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A bstract We consider the probability for a colour-singlet pair to emit a gluon, in strongly and smoothly ordered antenna showers. We expand to second order in α s and compare to the second-order QCD matrix elements for Z → 3 jets, neglecting terms suppressed by . We give a prescription that corrects the shower to the matrix-element result at this order for both soft and hard emissions, thereby explicitly reducing its dependence on evolution- and renormalization-scale choices. We confirm that the choice of p ⊥ for both of these scales absorbs all logarithms through , and contrast this with various alternatives. We include these corrections in the vincia shower generator and study the impact on LEP event-shape and fragmentation observables. An uncertainty estimate is provided for each event, in the form of a vector of alternative weights.

A bstract We survey the expected polarization of the top produced in the decay of a scalar top quark, . The phenomenology is quite interesting, since the expected polarization depends both on the mixing in the stop and neutralino sectors and on the mass differences between the stop and the neutralino. We find that a mixed stop behaves almost like a right-handed stop due to the larger hypercharge that enters the stop/top/gaugino coupling and that these polarisation effects disappear, when . After a discussion on the expected top polarization from the decay of a scalar top quark, we focus on the interplay of polarization and kinematics at the LHC. We discuss different probes of the top polarization in terms of lab-frame observables. We find that these observables faithfully reflect the polarization of the parent top-quark, but also have a non-trivial dependence on the kinematics of the stop production and decay process. In addition, we illustrate the effect of top polarization on the energy and transverse momentum of the decay lepton in the laboratory frame. Our results show that both spectra are softened substantially in case of a negatively polarized top, particularly for a large mass difference between the stop and the neutralino. Thus, the search strategies, and the conclusions that can be drawn from them, depends not just on the mass difference due to the usual kinematic effects but also on the effects of top polarization on the decay kinematics the extent of which depends in turn on the said mass difference.

A bstract The polarisation of top quarks produced in high energy processes can be a very sensitive probe of physics beyond the Standard Model. The kinematical distributions of the decay products of the top quark can provide clean information on the polarisation of the produced top and thus can probe new physics effects in the top quark sector. We study some of the recently proposed polarisation observables involving the decay products of the top quark in the context of H − t and W t production. We show that the effect of the top polarisation on the decay lepton azimuthal angle distribution, studied recently for these processes at leading order in QCD, is robust with respect to the inclusion of next-to-leading order and parton shower corrections. We also consider the leptonic polar angle, as well as recently proposed energy-related distributions of the top decay products. We construct asymmetry parameters from these observables, which can be used to distinguish the new physics signal from the W t background and discriminate between different values of tan β and m H  − in a general type II two-Higgs doublet model. Finally, we show that similar observables may be useful in separating a Standard Model W t signal from the much larger QCD induced top pair production background.

We consider the probability for a colour-singlet qqbar pair to emit a gluon, in strongly and smoothly ordered antenna showers. We expand to second order in alphaS and compare to the second-order QCD matrix elements for Z -> 3 jets, neglecting terms suppressed by 1/NC^2. We give a prescription that corrects the shower to the matrix-element result at this order for both soft and hard emissions, thereby explicitly reducing its dependence on evolution- and renormalization-scale choices. We confirm that the choice of pT for both of these scales absorbs all logarithms through order alphaS^2, and contrast this with various alternatives. We include these corrections in the VINCIA shower generator and study the impact on LEP event-shape and fragmentation observables. An uncertainty estimate is provided for each event, in the form of a vector of alternative weights.

We survey the expected polarization of the top produced in the decay of a scalar top quark, \\(\\tilde t \\rightarrow {\\tilde t}\\chi_i^0, i =1-2\\). The phenomenology is quite interesting, since the expected polarization depends both on the mixing in the stop and neutralino sectors and on the mass differences between the stop and the neutralino. We find that a mixed stop behaves almost like a right-handed stop due to the larger hypercharge that enters the stop/top/gaugino coupling and that these polarisation effects disappear, when \\(m_{\\tilde t_1} \\approx m_t+m_{\\tilde\\chi^0_i}\\). After a discussion on the expected top polarization from the decay of a scalar top quark, we focus on the interplay of polarization and kinematics at the LHC. We discuss different probes of the top polarization in terms of lab-frame observables. We find that these observables faithfully reflect the polarization of the parent top-quark, but also have a non-trivial dependence on the kinematics of the stop production and decay process. In addition, we illustrate the effect of top polarization on the energy and transverse momentum of the decay lepton in the laboratory frame. Our results show that both spectra are softened substantially in case of a negatively polarized top, particularly for a large mass difference between the stop and the neutralino. Thus, the search strategies, and the conclusions that can be drawn from them, depends not just on the mass difference \\(m_{\\tilde t} - m_{\\tilde\\chi_{i}^{0}}\\) due to the usual kinematic effects but also on the effects of top polarization on the decay kinematics the extent of which depends in turn on the said mass difference.

We summarise a recent study looking at top quark polarisation effects in charged Higgs boson production. Lab frame angular and energy observables relating to leptonic decays of top quarks are analysed, and corresponding asymmetry parameters obtained. These are shown to be sensitive to top polarisation and robust with respect to higher order corrections. Thus, they are an efficient probe of charged Higgs parameter space.

Primary Sjögren's syndrome (pSS) is a systemic auto-immune disease typified by dryness of the mouth and eyes. A majority of patients with pSS have a type-I interferon (IFN)-signature, which is defined as the increased expression of IFN-induced genes in circulating immune cells and is associated with increased disease activity. As plasmacytoid dendritic cells (pDC) are the premier type-I IFN-producing cells and are present at the site of inflammation, they are thought to play a significant role in pSS pathogenesis. Considering the lack of data on pDC regulation and function in pSS patients, we here provided the first in-depth molecular characterization of pSS pDCs. In addition, a group of patients with non-Sjögren's sicca (nSS) was included; these poorly studied patients suffer from complaints similar to pSS patients, but are not diagnosed with Sjögren's syndrome. We isolated circulating pDCs from two independent cohorts of patients and controls (each = 31) and performed RNA-sequencing, after which data-driven networks and modular analysis were used to identify robustly reproducible transcriptional \"signatures\" of differential and co-expressed genes. Four signatures were identified, including an IFN-induced gene signature and a ribosomal protein gene-signature, that indicated pDC activation. Comparison with a dataset of activated pDCs showed that pSS pDCs have higher expression of many genes also upregulated upon pDC activation. Corroborating this transcriptional profile, pSS pDCs produced higher levels of pro-inflammatory cytokines, including type-I IFN, upon stimulation with endosomal Toll-like receptor ligands. In this setting, cytokine production was associated with expression of hub-genes from the IFN-induced and ribosomal protein gene-signatures, indicating that the transcriptional profile of pSS pDCs underlies their enhanced cytokine production. In all transcriptional analyses, nSS patients formed an intermediate group in which some patients were molecularly similar to pSS patients. Furthermore, we used the identified transcriptional signatures to develop a discriminative classifier for molecular stratification of patients with sicca. Altogether, our data provide in-depth characterization of the aberrant regulation of pDCs from patients with nSS and pSS and substantiate their perceived role in the immunopathology of pSS, supporting studies that target pDCs, type-I IFNs, or IFN-signaling in pSS.

IntroductionPsoriatic arthritis (PsA) is a chronic, inflammatory, musculoskeletal disease that affects up to 30% of patients with psoriasis. Current challenges in clinical care and research include personalised treatment, understanding the divergence of therapy response and unravelling the multifactorial pathophysiology of this complex disease. Moreover, there is an urgent clinical need to predict, assess and understand the cellular and molecular pathways underlying the response to disease-modifying antirheumatic drugs (DMARDs). The TOFA-PREDICT clinical trial addresses this need. Our primary objective is to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in PsA.Methods and analysisIn this investigator-initiated, phase III, multicentre, open-label, four-arm randomised controlled trial, we plan to integrate clinical, molecular and imaging parameters of 160 patients with PsA. DMARD-naïve patients are randomised to methotrexate or tofacitinib. Additionally, patients who are non-responsive to conventional synthetic (cs)DMARDs continue their current csDMARD and are randomised to etanercept or tofacitinib. This results in four arms each with 40 patients. Patients are followed for 1 year. Treatment response is defined as minimal disease activity at week 16. Clinical data, biosamples and images are collected at baseline, 4 weeks and 16 weeks; at treatment failure (treatment switch) and 52 weeks. For the first 80 patients, we will use a systems medicine approach to assess multiomics biomarkers and develop a prediction model for treatment response. Subsequently, data from the second 80 patients will be used for validation.Ethics and disseminationThe study was approved by the Medical Research Ethics Committee in Utrecht, Netherlands, is registered in the European Clinical Trials Database and is carried out in accordance with the Declaration of Helsinki. The study’s progress is monitored by Julius Clinical, a science-driven contract research organisation.Trial registration numberEudraCT: 2017-003900-28.

We present the activities of the \"New Physics\" working group for the \"Physics at TeV Colliders\" workshop (Les Houches, France, 30 May-17 June, 2011). Our report includes new agreements on formats for interfaces between computational tools, new tool developments, important signatures for searches at the LHC, recommendations for presentation of LHC search results, as well as additional phenomenological studies.

The use of Extracorporeal Membrane Oxygenation (ECMO) remains associated with high rates of complications, weaning failure and mortality which can be partly explained by a knowledge gap on how to properly manage patients on ECMO support. To address relevant patient management issues, we designed a “Randomized Embedded Multifactorial Adaptive Platform (REMAP)” in the setting of ECMO (REMAP ECMO) and a first embedded randomized controlled trial (RCT) investigating the effects of routine early left ventricular (LV) unloading through intra-aortic balloon pumping (IABP). REMAP ECMO describes a registry-based platform allowing for the embedding of multiple response adaptive RCTs (trial domains) which can perpetually address the effect of relevant patient management issues on ECMO weaning success. A first trial domain studies the effects of LV unloading by means of an IABP as an adjunct to veno-arterial (V-A) ECMO versus V-A ECMO alone on ECMO weaning success at 30 days in adult cardiogenic shock patients admitted to the Intensive Care Unit (ICU). The primary outcome of this trial is “successful weaning from ECMO” being defined as a composite of survival without the need for mechanical circulatory support, heart transplantation, or left ventricular assist device (LVAD) at 30 days after initiation of ECMO. Secondary outcomes include the need for interventional escalation of LV unloading strategy, mechanistic endpoints, survival characteristics until 1 year after ECMO initiation, and quality of life. Trial data will be analysed using a Bayesian statistical framework. The adaptive design allows for a high degree of flexibility, such as response adaptive randomization and early stopping of the trial for efficacy or futility. The REMAP ECMO LV unloading study is approved by the Medical Ethical Committee of the Erasmus Medical Center and is publicly registered. This REMAP ECMO trial platform enables the efficient roll-out of multiple RCTs on relevant patient management issues. A first embedded trial domain will compare routine LV unloading by means of an IABP as an adjunct to V-A ECMO versus V-A ECMO alone. ClinicalTrials.gov, NCT05913622