds were more strongly associated with metabolic syndrome in boys than in girls. Both the CDC and FGram standards are predictive of metabolic syndrome. The diagnostic utility of the CDC thresholds outperformed the FGram values for boys, whereas FGram standards were slightly better thresholds for girls. The use of a common set of thresholds for school and clinical applications would provide advantages for public health and clinical research and practice.

"Mind the gap!" Evaluation of the performance gap attributable to exception reporting and target thresholds in the new GMS contract: National database analysis.

PubMed

Fleetcroft, Robert; Steel, Nicholas; Cookson, Richard; Howe, Amanda

2008-06-17

The 2003 revision of the UK GMS contract rewards general practices for performance against clinical quality indicators. Practices can exempt patients from treatment, and can receive maximum payment for less than full coverage of eligible patients. This paper aims to estimate the gap between the percentage of maximum incentive gained and the percentage of patients receiving indicated care (the pay-performance gap), and to estimate how much of the gap is attributable respectively to thresholds and to exception reporting. Analysis of Quality Outcomes Framework data in the National Primary Care Database and exception reporting data from the Information Centre from 8407 practices in England in 2005 - 6. The main outcome measures were the gap between the percentage of maximum incentive gained and the percentage of patients receiving indicated care at the practice level, both for individual indicators and a combined composite score. An additional outcome was the percentage of that gap attributable respectively to exception reporting and maximum threshold targets set at less than 100%. The mean pay-performance gap for the 65 aggregated clinical indicators was 13.3% (range 2.9% to 48%). 52% of this gap (6.9% of eligible patients) is attributable to thresholds being set at less than 100%, and 48% to patients being exception reported. The gap was greater than 25% in 9 indicators: beta blockers and cholesterol control in heart disease; cholesterol control in stroke; influenza immunization in asthma; blood pressure, sugar and cholesterol control in diabetes; seizures in epilepsy and treatment of hypertension. Threshold targets and exception reporting introduce an incentive ceiling, which substantially reduces the percentage of eligible patients that UK practices need to treat in order to receive maximum incentive payments for delivering that care. There are good clinical reasons for exception reporting, but after unsuitable patients have been exempted from treatment, there is no reason why all maximum thresholds should not be 100%, whilst retaining the current lower thresholds to provide incentives for lower performing practices.

Rapid exclusion of the diagnosis of immune HIT by AcuStar HIT and heparin-induced multiple electrode aggregometry.

PubMed

Minet, V; Baudar, J; Bailly, N; Douxfils, J; Laloy, J; Lessire, S; Gourdin, M; Devalet, B; Chatelain, B; Dogné, J M; Mullier, F

2014-06-01

Accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential but remains challenging. We have previously demonstrated, in a retrospective study, the usefulness of the combination of the 4Ts score, AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) with optimized thresholds. We aimed at exploring prospectively the performances of our optimized diagnostic algorithm on suspected HIT patients. The secondary objective is to evaluate performances of AcuStar HIT-Ab (PF4-H) in comparison with the clinical outcome. 116 inpatients with clinically suspected immune HIT were included. Our optimized diagnostic algorithm was applied to each patient. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) of the overall diagnostic strategy as well as AcuStar HIT-Ab (at manufacturer's thresholds and at our thresholds) were calculated using clinical diagnosis as the reference. Among 116 patients, 2 patients had clinically-diagnosed HIT. These 2 patients were positive on AcuStar HIT-Ab, AcuStar HIT-IgG and HIMEA. Using our optimized algorithm, all patients were correctly diagnosed. AcuStar HIT-Ab at our cut-off (>9.41 U/mL) and at manufacturer's cut-off (>1.00 U/mL) showed both a sensitivity of 100.0% and a specificity of 99.1% and 90.4%, respectively. The combination of the 4Ts score, the HemosIL® AcuStar HIT and HIMEA with optimized thresholds may be useful for the rapid and accurate exclusion of the diagnosis of immune HIT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity.

PubMed

Vaegter, Henrik B; Graven-Nielsen, Thomas

2016-07-01

Pain biomarkers are warranted for individualized pain management. Based on different pain modulatory phenotypes, the objectives of this study were to explore the existence of subgroups within patients with nonmalignant chronic pain and to investigate differences in clinical pain and pain hypersensitivity between subgroups. Cuff algometry was performed on lower legs in 400 patients with chronic pain to assess pressure pain threshold, pressure pain tolerance, temporal summation of pain (TSP: increase in pain scores to 10 repeated stimulations), and conditioned pain modulation (CPM: increase in cuff pressure pain threshold during cuff pain conditioning on the contralateral leg). Heat detection and heat pain thresholds at clinical painful and nonpainful body areas were assessed. Based on TSP and CPM, 4 distinct groups were formed: group 1 (n = 85) had impaired CPM and facilitated TSP; group 2 (n = 148) had impaired CPM and normal TSP; group 3 (n = 45) had normal CPM and facilitated TSP; and group 4 (n = 122) had normal CPM and normal TSP. Group 1 showed more pain regions than the other 3 groups (P < 0.001), indicating that impaired CPM and facilitated TSP play an important role in widespread pain. Groups 1 and 2 compared with group 4 had lower heat pain threshold at nonpainful areas and lower cuff pressure pain tolerance (P < 0.02), indicating that CPM plays a role for widespread hyperalgesia. Moreover, group 1 demonstrated higher clinical pain scores than group 4 (P < 0.05). Although not different between subgroups, patients were profiled on demographics, disability, pain catastrophizing, and fear of movement. Future research should investigate interventions tailored towards these subgroups.

Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery.

PubMed

Mazer, C David; Whitlock, Richard P; Fergusson, Dean A; Hall, Judith; Belley-Cote, Emilie; Connolly, Katherine; Khanykin, Boris; Gregory, Alexander J; de Médicis, Étienne; McGuinness, Shay; Royse, Alistair; Carrier, François M; Young, Paul J; Villar, Juan C; Grocott, Hilary P; Seeberger, Manfred D; Fremes, Stephen; Lellouche, François; Syed, Summer; Byrne, Kelly; Bagshaw, Sean M; Hwang, Nian C; Mehta, Chirag; Painter, Thomas W; Royse, Colin; Verma, Subodh; Hare, Gregory M T; Cohen, Ashley; Thorpe, Kevin E; Jüni, Peter; Shehata, Nadine

2017-11-30

The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red-cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red-cell transfusion and other clinical outcomes. The primary outcome occurred in 11.4% of the patients in the restrictive-threshold group, as compared with 12.5% of those in the liberal-threshold group (absolute risk difference, -1.11 percentage points; 95% confidence interval [CI], -2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive-threshold group and 3.6% in the liberal-threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red-cell transfusion occurred in 52.3% of the patients in the restrictive-threshold group, as compared with 72.6% of those in the liberal-threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between-group differences with regard to the other secondary outcomes. In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Twelve automated thresholding methods for segmentation of PET images: a phantom study.

PubMed

Prieto, Elena; Lecumberri, Pablo; Pagola, Miguel; Gómez, Marisol; Bilbao, Izaskun; Ecay, Margarita; Peñuelas, Iván; Martí-Climent, Josep M

2012-06-21

Tumor volume delineation over positron emission tomography (PET) images is of great interest for proper diagnosis and therapy planning. However, standard segmentation techniques (manual or semi-automated) are operator dependent and time consuming while fully automated procedures are cumbersome or require complex mathematical development. The aim of this study was to segment PET images in a fully automated way by implementing a set of 12 automated thresholding algorithms, classical in the fields of optical character recognition, tissue engineering or non-destructive testing images in high-tech structures. Automated thresholding algorithms select a specific threshold for each image without any a priori spatial information of the segmented object or any special calibration of the tomograph, as opposed to usual thresholding methods for PET. Spherical (18)F-filled objects of different volumes were acquired on clinical PET/CT and on a small animal PET scanner, with three different signal-to-background ratios. Images were segmented with 12 automatic thresholding algorithms and results were compared with the standard segmentation reference, a threshold at 42% of the maximum uptake. Ridler and Ramesh thresholding algorithms based on clustering and histogram-shape information, respectively, provided better results that the classical 42%-based threshold (p < 0.05). We have herein demonstrated that fully automated thresholding algorithms can provide better results than classical PET segmentation tools.

Twelve automated thresholding methods for segmentation of PET images: a phantom study

NASA Astrophysics Data System (ADS)

Prieto, Elena; Lecumberri, Pablo; Pagola, Miguel; Gómez, Marisol; Bilbao, Izaskun; Ecay, Margarita; Peñuelas, Iván; Martí-Climent, Josep M.

2012-06-01

Tumor volume delineation over positron emission tomography (PET) images is of great interest for proper diagnosis and therapy planning. However, standard segmentation techniques (manual or semi-automated) are operator dependent and time consuming while fully automated procedures are cumbersome or require complex mathematical development. The aim of this study was to segment PET images in a fully automated way by implementing a set of 12 automated thresholding algorithms, classical in the fields of optical character recognition, tissue engineering or non-destructive testing images in high-tech structures. Automated thresholding algorithms select a specific threshold for each image without any a priori spatial information of the segmented object or any special calibration of the tomograph, as opposed to usual thresholding methods for PET. Spherical 18F-filled objects of different volumes were acquired on clinical PET/CT and on a small animal PET scanner, with three different signal-to-background ratios. Images were segmented with 12 automatic thresholding algorithms and results were compared with the standard segmentation reference, a threshold at 42% of the maximum uptake. Ridler and Ramesh thresholding algorithms based on clustering and histogram-shape information, respectively, provided better results that the classical 42%-based threshold (p < 0.05). We have herein demonstrated that fully automated thresholding algorithms can provide better results than classical PET segmentation tools.

More inclusive bipolar mixed depression definitions by requiring fewer non-overlapping mood elevation symptoms.

PubMed

Kim, W; Kim, H; Citrome, L; Akiskal, H S; Goffin, K C; Miller, S; Holtzman, J N; Hooshmand, F; Wang, P W; Hill, S J; Ketter, T A

2016-09-01

Assess strengths and limitations of mixed bipolar depression definitions made more inclusive than that of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) by requiring fewer than three 'non-overlapping' mood elevation symptoms (NOMES). Among bipolar disorder (BD) out-patients assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, we assessed prevalence, demographics, and clinical correlates of mixed vs. pure depression, using less inclusive (≥3 NOMES, DSM-5), more inclusive (≥2 NOMES), and most inclusive (≥1 NOMES) definitions. Among 153 depressed BD, compared to less inclusive DSM-5 threshold, our more and most inclusive thresholds, yielded approximately two- and five-fold higher mixed depression rates (7.2%, 15.0%, and 34.6% respectively), and important statistically significant clinical correlates for mixed compared to pure depression (e.g. more lifetime anxiety disorder comorbidity, more current irritability), which were not significant using the DSM-5 threshold. Further studies assessing strengths and limitations of more inclusive mixed depression definitions are warranted, including assessing the extent to which enhanced statistical power vs. other factors contributes to more vs. less inclusive mixed bipolar depression thresholds having more statistically significant clinical correlates, and whether 'overlapping' mood elevation symptoms should be counted. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Decision curve analysis: a novel method for evaluating prediction models.

PubMed

Vickers, Andrew J; Elkin, Elena B

2006-01-01

Diagnostic and prognostic models are typically evaluated with measures of accuracy that do not address clinical consequences. Decision-analytic techniques allow assessment of clinical outcomes but often require collection of additional information and may be cumbersome to apply to models that yield a continuous result. The authors sought a method for evaluating and comparing prediction models that incorporates clinical consequences,requires only the data set on which the models are tested,and can be applied to models that have either continuous or dichotomous results. The authors describe decision curve analysis, a simple, novel method of evaluating predictive models. They start by assuming that the threshold probability of a disease or event at which a patient would opt for treatment is informative of how the patient weighs the relative harms of a false-positive and a false-negative prediction. This theoretical relationship is then used to derive the net benefit of the model across different threshold probabilities. Plotting net benefit against threshold probability yields the "decision curve." The authors apply the method to models for the prediction of seminal vesicle invasion in prostate cancer patients. Decision curve analysis identified the range of threshold probabilities in which a model was of value, the magnitude of benefit, and which of several models was optimal. Decision curve analysis is a suitable method for evaluating alternative diagnostic and prognostic strategies that has advantages over other commonly used measures and techniques.

Pure-tone audiometry outside a sound booth using earphone attentuation, integrated noise monitoring, and automation.

PubMed

Swanepoel, De Wet; Matthysen, Cornelia; Eikelboom, Robert H; Clark, Jackie L; Hall, James W

2015-01-01

Accessibility of audiometry is hindered by the cost of sound booths and shortage of hearing health personnel. This study investigated the validity of an automated mobile diagnostic audiometer with increased attenuation and real-time noise monitoring for clinical testing outside a sound booth. Attenuation characteristics and reference ambient noise levels for the computer-based audiometer (KUDUwave) was evaluated alongside the validity of environmental noise monitoring. Clinical validity was determined by comparing air- and bone-conduction thresholds obtained inside and outside the sound booth (23 subjects). Twenty-three normal-hearing subjects (age range, 20-75 years; average age 35.5) and a sub group of 11 subjects to establish test-retest reliability. Improved passive attenuation and valid environmental noise monitoring was demonstrated. Clinically, air-conduction thresholds inside and outside the sound booth, corresponded within 5 dB or less > 90% of instances (mean absolute difference 3.3 ± 3.2 SD). Bone conduction thresholds corresponded within 5 dB or less in 80% of comparisons between test environments, with a mean absolute difference of 4.6 dB (3.7 SD). Threshold differences were not statistically significant. Mean absolute test-retest differences outside the sound booth was similar to those in the booth. Diagnostic pure-tone audiometry outside a sound booth, using automated testing, improved passive attenuation, and real-time environmental noise monitoring demonstrated reliable hearing assessments.

Safety and clinical performance of acoustic reflex tests.

PubMed

Hunter, L L; Ries, D T; Schlauch, R S; Levine, S C; Ward, W D

1999-12-01

Safety and effectiveness of acoustic reflex tests are important issues because these tests are widely applied to screen for retrocochlear pathology. Previous studies have reported moderately high sensitivity and specificity for detection of acoustic neuroma. However, there have been reports of possible iatrogenic hearing loss resulting from acoustic reflex threshold (ART) and decay (ARD) tests. This study assessed safety and clinical performance of ART tests for detection of acoustic neuroma. We report a case in which ARD testing resulted in a significant bilateral permanent threshold shift. This case was the impetus for us to investigate the clinical utility of ART and ARD tests. We analyzed sensitivity and specificity of ART, as well as asymmetry in pure-tone thresholds (PTT) for detection of acoustic neuroma in 56 tumor and 108 non-tumor ears. Sensitivity and specificity were higher for PTT asymmetry than for ART. Ipsilateral ART at 1000 Hz had poor sensitivity and specificity for detection of acoustic neuroma, and involves some potential risk to residual hearing for presentation levels higher than 115 dB SPL. Approximately half of the acoustic neuroma group had ipsilateral ARTs that would require administration of ARD tests at levels exceeding 115 dB SPL. Therefore, we conclude that PTT asymmetry is a more effective test for detection of acoustic neuroma, and involves no risk to residual hearing. Future studies of contralateral reflex threshold and ARD in combination with PTT asymmetry are recommended.

Amplitudes of Pain-Related Evoked Potentials Are Useful to Detect Small Fiber Involvement in Painful Mixed Fiber Neuropathies in Addition to Quantitative Sensory Testing – An Electrophysiological Study

PubMed Central

Hansen, Niels; Kahn, Ann-Kathrin; Zeller, Daniel; Katsarava, Zaza; Sommer, Claudia; Üçeyler, Nurcan

2015-01-01

To investigate the usefulness of pain-related evoked potentials (PREP) elicited by electrical stimulation for the identification of small fiber involvement in patients with mixed fiber neuropathy (MFN). Eleven MFN patients with clinical signs of large fiber impairment and neuropathic pain and ten healthy controls underwent clinical and electrophysiological evaluation. Small fiber function, electrical conductivity and morphology were examined by quantitative sensory testing (QST), PREP, and skin punch biopsy. MFN was diagnosed following clinical and electrophysiological examination (chronic inflammatory demyelinating neuropathy: n = 6; vasculitic neuropathy: n = 3; chronic axonal ­neuropathy: n = 2). The majority of patients with MFN characterized their pain by descriptors that mainly represent C-fiber-mediated pain. In QST, patients displayed elevated cold, warm, mechanical, and vibration detection thresholds and cold pain thresholds indicative of MFN. PREP amplitudes in patients correlated with cold (p < 0.05) and warm detection thresholds (p < 0.05). Burning pain and the presence of par-/dysesthesias correlated negatively with PREP amplitudes (p < 0.05). PREP amplitudes correlating with cold and warm detection thresholds, burning pain, and par-/dysesthesias support employing PREP amplitudes as an additional tool in conjunction with QST for detecting small fiber impairment in patients with MFN. PMID:26696950

"Threshold-crossing": A Useful Way to Establish the Counterfactual in Clinical Trials?

PubMed

Eichler, H-G; Bloechl-Daum, B; Bauer, P; Bretz, F; Brown, J; Hampson, L V; Honig, P; Krams, M; Leufkens, H; Lim, R; Lumpkin, M M; Murphy, M J; Pignatti, F; Posch, M; Schneeweiss, S; Trusheim, M; Koenig, F

2016-12-01

A central question in the assessment of benefit/harm of new treatments is: how does the average outcome on the new treatment (the factual) compare to the average outcome had patients received no treatment or a different treatment known to be effective (the counterfactual)? Randomized controlled trials (RCTs) are the standard for comparing the factual with the counterfactual. Recent developments necessitate and enable a new way of determining the counterfactual for some new medicines. For select situations, we propose a new framework for evidence generation, which we call "threshold-crossing." This framework leverages the wealth of information that is becoming available from completed RCTs and from real world data sources. Relying on formalized procedures, information gleaned from these data is used to estimate the counterfactual, enabling efficacy assessment of new drugs. We propose future (research) activities to enable "threshold-crossing" for carefully selected products and indications in which RCTs are not feasible. © 2016 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Binge Eating, Purging, or Both: Eating Disorder Psychopathology Findings from an Internet Community Survey

PubMed Central

Roberto, Christina A.; Grilo, Carlos M.; Masheb, Robin M.; White, Marney A.

2010-01-01

Objective This study aimed to compare bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD) on clinically significant variables and examine the utility of once versus twice-weekly diagnostic thresholds for disturbed eating behaviors. Method 234 women with BN, BED, or PD were identified through self-report measures via an online survey and categorized based on either once-weekly or twice-weekly disturbed eating behaviors. Results BN emerged as a more severe disorder than BED and PD. The three groups differed significantly in self-reported restraint and disinhibition and the BN and BED groups reported higher levels of depression than PD. For BN, those engaging in behaviors twice-weekly versus once-weekly were more symptomatic. Discussion The BN, BED, and PD groups differed in clinically meaningful ways. Future research need to clarify the relationship between mood disturbances and eating behaviors. Reducing the twice-weekly behavior threshold for BN would capture individuals with clinically significant eating disorders, though the twice-weekly threshold may provide important information about disorder severity for both BN and BED. PMID:19862702

Comparison of the cytotoxicity of clinically relevant cobalt-chromium and alumina ceramic wear particles in vitro.

PubMed

Germain, M A; Hatton, A; Williams, S; Matthews, J B; Stone, M H; Fisher, J; Ingham, E

2003-02-01

Concern over polyethylene wear particle induced aseptic loosening of metal-on-polyethylene hip prostheses has led to renewed interest in alternative materials such as metal-on-metal and alumina ceramic-on-alumina ceramic for total hip replacement. This study compared the effects of clinically relevant cobalt-chromium and alumina ceramic wear particles on the viability of U937 histiocytes and L929 fibroblasts in vitro. Clinically relevant cobalt-chromium wear particles were generated using a flat pin-on-plate tribometer. The mean size of the clinically relevant metal particles was 29.5+/-6.3 nm (range 5-200 nm). Clinically relevant alumina ceramic particles were generated in the Leeds MkII anatomical hip simulator from a Mittelmieier prosthesis using micro-separation motion. This produced particles with a bimodal size distribution. The majority (98%) of the clinically relevant alumina ceramic wear debris was 5-20 nm in size. The cytotoxicity of the clinically relevant wear particles was compared to commercially available cobalt-chromium (9.87 microm+/-5.67) and alumina ceramic (0.503+/-0.19 microm) particles. The effects of the particles on the cells over a 5 day period at different particle volume (microm(3)) to cell number ratios were tested and viability determined using ATP-Lite(TM). Clinically relevant cobalt-chromium particles 50 and 5 microm(3) per cell reduced the viability of U937 cells by 97% and 42% and reduced the viability of L929 cells by 95% and 73%, respectively. At 50 microm(3) per cell, the clinically relevant ceramic particles reduced U937 cell viability by 18%. None of the other concentrations of the clinically relevant particles were toxic. The commercial cobalt-chromium and alumina particles did not affect the viability of either the U937 histiocytes or the L929 fibroblasts.Thus at equivalent particle volumes the clinically relevant cobalt-chromium particles were more toxic then the alumina ceramic particles. This study has emphasised the fact that the nature, size and volume of particles are important in assessing biological effects of wear debris on cells in vitro.

Plague epizootic cycles in Central Asia.

PubMed

Reijniers, Jonas; Begon, Mike; Ageyev, Vladimir S; Leirs, Herwig

2014-06-01

Infection thresholds, widely used in disease epidemiology, may operate on host abundance and, if present, on vector abundance. For wildlife populations, host and vector abundances often vary greatly across years and consequently the threshold may be crossed regularly, both up- and downward. Moreover, vector and host abundances may be interdependent, which may affect the infection dynamics. Theory predicts that if the relevant abundance, or combination of abundances, is above the threshold, then the infection is able to spread; if not, it is bound to fade out. In practice, though, the observed level of infection may depend more on past than on current abundances. Here, we study the temporal dynamics of plague (Yersinia pestis infection), its vector (flea) and its host (great gerbil) in the PreBalkhash region in Kazakhstan. We describe how host and vector abundances interact over time and how this interaction drives the dynamics of the system around the infection threshold, consequently affecting the proportion of plague-infected sectors. We also explore the importance of the interplay between biological and detectability delays in generating the observed dynamics.

Novel Analog For Muscle Deconditioning

NASA Technical Reports Server (NTRS)

Ploutz-Snyder, Lori; Ryder, Jeff; Buxton, Roxanne; Redd. Elizabeth; Scott-Pandorf, Melissa; Hackney, Kyle; Fiedler, James; Ploutz-Snyder, Robert; Bloomberg, Jacob

2011-01-01

Existing models (such as bed rest) of muscle deconditioning are cumbersome and expensive. We propose a new model utilizing a weighted suit to manipulate strength, power, or endurance (function) relative to body weight (BW). Methods: 20 subjects performed 7 occupational astronaut tasks while wearing a suit weighted with 0-120% of BW. Models of the full relationship between muscle function/BW and task completion time were developed using fractional polynomial regression and verified by the addition of pre-and postflightastronaut performance data for the same tasks. Splineregression was used to identify muscle function thresholds below which task performance was impaired. Results: Thresholds of performance decline were identified for each task. Seated egress & walk (most difficult task) showed thresholds of leg press (LP) isometric peak force/BW of 18 N/kg, LP power/BW of 18 W/kg, LP work/BW of 79 J/kg, isokineticknee extension (KE)/BW of 6 Nm/kg, and KE torque/BW of 1.9 Nm/kg.Conclusions: Laboratory manipulation of relative strength has promise as an appropriate analog for spaceflight-induced loss of muscle function, for predicting occupational task performance and establishing operationally relevant strength thresholds.

A piecewise regression approach for determining biologically relevant hydraulic thresholds for the protection of fishes at river infrastructure.

PubMed

Boys, C A; Robinson, W; Miller, B; Pflugrath, B; Baumgartner, L J; Navarro, A; Brown, R; Deng, Z

2016-05-01

A piecewise regression approach was used to objectively quantify barotrauma injury thresholds in two physoclistous species, Murray cod Maccullochella peelii and silver perch Bidyanus bidyanus, following simulated infrastructure passage in a barometric chamber. The probability of injuries such as swimbladder rupture, exophthalmia and haemorrhage, and emphysema in various organs increased as the ratio between the lowest exposure pressure and the acclimation pressure (ratio of pressure change, R(NE:A) ) reduced. The relationship was typically non-linear and piecewise regression was able to quantify thresholds in R(NE:A) that once exceeded resulted in a substantial increase in barotrauma injury. Thresholds differed among injury types and between species but by applying a multispecies precautionary principle, the maintenance of exposure pressures at river infrastructure above 70% of acclimation pressure (R(NE:A) of 0·7) should protect downstream migrating juveniles of these two physoclistous species sufficiently. These findings have important implications for determining the risk posed by current infrastructures and informing the design and operation of new ones. © 2016 The Fisheries Society of the British Isles.

Development of water quality thresholds during dredging for the protection of benthic primary producer habitats.

PubMed

Sofonia, Jeremy J; Unsworth, Richard K F

2010-01-01

Given the potential for adverse effects of ocean dredging on marine organisms, particularly benthic primary producer communities, the management and monitoring of those activities which cause elevated turbidity and sediment loading is critical. In practice, however, this has proven challenging as the development of water quality threshold values, upon which management responses are based, are subject to a large number of physical and biological parameters that are spatially and temporally specific. As a consequence, monitoring programs to date have taken a wide range of different approaches, most focusing on measures of turbidity reported as nephelometric turbidity units (NTU). This paper presents a potential approach in the determination of water quality thresholds which utilises data gathered through the long-term deployment of in situ water instruments, but suggests a focus on photosynthetic active radiation (PAR) rather than NTU as it is more relevant biologically and inclusive of other site conditions. A simple mathematical approach to data interpretation is also presented which facilitates threshold value development, not individual values of concentrations over specific intervals, but as an equation which may be utilized in numerical modelling.

Using pixel intensity as a self-regulating threshold for deterministic image sampling in Milano Retinex: the T-Rex algorithm

NASA Astrophysics Data System (ADS)

Lecca, Michela; Modena, Carla Maria; Rizzi, Alessandro

2018-01-01

Milano Retinexes are spatial color algorithms, part of the Retinex family, usually employed for image enhancement. They modify the color of each pixel taking into account the surrounding colors and their position, catching in this way the local spatial color distribution relevant to image enhancement. We present T-Rex (from the words threshold and Retinex), an implementation of Milano Retinex, whose main novelty is the use of the pixel intensity as a self-regulating threshold to deterministically sample local color information. The experiments, carried out on real-world pictures, show that T-Rex image enhancement performance are in line with those of the Milano Retinex family: T-Rex increases the brightness, the contrast, and the flatness of the channel distributions of the input image, making more intelligible the content of pictures acquired under difficult light conditions.

Effective sextic superpotential and B-L violation in NMSGUT

NASA Astrophysics Data System (ADS)

Aulakh, C. S.; Awasthi, R. L.; Krishna, Shri

2017-10-01

We list operators of the superpotential of the effective MSSM that emerge from the NMSGUT up to sextic degree. We give illustrative expressions for the coefficients in terms of NMSGUT parameters. We also estimate the impact of GUT scale threshold corrections on these effective operators in view of the demonstration that B violation via quartic superpotential terms can be suppressed to acceptable levels after including such corrections in the NMSGUT. We find a novel B, B-L violating quintic operator that leads to the decay mode n→ e^- K^+. We also remark that the threshold corrections to the Type-I seesaw mechanism make the deviation of right-handed neutrino masses from the GUT scale more natural while Type-II seesaw neutrino masses, which earlier tended to utterly negligible receive threshold enhancement. Our results are of relevance for analysing B-L violating operator-based, sphaleron-safe, baryogenesis.

Near-threshold NN→dπ reaction in chiral perturbation theory

NASA Astrophysics Data System (ADS)

Gårdestig, A.; Phillips, D. R.; Elster, Ch.

2006-02-01

The near-threshold np→dπ0 cross section is calculated in chiral perturbation theory to next-to-leading order in the expansion parameter √(Mmπ)/Λχ. At this order irreducible pion loops contribute to the relevant pion-production operator. Although their contribution to this operator is finite, considering initial- and final-state distortions produces a linear divergence in its matrix elements. We renormalize this divergence by introducing a counterterm, whose value we choose to reproduce the threshold np→dπ0 cross section measured at TRIUMF. The energy dependence of this cross section is then predicted in chiral perturbation theory, being determined by the production of p-wave pions, and also by energy dependence in the amplitude for the production of s-wave pions. With an appropriate choice of the counterterm, the chiral prediction for this energy dependence converges well.

New method to evaluate the 7Li(p, n)7Be reaction near threshold

NASA Astrophysics Data System (ADS)

Herrera, María S.; Moreno, Gustavo A.; Kreiner, Andrés J.

2015-04-01

In this work a complete description of the 7Li(p, n)7Be reaction near threshold is given using center-of-mass and relative coordinates. It is shown that this standard approach, not used before in this context, leads to a simple mathematical representation which gives easy access to all relevant quantities in the reaction and allows a precise numerical implementation. It also allows in a simple way to include proton beam-energy spread affects. The method, implemented as a C++ code, was validated both with numerical and experimental data finding a good agreement. This tool is also used here to analyze scattered published measurements such as (p, n) cross sections, differential and total neutron yields for thick targets. Using these data we derive a consistent set of parameters to evaluate neutron production near threshold. Sensitivity of the results to data uncertainty and the possibility of incorporating new measurements are also discussed.

Scaling properties of ballistic nano-transistors

PubMed Central

2011-01-01

Recently, we have suggested a scale-invariant model for a nano-transistor. In agreement with experiments a close-to-linear thresh-old trace was found in the calculated ID - VD-traces separating the regimes of classically allowed transport and tunneling transport. In this conference contribution, the relevant physical quantities in our model and its range of applicability are discussed in more detail. Extending the temperature range of our studies it is shown that a close-to-linear thresh-old trace results at room temperatures as well. In qualitative agreement with the experiments the ID - VG-traces for small drain voltages show thermally activated transport below the threshold gate voltage. In contrast, at large drain voltages the gate-voltage dependence is weaker. As can be expected in our relatively simple model, the theoretical drain current is larger than the experimental one by a little less than a decade. PMID:21711899

The effectiveness and cost-effectiveness of cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients on dialysis: a systematic review and economic evaluation.

PubMed

Garside, R; Pitt, M; Anderson, R; Mealing, S; Roome, C; Snaith, A; D'Souza, R; Welch, K; Stein, K

2007-05-01

To establish the effectiveness and cost-effectiveness of cinacalcet for the treatment of secondary hyperparathyroidism (SHPT) for people on dialysis due to end-stage renal disease (ESRD). Electronic databases were searched up to February 2006. Included randomised controlled trials (RCTs) on the clinical effectiveness of cinacalcet for SHPT in ESRD were critically appraised, had relevant data extracted and were summarised narratively. A Markov (state transition) model was developed that compared cinacalcet in addition to current standard treatment with phosphate binders and vitamin D to standard treatment alone. A simulated cohort of 1000 people aged 55 with SHPT was modelled until the whole cohort was dead. Incremental costs and quality-adjusted life-years (QALYs) were calculated. Extensive one-way sensitivity analysis was undertaken as well as probabilistic sensitivity analysis. Seven trials comparing cinacalcet plus standard treatment with placebo plus standard treatment were included in the systematic review. A total of 846 people were randomised to receive cinacalcet. Cinacalcet was more effective at meeting parathyroid hormone (PTH) target levels (40% vs 5% in placebo, p < 0.001). In those patients meeting PTH targets, 90% also experienced a reduction in calcium-phosphate product levels, compared with 1% in placebo. Significantly fewer people treated with cinacalcet were hospitalised for cardiovascular events, although no difference was seen in all-cause hospitalisation or mortality. Significantly fewer fractures and parathyroidectomies were also seen with cinacalcet. Findings on all patient-based clinical outcomes were based on small numbers. The authors' economic model estimated that, compared to standard treatment alone, cinacalcet in addition to standard care costs an additional 21,167 pounds and confers 0.34 QALYs (or 18 quality-adjusted weeks) per person. The incremental cost-effectiveness ratio (ICER) was 61,890 pounds/QALY. In most cases, even extreme adjustments to individual parameters did not result in an ICER below a willingness-to-pay threshold of 30,000 pounds/QALY with probabilistic analysis showing only 0.5% of simulations to be cost-effective at this threshold. Altering the assumptions in the model through using different data sources for the inputs produced a range of ICERs from 39,000 pounds to 92,000 pounds/QALY. Cinacalcet in addition to standard care is more effective than placebo plus standard care at reducing PTH levels without compromising calcium levels. However, there is limited information about the impact of this reduction on patient-relevant clinical outcomes. Given the short follow-up in the trials, it is unclear how data should be extrapolated to the long term. Together with the high drug cost, this leads to cinacalcet being unlikely to be considered cost-effective. Recommendations for future research include obtaining accurate estimates of the multivariate relationship between biochemical disruption in SHPT and long-term clinical outcomes.

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

Wu Shioumin; Kruijs, Robbert van de; Zoethout, Erwin

Ion sputtering yields for Ru, Mo, and Si under Ar{sup +} ion bombardment in the near-threshold energy range have been studied using an in situ weight-loss method with a Kaufman ion source, Faraday cup, and quartz crystal microbalance. The results are compared to theoretical models. The accuracy of the in situ weight-loss method was verified by thickness-decrease measurements using grazing incidence x-ray reflectometry, and results from both methods are in good agreement. These results provide accurate data sets for theoretical modeling in the near-threshold sputter regime and are of relevance for (optical) surfaces exposed to plasmas, as, for instance, inmore » extreme ultraviolet photolithography.« less

[Clinical diagnosis of Treacher Collins syndrome and the efficacy of using BAHA].

PubMed

Wang, Y B; Chen, X W; Wang, P; Fan, X M; Fan, Y; Liu, Q; Gao, Z Q

2017-04-20

Objective: To evaluate the efficacy of soft or implanted BAHA in the patients of Treacher Collins syndrome(TCS). Method: Six patients of TCS were studied. The Teber scoring system was used to evaluate the deformity degree. The air and bone auditory thresholds were assessed by auditory brain stem response(ABR). The infant-toddler meaningful auditory integration scale(IT-MAIS) was used to assess the auditory development at three time levels: baseline,3 months and 6 months. The hearing threshold and speech recognition score were measured under unaided and aided conditions. Result: The average score of deformity degree was 14.0±0.6. The TCOF1 gene was tested in two patients. The bone conduction hearing thresholds of patients was（18.0±4.5）dBnHL and the air conduction hearing thresholds was （70.5±7.0）dBnHL. The IT-MAIS total, detection and perception scores were improved significantly after wearing softband BAHA and approached the normal level in the 2 patients under 2 years old. The hearing thresholds of 6 patients in unaided and softband BAHA conditions were（65.8±3.8）dBHL and （30.0±3.2）dBHL ( P <0.01) respectively, and 1 implanted BAHA was 15 dBHL. The speech recognition scores of 3 patients in unaided and softband BAHA conditions were（31.7±3.5）% and（86.0±1.7）%( P <0.05) respectively, and 1 implanted BAHA was 96%. Conclusion: Whenever the patient was diagnosed as TCS by the clinical manifestations and genetic testing, BAHA system could help to rehabilitate the hearing to a normal condition. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Self-administered hearing loss screening using an interactive, tablet play audiometer with ear bud headphones.

PubMed

Yeung, Jeffrey C; Heley, Sophie; Beauregard, Yves; Champagne, Sandra; Bromwich, Matthew A

2015-08-01

The timely diagnosis and treatment of acquired hearing loss in the pediatric population has significant implications for a child's development. Audiological assessment in children, however, carries both technological and logistical challenges. Typically, specialized methods (such as play audiometry) are required to maintain the child's attention and can be resource intensive. These challenges were previously addressed by a novel, calibrated, interactive play audiometer for Apple(®) iOS(®) called "ShoeBOX Audiometry". This device has potential applications for deployment in environments where traditional clinical audiometry is either unavailable or impractical. The objective of this study was to assess the screening capability of the tablet audiometer in an uncontrolled environment using consumer ear-bud headphones. Consecutive patients presenting to the Audiology Clinic at the Children's Hospital of Eastern Ontario (ages 4 and older) were recruited. Participants' hearing was evaluted using the tablet audiometer calibrated to Apple(®) In-Ear headphones. The warble tone thresholds obtained were compared to gold standard measurements taken with a traditional clinical audiometer inside a soundbooth. 80 patients were enrolled. The majority of participants were capable of completing an audiologic assessment using the tablet computer. Due to ambient noise levels outside a soundbooth, thresholds obtained at 500Hz were not consistent with traditional audiometry. Excluding 500Hz threholds, the tablet audiometer demonstrated strong negative predictive value (89.7%) as well as strong sensitivity (91.2%) for hearing loss. Thresholds obtained in an uncontrolled setting are not reflective of diagnostic thresholds due to the uncalibrated nature of the headphones and variability of the setting without a booth. Nevertheless, the tablet audiometer proved to be both a valid and sensitive instrument for unsupervised screening of warble-tone thresholds in children. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Optimizing the rapid measurement of detection thresholds in infants

PubMed Central

Jones, Pete R.; Kalwarowsky, Sarah; Braddick, Oliver J.; Atkinson, Janette; Nardini, Marko

2015-01-01

Accurate measures of perceptual threshold are difficult to obtain in infants. In a clinical context, the challenges are particularly acute because the methods must yield meaningful results quickly and within a single individual. The present work considers how best to maximize speed, accuracy, and reliability when testing infants behaviorally and suggests some simple principles for improving test efficiency. Monte Carlo simulations, together with empirical (visual acuity) data from 65 infants, are used to demonstrate how psychophysical methods developed with adults can produce misleading results when applied to infants. The statistical properties of an effective clinical infant test are characterized, and based on these, it is shown that (a) a reduced (false-positive) guessing rate can greatly increase test efficiency, (b) the ideal threshold to target is often below 50% correct, and (c) simply taking the max correct response can often provide the best measure of an infant's perceptual sensitivity. PMID:26237298

Emerging Evidence of Thresholds for Beneficial Effects from Vitamin D Supplementation.

PubMed

Scragg, Robert

2018-05-03

Publications from clinical trials of vitamin D supplementation have increased substantially over the last 15 years. Yet, despite the growing number of randomized controlled trials, meta-analyses of these studies have drawn inconsistent conclusions. Many meta-analyses assume that vitamin D is a pharmacological agent, and give scant consideration of it being a nutrient. This limits their potential to detect beneficial effects in participants with vitamin D deficiency. An increasing body of evidence from both observational studies and clinical trials supports the presence of thresholds in vitamin D status below which disease risk increases and vitamin supplementation has beneficial effects. Future supplementation trials which seek to replicate these findings should recruit sufficient numbers of participants with low vitamin D levels, and not give low-dose vitamin D to the placebo group. If the presence of vitamin D thresholds for beneficial effects is confirmed, this would strengthen the need for vitamin D fortification of foods.

[Comparison of reproducibility measurements for calibration of dental caries epidemiological surveys].

PubMed

Assaf, Andréa Videira; Zanin, Luciane; Meneghim, Marcelo de Castro; Pereira, Antonio Carlos; Ambrosano, Gláucia Maria Bovi

2006-09-01

This study compares three measurements (Kappa, general agreement percentage, or GAP, and dice index) used to determine the reproducibility of caries diagnosis in epidemiological surveys under different clinical diagnostic thresholds. Eleven examiners with previous experience in epidemiological surveys were submitted to a theoretical and clinical calibration process. Data analysis used two caries detection thresholds: World Health Organization (WHO) and WHO with the inclusion of initial enamel lesions (WHO + IL). Twenty-three children 6-7 years of age were examined, with and without caries. Mean values for Kappa index, GAP, and Dice were considered high (> 0.90), except for the dice index for the WHO + IL threshold (0.69). Since Kappa is an adjusted agreement index, it can be considered the instrument of choice for calibration of examiners. However, when it is impossible to use, the GAP is recommended together with the dice index in order to orient and improve examiners when examining caries lesions.

Comparison of Versant HBV DNA 3.0 and COBAS AmpliPrep-COBAS TaqMan assays for hepatitis B DNA quantitation: Possible clinical implications.

PubMed

Garbuglia, A R; Angeletti, C; Lauria, F N; Zaccaro, P; Cocca, A M; Pisciotta, M; Solmone, M; Capobianchi, M R

2007-12-01

We compared two commercial assays for HBV DNA quantitation, Versant HBV 3.0, System 340 (bDNA; Bayer Diagnostics) and COBAS AmpliPrep-COBAS TaqMan HBV Test (TaqMan; Roche Diagnostics). Analytical sensitivity, calculated on WHO International Standard, predicted 95% detection rate at 11.4 and 520.2IU/ml for TaqMan and bDNA, respectively. Specificity, established on 50 blood donor samples, was 100% and 84% for TaqMan and bDNA, respectively. When using clinical samples, HBV DNA was detected by TaqMan in 21/55 samples negative to bDNA. Mean values of HBV DNA obtained with bDNA were higher than those obtained with TaqMan (4.09log(10)+/-1.90 versus 3.39log(10)+/-2.41, p<0.001), and 24.4% of samples showed differences in viral load values >0.5log(10), without association with HBV genotype. There was a good correlation for HBV DNA concentrations measured by the two assays (r=0.94; p<0.001) within the overlapping range, and the distribution of results with respect to relevant clinical threshold recently confirmed (20,000 and 2000IU/ml) was similar. Approximately 50% of samples with low HBV DNA, appreciated by TaqMan but not by bDNA, were successfully sequenced in pol region, where drug resistance mutations are located.

Assessment of depression in medical patients: a systematic review of the utility of the Beck Depression Inventory-II.

PubMed

Wang, Yuan-Pang; Gorenstein, Clarice

2013-09-01

To perform a systematic review of the utility of the Beck Depression Inventory for detecting depression in medical settings, this article focuses on the revised version of the scale (Beck Depression Inventory-II), which was reformulated according to the DSM-IV criteria for major depression. We examined relevant investigations with the Beck Depression Inventory-II for measuring depression in medical settings to provide guidelines for practicing clinicians. Considering the inclusion and exclusion criteria seventy articles were retained. Validation studies of the Beck Depression Inventory-II, in both primary care and hospital settings, were found for clinics of cardiology, neurology, obstetrics, brain injury, nephrology, chronic pain, chronic fatigue, oncology, and infectious disease. The Beck Depression Inventory-II showed high reliability and good correlation with measures of depression and anxiety. Its threshold for detecting depression varied according to the type of patients, suggesting the need for adjusted cut-off points. The somatic and cognitive-affective dimension described the latent structure of the instrument. The Beck Depression Inventory-II can be easily adapted in most clinical conditions for detecting major depression and recommending an appropriate intervention. Although this scale represents a sound path for detecting depression in patients with medical conditions, the clinician should seek evidence for how to interpret the score before using the Beck Depression Inventory-II to make clinical decisions.

Toxicity assessment strategies, data requirements, and risk assessment approaches to derive health based guidance values for non-relevant metabolites of plant protection products.

PubMed

Dekant, Wolfgang; Melching-Kollmuss, Stephanie; Kalberlah, Fritz

2010-03-01

In Europe, limits for tolerable concentrations of "non-relevant metabolites" for active ingredients (AI) of plant protection products in drinking water between 0.1 and 10 microg/L are discussed depending on the toxicological information available. "Non-relevant metabolites" are degradation products of AIs, which do not or only partially retain the targeted toxicities of AIs. For "non-relevant metabolites" without genotoxicity (to be confirmed by testing in vitro), the application of the concept of "thresholds of toxicological concern" results in a health-based drinking water limit of 4.5 microg/L even for Cramer class III compounds, using the TTC threshold of 90 microg/person/day (divided by 10 and 2). Taking into account the thresholds derived from two reproduction toxicity data bases a drinking water limit of 3.0 microg/L is proposed. Therefore, for "non-relevant metabolites" whose drinking water concentration is below 3.0 microg/L, no toxicity testing is necessary. This work develops a toxicity assessment strategy as a basis to delineate health-based limits for "non-relevant metabolites" in ground and drinking water. Toxicological testing is recommended to investigate, whether the metabolites are relevant or not, based on the hazard properties of the parent AIs, as outlined in the SANCO Guidance document. Also, genotoxicity testing of the water metabolites is clearly recommended. In this publication, tiered testing strategies are proposed for non-relevant metabolites, when drinking water concentrations >3.0 microg/L will occur. Conclusions based on structure-activity relationships and the detailed toxicity database on the parent AI should be included. When testing in animals is required for risk assessment, key aspects are studies along OECD-testing guidelines with "enhanced" study designs addressing additional endpoints such as reproductive toxicity and a developmental screening test to derive health-based tolerable drinking water limits with a limited number of animals. The testing strategies are similar to those used in the initial hazard assessment of high production volume (HPV) chemicals. For "non-relevant metabolites" which are also formed as products of the biotransformation of the parent AI in mammals, the proposed toxicity testing strategies uses the repeat-dose oral toxicity study combined with a reproductive/developmental screening as outlined in OECD test guidelines 407 and 422 with integration of determination of hormonal activities. For "non-relevant metabolites" not formed during biotransformation of the AI in mammals, the strategy relies on an "enhanced" 90-day oral study covering additional endpoints regarding hormonal effects and male and female fertility in combination with a prenatal developmental toxicity study (OECD test guideline 414). The integration of the results of these studies into the risk assessment process applies large minimal margins of exposure (MOEs) to compensate for the shorter duration of the studies. The results of the targeted toxicity testing will provide a science basis for setting tolerable drinking water limits for "non-relevant metabolites" based on their toxicology. Based on the recommendations given in the SANCO guidance document and the work described in this and the accompanying paper, a concise re-evaluation of the Guidance document is proposed. (c) 2009 Elsevier Inc. All rights reserved.

Reimbursement of licensed cell and gene therapies across the major European healthcare markets

PubMed Central

Jørgensen, Jesper; Kefalas, Panos

2015-01-01

Objective The aim of this research is to identify the pricing, reimbursement, and market access (P&R&MA) considerations most relevant to advanced therapy medicinal products (ATMPs) in the Big5EU, and to inform their manufacturers about the key drivers for securing adoption at a commercially viable reimbursed price. Methodology The research was structured following three main steps: 1) Identifying the market access pathways relevant to ATMPs through secondary research; 2) Validating the secondary research findings and addressing any data gaps in primary research, by qualitative interviews with national, regional, and local-level payers and their clinical and economic advisors; 3) Collating of primary and secondary findings to compare results across countries. Results The incremental clinical benefit forms the basis for all P&R&MA processes. Budget impact is a key consideration, regardless of geography. Cost-effectiveness analyses are increasingly applied; however, only the United Kingdom has a defined threshold that links the cost per quality-adjusted life year (QALY) specifically and methodologically to the reimbursed price. Funding mechanisms to enable adoption of new and more expensive therapies exist in all countries, albeit to varying extents. Willingness to pay is typically higher in smaller patient populations, especially in populations with high disease burden. Outcomes modelling and risk-sharing agreements (RSAs) provide strategies to address the data gap and uncertainties often associated with trials in niche populations. Conclusions The high cost of ATMPs, coupled with the uncertainty at launch around their long-term claims, present challenges for their adoption at a commercially viable reimbursed price. Targeting populations of high disease burden and unmet needs may be advantageous, as the potential for improvement in clinical benefit is greater, as well as the potential for capitalising on healthcare cost offsets. Also, targeting small populations can also help reduce both payers’ budget impact concerns and the risk of reimbursement restrictions being imposed. PMID:27123175

Modeling Disease Severity in Multiple Sclerosis Using Electronic Health Records

PubMed Central

Xia, Zongqi; Secor, Elizabeth; Chibnik, Lori B.; Bove, Riley M.; Cheng, Suchun; Chitnis, Tanuja; Cagan, Andrew; Gainer, Vivian S.; Chen, Pei J.; Liao, Katherine P.; Shaw, Stanley Y.; Ananthakrishnan, Ashwin N.; Szolovits, Peter; Weiner, Howard L.; Karlson, Elizabeth W.; Murphy, Shawn N.; Savova, Guergana K.; Cai, Tianxi; Churchill, Susanne E.; Plenge, Robert M.; Kohane, Isaac S.; De Jager, Philip L.

2013-01-01

Objective To optimally leverage the scalability and unique features of the electronic health records (EHR) for research that would ultimately improve patient care, we need to accurately identify patients and extract clinically meaningful measures. Using multiple sclerosis (MS) as a proof of principle, we showcased how to leverage routinely collected EHR data to identify patients with a complex neurological disorder and derive an important surrogate measure of disease severity heretofore only available in research settings. Methods In a cross-sectional observational study, 5,495 MS patients were identified from the EHR systems of two major referral hospitals using an algorithm that includes codified and narrative information extracted using natural language processing. In the subset of patients who receive neurological care at a MS Center where disease measures have been collected, we used routinely collected EHR data to extract two aggregate indicators of MS severity of clinical relevance multiple sclerosis severity score (MSSS) and brain parenchymal fraction (BPF, a measure of whole brain volume). Results The EHR algorithm that identifies MS patients has an area under the curve of 0.958, 83% sensitivity, 92% positive predictive value, and 89% negative predictive value when a 95% specificity threshold is used. The correlation between EHR-derived and true MSSS has a mean R2 = 0.38±0.05, and that between EHR-derived and true BPF has a mean R2 = 0.22±0.08. To illustrate its clinical relevance, derived MSSS captures the expected difference in disease severity between relapsing-remitting and progressive MS patients after adjusting for sex, age of symptom onset and disease duration (p = 1.56×10−12). Conclusion Incorporation of sophisticated codified and narrative EHR data accurately identifies MS patients and provides estimation of a well-accepted indicator of MS severity that is widely used in research settings but not part of the routine medical records. Similar approaches could be applied to other complex neurological disorders. PMID:24244385

A one-year economic evaluation of six alternative strategies in the management of uninvestigated upper gastrointestinal symptoms in Canadian primary care.

PubMed

Barkun, Alan N; Crott, Ralph; Fallone, Carlo A; Kennedy, Wendy A; Lachaine, Jean; Levinton, Carey; Armstrong, David; Chiba, Naoki; Thomson, Alan; Veldhuyzen van Zanten, Sander; Sinclair, Paul; Escobedo, Sergio; Chakraborty, Bijan; Smyth, Sandra; White, Robert; Kalra, Helen; Nevin, Krista

2010-08-01

The cost-effectiveness of initial strategies in managing Canadian patients with uninvestigated upper gastrointestinalsymptoms remains controversial. To assess the cost-effectiveness of six management approaches to uninvestigated upper gastrointestinal symptoms in the Canadian setting. The present study analyzed data from four randomized trials assessing homogeneous and complementary populations of Canadian patients with uninvestigated upper gastrointestinal symptoms with comparable outcomes. Symptom-free months, qualityadjusted life-years (QALYs) and direct costs in Canadian dollars of two management approaches based on the Canadian Dyspepsia Working Group (CanDys) Clinical Management Tool, and four additional strategies (two empirical antisecretory agents, and two prompt endoscopy) were examined and compared. Prevalence data, probabilities, utilities and costs were included in a Markov model, while sensitivity analysis used Monte Carlo simulations. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were determined. Empirical omeprazole cost $226 per QALY ($49 per symptom-free month) per patient. CanDys omeprazole and endoscopy approaches were more effective than empirical omeprazole, but more costly. Alternatives using H2-receptor antagonists were less effective than those using a proton pump inhibitor. No significant differences were found for most incremental cost-effectiveness ratios. As willingness to pay (WTP) thresholds rose from $226 to $24,000 per QALY, empirical antisecretory approaches were less likely to be the most costeffective choice, with CanDys omeprazole progressively becoming a more likely option. For WTP values ranging from $24,000 to $70,000 per QALY, the most clinically relevant range, CanDys omeprazole was the most cost-effective strategy (32% to 46% of the time), with prompt endoscopy-proton pump inhibitor favoured at higher WTP values. Although no strategy was the indisputable cost effective option, CanDys omeprazole may be the strategy of choiceover a clinically relevant range of WTP assumptions in the initial management of Canadian patients with uninvestigated dyspepsia.

Development and validation of the Learning Disabilities Needs Assessment Tool (LDNAT), a HoNOS-based needs assessment tool for use with people with intellectual disability.

PubMed

Painter, J; Trevithick, L; Hastings, R P; Ingham, B; Roy, A

2016-12-01

In meeting the needs of individuals with intellectual disabilities (ID) who access health services, a brief, holistic assessment of need is useful. This study outlines the development and testing of the Learning Disabilities Needs Assessment Tool (LDNAT), a tool intended for this purpose. An existing mental health (MH) tool was extended by a multidisciplinary group of ID practitioners. Additional scales were drafted to capture needs across six ID treatment domains that the group identified. LDNAT ratings were analysed for the following: item redundancy, relevance, construct validity and internal consistency (n = 1692); test-retest reliability (n = 27); and concurrent validity (n = 160). All LDNAT scales were deemed clinically relevant with little redundancy apparent. Principal component analysis indicated three components (developmental needs, challenging behaviour, MH and well-being). Internal consistency was good (Cronbach alpha 0.80). Individual item test-retest reliability was substantial-near perfect for 20 scales and slight-fair for three scales. Overall reliability was near perfect (intra-class correlation = 0.91). There were significant associations with five of six condition-specific measures, i.e. the Waisman Activities of Daily Living Scale (general ability/disability), Threshold Assessment Grid (risk), Behaviour Problems Inventory for Individuals with Intellectual Disabilities-Short Form (challenging behaviour) Social Communication Questionnaire (autism) and a bespoke physical health questionnaire. Additionally, the statistically significant correlations between these tools and the LDNAT components made sense clinically. There were no statistically significant correlations with the Psychiatric Assessment Schedules for Adults with Developmental Disabilities (a measure of MH symptoms in people with ID). The LDNAT had clinically utility when rating the needs of people with ID prior to condition-specific assessment(s). Analyses of internal and external validity were promising. Further evaluation of its sensitivity to changes in needs is now required. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

The importance of staphylococci and threshold value of somatic cell count for diagnosis of sub-clinical mastitis in Pirlak sheep at mid-lactation.

PubMed

Ozenc, E; Seker, E; Baki Acar, D; Birdane, M K; Darbaz, I; Dogan, N

2011-12-01

This study investigated the bacterial agents causing sub-clinical mastitis and the mean somatic cell counts (SCC) of milk in Pirlak sheep at mid-lactation. The percentage of infected udder halves was 11.4% (53/464). The most frequently isolated species were coagulase-negative staphylococci (CNS) (64.2%), followed by Staphylococcus aureus (24.5%) and Escherichia coli (11.3%). Among the CNS, the most common species was Staphylococcus epidermidis (38.2%). The other species isolated from milk samples were Staphylococcus xylosus (17.7%), Staphylococcus chromogenes (14.7%), Staphylococcus simulans (8.8%) and Staphylococcus hyicus (8.8%). The mean SCC for culture positive and negative samples was 1742×10(3) and 161×10(3) cells/ml, respectively. A significant difference (p<0.05) was determined between with and without microbial growth groups in terms of the SCC values. Threshold limit for SCC was 374×10(3) cells/ml for Pirlak sheep. In conclusion, it was considered that SCC is an important predictor of sub-clinical mastitis in Pirlak sheep. This is the first study to describe the bacterial agents causing sub-clinical mastitis and threshold limit for SCC in Pirlak sheep in Turkey. © 2011 Blackwell Verlag GmbH.

Increased hs-CRP and decreased 1,25-dihydroxyvitamin D are associated with increased left ventricle lead threshold.

PubMed

Gözübüyük, Gökhan; Koç, Mevlüt; Kaypaklı, Onur; Şahin, Durmuş Yıldıray

2016-11-01

There are not enough data about threshold changes in patients with CRT. In this study, we aimed to investigate frequency of significant threshold increase of left ventricle lead and to determine clinical, demographic, medical and laboratory parameters that associated with threshold increase in CRT implanted patients. We included CRT implanted 200 patients (124 males, 76 females; mean age 65.8 ± 10.3 years) to this study. Basal and third month LV R wave amplitude, electrode impedance, and threshold values were recorded. Threshold increase was accepted as ≥0.1 V and significant increase as >1 V. Patients were divided into two groups: increased threshold and non-increased threshold for LV lead. Number of patients with increased LV threshold was 68 (37.6 %). Furthermore, 8 % of patients had severe increase (≥1 V) in LV threshold. We observed that serum levels of hs-CRP and 1,25 (OH)2 vitamin D were independently associated with increased LV threshold. We showed that 1 mg/dl increase in hs-CRP and the 1 mg/dl decrease in vitamin D are associated with 25.3 and 4.5 % increase in the odds of increased LV threshold, respectively. Increased hs-CRP and decreased 1,25 (OH)2 vitamin D are the strongest predictors of increased LV lead thresholds. We suggest that hs-CRP and 1,25 (OH)2 vitamin D may be used as markers to predict and follow the patients with increased thresholds. It may be useful to finalize CRT procedure with more appropriate basal threshold in patients with high serum hs-CRP and low 1,25 (OH)2 vitamin D levels.

Threshold and channel interaction in cochlear implant users: evaluation of the tripolar electrode configuration.

PubMed

Bierer, Julie Arenberg

2007-03-01

The efficacy of cochlear implants is limited by spatial and temporal interactions among channels. This study explores the spatially restricted tripolar electrode configuration and compares it to bipolar and monopolar stimulation. Measures of threshold and channel interaction were obtained from nine subjects implanted with the Clarion HiFocus-I electrode array. Stimuli were biphasic pulses delivered at 1020 pulses/s. Threshold increased from monopolar to bipolar to tripolar stimulation and was most variable across channels with the tripolar configuration. Channel interaction, quantified by the shift in threshold between single- and two-channel stimulation, occurred for all three configurations but was largest for the monopolar and simultaneous conditions. The threshold shifts with simultaneous tripolar stimulation were slightly smaller than with bipolar and were not as strongly affected by the timing of the two channel stimulation as was monopolar. The subjects' performances on clinical speech tests were correlated with channel-to-channel variability in tripolar threshold, such that greater variability was related to poorer performance. The data suggest that tripolar channels with high thresholds may reveal cochlear regions of low neuron survival or poor electrode placement.

The impact of cochlear fine structure on hearing thresholds and DPOAE levels

NASA Astrophysics Data System (ADS)

Lee, Jungmee; Long, Glenis; Talmadge, Carrick L.

2004-05-01

Although otoacoustic emissions (OAE) are used as clinical and research tools, the correlation between OAE behavioral estimates of hearing status is not large. In normal-hearing individuals, the level of OAEs can vary as much as 30 dB when the frequency is changed less than 5%. These pseudoperiodic variations of OAE level with frequency are known as fine structure. Hearing thresholds measured with high-frequency resolution reveals a similar (up to 15 dB) fine structure. We examine the impact of OAE and threshold fine structures on the prediction of auditory thresholds from OAE levels. Distortion product otoacoustic emissions (DPOAEs) were measured with sweeping primary tones. Psychoacoustic detection thresholds were measured using pure tones, sweep tones, FM tones, and narrow-band noise. Sweep DPOAE and narrow-band threshold estimates provide estimates that are less influenced by cochlear fine structure and should lead to a higher correlation between OAE levels and psychoacoustic thresholds. [Research supported by PSC CUNY, NIDCD, National Institute on Disability and Rehabilitation Research in U.S. Department of Education, and The Ministry of Education in Korea.

Cortical activity is more stable when sensory stimuli are consciously perceived

PubMed Central

Schurger, Aaron; Sarigiannidis, Ioannis; Naccache, Lionel; Sitt, Jacobo D.; Dehaene, Stanislas

2015-01-01

According to recent evidence, stimulus-tuned neurons in the cerebral cortex exhibit reduced variability in firing rate across trials, after the onset of a stimulus. However, in order for a reduction in variability to be directly relevant to perception and behavior, it must be realized within trial—the pattern of activity must be relatively stable. Stability is characteristic of decision states in recurrent attractor networks, and its possible relevance to conscious perception has been suggested by theorists. However, it is difficult to measure on the within-trial time scales and broadly distributed spatial scales relevant to perception. We recorded simultaneous magneto- and electroencephalography (MEG and EEG) data while subjects observed threshold-level visual stimuli. Pattern-similarity analyses applied to the data from MEG gradiometers uncovered a pronounced decrease in variability across trials after stimulus onset, consistent with previous single-unit data. This was followed by a significant divergence in variability depending upon subjective report (seen/unseen), with seen trials exhibiting less variability. Applying the same analysis across time, within trial, we found that the latter effect coincided in time with a difference in the stability of the pattern of activity. Stability alone could be used to classify data from individual trials as “seen” or “unseen.” The same metric applied to EEG data from patients with disorders of consciousness exposed to auditory stimuli diverged parametrically according to clinically diagnosed level of consciousness. Differences in signal strength could not account for these results. Conscious perception may involve the transient stabilization of distributed cortical networks, corresponding to a global brain-scale decision. PMID:25847997

The Cost-Effectiveness of Dual Mobility Implants for Primary Total Hip Arthroplasty: A Computer-Based Cost-Utility Model.

PubMed

Barlow, Brian T; McLawhorn, Alexander S; Westrich, Geoffrey H

2017-05-03

Dislocation remains a clinically important problem following primary total hip arthroplasty, and it is a common reason for revision total hip arthroplasty. Dual mobility (DM) implants decrease the risk of dislocation but can be more expensive than conventional implants and have idiosyncratic failure mechanisms. The purpose of this study was to investigate the cost-effectiveness of DM implants compared with conventional bearings for primary total hip arthroplasty. Markov model analysis was conducted from the societal perspective with use of direct and indirect costs. Costs, expressed in 2013 U.S. dollars, were derived from the literature, the National Inpatient Sample, and the Centers for Medicare & Medicaid Services. Effectiveness was expressed in quality-adjusted life years (QALYs). The model was populated with health state utilities and state transition probabilities derived from previously published literature. The analysis was performed for a patient's lifetime, and costs and effectiveness were discounted at 3% annually. The principal outcome was the incremental cost-effectiveness ratio (ICER), with a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses were performed to explore relevant uncertainty. In the base case, DM total hip arthroplasty showed absolute dominance over conventional total hip arthroplasty, with lower accrued costs ($39,008 versus $40,031 U.S. dollars) and higher accrued utility (13.18 versus 13.13 QALYs) indicating cost-savings. DM total hip arthroplasty ceased being cost-saving when its implant costs exceeded those of conventional total hip arthroplasty by $1,023, and the cost-effectiveness threshold for DM implants was $5,287 greater than that for conventional implants. DM was not cost-effective when the annualized incremental probability of revision from any unforeseen failure mechanism or mechanisms exceeded 0.29%. The probability of intraprosthetic dislocation exerted the most influence on model results. This model determined that, compared with conventional bearings, DM implants can be cost-saving for routine primary total hip arthroplasty, from the societal perspective, if newer-generation DM implants meet specific economic and clinical benchmarks. The differences between these thresholds and the performance of other contemporary bearings were frequently quite narrow. The results have potential application to the postmarket surveillance of newer-generation DM components. Economic and decision analysis Level III. See Instructions for Authors for a complete description of levels of evidence.

Spinal cord normalization in multiple sclerosis.

PubMed

Oh, Jiwon; Seigo, Michaela; Saidha, Shiv; Sotirchos, Elias; Zackowski, Kathy; Chen, Min; Prince, Jerry; Diener-West, Marie; Calabresi, Peter A; Reich, Daniel S

2014-01-01

Spinal cord (SC) pathology is common in multiple sclerosis (MS), and measures of SC-atrophy are increasingly utilized. Normalization reduces biological variation of structural measurements unrelated to disease, but optimal parameters for SC volume (SCV)-normalization remain unclear. Using a variety of normalization factors and clinical measures, we assessed the effect of SCV normalization on detecting group differences and clarifying clinical-radiological correlations in MS. 3T cervical SC-MRI was performed in 133 MS cases and 11 healthy controls (HC). Clinical assessment included expanded disability status scale (EDSS), MS functional composite (MSFC), quantitative hip-flexion strength ("strength"), and vibration sensation threshold ("vibration"). SCV between C3 and C4 was measured and normalized individually by subject height, SC-length, and intracranial volume (ICV). There were group differences in raw-SCV and after normalization by height and length (MS vs. HC; progressive vs. relapsing MS-subtypes, P < .05). There were correlations between clinical measures and raw-SCV (EDSS:r = -.20; MSFC:r = .16; strength:r = .35; vibration:r = -.19). Correlations consistently strengthened with normalization by length (EDSS:r = -.43; MSFC:r = .33; strength:r = .38; vibration:r = -.40), and height (EDSS:r = -.26; MSFC:r = .28; strength:r = .22; vibration:r = -.29), but diminished with normalization by ICV (EDSS:r = -.23; MSFC:r = -.10; strength:r = .23; vibration:r = -.35). In relapsing MS, normalization by length allowed statistical detection of correlations that were not apparent with raw-SCV. SCV-normalization by length improves the ability to detect group differences, strengthens clinical-radiological correlations, and is particularly relevant in settings of subtle disease-related SC-atrophy in MS. SCV-normalization by length may enhance the clinical utility of measures of SC-atrophy. Copyright © 2014 by the American Society of Neuroimaging.

Reliable jitter and shimmer measurements in voice clinics: the relevance of vowel, gender, vocal intensity, and fundamental frequency effects in a typical clinical task.

PubMed

Brockmann, Meike; Drinnan, Michael J; Storck, Claudio; Carding, Paul N

2011-01-01

The aims of this study were to examine vowel and gender effects on jitter and shimmer in a typical clinical voice task while correcting for the confounding effects of voice sound pressure level (SPL) and fundamental frequency (F(0)). Furthermore the relative effect sizes of vowel, gender, voice SPL, and F(0) were assessed, and recommendations for clinical measurements were derived. With this cross-sectional single cohort study, 57 healthy adults (28 women, 29 men) aged 20-40 years were investigated. Three phonations of /a/, /o/, and /i/ at "normal" voice loudness were analyzed using Praat (software). The effects of vowel, gender, voice SPL, and F(0) on jitter and shimmer were assessed using descriptive and inferential (analysis of covariance) statistics. The effect sizes were determined with the eta-squared statistic. Vowels, gender, voice SPL, and F(0), each had significant effects either on jitter or on shimmer, or both. Voice SPL was the most important factor, whereas vowel, gender, and F(0) effects were comparatively small. Because men had systematically higher voice SPL, the gender effects on jitter and shimmer were smaller when correcting for SPL and F(0). Surprisingly, in clinical assessments, voice SPL has the single biggest impact on jitter and shimmer. Vowel and gender effects were clinically important, whereas fundamental frequency had a relatively small influence. Phonations at a predefined voice SPL (80 dB minimum) and vowel (/a/) would enhance measurement reliability. Furthermore, gender-specific thresholds applying these guidelines should be established. However, the efficiency of these measures should be verified and tested with patients. Copyright © 2011 The Voice Foundation. All rights reserved.

Pain Sensitivity Subgroups in Individuals With Spine Pain: Potential Relevance to Short-Term Clinical Outcome

PubMed Central

Bialosky, Joel E.; Robinson, Michael E.

2014-01-01

Background Cluster analysis can be used to identify individuals similar in profile based on response to multiple pain sensitivity measures. There are limited investigations into how empirically derived pain sensitivity subgroups influence clinical outcomes for individuals with spine pain. Objective The purposes of this study were: (1) to investigate empirically derived subgroups based on pressure and thermal pain sensitivity in individuals with spine pain and (2) to examine subgroup influence on 2-week clinical pain intensity and disability outcomes. Design A secondary analysis of data from 2 randomized trials was conducted. Methods Baseline and 2-week outcome data from 157 participants with low back pain (n=110) and neck pain (n=47) were examined. Participants completed demographic, psychological, and clinical information and were assessed using pain sensitivity protocols, including pressure (suprathreshold pressure pain) and thermal pain sensitivity (thermal heat threshold and tolerance, suprathreshold heat pain, temporal summation). A hierarchical agglomerative cluster analysis was used to create subgroups based on pain sensitivity responses. Differences in data for baseline variables, clinical pain intensity, and disability were examined. Results Three pain sensitivity cluster groups were derived: low pain sensitivity, high thermal static sensitivity, and high pressure and thermal dynamic sensitivity. There were differences in the proportion of individuals meeting a 30% change in pain intensity, where fewer individuals within the high pressure and thermal dynamic sensitivity group (adjusted odds ratio=0.3; 95% confidence interval=0.1, 0.8) achieved successful outcomes. Limitations Only 2-week outcomes are reported. Conclusions Distinct pain sensitivity cluster groups for individuals with spine pain were identified, with the high pressure and thermal dynamic sensitivity group showing worse clinical outcome for pain intensity. Future studies should aim to confirm these findings. PMID:24764070

The prevalence and moderators of clinical pain in people with schizophrenia: a systematic review and large scale meta-analysis.

PubMed

Stubbs, Brendon; Mitchell, Alex J; De Hert, Marc; Correll, Christoph U; Soundy, Andy; Stroobants, Marc; Vancampfort, Davy

2014-12-01

People with schizophrenia frequently have physical comorbidities that can cause pain. Experimental studies report reduced pain sensitivity among schizophrenia patients, but it remains unclear if clinically relevant pain is less prevalent in schizophrenia. We systematically searched major electronic databases from inception till 03/2014. Articles were included that reported the prevalence of clinical pain in people with schizophrenia. Two independent authors conducted searches, completed methodological quality assessment and extracted data. A random effects relative risks (RR) meta-analysis was conducted to determine the prevalence of all-cause and specific pain in schizophrenia, and the relative prevalence compared to the general population, and to assess moderators. Altogether, 14 studies were included encompassing 242,703 individuals with schizophrenia (30.2-55.8 years) and 4,259,221 controls. Different types of pain were considered. The overall pooled prevalence of clinical pain in people with schizophrenia was 34.7% (95% CI=23.6-46.6). In the comparative analysis involving 7 studies with controls, the RR was 0.99 (95% CI=0.83-1.19). The pooled prevalence of headache among 94,043 individuals with schizophrenia was 29.9% (95% CI=3-69%) and the RR compared to 4,248,284 controls was 1.32 (95% CI=0.85-2.07). In moderator analyses, neither age, sex, study quality or pain assessment method influenced pain prevalence. Clinical pain affects a third of people with schizophrenia and levels are similar with age- and sex-comparable controls. Future research is needed to determine if similar clinical pain prevalences in schizophrenia occur despite having more painful conditions, resulting from under-reporting, higher pain thresholds or lower help seeking behaviours. Copyright © 2014 Elsevier B.V. All rights reserved.

Defining thresholds of specific IgE levels to grass pollen and birch pollen allergens improves clinical interpretation.

PubMed

Van Hoeyveld, Erna; Nickmans, Silvie; Ceuppens, Jan L; Bossuyt, Xavier

2015-10-23

Cut-off values and predictive values are used for the clinical interpretation of specific IgE antibody results. However, cut-off levels are not well defined, and predictive values are dependent on the prevalence of disease. The objective of this study was to document clinically relevant diagnostic accuracy of specific IgE for inhalant allergens (grass pollen and birch pollen) based on test result interval-specific likelihood ratios. Likelihood ratios are independent of the prevalence and allow to provide diagnostic accuracy information for test result intervals. In a prospective study we included consecutive adult patients presenting at an allergy clinic with complaints of rhinitis or rhinoconjunctivitis. The standard for diagnosis was a suggestive clinical history of grass or birch pollen allergy and a positive skin test. Specific IgE was determined with the ImmunoCAP Fluorescence Enzyme Immuno-Assay. We established specific IgE test result interval related likelihood ratios for clinical allergy to inhalant allergens (grass pollen, rPhl p 1,5, birch pollen, rBet v 1). The likelihood ratios for allergy increased with increasing specific IgE antibody levels. The likelihood ratio was <0.03 for specific IgE <0.1 kU/L, between 0.1 and 1.4 for specific IgE between 0.1 kU/L and 0.35 kU/L, between 1.4 and 4.2 for specific IgE between 0.35 kU/L and 3.5 kU/L, >6.3 for specific IgE>0.7, and very high (∞) for specific IgE >3.5 kU/L. Test result interval specific likelihood ratios provide a useful tool for the interpretation of specific IgE test results for inhalant allergens. Copyright © 2015 Elsevier B.V. All rights reserved.

Adolescent depression: clinical features and therapeutic strategies.

PubMed

Nardi, B; Francesconi, G; Catena-Dell'osso, M; Bellantuono, C

2013-06-01

Major depressive disorder (MDD) is a common disorder during adolescence and it is associated with an increased risk of suicide, poor school performance, impaired social skills, social withdrawal and substance abuse. Further, as many depressive episode in adolescents do not reach the diagnostic threshold for MDD, the disorder remains undetected. This review aims to provide an update of clinical features of adolescent MDD and to focus on the most appropriate therapeutic strategies to adopt in clinical practice. We reviewed the international literature to identify studies focusing on clinical features and therapeutic options in adolescents affected by MDD. PubMed, Medline and Cochrane Library databases were searched for English language papers. The clinical picture of depression is variable with sex and age. Somatic complaints, particularly headache and fatigue, are a common presentation in adolescent MDD. Irritability is present most frequently in female and it is related to the severity of MDD. Adolescent MDD is also characterized by a high rates of suicides. The therapeutic strategy in adolescent depression includes psychotropic medications, psychotherapy or a combination of both treatments, with selection of the most appropriate strategy depending on symptom severity. As first-line treatment the traditional cognitive behavioural therapy (CBT), as well as the cognitive Post-Rationalist (PR) approach, are so far considered the goal standard. The therapeutic approach to the adolescent affected by MMD should respect the person in his/her psycho-physical entirety. The intervention may help the subject in seeking a more stable and adaptable identity. It is relevant to have a good knowledge of the peculiar clinical picture of adolescent MDD in order to make an early identification of the disorder and to define an appropriate personalized therapeutic program.

21 CFR 1271.75 - How do I screen a donor?

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Risk factors for, and clinical evidence of, relevant communicable disease agents and diseases... risk factors for and clinical evidence of relevant cell-associated communicable disease agents and... having either of the following: (1) A risk factor for or clinical evidence of any of the relevant...

Thermal perception thresholds among workers in a cold climate.

PubMed

Burström, Lage; Björ, Bodil; Nilsson, Tohr; Pettersson, Hans; Rödin, Ingemar; Wahlström, Jens

2017-10-01

To investigate whether exposure to cold could influence the thermal perception thresholds in a working population. This cross-sectional study was comprised of 251 males and females and was carried out at two mines in the northern part of Norway and Sweden. The testing included a baseline questionnaire, a clinical examination and measurements of thermal perception thresholds, on both hands, the index (Digit 2) and little (Digit 5) fingers, for heat and cold. The thermal perception thresholds were affected by age, gender and test site. The thresholds were impaired by experiences of frostbite in the fingers and the use of medication that potentially could affect neurosensory functions. No differences were found between the calculated normative values for these workers and those in other comparative investigations conducted in warmer climates. The study provided no support for the hypothesis that living and working in cold climate will lead to impaired thermal perception thresholds. Exposure to cold that had caused localized damage in the form of frostbite was shown to lead to impaired thermal perception.

Modelling the regulatory system for diabetes mellitus with a threshold window

NASA Astrophysics Data System (ADS)

Yang, Jin; Tang, Sanyi; Cheke, Robert A.

2015-05-01

Piecewise (or non-smooth) glucose-insulin models with threshold windows for type 1 and type 2 diabetes mellitus are proposed and analyzed with a view to improving understanding of the glucose-insulin regulatory system. For glucose-insulin models with a single threshold, the existence and stability of regular, virtual, pseudo-equilibria and tangent points are addressed. Then the relations between regular equilibria and a pseudo-equilibrium are studied. Furthermore, the sufficient and necessary conditions for the global stability of regular equilibria and the pseudo-equilibrium are provided by using qualitative analysis techniques of non-smooth Filippov dynamic systems. Sliding bifurcations related to boundary node bifurcations were investigated with theoretical and numerical techniques, and insulin clinical therapies are discussed. For glucose-insulin models with a threshold window, the effects of glucose thresholds or the widths of threshold windows on the durations of insulin therapy and glucose infusion were addressed. The duration of the effects of an insulin injection is sensitive to the variation of thresholds. Our results indicate that blood glucose level can be maintained within a normal range using piecewise glucose-insulin models with a single threshold or a threshold window. Moreover, our findings suggest that it is critical to individualise insulin therapy for each patient separately, based on initial blood glucose levels.

Comparison of algorithms of testing for use in automated evaluation of sensation.

PubMed

Dyck, P J; Karnes, J L; Gillen, D A; O'Brien, P C; Zimmerman, I R; Johnson, D M

1990-10-01

Estimates of vibratory detection threshold may be used to detect, characterize, and follow the course of sensory abnormality in neurologic disease. The approach is especially useful in epidemiologic and controlled clinical trials. We studied which algorithm of testing and finding threshold should be used in automatic systems by comparing among algorithms and stimulus conditions for the index finger of healthy subjects and for the great toe of patients with mild neuropathy. Appearance thresholds obtained by linear ramps increasing at a rate less than 4.15 microns/sec provided accurate and repeatable thresholds compared with thresholds obtained by forced-choice testing. These rates would be acceptable if only sensitive sites were studied, but they were too slow for use in automatic testing of insensitive parts. Appearance thresholds obtained by fast linear rates (4.15 or 16.6 microns/sec) overestimated threshold, especially for sensitive parts. Use of the mean of appearance and disappearance thresholds, with the stimulus increasing exponentially at rates of 0.5 or 1.0 just noticeable difference (JND) units per second, and interspersion of null stimuli, Békésy with null stimuli, provided accurate, repeatable, and fast estimates of threshold for sensitive parts. Despite the good performance of Békésy testing, we prefer forced choice for evaluation of the sensation of patients with neuropathy.

A principled approach to setting optimal diagnostic thresholds: where ROC and indifference curves meet.

PubMed

Irwin, R John; Irwin, Timothy C

2011-06-01

Making clinical decisions on the basis of diagnostic tests is an essential feature of medical practice and the choice of the decision threshold is therefore crucial. A test's optimal diagnostic threshold is the threshold that maximizes expected utility. It is given by the product of the prior odds of a disease and a measure of the importance of the diagnostic test's sensitivity relative to its specificity. Choosing this threshold is the same as choosing the point on the Receiver Operating Characteristic (ROC) curve whose slope equals this product. We contend that a test's likelihood ratio is the canonical decision variable and contrast diagnostic thresholds based on likelihood ratio with two popular rules of thumb for choosing a threshold. The two rules are appealing because they have clear graphical interpretations, but they yield optimal thresholds only in special cases. The optimal rule can be given similar appeal by presenting indifference curves, each of which shows a set of equally good combinations of sensitivity and specificity. The indifference curve is tangent to the ROC curve at the optimal threshold. Whereas ROC curves show what is feasible, indifference curves show what is desirable. Together they show what should be chosen. Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Generalizing a complex model for gully threshold identification in the Mediterranean environment

NASA Astrophysics Data System (ADS)

Torri, D.; Borselli, L.; Iaquinta, P.; Iovine, G.; Poesen, J.; Terranova, O.

2012-04-01

Among the physical processes leading to land degradation, soil erosion by water is the most important and gully erosion may contribute, at places, to 70% of the total soil loss. Nevertheless, gully erosion has often been neglected in water soil erosion modeling, whilst more prominence has been given to rill and interrill erosion. Both to facilitate the processing by agricultural machinery and to take advantage of all the arable land, gullies are commonly removed at each crop cycle, with significant soil losses due to the repeated excavation of the channel by the successive rainstorm. When the erosive forces of overland flow exceed the strength of the soil particles to detachment and displacement, water erosion occurs and usually a channel is formed. As runoff is proportional to the local catchment area, a relationship between local slope, S, and contributing area, A, is supposed to exists. A "geomorphologic threshold" scheme is therefore suitable to interpret the physical process of gully initiation: accordingly, a gully is formed when a hydraulic threshold for incision exceeds the resistance of the soil particles to detachment and transport. Similarly, it appears reasonable that a gully ends when there is a reduction of slope, or the concentrated flow meets more resistant soil-vegetation complexes. This study aims to predict the location of the beginning of gullies in the Mediterranean environment, based on an evaluation of S and A by means of a mathematical model. For the identification of the areas prone to gully erosion, the model employs two empirical thresholds relevant to the head (Thead) and to the end (Tend) of the gullies (of the type SA^ b>Thead, SA^ b

Methods for the estimation of the National Institute for Health and Care Excellence cost-effectiveness threshold.

PubMed

Claxton, Karl; Martin, Steve; Soares, Marta; Rice, Nigel; Spackman, Eldon; Hinde, Sebastian; Devlin, Nancy; Smith, Peter C; Sculpher, Mark

2015-02-01

Cost-effectiveness analysis involves the comparison of the incremental cost-effectiveness ratio of a new technology, which is more costly than existing alternatives, with the cost-effectiveness threshold. This indicates whether or not the health expected to be gained from its use exceeds the health expected to be lost elsewhere as other health-care activities are displaced. The threshold therefore represents the additional cost that has to be imposed on the system to forgo 1 quality-adjusted life-year (QALY) of health through displacement. There are no empirical estimates of the cost-effectiveness threshold used by the National Institute for Health and Care Excellence. (1) To provide a conceptual framework to define the cost-effectiveness threshold and to provide the basis for its empirical estimation. (2) Using programme budgeting data for the English NHS, to estimate the relationship between changes in overall NHS expenditure and changes in mortality. (3) To extend this mortality measure of the health effects of a change in expenditure to life-years and to QALYs by estimating the quality-of-life (QoL) associated with effects on years of life and the additional direct impact on QoL itself. (4) To present the best estimate of the cost-effectiveness threshold for policy purposes. Earlier econometric analysis estimated the relationship between differences in primary care trust (PCT) spending, across programme budget categories (PBCs), and associated disease-specific mortality. This research is extended in several ways including estimating the impact of marginal increases or decreases in overall NHS expenditure on spending in each of the 23 PBCs. Further stages of work link the econometrics to broader health effects in terms of QALYs. The most relevant 'central' threshold is estimated to be £12,936 per QALY (2008 expenditure, 2008-10 mortality). Uncertainty analysis indicates that the probability that the threshold is < £20,000 per QALY is 0.89 and the probability that it is < £30,000 per QALY is 0.97. Additional 'structural' uncertainty suggests, on balance, that the central or best estimate is, if anything, likely to be an overestimate. The health effects of changes in expenditure are greater when PCTs are under more financial pressure and are more likely to be disinvesting than investing. This indicates that the central estimate of the threshold is likely to be an overestimate for all technologies which impose net costs on the NHS and the appropriate threshold to apply should be lower for technologies which have a greater impact on NHS costs. The central estimate is based on identifying a preferred analysis at each stage based on the analysis that made the best use of available information, whether or not the assumptions required appeared more reasonable than the other alternatives available, and which provided a more complete picture of the likely health effects of a change in expenditure. However, the limitation of currently available data means that there is substantial uncertainty associated with the estimate of the overall threshold. The methods go some way to providing an empirical estimate of the scale of opportunity costs the NHS faces when considering whether or not the health benefits associated with new technologies are greater than the health that is likely to be lost elsewhere in the NHS. Priorities for future research include estimating the threshold for subsequent waves of expenditure and outcome data, for example by utilising expenditure and outcomes available at the level of Clinical Commissioning Groups as well as additional data collected on QoL and updated estimates of incidence (by age and gender) and duration of disease. Nonetheless, the study also starts to make the other NHS patients, who ultimately bear the opportunity costs of such decisions, less abstract and more 'known' in social decisions. The National Institute for Health Research-Medical Research Council Methodology Research Programme.

Prevention of Glucocorticoid-Induced Osteoporosis: Clinical audit to evaluate the implementation of National Osteoporosis Guideline Group 2017 guidelines in a primary care setting.

PubMed

Carter, Matthew

2018-04-12

Treatment with glucocorticoids is the leading cause of drug-induced osteoporosis. National Osteoporosis Guideline Group (NOGG) 2017 guidelines advise a case-finding strategy for patients at risk. The aims of the audit were to evaluate the implementation of the NOGG 2017 guidelines for patients receiving long-term glucocorticoid therapy in a suburban general practice, to instigate changes to ensure 90% of patients are investigated and treated appropriately, and to evaluate impact at a 6-mo re-audit. Reporting Analysis and Intelligence Delivering Results (RAIDR) is a health-care intelligence tool accessing primary care clinical data. Using RAIDR, data on relevant osteoporotic risk factors were combined to produce FRAX scores for patients who had been prescribed glucocorticoids 3 or more times in the past 12 months. FRAX data were displayed in a NOGG guidance graph for major osteoporotic fracture probability. Patients were assessed as high, intermediate, or low risk. High- and intermediate-risk patients above the NOGG threshold were recommended to start bisphosphonates; these patients were sent a prescription for alendronate and a letter of explanation. There were no intermediate patients below the NOGG threshold. Low-risk patients were recommended to have lifestyle advice; a leaflet was produced and sent to these patients. Initial results showed that only 25% of patients recommended to be on bisphosphonates were taking them. Steps were taken to educate the general practitioners in the FRAX tool and NOGG guidelines; the chronic obstructive pulmonary disease annual template was amended to aid adherence by alerting the nurse to the number of glucocorticoid courses prescribed, with additional boxes for prescribing alendronate and printing the lifestyle leaflet; and 2-monthly RAIDR searches by the practice pharmacist were started. A re-audit 6 mo later showed improvement to 92%. This audit showed that education, reminders, and simple computer prompts can greatly improve the implementation of NOGG guidelines for glucocorticoid-induced osteoporosis. Copyright © 2018 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Determination of ReQuest-based symptom thresholds to define symptom relief in GERD clinical studies.

PubMed

Stanghellini, Vincenzo; Armstrong, David; Mönnikes, Hubert; Berghöfer, Peter; Gatz, Gudrun; Bardhan, Karna Dev

2007-01-01

The growing importance of symptom assessment is evident from the numerous clinical studies on gastroesophageal reflux disease (GERD) assessing treatment-induced symptom relief. However, to date, the a priori selection of criteria defining symptom relief has been arbitrary. The present study was designed to prospectively identify GERD symptom thresholds for the broad spectrum of GERD-related symptoms assessed by the validated reflux questionnaire (ReQuest) and its subscales, ReQuest-GI (gastrointestinal symptoms) and ReQuest-WSO (general well-being, sleep disturbances, other complaints), in individuals without evidence of GERD. In this 4-day evaluation in Germany, 385 individuals without evidence of GERD were included. On the first day, participants completed the ReQuest, the Gastrointestinal Symptom Rating Scale, and the Psychological General Well-Being scale. On the other days, participants filled in the ReQuest only. GERD symptom thresholds were calculated for ReQuest and its subscales, based on the respective 90th percentiles. GERD symptom thresholds were 3.37 for ReQuest, 0.95 for ReQuest-GI, and 2.46 for ReQuest-WSO. Even individuals without evidence of GERD may experience some mild symptoms that are commonly ascribed to GERD. GERD symptom thresholds derived in this study can be used to define the global symptom relief in patients with GERD. Copyright 2007 S. Karger AG, Basel.

Amyloid and tau signatures of brain metabolic decline in preclinical Alzheimer's disease.

PubMed

Pascoal, Tharick A; Mathotaarachchi, Sulantha; Shin, Monica; Park, Ah Yeon; Mohades, Sara; Benedet, Andrea L; Kang, Min Su; Massarweh, Gassan; Soucy, Jean-Paul; Gauthier, Serge; Rosa-Neto, Pedro

2018-06-01

We aimed to determine the amyloid (Aβ) and tau biomarker levels associated with imminent Alzheimer's disease (AD) - related metabolic decline in cognitively normal individuals. A threshold analysis was performed in 120 cognitively normal elderly individuals by modelling 2-year declines in brain glucose metabolism measured with [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) as a function of [ 18 F]florbetapir Aβ positron emission tomography (PET) and cerebrospinal fluid phosphorylated tau biomarker thresholds. Additionally, using a novel voxel-wise analytical framework, we determined the sample sizes needed to test an estimated 25% drugeffect with 80% of power on changes in FDG uptake over 2 years at every brain voxel. The combination of [ 18 F]florbetapir standardized uptake value ratios and phosphorylated-tau levels more than one standard deviation higher than their respective thresholds for biomarker abnormality was the best predictor of metabolic decline in individuals with preclinical AD. We also found that a clinical trial using these thresholds would require as few as 100 individuals to test a 25% drug effect on AD-related metabolic decline over 2 years. These results highlight the new concept that combined Aβ and tau thresholds can predict imminent neurodegeneration as an alternative framework with a high statistical power for testing the effect of disease-modifying therapies on [ 18 F]FDG uptake decline over a typical 2-year clinical trial period in individuals with preclinical AD.

Cochlear third window in the scala vestibuli: an animal model.

PubMed

Preis, Michal; Attias, Joseph; Hadar, Tuvia; Nageris, Ben I

2009-08-01

Pathologic third window has been investigated in both animals and humans, with a third window located in the vestibular apparatus, specifically, dehiscence of the superior semicircular canal, serving as the clinical model. The present study sought to examine the effect of a cochlear third window in the scala vestibuli on the auditory thresholds in fat sand rats that have a unique anatomy of the inner ear that allows for easy surgical access. The experiment included 7 healthy 6-month-old fat sand rats (a total of 10 ears). A pathologic third window was induced by drilling a hole in the bony labyrinth over the scala vestibuli, with preservation of the membranous labyrinth. Auditory brainstem responses to high- and low-frequency acoustic stimuli delivered via air and bone conduction were recorded before and after the procedure. In the preoperative auditory brainstem response recordings, air-conduction thresholds (ACTs) to clicks and tone bursts averaged 9 and 10 dB, respectively, and bone-conduction thresholds averaged 4.5 and 2.9 dB, respectively. Postfenestration ACTs averaged 41 and 42.2 dB, and bone-conduction thresholds averaged 1.1 and 4.3 dB. The change in ACT was statistically significant (p < 0.01). The presence of a cochlear third window in the scala vestibuli affects auditory thresholds by causing a decrease in sensitivity to air-conducted sound stimuli. These findings agree with the theoretical model and clinical findings.

Locoregional Tumor Extension and Preoperative Smoking are Significant Risk Factors for Early Recurrence After Esophagectomy for Cancer.

PubMed

Mantziari, Styliani; Allemann, Pierre; Winiker, Michael; Demartines, Nicolas; Schäfer, Markus

2018-07-01

Tumor recurrence during the first year after oncological esophagectomy has been reported in up to 17-66% of patients. However, little is known as to the risk factors potentially associated with this adverse outcome. The aim of this retrospective observational study was to identify clinically relevant parameters associated with early recurrence. All patients with squamous cell cancer or adenocarcinoma of the esophagus or gastroesophageal junction, operated with curative intent in our center from 2000 to 2014, were screened for this study. Univariate analysis was conducted to identify variables potentially associated with early recurrence, and clinically relevant parameters with P < 0.1 were included in multiple logistic regression. Survival analyses were conducted with the Kaplan-Meier method. Significance threshold was set at P < 0.05. Among the 164 included patients, 46 (28%) presented early recurrence. Eight patients (17.4%) had locoregional and 38 patients (82.6%) metastatic recurrence. Advanced T and N stages, lymph node capsular effraction, a high positive-to-resected lymph node ratio, positive resection margins, poor response to neoadjuvant treatment, preoperative active smoking, malnutrition and dysphagia were associated with early recurrence on a univariate level. In multivariable analysis, preoperative smoking (OR 2.76, 95% CI 1.28-6.17), pT stage (OR 1.72, 95% CI 1.18-2.58) and an increased positive-to-resected lymph node ratio (OR 6.72, 95% CI 1.08-48.51) remained independently associated with ER. Our study identified both patient- and tumor-related parameters as risk factors for early recurrence after oncological esophagectomy. Of particular interest, active smoking was significantly associated with this adverse outcome, highlighting the importance of preoperative smoking cessation.

Comparison of automated versus manual neutrophil counts for the detection of cellular abnormalities in dogs receiving chemotherapy: 50 cases (May to June 2008).

PubMed

Cora, Michelle C; Neel, Jennifer A; Grindem, Carol B; Kissling, Grace E; Hess, Paul R

2013-06-01

To determine the frequency of clinically relevant abnormalities missed by failure to perform a blood smear evaluation in a specific subset of dogs receiving chemotherapy and to compare automated and manual neutrophil counts in the same population. Retrospective case series. 50 dogs receiving chemotherapy with a total nucleated cell count > 4,000 nucleated cells/μL. 50 blood smears were evaluated for abnormalities that have strong potential to change the medical plan for a patient: presence of blast cells, band neutrophils, nucleated RBCs, toxic change, hemoparasites, schistocytes, and spherocytes. Automated and manual neutrophil counts were compared. Blood smears from 10 (20%) patients had ≥ 1 abnormalities. Blast cells were identified on 4 (8%) blood smears, increased nucleated RBCs were identified on 5 (10%), and very mild toxic change was identified on 2 (4%). Correlation coefficient of the neutrophil counts was 0.96. Analysis revealed a slight bias between the automated and manual neutrophil counts (mean ± SD difference, -0.43 × 10(3)/μL ± 1.10 × 10(3)/μL). In this series of patients, neutrophil count correlation was very good. Clinically relevant abnormalities were found on 20% of the blood smears. An automated CBC appears to be accurate for neutrophil counts, but a microscopic examination of the corresponding blood smear is still recommended; further studies are needed to determine whether the detection or frequency of these abnormalities would differ dependent on chemotherapy protocol, neoplastic disease, and decision thresholds used by the oncologist in the ordering of a CBC without a blood smear evaluation.

Mechanical sensibility in free and island flaps of the foot.

PubMed

Rautio, J; Kekoni, J; Hämäläinen, H; Härmä, M; Asko-Seljavaara, S

1989-04-01

Mechanical sensibility in 20 free skin flaps and four dorsalis pedis island flaps, used for the reconstruction of foot defects, was analyzed with conventional clinical methods and by determining sensibility thresholds to vibration frequencies of 20, 80, and 240 Hz. To eliminate inter-individual variability, a score was calculated for each frequency by dividing the thresholds determined for each flap with values obtained from the corresponding area on the uninjured foot. The soft tissue stability of the reconstruction was assessed. Patients were divided into three groups according to the scores. In the group of flaps with the best sensibility, the threshold increases were low at all frequencies. In the group with intermediate sensibility, the relative threshold increases were greater, the higher the frequency. In the group with the poorest sensibility, no thresholds were obtained with 240 Hz frequency and the thresholds increases were very high at all frequencies. Sensibility was not related to the length of follow-up time, nor to the type or size of the flap. However, flap sensibility was closely associated with that of the recipient area, where sensibility was usually inferior to that of normal skin. The island flaps generally had better sensibility than the free flaps. There was a good correspondence between the levels of sensibility determined by clinical and quantitative methods. The quantitative data on the level of sensibility obtained with the psychophysical method were found to be reliable and free from observer bias, and are therefore recommended for future studies. The degree of sensibility may have contributed to, but was not essential for, good soft-tissue stability of the reconstruction.

Computer-aided detection of renal calculi from noncontrast CT images using TV-flow and MSER features.

PubMed

Liu, Jianfei; Wang, Shijun; Turkbey, Evrim B; Linguraru, Marius George; Yao, Jianhua; Summers, Ronald M

2015-01-01

Renal calculi are common extracolonic incidental findings on computed tomographic colonography (CTC). This work aims to develop a fully automated computer-aided diagnosis system to accurately detect renal calculi on CTC images. The authors developed a total variation (TV) flow method to reduce image noise within the kidneys while maintaining the characteristic appearance of renal calculi. Maximally stable extremal region (MSER) features were then calculated to robustly identify calculi candidates. Finally, the authors computed texture and shape features that were imported to support vector machines for calculus classification. The method was validated on a dataset of 192 patients and compared to a baseline approach that detects calculi by thresholding. The authors also compared their method with the detection approaches using anisotropic diffusion and nonsmoothing. At a false positive rate of 8 per patient, the sensitivities of the new method and the baseline thresholding approach were 69% and 35% (p < 1e - 3) on all calculi from 1 to 433 mm(3) in the testing dataset. The sensitivities of the detection methods using anisotropic diffusion and nonsmoothing were 36% and 0%, respectively. The sensitivity of the new method increased to 90% if only larger and more clinically relevant calculi were considered. Experimental results demonstrated that TV-flow and MSER features are efficient means to robustly and accurately detect renal calculi on low-dose, high noise CTC images. Thus, the proposed method can potentially improve diagnosis.

A comparison of DSM-III-R and ICD-10 personality disorder criteria in an out-patient population.

PubMed

Sara, G; Raven, P; Mann, A

1996-01-01

This study reports the results of a comparison of DSM-III-R and ICD-10 personality disorder criteria by application of both sets of criteria to the same group of patients. Despite the clinical relevance of these disorders and the need for reliable diagnostic criteria, such a comparison has not previously been reported. DSM-III-R and ICD-10 have converged in their classification of personality disorders, but some important differences between the two systems remain. Personality disorder diagnoses from both systems were obtained in 52 out-patients, using the Standardized Assessment of Personality (SAP), a brief, informant-based interview which yields diagnoses in both DSM-III-R and ICD-10. For individual personality disorder diagnoses, agreement between systems was limited. Thirty-four subjects received a personality disorder diagnosis that had an equivalent form in both systems, but only 10 subjects (29%) received the same primary diagnosis in each system. There was a difference in rate of diagnosis, with ICD-10 making significantly more personality disorder diagnoses. The lower diagnostic threshold of the ICD-10 contributed most of this effect. Further modifications in ICD-10 Diagnostic Criteria for Research (DCR) and DSM-IV to the personality disorder category have been considered. The omission in DSM-IV of three categories unique to that system and the raising of the threshold in ICD-10 DCR, do seem to have been helpful in promoting convergence.

Assessing the significance of pedobarographic signals using random field theory.

PubMed

Pataky, Todd C

2008-08-07

Traditional pedobarographic statistical analyses are conducted over discrete regions. Recent studies have demonstrated that regionalization can corrupt pedobarographic field data through conflation when arbitrary dividing lines inappropriately delineate smooth field processes. An alternative is to register images such that homologous structures optimally overlap and then conduct statistical tests at each pixel to generate statistical parametric maps (SPMs). The significance of SPM processes may be assessed within the framework of random field theory (RFT). RFT is ideally suited to pedobarographic image analysis because its fundamental data unit is a lattice sampling of a smooth and continuous spatial field. To correct for the vast number of multiple comparisons inherent in such data, recent pedobarographic studies have employed a Bonferroni correction to retain a constant family-wise error rate. This approach unfortunately neglects the spatial correlation of neighbouring pixels, so provides an overly conservative (albeit valid) statistical threshold. RFT generally relaxes the threshold depending on field smoothness and on the geometry of the search area, but it also provides a framework for assigning p values to suprathreshold clusters based on their spatial extent. The current paper provides an overview of basic RFT concepts and uses simulated and experimental data to validate both RFT-relevant field smoothness estimations and RFT predictions regarding the topological characteristics of random pedobarographic fields. Finally, previously published experimental data are re-analysed using RFT inference procedures to demonstrate how RFT yields easily understandable statistical results that may be incorporated into routine clinical and laboratory analyses.

Computer-aided detection of renal calculi from noncontrast CT images using TV-flow and MSER features

PubMed Central

Liu, Jianfei; Wang, Shijun; Turkbey, Evrim B.; Linguraru, Marius George; Yao, Jianhua; Summers, Ronald M.

2015-01-01

Purpose: Renal calculi are common extracolonic incidental findings on computed tomographic colonography (CTC). This work aims to develop a fully automated computer-aided diagnosis system to accurately detect renal calculi on CTC images. Methods: The authors developed a total variation (TV) flow method to reduce image noise within the kidneys while maintaining the characteristic appearance of renal calculi. Maximally stable extremal region (MSER) features were then calculated to robustly identify calculi candidates. Finally, the authors computed texture and shape features that were imported to support vector machines for calculus classification. The method was validated on a dataset of 192 patients and compared to a baseline approach that detects calculi by thresholding. The authors also compared their method with the detection approaches using anisotropic diffusion and nonsmoothing. Results: At a false positive rate of 8 per patient, the sensitivities of the new method and the baseline thresholding approach were 69% and 35% (p < 1e − 3) on all calculi from 1 to 433 mm3 in the testing dataset. The sensitivities of the detection methods using anisotropic diffusion and nonsmoothing were 36% and 0%, respectively. The sensitivity of the new method increased to 90% if only larger and more clinically relevant calculi were considered. Conclusions: Experimental results demonstrated that TV-flow and MSER features are efficient means to robustly and accurately detect renal calculi on low-dose, high noise CTC images. Thus, the proposed method can potentially improve diagnosis. PMID:25563255

Minimum Performance on Clinical Tests of Physical Function to Predict Walking 6,000 Steps/Day in Knee Osteoarthritis: An Observational Study.

PubMed

Master, Hiral; Thoma, Louise M; Christiansen, Meredith B; Polakowski, Emily; Schmitt, Laura A; White, Daniel K

2018-07-01

Evidence of physical function difficulties, such as difficulty rising from a chair, may limit daily walking for people with knee osteoarthritis (OA). The purpose of this study was to identify minimum performance thresholds on clinical tests of physical function predictive to walking ≥6,000 steps/day. This benchmark is known to discriminate people with knee OA who develop functional limitation over time from those who do not. Using data from the Osteoarthritis Initiative, we quantified daily walking as average steps/day from an accelerometer (Actigraph GT1M) worn for ≥10 hours/day over 1 week. Physical function was quantified using 3 performance-based clinical tests: 5 times sit-to-stand test, walking speed (tested over 20 meters), and 400-meter walk test. To identify minimum performance thresholds for daily walking, we calculated physical function values corresponding to high specificity (80-95%) to predict walking ≥6,000 steps/day. Among 1,925 participants (mean ± SD age 65.1 ± 9.1 years, mean ± SD body mass index 28.4 ± 4.8 kg/m 2 , and 55% female) with valid accelerometer data, 54.9% walked ≥6,000 steps/day. High specificity thresholds of physical function for walking ≥6,000 steps/day ranged 11.4-14.0 seconds on the 5 times sit-to-stand test, 1.13-1.26 meters/second for walking speed, or 315-349 seconds on the 400-meter walk test. Not meeting these minimum performance thresholds on clinical tests of physical function may indicate inadequate physical ability to walk ≥6,000 steps/day for people with knee OA. Rehabilitation may be indicated to address underlying impairments limiting physical function. © 2017, American College of Rheumatology.

Hypothesis-based weight-of-evidence evaluation and risk assessment for naphthalene carcinogenesis

PubMed Central

Bailey, Lisa A.; Nascarella, Marc A.; Kerper, Laura E.; Rhomberg, Lorenz R.

2016-01-01

Inhalation of naphthalene causes olfactory epithelial nasal tumors in rats (but not in mice) and benign lung adenomas in mice (but not in rats). The limited available human data have not identified an association between naphthalene exposure and increased respiratory cancer risk. Assessing naphthalene's carcinogenicity in humans, therefore, depends entirely on experimental evidence from rodents. We evaluated the respiratory carcinogenicity of naphthalene in rodents, and its potential relevance to humans, using our Hypothesis-Based Weight-of-Evidence (HBWoE) approach. We systematically and comparatively reviewed data relevant to key elements in the hypothesized modes of action (MoA) to determine which is best supported by the available data, allowing all of the data from each realm of investigation to inform interpretation of one another. Our analysis supports a mechanism that involves initial metabolism of naphthalene to the epoxide, followed by GSH depletion, cytotoxicity, chronic inflammation, regenerative hyperplasia, and tumor formation, with possible weak genotoxicity from downstream metabolites occurring only at high cytotoxic doses, strongly supporting a non-mutagenic threshold MoA in the rat nose. We also conducted a dose–response analysis, based on the likely MoA, which suggests that the rat nasal MoA is not relevant in human respiratory tissues at typical environmental exposures. Our analysis illustrates how a thorough WoE evaluation can be used to support a MoA, even when a mechanism of action cannot be fully elucidated. A non-mutagenic threshold MoA for naphthalene-induced rat nasal tumors should be considered as a basis to determine human relevance and to guide regulatory and risk-management decisions. PMID:26202831

Mobile phone interference with medical equipment and its clinical relevance: a systematic review.

PubMed

Lawrentschuk, Nathan; Bolton, Damien M

2004-08-02

To conduct a systematic review of studies on clinically relevant digital mobile phone electromagnetic interference with medical equipment. MEDLINE and SUMSEARCH were searched for the period 1966-2004. The Cochrane Library and Database of Abstracts of Reviews of Effects were also searched for systematic reviews. Studies were eligible if published in a peer-reviewed journal in English, and if they included testing of digital mobile phones for clinically relevant interference with medical equipment used to monitor or treat patients, but not implantable medical devices. As there was considerable heterogeneity in medical equipment studied and the conduct of testing, results were summarised rather than subjected to meta-analysis. Clinically relevant electromagnetic interference (EMI) secondary to mobile phones potentially endangering patients occurred in 45 of 479 devices tested at 900 MHz and 14 of 457 devices tested at 1800 MHz. However, in the largest studies, the prevalence of clinically relevant EMI was low. Most clinically relevant EMI occurred when mobile phones were used within 1 m of medical equipment. Although testing was not standardised between studies and equipment tested was not identical, it is of concern that at least 4% of devices tested in any study were susceptible to clinically relevant EMI. All studies recommend some type of restriction of mobile phone use in hospitals, with use greater than 1 m from equipment and restrictions in clinical areas being the most common.

Sustainability and Higher Education: From Arborescent to Rhizomatic Thinking

ERIC Educational Resources Information Center

Le Grange, Lesley Lionel Leonard

2011-01-01

Currently, global society is delicately poised on a civilisational threshold similar to that of the feudal era. This is a time when outmoded institutions, values, and systems of thought and their associated dogmas are ripe for transcendence by more relevant systems of organization and knowledge (Davidson, 2000). The foundations of the modern era…

Keeping Holocaust Education Relevant in a Changing Landscape: Seventy Years On

ERIC Educational Resources Information Center

Nesfield, Victoria

2015-01-01

January 2015 marked the seventieth anniversary of the liberation of Auschwitz-Birkenau by the Soviet Army. In 2014 alone, over one and a half million visitors crossed the same threshold, beneath the infamous words: "Arbeit Macht Frei." Of these visitors, a majority were organised educational groups, particularly high school, college and…

Understanding the side effects of classical biological control

Treesearch

Dean Pearson

2008-01-01

Classical biological control involves the use of imported natural enemies to suppress or control populations of the target pest species below an economically or ecologically relevant threshold. Biological control is a useful tool for mitigating the impacts of exotic invasive plants; however, its application is not without risk (see Carruthers and D’Antonio...

The cost-effectiveness of the Olweus Bullying Prevention Program: Results from a modelling study.

PubMed

Beckman, Linda; Svensson, Mikael

2015-12-01

Exposure to bullying affects around 3-5 percent of adolescents in secondary school and is related to various mental health problems. Many different anti-bullying programmes are currently available, but economic evaluations are lacking. The aim of this study is to identify the cost effectiveness of the Olweus Bullying Prevention Program (OBPP). We constructed a decision-tree model for a Swedish secondary school, using a public payer perspective, and retrieved data on costs and effects from the published literature. Probabilistic sensitivity analysis to reflect the uncertainty in the model was conducted. The base-case analysis showed that using the OBPP to reduce the number of victims of bullying costs 131,250 Swedish kronor (€14,470) per victim spared. Compared to a relevant threshold of the societal value of bullying reduction, this indicates that the programme is cost-effective. Using a relevant willingness-to-pay threshold shows that the OBPP is a cost-effective intervention. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch

PubMed Central

Poole, Kate; Herget, Regina; Lapatsina, Liudmila; Ngo, Ha-Duong; Lewin, Gary R.

2014-01-01

In sensory neurons, mechanotransduction is sensitive, fast and requires mechanosensitive ion channels. Here we develop a new method to directly monitor mechanotransduction at defined regions of the cell-substrate interface. We show that molecular-scale (~13 nm) displacements are sufficient to gate mechanosensitive currents in mouse touch receptors. Using neurons from knockout mice, we show that displacement thresholds increase by one order of magnitude in the absence of stomatin-like protein 3 (STOML3). Piezo1 is the founding member of a class of mammalian stretch-activated ion channels, and we show that STOML3, but not other stomatin-domain proteins, brings the activation threshold for Piezo1 and Piezo2 currents down to ~10 nm. Structure–function experiments localize the Piezo modulatory activity of STOML3 to the stomatin domain, and higher-order scaffolds are a prerequisite for function. STOML3 is the first potent modulator of Piezo channels that tunes the sensitivity of mechanically gated channels to detect molecular-scale stimuli relevant for fine touch. PMID:24662763

Measurement and interpretation of threshold stress intensity factors for steels in high-pressure hydrogen gas.

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

Dadfarnia, Mohsen; Nibur, Kevin A.; San Marchi, Christopher W.

2010-07-01

Threshold stress intensity factors were measured in high-pressure hydrogen gas for a variety of low alloy ferritic steels using both constant crack opening displacement and rising crack opening displacement procedures. The sustained load cracking procedures are generally consistent with those in ASME Article KD-10 of Section VIII Division 3 of the Boiler and Pressure Vessel Code, which was recently published to guide design of high-pressure hydrogen vessels. Three definitions of threshold were established for the two test methods: K{sub THi}* is the maximum applied stress intensity factor for which no crack extension was observed under constant displacement; K{sub THa} ismore » the stress intensity factor at the arrest position for a crack that extended under constant displacement; and K{sub JH} is the stress intensity factor at the onset of crack extension under rising displacement. The apparent crack initiation threshold under constant displacement, K{sub THi}*, and the crack arrest threshold, K{sub THa}, were both found to be non-conservative due to the hydrogen exposure and crack-tip deformation histories associated with typical procedures for sustained-load cracking tests under constant displacement. In contrast, K{sub JH}, which is measured under concurrent rising displacement and hydrogen gas exposure, provides a more conservative hydrogen-assisted fracture threshold that is relevant to structural components in which sub-critical crack extension is driven by internal hydrogen gas pressure.« less

Measurement and interpretation of threshold stress intensity factors for steels in high-pressure hydrogen gas.

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

Nibur, Kevin A.

2010-11-01

Threshold stress intensity factors were measured in high-pressure hydrogen gas for a variety of low alloy ferritic steels using both constant crack opening displacement and rising crack opening displacement procedures. The sustained load cracking procedures are generally consistent with those in ASME Article KD-10 of Section VIII Division 3 of the Boiler and Pressure Vessel Code, which was recently published to guide design of high-pressure hydrogen vessels. Three definitions of threshold were established for the two test methods: K{sub THi}* is the maximum applied stress intensity factor for which no crack extension was observed under constant displacement; K{sub THa} ismore » the stress intensity factor at the arrest position for a crack that extended under constant displacement; and K{sub JH} is the stress intensity factor at the onset of crack extension under rising displacement. The apparent crack initiation threshold under constant displacement, K{sub THi}*, and the crack arrest threshold, K{sub THa}, were both found to be non-conservative due to the hydrogen exposure and crack-tip deformation histories associated with typical procedures for sustained-load cracking tests under constant displacement. In contrast, K{sub JH}, which is measured under concurrent rising displacement and hydrogen gas exposure, provides a more conservative hydrogen-assisted fracture threshold that is relevant to structural components in which sub-critical crack extension is driven by internal hydrogen gas pressure.« less

Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease.

PubMed

Tashkin, Donald P; Wechsler, Michael E

2018-01-01

COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD.

Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease

PubMed Central

Tashkin, Donald P; Wechsler, Michael E

2018-01-01

COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. PMID:29403271

Robust ultrasensitive tunneling-FET biosensor for point-of-care diagnostics

PubMed Central

Gao, Anran; Lu, Na; Wang, Yuelin; Li, Tie

2016-01-01

For point-of-care (POC) applications, robust, ultrasensitive, small, rapid, low-power, and low-cost sensors are highly desirable. Here, we present a novel biosensor based on a complementary metal oxide semiconductor (CMOS)-compatible silicon nanowire tunneling field-effect transistor (SiNW-TFET). They were fabricated “top-down” with a low-cost anisotropic self-stop etching technique. Notably, the SiNW-TFET device provided strong anti-interference capacity by applying the inherent ambipolarity via both pH and CYFRA21-1 sensing. This offered a more robust and portable general protocol. The specific label-free detection of CYFRA21-1 down to 0.5 fgml−1 or ~12.5 aM was achieved using a highly responsive SiNW-TFET device with a minimum sub-threshold slope (SS) of 37 mVdec−1. Furthermore, real-time measurements highlighted the ability to use clinically relevant samples such as serum. The developed high performance diagnostic system is expected to provide a generic platform for numerous POC applications. PMID:26932158

Vitamin B supplementation for diabetic peripheral neuropathy.

PubMed

Jayabalan, Bhavani; Low, Lian Leng

2016-02-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. Copyright © Singapore Medical Association.

Magnetic Field-Induced T Cell Receptor Clustering by Nanoparticles Enhances T Cell Activation and Stimulates Antitumor Activity

PubMed Central

2015-01-01

Iron–dextran nanoparticles functionalized with T cell activating proteins have been used to study T cell receptor (TCR) signaling. However, nanoparticle triggering of membrane receptors is poorly understood and may be sensitive to physiologically regulated changes in TCR clustering that occur after T cell activation. Nano-aAPC bound 2-fold more TCR on activated T cells, which have clustered TCR, than on naive T cells, resulting in a lower threshold for activation. To enhance T cell activation, a magnetic field was used to drive aggregation of paramagnetic nano-aAPC, resulting in a doubling of TCR cluster size and increased T cell expansion in vitro and after adoptive transfer in vivo. T cells activated by nano-aAPC in a magnetic field inhibited growth of B16 melanoma, showing that this novel approach, using magnetic field-enhanced nano-aAPC stimulation, can generate large numbers of activated antigen-specific T cells and has clinically relevant applications for adoptive immunotherapy. PMID:24564881

MRI-leukoaraiosis thresholds and the phenotypic expression of dementia

PubMed Central

Mitchell, Sandra M.; Brumback, Babette; Tanner, Jared J.; Schmalfuss, Ilona; Lamar, Melissa; Giovannetti, Tania; Heilman, Kenneth M.; Libon, David J.

2012-01-01

Objective: To examine the concept of leukoaraiosis thresholds on working memory, visuoconstruction, memory, and language in dementia. Methods: A consecutive series of 83 individuals with insidious onset/progressive dementia clinically diagnosed with Alzheimer disease (AD) or small vessel vascular dementia (VaD) completed neuropsychological measures assessing working memory, visuoconstruction, episodic memory, and language. A clinical MRI scan was used to quantify leukoaraiosis, total white matter, hippocampus, lacune, and intracranial volume. We performed analyses to detect the lowest level of leukoaraiosis associated with impairment on the neuropsychological measures. Results: Leukoaraiosis ranged from 0.63% to 23.74% of participants' white matter. Leukoaraiosis explained a significant amount of variance in working memory performance when it involved 3% or more of the white matter with curve estimations showing the relationship to be nonlinear in nature. Greater leukoaraiosis (13%) was implicated for impairment in visuoconstruction. Relationships between leukoaraiosis, episodic memory, and language measures were linear or flat. Conclusions: Leukoaraiosis involves specific threshold points for working memory and visuoconstructional tests in AD/VaD spectrum dementia. These data underscore the need to better understand the threshold at which leukoaraiosis affects and alters the phenotypic expression in insidious onset dementia syndromes. PMID:22843264

Effect of a single session of muscle-biased therapy on pain sensitivity: a systematic review and meta-analysis of randomized controlled trials

PubMed Central

Gay, Charles W; Alappattu, Meryl J; Coronado, Rogelio A; Horn, Maggie E; Bishop, Mark D

2013-01-01

Background Muscle-biased therapies (MBT) are commonly used to treat pain, yet several reviews suggest evidence for the clinical effectiveness of these therapies is lacking. Inadequate treatment parameters have been suggested to account for inconsistent effects across studies. Pain sensitivity may serve as an intermediate physiologic endpoint helping to establish optimal MBT treatment parameters. The purpose of this review was to summarize the current literature investigating the short-term effect of a single dose of MBT on pain sensitivity in both healthy and clinical populations, with particular attention to specific MBT parameters of intensity and duration. Methods A systematic search for articles meeting our prespecified criteria was conducted using Cumulative Index to Nursing and Allied Health Literature (CINAHL) and MEDLINE from the inception of each database until July 2012, in accordance with guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analysis. Relevant characteristics from studies included type, intensity, and duration of MBT and whether short-term changes in pain sensitivity and clinical pain were noted with MBT application. Study results were pooled using a random-effects model to estimate the overall effect size of a single dose of MBT on pain sensitivity as well as the effect of MBT, dependent on comparison group and population type. Results Reports from 24 randomized controlled trials (23 articles) were included, representing 36 MBT treatment arms and 29 comparative groups, where 10 groups received active agents, 11 received sham/inert treatments, and eight received no treatment. MBT demonstrated a favorable and consistent ability to modulate pain sensitivity. Short-term modulation of pain sensitivity was associated with short-term beneficial effects on clinical pain. Intensity of MBT, but not duration, was linked with change in pain sensitivity. A meta-analysis was conducted on 17 studies that assessed the effect of MBT on pressure pain thresholds. The results suggest that MBT had a favorable effect on pressure pain thresholds when compared with no-treatment and sham/inert groups, and effects comparable with those of other active treatments. Conclusion The evidence supports the use of pain sensitivity measures by future research to help elucidate optimal therapeutic parameters for MBT as an intermediate physiologic marker. PMID:23403507

Why do adults with dyslexia have poor global motion sensitivity?

PubMed

Conlon, Elizabeth G; Lilleskaret, Gry; Wright, Craig M; Stuksrud, Anne

2013-01-01

Two experiments aimed to determine why adults with dyslexia have higher global motion thresholds than typically reading controls. In Experiment 1, the dot density and number of animation frames presented in the dot stimulus were manipulated because of findings that use of a high dot density can normalize coherence thresholds in individuals with dyslexia. Dot densities were 14.15 and 3.54 dots/deg(2). These were presented for five (84 ms) or eight (134 ms) frames. The dyslexia group had higher coherence thresholds in all conditions than controls. However, in the high dot density, long duration condition, both reader groups had the lowest thresholds indicating normal temporal recruitment. These results indicated that the dyslexia group could sample the additional signals dots over space and then integrate these with the same efficiency as controls. In Experiment 2, we determined whether briefly presenting a fully coherent prime moving in either the same or opposite direction of motion to a partially coherent test stimulus would systematically increase and decrease global motion thresholds in the reader groups. When the direction of motion in the prime and test was the same, global motion thresholds increased for both reader groups. The increase in coherence thresholds was significantly greater for the dyslexia group. When the motion of the prime and test were presented in opposite directions, coherence thresholds were reduced in both groups. No group threshold differences were found. We concluded that the global motion processing deficit found in adults with dyslexia can be explained by undersampling of the target motion signals. This might occur because of difficulties directing attention to the relevant motion signals in the random dot pattern, and not a specific difficulty integrating global motion signals. These effects are most likely to occur in the group with dyslexia when more complex computational processes are required to process global motion.

Why do adults with dyslexia have poor global motion sensitivity?

PubMed Central

Conlon, Elizabeth G.; Lilleskaret, Gry; Wright, Craig M.; Stuksrud, Anne

2013-01-01

Two experiments aimed to determine why adults with dyslexia have higher global motion thresholds than typically reading controls. In Experiment 1, the dot density and number of animation frames presented in the dot stimulus were manipulated because of findings that use of a high dot density can normalize coherence thresholds in individuals with dyslexia. Dot densities were 14.15 and 3.54 dots/deg2. These were presented for five (84 ms) or eight (134 ms) frames. The dyslexia group had higher coherence thresholds in all conditions than controls. However, in the high dot density, long duration condition, both reader groups had the lowest thresholds indicating normal temporal recruitment. These results indicated that the dyslexia group could sample the additional signals dots over space and then integrate these with the same efficiency as controls. In Experiment 2, we determined whether briefly presenting a fully coherent prime moving in either the same or opposite direction of motion to a partially coherent test stimulus would systematically increase and decrease global motion thresholds in the reader groups. When the direction of motion in the prime and test was the same, global motion thresholds increased for both reader groups. The increase in coherence thresholds was significantly greater for the dyslexia group. When the motion of the prime and test were presented in opposite directions, coherence thresholds were reduced in both groups. No group threshold differences were found. We concluded that the global motion processing deficit found in adults with dyslexia can be explained by undersampling of the target motion signals. This might occur because of difficulties directing attention to the relevant motion signals in the random dot pattern, and not a specific difficulty integrating global motion signals. These effects are most likely to occur in the group with dyslexia when more complex computational processes are required to process global motion. PMID:24376414

Optimal Threshold Determination for Interpreting Semantic Similarity and Particularity: Application to the Comparison of Gene Sets and Metabolic Pathways Using GO and ChEBI

PubMed Central

Bettembourg, Charles; Diot, Christian; Dameron, Olivier

2015-01-01

Background The analysis of gene annotations referencing back to Gene Ontology plays an important role in the interpretation of high-throughput experiments results. This analysis typically involves semantic similarity and particularity measures that quantify the importance of the Gene Ontology annotations. However, there is currently no sound method supporting the interpretation of the similarity and particularity values in order to determine whether two genes are similar or whether one gene has some significant particular function. Interpretation is frequently based either on an implicit threshold, or an arbitrary one (typically 0.5). Here we investigate a method for determining thresholds supporting the interpretation of the results of a semantic comparison. Results We propose a method for determining the optimal similarity threshold by minimizing the proportions of false-positive and false-negative similarity matches. We compared the distributions of the similarity values of pairs of similar genes and pairs of non-similar genes. These comparisons were performed separately for all three branches of the Gene Ontology. In all situations, we found overlap between the similar and the non-similar distributions, indicating that some similar genes had a similarity value lower than the similarity value of some non-similar genes. We then extend this method to the semantic particularity measure and to a similarity measure applied to the ChEBI ontology. Thresholds were evaluated over the whole HomoloGene database. For each group of homologous genes, we computed all the similarity and particularity values between pairs of genes. Finally, we focused on the PPAR multigene family to show that the similarity and particularity patterns obtained with our thresholds were better at discriminating orthologs and paralogs than those obtained using default thresholds. Conclusion We developed a method for determining optimal semantic similarity and particularity thresholds. We applied this method on the GO and ChEBI ontologies. Qualitative analysis using the thresholds on the PPAR multigene family yielded biologically-relevant patterns. PMID:26230274

Spatio-Temporal Regression Based Clustering of Precipitation Extremes in a Presence of Systematically Missing Covariates

NASA Astrophysics Data System (ADS)

Kaiser, Olga; Martius, Olivia; Horenko, Illia

2017-04-01

Regression based Generalized Pareto Distribution (GPD) models are often used to describe the dynamics of hydrological threshold excesses relying on the explicit availability of all of the relevant covariates. But, in real application the complete set of relevant covariates might be not available. In this context, it was shown that under weak assumptions the influence coming from systematically missing covariates can be reflected by a nonstationary and nonhomogenous dynamics. We present a data-driven, semiparametric and an adaptive approach for spatio-temporal regression based clustering of threshold excesses in a presence of systematically missing covariates. The nonstationary and nonhomogenous behavior of threshold excesses is describes by a set of local stationary GPD models, where the parameters are expressed as regression models, and a non-parametric spatio-temporal hidden switching process. Exploiting nonparametric Finite Element time-series analysis Methodology (FEM) with Bounded Variation of the model parameters (BV) for resolving the spatio-temporal switching process, the approach goes beyond strong a priori assumptions made is standard latent class models like Mixture Models and Hidden Markov Models. Additionally, the presented FEM-BV-GPD provides a pragmatic description of the corresponding spatial dependence structure by grouping together all locations that exhibit similar behavior of the switching process. The performance of the framework is demonstrated on daily accumulated precipitation series over 17 different locations in Switzerland from 1981 till 2013 - showing that the introduced approach allows for a better description of the historical data.

Determination of the Oswestry Disability Index score equivalent to a "satisfactory symptom state" in patients undergoing surgery for degenerative disorders of the lumbar spine-a Spine Tango registry-based study.

PubMed

van Hooff, Miranda L; Mannion, Anne F; Staub, Lukas P; Ostelo, Raymond W J G; Fairbank, Jeremy C T

2016-10-01

The achievement of a given change score on a valid outcome instrument is commonly used to indicate whether a clinically relevant change has occurred after spine surgery. However, the achievement of such a change score can be dependent on baseline values and does not necessarily indicate whether the patient is satisfied with the current state. The achievement of an absolute score equivalent to a patient acceptable symptom state (PASS) may be a more stringent measure to indicate treatment success. This study aimed to estimate the score on the Oswestry Disability Index (ODI, version 2.1a; 0-100) corresponding to a PASS in patients who had undergone surgery for degenerative disorders of the lumbar spine. This is a cross-sectional study of diagnostic accuracy using follow-up data from an international spine surgery registry. The sample includes 1,288 patients with degenerative lumbar spine disorders who had undergone elective spine surgery, registered in the EUROSPINE Spine Tango Spine Surgery Registry. The main outcome measure was the ODI (version 2.1a). Surgical data and data from the ODI and Core Outcome Measures Index (COMI) were included to determine the ODI threshold equivalent to PASS at 1 year (±1.5 months; n=780) and 2 years (±2 months; n=508) postoperatively. The symptom-specific well-being item of the COMI was used as the external criterion in the receiver operating characteristic (ROC) analysis to determine the ODI threshold equivalent to PASS. Separate sensitivity analyses were performed based on the different definitions of an "acceptable state" and for subgroups of patients. JF is a copyright holder of the ODI. The ODI threshold for PASS was 22, irrespective of the time of follow-up (area under the curve [AUC]: 0.89 [sensitivity {Se}: 78.3%, specificity {Sp}: 82.1%] and AUC: 0.91 [Se: 80.7%, Sp: 85.6] for the 1- and 2-year follow-ups, respectively). Sensitivity analyses showed that the absolute ODI-22 threshold for the two follow-up time-points were robust. A stricter definition of PASS resulted in lower ODI thresholds, varying from 16 (AUC=0.89; Se: 80.2%, Sp: 82.0%) to 18 (AUC=0.90; Se: 82.4%, Sp: 80.4%) depending on the time of follow-up. An ODI score ≤22 indicates the achievement of an acceptable symptom state and can hence be used as a criterion of treatment success alongside the commonly used change score measures. At the individual level, the threshold could be used to indicate whether or not a patient with a lumbar spine disorder is a "responder" after elective surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessing cancer drugs for reimbursement: methodology, relationship between effect size and medical need.

PubMed

de Sahb-Berkovitch, Rima; Woronoff-Lemsi, Marie-Christine; Molimard, Mathieu

2010-01-01

Reimbursement is assessed by the Transparency Commission from the Health Authority (HAS) using a medical benefit (SMR) score that gives access to reimbursement, an "improvement of medical service rendered" (ASMR) that determines the added therapeutic value, and the target population. Assessing cancer drugs for reimbursement raises the same issues as other therapeutic classes, with some key differences. Overall survival (OS) is considered by the Transparency Commission as the endpoint for assessing clinical benefit, and yet it is not an applicable primary endpoint in all types of cancer. Later lines of treatment, particularly during the development process, may make it difficult to interpret OS as the primary endpoint. Therefore, progression-free survival (PFS) for metastatic situations and disease-free survival (DFS) in adjuvant situations are wholly relevant endpoints for decisions on the reimbursement of a new cancer drug. Effect size is assessed using actuarial survival curves of the product versus the comparator, and it is difficult to summarise them into one single parameter. Results are generally interpreted based on median survival, which is fragmented because it only measures one point of the curve. The hazard ratio measures the effect of treatment throughout the duration of survival and is therefore more comprehensive in quantifying clinical benefit. Determining an effect size threshold for granting reimbursement is difficult given the diversity of cancer settings and the level of medical need, which influences assessment of the clinical relevance of the observed difference. Rapid progress in comparators (700 molecules in development) and the identification of predictive factors of efficacy (biomarkers, histology, etc.) during development may lead to different ASMR scores per population, or to the restriction of the target population to a subgroup of the marketing authorisation (MA) population in which the expected effect size is greater. To address these issues, the roundtable recommends the possibility of early scientific opinions by the office of the Transparency Commission in order to discuss comparators and the relevance of responder subgroups. It also recommends the possibility of granting a temporary ASMR, on condition of subsequent confirmation by production of data, when reimbursement appears justified in a subpopulation of the MA for which only subgroup analysis is available. © 2010 Société Française de Pharmacologie et de Thérapeutique.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation.

PubMed

Muelken, Peter; Schmidt, Clare E; Shelley, David; Tally, Laura; Harris, Andrew C

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e.g., anxiety-like behavior, somatic signs), may be useful for understanding the development of the nicotine withdrawal syndrome.

Non-vitamin K antagonist oral anticoagulants compared with warfarin at different levels of INR control in atrial fibrillation: A meta-analysis of randomized trials.

PubMed

Carmo, João; Ferreira, Jorge; Costa, Francisco; Carmo, Pedro; Cavaco, Diogo; Carvalho, Salomé; Morgado, Francisco; Adragão, Pedro; Mendes, Miguel

2017-10-01

The efficacy and safety of warfarin for stroke prevention in atrial fibrillation (AF) depend on the time in the therapeutic range (TTR) with an international normalised ratio (INR) of 2.0-3.0. This meta-analysis focused the relative efficacy and safety of non-VKA oral anticoagulants (NOAC) compared with warfarin at different thresholds of centre's TTR (cTTR). We searched PubMed, Embase, CENTRAL and websites of regulatory agencies, limiting searches to randomized phase 3 trials. Primary outcomes were stroke or systemic embolism (SSE) and major or non-major clinically relevant (NMCR) bleeding. We used a random-effects model to pool effect on outcomes according to different thresholds of cTTR. Four TTR sub-studies with a total of 71,222 patients were included. The benefit of NOAC in reducing SSE compared with warfarin was significantly higher in patients at cTTR<60% (HR 0.79, 95% CI 0.68-0.90) and at 60% to <70% (0.82, 0.71-0.95) but not at ≥70% (1.00, 0.82-1.23) with a significant interaction for cTTR<70% or ≥70% (p=0.042). The risk of major or NMCR bleeding was significantly lower with NOAC as compared with warfarin in patients at all sub-groups (0.67, 0.54-0.83 for patients at cTTR<60% and 0.75, 0.63-0.89 at 60% to <70%) except for cTTR≥70% (HR 0.84, 0.64-1.11), but the interaction for cTTR<70% or ≥70% was not statistically significant (p=0.271). The superiority in efficacy of NOAC compared with warfarin for stroke prevention is lost above a cTTR threshold of approximately 70%, but the relative safety appears to be less modified by the centre-based quality of INR control. Copyright © 2017 Elsevier B.V. All rights reserved.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

PubMed Central

Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e.g., anxiety-like behavior, somatic signs), may be useful for understanding the development of the nicotine withdrawal syndrome. PMID:26658557

CD4 Enumeration Technologies: A Systematic Review of Test Performance for Determining Eligibility for Antiretroviral Therapy

PubMed Central

Peeling, Rosanna W.; Sollis, Kimberly A.; Glover, Sarah; Crowe, Suzanne M.; Landay, Alan L.; Cheng, Ben; Barnett, David; Denny, Thomas N.; Spira, Thomas J.; Stevens, Wendy S.; Crowley, Siobhan; Essajee, Shaffiq; Vitoria, Marco; Ford, Nathan

2015-01-01

Background Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. Methods and Findings Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. Conclusions A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed. PMID:25790185

Qcritical as a Geomorphically and Biologically Relevant Flow Threshold for Stormwater Management and Catchment-scale Stream Restoration

NASA Astrophysics Data System (ADS)

Hawley, R. J.; Vietz, G. J.; Wooten, M. S.

2016-12-01

The threshold discharge that initiates streambed mobilization (Qcritical) is one of the most mechanistically-important flows for geomorphic function and biological integrity in stream ecosystems. Increased frequency and duration of flows that exceed Qcritical are a dominant driver of geomorphic instability and excess benthic disturbance in urban/suburban streams (i.e. the urban disturbance regime). Qcritical frequency also corresponds to measures of stream integrity in reference streams, with both geomorphic stability and biological indices significantly correlated to time since a Qcritical event in one 7-y study. Indeed, reference site macroinvertebrate communities during years with atypically frequent Qcritical events were more similar to sites draining watersheds with 30% imperviousness than to reference site communities of more typical rainfall years. Despite its biophysical relevance to stream ecosystems, Qcritical is one of the most overlooked and misunderstood flows in the stormwater management and stream restoration fields. Regional stormwater policies and stream restoration design guidance are often based on the misplaced assumption that streambed erosion does not occur at sub-bankfull events (often assumed to correspond to the 1-y recurrence discharge). Using an international database of nearly 200 sites we show that Qcritical varies by several orders of magnitude as a function of streambed particle size. Qcritical in sand-dominated streams is likely to be orders of magnitude less than the 1-yr discharge, whereas Qcritical in cobble/boulder dominated streams could be much larger than the 1-yr discharge, implying that stormwater/restoration policies focused on the 1-yr event could lack efficacy in many stream settings. Qcritical is a geomorphically- and biologically-relevant discharge threshold when developing stormwater management policies intended to protect streams from excess erosion, designing watershed-scale restoration efforts to restore a more natural disturbance regime, or reconstructing stream reaches designed to restore sediment continuity. Incorporation of Qcritical into such restoration and management efforts ensures that designs are actually tailored to the mechanisms that drive channel erosion and disturbance to the benthos.

Scaling Soil Microbe-Water Interactions from Pores to Ecosystems

NASA Astrophysics Data System (ADS)

Manzoni, S.; Katul, G. G.

2014-12-01

The spatial scales relevant to soil microbial activity are much finer than scales relevant to whole-ecosystem function and biogeochemical cycling. On the one hand, how to link such different scales and develop scale-aware biogeochemical and ecohydrological models remains a major challenge. On the other hand, resolving these linkages is becoming necessary for testing ecological hypotheses and resolving data-theory inconsistencies. Here, the relation between microbial respiration and soil moisture expressed in water potential is explored. Such relation mediates the water availability effects on ecosystem-level heterotrophic respiration and is of paramount importance for understanding CO2 emissions under increasingly variable rainfall regimes. Respiration has been shown to decline as the soil dries in a remarkably consistent way across climates and soil types (open triangles in Figure). Empirical models based on these respiration-moisture relations are routinely used in Earth System Models to predict moisture effects on ecosystem respiration. It has been hypothesized that this consistency in microbial respiration decline is due to breakage of water film continuity causing in turn solute diffusion limitations in dry conditions. However, this hypothesis appears to be at odds with what is known about soil hydraulic properties. Water film continuity estimated from soil water retention (SWR) measurements at the 'Darcy' scale breaks at far less negative water potential (<-0.1 MPa) levels than where microbial respiration ceases (approximately -15 MPa) as shown in the Figure (violet frequency distribution). Also, this threshold point inferred from SWR shows strong texture dependence, in contrast to the respiration curves. Employing theoretical tools from percolation theory, it is demonstrated that hydrological measurements can be spatially downscaled at a micro-level relevant to microbial activity. Such downscaling resolves the inconsistency between respiration thresholds and hydrological thresholds. This result, together with observations of residual microbial activity well below -15 MPa (dashed back curve in Figure), lends support to the hypothesis that soil microbes are substrate-limited in dry conditions.

Clinical relevance of findings in trials of CBT for depression.

PubMed

Lepping, P; Whittington, R; Sambhi, R S; Lane, S; Poole, R; Leucht, S; Cuijpers, P; McCabe, R; Waheed, W

2017-09-01

Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We identified RCTs of CBT that used the Hamilton Rating Scale for Depression (HAMD). HAMD scores were translated into Clinical Global Impression - Change scale (CGI-I) scores to measure clinical relevance. One hundred and seventy datasets from 82 studies were included. The mean percentage HAMD change for treatment arms was 53.66%, and 29.81% for control arms, a statistically significant difference. Combined active therapies showed the biggest improvement on CGI-I score, followed by CBT alone. All active treatments had better than expected HAMD percentage reduction and CGI-I scores. CBT has a clinically relevant effect in depression, with a notional CGI-I score of 2.2, indicating a significant clinical response. The non-specific or placebo effect of being in a psychotherapy trial was a 29% reduction of HAMD. Copyright © 2017. Published by Elsevier Masson SAS.

A Peep into the Uncertainty-Complexity-Relevance Modeling Trilemma through Global Sensitivity and Uncertainty Analysis

NASA Astrophysics Data System (ADS)

Munoz-Carpena, R.; Muller, S. J.; Chu, M.; Kiker, G. A.; Perz, S. G.

2014-12-01

Model Model complexity resulting from the need to integrate environmental system components cannot be understated. In particular, additional emphasis is urgently needed on rational approaches to guide decision making through uncertainties surrounding the integrated system across decision-relevant scales. However, in spite of the difficulties that the consideration of modeling uncertainty represent for the decision process, it should not be avoided or the value and science behind the models will be undermined. These two issues; i.e., the need for coupled models that can answer the pertinent questions and the need for models that do so with sufficient certainty, are the key indicators of a model's relevance. Model relevance is inextricably linked with model complexity. Although model complexity has advanced greatly in recent years there has been little work to rigorously characterize the threshold of relevance in integrated and complex models. Formally assessing the relevance of the model in the face of increasing complexity would be valuable because there is growing unease among developers and users of complex models about the cumulative effects of various sources of uncertainty on model outputs. In particular, this issue has prompted doubt over whether the considerable effort going into further elaborating complex models will in fact yield the expected payback. New approaches have been proposed recently to evaluate the uncertainty-complexity-relevance modeling trilemma (Muller, Muñoz-Carpena and Kiker, 2011) by incorporating state-of-the-art global sensitivity and uncertainty analysis (GSA/UA) in every step of the model development so as to quantify not only the uncertainty introduced by the addition of new environmental components, but the effect that these new components have over existing components (interactions, non-linear responses). Outputs from the analysis can also be used to quantify system resilience (stability, alternative states, thresholds or tipping points) in the face of environmental and anthropogenic change (Perz, Muñoz-Carpena, Kiker and Holt, 2013), and through MonteCarlo mapping potential management activities over the most important factors or processes to influence the system towards behavioral (desirable) outcomes (Chu-Agor, Muñoz-Carpena et al., 2012).

Drug development in neuropsychopharmacology.

PubMed

Fritze, Jürgen

2008-03-01

Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

A threshold-free summary index of prediction accuracy for censored time to event data.

PubMed

Yuan, Yan; Zhou, Qian M; Li, Bingying; Cai, Hengrui; Chow, Eric J; Armstrong, Gregory T

2018-05-10

Prediction performance of a risk scoring system needs to be carefully assessed before its adoption in clinical practice. Clinical preventive care often uses risk scores to screen asymptomatic population. The primary clinical interest is to predict the risk of having an event by a prespecified future time t 0 . Accuracy measures such as positive predictive values have been recommended for evaluating the predictive performance. However, for commonly used continuous or ordinal risk score systems, these measures require a subjective cutoff threshold value that dichotomizes the risk scores. The need for a cutoff value created barriers for practitioners and researchers. In this paper, we propose a threshold-free summary index of positive predictive values that accommodates time-dependent event status and competing risks. We develop a nonparametric estimator and provide an inference procedure for comparing this summary measure between 2 risk scores for censored time to event data. We conduct a simulation study to examine the finite-sample performance of the proposed estimation and inference procedures. Lastly, we illustrate the use of this measure on a real data example, comparing 2 risk score systems for predicting heart failure in childhood cancer survivors. Copyright © 2018 John Wiley & Sons, Ltd.

Platelet-rich plasma versus autologous blood versus steroid injection in lateral epicondylitis: systematic review and network meta-analysis.

PubMed

Arirachakaran, Alisara; Sukthuayat, Amnat; Sisayanarane, Thaworn; Laoratanavoraphong, Sorawut; Kanchanatawan, Wichan; Kongtharvonskul, Jatupon

2016-06-01

Clinical outcomes between the use of platelet-rich plasma (PRP), autologous blood (AB) and corticosteroid (CS) injection in lateral epicondylitis are still controversial. A systematic review and network meta-analysis of randomized controlled trials was conducted with the aim of comparing relevant clinical outcomes between the use of PRP, AB and CS injection. Medline and Scopus databases were searched from inception to January 2015. A network meta-analysis was performed by applying weight regression for continuous outcomes and a mixed-effect Poisson regression for dichotomous outcomes. Ten of 374 identified studies were eligible. When compared to CS, AB injection showed significantly improved effects with unstandardized mean differences (UMD) in pain visual analog scale (VAS), Disabilities of Arm Shoulder and Hand (DASH), Patient-Related Tennis Elbow Evaluation (PRTEE) score and pressure pain threshold (PPT) of -2.5 (95 % confidence interval, -3.5, -1.5), -25.5 (-33.8, -17.2), -5.3 (-9.1, -1.6) and 9.9 (5.6, 14.2), respectively. PRP injections also showed significantly improved VAS and DASH scores when compared with CS. PRP showed significantly better VAS with UMD when compared to AB injection. AB injection has a higher risk of adverse effects, with a relative risk of 1.78 (1.00, 3.17), when compared to CS. The network meta-analysis suggested no statistically significant difference in multiple active treatment comparisons of VAS, DASH and PRTEE when comparing PRP and AB injections. However, AB injection had improved DASH score and PPT when compared with PRP injection. In terms of adverse effects, AB injection had a higher risk than PRP injection. This network meta-analysis provided additional information that PRP injection can improve pain and lower the risk of complications, whereas AB injection can improve pain, disabilities scores and pressure pain threshold but has a higher risk of complications. Level I evidence.

Investigating Various Thresholds as Immunohistochemistry Cutoffs for Observer Agreement.

PubMed

Ali, Asif; Bell, Sarah; Bilsland, Alan; Slavin, Jill; Lynch, Victoria; Elgoweini, Maha; Derakhshan, Mohammad H; Jamieson, Nigel B; Chang, David; Brown, Victoria; Denley, Simon; Orange, Clare; McKay, Colin; Carter, Ross; Oien, Karin A; Duthie, Fraser R

2017-10-01

Clinical translation of immunohistochemistry (IHC) biomarkers requires reliable and reproducible cutoffs or thresholds for interpretation of immunostaining. Most IHC biomarker research focuses on the clinical relevance (diagnostic, prognostic, or predictive utility) of cutoffs, with less emphasis on observer agreement using these cutoffs. From the literature, we identified 3 commonly used cutoffs of 10% positive epithelial cells, 20% positive epithelial cells, and moderate to strong staining intensity (+2/+3 hereafter) to use for investigating observer agreement. A series of 36 images of microarray cores stained for 4 different IHC biomarkers, with variable staining intensity and percentage of positive cells, was used for investigating interobserver and intraobserver agreement. Seven pathologists scored the immunostaining in each image using the 3 cutoffs for positive and negative staining. Kappa (κ) statistic was used to assess the strength of agreement for each cutoff. The interobserver agreement between all 7 pathologists using the 3 cutoffs was reasonably good, with mean κ scores of 0.64, 0.59, and 0.62, respectively, for 10%, 20%, and +2/+3 cutoffs. A good agreement was observed for experienced pathologists using the 10% cutoff, and their agreement was statistically higher than for junior pathologists (P=0.02). In addition, the mean intraobserver agreement for all 7 pathologists using the 3 cutoffs was reasonably good, with mean κ scores of 0.71, 0.60, and 0.73, respectively, for 10%, 20%, and +2/+3 cutoffs. For all 3 cutoffs, a positive correlation was observed with perceived ease of interpretation (P<0.003). Finally, cytoplasmic-only staining achieved higher agreement using all 3 cutoffs than mixed staining patterns. All 3 cutoffs investigated achieve reasonable strength of agreement, modestly decreasing interobserver and intraobserver variability in IHC interpretation. These cutoffs have previously been used in cancer pathology, and this study provides evidence that these cutoffs can be reproducible between practicing pathologists.

Physician reasons for nonpharmacologic treatment of hyperglycemia in older patients newly diagnosed with type 2 diabetes mellitus.

PubMed

Marrett, Elizabeth; Zhang, Qiaoyi; Kanitscheider, Claudia; Davies, Michael J; Radican, Larry; Feinglos, Mark N

2012-11-01

To identify reasons why primary care physicians (PCPs) do not treat older patients newly diagnosed with type 2 diabetes mellitus (T2DM) with antihyperglycemic agents following diagnosis. US PCPs were surveyed via the internet regarding their reasons for not treating patients aged >65 years diagnosed with T2DM and had not yet initiated antihyperglycemic therapy for ≥6 months after diagnosis. PCPs were requested to provide relevant clinical information for untreated older patients and select applicable reasons for not initiating treatment from a list of 35 possibilities, grouped into five categories. A total of 508 PCPs completed the online survey and provided complete clinical data for 770 patients. The reasons provided by the first-ranked physician for not initiating antihyperglycemic therapy were related to diet and exercise (57.5%); mild hyperglycemia (23.8%); patient's concerns (13.4%); concerns about antihyperglycemic agents (3.0%); and comorbidities and polypharmacy (2.3%). The "diet and exercise" category was the most common first-ranked non-treatment reason, regardless of recent hemoglobin A(1c) (HbA(1c)) stratum. Reasons within the "patient's concerns," "concerns related to antihyperglycemic agents," and "comorbidities and polypharmacy" categories tended to be selected more often as first-ranked reasons by physicians for patients with higher HbA(1c) values. Of the 158 patients whose physicians planned to initiate antihyperglycemic therapy within the next month, 54.4% already had a most recent HbA(1c) value above their physician-stated threshold for treatment initiation. In the PCPs studied, there was a tendency to select appropriate reasons for non-treatment with antihyperglycemic agents given their patients' glycemic status. However, there was inertia related to the initiation of pharmacological therapy in some older patients with newly diagnosed T2DM. Important factors included physicians' perceptions of "mild" hyperglycemia and the HbA(1c) threshold for using antihyperglycemic agents.

Study of the coalescence/splash threshold of droplet impact on liquid films and its relevance in assessing airborne particle release.

PubMed

Motzkus, C; Gensdarmes, F; Géhin, E

2011-10-15

Impingement of droplets on surfaces occurs in many industrial and natural processes. The study of droplet break-up is fundamental in order to determine the potential sources of airborne contamination for scenarios of hazardous liquid falls such as dripping. There are very few data in the literature describing the case of impact of millimetre-size droplets. The purposes of this work were to study experimentally particle emission during the impact of droplets on a liquid film and to assess the use of coalescence/splash relations to predict airborne particle release. The results are described using dimensionless numbers taking into account the inertial, viscosity and surface tension forces. Experiments were carried out for Weber numbers between 62 and 1754 and for Ohnesorge numbers between 2.0×10(-3) and 1.5×10(-2). New results on coalescence/splash thresholds are obtained using highly sensitive aerosol measurement and allow a prediction concerning the presence or absence of airborne particles according to a threshold relation. Moreover, we propose a modification of the Cossali et al.'s relation in order to describe the coalescence/prompt splash threshold. Copyright © 2011 Elsevier Inc. All rights reserved.

A piecewise regression approach for determining biologically relevant hydraulic thresholds for the protection of fish at river infrastructure

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

Boys, Craig A.; Robinson, Wayne; Miller, Brett

2016-05-13

Barotrauma injury can occur when fish are exposed to rapid decompression during downstream passage through river infrastructure. A piecewise regression approach was used to objectively quantify barotrauma injury thresholds in two physoclistous species (Murray cod Maccullochella peelii and silver perch Bidyanus bidyanus) following simulated infrastructure passage in barometric chambers. The probability of injuries such as swim bladder rupture; exophthalmia; and haemorrhage and emphysema in various organs increased as the ratio between the lowest exposure pressure and the acclimation pressure (ratio of pressure change RPCE/A) fell. The relationship was typically non-linear and piecewise regression was able to quantify thresholds in RPCE/Amore » that once exceeded resulted in a substantial increase in barotrauma injury. Thresholds differed among injury types and between species but by applying a multi-species precautionary principle, the maintenance of exposure pressures at river infrastructure above 70% of acclimation pressure (RPCE/A of 0.7) should sufficiently protect downstream migrating juveniles of these two physoclistous species. These findings have important implications for determining the risk posed by current infrastructures and informing the design and operation of new ones.« less

The effect of threshold amounts for reporting malpractice payments to the National Practitioner Data Bank: analysis using the closed claims data base of the Office of the Assistant Secretary of Defense (Health Affairs).

PubMed

Metter, E J; Granville, R L; Kussman, M J

1997-04-01

The study determines the extent to which payment thresholds for reporting malpractice claims to the National Practitioner Data Bank identifies substandard health care delivery in the Department of Defense. Relevant data were available on 2,291 of 2,576 medical malpractice claims reported to the closed medical malpractice case data base of the Office of the Assistant Secretary of Defense (Health Affairs). Amount paid was analyzed as a diagnostic test using standard of care assessment from each military Surgeon General office as the criterion. Using different paid threshold amounts per claim as a positive test, the sensitivity of identifying substandard care declined from 0.69 for all paid cases to 0.41 for claims over $40,000. Specificity increased from 0.75 for all paid claims to 0.89 for claims over $40,000. Positive and negative predictive values and likelihood ratio were similar at all thresholds. Malpractice case payment was of limited value for identifying substandard medical practice. All paid claims missed about 30% of substandard care, and reported about 25% of acceptable medical practice.

The dual rod system of amphibians supports colour discrimination at the absolute visual threshold

PubMed Central

Yovanovich, Carola A. M.; Koskela, Sanna M.; Nevala, Noora; Kondrashev, Sergei L.

2017-01-01

The presence of two spectrally different kinds of rod photoreceptors in amphibians has been hypothesized to enable purely rod-based colour vision at very low light levels. The hypothesis has never been properly tested, so we performed three behavioural experiments at different light intensities with toads (Bufo) and frogs (Rana) to determine the thresholds for colour discrimination. The thresholds of toads were different in mate choice and prey-catching tasks, suggesting that the differential sensitivities of different spectral cone types as well as task-specific factors set limits for the use of colour in these behavioural contexts. In neither task was there any indication of rod-based colour discrimination. By contrast, frogs performing phototactic jumping were able to distinguish blue from green light down to the absolute visual threshold, where vision relies only on rod signals. The remarkable sensitivity of this mechanism comparing signals from the two spectrally different rod types approaches theoretical limits set by photon fluctuations and intrinsic noise. Together, the results indicate that different pathways are involved in processing colour cues depending on the ecological relevance of this information for each task. This article is part of the themed issue ‘Vision in dim light’. PMID:28193811

Evolution of complex density-dependent dispersal strategies.

PubMed

Parvinen, Kalle; Seppänen, Anne; Nagy, John D

2012-11-01

The question of how dispersal behavior is adaptive and how it responds to changes in selection pressure is more relevant than ever, as anthropogenic habitat alteration and climate change accelerate around the world. In metapopulation models where local populations are large, and thus local population size is measured in densities, density-dependent dispersal is expected to evolve to a single-threshold strategy, in which individuals stay in patches with local population density smaller than a threshold value and move immediately away from patches with local population density larger than the threshold. Fragmentation tends to convert continuous populations into metapopulations and also to decrease local population sizes. Therefore we analyze a metapopulation model, where each patch can support only a relatively small local population and thus experience demographic stochasticity. We investigated the evolution of density-dependent dispersal, emigration and immigration, in two scenarios: adult and natal dispersal. We show that density-dependent emigration can also evolve to a nonmonotone, "triple-threshold" strategy. This interesting phenomenon results from an interplay between the direct and indirect benefits of dispersal and the costs of dispersal. We also found that, compared to juveniles, dispersing adults may benefit more from density-dependent vs. density-independent dispersal strategies.

A sparse representation of the pathologist's interaction with whole slide images to improve the assigned relevance of regions of interest

NASA Astrophysics Data System (ADS)

Santiago, Daniel; Corredor, Germán.; Romero, Eduardo

2017-11-01

During a diagnosis task, a Pathologist looks over a Whole Slide Image (WSI), aiming to find out relevant pathological patterns. Nonetheless, a virtual microscope captures these structures, but also other cellular patterns with different or none diagnostic meaning. Annotation of these images depends on manual delineation, which in practice becomes a hard task. This article contributes a new method for detecting relevant regions in WSI using the routine navigations in a virtual microscope. This method constructs a sparse representation or dictionary of each navigation path and determines the hidden relevance by maximizing the incoherence between several paths. The resulting dictionaries are then projected onto each other and relevant information is set to the dictionary atoms whose similarity is higher than a custom threshold. Evaluation was performed with 6 pathological images segmented from a skin biopsy already diagnosed with basal cell carcinoma (BCC). Results show that our proposal outperforms the baseline by more than 20%.

Effects of acute hypoxia on the determination of anaerobic threshold using the heart rate-work rate relationships during incremental exercise tests.

PubMed

Ozcelik, O; Kelestimur, H

2004-01-01

Anaerobic threshold which describes the onset of systematic increase in blood lactate concentration is a widely used concept in clinical and sports medicine. A deflection point between heart rate-work rate has been introduced to determine the anaerobic threshold non-invasively. However, some researchers have consistently reported a heart rate deflection at higher work rates, while others have not. The present study was designed to investigate whether the heart rate deflection point accurately predicts the anaerobic threshold under the condition of acute hypoxia. Eight untrained males performed two incremental exercise tests using an electromagnetically braked cycle ergometer: one breathing room air and one breathing 12 % O2. The anaerobic threshold was estimated using the V-slope method and determined from the increase in blood lactate and the decrease in standard bicarbonate concentration. This threshold was also estimated by in the heart rate-work rate relationship. Not all subjects exhibited a heart rate deflection. Only two subjects in the control and four subjects in the hypoxia groups showed a heart rate deflection. Additionally, the heart rate deflection point overestimated the anaerobic threshold. In conclusion, the heart rate deflection point was not an accurate predictor of anaerobic threshold and acute hypoxia did not systematically affect the heart rate-work rate relationships.

Equivalence and test-retest reproducibility of conventional and extended-high-frequency audiometric thresholds obtained using pure-tone and narrow-band-noise stimuli.

PubMed

John, Andrew B; Kreisman, Brian M

2017-09-01

Extended high-frequency (EHF) audiometry is useful for evaluating ototoxic exposures and may relate to speech recognition, localisation and hearing aid benefit. There is a need to determine whether common clinical practice for EHF audiometry using tone and noise stimuli is reliable. We evaluated equivalence and compared test-retest (TRT) reproducibility for audiometric thresholds obtained using pure tones and narrowband noise (NBN) from 0.25 to 16 kHz. Thresholds and test-retest reproducibility for stimuli in the conventional (0.25-6 kHz) and EHF (8-16 kHz) frequency ranges were compared in a repeated-measures design. A total of 70 ears of adults with normal hearing. Thresholds obtained using NBN were significantly lower than thresholds obtained using pure tones from 0.5 to 16 kHz, but not 0.25 kHz. Good TRT reproducibility (within 2 dB) was observed for both stimuli at all frequencies. Responses at the lower limit of the presentation range for NBN centred at 14 and 16 kHz suggest unreliability for NBN as a threshold stimulus at these frequencies. Thresholds in the conventional and EHF ranges showed good test-retest reproducibility, but differed between stimulus types. Care should be taken when comparing pure-tone thresholds with NBN thresholds especially at these frequencies.

Reliability of TMS phosphene threshold estimation: Toward a standardized protocol.

PubMed

Mazzi, Chiara; Savazzi, Silvia; Abrahamyan, Arman; Ruzzoli, Manuela

Phosphenes induced by transcranial magnetic stimulation (TMS) are a subjectively described visual phenomenon employed in basic and clinical research as index of the excitability of retinotopically organized areas in the brain. Phosphene threshold estimation is a preliminary step in many TMS experiments in visual cognition for setting the appropriate level of TMS doses; however, the lack of a direct comparison of the available methods for phosphene threshold estimation leaves unsolved the reliability of those methods in setting TMS doses. The present work aims at fulfilling this gap. We compared the most common methods for phosphene threshold calculation, namely the Method of Constant Stimuli (MOCS), the Modified Binary Search (MOBS) and the Rapid Estimation of Phosphene Threshold (REPT). In two experiments we tested the reliability of PT estimation under each of the three methods, considering the day of administration, participants' expertise in phosphene perception and the sensitivity of each method to the initial values used for the threshold calculation. We found that MOCS and REPT have comparable reliability when estimating phosphene thresholds, while MOBS estimations appear less stable. Based on our results, researchers and clinicians can estimate phosphene threshold according to MOCS or REPT equally reliably, depending on their specific investigation goals. We suggest several important factors for consideration when calculating phosphene thresholds and describe strategies to adopt in experimental procedures. Copyright © 2017 Elsevier Inc. All rights reserved.

Identifying thresholds for relationships between impacts of rationing of nursing care and nurse- and patient-reported outcomes in Swiss hospitals: a correlational study.

PubMed

Schubert, Maria; Clarke, Sean P; Glass, Tracy R; Schaffert-Witvliet, Bianca; De Geest, Sabina

2009-07-01

In the Rationing of Nursing Care in Switzerland Study, implicit rationing of care was the only factor consistently significantly associated with all six studied patient outcomes. These results highlight the importance of rationing as a new system factor regarding patient safety and quality of care. Since at least some rationing of care appears inevitable, it is important to identify the thresholds of its influences in order to minimize its negative effects on patient outcomes. To describe the levels of implicit rationing of nursing care in a sample of Swiss acute care hospitals and to identify clinically meaningful thresholds of rationing. Descriptive cross-sectional multi-center study. Five Swiss-German and three Swiss-French acute care hospitals. 1338 nurses and 779 patients. Implicit rationing of nursing care was measured using the newly developed Basel Extent of Rationing of Nursing Care (BERNCA) instrument. Other variables were measured using survey items from the International Hospital Outcomes Study battery. Data were summarized using appropriate descriptive measures, and logistic regression models were used to define a clinically meaningful rationing threshold level. For the studied patient outcomes, identified rationing threshold levels varied from 0.5 (i.e., between 0 ('never') and 1 ('rarely') to 2 ('sometimes')). Three of the identified patient outcomes (nosocomial infections, pressure ulcers, and patient satisfaction) were particularly sensitive to rationing, showing negative consequences anywhere it was consistently reported (i.e., average BERNCA scores of 0.5 or above). In other cases, increases in negative outcomes were first observed from the level of 1 (average ratings of rarely). Rationing scores generated using the BERNCA instrument provide a clinically meaningful method for tracking the correlates of low resources or difficulties in resource allocation on patient outcomes. Thresholds identified here provide parameters for administrators to respond to whenever rationing reports exceed the determined level of '0.5' or '1'. Since even very low levels of rationing had negative consequences on three of the six studied outcomes, it is advisable to treat consistent evidence of any rationing as a significant threat to patient safety and quality of care.

Freezing of Gait Detection in Parkinson's Disease: A Subject-Independent Detector Using Anomaly Scores.

PubMed

Pham, Thuy T; Moore, Steven T; Lewis, Simon John Geoffrey; Nguyen, Diep N; Dutkiewicz, Eryk; Fuglevand, Andrew J; McEwan, Alistair L; Leong, Philip H W

2017-11-01

Freezing of gait (FoG) is common in Parkinsonian gait and strongly relates to falls. Current clinical FoG assessments are patients' self-report diaries and experts' manual video analysis. Both are subjective and yield moderate reliability. Existing detection algorithms have been predominantly designed in subject-dependent settings. In this paper, we aim to develop an automated FoG detector for subject independent. After extracting highly relevant features, we apply anomaly detection techniques to detect FoG events. Specifically, feature selection is performed using correlation and clusterability metrics. From a list of 244 feature candidates, 36 candidates were selected using saliency and robustness criteria. We develop an anomaly score detector with adaptive thresholding to identify FoG events. Then, using accuracy metrics, we reduce the feature list to seven candidates. Our novel multichannel freezing index was the most selective across all window sizes, achieving sensitivity (specificity) of (). On the other hand, freezing index from the vertical axis was the best choice for a single input, achieving sensitivity (specificity) of () for ankle and () for back sensors. Our subject-independent method is not only significantly more accurate than those previously reported, but also uses a much smaller window (e.g., versus ) and/or lower tolerance (e.g., versus ).Freezing of gait (FoG) is common in Parkinsonian gait and strongly relates to falls. Current clinical FoG assessments are patients' self-report diaries and experts' manual video analysis. Both are subjective and yield moderate reliability. Existing detection algorithms have been predominantly designed in subject-dependent settings. In this paper, we aim to develop an automated FoG detector for subject independent. After extracting highly relevant features, we apply anomaly detection techniques to detect FoG events. Specifically, feature selection is performed using correlation and clusterability metrics. From a list of 244 feature candidates, 36 candidates were selected using saliency and robustness criteria. We develop an anomaly score detector with adaptive thresholding to identify FoG events. Then, using accuracy metrics, we reduce the feature list to seven candidates. Our novel multichannel freezing index was the most selective across all window sizes, achieving sensitivity (specificity) of (). On the other hand, freezing index from the vertical axis was the best choice for a single input, achieving sensitivity (specificity) of () for ankle and () for back sensors. Our subject-independent method is not only significantly more accurate than those previously reported, but also uses a much smaller window (e.g., versus ) and/or lower tolerance (e.g., versus ).

Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

PubMed

Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Dentists' perspectives on caries-related treatment decisions.

PubMed

Gomez, J; Ellwood, R P; Martignon, S; Pretty, I A

2014-06-01

To assess the impact of patient risk status on Colombian dentists' caries related treatment decisions for early to intermediate caries lesions (ICDAS code 2 to 4). A web-based questionnaire assessed dentists' views on the management of early/intermediate lesions. The questionnaire included questions on demographic characteristics, five clinical scenarios with randomised levels of caries risk, and two questions on different clinical and radiographic sets of images with different thresholds of caries. Questionnaires were completed by 439 dentists. For the two scenarios describing occlusal lesions ICDAS code 2, dentists chose to provide a preventive option in 63% and 60% of the cases. For the approximal lesion ICDAS code 2, 81% of the dentists chose to restore. The main findings of the binary logistic regression analysis for the clinical scenarios suggest that for the ICDAS code 2 occlusal lesions, the odds of a high caries risk patient having restorations is higher than for a low caries risk patient. For the questions describing different clinical thresholds of caries, most dentists would restore at ICDAS code 2 (55%) and for the question showing different radiographic thresholds images, 65% of dentists would intervene operatively at the inner half of enamel. No significant differences with respect to risk were found for these questions with the logistic regression. The results of this study indicate that Colombian dentists have not yet fully adopted non-invasive treatment for early caries lesions.

Neodymium: YAG laser damage threshold. A comparison of injection-molded and lathe-cut polymethylmethacrylate intraocular lenses.

PubMed

Wilson, S E; Brubaker, R F

1987-01-01

The possibility that injection-molded intraocular lenses (IOLs) with imperfections called iridescent clefts could have a decreased threshold to neodymium: YAG (Nd:YAG) laser-induced damage was investigated. Thresholds for Nd:YAG laser-induced damage were determined for injection-molded and lathe-cut polymethylmethacrylate lenses. When aimed at a membrane in contact with a posterior convex surface, the average thresholds were 0.96 +/- 0.18 mJ (Standard deviation [SD]) and 1.80 +/- 0.55 mJ, respectively. The difference was significant at P = 0.001. When injection-molding polymethylmethacrylate was used to make lathe-cut IOLs, very few iridescent clefts were present, and the threshold to Nd:YAG laser-induced damage was 0.94 +/- 0.25 mJ. Iridescent clefts are therefore produced during the injection-molding process but they do not lower the threshold to Nd:YAG laser-induced damage. Rather, the reduced threshold in injection-molded lenses is most probably a result of the polymethylmethacrylate used in their manufacture. Clinically, iridescent clefts in a lens suggest that it has been manufactured by an injection-molding process and that Nd:YAG laser posterior capsulotomy must be performed at the lowest possible energy level to avoid damage.

Psychophysics with children: Investigating the effects of attentional lapses on threshold estimates.

PubMed

Manning, Catherine; Jones, Pete R; Dekker, Tessa M; Pellicano, Elizabeth

2018-03-26

When assessing the perceptual abilities of children, researchers tend to use psychophysical techniques designed for use with adults. However, children's poorer attentiveness might bias the threshold estimates obtained by these methods. Here, we obtained speed discrimination threshold estimates in 6- to 7-year-old children in UK Key Stage 1 (KS1), 7- to 9-year-old children in Key Stage 2 (KS2), and adults using three psychophysical procedures: QUEST, a 1-up 2-down Levitt staircase, and Method of Constant Stimuli (MCS). We estimated inattentiveness using responses to "easy" catch trials. As expected, children had higher threshold estimates and made more errors on catch trials than adults. Lower threshold estimates were obtained from psychometric functions fit to the data in the QUEST condition than the MCS and Levitt staircases, and the threshold estimates obtained when fitting a psychometric function to the QUEST data were also lower than when using the QUEST mode. This suggests that threshold estimates cannot be compared directly across methods. Differences between the procedures did not vary significantly with age group. Simulations indicated that inattentiveness biased threshold estimates particularly when threshold estimates were computed as the QUEST mode or the average of staircase reversals. In contrast, thresholds estimated by post-hoc psychometric function fitting were less biased by attentional lapses. Our results suggest that some psychophysical methods are more robust to attentiveness, which has important implications for assessing the perception of children and clinical groups.

Prognostic Effect and Longitudinal Hemodynamic Assessment of Borderline Pulmonary Hypertension.

PubMed

Assad, Tufik R; Maron, Bradley A; Robbins, Ivan M; Xu, Meng; Huang, Shi; Harrell, Frank E; Farber-Eger, Eric H; Wells, Quinn S; Choudhary, Gaurav; Hemnes, Anna R; Brittain, Evan L

2017-12-01

Pulmonary hypertension (PH) is diagnosed by a mean pulmonary arterial pressure (mPAP) value of at least 25 mm Hg during right heart catheterization (RHC). While several studies have demonstrated increased mortality in patients with mPAP less than that threshold, little is known about the natural history of borderline PH. To test the hypothesis that patients with borderline PH have decreased survival compared with patients with lower mPAP and frequently develop overt PH and to identify clinical correlates of borderline PH. Retrospective cohort study from 1998 to 2014 at Vanderbilt University Medical Center, comprising all patients undergoing routine RHC for clinical indication. We extracted demographics, clinical data, invasive hemodynamics, echocardiography, and vital status for all patients. Patients with mPAP values of 18 mm Hg or less, 19 to 24 mm Hg, and at least 25 mm Hg were classified as reference, borderline PH, and PH, respectively. Mean pulmonary arterial pressure. Our primary outcome was all-cause mortality after adjusting for clinically relevant covariates in a Cox proportional hazards model. Our secondary outcome was the diagnosis of overt PH in patients initially diagnosed with borderline PH. Both outcomes were determined prior to data analysis. We identified 4343 patients (mean [SD] age, 59 [15] years, 51% women, and 86% white) among whom the prevalence of PH and borderline PH was 62% and 18%, respectively. Advanced age, features of the metabolic syndrome, and chronic heart and lung disease were independently associated with a higher likelihood of borderline PH compared with reference patients in a logistic regression model. After adjusting for 34 covariates in a Cox proportional hazards model, borderline PH was associated with increased mortality compared with reference patients (hazard ratio, 1.31; 95% CI, 1.04-1.65; P = .001). The hazard of death increased incrementally with higher mPAP, without an observed threshold. In the 70 patients with borderline PH who underwent a repeated RHC, 43 (61%) had developed overt PH, with a median increase in mPAP of 5 mm Hg (interquartile range, -1 to 11 mm Hg; P < .001). Borderline PH is common in patients undergoing RHC and is associated with significant comorbidities, progression to overt PH, and decreased survival. Small increases in mPAP, even at values currently considered normal, are independently associated with increased mortality. Prospective studies are warranted to determine whether early intervention or closer monitoring improves clinical outcomes in these patients.

Between-airport heterogeneity in air toxics emissions associated with individual cancer risk thresholds and population risks

PubMed Central

2009-01-01

Background Airports represent a complex source type of increasing importance contributing to air toxics risks. Comprehensive atmospheric dispersion models are beyond the scope of many applications, so it would be valuable to rapidly but accurately characterize the risk-relevant exposure implications of emissions at an airport. Methods In this study, we apply a high resolution atmospheric dispersion model (AERMOD) to 32 airports across the United States, focusing on benzene, 1,3-butadiene, and benzo [a]pyrene. We estimate the emission rates required at these airports to exceed a 10-6 lifetime cancer risk for the maximally exposed individual (emission thresholds) and estimate the total population risk at these emission rates. Results The emission thresholds vary by two orders of magnitude across airports, with variability predicted by proximity of populations to the airport and mixing height (R2 = 0.74–0.75 across pollutants). At these emission thresholds, the population risk within 50 km of the airport varies by two orders of magnitude across airports, driven by substantial heterogeneity in total population exposure per unit emissions that is related to population density and uncorrelated with emission thresholds. Conclusion Our findings indicate that site characteristics can be used to accurately predict maximum individual risk and total population risk at a given level of emissions, but that optimizing on one endpoint will be non-optimal for the other. PMID:19426510

Doctoral conceptual thresholds in cellular and molecular biology

NASA Astrophysics Data System (ADS)

Feldon, David F.; Rates, Christopher; Sun, Chongning

2017-12-01

In the biological sciences, very little is known about the mechanisms by which doctoral students acquire the skills they need to become independent scientists. In the postsecondary biology education literature, identification of specific skills and effective methods for helping students to acquire them are limited to undergraduate education. To establish a foundation from which to investigate the developmental trajectory of biologists' research skills, it is necessary to identify those skills which are integral to doctoral study and distinct from skills acquired earlier in students' educational pathways. In this context, the current study engages the framework of threshold concepts to identify candidate skills that are both obstacles and significant opportunities for developing proficiency in conducting research. Such threshold concepts are typically characterised as transformative, integrative, irreversible, and challenging. The results from interviews and focus groups with current and former doctoral students in cellular and molecular biology suggest two such threshold concepts relevant to their subfield: the first is an ability to effectively engage primary research literature from the biological sciences in a way that is critical without dismissing the value of its contributions. The second is the ability to conceptualise appropriate control conditions necessary to design and interpret the results of experiments in an efficient and effective manner for research in the biological sciences as a discipline. Implications for prioritising and sequencing graduate training experiences are discussed on the basis of the identified thresholds.

Clinicomanometric factors associated with clinically relevant esophagogastric junction outflow obstruction from the Sandhill high-resolution manometry system.

PubMed

Song, B G; Min, Y W; Lee, H; Min, B-H; Lee, J H; Rhee, P-L; Kim, J J

2018-03-01

Integrated relaxation pressure (IRP) is a key metric for diagnosing esophagogastric junction outflow obstruction (EGJOO). However, its normal value might be different according to the manufacturer of high-resolution manometry (HRM). This study aimed to investigate optimal value of IRP for diagnosing EGJOO in Sandhill HRM and to find clinicomanometric variables to segregate clinically relevant EGJOO. We analyzed 262 consecutive subjects who underwent HRM between June 2011 and December 2016 showing elevated median IRP (> 15 mm Hg) but did not satisfy criteria for achalasia. Clinically relevant subjects were defined as follows: (i) subsequent HRM met achalasia criteria during follow-up (early achalasia); (ii) Eckardt score was decreased at least two points without exceeding a score of 3 after pneumatic dilatation (variant achalasia); and (iii) significant passage disturbance on esophagogram without structural abnormality (possible achalasia). Seven subjects were clinically relevant, including two subjects with early achalasia, four subjects with variant achalasia, and one subject with possible achalasia. All clinically relevant subjects had IRP 20 mm Hg or above. Among subjects (n = 122) with IRP 20 mm Hg or more, clinically relevant group (n = 7) had significantly higher rate of dysphagia (100% vs 24.3%, P < .001) and compartmentalized pressurization (85.7% vs 21.7%, P = .001) compared to clinically non-relevant group (n = 115). Our results suggest that IRP of 20 mm Hg or higher could segregate clinically relevant subjects showing EGJOO in Sandhill HRM. Additionally, if subjects have both dysphagia and compartmentalized pressurization, careful follow-up is essential. © 2017 John Wiley & Sons Ltd.

Long-term potentiation and long-term depression: a clinical perspective

PubMed Central

Bliss, Timothy V.P.; Cooke, Sam F

2011-01-01

Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke. PMID:21779718

Pre- and Postoperative Imaging of the Aortic Root

PubMed Central

Chan, Frandics P.; Mitchell, R. Scott; Miller, D. Craig; Fleischmann, Dominik

2016-01-01

Three-dimensional datasets acquired using computed tomography and magnetic resonance imaging are ideally suited for characterization of the aortic root. These modalities offer different advantages and limitations, which must be weighed according to the clinical context. This article provides an overview of current aortic root imaging, highlighting normal anatomy, pathologic conditions, imaging techniques, measurement thresholds, relevant surgical procedures, postoperative complications and potential imaging pitfalls. Patients with a range of clinical conditions are predisposed to aortic root disease, including Marfan syndrome, bicuspid aortic valve, vascular Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Various surgical techniques may be used to repair the aortic root, including placement of a composite valve graft, such as the Bentall and Cabrol procedures; placement of an aortic root graft with preservation of the native valve, such as the Yacoub and David techniques; and implantation of a biologic graft, such as a homograft, autograft, or xenograft. Potential imaging pitfalls in the postoperative period include mimickers of pathologic processes such as felt pledgets, graft folds, and nonabsorbable hemostatic agents. Postoperative complications that may be encountered include pseudoaneurysms, infection, and dehiscence. Radiologists should be familiar with normal aortic root anatomy, surgical procedures, and postoperative complications, to accurately interpret pre- and postoperative imaging performed for evaluation of the aortic root. Online supplemental material is available for this article. ©RSNA, 2015 PMID:26761529

Neurometric amplitude-modulation detection threshold in the guinea-pig ventral cochlear nucleus

PubMed Central

Sayles, Mark; Füllgrabe, Christian; Winter, Ian M

2013-01-01

Amplitude modulation (AM) is a pervasive feature of natural sounds. Neural detection and processing of modulation cues is behaviourally important across species. Although most ecologically relevant sounds are not fully modulated, physiological studies have usually concentrated on fully modulated (100% modulation depth) signals. Psychoacoustic experiments mainly operate at low modulation depths, around detection threshold (∼5% AM). We presented sinusoidal amplitude-modulated tones, systematically varying modulation depth between zero and 100%, at a range of modulation frequencies, to anaesthetised guinea-pigs while recording spikes from neurons in the ventral cochlear nucleus (VCN). The cochlear nucleus is the site of the first synapse in the central auditory system. At this locus significant signal processing occurs with respect to representation of AM signals. Spike trains were analysed in terms of the vector strength of spike synchrony to the amplitude envelope. Neurons showed either low-pass or band-pass temporal modulation transfer functions, with the proportion of band-pass responses increasing with increasing sound level. The proportion of units showing a band-pass response varies with unit type: sustained chopper (CS) > transient chopper (CT) > primary-like (PL). Spike synchrony increased with increasing modulation depth. At the lowest modulation depth (6%), significant spike synchrony was only observed near to the unit's best modulation frequency for all unit types tested. Modulation tuning therefore became sharper with decreasing modulation depth. AM detection threshold was calculated for each individual unit as a function of modulation frequency. Chopper units have significantly better AM detection thresholds than do primary-like units. AM detection threshold is significantly worse at 40 dB vs. 10 dB above pure-tone spike rate threshold. Mean modulation detection thresholds for sounds 10 dB above pure-tone spike rate threshold at best modulation frequency are (95% CI) 11.6% (10.0–13.1) for PL units, 9.8% (8.2–11.5) for CT units, and 10.8% (8.4–13.2) for CS units. The most sensitive guinea-pig VCN single unit AM detection thresholds are similar to human psychophysical performance (∼3% AM), while the mean neurometric thresholds approach whole animal behavioural performance (∼10% AM). PMID:23629508