Keratinocyte growth factor in acute lung injury to reduce pulmonary dysfunction – a randomised placebo-controlled trial (KARE): study protocol

Abstract Background Acute lung injury is a common, devastating clinical syndrome associated with substantial mortality and morbidity with currently no proven therapeutic interventional strategy to improve patient outcomes. The objectives of this study are to test the potential therapeutic effects of keratinocyte growth factor for patients with acute lung injury on oxygenation and biological indicators of acute inflammation, lung epithelial and endothelial function, protease:antiprotease balance, and lung extracellular matrix degradation and turnover. Methods/design This will be a prospective, randomised, double-blind, allocation-concealed, placebo-controlled, phase 2, multicentre trial. Randomisation will be stratified by presence of severe sepsis requiring vasopressors. Patients in an ICU fulfilling the American–European Consensus Conference Definition of acute lung injury will be randomised in a 1:1 ratio to receive an intravenous bolus of either keratinocyte growth factor (palifermin, 60 μg/kg) or placebo (0.9% sodium chloride solution) daily for a maximum of 6 days. The primary endpoint of this clinical study is to evaluate the efficacy of palifermin to improve the oxygenation index at day 7 or the last available oxygenation index prior to patient discontinuation from the study.A formal statistical analysis plan has been constructed. Analyses will be carried out on an intention-to-treat basis. A single analysis is planned at the end of the trial. P = 0.05 will be considered statistically significant and all tests will be two-sided. For continuously distributed outcomes, differences between groups will be tested using independent-sample t tests, analysis of variance and analysis of covariance with transformation of variables to normality or nonparametric equivalents. The trial will be reported in line with the Consolidated Standards of Reporting Trials (Consort 2010 guidelines). Trial registration http://ISRCTN9569067

Differential cross sections and spin density matrix elements for the reaction gamma p -> p omega

High-statistics differential cross sections and spin density matrix elements for the reaction gamma p -> p omega have been measured using the CLAS at Jefferson Lab for center-of-mass (CM) energies from threshold up to 2.84 GeV. Results are reported in 112 10-MeV wide CM energy bins, each subdivided into cos(theta_CM) bins of width 0.1. These are the most precise and extensive omega photoproduction measurements to date. A number of prominent structures are clearly present in the data. Many of these have not previously been observed due to limited statistics in earlier measurements

Exclusive ρ0\rho^0 electroproduction on the proton at CLAS

The $e p\to e^\prime p \rho^0$ reaction has been measured, using the 5.754 GeV electron beam of Jefferson Lab and the CLAS detector. This represents the largest ever set of data for this reaction in the valence region. Integrated and differential cross sections are presented. The $W$, $Q^2$ and $t$ dependences of the cross section are compared to theoretical calculations based on $t$-channel meson-exchange Regge theory on the one hand and on quark handbag diagrams related to Generalized Parton Distributions (GPDs) on the other hand. The Regge approach can describe at the $\approx$ 30% level most of the features of the present data while the two GPD calculations that are presented in this article which succesfully reproduce the high energy data strongly underestimate the present data. The question is then raised whether this discrepancy originates from an incomplete or inexact way of modelling the GPDs or the associated hard scattering amplitude or whether the GPD formalism is simply inapplicable in this region due to higher-twists contributions, incalculable at present.Comment: 29 pages, 29 figure

Resolving the neural circuits of anxiety

Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIH Director’s New Innovator Award DP2-DK-102256-01)National Institute of Mental Health (U.S.) (NIH) R01-MH102441-01)JPB Foundatio

Factors affecting awareness of emergency contraception among college students in Kathmandu, Nepal

<p>Abstract</p> <p>Background</p> <p>In Nepal, Emergency Contraception (EC) could play a critical role in reducing unintended pregnancies, but very few people aware about it. This paper aims to investigate the level of awareness and factors influencing awareness of EC among college students.</p> <p>Methods</p> <p>A cross-sectional study was carried out in April-May 2006. Structured self-administered questionnaires were administered to 1,137 college students (573 males and 564 females) in Kathmandu valley. The association between awareness of EC and the explanatory variables were first assessed in bivariate analysis using the Chi-square test. The associations were further explored using a multivariate logistic analysis.</p> <p>Results</p> <p>Only about two-thirds of college students (68%) had ever heard about EC. Bivariate analysis shows that males were more aware (72%) of EC than were females (64%). Similarly, the awareness level was significantly higher among younger, unmarried youth who were from outside Kathmandu Valley, who lived with friends, and who had received reproductive health (RH) education in school/college. The study also found that students' sex, permanent place of residence (district), and RH education are significant predictors of awareness of EC. Males are 1.5 times more likely to be aware of EC compared to females. Furthermore, students who lived in Kathmandu Valley were 41% less likely to be aware of EC than were students from outside Kathmandu Valley. On the other hand, those students who received RH education in school/college were almost nine times more likely to be aware of EC compared to those who did not receive such education.</p> <p>Conclusion</p> <p>Awareness of the EC is low among college students in Nepal. Health education initiatives should target students as they are more likely to be sexually active. There is a need to further educate students about EC which can help to reduce unintended pregnancies, many of which result in unsafe abortion and take a large toll on women's health.</p

Correlates of unintended pregnancy among currently pregnant married women in Nepal

<p>Abstract</p> <p>Background</p> <p>Women living in every country, irrespective of its development status, have been facing the problem of unintended pregnancy. Unintended pregnancy is an important public health issue in both developing and developed countries because of its negative association with the social and health outcomes for both mothers and children. This study aims to determine the prevalence and the factors influencing unintended pregnancy among currently pregnant married women in Nepal.</p> <p>Methods</p> <p>This paper reports on data drawn from Nepal Demographic and Health Survey (NDHS) which is a nationally representative survey. The analysis is restricted to currently pregnant married women at the time of survey. Association between unintended pregnancy and the explanatory variables was assessed in bivariate analysis using Chi-square tests. Logistic regression was used to assess the net effect of several independent variables on unintended pregnancy.</p> <p>Results</p> <p>More than two-fifth of the currently pregnant women (41%) reported that their current pregnancy was unintended. The results indicate that age of women, age at first marriage, ideal number of children, religion, exposure to radio and knowledge of family planning methods were key predictors of unintended pregnancy. Experience of unintended pregnancy augments with women's age (odds ratio, 1.11). Similarly, increase in the women's age at first marriage reduces the likelihood of unintended pregnancy (odds ratio, 0.93). Those who were exposed to the radio were less likely (odds ratio, 0.63) to have unintended pregnancy compared to those who were not. Furthermore, those women who had higher level of knowledge about family planning methods were less likely to experience unintended pregnancy (odds ratio, 0.60) compared to those having lower level of knowledge.</p> <p>Conclusion</p> <p>One of the important factors contributing to high level of maternal and infant mortality is unintended pregnancy. Programs should aim to reduce unintended pregnancy by focusing on all these identified factors so that infant and maternal mortality and morbidity as well as the need for abortion are decreased and the overall well-being of the family is maintained and enhanced.</p

Compliance with the smoke-free public places legislation in Nepal: A cross-sectional study from Biratnagar Metropolitan City

Background Smoke-free legislation banning tobacco smoking in public places was implemented across Nepal in 2014 with the ambition to reduce the impact of second-hand smoking. As part of a comprehensive policy package on tobacco control, the implementation of the legislation has seen a marked reduction in tobacco consumption. Yet there remains uncertainty about the level of compliance with smoke-free public places. Objectives This study assesses the compliance with smoke-free laws in public places and the factors associated with active smoking in public places in Biratnagar Metropolitan City, Nepal. Methods A cross-sectional study was conducted in the Biratnagar metropolitan city in Province 1 of Nepal from July to December 2019. A total of 725 public places within the metropolitan city were surveyed using a structured survey tool. Active smoking was the primary outcome of the study which was defined as smoking by any person during the data collection time at the designated public place. Results The overall compliance with smoke-free legislation was 56.4%. The highest compliance (75.0%) was observed in Government office buildings. The lowest compliance was observed in eateries, entertainment, and shopping venues (26.3%). There was a statistically significant association between active smoking and the presence of ‘no smoking’ notices appended at the entrance and the odds of active smoking in eateries, entertainment, hospitality, shopping venues, transportations and transits was higher compared to education and health care institutions. None of the ‘no smoking’ notices displayed fully adhered to the contents as prescribed by the law. Conclusion As more than half of the public places complied with the requirements of the legislation, there was satisfactory overall compliance with the smoke-free public places law in this study. The public venues (eateries, shopping venues and transportations) that are more frequently visited and have a high turnover of the public have lower compliance with the legislation. The content of the message in the ‘no smoking’ notices needs close attention to adhere to the legal requirements

Maintenance of broad neutralizing antibodies and memory B cells 1 year post-infection is predicted by SARS-CoV-2-specific CD4+ T cell responses

Understanding the long-term maintenance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity is critical for predicting protection against reinfection. In an age- and gender-matched cohort of 24 participants, the association of disease severity and early immune responses on the maintenance of humoral immunity 12 months post-infection is examined. All severely affected participants maintain a stable subset of SARS-CoV-2 receptor-binding domain (RBD)-specific memory B cells (MBCs) and good neutralizing antibody breadth against the majority of the variants of concern, including the Delta variant. Modeling these immune responses against vaccine efficacy data indicate a 45%–76% protection against symptomatic infection (variant dependent). Overall, these findings indicate durable humoral responses in most participants after infection, reasonable protection against reinfection, and implicate baseline antigen-specific CD4+ T cell responses as a predictor of maintenance of antibody neutralization breadth and RBD-specific MBC levels at 12 months post-infection