223 research outputs found
Novel—and “Neu”—Therapeutic Possibilities for Heart Failure⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Impact of changing US cigarette smoking patterns on incident cancer: Risks of 20 smoking-related cancers among the women and men of the NIH-AARP cohort
Background: Historically, US women started smoking at a later age than men and had lower relative risks for smoking-related cancers. However, more recent birth cohorts of women and men have similar smoking histories and have now reached the high-risk age for cancer. The impact of these changes on cancer incidence has not been systematically examined. Methods: Relative risks (RR), 95% confidence intervals (CI) and attributable fractions were calculated for cigarette smoking and incidence of 20 smoking-related cancers in 186 057 women and 266 074 men of the National Institutes of Health-AARP cohort, aged 50 to 71 years in 1995 and followed for 11 years. Results: In the cohort, which included participants born between 1924 and 1945, most women and men started smoking as teenagers. RRs for current vs never smoking were similar in women and men for the following cancers: lung squamous-cell (RR women: 121.4, 95% CI: 57.3–257.4; RR men:114.6, 95% CI: 61.2–214.4), lung adenocarcinoma (RR women: 11.7, 95% CI: 9.8–14.0; RR men: 15.6, 95% CI: 12.5–19.6), laryngeal (RR women: 37.0, 95% CI: 14.9–92.3; RR men: 13.8, 95% CI: 9.3–20.2), oral cavity-pharyngeal (RR women:4.4, 95% CI: 3.3–6.0; RR men: 3.8, 95% CI: 3.0–4.7), oesophageal squamous cell (RR women: 7.3, 95% CI: 3.5–15.5; RR men: 6.2, 95% CI: 2.8–13.7), bladder (RR women: 4.7, 95% CI: 3.7–5.8; RR men: 4.0, 95% CI: 3.5–4.5), colon (RR women: 1.3, 95% CI: 1.2–1.5; RR men: 1.3, 95% CI: 1.1–1.4), and at other sites, with similar attributable fractions. Conclusions: RRs for current smoking and incidence of many smoking-related cancers are now similar in US women and men, likely reflecting converging smoking patterns
Reviving the Modern Rule in the Interpretation of Tax Statutes: Baby Steps Taken in Canada Trustco, Mathew, Placer Dome and Imperial Oil
Predicting Adverse Outcomes for Shiga Toxin–Producing Escherichia coli Infections in Emergency Departments
Objective: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting. Study design: We reviewed medical records of children \u3c18 years old infected with STEC and treated in 1 of 38 participating emergency departments in North America between 2011 and 2015. The HUS severity score (hemoglobin [g/dL] plus 2-times serum creatinine [mg/dL]) was calculated using first available laboratory results. Children with scores \u3e13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness. Results: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children \u3c5 years old (area under the curve 0.77, 95% CI 0.68-0.87). For children \u3c5 years, greatest net benefit was achieved for a threshold probability \u3e26%. Conclusions: The HUS severity score was able to discriminate between high- and low-risk children \u3c5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold
Intersecting D3-branes and Holography
We study a defect conformal field theory describing D3-branes intersecting
over two space-time dimensions. This theory admits an exact Lagrangian
description which includes both two- and four-dimensional degrees of freedom,
has (4,4) supersymmetry and is invariant under global conformal
transformations. Both two- and four-dimensional contributions to the action are
conveniently obtained in a two-dimensional (2,2) superspace. In a suitable
limit, the theory has a dual description in terms of a probe D3-brane wrapping
an AdS_3 x S^1 slice of AdS_5 x S^5. We consider the AdS/CFT dictionary for
this set-up. In particular we find classical probe fluctuations corresponding
to the holomorphic curve wy=c\alpha^{\prime}. These fluctuations are dual to
defect fields containing massless two-dimensional scalars which parameterize
the classical Higgs branch, but do not correspond to states in the Hilbert
space of the CFT. We also identify probe fluctuations which are dual to BPS
superconformal primary operators and to their descendants. A
non-renormalization theorem is conjectured for the correlators of these
operators, and verified to order g^2.Comment: 46 pages, 5 figures, Latex, minor corrections to section 4.2, version
published in Phys. Rev.
Preliminary Report: Missense mutations in the APOL gene family are associated with end stage kidney disease risk previously attributed to the MYH9 gene
MYH9 has been proposed as a major genetic risk locus for a spectrum of
non-diabetic end stage kidney disease (ESKD). We use recently released
sequences from the 1000 Genomes Project to identify two western African
specific missense mutations (S342G and I384M) in the neighbouring APOL1 gene,
and demonstrate that these are more strongly associated with ESKD than
previously reported MYH9 variants. We also show that the distribution of these
risk variants in African populations is consistent with the pattern of African
ancestry ESKD risk previously attributed to the MYH9 gene. Additional
associations were also found among other members of the APOL gene family, and
we propose that ESKD risk is caused by western African variants in members of
the APOL gene family, which evolved to confer protection against pathogens,
such as Trypanosoma.Comment: 25 pages, 6 figure
Cosmological parameters from CMB and other data: a Monte-Carlo approach
We present a fast Markov Chain Monte-Carlo exploration of cosmological
parameter space. We perform a joint analysis of results from recent CMB
experiments and provide parameter constraints, including sigma_8, from the CMB
independent of other data. We next combine data from the CMB, HST Key Project,
2dF galaxy redshift survey, supernovae Ia and big-bang nucleosynthesis. The
Monte Carlo method allows the rapid investigation of a large number of
parameters, and we present results from 6 and 9 parameter analyses of flat
models, and an 11 parameter analysis of non-flat models. Our results include
constraints on the neutrino mass (m_nu < 0.3eV), equation of state of the dark
energy, and the tensor amplitude, as well as demonstrating the effect of
additional parameters on the base parameter constraints. In a series of
appendices we describe the many uses of importance sampling, including
computing results from new data and accuracy correction of results generated
from an approximate method. We also discuss the different ways of converting
parameter samples to parameter constraints, the effect of the prior, assess the
goodness of fit and consistency, and describe the use of analytic
marginalization over normalization parameters.Comment: Quintessence results now include perturbations. Changes to match
version accepted by PRD. MCMC code and data are available at
http://cosmologist.info/cosmomc/ along with a B&W printer-friendly version of
the pape
Proof of impact and pipeline planning: directions and challenges for social audit in the health sector
Social audits are typically observational studies, combining qualitative and quantitative uptake of evidence with consultative interpretation of results. This often falters on issues of causality because their cross-sectional design limits interpretation of time relations and separation out of other indirect associations
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis
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