An ``Improved" Lattice Study of Semi-leptonic Decays of D-Mesons

We present results of a lattice computation of the matrix elements of the vector and axial-vector currents which are relevant for the semi-leptonic decays $D \rightarrow K$ and $D \rightarrow K^*$. The computations are performed in the quenched approximation to lattice QCD on a $24^3 \times 48$ lattice at $\beta=6.2$, using an $O(a)$-improved fermionic action. In the limit of zero lepton masses the semi-leptonic decays $D \rightarrow K$ and $D \rightarrow K^*$ are described by four form factors: $f^{+}_K,V,A_1$ and $A_2$, which are functions of $q^2$, where $q^{\mu}$ is the four-momentum transferred in the process. Our results for these form factors at $q^2=0$ are: f^+_K(0)=0.67 \er{7}{8} , V(0)=1.01 \err{30}{13} , A_1(0)=0.70 \err{7}{10} , A_2(0)=0.66 \err{10}{15} , which are consistent with the most recent experimental world average values. We have also determined the $q^2$ dependence of the form factors, which we find to be reasonably well described by a simple pole-dominance model. Results for other form factors, including those relevant to the decays \dpi and \drho, are also given.Comment: 41 pages, uuencoded compressed postscript file containing 14 figures, LaTeX, Edinburgh Preprint 94/546 and Southampton Preprint SHEP 93/94-3

Lattice QCD with mixed actions

We discuss some of the implications of simulating QCD when the action used for the sea quarks is different from that used for the valence quarks. We present exploratory results for the hadron mass spectrum and pseudoscalar meson decay constants using improved staggered sea quarks and HYP-smeared overlap valence quarks. We propose a method for matching the valence quark mass to the sea quark mass and demonstrate it on UKQCD clover data in the simpler case where the sea and valence actions are the same.Comment: 15 pages, 10 figures some minor modification to text and figures. Accepted for publicatio

Improving constraints on tan(beta)/m_H using B \to D tau \bar{nu}

We study the q^2 dependence of the exclusive decay mode B \to D tau \bar{nu} in type II two Higgs doublet models and show that this mode may be used to put stringent bounds on tan(beta)/m_H. There are currently rather large theoretical uncertainties in the q^2 distribution, but these may be significantly reduced by future measurements of the analogous distribution for B \to D(e,mu)\bar{nu}. We estimate that this reduction in the theoretical uncertainties would eventually (i.e., with sufficient data) allow one to push the upper bound on tan(beta)/m_H down to about 0.06 GeV^{-1}. This would represent an improvement on the current bound by about a factor of 7. We then apply the method of optimized observables which allows us to estimate the reach of an experiment with a given number of events. We thus find that an experiment with, for example, 10^3 events could set a 2\sigma upper bound on tan(beta)/m_H of 0.07 GeV^{-1} or could differentiate at the 4.6\sigma level between a 2HDM with tan(beta)/m_H = 0.1 GeV^{-1} and the SM.Comment: 19 pages, Late

Breeding on the leading edge of a northward range expansion: differences in morphology and the stress response in the arctic Gambel's white-crowned sparrow

Individuals at the forefront of a range shift are likely to exhibit phenotypic traits that distinguish them from the population breeding within the historic range. Recent studies have examined morphological, physiological and behavioral phenotypes of individuals at the edge of their range. Several studies have found differences in the hypothalamic-pituitary-adrenal (HPA) axis activity in response to acute restraint stress in individuals at the range limits. HPA axis activation leads to elevations in glucocorticoids that regulate physiology and behavior. Here we compare the hormonal profiles and morphometrics from Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) breeding at the northern limit of the population's range to those birds breeding within the historic population range. Birds breeding at the northern limit experienced a harsher environment with colder temperatures; however, we found no differences in arthropod prey biomass between the northern limit and more southern (historic) sites. Males at the northern limit had higher body condition scores (mass corrected for body size) compared to individuals within the historic range, but no differences were found in beak and tarsus lengths, wing chord, muscle profile or fat stores. In males during the pre-parental stage, before breeding commenced, HPA axis activity was elevated in birds at the northern limit of the range, but no differences were found during the parental or molt stages. Females showed no differences in HPA axis activity during the parental stage. This study suggests that "pioneering" individuals at the limits of their breeding range exhibit physiology and morphology that are distinct from individuals within the historic range

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A Risk Prediction Model for Mortality Among Smokers in the COPDGene® Study.

BackgroundRisk factor identification is a proven strategy in advancing treatments and preventive therapy for many chronic conditions. Quantifying the impact of those risk factors on health outcomes can consolidate and focus efforts on individuals with specific high-risk profiles. Using multiple risk factors and longitudinal outcomes in 2 independent cohorts, we developed and validated a risk score model to predict mortality in current and former cigarette smokers.MethodsWe obtained extensive data on current and former smokers from the COPD Genetic Epidemiology (COPDGene®) study at enrollment. Based on physician input and model goodness-of-fit measures, a subset of variables was selected to fit final Weibull survival models separately for men and women. Coefficients and predictors were translated into a point system, allowing for easy computation of mortality risk scores and probabilities. We then used the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) cohort for external validation of our model.ResultsOf 9867 COPDGene participants with standard baseline data, 17.6% died over 10 years of follow-up, and 9074 of these participants had the full set of baseline predictors (standard plus 6-minute walk distance and computed tomography variables) available for full model fits. The average age of participants in the cohort was 60 for both men and women, and the average predicted 10-year mortality risk was 18% for women and 25% for men. Model time-integrated area under the receiver operating characteristic curve statistics demonstrated good predictive model accuracy (0.797 average), validated in the external cohort (0.756 average). Risk of mortality was impacted most by 6-minute walk distance, forced expiratory volume in 1 second and age, for both men and women.ConclusionsCurrent and former smokers exhibited a wide range of mortality risk over a 10- year period. Our models can identify higher risk individuals who can be targeted for interventions to reduce risk of mortality, for participants with or without chronic obstructive pulmonary disease (COPD) using current Global initiative for obstructive Lung Disease (GOLD) criteria