409 research outputs found
Sex Differences in Associations of Depressive Symptoms with Cardiovascular Risk Factors and Metabolic Syndrome among African Americans
Development of Cut-points for Determining Activity Intensity From a Wrist-worn ActiGraph Accelerometer in Free-living Adults
Despite recent popularity of wrist-worn accelerometers for assessing free-living physical behaviours, there is a lack of user-friendly methods to characterize physical activity from a wrist-worn ActiGraph accelerometer. Participants in this study completed a laboratory protocol and/or 3–8 hours of directly observed free-living (criterion measure of activity intensity) while wearing ActiGraph GT9X Link accel- erometers on the right hip and non-dominant wrist. All laboratory data (n = 36) and 11 participants’ free- living data were used to develop vector magnitude count cut-points (counts/min) for activity intensity for the wrist-worn accelerometer, and 12 participants’ free-living data were used to cross-validate cut-point accuracy. The cut-points were: \u3c2,860 counts/min (sedentary); 2,860–3,940 counts/min (light); and ≥3,941counts/min (moderate-to-vigorous (MVPA)). These cut-points had an accuracy of 70.8% for asses- sing free-living activity intensity, whereas Sasaki/Freedson cut-points for the hip accelerometer had an accuracy of 77.1%, and Hildebrand Euclidean Norm Minus One (ENMO) cut-points for the wrist accel- erometer had an accuracy of 75.2%. While accuracy was higher for a hip-worn accelerometer and for ENMO wrist cut-points, the high wear compliance of wrist accelerometers shown in past work and the ease of use of count-based analysis methods may justify use of these developed cut-points until more accurate, equally usable methods can be developed
Insights into the behaviour of systems biology models from dynamic sensitivity and identifiability analysis: a case study of an NF-kB signaling pathway
Mathematical modelling offers a variety of useful techniques to help in understanding the intrinsic behaviour of complex signal transduction networks. From the system engineering point of view, the dynamics of metabolic and signal transduction models can always be described by nonlinear ordinary differential equations (ODEs) following mass balance principles. Based on the state-space formulation, many methods from the area of automatic control can conveniently be applied to the modelling, analysis and design of cell networks. In the present study, dynamic sensitivity analysis is performed on a model of the IB-NF-B signal pathway system. Univariate analysis of the Euclidean-form overall sensitivities shows that only 8 out of the 64 parameters in the model have major influence on the nuclear NF-B oscillations. The sensitivity matrix is then used to address correlation analysis, identifiability assessment and measurement set selection within the framework of least squares estimation and multivariate analysis. It is shown that certain pairs of parameters are exactly or highly correlated to each other in terms of their effects on the measured variables. The experimental design strategy provides guidance on which proteins should best be considered for measurement such that the unknown parameters can be estimated with the best statistical precision. The whole analysis scheme we describe provides efficient parameter estimation techniques for complex cell networks
The Vermont oxford neonatal encephalopathy registry: Rationale, methods, and initial results
BACKGROUND: In 2006, the Vermont Oxford Network (VON) established the Neonatal Encephalopathy Registry (NER) to characterize infants born with neonatal encephalopathy, describe evaluations and medical treatments, monitor hypothermic therapy (HT) dissemination, define clinical research questions, and identify opportunities for improved care. METHODS: Eligible infants were ≥ 36 weeks with seizures, altered consciousness (stupor, coma) during the first 72 hours of life, a 5 minute Apgar score of ≤ 3, or receiving HT. Infants with central nervous system birth defects were excluded. RESULTS: From 2006–2010, 95 centers registered 4232 infants. Of those, 59% suffered a seizure, 50% had a 5 minute Apgar score of ≤ 3, 38% received HT, and 18% had stupor/coma documented on neurologic exam. Some infants experienced more than one eligibility criterion. Only 53% had a cord gas obtained and only 63% had a blood gas obtained within 24 hours of birth, important components for determining HT eligibility. Sixty-four percent received ventilator support, 65% received anticonvulsants, 66% had a head MRI, 23% had a cranial CT, 67% had a full channel encephalogram (EEG) and 33% amplitude integrated EEG. Of all infants, 87% survived. CONCLUSIONS: The VON NER describes the heterogeneous population of infants with NE, the subset that received HT, their patterns of care, and outcomes. The optimal routine care of infants with neonatal encephalopathy is unknown. The registry method is well suited to identify opportunities for improvement in the care of infants affected by NE and study interventions such as HT as they are implemented in clinical practice
Mitochondrial Dysfunction Accounts for the Stochastic Heterogeneity in Telomere-Dependent Senescence
Aging is an inherently stochastic process, and its hallmark is heterogeneity between organisms, cell types, and clonal populations, even in identical environments. The replicative lifespan of primary human cells is telomere dependent; however, its heterogeneity is not understood. We show that mitochondrial superoxide production increases with replicative age in human fibroblasts despite an adaptive UCP-2–dependent mitochondrial uncoupling. This mitochondrial dysfunction is accompanied by compromised [Ca(2+)](i) homeostasis and other indicators of a retrograde response in senescent cells. Replicative senescence of human fibroblasts is delayed by mild mitochondrial uncoupling. Uncoupling reduces mitochondrial superoxide generation, slows down telomere shortening, and delays formation of telomeric γ-H2A.X foci. This indicates mitochondrial production of reactive oxygen species (ROS) as one of the causes of replicative senescence. By sorting early senescent (SES) cells from young proliferating fibroblast cultures, we show that SES cells have higher ROS levels, dysfunctional mitochondria, shorter telomeres, and telomeric γ-H2A.X foci. We propose that mitochondrial ROS is a major determinant of telomere-dependent senescence at the single-cell level that is responsible for cell-to-cell variation in replicative lifespan
A Burgessian critique of nominalistic tendencies in contemporary mathematics and its historiography
We analyze the developments in mathematical rigor from the viewpoint of a
Burgessian critique of nominalistic reconstructions. We apply such a critique
to the reconstruction of infinitesimal analysis accomplished through the
efforts of Cantor, Dedekind, and Weierstrass; to the reconstruction of Cauchy's
foundational work associated with the work of Boyer and Grabiner; and to
Bishop's constructivist reconstruction of classical analysis. We examine the
effects of a nominalist disposition on historiography, teaching, and research.Comment: 57 pages; 3 figures. Corrected misprint
Brain arteriolosclerosis
Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer’s disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g. hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that include consideration of comorbid diseases, B-ASC is independently associated with impairments in global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability
Evaluating assumptions of scales for subjective assessment of thermal environments – Do laypersons perceive them the way, we researchers believe?
International audienc
Growth of Long Range Forward-Backward Multiplicity Correlations with Centrality in Au+Au Collisions at = 200 GeV
Forward-backward multiplicity correlation strengths have been measured with
the STAR detector for Au+Au and collisions at =
200 GeV. Strong short and long range correlations (LRC) are seen in central
Au+Au collisions. The magnitude of these correlations decrease with decreasing
centrality until only short range correlations are observed in peripheral Au+Au
collisions. Both the Dual Parton Model (DPM) and the Color Glass Condensate
(CGC) predict the existence of the long range correlations. In the DPM the
fluctuation in the number of elementary (parton) inelastic collisions produces
the LRC. In the CGC longitudinal color flux tubes generate the LRC. The data is
in qualitative agreement with the predictions from the DPM and indicates the
presence of multiple parton interactions.Comment: 6 pages, 3 figures The abstract has been slightly modifie
K/pi Fluctuations at Relativistic Energies
We report results for fluctuations from Au+Au collisions at
= 19.6, 62.4, 130, and 200 GeV using the STAR detector at the
Relativistic Heavy Ion Collider. Our results for fluctuations in
central collisions show little dependence on the incident energies studied and
are on the same order as results observed by NA49 at the Super Proton
Synchrotron in central Pb+Pb collisions at = 12.3 and 17.3 GeV.
We also report results for the collision centrality dependence of
fluctuations as well as results for , ,
, and fluctuations. We observe that the
fluctuations scale with the multiplicity density, , rather than the
number of participating nucleons.Comment: 6 pages, 4 figure
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