2,994 research outputs found
Thermal analysis of high-bandwidth and energy-efficient 980 nm VCSELs with optimized quantum well gain peak-to-cavity resonance wavelength offset
This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in Appl. Phys. Lett. 111, 243508 (2017) and may be found at https://doi.org/10.1063/1.5003288.The static and dynamic performance of vertical-cavity surface-emitting lasers (VCSELs) used as light-sources for optical interconnects is highly influenced by temperature. We study the effect of temperature on the performance of high-speed energy-efficient 980 nm VCSELs with a peak wavelength of the quantum well offset to the wavelength of the fundamental longitudinal device cavity mode so that they are aligned at around 60 °C. A simple method to obtain the thermal resistance of the VCSELs as a function of ambient temperature is described, allowing us to extract the active region temperature and the temperature dependence of the dynamic and static parameters. At low bias currents, we can see an increase of the −3 dB modulation bandwidth f−3dB with increasing active region temperature, which is different from the classically known situation. From the detailed analysis of f−3dB versus the active region temperature, we obtain a better understanding of the thermal limitations of VCSELs, giving a basis for next generation device designs with improved temperature stability
Association of metabolic dysregulation with volumetric brain magnetic resonance imaging and cognitive markers of subclinical brain aging in middle-aged adults: the Framingham Offspring Study.
ObjectiveDiabetic and prediabtic states, including insulin resistance, fasting hyperglycemia, and hyperinsulinemia, are associated with metabolic dysregulation. These components have been individually linked to increased risks of cognitive decline and Alzheimer's disease. We aimed to comprehensively relate all of the components of metabolic dysregulation to cognitive function and brain magnetic resonance imaging (MRI) in middle-aged adults.Research design and methodsFramingham Offspring participants who underwent volumetric MRI and detailed cognitive testing and were free of clinical stroke and dementia during examination 7 (1998-2001) constituted our study sample (n = 2,439; 1,311 women; age 61 ± 9 years). We related diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, and glycohemoglobin levels to cross-sectional MRI measures of total cerebral brain volume (TCBV) and hippocampal volume and to verbal and visuospatial memory and executive function. We serially adjusted for age, sex, and education alone (model A), additionally for other vascular risk factors (model B), and finally, with the inclusion of apolipoprotein E-ε4, plasma homocysteine, C-reactive protein, and interleukin-6 (model C).ResultsWe observed an inverse association between all indices of metabolic dysfunction and TCBV in all models (P < 0.030). The observed difference in TCBV between participants with and without diabetes was equivalent to approximately 6 years of chronologic aging. Diabetes and elevated glycohemoglobin, HOMA-IR, and fasting insulin were related to poorer executive function scores (P < 0.038), whereas only HOMA-IR and fasting insulin were inversely related to visuospatial memory (P < 0.007).ConclusionsMetabolic dysregulation, especially insulin resistance, was associated with lower brain volumes and executive function in a large, relatively healthy, middle-aged, community-based cohort
Formality and informality in the summative assessment of motor vehicle apprentices: a case study
This article explores the interaction of formal and informal attributes of competence‐based assessment. Specifically, it presents evidence from a small qualitative case study of summative assessment practices for competence‐based qualifications within apprenticeships in the motor industry in England. The data are analysed through applying an adaptation of a framework for exploring the interplay of formality and informality in learning. This analysis reveals informal mentoring as a significant element which influences not only the process of assessment, but also its outcomes. We offer different possible interpretations of the data and their analysis, and conclude that, whichever interpretation is adopted, there appears to be a need for greater capacity‐building for assessors at a local level. This could acknowledge a more holistic role for assessors; recognise the importance of assessors’ informal practices in the formal retention and achievement of apprentices; and enhance awareness of inequalities that may be reinforced by both informal and formal attributes of assessment practices
The Stroke Data Bank: Design, Methods, and Baseline Characteristics
The National Institute of Neurological and Communicative Disorders and Stroke Initiated the Stroke Data Bank, which is a Multicenter Project to Prospectively Collect Data on the Clinical Course and Sequelae of Stroke. Additional Objectives Were to Provide Information that Would Enable a Standard Diagnostic Clinical Evaluation, to Identify Prognostic Factors, and to Provide Planning Data for Future Studies. a Brief Description of the Structure and Methods Precede the Baseline Characterization of 1,805 Patients Enrolled in the Stroke Data Bank between July 1983 and June 1986. Two Thirds of These Patients Were Admitted within 24 Hours after Stroke Onset. Medical History, Neurologic History, and Hospitalization Summaries Are Presented Separately for the Following Stroke Subtypes: Infarction, Unknown Cause; Embolism from Cardiac Source; Infarction Due to Atherosclerosis; Lacune; Parenchy-Matous or Intracerebral Hemorrhage; Subarachnoid Hemorrhage; and Other. the Utility and Limitations of These Data Are Discussed. © 1988 American Heart Association, Inc
Treatment recommendations for psoriatic arthritis
Objective: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion. Methods: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire. Results: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective. Conclusions: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available
Modeling HER2 Effects on Cell Behavior from Mass Spectrometry Phosphotyrosine Data
Cellular behavior in response to stimulatory cues is governed by information encoded within a complex intracellular signaling network. An understanding of how phenotype is determined requires the distributed characterization of signaling processes (e.g., phosphorylation states and kinase activities) in parallel with measures of resulting cell function. We previously applied quantitative mass spectrometry methods to characterize the dynamics of tyrosine phosphorylation in human mammary epithelial cells with varying human epidermal growth factor receptor 2 (HER2) expression levels after treatment with epidermal growth factor (EGF) or heregulin (HRG). We sought to identify potential mechanisms by which changes in tyrosine phosphorylation govern changes in cell migration or proliferation, two behaviors that we measured in the same cell system. Here, we describe the use of a computational linear mapping technique, partial least squares regression (PLSR), to detail and characterize signaling mechanisms responsible for HER2-mediated effects on migration and proliferation. PLSR model analysis via principal component inner products identified phosphotyrosine signals most strongly associated with control of migration and proliferation, as HER2 expression or ligand treatment were individually varied. Inspection of these signals revealed both previously identified and novel pathways that correlate with cell behavior. Furthermore, we isolated elements of the signaling network that differentially give rise to migration and proliferation. Finally, model analysis identified nine especially informative phosphorylation sites on six proteins that recapitulated the predictive capability of the full model. A model based on these nine sites and trained solely on data from a low HER2-expressing cell line a priori predicted migration and proliferation in a HER2-overexpressing cell line. We identify the nine signals as a “network gauge,” meaning that when interrogated together and integrated according to the quantitative rules of the model, these signals capture information content in the network sufficiently to predict cell migration and proliferation under diverse ligand treatments and receptor expression levels. Examination of the network gauge in the context of previous literature indicates that endocytosis and activation of phosphoinositide 3-kinase (PI3K)-mediated pathways together represent particularly strong loci for the integration of the multiple pathways mediating HER2′s control of mammary epithelial cell proliferation and migration. Thus, a PLSR modeling approach reveals critical signaling processes regulating HER2-mediated cell behavior
Genetic Correlates of Brain Aging on MRI and Cognitive Test Measures: A Genome-Wide Association and Linkage Analysis in the Framingham Study
BACKGROUND: Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. METHODS: A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999–2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency ≥ 0.10, genotypic call rate ≥ 0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. RESULTS: The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 × 10-6) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 × 10-8) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously reported linkage of WMH on chromosome 4 and describe linkage of reading performance to a marker on chromosome 18 (GATA11A06), previously linked to dyslexia (LOD scores = 2.2 and 5.1). CONCLUSION: Our results suggest that genes associated with clinical neurological disease also have detectable effects on subclinical phenotypes. These hypothesis generating data illustrate the use of an unbiased approach to discover novel pathways that may be involved in brain aging, and could be used to replicate observations made in other studies.National Institutes of Health National Center for Research Resources Shared Instrumentation grant (ISI0RR163736-01A1); National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institute of Aging (5R01-AG08122, 5R01-AG16495); National Institute of Neurological Disorders and Stroke (5R01-NS17950
Gender and Aphasia in the Stroke Data Bank
Aphasia Was Present in 19.4% of the Men and 22.5% of the Women in the Stroke Data Bank. There Were No Gender Differences in Aphasia Incidence among the Intracerebral Hemorrhages. Aphasia Was More Frequent among Women with Infarcts (37.0%) Than Men (28.3%). When Stroke Mechanism Was Controlled For, There Was an Excess of Aphasia among the Women with Stroke Due to Cardiac Embolism. When Stroke Site Was Controlled For, There Were No Gender Differences in Aphasia Frequency. Wernicke′s, Global, and Anomic Aphasias Were More Common in Women Than Men; Broca′s Aphasia Was Somewhat More Common in Men. Although There Were No Gender Differences in Infarct Size overall, Men with Aphasia Had Larger Infarcts Than Women with Aphasia. Although Gender Differences Were Small, the Infarct Lesions Producing Aphasia in Men Were More Posteriorly Placed and the Infarct Lesions in Women Were More Anteriorly Placed, Suggesting Possible Gender Differences in the Positioning of the Language Zone in the Brain. © 1994 Academic Press, Inc
Serum Cholesterol and Cognitive Performance in the Framingham Heart Study
Objective: The objective of this study was to examine the relationship between total cholesterol (TC) and cognitive performance within the context of the Framingham Heart Study, a large, community-based, prospective investigation of cardiovascular risk factors. Methods: Participants were 789 men and 1105 women from the Framingham Heart Study original cohort who were free of dementia and stroke and who received biennial TC determinations over a 16- to 18-year surveillance period. Cognitive tests were administered 4 to 6 years subsequent to the surveillance period and consisted of measures of learning, memory, attention/ concentration, abstract reasoning, concept formation, and organizational abilities. Statistical models were adjusted for multiple demographic and biological covariates. Results: There was a significant positive linear association between TC and measures of verbal fluency, attention/concentration, abstract reasoning, and a composite score measuring multiple cognitive domains. Performance levels for three clinically defined groups were examined. Participants with “desirable” TC levels (/dL) performed less well than participants with borderline-high TC levels (200–239 mg/dL) and participants with high TC levels (∃240 mg/dL). Conclusions: Lower naturally occurring TC levels are associated with poorer performance on cognitive measures, which place high demands on abstract reasoning, attention/concentration, word fluency, and executive functioning
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