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The production of prompt Î+c baryons has been measured at midrapidity in the transverse momentum interval 0<pT<1 GeV/c for the first time, in pp and p-Pb collisions at a centre-of-mass energy per nucleon-nucleon collision sNNââââ=5.02 TeV. The measurement was performed in the decay channel Î+câpK0S by applying new decay reconstruction techniques using a Kalman-Filter vertexing algorithm and adopting a machine-learning approach for the candidate selection. The pT-integrated Î+c production cross sections in both collision systems were determined and used along with the measured yields in Pb-Pb collisions to compute the pT-integrated nuclear modification factors RpPb and RAA of Î+c baryons, which are compared to model calculations that consider nuclear modification of the parton distribution functions. The Î+c/D0 baryon-to-meson yield ratio is reported for pp and p-Pb collisions. Comparisons with models that include modified hadronisation processes are presented, and the implications of the results on the understanding of charm hadronisation in hadronic collisions are discussed. A significant (3.7Ï) modification of the mean transverse momentum of Î+c baryons is seen in p-Pb collisions with respect to pp collisions, while the pT-integrated Î+c/D0 yield ratio was found to be consistent between the two collision systems within the uncertainties.
The production of prompt Î+c baryons has been measured at midrapidity in the transverse momentum interval 0<pT<1 GeV/c for the first time, in pp and p-Pb collisions at a centre-of-mass energy per nucleon-nucleon collision sNNââââ=5.02 TeV. The measurement was performed in the decay channel Î+câpK0S by applying new decay reconstruction techniques using a Kalman-Filter vertexing algorithm and adopting a machine-learning approach for the candidate selection. The pT-integrated Î+c production cross sections in both collision systems were determined and used along with the measured yields in Pb-Pb collisions to compute the pT-integrated nuclear modification factors RpPb and RAA of Î+c baryons, which are compared to model calculations that consider nuclear modification of the parton distribution functions. The Î+c/D0 baryon-to-meson yield ratio is reported for pp and p-Pb collisions. Comparisons with models that include modified hadronisation processes are presented, and the implications of the results on the understanding of charm hadronisation in hadronic collisions are discussed. A significant (3.7Ï) modification of the mean transverse momentum of Î+c baryons is seen in p-Pb collisions with respect to pp collisions, while the pT-integrated Î+c/D0 yield ratio was found to be consistent between the two collision systems within the uncertainties.
Background: Biological psychiatry aims to understand mental disorders in terms of altered neurobiological pathways. However, for one of the most prevalent and disabling mental disorders, Major Depressive Disorder (MDD), patients only marginally differ from healthy individuals on the group-level. Whether Precision Psychiatry can solve this discrepancy and provide specific, reliable biomarkers remains unclear as current Machine Learning (ML) studies suffer from shortcomings pertaining to methods and data, which lead to substantial over-as well as underestimation of true model accuracy.
Methods: Addressing these issues, we quantify classification accuracy on a single-subject level in N=1,801 patients with MDD and healthy controls employing an extensive multivariate approach across a comprehensive range of neuroimaging modalities in a well-curated cohort, including structural and functional Magnetic Resonance Imaging, Diffusion Tensor Imaging as well as a polygenic risk score for depression.
Findings Training and testing a total of 2.4 million ML models, we find accuracies for diagnostic classification between 48.1% and 62.0%. Multimodal data integration of all neuroimaging modalities does not improve model performance. Similarly, training ML models on individuals stratified based on age, sex, or remission status does not lead to better classification. Even under simulated conditions of perfect reliability, performance does not substantially improve. Importantly, model error analysis identifies symptom severity as one potential target for MDD subgroup identification.
Interpretation: Although multivariate neuroimaging markers increase predictive power compared to univariate analyses, single-subject classification â even under conditions of extensive, best-practice Machine Learning optimization in a large, harmonized sample of patients diagnosed using state-of-the-art clinical assessments â does not reach clinically relevant performance. Based on this evidence, we sketch a course of action for Precision Psychiatry and future MDD biomarker research.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1â90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63â80 Hz) in occipital regions and upregulated low frequency (5â28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt(s_NN)=130 GeV using the STAR TPC at RHIC. The elliptic flow signal, v_2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software StataÂź and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1â25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0â88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%âsubcutaneous; 29%âintravenous; 1%âunknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
Using the notion of a root datum of a reductive group G we propose a tropical analogue of a principal G-bundle on a metric graph. We focus on the case G=GLn, i.e. the case of vector bundles. Here we give a characterization of vector bundles in terms of multidivisors and use this description to prove analogues of the Weil--Riemann--Roch theorem and the Narasimhan--Seshadri correspondence. We proceed by studying the process of tropicalization. In particular, we show that the non-Archimedean skeleton of the moduli space of semistable vector bundles on a Tate curve is isomorphic to a certain component of the moduli space of semistable tropical vector bundles on its dual metric graph.
Improved risk stratification in prevention by use of a panel of selected circulating microRNAs
(2017)
Risk stratification is crucial in prevention. Circulating microRNAs have been proposed as biomarkers in cardiovascular disease. Here a miR panel consisting of miRs related to different cardiovascular pathophysiologies, was evaluated to predict outcome in the context of prevention. MiR-34a, miR-223, miR-378, miR-499 and miR-133 were determined from peripheral blood by qPCR and combined to a risk panel. As derivation cohort, 178 individuals of the DETECT study, and as validation cohort, 129 individuals of the SHIP study were used in a case-control approach. Overall mortality and cardiovascular events were outcome measures. The Framingham Risk Score(FRS) and the SCORE system were applied as risk classification systems. The identified miR panel was significantly associated with mortality given by a hazard ratio(HR) of 3.0 (95% (CI): 1.09â8.43; pâ=â0.034) and of 2.9 (95% CI: 1.32â6.33; pâ=â0.008) after adjusting for the FRS in the derivation cohort. In a validation cohort the miR-panel had a HR of 1.31 (95% CI: 1.03â1.66; pâ=â0.03) and of 1.29 (95% CI: 1.02â1.64; pâ=â0.03) in a FRS/SCORE adjusted-model. A FRS/SCORE risk model was significantly improved to predict mortality by the miR panel with continuous net reclassification index of 0.42/0.49 (pâ=â0.014/0.005). The present miR panel of 5 circulating miRs is able to improve risk stratification in prevention with respect to mortality beyond the FRS or SCORE.