Showing papers by "University of Paris published in 2009"
University of Udine1, International School for Advanced Studies2, National Research Council3, Massachusetts Institute of Technology4, University of Paris5, Princeton University6, University of Minnesota7, ParisTech8, University of Milan9, International Centre for Theoretical Physics10, University of Paderborn11, ETH Zurich12, École Polytechnique Fédérale de Lausanne13
TL;DR: QUANTUM ESPRESSO as discussed by the authors is an integrated suite of computer codes for electronic-structure calculations and materials modeling, based on density functional theory, plane waves, and pseudopotentials (norm-conserving, ultrasoft, and projector-augmented wave).
Abstract: QUANTUM ESPRESSO is an integrated suite of computer codes for electronic-structure calculations and materials modeling, based on density-functional theory, plane waves, and pseudopotentials (norm-conserving, ultrasoft, and projector-augmented wave). The acronym ESPRESSO stands for opEn Source Package for Research in Electronic Structure, Simulation, and Optimization. It is freely available to researchers around the world under the terms of the GNU General Public License. QUANTUM ESPRESSO builds upon newly-restructured electronic-structure codes that have been developed and tested by some of the original authors of novel electronic-structure algorithms and applied in the last twenty years by some of the leading materials modeling groups worldwide. Innovation and efficiency are still its main focus, with special attention paid to massively parallel architectures, and a great effort being devoted to user friendliness. QUANTUM ESPRESSO is evolving towards a distribution of independent and interoperable codes in the spirit of an open-source project, where researchers active in the field of electronic-structure calculations are encouraged to participate in the project by contributing their own codes or by implementing their own ideas into existing codes.
19,985 citations
Charité1, Leiden University2, Maastricht University3, Dokuz Eylül University4, Ruhr University Bochum5, University of Córdoba (Spain)6, University of Paris7, Sun Yat-sen University8, Ege University9, University of Alberta10, Ghent University11, University of Copenhagen12, Fırat University13, Barking, Havering and Redbridge University Hospitals NHS Trust14, Chung Shan Medical University15
TL;DR: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial spondyloarthritis in those with chronic back pain.
Abstract: Objective: To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). Methods: All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (⩾3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. Results: Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having “non-radiographic” axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature (“imaging arm”) or the presence of HLA-B27 plus at least two SpA features (“clinical arm”). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). Conclusion: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. Trial registration number: NCT00328068.
2,704 citations
TL;DR: Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care.
Abstract: Summary Background Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens. Methods In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m 2 per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French–American–British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799. Findings Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21·1 months (IQR 15·1–26·9), median overall survival was 24·5 months (9·9–not reached) for the azacitidine group versus 15·0 months (5·6–24·1) for the conventional care group (hazard ratio 0·58; 95% CI 0·43–0·77; stratified log-rank p=0·0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50·8% (95% CI 42·1–58·8) of patients in the azacitidine group were alive compared with 26·2% (18·7–34·3) in the conventional care group (p Interpretation Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care. Funding Celgene Corporation.
2,282 citations
TL;DR: In this article, the authors used a continuous wave Doppler (Doppler) to detect aortic regurgitation, MS mitral stenosis, MVA mitral valve area, DP pressure gradient, RV right ventricle, RVOT right ventricular outflow tract, SV stroke volume.
Abstract: Abbreviations: AR aortic regurgitation, AS aortic stenosis, AVA aortic valve area, CSA cross sectional area, CWD continuous wave Doppler, D diameter, HOCM hypertrophic obstructive cardiomyopathy, LV left ventricle, LVOT left ventricular outflow tract, MR mitral regurgitation, MS mitral stenosis, MVA mitral valve area, DP pressure gradient, RV right ventricle, RVOT right ventricular outflow tract, SV stroke volume, TEE transesophageal echocardiography, T1/2 pressure half-time, TR tricuspid regurgitation, TS tricuspid stenosis, V velocity, VSD ventricular septal defect, VTI velocity time integral
2,163 citations
University of Washington1, University of Paris2, Queen Mary University of London3, McMaster University4, Cornell University5, University of Pennsylvania6, University of New South Wales7, Medical University of Vienna8, Sapienza University of Rome9, Scripps Research Institute10, Boston Children's Hospital11, University of Toronto12, University of Oklahoma Health Sciences Center13
TL;DR: An International Working Group of recognized expert clinicians convened a 2-day structured meeting to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response.
2,127 citations
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Abstract: The proximity operator of a convex function is a natural extension of the notion of a projection operator onto a convex set. This tool, which plays a central role in the analysis and the numerical solution of convex optimization problems, has recently been introduced in the arena of signal processing, where it has become increasingly important. In this paper, we review the basic properties of proximity operators which are relevant to signal processing and present optimization methods based on these operators. These proximal splitting methods are shown to capture and extend several well-known algorithms in a unifying framework. Applications of proximal methods in signal recovery and synthesis are discussed.
2,095 citations
TL;DR: Here, it is demonstrated the synthesis and application of ultrapure isotopically controlled single-crystal chemical vapour deposition (CVD) diamond with a remarkably low concentration of paramagnetic impurities, and single electron spins show the longest room-temperature spin dephasing times ever observed in solid-state systems.
Abstract: As quantum mechanics ventures into the world of applications and engineering, materials science faces the necessity to design matter to quantum grade purity. For such materials, quantum effects define their physical behaviour and open completely new (quantum) perspectives for applications. Carbon-based materials are particularly good examples, highlighted by the fascinating quantum properties of, for example, nanotubes or graphene. Here, we demonstrate the synthesis and application of ultrapure isotopically controlled single-crystal chemical vapour deposition (CVD) diamond with a remarkably low concentration of paramagnetic impurities. The content of nuclear spins associated with the (13)C isotope was depleted to 0.3% and the concentration of other paramagnetic defects was measured to be <10(13) cm(-3). Being placed in such a spin-free lattice, single electron spins show the longest room-temperature spin dephasing times ever observed in solid-state systems (T2=1.8 ms). This benchmark will potentially allow observation of coherent coupling between spins separated by a few tens of nanometres, making it a versatile material for room-temperature quantum information processing devices. We also show that single electron spins in the same isotopically engineered CVD diamond can be used to detect external magnetic fields with a sensitivity reaching 4 nT Hz(-1/2) and subnanometre spatial resolution.
1,751 citations
National Institutes of Health1, Norwegian University of Science and Technology2, National Research Council3, University of São Paulo4, University of Tübingen5, University of Coimbra6, French Institute of Health and Medical Research7, University of Paris8, Chang Gung University9, Columbia University10, Mayo Clinic11, Tel Aviv University12, Technion – Israel Institute of Technology13, Rambam Health Care Campus14, Tel Aviv Sourasky Medical Center15, University of Rostock16, University Health Network17, National Taiwan Normal University18, University of Washington19, University of Tokyo20, Kobe University21, Magna Græcia University22, University of Toronto23, Duke University24, Singapore General Hospital25
TL;DR: Data collected demonstrate that there is a strong association between GBA mutations and Parkinson's disease, and those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were morelikely to have atypical clinical manifestations.
Abstract: Background Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. Methods Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel–Haenszel procedure used to estimate odds ratios across centers. Results All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of p...
1,629 citations
TL;DR: It is shown that dying tumor cells release ATP, which then acts on P2X7 purinergic receptors from DCs and triggers the NOD-like receptor family, pyrin domain containing-3 protein (NLRP3)-dependent caspase-1 activation complex ('inflammasome'), allowing for the secretion of interleukin-1 β (IL-1β).
Abstract: The therapeutic efficacy of anticancer chemotherapies may depend on dendritic cells (DCs), which present antigens from dying cancer cells to prime tumor-specific interferon-gamma (IFN-gamma)-producing T lymphocytes. Here we show that dying tumor cells release ATP, which then acts on P2X(7) purinergic receptors from DCs and triggers the NOD-like receptor family, pyrin domain containing-3 protein (NLRP3)-dependent caspase-1 activation complex ('inflammasome'), allowing for the secretion of interleukin-1beta (IL-1beta). The priming of IFN-gamma-producing CD8+ T cells by dying tumor cells fails in the absence of a functional IL-1 receptor 1 and in Nlpr3-deficient (Nlrp3(-/-)) or caspase-1-deficient (Casp-1(-/-)) mice unless exogenous IL-1beta is provided. Accordingly, anticancer chemotherapy turned out to be inefficient against tumors established in purinergic receptor P2rx7(-/-) or Nlrp3(-/-) or Casp1(-/-) hosts. Anthracycline-treated individuals with breast cancer carrying a loss-of-function allele of P2RX7 developed metastatic disease more rapidly than individuals bearing the normal allele. These results indicate that the NLRP3 inflammasome links the innate and adaptive immune responses against dying tumor cells.
1,628 citations
TL;DR: Lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD, and progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT.
Abstract: X-linked adrenoleukodystrophy (ALD) is a severe brain demyelinating disease in boys that is caused by a deficiency in ALD protein, an adenosine triphosphate–binding cassette transporter encoded by the ABCD1 gene. ALD progression can be halted by allogeneic hematopoietic cell transplantation (HCT). We initiated a gene therapy trial in two ALD patients for whom there were no matched donors. Autologous CD34 + cells were removed from the patients, genetically corrected ex vivo with a lentiviral vector encoding wild-type ABCD1 , and then re-infused into the patients after they had received myeloablative treatment. Over a span of 24 to 30 months of follow-up, we detected polyclonal reconstitution, with 9 to 14% of granulocytes, monocytes, and T and B lymphocytes expressing the ALD protein. These results strongly suggest that hematopoietic stem cells were transduced in the patients. Beginning 14 to 16 months after infusion of the genetically corrected cells, progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT. Thus, lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD.
1,378 citations
University of Louisville1, University of Pittsburgh2, Royal Brisbane and Women's Hospital3, Carolinas Medical Center4, Beaumont Hospital5, University of Cincinnati6, Seoul National University7, Iwate Medical University8, Toho University9, Kaohsiung Medical University10, University of Paris11, University of Texas MD Anderson Cancer Center12, McGill University13, University of California, Los Angeles14, Memorial Sloan Kettering Cancer Center15, Mayo Clinic16, University of Chicago17, Icahn School of Medicine at Mount Sinai18, University of Hong Kong19, Duke University20, Vanderbilt University21, Roger Williams Medical Center22, Northwestern University23, University of Duisburg-Essen24, Washington University in St. Louis25
TL;DR: Laparoscopic liver surgery is a safe and effective approach to the management of surgical liver disease in the hands of trained surgeons with experience in hepatobiliary and laparoscopic surgery, and national and international societies should become involved in the goal of establishing training standards and credentialing.
Abstract: Objective:To summarize the current world position on laparoscopic liver surgery.Summary Background Data:Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver re
TL;DR: This review focuses on current knowledge of the pathways of redox regulation, with discussion of the somewhat juxtaposed hypotheses of "oxidative damage" versus "Oxidative signaling," within the wider context of physiological function, from plant cell biology to potential applications.
Abstract: Reactive oxygen species (ROS) have multifaceted roles in the orchestration of plant gene expression and gene-product regulation. Cellular redox homeostasis is considered to be an “integrator” of information from metabolism and the environment controlling plant growth and acclimation responses, as well as cell suicide events. The different ROS forms influence gene expression in specific and sometimes antagonistic ways. Low molecular antioxidants (e.g., ascorbate, glutathione) serve not only to limit the lifetime of the ROS signals but also to participate in an extensive range of other redox signaling and regulatory functions. In contrast to the low molecular weight antioxidants, the “redox” states of components involved in photosynthesis such as plastoquinone show rapid and often transient shifts in response to changes in light and other environmental signals. Whereas both types of “redox regulation” are intimately linked through the thioredoxin, peroxiredoxin, and pyridine nucleotide pools, they ...
TL;DR: An important adaptive role for metabolism diversification within group B2 and Shigella strains is found, but few or no extraint intestinal virulence-specific genes are identified, which could render difficult the development of a vaccine against extraintestinal infections.
Abstract: The Escherichia coli species represents one of the best-studied model organisms, but also encompasses a variety of commensal and pathogenic strains that diversify by high rates of genetic change. We uniformly (re-) annotated the genomes of 20 commensal and pathogenic E. coli strains and one strain of E. fergusonii (the closest E. coli related species), including seven that we sequenced to completion. Within the approximately 18,000 families of orthologous genes, we found approximately 2,000 common to all strains. Although recombination rates are much higher than mutation rates, we show, both theoretically and using phylogenetic inference, that this does not obscure the phylogenetic signal, which places the B2 phylogenetic group and one group D strain at the basal position. Based on this phylogeny, we inferred past evolutionary events of gain and loss of genes, identifying functional classes under opposite selection pressures. We found an important adaptive role for metabolism diversification within group B2 and Shigella strains, but identified few or no extraintestinal virulence-specific genes, which could render difficult the development of a vaccine against extraintestinal infections. Genome flux in E. coli is confined to a small number of conserved positions in the chromosome, which most often are not associated with integrases or tRNA genes. Core genes flanking some of these regions show higher rates of recombination, suggesting that a gene, once acquired by a strain, spreads within the species by homologous recombination at the flanking genes. Finally, the genome's long-scale structure of recombination indicates lower recombination rates, but not higher mutation rates, at the terminus of replication. The ensuing effect of background selection and biased gene conversion may thus explain why this region is A+T-rich and shows high sequence divergence but low sequence polymorphism. Overall, despite a very high gene flow, genes co-exist in an organised genome.
Christopher Newton-Cheh1, Christopher Newton-Cheh2, Toby Johnson3, Toby Johnson4 +359 more•Institutions (64)
TL;DR: In this paper, the association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2(P = 1 × 10-23), FGF5 (P=1 × 10 -21), SH2B3(P= 3 × 10−18), MTHFR(MTHFR), c10orf107(P), ZNF652(ZNF652), PLCD3 (P,P = 5 × 10 −9),
Abstract: Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
Harvard University1, Broad Institute2, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico3, McMaster University4, McGill University5, University of Leicester6, University of Lübeck7, University of Pennsylvania8, Vanderbilt University9, University of Missouri–Kansas City10, University of Münster11, University of Verona12, Queen's University Belfast13, University of Washington14, Boston University15, University of Helsinki16, National Institute for Health and Welfare17, Lund University18, University of Cambridge19, Vita-Salute San Raffaele University20, University of Ferrara21, University of Turin22, Hebrew University of Jerusalem23, University of Girona24, University of Milan25, University of Leeds26, University of Regensburg27, Ludwig Maximilian University of Munich28, University of Kiel29, Wellcome Trust Sanger Institute30, University of Paris31, MedStar Washington Hospital Center32, deCODE genetics33, University of Iceland34
TL;DR: SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with my Cardiovascular Infarction risk.
Abstract: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls We carried out replication in an independent sample with an effective sample size of up to 19,492 SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9) We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3) We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk
TL;DR: Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes, and suggests that glucose-lowering regimens should be tailored to the individual.
Abstract: Improved glucose control in type 2 diabetes is known to reduce the risk of microvascular events. There is, however, continuing uncertainty about its impact on macrovascular disease. The aim of these analyses was to generate more precise estimates of the effects of more-intensive, compared with less-intensive, glucose control on the risk of major cardiovascular events amongst patients with type 2 diabetes. A prospectively planned group-level meta-analysis in which characteristics of trials to be included, outcomes of interest, analyses and subgroup definitions were all pre-specified. A total of 27,049 participants and 2,370 major vascular events contributed to the meta-analyses. Allocation to more-intensive, compared with less-intensive, glucose control reduced the risk of major cardiovascular events by 9% (HR 0.91, 95% CI 0.84–0.99), primarily because of a 15% reduced risk of myocardial infarction (HR 0.85, 95% CI 0.76–0.94). Mortality was not decreased, with non-significant HRs of 1.04 for all-cause mortality (95% CI 0.90–1.20) and 1.10 for cardiovascular death (95% CI 0.84–1.42). Intensively treated participants had significantly more major hypoglycaemic events (HR 2.48, 95% CI 1.91–3.21). Exploratory subgroup analyses suggested the possibility of a differential effect for major cardiovascular events in participants with and without macrovascular disease (HR 1.00, 95% CI 0.89–1.13, vs HR 0.84, 95% CI 0.74–0.94, respectively; interaction p = 0.04). Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes. The analyses suggest that glucose-lowering regimens should be tailored to the individual.
TL;DR: In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously, one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with standard therapy.
Abstract: Background In patients with chronic infection with hepatitis C virus (HCV) genotype 1, treatment with peginterferon alfa and ribavirin for 48 weeks results in rates of sustained virologic response of 40 to 50%. Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment. Methods A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were randomly assigned to receive one of four treatments involving various combinations of telaprevir (1250 mg on day 1, then 750 mg every 8 hours), peginterferon alfa-2a (180 μg weekly), and ribavirin (dose according to body weight). The T12PR24 group (81 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks, followed by peginterferon alfa-2a and ribavirin for 12 more weeks. The T12PR12 group (82 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks. The T12P12 group (78 patients) received telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks. The PR48 (control) group (82 patients) received peginterferon alfa-2a and ribavirin for 48 weeks. The primary end point, a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy), was compared between the control group and the combined T12P12 and T12PR12 groups. Results The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48% (77 of 160 patients), as compared with 46% (38 of 82) in the PR48 (control) group (P = 0.89). The rate was 60% (49 of 82 patients) in the T12PR12 group (P = 0.12 for the comparison with the PR48 group), as compared with 36% (28 of 78 patients) in the T12P12 group (P = 0.003; P = 0.20 for the comparison with the PR48 group). The rate was significantly higher in the T12PR24 group (69% [56 of 81 patients]) than in the PR48 group (P = 0.004). The adverse events with increased frequency in the telaprevir-based groups were pruritus, rash, and anemia. Conclusions In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously, one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with standard therapy. Response rates were lowest with the regimen that did not include ribavirin. (ClinicalTrials.gov number, NCT00372385.)
TL;DR: In patients with STEMI undergoing PCI, prasugrel is more effective than clopidogrel for prevention of ischaemic events, without an apparent excess in bleeding.
University of Milano-Bicocca1, University of Paris2, University of Brescia3, University of Bologna4, University of Lausanne5, Queen Mary University of London6, Ghent University7, University of Barcelona8, University of Glasgow9, Istanbul University10, Katholieke Universiteit Leuven11, Hannover Medical School12, University of Manchester13, University of Oslo14, Joseph Fourier University15, Gdańsk Medical University16, University of Copenhagen17, University of Münster18, University of Valencia19, Complutense University of Madrid20, University of Erlangen-Nuremberg21, Maastricht University22, University of Amsterdam23, University of Milan24
TL;DR: The objective of this study was to establish a baseline for the design of a systematic literature review of this type of treatment for high blood pressure using a simple, straightforward, and scalable procedure.
Abstract: Abbreviations ACE: angiotensin-converting enzyme; BP: blood pressure; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; ET: endothelin; IMT: carotid intima-media thickness; JNC: Joint National Commit
TL;DR: In this article, the authors provide a more direct test of the gender roles hypothesis by analyzing community epidemiological data collected from respondents surveyed in 15 countries as part of the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative.
Abstract: Epidemiological surveys have consistently documented significantly higher rates of anxiety and mood disorders among women than men1, 2 and significantly higher rates of externalizing and substance use disorders among men than women.3–5 Although a number of biological, psychosocial, and biopsychosocial hypotheses have been proposed to account for these patterns,6–8 evidence that gender differences in depression9, 10 and substance use11–13 have narrowed in a number of countries has led to a special interest in the “gender roles” hypothesis. The latter asserts that gender differences in the prevalence of mental disorders are due to differences in the typical stressors, coping resources, and opportunity structures for expressing psychological distress made available differentially to women and men in different countries at different points in history.14, 15 Consistent with this hypothesis, evidence of decreasing gender differences in depression and substance use has been found largely in countries where the roles of women have improved in terms of opportunities for employment, access to birth control, and other indicators of increasing gender role equality, while trend studies in countries where gender roles have been more static11, 16 or over periods of historical time when gender role changes have been small17 have failed to document a reduction in gender differences in depression or substance use.
Most research aimed at investigating the gender roles hypothesis has focused on individual-level variation in roles in a single country at a single point in time.18–20 This approach is limited in three ways. First, selection bias into roles due to pre-existing mental illness (e.g., women with agoraphobia having a higher probability than other women of becoming homemakers rather than seeking employment outside the home) confounds attempts to evaluate the causal effects of gender roles. Second, gender differences are largely confined to differences in lifetime risk, with much less evidence for gender differences in recent prevalence among lifetime cases.21 This means that investigation of the determinants of gender difference should focus on lifetime first onset rather than on the recent prevalence that has been the focus of most studies. Third, as the gender roles hypothesis is a hypothesis about the effects of social context, a rigorous test of the hypothesis requires an analysis of societal-level time-space variation rather than analysis of the individual-level variation that has been the focus of most studies.
A small number of cross-national comparative studies have examined spatial variation in gender differences in depression22 and alcohol abuse13 at a point in time or, more rarely, at two points in time.11 Although these studies raised the possibility that gender roles might be associated with variation in the magnitude of gender differences in these outcomes, they were unable to test this hypothesis due to the small number of cross-sectional country-level observations included in the analyses. The current report provides a more direct test of the gender roles hypothesis by analyzing community epidemiological data collected from respondents surveyed in 15 countries as part of the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative.21 Previous cross-national comparisons of gender differences in mental illness focused on cross-sectional differences. We, in comparison, use retrospective reports obtained in the WMH surveys about lifetime occurrence and age-of-onset of mental disorders in different birth cohorts to study time-space variation in lifetime risk. Specifically, we examine both variation across cohorts within a single country (i.e., temporal variation) and variation across countries within a single cohort (i.e., special variation) in lifetime risk of mental disorders as a function of time-space variation in the traditionality of gender roles. Lifetime risk is the focus rather than recent prevalence even though accuracy of reporting is doubtlessly better for recent episodes than lifetime occurrence in order to address the fact that gender differences in lifetime risk are much more robust than gender differences in current prevalence among lifetime cases
TL;DR: The CYP2C19*2 genetic variant is a major determinant of prognosis in young patients who are receiving clopidogrel treatment after myocardial infarction and is the only independent predictor of cardiovascular events.
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TL;DR: In this article, the authors compare the potential of different quantum repeater protocols quantitatively, with a focus on the most immediate goal of outperforming the direct transmission of photons, and compare different approaches to realize quantum repeaters.
Abstract: The distribution of quantum states over long distances is limited by photon loss. Straightforward amplification as in classical telecommunications is not an option in quantum communication because of the no-cloning theorem. This problem could be overcome by implementing quantum repeater protocols, which create long-distance entanglement from shorter-distance entanglement via entanglement swapping. Such protocols require the capacity to create entanglement in a heralded fashion, to store it in quantum memories, and to swap it. One attractive general strategy for realizing quantum repeaters is based on the use of atomic ensembles as quantum memories, in combination with linear optical techniques and photon counting to perform all required operations. Here we review the theoretical and experimental status quo of this very active field. We compare the potential of different approaches quantitatively, with a focus on the most immediate goal of outperforming the direct transmission of photons.
Columbia University1, University of Miami2, University of North Carolina at Chapel Hill3, SUNY Downstate Medical Center4, University College London5, Cambridge University Hospitals NHS Foundation Trust6, University of California, San Francisco7, University of California, Los Angeles8, University of Alabama at Birmingham9, Rio de Janeiro State University10, University of Guadalajara11, University of Düsseldorf12, New York University13, University of Barcelona14, Shanghai Jiao Tong University15, University of Lisbon16, Stellenbosch University17, Guy's and St Thomas' NHS Foundation Trust18, Oregon Health & Science University19, University of Padua20, University of Leeds21, North Shore-LIJ Health System22, Northwestern University23, Medical University of South Carolina24, University of Birmingham25, Sun Yat-sen University26, Lille University of Science and Technology27, Charité28, Rutgers University29, Federal University of São Paulo30, University of Debrecen31, Imperial College London32, Emory University33, University of Liège34, University of Pittsburgh35, University of Paris36, University of the Witwatersrand37, California State University, Long Beach38, Royal Melbourne Hospital39, University of Texas Southwestern Medical Center40, Autonomous University of Barcelona41, Pennsylvania State University42, Johns Hopkins University43, University of Szeged44, Duke University45, University of Colorado Denver46, Harvard University47, University of Cape Town48, University of Malaya49, Peking Union Medical College50
TL;DR: Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
Abstract: Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
University of Oxford1, University of Paris2, University of Barcelona3, Southend University Hospital NHS Foundation Trust4, University of Zurich5, University of Groningen6, Boston University7, Norfolk and Norwich University Hospital8, Lund University9, Food and Drug Administration10, Istanbul University11
TL;DR: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.
Abstract: Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. Methods: An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.
TL;DR: A classification for primary abdominal wall hernias and a division into subgroups for incisional abdominal wallHernias, concerning the localisation of the hernia, was formulated.
Abstract: Purpose
A classification for primary and incisional abdominal wall hernias is needed to allow comparison of publications and future studies on these hernias. It is important to know whether the populations described in different studies are comparable.
TL;DR: The aim of this paper was to detail the recommended approach to the echocardiographic evaluation of valve stenosis, including recommendations for specific measures of stenosis severity, details of data acquisition and measurement, and grading of severity.
Abstract: AR = aortic regurgitation
AS = aortic stenosis
AVA = aortic valve area
CSA = cross sectional area
CWD = continuous wave Doppler
D = diameter
HOCM = hypertrophic obstructive cardiomyopathy
LV = left ventricle
LVOT = left ventricular outflow tract
MR = mitral regurgitation
MS = mitral stenosis
MVA = mitral valve area
ΔP = pressure gradient
RV = right ventricle
RVOT = right ventricular outflow tract
SV = stroke volume
TEE = transesophageal echocardiography
T 1/2 = pressure half-time
TR = tricuspid regurgitation
TS = tricuspid stenosis
V = velocity
VSD = ventricular septal defect
VTI =velocity time integral
Valve stenosis is a common heart disorder and an important cause of cardiovascular morbidity and mortality. Echocardiography has become the key tool for the diagnosis and evaluation of valve disease, and is the primary non-invasive imaging method for valve stenosis assessment. Clinical decision-making is based on echocardiographic assessment of the severity of valve stenosis, so it is essential that standards be adopted to maintain accuracy and consistency across echocardiographic laboratories when assessing and reporting valve stenosis. The aim of this paper was to detail the recommended approach to the echocardiographic evaluation of valve stenosis, including recommendations for specific measures of stenosis severity, details of data acquisition and measurement, and grading of severity. These recommendations are based on the scientific literature and on the consensus of a panel of experts.
This document discusses a number of proposed methods for evaluation of stenosis severity. On the basis of a comprehensive literature review and expert consensus, these methods were categorized for clinical practice as:
TL;DR: In this paper, a code CIGALE (Code Investigating GALaxy Emission) that uses model spectra composed of the Maraston (or PEGASE) stellar population models, synthetic attenuation functions based on a modified Calzetti law, spectral line templates, the Dale & Helou dust emission models, and optional spectral templates of obscured AGN is presented.
Abstract: Aims. Photometric data of galaxies covering the rest-frame wavelength range from far-UV to far-IR make it possible to derive galaxy properties with a high reliability by fitting the attenuated stellar emission and the related dust emission at the same time.Methods. For this purpose we wrote the code CIGALE (Code Investigating GALaxy Emission) that uses model spectra composed of the Maraston (or PEGASE) stellar population models, synthetic attenuation functions based on a modified Calzetti law, spectral line templates, the Dale & Helou dust emission models, and optional spectral templates of obscured AGN. Depending on the input redshifts, filter fluxes were computed for the model set and compared to the galaxy photometry by carrying out a Bayesian-like analysis. CIGALE was tested by analysing 39 nearby galaxies selected from SINGS. The reliability of the different model parameters was evaluated by studying the resulting expectation values and their standard deviations in relation to the input model grid. Moreover, the influence of the filter set and the quality of photometric data on the code results was estimated.Results. For up to 17 filters with effective wavelengths between 0.15 and 160 μ m, we find robust results for the mass, star formation rate, effective age of the stellar population at 4000 A, bolometric luminosity, luminosity absorbed by dust, and attenuation in the far-UV. Details of the star formation history (excepting the burst fraction) and the shape of the attenuation curve are difficult to investigate with the available broad-band UV and optical photometric data. A study of the mutual relations between the reliable properties confirms the dependence of star formation activity on morphology in the local Universe and indicates a significant drop in this activity at about 1011 towards higher total stellar masses. The dustiest galaxies in the SINGS sample are present in the same mass range. On the other hand, the far-UV attenuation of our sample galaxies does not appear to show a significant dependence on star formation activity.Conclusions. The results for our SINGS test sample demonstrate that CIGALE can be a valuable tool for studying basic properties of galaxies in the near and distant Universe if UV-to-IR data are available.
TL;DR: In this paper, the authors present a complete overview of the instrument and platform behavior for all environmental conditions for CoRoT, and show that the performance specifications are easily satisfied when the environmental conditions are favorable.
Abstract: Context. CoRoT is a space telescope dedicated to stellar seismology and the search for extrasolar planets. The mission is led by the CNES in association with French laboratories and has a large international participation. The European Space Agency (ESA), Austria, Belgium, and Germany contribute to the payload, and Spain and Brazil contribute to the ground segment. Development of the spacecraft, which is based on a PROTEUS low earth orbit (LEO) recurrent platform, commenced in October 2000, and the satellite was launched on December 27, 2006. Aims. The instrument and platform characteristics prior to launch have been described in ESA publication (SP-1306). In the present paper we explain the behaviour in flight, based on raw and corrected data. Methods. Five runs have been completed since January 2007. The data used here are essentially those acquired during the commissioning phase and from a long run that lasted 146 days. These enable us to give a complete overview of the instrument and platform behaviour for all environmental conditions. The ground based data processing is not described in detail because the most important method has been published elsewhere. Results. We show that the performance specifications are easily satisfied when the environmental conditions are favourable. Most of the perturbations, hence data corrections, are related to LEO perturbations: high energy particles inside the South Atlantic Anomaly (SAA), eclipses and temperature variations, and line of sight fluctuations due to the attitude control system. Straylight due to the reflected light from the earth, which is controlled by the telescope and baffle design, appears to be negligible.
Charité1, Maastricht University2, Leiden University3, Ruhr University Bochum4, National Autonomous University of Mexico5, University of Córdoba (Spain)6, University of California, San Francisco7, VU University Amsterdam8, University of Paris9, University of Leeds10, University of Toronto11, University of Helsinki12, University of Alberta13, Ghent University14, Glasgow Royal Infirmary15, Katholieke Universiteit Leuven16
TL;DR: The ASAS group has developed candidate criteria for the classification of axial SpA that include patients without radiographic sacroiliitis, and the candidate criteria need to be validated in an independent international study.
Abstract: Objective: Non-radiographic axial spondyloarthritis (SpA) is characterised by a lack of definitive radiographic sacroiliitis and is considered an early stage of ankylosing spondylitis. The objective of this study was to develop candidate classification criteria for axial SpA that include patients with but also without radiographic sacroiliitis. Methods: Seventy-one patients with possible axial SpA, most of whom were lacking definite radiographic sacroiliitis, were reviewed as “paper patients” by 20 experts from the Assessment of SpondyloArthritis international Society (ASAS). Unequivocally classifiable patients were identified based on the aggregate expert opinion in conjunction with the expert-reported level of certainty of their judgement. Draft criteria for axial SpA were formulated and tested using classifiable patients. Results: Active sacroiliitis on magnetic resonance imaging (MRI) (odds ratio 45, 95% CI 5.3 to 383; p x rays in conjunction with one SpA feature or, if sacroilitiis is absent, in the presence of at least three SpA features. In a second set of candidate criteria, inflammatory back pain is obligatory in the clinical arm (sensitivity 86.1%; specificity 94.7%). Conclusion: The ASAS group has developed candidate criteria for the classification of axial SpA that include patients without radiographic sacroiliitis. The candidate criteria need to be validated in an independent international study.
TL;DR: In this article, the effects of albuminuria and reduced estimated GFR (eGFR) on the risk for cardiovascular and renal events among individuals with type 2 diabetes were investigated. But, there was no evidence of an interaction between the effect of higher eGFR and lower UACR.
Abstract: There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR >300 mg/g and eGFR <60 ml/min per 1.73 m(2) at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors. In conclusion, high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes.