MadGraph/MadEvent v4: The New Web Generation

We present the latest developments of the MadGraph/MadEvent Monte Carlo event generator and several applications to hadron collider physics. In the current version events at the parton, hadron and detector level can be generated directly from a web interface, for arbitrary processes in the Standard Model and in several physics scenarios beyond it (HEFT, MSSM, 2HDM). The most important additions are: a new framework for implementing user-defined new physics models; a standalone running mode for creating and testing matrix elements; generation of events corresponding to different processes, such as signal(s) and backgrounds, in the same run; two platforms for data analysis, where events are accessible at the parton, hadron and detector level; and the generation of inclusive multi-jet samples by combining parton-level events with parton showers. To illustrate the new capabilities of the package some applications to hadron collider physics are presented: 1) Higgs search in pp \to H \to W^+W^-: signal and backgrounds. 2) Higgs CP properties: pp \to H jj$in the HEFT. 3) Spin of a new resonance from lepton angular distributions. 4) Single-top and Higgs associated production in a generic 2HDM. 5) Comparison of strong SUSY pair production at the SPS points. 6) Inclusive W+jets matched samples: comparison with the Tevatron data.Comment: 38 pages, 15 figure

Heart disease in the Netherlands: A quantitative update

In this review we discuss cardiovascular mortality, incidence and prevalence of heart disease, and cardiac interventions and surgery in the Netherlands. We combined most recently available data from various Dutch cardiovascular registries, Dutch Hospital Data (LMR), Statistics Netherlands (CBS), and population-based cohort studies, to provide a broad quantitative update. The absolute number of people dying from cardiovascular diseases is declining and cardiovascular conditions are no longer the leading cause of death in the Netherlands. However, a substantial burden of morbidity persists with 400,000 hospitalisations for cardiovascular disease involving over 80,000 cardiac interventions annually. In the Netherlands alone, an estimated 730,000 persons are currently diagnosed with coronary heart disease, 120,000 with heart failure, and 260,000 with atrial fibrillation. These numbers emphasise the continuous need for dedicated research on prevention, diagnosis, and treatment of heart disease in our country

The consistency of the treatment effect of an ACE-inhibitor based treatment regimen in patients with vascular disease or high risk of vascular disease: A combined analysis of individual data of ADVANCE, EUROPA, and PROGRESS trials

AimsAngiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using individual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of perindopril-based regimen in patients with vascular disease or at high risk of vascular disease.Methods and resultsWe studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a perindopril-based treatment regimen or placebo. The perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89; 95 confidence interval (CI) 0.82-0.96; P = 0.006], cardiovascular mortality (HR 0.85; 95 CI 0.76-0.95; P = 0.004), non-fatal myocardial infarction (HR 0.80; 95 CI 0.71-0.90; P < 0.001), stroke (HR 0.82; 95 CI 0.74-0.92; P = 0.002), and heart failure (HR 0.84; 95 CI 0.72-0.96; P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure.ConclusionThis study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (perindopril-indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease

Individualized angiotensin-converting enzyme (ACE)-inhibitor therapy in stable coronary artery disease based on clinical and pharmacogenetic determinants: The PERindopril GENEtic (PERGENE) risk model

Background-Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model. Methods and Results-Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 t

Spallation reactions. A successful interplay between modeling and applications

The spallation reactions are a type of nuclear reaction which occur in space by interaction of the cosmic rays with interstellar bodies. The first spallation reactions induced with an accelerator took place in 1947 at the Berkeley cyclotron (University of California) with 200 MeV deuterons and 400 MeV alpha beams. They highlighted the multiple emission of neutrons and charged particles and the production of a large number of residual nuclei far different from the target nuclei. The same year R. Serber describes the reaction in two steps: a first and fast one with high-energy particle emission leading to an excited remnant nucleus, and a second one, much slower, the de-excitation of the remnant. In 2010 IAEA organized a worskhop to present the results of the most widely used spallation codes within a benchmark of spallation models. If one of the goals was to understand the deficiencies, if any, in each code, one remarkable outcome points out the overall high-quality level of some models and so the great improvements achieved since Serber. Particle transport codes can then rely on such spallation models to treat the reactions between a light particle and an atomic nucleus with energies spanning from few tens of MeV up to some GeV. An overview of the spallation reactions modeling is presented in order to point out the incomparable contribution of models based on basic physics to numerous applications where such reactions occur. Validations or benchmarks, which are necessary steps in the improvement process, are also addressed, as well as the potential future domains of development. Spallation reactions modeling is a representative case of continuous studies aiming at understanding a reaction mechanism and which end up in a powerful tool.Comment: 59 pages, 54 figures, Revie

JAK2 aberrations in childhood B-cell precursor acute lymphoblastic leukemia

JAK2 abnormalities may serve as target for precision medicines in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In the current study we performed a screening for JAK2 mutations and translocations, analyzed the clinical outcome and studied the efficacy of two JAK inhibitors in primary BCP-ALL cells. Importantly, we identify a number of limitations of JAK inhibitor therapy. JAK2 mutations mainly occurred in the poor prognostic subtypes BCR-ABL1-like and non- BCR-ABL1-like B-other (negative for sentinel cytogenetic lesions). JAK2 translocations were restricted to BCR-ABL1-like cases. Momelotinib and ruxolitinib were cytotoxic in both JAK2 translocated and JAK2 mutated cells, although efficacy in JAK2 mutated cells highly depended on cytokine receptor activation by TSLP. However, our data also suggest that the effect of JAK inhibition may be compromised by mutations in alternative survival pathways and microenvironment-induced resistance. Furthermore, inhibitors induced accumulation of phosphorylated JAK2Y1007, which resulted in a profound re-activation of JAK2 signaling upon release of the inhibitors. This preclinical evidence implies that further optimization and evaluation of JAK inhibitor treatment is necessary prior to its clinical integration in pediatric BCP-ALL

Le magmatisme de la région de Kwyjibo, Province\ud du Grenville (Canada) : intérêt pour les\ud minéralisations de type fer-oxydes associées

The granitic plutons located north of the Kwyjibo property in Quebec’s Grenville Province are of\ud Mesoproterozoic age and belong to the granitic Canatiche Complex . The rocks in these plutons are calc-alkalic, K-rich,\ud and meta- to peraluminous. They belong to the magnetite series and their trace element characteristics link them to\ud intraplate granites. They were emplaced in an anorogenic, subvolcanic environment, but they subsequently underwent\ud significant ductile deformation. The magnetite, copper, and fluorite showings on the Kwyjibo property are polyphased\ud and premetamorphic; their formation began with the emplacement of hydraulic, magnetite-bearing breccias, followed by\ud impregnations and veins of chalcopyrite, pyrite, and fluorite, and ended with a late phase of mineralization, during\ud which uraninite, rare earths, and hematite were emplaced along brittle structures. The plutons belong to two families:\ud biotite-amphibole granites and leucogranites. The biotite-amphibole granites are rich in iron and represent a potential\ud heat and metal source for the first, iron oxide phase of mineralization. The leucogranites show a primary enrichment in\ud REE (rare-earth elements), F, and U, carried mainly in Y-, U-, and REE-bearing niobotitanates. They are metamict and\ud underwent a postmagmatic alteration that remobilized the uranium and the rare earths. The leucogranites could also be\ud a source of rare earths and uranium for the latest mineralizing events

Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty

A randomised trial of 367 patients with acute myocardial infarction was performed to determine whether an invasive strategy combining thrombolysis with recombinant tissue-type plasminogen activator (rTPA), heparin, and acetylsalicylic acid, and immediate percutaneous transluminal coronary angioplasty (PTCA) would be superior to a noninvasive strategy with the same medical treatment but without immediate angiography and PTCA. Intravenous infusion of 100 mg rTPA was started within 5 h after onset of symptoms (median 156 min). Angiography was performed 6-165 min later in 180 out of 183 patients allocated to the invasive strategy; 184 patients were allocated to the non-invasive strategy. Immediate PTCA reduced the percentage stenosis of the infarc

Aging selectively dampens oscillation of lipid abundance in white and brown adipose tissue

Lipid metabolism is under the control of the circadian system and circadian dysregulation has been linked to obesity and dyslipidemia. These factors and outcomes have also been associated to, or affected by, the process of aging. Here, we investigated whether murine white (WAT) and brown (BAT) adipose tissue lipids exhibit rhythmicity and if this is affected by aging. To this end, we have measured the 24 h lipid profiles of WAT and BAT using a global lipidomics analysis of >1100 lipids. We observed rhythmicity in nearly all lipid classes including glycerolipids, glycerophospholipids, sterol lipids and sphingolipids. Overall, similar to 22% of the analyzed lipids were considered rhythmic in WAT and BAT. Despite a general accumulation of lipids upon aging the fraction of oscillating lipids decreased in both tissues to 14% and 18%, respectively. Diurnal profiles of lipids in BAT appeared to depend on the lipid acyl chain length and this specific regulation was lost in aged mice. Our study revealed how aging affects the rhythmicity of lipid metabolism and could contribute to the quest for targets that improve diurnal lipid homeostasis to maintain cardiometabolic health during aging.Diabetes mellitus: pathophysiological changes and therap