Bapineuzumab for mild to moderate Alzheimer's disease in two global, randomized, phase 3 trials

Background: Our objective was to evaluate the efficacy (clinical and biomarker) and safety of intravenous bapineuzumab in patients with mild to moderate Alzheimer's disease (AD).Methods: Two of four phase 3, multicenter, randomized, double-blind, placebo-controlled, 18-month trials were conducted globally: one in apolipoprotein E epsilon 4 carriers and another in noncarriers. Patients received bapineuzumab 0.5 mg/kg (both trials) or 1.0 mg/kg (noncarrier trial) or placebo every 13 weeks. Coprimary endpoints were change from baseline to week 78 on the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale and the Disability Assessment for Dementia.Results: A total of 683 and 329 patients completed the current carrier and noncarrier trials, respectively, which were terminated prematurely owing to lack of efficacy in the two other phase 3 trials of bapineuzumab in AD. The current trials showed no significant difference between bapineuzumab and placebo for the coprimary endpoints and no effect of bapineuzumab on amyloid load or cerebrospinal fluid phosphorylated tau. (Both measures were stable over time in the placebo group.) Amyloid-related imaging abnormalities with edema or effusion were confirmed as the most notable adverse event.Conclusions: These phase 3 global trials confirmed lack of efficacy of bapineuzumab at tested doses on clinical endpoints in patients with mild to moderate AD. Some differences in the biomarker results were seen compared with the other phase 3 bapineuzumab trials. No unexpected adverse events were observed

The effects of acute tryptophan depletion on costly information sampling: impulsivity or aversive processing?

RATIONALE: The neurotransmitter serotonin (5-HT) has been implicated in both aversive processing and impulsivity. Reconciling these accounts, recent studies have demonstrated that 5-HT is important for punishment-induced behavioural inhibition. These studies focused on situations where actions lead directly to punishments. However, decision-making often involves making tradeoffs between small 'local' costs and larger 'global' losses. OBJECTIVE: We aimed to distinguish whether 5-HT promotes avoidance of local losses, global losses, or both, in contrast to an overall effect on reflection impulsivity. We further examined the influence of individual differences in sub-clinical depression, anxiety and impulsivity on global and local loss avoidance. METHODS: Healthy volunteers (N = 21) underwent an acute tryptophan depletion procedure in a double-blind, placebo-controlled crossover design. We measured global and local loss avoidance in a decision-making task where subjects could sample information at a small cost to avoid making incorrect decisions, which resulted in large losses. RESULTS: Tryptophan depletion removed the suppressive effects of small local costs on information sampling behaviour. Sub-clinical depressive symptoms produced effects on information sampling similar to (but independent from) those of tryptophan depletion. Dispositional anxiety was related to global loss avoidance. However, trait impulsivity was unrelated to information sampling. CONCLUSIONS: The current findings are consistent with recent theoretical work that characterises 5-HT as pruning a tree of potential decisions, eliminating options expected to lead to aversive outcomes. Our results extend this account by proposing that 5-HT promotes reflexive avoidance of relatively immediate aversive outcomes, potentially at the expense of more globally construed future losses

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

Human Decision Making Based on Variations in Internal Noise: An EEG Study

Perceptual decision making is prone to errors, especially near threshold. Physiological, behavioural and modeling studies suggest this is due to the intrinsic or ‘internal’ noise in neural systems, which derives from a mixture of bottom-up and top-down sources. We show here that internal noise can form the basis of perceptual decision making when the external signal lacks the required information for the decision. We recorded electroencephalographic (EEG) activity in listeners attempting to discriminate between identical tones. Since the acoustic signal was constant, bottom-up and top-down influences were under experimental control. We found that early cortical responses to the identical stimuli varied in global field power and topography according to the perceptual decision made, and activity preceding stimulus presentation could predict both later activity and behavioural decision. Our results suggest that activity variations induced by internal noise of both sensory and cognitive origin are sufficient to drive discrimination judgments

Designing and assessing numeracy training for journalists: Toward improving quantitative reasoning among media consumers

Journalists inform multitudes of people. However, they sometimes over-focus on the narrative, failing to integrate critical quantitative information effectively. The Numerically Driven Inferencing (NDI) paradigm's research (e.g., Ranney et al., 2001; Munnich, Ranney, & Appel, 2004) suggested that a curricular module highlighting evidential/scientific thinking might enhance reporters' quantitative and analytic skills. The resulting controlled experiment involved 55 first-year journalism graduate students, our "Numbers, News, and Evidence" module, 4.5 classroom hours, 20 homework hours, and several (e.g., Pre-, Mid- and Final-test) assessments. Post-module findings indicate success: Relative to control data, the experimental group improved on the main numeracy measures: 1) estimation accuracy and 2) math competence involving simple problem solving, data analyses, and exponential growth. Students and faculty both concluded that future students should also receive numeracy modules. The module apparently influenced students' attitudes about numerical information, too. The collective results may benefit journalists, their instructors, and media consumers