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To examine the development of religious identity during the teenage years, adolescents (N = 477) from Latin American, Asian, and European backgrounds completed questionnaires in the 10th, 11th, and 12th grades (10th grade age: M = 15.81, SD = 0.36). Results indicated that religious identity remained stable across high school whereas religious participation declined. Even after controlling for ethnic differences in religious affiliation, socioeconomic background, and generational status, adolescents from Latin American and Asian backgrounds reported higher levels of religious identity and adolescents from Latin American backgrounds reported higher rates of religious participation. Within individual adolescents, changes in religious identity were associated with changes in ethnic and family identities, suggesting important linkages in the development of these social identities during adolescence.

A survey of genetic variation in Native American and Siberian populations reveals that Native Americans are descended from at least three streams of gene flow from Asia: after the initial peopling of the continent there was a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. The roads to the Americas The settlement of the Americas occurred at least 15,000 years ago by means of the Beringia land bridge that existed between Asia and America during the ice ages. Key questions about how many migrations were involved and subsequent dispersal patterns within the Americas remain unresolved. This new survey of genetic variation in Native American and Siberian populations shows that Native Americans descend from at least three waves of migration from Asia. After the initial peopling of the continent there was a southward expansion along the coast, with sequential population splits and little gene flow after divergence, particularly in South America. The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved 1 , 2 , 3 , 4 , 5 . One contentious issue is whether the settlement occurred by means of a single 6 , 7 , 8 migration or multiple streams of migration from Siberia 9 , 10 , 11 , 12 , 13 , 14 , 15 . The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call ‘First American’. However, speakers of Eskimo–Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is common and occurs in 6–8% of all patients fulfilling the diagnostic criteria for acute myocardial infarction (AMI). This paper describes the rationale behind the trial ‘Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment (ACEI/ARB) of MINOCA patients’ (MINOCA-BAT) and the need to improve the secondary preventive treatment of MINOCA patients. MINOCA-BAT is a registry-based, randomized, parallel, open-label, multicenter trial with 2:2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce the composite endpoint of death of any cause, readmission because of AMI, ischemic stroke or heart failure in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 3500 patients will be randomized into four groups; e.g. ACEI/ARB and beta blocker, beta blocker only, ACEI/ARB only and neither ACEI/ARB nor beta blocker, and followed for a mean of 4 years. While patients with MINOCA have an increased risk of serious cardiovascular events and death, whether conventional secondary preventive therapies are beneficial has not been assessed in randomized trials. There is a limited basis for guideline recommendations in MINOCA. Furthermore, studies of routine clinical practice suggest that use of secondary prevention therapies in MINOCA varies considerably. Thus results from this trial may influence future treatment strategies and guidelines specific to MINOCA patients.

This study reports on 382 COVID-19 patients having undergone allogeneic ( n  = 236) or autologous ( n  = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age ( p  = 0.02), need for ICU ( p  < 0.0001) and moderate/high immunodeficiency index ( p  = 0.04) increased the risk while better performance status ( p  = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.

In this review, the phenomenon of grain boundary (GB) wetting by the second solid phase is analyzed for the high entropy alloys (HEAs). Similar to the GB wetting by the liquid phase, the GB wetting by the second solid phase can be incomplete (partial) or complete. In the former case, the second solid phase forms in the GB of a matrix, the chain of (usually lenticular) precipitates with a certain non-zero contact angle. In the latter case, it forms in the GB continuous layers between matrix grains which completely separate the matrix crystallites. The GB wetting by the second solid phase can be observed in HEAs produced by all solidification-based technologies. The particle chains or continuous layers of a second solid phase form in GBs also without the mediation of a liquid phase, for example by solid-phase sintering or coatings deposition. To describe the GB wetting by the second solid phase, the new GB tie-lines should be considered in the two- or multiphase areas in the multicomponent phase diagrams for HEAs. The GB wetting by the second solid phase can be used to improve the properties of HEAs by applying the so-called grain boundary engineering methods.

BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform.RESULTSThis study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways.CONCLUSIONThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.FUNDINGMark and Lisa Schwartz; the National Institutes of Health (U19AI082630); the American Lung Association; the Executive Committee on Research at Massachusetts General Hospital; the Chan Zuckerberg Initiative; Arthur, Sandra, and Sarah Irving for the David P. Ryan, MD, Endowed Chair in Cancer Research; an EMBO Long-Term Fellowship (ALTF 486-2018); a Cancer Research Institute/Bristol Myers Squibb Fellowship (CRI2993); the Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH awards UL1TR001102 and UL1TR002541-01); and by the Harvard University Center for AIDS Research (National Institute of Allergy and Infectious Diseases, 5P30AI060354).

The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model. All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel. The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6-17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person. This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem.

In this review, the phenomenon of grain boundary (GB) wetting by melt is analyzed for multicomponent alloys without principal components (also called high-entropy alloys or HEAs) containing titanium. GB wetting can be complete or partial. In the former case, the liquid phase forms the continuous layers between solid grains and completely separates them. In the latter case of partial GB wetting, the melt forms the chain of droplets in GBs, with certain non-zero contact angles. The GB wetting phenomenon can be observed in HEAs produced by all solidification-based technologies. GB leads to the appearance of novel GB tie lines Twmin and Twmax in the multicomponent HEA phase diagrams. The so-called grain-boundary engineering of HEAs permits the use of GB wetting to improve the HEAs’ properties or, alternatively, its exclusion if the GB layers of a second phase are detrimental.

Introduction The mitogen-activated protein kinase (MAPK) signalling network aberrations in metastatic colorectal cancer (mCRC) generate intrinsic dynamic effects and temporal variations that are crucial but often overlooked in clinical trial populations. Here, we investigate the time-varying impact of MAPK pathway mutation genotype on each treatment line’s contribution to the overall clinical course. Methods The PROMETEO study focused on mCRC patients undergoing second-line treatment at 20 hospitals. We evaluated genotypes and employed flexible models to analyse the dynamic effect of each mutation. Results We examined data derived from 1160 patients. The effects of KRAS G12C or G12V, and BRAF V600E are clearly time-varying, with unexpected consequences such as the deleterious effect of BRAF V600E vs other genotypes dissipating over time when subjects receive antiangiogenics, or KRAS G12V and G12C showing increasing aggressiveness over time. Thus, contrary to expectations, the 12-month survival rate from the second line for those who survived >6 months was 49.9% (95% CI, 32.7–67.3) for KRAS G12C and 59% (95% CI, 38.5–80.6) for BRAF V600E. Conclusions The dynamic perspective is essential for understanding the behaviour of tumours with specific genotypes, especially from the second line onward. This may be relevant in patient monitoring and treatment decision-making, particularly in cases with distinct mutations.

Measuring temporal discounting through the use of intertemporal choice tasks is now the gold standard method for quantifying human choice impulsivity (impatience) in neuroscience, psychology, behavioral economics, public health and computational psychiatry. A recent area of growing interest is individual differences in discounting levels, as these may predispose to (or protect from) mental health disorders, addictive behaviors, and other diseases. At the same time, more and more studies have been dedicated to the quantification of individual attitudes towards risk, which have been measured in many clinical and non-clinical populations using closely related techniques. Economists have pointed to interactions between measurements of time preferences and risk preferences that may distort estimations of the discount rate. However, although becoming standard practice in economics, discount rates and risk preferences are rarely measured simultaneously in the same subjects in other fields, and the magnitude of the imposed distortion is unknown in the assessment of individual differences. Here, we show that standard models of temporal discounting -such as a hyperbolic discounting model widely present in the literature which fails to account for risk attitudes in the estimation of discount rates- result in a large and systematic pattern of bias in estimated discounting parameters. This can lead to the spurious attribution of differences in impulsivity between individuals when in fact differences in risk attitudes account for observed behavioral differences. We advance a model which, when applied to standard choice tasks typically used in psychology and neuroscience, provides both a better fit to the data and successfully de-correlates risk and impulsivity parameters. This results in measures that are more accurate and thus of greater utility to the many fields interested in individual differences in impulsivity.