Comment on form factor shape and extraction of |V_ub| from B --> pi l nu

We point out that current experimental data for partial B --> pi l nu branching fractions reduce the theoretical input required for a precise extraction of |V_ub| to the form factor normalization at a single value of the pion energy. We show that the heavy-quark expansion provides a bound on the form factor shape that is orders of magnitude more stringent than conventional unitarity bounds. We find |V_ub| = (3.7 +/- 0.2 +/- 0.1) x [0.8/F_+(16 GeV^2)]. The first error is from the experimental branching fractions, and the second is a conservative bound on the residual form factor shape uncertainty, both of which will improve with additional data. Together with current and future lattice determinations of the form factor normalization this result gives an accurate, model independent determination of |V_ub|. We further extract semileptonic shape observables such as |V_ub F_+(0)| = 0.92 +/- 0.11 +/- 0.03 and show how these observables can be used to test factorization and to determine low-energy parameters in hadronic B decays.Comment: 14 pages, 3 figures; journal version, results and conclusions unchange

The Risk of Venous Thromboembolism Attributed to Established Prothrombotic Genotypes

Background - The proportion of venous thromboembolism (VTE) events that can be attributed to established prothrombotic genotypes has been scarcely investigated in the general population. We aimed to estimate the proportion of VTEs in the population that could be attributed to established prothrombotic genotypes using a population-based case-cohort. Methods - Cases with incident VTE (n = 1,493) and a randomly sampled subcohort (n = 13,069) were derived from the Tromsø Study (1994–2012) and the Nord-Trøndelag Health (HUNT) study (1995–2008). DNA samples were genotyped for 17 single-nucleotide polymorphisms (SNPs) associated with VTE. Hazard ratios with 95% confidence intervals (CIs) were estimated in Cox regression models. Population-attributable fractions (PAFs) with 95% bias-corrected CIs (based on 10,000 bootstrap samples) were estimated using a cumulative model where SNPs significantly associated with VTE were added one by one in ranked order of the individual PAFs. Results - Six SNPs were significantly associated with VTE (rs1799963 [Prothrombin], rs2066865 [FGG], rs6025 [FV Leiden], rs2289252 [F11], rs2036914 [F11], and rs8176719 [ABO]). The cumulative PAF for the six-SNP model was 45.3% (95% CI: 19.7–71.6) for total VTE and 61.7% (95% CI: 19.6–89.3) for unprovoked VTE. The PAF for prothrombotic genotypes was higher for deep vein thrombosis (DVT; 52.9%) than for PE (33.8%), and higher for those aged <70 years (66.1%) than for those aged ≥70 years (24.9%). Conclusion - Our findings suggest that 45 to 62% of all VTE events in the population can be attributed to known prothrombotic genotypes. The PAF of established prothrombotic genotypes was higher in DVT than in PE, and higher in the young than in the elderly

Treatment completion for latent tuberculosis infection in Norway: a prospective cohort study

Background: Successful treatment of latent tuberculosis infection (LTBI) is essential to reduce tuberculosis (TB) incidence rates in low-burden countries. This study measures treatment completion and determinants of non-completion of LTBI treatment in Norway in 2016. Methods: This prospective cohort study included all individuals notified with LTBI treatment to the Norwegian Surveillance System for Infectious Diseases (MSIS) in 2016. We obtained data from MSIS and from a standardized form that was sent to health care providers at the time of patient notification to MSIS. We determined completion rates. Pearson’s chi squared test was used to study associations between pairs of categorical variables and separate crude and multivariable logistic regression models were used to identify factors associated with treatment completion and adverse drug effects. Results: We obtained information on treatment completion from 719 of the 726 individuals notified for LTBI treatment in 2016. Overall, 91% completed treatment. Treatment completion was highest in the foreign-born group [foreign-born, n = 562 (92%) vs Norwegian-born, n = 115 (85%), p = 0.007]. Treatment completion did not differ significantly between prescribed regimens (p = 0.124). Adverse events were the most common reason for incomplete treatment. We found no significant differences in adverse events when comparing weekly rifapentine (3RPH) with three months daily isoniazid and rifampicin (3RH). However, there were significantly fewer adverse events with 3RPH compared to other regimens (p = 0.037). Age over 35 years was significantly associated with adverse events irrespective of regimen (p = 0.024), whereas immunosuppression was not significantly associated with adverse events after adjusting for other variables (p = 0.306). Treatment under direct observation had a significant effect on treatment completion for foreign-born (multivariate Wald p-value = 0.017), but not for Norwegian-born (multivariate Wald p-value = 0.408) individuals. Conclusions: We report a very high treatment completion rate, especially among individuals from countries with high TB incidence. The follow-up from tuberculosis-coordinators and the frequent use of directly observed treatment probably contributes to this. Few severe adverse events were reported, even with increased age and in individuals that are more susceptible. While these results are promising, issues of cost-effectiveness and targeting treatment to individuals at highest risk of TB are important components of public health impact.publishedVersio

The Global Brain Health Survey: Development of a Multi-Language Survey of Public Views on Brain Health.

Background: Brain health is a multi-faceted concept used to describe brain physiology, cognitive function, mental health and well-being. Diseases of the brain account for one third of the global burden of disease and are becoming more prevalent as populations age. Diet, social interaction as well as physical and cognitive activity are lifestyle factors that can potentially influence facets of brain health. Yet, there is limited knowledge about the population's awareness of brain health and willingness to change lifestyle to maintain a healthy brain. This paper introduces the Global Brain Health Survey protocol, designed to assess people's perceptions of brain health and factors influencing brain health. Methods: The Global Brain Health Survey is an anonymous online questionnaire available in 14 languages to anyone above the age of 18 years. Questions focus on (1) willingness and motivation to maintain or improve brain health, (2) interest in learning more about individual brain health using standardized tests, and (3) interest in receiving individualized support to take care of own brain health. The survey questions were developed based on results from a qualitative interview study investigating brain health perceptions among participants in brain research studies. The survey includes 28 questions and takes 15-20 min to complete. Participants provide electronically informed consent prior to participation. The current survey wave was launched on June 4, 2019 and will close on August 31, 2020. We will provide descriptive statistics of samples distributions including analyses of differences as a function of age, gender, education, country of residence, and we will examine associations between items. The European Union funded Lifebrain project leads the survey in collaboration with national brain councils in Norway, Germany, and Belgium, Brain Foundations in the Netherlands and Sweden, the National University of Ostroh Academy and the Women's Brain Project. Discussion: Results from this survey will provide new insights in peoples' views on brain health, in particular, the extent to which the adoption of positive behaviors can be encouraged. The results will contribute to the development of policy recommendations for supporting population brain health, including measures tailored to individual needs, knowledge, motivations and life situations

Mechanisms of congenital heart disease caused by NAA15 haploinsufficiency

Rationale: NAA15 is a component of the N-terminal (Nt) acetyltransferase complex, NatA. The mechanism by which NAA15 haploinsufficiency causes congenital heart disease (CHD) remains unknown. To better understand molecular processes by which NAA15 haploinsufficiency perturbs cardiac development, we introduced NAA15 variants into human induced pluripotent stem cells (iPSCs) and assessed the consequences of these mutations on RNA and protein expression. Objective: We aim to understand the role of NAA15 haploinsufficiency in cardiac development by investigating proteomic effects on NatA complex activity, and identifying proteins dependent upon a full amount of NAA15. Methods and Results: We introduced heterozygous LoF, compound heterozygous and missense residues (R276W) in iPS cells using CRISPR/Cas9. Haploinsufficient NAA15 iPS cells differentiate into cardiomyocytes, unlike NAA15-null iPS cells, presumably due to altered composition of NatA. Mass spectrometry (MS) analyses reveal ~80% of identified iPS cell NatA targeted proteins displayed partial or complete Nt-acetylation. Between null and haploinsufficient NAA15 cells Nt-acetylation levels of 32 and 9 NatA-specific targeted proteins were reduced, respectively. Similar acetylation loss in few proteins occurred in NAA15 R276W iPSCs. In addition, steady-state protein levels of 562 proteins were altered in both null and haploinsufficient NAA15 cells; eighteen were ribosomal-associated proteins. At least four proteins were encoded by genes known to cause autosomal dominant CHD. Conclusions: These studies define a set of human proteins that requires a full NAA15 complement for normal synthesis and development. A 50% reduction in the amount of NAA15 alters levels of at least 562 proteins and Nt-acetylation of only 9 proteins. One or more modulated proteins are likely responsible for NAA15-haploinsufficiency mediated CHD. Additionally, genetically engineered iPS cells provide a platform for evaluating the consequences of amino acid sequence variants of unknown significance on NAA15 function

Social capital and health: Does egalitarianism matter? A literature review

The aim of the paper is to critically review the notion of social capital and review empirical literature on the association between social capital and health across countries. The methodology used for the review includes a systematic search on electronic databases for peer-reviewed published literature. We categorize studies according to level of analysis (single and multilevel) and examine whether studies reveal a significant health impact of individual and area level social capital. We compare the study conclusions according to the country's degrees of economic egalitarianism. Regardless of study design, our findings indicate that a positive association (fixed effect) exists between social capital and better health irrespective of countries degree of egalitarianism. However, we find that the between-area variance (random effect) in health tends to be lower in more egalitarian countries than in less egalitarian countries. Our tentative conclusion is that an association between social capital and health at the individual level is robust with respect to the degree of egalitarianism within a country. Area level or contextual social capital may be less salient in egalitarian countries in explaining health differences across places

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011