Genome-wide scan of copy number variation in late-onset Alzheimer's disease.

Alzheimer's disease is a complex and progressive neurodegenerative disease leading to loss of memory, cognitive impairment, and ultimately death. To date, six large-scale genome-wide association studies have been conducted to identify SNPs that influence disease predisposition. These studies have confirmed the well-known APOE epsilon4 risk allele, identified a novel variant that influences disease risk within the APOE epsilon4 population, found a SNP that modifies the age of disease onset, as well as reported the first sex-linked susceptibility variant. Here we report a genome-wide scan of Alzheimer's disease in a set of 331 cases and 368 controls, extending analyses for the first time to include assessments of copy number variation. In this analysis, no new SNPs show genome-wide significance. We also screened for effects of copy number variation, and while nothing was significant, a duplication in CHRNA7 appears interesting enough to warrant further investigation.

Universal quantum viscosity in a unitary Fermi gas.

A Fermi gas of atoms with resonant interactions is predicted to obey universal hydrodynamics, in which the shear viscosity and other transport coefficients are universal functions of the density and temperature. At low temperatures, the viscosity has a universal quantum scale ħ n, where n is the density and ħ is Planck's constant h divided by 2π, whereas at high temperatures the natural scale is p(T)(3)/ħ(2), where p(T) is the thermal momentum. We used breathing mode damping to measure the shear viscosity at low temperature. At high temperature T, we used anisotropic expansion of the cloud to find the viscosity, which exhibits precise T(3/2) scaling. In both experiments, universal hydrodynamic equations including friction and heating were used to extract the viscosity. We estimate the ratio of the shear viscosity to the entropy density and compare it with that of a perfect fluid.

Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania.

Fixed dose combination abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) among HIV-1 and tuberculosis (TB)-coinfected patients was evaluated and outcomes between early vs. delayed initiation were compared. In a randomized, pilot study conducted in the Kilimanjaro Region of Tanzania, HIV-infected inpatients with smear-positive TB and total lymphocyte count <1200/mm(3) were randomized to initiate ABC/3TC/ZDV either 2 (early) or 8 (delayed) weeks after commencing antituberculosis therapy and were followed for 104 weeks. Of 94 patients screened, 70 enrolled (41% female, median CD4 count 103 cells/mm(3)), and 33 in each group completed 104 weeks. Two deaths and 12 serious adverse events (SAEs) were observed in the early arm vs. one death, one clinical failure, and seven SAEs in the delayed arm (p = 0.6012 for time to first grade 3/4 event, SAE, or death). CD4 cell increases were +331 and +328 cells/mm(3), respectively. TB-immune reconstitution inflammatory syndromes (TB-IRIS) were not observed in any subject. Using intent-to-treat (ITT), missing = failure analyses, 74% (26/35) vs. 89% (31/35) randomized to early vs. delayed therapy had HIV RNA levels <400 copies/ml at 104 weeks (p = 0.2182) and 66% (23/35) vs. 74% (26/35), respectively, had HIV RNA levels <50 copies/ml (p = 0.6026). In an analysis in which switches from ABC/3TC/ZDV = failure, those receiving early therapy were less likely to be suppressed to <400 copies/ml [60% (21/35) vs. 86% (30/35), p = 0.030]. TB-IRIS was not observed among the 70 coinfected subjects beginning antiretroviral treatment. ABC/3TC/ZDV was well tolerated and resulted in steady immunologic improvement. Rates of virologic suppression were similar between early and delayed treatment strategies with triple nucleoside regimens when substitutions were allowed.

Changing American Congregations: Findings from the Third Wave of the National Congregations Study

The third wave of the National Congregations Study (NCS-III) was conducted in 2012. The 2012 General Social Survey asked respondents who attend religious services to name their religious congregation, producing a nationally representative cross-section of congregations from across the religious spectrum. Data about these congregations was collected via a 50-minute interview with one key informant from 1,331 congregations. Information was gathered about multiple aspects of congregations’ social composition, structure, activities, and programming. Approximately two-thirds of the NCS-III questionnaire replicates items from 1998 or 2006-07 NCS waves. Each congregation was geocoded, and selected data from the 2010 United States census or American Community Survey have been appended. We describe NCS-III methodology and use the cumulative NCS dataset (containing 4,071 cases) to describe five trends: more ethnic diversity, greater acceptance of gays and lesbians, increasingly informal worship styles, declining size (but not from the perspective of the average attendee), and declining denominational affiliation.

A meta-analysis of the effectiveness of intelligent tutoring systems on college students' academic learning

© 2013 American Psychological Association.This meta-analysis synthesizes research on the effectiveness of intelligent tutoring systems (ITS) for college students. Thirty-five reports were found containing 39 studies assessing the effectiveness of 22 types of ITS in higher education settings. Most frequently studied were AutoTutor, Assessment and Learning in Knowledge Spaces, eXtended Tutor-Expert System, and Web Interface for Statistics Education. Major findings include (a) Overall, ITS had a moderate positive effect on college students' academic learning (g = .32 to g = .37); (b) ITS were less effective than human tutoring, but they outperformed all other instruction methods and learning activities, including traditional classroom instruction, reading printed text or computerized materials, computer-assisted instruction, laboratory or homework assignments, and no-treatment control; (c) ITS's effectiveness did not significantly differ by different ITS, subject domain, or the manner or degree of their involvement in instruction and learning; and (d) effectiveness in earlier studies appeared to be significantly greater than that in more recent studies. In addition, there is some evidence suggesting the importance of teachers and pedagogy in ITS-assisted learning.

Drug-drug interaction studies of cardiovascular drugs involving P-glycoprotein, an efflux transporter, on the pharmacokinetics of edoxaban, an oral factor Xa inhibitor.

BACKGROUND: Edoxaban, an oral direct factor Xa inhibitor, is in development for thromboprophylaxis, including prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). P-glycoprotein (P-gp), an efflux transporter, modulates absorption and excretion of xenobiotics. Edoxaban is a P-gp substrate, and several cardiovascular (CV) drugs have the potential to inhibit P-gp and increase drug exposure. OBJECTIVE: To assess the potential pharmacokinetic interactions of edoxaban and 6 cardiovascular drugs used in the management of AF and known P-gp substrates/inhibitors. METHODS: Drug-drug interaction studies with edoxaban and CV drugs with known P-gp substrate/inhibitor potential were conducted in healthy subjects. In 4 crossover, 2-period, 2-treatment studies, subjects received edoxaban 60 mg alone and coadministered with quinidine 300 mg (n = 42), verapamil 240 mg (n = 34), atorvastatin 80 mg (n = 32), or dronedarone 400 mg (n = 34). Additionally, edoxaban 60 mg alone and coadministered with amiodarone 400 mg (n = 30) or digoxin 0.25 mg (n = 48) was evaluated in a single-sequence study and 2-cohort study, respectively. RESULTS: Edoxaban exposure measured as area under the curve increased for concomitant administration of edoxaban with quinidine (76.7 %), verapamil (52.7 %), amiodarone (39.8 %), and dronedarone (84.5 %), and exposure measured as 24-h concentrations for quinidine (11.8 %), verapamil (29.1 %), and dronedarone (157.6 %) also increased. Administration of edoxaban with amiodarone decreased the 24-h concentration for edoxaban by 25.7 %. Concomitant administration with digoxin or atorvastatin had minimal effects on edoxaban exposure. CONCLUSION: Coadministration of the P-gp inhibitors quinidine, verapamil, and dronedarone increased edoxaban exposure. Modest/minimal effects were observed for amiodarone, atorvastatin, and digoxin.