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Search Results: 1 - 10 of 224649 matches for " Neal R. Swerdlow "
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Association Analysis of 94 Candidate Genes and Schizophrenia-Related Endophenotypes
Tiffany A. Greenwood, Gregory A. Light, Neal R. Swerdlow, Allen D. Radant, David L. Braff
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0029630
Abstract: While it is clear that schizophrenia is highly heritable, the genetic basis of this heritability is complex. Human genetic, brain imaging, and model organism studies have met with only modest gains. A complementary research tactic is to evaluate the genetic substrates of quantitative endophenotypes with demonstrated deficits in schizophrenia patients. We used an Illumina custom 1,536-SNP array to interrogate 94 functionally relevant candidate genes for schizophrenia and evaluate association with both the qualitative diagnosis of schizophrenia and quantitative endophenotypes for schizophrenia. Subjects included 219 schizophrenia patients and normal comparison subjects of European ancestry and 76 schizophrenia patients and normal comparison subjects of African ancestry, all ascertained by the UCSD Schizophrenia Research Program. Six neurophysiological and neurocognitive endophenotype test paradigms were assessed: prepulse inhibition (PPI), P50 suppression, the antisaccade oculomotor task, the Letter-Number Span Test, the California Verbal Learning Test-II, and the Wisconsin Card Sorting Test-64 Card Version. These endophenotype test paradigms yielded six primary endophenotypes with prior evidence of heritability and demonstrated schizophrenia-related impairments, as well as eight secondary measures investigated as candidate endophenotypes. Schizophrenia patients showed significant deficits on ten of the endophenotypic measures, replicating prior studies and facilitating genetic analyses of these phenotypes. A total of 38 genes were found to be associated with at least one endophenotypic measure or schizophrenia with an empirical p-value<0.01. Many of these genes have been shown to interact on a molecular level, and eleven genes displayed evidence for pleiotropy, revealing associations with three or more endophenotypic measures. Among these genes were ERBB4 and NRG1, providing further support for a role of these genes in schizophrenia susceptibility. The observation of extensive pleiotropy for some genes and singular associations for others in our data may suggest both converging and independent genetic (and neural) pathways mediating schizophrenia risk and pathogenesis.
Characterization of Neurophysiologic and Neurocognitive Biomarkers for Use in Genomic and Clinical Outcome Studies of Schizophrenia
Gregory A. Light, Neal R. Swerdlow, Anthony J. Rissling, Allen Radant, Catherine A. Sugar, Joyce Sprock, Marlena Pela, Mark A. Geyer, David L. Braff
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039434
Abstract: Background Endophenotypes are quantitative, laboratory-based measures representing intermediate links in the pathways between genetic variation and the clinical expression of a disorder. Ideal endophenotypes exhibit deficits in patients, are stable over time and across shifts in psychopathology, and are suitable for repeat testing. Unfortunately, many leading candidate endophenotypes in schizophrenia have not been fully characterized simultaneously in large cohorts of patients and controls across these properties. The objectives of this study were to characterize the extent to which widely-used neurophysiological and neurocognitive endophenotypes are: 1) associated with schizophrenia, 2) stable over time, independent of state-related changes, and 3) free of potential practice/maturation or differential attrition effects in schizophrenia patients (SZ) and nonpsychiatric comparison subjects (NCS). Stability of clinical and functional measures was also assessed. Methods Participants (SZ n = 341; NCS n = 205) completed a battery of neurophysiological (MMN, P3a, P50 and N100 indices, PPI, startle habituation, antisaccade), neurocognitive (WRAT-3 Reading, LNS-forward, LNS-reorder, WCST-64, CVLT-II). In addition, patients were rated on clinical symptom severity as well as functional capacity and status measures (GAF, UPSA, SOF). 223 subjects (SZ n = 163; NCS n = 58) returned for retesting after 1 year. Results Most neurophysiological and neurocognitive measures exhibited medium-to-large deficits in schizophrenia, moderate-to-substantial stability across the retest interval, and were independent of fluctuations in clinical status. Clinical symptoms and functional measures also exhibited substantial stability. A Longitudinal Endophenotype Ranking System (LERS) was created to rank neurophysiological and neurocognitive biomarkers according to their effect sizes across endophenotype criteria. Conclusions The majority of neurophysiological and neurocognitive measures exhibited deficits in patients, stability over a 1-year interval and did not demonstrate practice or time effects supporting their use as endophenotypes in neural substrate and genomic studies. These measures hold promise for informing the “gene-to-phene gap” in schizophrenia research.
Do Patients with Asymptomatic Congenital Complete Heart Block Require a Pacemaker for Non-Cardiac Surgery?  [PDF]
Barry Swerdlow
Open Journal of Anesthesiology (OJAnes) , 2018, DOI: 10.4236/ojanes.2018.84014
Abstract: The appropriate preparation of the patient with asymptomatic congenital complete heart block (CCHB) and a narrow QRS complex for elective non-cardiac surgery is controversial. Prophylactic temporary pacemaker insertion is associated with well-defined risks, and less invasive techniques exist to treat transient, hemodynamically significant intraoperative brady-arrhythmias. The present case report details the performance of general anesthesia for arthroscopic knee surgery in an adult patient with this condition without a pacemaker. Documentation of preoperative chronotropic competence with isoproterenol may be of value in deciding whether to proceed without temporary pacing capability in this setting.
The Online Challenge: Why Not Teach Music History Unconventionally?
Jocelyn R. Neal
Journal of Music History Pedagogy , 2011,
Abstract: As the proliferation of online courses reaches into the fields of music history and music theory, more colleagues are contemplating the efficacy and desirability of getting involved, while some institutions are pushing faculty into the new medium of instruction. This essay explores one such instance of online instruction by first outlining the format and implementation system at a major state university, then reflecting on both the positive and negative experiences encountered by the instructor, who has taught online music history and music fundamentals courses for the past seven years.
An Improved Acceptance Procedure for the Hybrid Monte Carlo Algorithm
R. M. Neal
Physics , 1992,
Abstract: The probability of accepting a candidate move in the hybrid Monte Carlo algorithm can be increased by considering a transition to be between windows of several states at the beginning and end of the trajectory, with a state within the selected window being chosen according to the Boltzmann probabilities. The detailed balance condition used to justify the algorithm still holds with this procedure, provided the start state is randomly positioned within its window. The new procedure is shown empirically to significantly improve performance for a test system of uncoupled oscillators.
Suppressing Random Walks in Markov Chain Monte Carlo Using Ordered Overrelaxation
R. M. Neal
Physics , 1995,
Abstract: Markov chain Monte Carlo methods such as Gibbs sampling and simple forms of the Metropolis algorithm typically move about the distribution being sampled via a random walk. For the complex, high-dimensional distributions commonly encountered in Bayesian inference and statistical physics, the distance moved in each iteration of these algorithms will usually be small, because it is difficult or impossible to transform the problem to eliminate dependencies between variables. The inefficiency inherent in taking such small steps is greatly exacerbated when the algorithm operates via a random walk, as in such a case moving to a point n steps away will typically take around n^2 iterations. Such random walks can sometimes be suppressed using ``overrelaxed'' variants of Gibbs sampling (a.k.a. the heatbath algorithm), but such methods have hitherto been largely restricted to problems where all the full conditional distributions are Gaussian. I present an overrelaxed Markov chain Monte Carlo algorithm based on order statistics that is more widely applicable. In particular, the algorithm can be applied whenever the full conditional distributions are such that their cumulative distribution functions and inverse cumulative distribution functions can be efficiently computed. The method is demonstrated on an inference problem for a simple hierarchical Bayesian model.
The Refined Gross-Prasad Conjecture for Unitary Groups
R. Neal Harris
Mathematics , 2012,
Abstract: Let F be a number field, A_F its ring of adeles, and let {\pi}_n and {\pi}_{n+1} be irreducible, cuspidal, automorphic representations of SO_n(A_F) and SO_{n+1}(A_F), respectively. In 1991, Benedict Gross and Dipendra Prasad conjectured the non-vanishing of a certain period integral attached to {\pi}_n and {\pi}_{n+1} is equivalent to the non-vanishing of L(1/2, {\pi}_n x {\pi}_{n+1}). More recently, Atsushi Ichino and Tamotsu Ikeda gave a refinement of this conjecture as well as a proof of the first few cases (n = 2,3). Their conjecture gives an explicit relationship between the aforementioned L-value and period integral. We make a similar conjecture for unitary groups, and prove the first few cases. The first case of the conjecture will be proved using a theorem of Waldspurger, while the second case will use the machinery of the {\Theta}-correspondence.
On Deducing Conditional Independence from d-Separation in Causal Graphs with Feedback (Research Note)
R. M. Neal
Computer Science , 2011, DOI: 10.1613/jair.689
Abstract: Pearl and Dechter (1996) claimed that the d-separation criterion for conditional independence in acyclic causal networks also applies to networks of discrete variables that have feedback cycles, provided that the variables of the system are uniquely determined by the random disturbances. I show by example that this is not true in general. Some condition stronger than uniqueness is needed, such as the existence of a causal dynamics guaranteed to lead to the unique solution.
Mitochondrial Medicine and the Neurodegenerative Mitochondriopathies
Russell H. Swerdlow
Pharmaceuticals , 2009, DOI: 10.3390/ph2030150
Abstract: Neurodegenerative diseases are a common late-life scourge for which diseasemodifying treatments are sorely needed. Mitochondrial perturbation is commonly observed in these diseases, so pursuing treatment development strategies that target mitochondria or processes affected by mitochondria seems reasonable. This review discusses the rationale underlying past and current efforts to treat neurodegenerative diseases using mitochondrial medicine, and tries to predict how future efforts might proceed.
Rainfall and runoff water quality of the Pang and Lambourn, tributaries of the River Thames, south-eastern England
C. Neal,R. Skeffington,M. Neal,R. Wyatt
Hydrology and Earth System Sciences (HESS) & Discussions (HESSD) , 2004,
Abstract: The water quality of rainfall and runoff is described for two catchments of two tributaries of the River Thames, the Pang and Lambourn. Rainfall chemistry is variable and concentrations of most determinands decrease with increasing volume of catch probably due to 'wash out' processes. Two rainfall sites have been monitored, one for each catchment. The rainfall site on the Lambourn shows higher chemical concentrations than the one for the Pang which probably reflects higher amounts of local inputs from agricultural activity. Rainfall quality data at a long-term rainfall site on the Pang (UK National Air Quality Archive) shows chemistries similar to that for the Lambourn site, but with some clear differences. Rainfall chemistries show considerable variation on an event-to-event basis. Average water quality concentrations and flow-weighted concentrations as well as fluxes vary across the sites, typically by about 30%. Stream chemistry is much less variable due to the main source of water coming from aquifer sources of high storage. The relationship between rainfall and runoff chemistry at the catchment outlet is described in terms of the relative proportions of atmospheric and within-catchment sources. Remarkably, in view of the quantity of agricultural and sewage inputs to the streams, the catchments appear to be retaining both P and N. Keywords: water quality, nitrate, ammonium, phosphorus, ammonia, nitrogen dioxide, pH, alkalinity, nutrients, trace metals, rainfall, river, Pang, Lambourn, LOCAR
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