1,944 research outputs found
A fourth generation, anomalous like-sign dimuon charge asymmetry and the LHC
A fourth chiral generation, with in the range GeV and a moderate value of the CP-violating phase can explain the
anomalous like-sign dimuon charge asymmetry observed recently by the D0
collaboration. The required parameters are found to be consistent with
constraints from other and decays. The presence of such quarks, apart
from being detectable in the early stages of the LHC, would also have important
consequences in the electroweak symmetry breaking sector.Comment: 18 pages, 9 figures, Figure 1 is modified, more discussions are added
in section 2. new references adde
Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial
Background: Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause. Methods: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200–5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25–75 mL/min per 1·73m2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150. Findings: The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0–2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52–0·79) and those without diabetes (0·50, 0·35–0·72; pinteraction=0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45–0·73] vs 0·51 [0·34–0·75]; Pinteraction=0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53–0·92] vs 0·79 [0·40–1·55]; Pinteraction=0·78), and all-cause mortality (0·74 [0·56–0·98] vs 0·52 [0·29–0·93]; Pinteraction=0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51–0·78), glomerulonephritides (n=695; 0·43, 0·26–0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44–1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29–1·19; Pinteraction=0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes. Interpretation: Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease
Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis
Common fragile sites (cfs) are specific regions in the human genome that are
particularly prone to genomic instability under conditions of replicative
stress. Several investigations support the view that common fragile sites play
a role in carcinogenesis. We discuss a genome-wide approach based on graph
theory and Gene Ontology vocabulary for the functional characterization of
common fragile sites and for the identification of genes that contribute to
tumour cell biology. CFS were assembled in a network based on a simple measure
of correlation among common fragile site patterns of expression. By applying
robust measurements to capture in quantitative terms the non triviality of the
network, we identified several topological features clearly indicating
departure from the Erdos-Renyi random graph model. The most important outcome
was the presence of an unexpected large connected component far below the
percolation threshold. Most of the best characterized common fragile sites
belonged to this connected component. By filtering this connected component
with Gene Ontology, statistically significant shared functional features were
detected. Common fragile sites were found to be enriched for genes associated
to the immune response and to mechanisms involved in tumour progression such as
extracellular space remodeling and angiogenesis. Our results support the
hypothesis that fragile sites serve a function; we propose that fragility is
linked to a coordinated regulation of fragile genes expression.Comment: 18 pages, accepted for publication in BMC Bioinformatic
Viability of MSSM scenarios at very large tan(beta)
We investigate the MSSM with very large tan(beta) > 50, where the fermion
masses are strongly affected by loop-induced couplings to the "wrong" Higgs,
imposing perturbative Yukawa couplings and constraints from flavour physics.
Performing a low-energy scan of the MSSM with flavour-blind soft terms, we find
that the branching ratio of B->tau nu and the anomalous magnetic moment of the
muon are the strongest constraints at very large tan(beta) and identify the
viable regions in parameter space. Furthermore we determine the scale at which
the perturbativity of the Yukawa sector breaks down, depending on the
low-energy MSSM parameters. Next, we analyse the very large tan(beta) regime of
General Gauge Mediation (GGM) with a low mediation scale. We investigate the
requirements on the parameter space and discuss the implied flavour
phenomenology. We point out that the possibility of a vanishing Bmu term at a
mediation scale M = 100 TeV is challenged by the experimental data on B->tau nu
and the anomalous magnetic moment of the muon.Comment: 29 pages, 7 figures. v2: discussion in sections 1 and 4 expanded,
conclusions unchanged. Matches version published in JHE
Effects of dapagliflozin on mortality in patients with chronic kidney disease: a pre-specified analysis from the DAPA-CKD randomized controlled trial
AIMS : Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death. METHODS AND RESULTS : DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo. CONCLUSION : In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death
Gravitational physics with antimatter
The production of low-energy antimatter provides unique opportunities to
search for new physics in an unexplored regime. Testing gravitational
interactions with antimatter is one such opportunity. Here a scenario based on
Lorentz and CPT violation in the Standard- Model Extension is considered in
which anomalous gravitational effects in antimatter could arise.Comment: 5 pages, presented at the International Conference on Exotic Atoms
(EXA 2008) and the 9th International Conference on Low Energy Antiproton
Physics (LEAP 2008), Vienna, Austria, September 200
Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: A prespecified analysis of the DAPA-CKD trial
BACKGROUND: Despite renin-angiotensin-aldosterone-system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this pre-specified analysis of DAPA-CKD was to assess efficacy and safety of dapagliflozin in a small subgroup participants with FSGS confirmed by kidney biopsy. METHODS: In DAPA-CKD, patients with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g (22.6-565 mg/mol) were randomised to dapagliflozin 10mg once-daily or placebo as an adjunct to standard care, and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline ≥ 50%, end-stage kidney disease (ESKD), or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment). RESULTS: Of 104 participants with biopsy-confirmed FSGS, 45 were randomised to dapagliflozin and 59 to placebo. Mean (SD) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73m2 and median (IQR) UACR 1248 (749-2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomised to dapagliflozin and placebo, respectively (HR 0.62, 95%CI 0.17-2.17). Dapagliflozin led to a larger acute reduction (SE) in eGFR compared to placebo (-4.5 [95% CI - 5.9--3.1] vs - 0.9 [-2.1-0.4] mL/min/1.73m2 per 2 wks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were - 1.9 (-3.0--0.9) and - 4.0 (-4.9--3.0) mL/min/1.73m2/year, respectively (difference 2.0 [95%CI 0.6-3.5] mL/min/1.73m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin. CONCLUSION: Among DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared to placebo, although this difference was not statistically significant
A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy
Immunoglobulin A (IgA) nephropathy is a common form of glomerulonephritis, which despite use of renin-angiotensin-aldosterone-system blockers and immunosuppressants, often progresses to kidney failure. In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial, dapagliflozin reduced the risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes, including those with IgA nephropathy. Participants with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10mg or placebo, as adjunct to standard care. The primary composite endpoint was a sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from a kidney disease-related or cardiovascular cause. Of 270 participants with IgA nephropathy (254 [94%] confirmed by previous biopsy), 137 were randomized to dapagliflozin and 133 to placebo, and followed for median 2.1 years. Overall, mean age was 51.2 years; mean eGFR, 43.8 mL/min/1.73m2; and median urinary albumin-to-creatinine ratio, 900 mg/g. The primary outcome occurred in six (4%) participants on dapagliflozin and 20 (15%) on placebo (hazard ratio, 0.29; 95% confidence interval, 0.12, 0.73). Mean rates of eGFR decline with dapagliflozin and placebo were −3.5 and −4.7 mL/min/1.73m2/year, respectively. Dapagliflozin reduced the urinary albumin-to-creatinine ratio by 26% relative to placebo. Adverse events leading to study drug discontinuation were similar with dapagliflozin and placebo. There were fewer serious adverse events with dapagliflozin, and no new safety findings in this population. Thus, in participants with IgA nephropathy, dapagliflozin reduced the risk of chronic kidney disease progression with a favorable safety profile
The functional head of the Cambrian radiodontan (stem-group Euarthropoda) Amplectobelua symbrachiata
© The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article
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