Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

State Rankings of Postsecondary Achievement for Deaf People: 2012-2016

In this report, we analyze educational and employment outcomes across states in the United States, the District of Columbia, and Puerto Rico. We used 2012-2016 data from the American Community Survey (ACS), a national survey conducted by the U.S. Census Bureau. We limited our sample to individuals ages 25-64 to capture data for individuals more likely to have completed postsecondary education and training, those who are typically considered the “working age” population.This document was developed under a grant from the U.S. Department of Education, OSEP #HD326D160001. However, the contents do not necessarily represent the policy of the U.S. Department of Education, and you should not assume endorsement by the federal government.National Deaf Center on Postsecondary Outcome

ACCESS Is More Than Accommodations: 2018–2019 Deaf College Student National Accessibility Report

During the 2018–2019 academic year, the National Deaf Center on Postsecondary Outcomes (NDC) surveyed deaf students in higher education institutions across the nation. This report provides a comprehensive overview of results from the survey and offers suggestions for improving access and inclusion on campus for deaf students. The survey targets six key indicators of access and inclusion and provides data on the experience of more than 300 currently enrolled deaf college students.This publication was developed under a jointly funded grant through the Office of Special Education Programs and the Rehabilitation Services Administration, #H326D160001. However, the contents do not necessarily represent the positions or policies of the federal government.National Deaf Center on Postsecondary Outcome

NDC Data Dashboard

National Deaf Center on Postsecondary Outcome

Undergraduate Enrollment of Deaf Students in the United States

This report provides a comprehensive overview of undergraduate enrollment of deaf college students in the United States, serving as a resource for community members, advocates, educators, researchers, and policy makers.This report was developed under a jointly funded grant through the US Department of Education’s Office of Special Education Programs (OSEP) and the Rehabilitation Services Administration (RSA), #HD326D160001. However, the contents do not necessarily represent the positions or policies of the federal government.Educational Psycholog

Deaf People and Employment in the United States: 2019

This report provides a comprehensive overview of the most current data on employment trends and trajectories for deaf people in the United States, serving as a resource for community members, advocates, educators, researchers, and policy makers.This report was developed under a jointly funded grant through the US Department of Education’s Office of Special Education Programs (OSEP) and the Rehabilitation Services Administration (RSA), #HD326D160001. However, the contents do not necessarily represent the positions or policies of the federal government.Educational Psycholog

Deaf People and Educational Attainment in the United States: 2019

This report provides a comprehensive overview of the most current data on educational attainment trends and trajectories for deaf people in the United States, serving as a resource for community members, advocates, educators, researchers, and policy makers.This report was developed under a jointly funded grant through the US Department of Education’s Office of Special Education Programs (OSEP) and the Rehabilitation Services Administration (RSA), #HD326D160001. However, the contents do not necessarily represent the positions or policies of the federal government.Educational Psycholog

ACCESO Significa Más Que Acomodaciones de Accesibilidad: Reporte Nacional de Accesibilidad para los Estudiantes Sordos Universitarios 2018–2019

Durante el año académico 2018–2019, el Centro Nacional de Sordos sobre Resultados Posteriores a la Educación Media (NDC por sus siglas en inglés) encuestó a estudiantes sordos inscritos en instituciones de educación superior en todo el país. Este reporte proporciona un resumen de los resultados de la encuesta y ofrece sugerencias para mejorar el acceso y la inclusión de los estudiantes sordos en los campus universitarios. La encuesta apunta a seis categorías clave de acceso e inclusión y proporciona información específica sobre las experiencias de más de 300 estudiantes universitarios sordos inscritos en universidades actualmente.Este documento fue desarrollado bajo una subvención financiada conjuntamente a través de la Oficina de Programas de Educación Especial del Departamento de Educación de los Estados Unidos (OSEP por sus siglas en inglés) y la Administración de Servicios de Rehabilitación (RSA por sus siglas en inglés) #HD326D160001. Sin embargo, los contenidos no representan necesariamente las posiciones o políticas del gobierno federal.National Deaf Center on Postsecondary Outcome