Particle Acceleration in Cosmic Sites - Astrophysics Issues in our Understanding of Cosmic Rays

Laboratory experiments to explore plasma conditions and stimulated particle acceleration can illuminate aspects of the cosmic particle acceleration process. Here we discuss the cosmic-ray candidate source object variety, and what has been learned about their particle-acceleration characteristics. We identify open issues as discussed among astrophysicists. -- The cosmic ray differential intensity spectrum is a rather smooth power-law spectrum, with two kinks at the "knee" (~10^15 eV) and at the "ankle" (~3 10^18 eV). It is unclear if these kinks are related to boundaries between different dominating sources, or rather related to characteristics of cosmic-ray propagation. We believe that Galactic sources dominate up to 10^17 eV or even above, and the extragalactic origin of cosmic rays at highest energies merges rather smoothly with Galactic contributions throughout the 10^15--10^18 eV range. Pulsars and supernova remnants are among the prime candidates for Galactic cosmic-ray production, while nuclei of active galaxies are considered best candidates to produce ultrahigh-energy cosmic rays of extragalactic origin. Acceleration processes are related to shocks from violent ejections of matter from energetic sources such as supernova explosions or matter accretion onto black holes. Details of such acceleration are difficult, as relativistic particles modify the structure of the shock, and simple approximations or perturbation calculations are unsatisfactory. This is where laboratory plasma experiments are expected to contribute, to enlighten the non-linear processes which occur under such conditions.Comment: accepted for publication in EPJD, topical issue on Fundamental physics and ultra-high laser fields. From review talk at "Extreme Light Infrastructure" workshop, Sep 2008. Version-2 May 2009: adjust some wordings and references at EPJD proofs stag

Rehabilitation and outcomes after complicated vs uncomplicated mild TBI:results from the CENTER-TBI study

Background: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. Methods: Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale – Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury – Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. Results: Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL. Conclusions: Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach. Trial registration: ClinicalTrials.gov NCT02210221.</p

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease