Binary information is prevalent in the environment. In this study, we examined how people process repetition and alternation in binary sequences. Across four paradigms involving estimation, working memory, change detection, and visual search, we found that the number of alternations is under-estimated compared to repetitions (Experiment 1). Moreover, recall for binary sequences deteriorates as the sequence alternates more (Experiment 2). Changes in bits are also harder to detect as the sequence alternates more (Experiment 3). Finally, visual targets superimposed on bits of a binary sequence take longer to process as alternation increases (Experiment 4). Overall, our results indicate that compared to repetition, alternation in a binary sequence is less salient in the sense of requiring more attention for successful encoding. The current study thus reveals the cognitive constraints in the representation of alternation and provides a new explanation for the over-alternation bias in randomness perception.

The stability of integration is essential to numerical simulations especially when solving nonlinear problems. In this work, a continuum damage mechanics model proposed by the first author is implemented with an integration method named cutting plane algorithm (CPA) to improve the robustness of the simulation. This integration method is one type of return mapping algorithm that bypasses the need for computing the gradients. We compare the current integration method with the previous direct method, and the result shows that the cutting plane algorithm exhibits excellent performance under large loading rate conditions. To enhance accuracy of the new method, a control procedure is utilized in the implementation of the algorithm based on error analysis. Thereafter, the theory of poromechanics is utilized with the damage model to account for the effects of fluid diffusion. Laboratory tests simulated with finite element method illustrate distinct behaviors of shale with different loading rates and indicate the development of microcrack propagation under triaxial compression. Copyright © 2016 John Wiley & Sons, Ltd.

The factors driving β-diversity (variation in community composition) yield insights into the maintenance of biodiversity on the planet. Here we tested whether the mechanisms that underlie bacterial β-diversity vary over centimeters to continental spatial scales by comparing the composition of ammonia-oxidizing bacteria communities in salt marsh sediments. As observed in studies of macroorganisms, the drivers of salt marsh bacterial β-diversity depend on spatial scale. In contrast to macroorganism studies, however, we found no evidence of evolutionary diversification of ammonia-oxidizing bacteria taxa at the continental scale, despite an overall relationship between geographic distance and community similarity. Our data are consistent with the idea that dispersal limitation at local scales can contribute to β-diversity, even though the 16S rRNA genes of the relatively common taxa are globally distributed. These results highlight the importance of considering multiple spatial scales for understanding microbial biogeography.

To slow the transmission of COVID-19, countries around the world have implemented social distancing and stay-at-home policies-potentially leading people to rely more on household members for their sense of closeness and belonging. To understand the conditions under which people felt the most connected, we examined whether changes in overall feelings of social connection varied by household size and composition. In two pre-registered studies, undergraduates in Canada (NStudy 1 = 548) and adults primarily from the U.S. and U.K. (NStudy 2 = 336) reported their perceived social connection once before and once during the pandemic. In both studies, living with a partner robustly and uniquely buffered shifts in social connection during the first phases of the pandemic (βStudy 1 = .22, βStudy 2 = .16). In contrast, neither household size nor other aspects of household composition predicted changes in connection. We discuss implications for future social distancing policies that aim to balance physical health with psychological health.

Rates of Isoniazid Preventive Therapy (IPT) completion remain low in programmatic settings in sub-Saharan Africa. Differentiated HIV care models may improve IPT completion by addressing joint barriers to IPT and HIV treatment. However, the impact of differentiated care on IPT completion remains unknown. In a cross-sectional study of people with HIV on antiretroviral therapy in 5 communities in rural Uganda, we compared IPT completion between patients receiving HIV care via a differentiated care model versus a standard HIV care model and assessed multi-level predictors of IPT completion. A total of 103/144 (72%) patients received differentiated care and 85/161 (53%) received standard care completed IPT (p < 0.01). Adjusting for age, gender and community, patients receiving differentiated care had higher odds of completing IPT (aOR: 2.6, 95% CI: 1.5-4.5, p < 0.01). Predictors of IPT completion varied by the care model, and differentiated care modified the positive association between treatment completion and the belief in the efficacy of IPT and the negative association with side-effects. Patients receiving a multi-component differentiated care model had a higher odds of IPT completion than standard care, and the model's impact on health beliefs, social support, and perceived side effects to IPT may underlie this positive association.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P < 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was -0.53 (95% CI -0.89 to -0.17, nominal P = 0.004) in the 35 mg volagidemab group and -0.49 (95% CI -0.85 to -0.12, nominal P = 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.