Directed differentiation of embryonic stem cells using a bead-based combinatorial screening method

We have developed a rapid, bead-based combinatorial screening method to determine optimal combinations of variables that direct stem cell differentiation to produce known or novel cell types having pre-determined characteristics. Here we describe three experiments comprising stepwise exposure of mouse or human embryonic cells to 10,000 combinations of serum-free differentiation media, through which we discovered multiple novel, efficient and robust protocols to generate a number of specific hematopoietic and neural lineages. We further demonstrate that the technology can be used to optimize existing protocols in order to substitute costly growth factors with bioactive small molecules and/or increase cell yield, and to identify in vitro conditions for the production of rare developmental intermediates such as an embryonic lymphoid progenitor cell that has not previously been reported

Exploring the Differences in Positive Play Among Various Sports Wagering Behaviors

Recent technological advances and legislative changes have led to an increase of sports wagering across the United States, raising concerns about possible increases in problem gambling behaviors. This, in turn, points to an increased need to understand responsible gambling and how it relates to sports gambling behaviors. The present work utilizes the Positive Play Scale (PPS), a recent scale designed to measure the increasingly popular responsible gambling concept of Positive Play, to assess how various aspects of sports gambling relate to responsible gambling. Participants were recruited by YouGov Opinion polling and taken from two U.S. samples, and the present analyses look only at those who self-identified as sports gamblers (n = 561, Mage = 50.7). Gamblers’ location of gambling, types of bets wagered on, timing of gambling, and website used to gamble were assessed. Those who bet online in any capacity, as well as participating in in-game wagering, were found to be significantly less positive in their gambling behaviors. In addition, certain types of sports wagers such as moneylines appeared to be associated with higher positive play, while other types such as parlays were associated with less positive play. Finally, certain websites, particularly offshore websites, were associated with lower positive play behavior. Collectively, these results suggest that there are various aspects of sports wagering behaviors that are associated with positive play variations in gambling

F1000 and data publishing

BackgroundHIV-positive persons who use stimulants (eg, methamphetamine) experience profound health disparities, but it remains unclear whether these persist after highly active antiretroviral therapy (HAART) initiation. Conducted within the Multicenter AIDS Cohort Study, this investigation examined whether stimulant use is associated with progression to AIDS or all-cause mortality after the initiation of HAART.MethodsUsing marginal structural modeling, the cumulative proportion of visits where any stimulant use was reported (ie, 0%, 1%-49%, 50%-99%, and 100%) was examined as a time-varying predictor of (1) all-cause mortality and (2) AIDS or all-cause mortality.ResultsAmong the 1313 men who have sex with men (MSM) who initiated HAART, findings showed no significant association of any level of stimulant use with all-cause mortality. A competing risk analysis indicated that no level of stimulant use was associated with increased AIDS-related or non-AIDS mortality separately. Among the 648 participants without AIDS at HAART initiation, a secondary analysis indicated that stimulant use at 50% or more of study visits was associated with a 1.5-fold increase in the odds of progression to AIDS or all-cause mortality (adjusted odds ratio = 1.54; 95% confidence interval: 1.02 to 2.33; P < 0.05).ConclusionsHIV-positive stimulant-using MSM receiving HAART seem to face no greater overall risks for all-cause, AIDS-related, or non-AIDS mortality compared with nonusers. However, men without AIDS at HAART initiation who more frequently reported stimulant use demonstrated modestly increased odds of progression to AIDS or all-cause mortality. Comprehensive approaches are needed to optimize the effectiveness of HAART with stimulant-using MSM

Stimulant use and progression to AIDS or mortality after the initiation of highly active antiretroviral therapy.

BackgroundHIV-positive persons who use stimulants (eg, methamphetamine) experience profound health disparities, but it remains unclear whether these persist after highly active antiretroviral therapy (HAART) initiation. Conducted within the Multicenter AIDS Cohort Study, this investigation examined whether stimulant use is associated with progression to AIDS or all-cause mortality after the initiation of HAART.MethodsUsing marginal structural modeling, the cumulative proportion of visits where any stimulant use was reported (ie, 0%, 1%-49%, 50%-99%, and 100%) was examined as a time-varying predictor of (1) all-cause mortality and (2) AIDS or all-cause mortality.ResultsAmong the 1313 men who have sex with men (MSM) who initiated HAART, findings showed no significant association of any level of stimulant use with all-cause mortality. A competing risk analysis indicated that no level of stimulant use was associated with increased AIDS-related or non-AIDS mortality separately. Among the 648 participants without AIDS at HAART initiation, a secondary analysis indicated that stimulant use at 50% or more of study visits was associated with a 1.5-fold increase in the odds of progression to AIDS or all-cause mortality (adjusted odds ratio = 1.54; 95% confidence interval: 1.02 to 2.33; P < 0.05).ConclusionsHIV-positive stimulant-using MSM receiving HAART seem to face no greater overall risks for all-cause, AIDS-related, or non-AIDS mortality compared with nonusers. However, men without AIDS at HAART initiation who more frequently reported stimulant use demonstrated modestly increased odds of progression to AIDS or all-cause mortality. Comprehensive approaches are needed to optimize the effectiveness of HAART with stimulant-using MSM

Associations between Tobacco, Alcohol, and Drug Use with Coronary Artery Plaque among HIV-Infected and Uninfected Men in the Multicenter AIDS Cohort Study.

BACKGROUND:We characterized associations between smoking, alcohol, and recreational drug use and coronary plaque by HIV serostatus within the Multicenter AIDS Cohort Study (MACS). METHODS:MACS participants (N = 1005, 621 HIV+ and 384 HIV-) underwent non-contrast CT scanning to measure coronary artery calcium; 764 underwent coronary CT angiograms to evaluate plaque type and extent. Self-reported use of alcohol, tobacco, smoked/inhaled cocaine, methamphetamine, ecstasy, marijuana, inhaled nitrites, and erectile dysfunction drugs was obtained at semi-annual visits beginning 10 years prior to CT scanning. Multivariable logistic and linear regression models were performed, stratified by HIV serostatus. RESULTS:Among HIV+ men, current smoking, former smoking, and cumulative pack years of smoking were positively associated with multiple coronary plaque measures (coronary artery calcium presence and extent, total plaque presence and extent, calcified plaque presence, and stenosis >50%). Smoking was significantly associated with fewer plaque measures of comparable effect size among HIV- men; current smoking and calcified plaque extent was the only such association. Heavy alcohol use (>14 drinks/week) was associated with stenosis >50% among HIV+ men. Among HIV- men, low/moderate (1-14 drinks/week) and heavy alcohol use were inversely associated with coronary artery calcium and calcified plaque extent. Few significant associations between other recreational drug use and plaque measures were observed. CONCLUSION:Smoking is strongly associated with coronary plaque among HIV+ men, underscoring the value of smoking cessation for HIV+ persons. Alcohol use may protect against coronary artery calcium and calcified plaque progression in HIV- (but not HIV+) men. Few positive associations were observed between recreational drug use and coronary plaque measures