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This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Significant reductions in stratospheric ozone occur inside the polar vortices each spring when chlorine radicals produced by heterogeneous reactions on cold particle surfaces in winter destroy ozone mainly in two catalytic cycles, the ClO dimer cycle and the ClO/BrO cycle. Chlorofluorocarbons (CFCs), which are responsible for most of the chlorine currently present in the stratosphere, have been banned by the Montreal Protocol and its amendments, and the ozone layer is predicted to recover to 1980 levels within the next few decades. During the same period, however, climate change is expected to alter the temperature, circulation patterns and chemical composition in the stratosphere, and possible geo-engineering ventures to mitigate climate change may lead to additional changes. To realistically predict the response of the ozone layer to such influences requires the correct representation of all relevant processes. The European project RECONCILE has comprehensively addressed remaining questions in the context of polar ozone depletion, with the objective to quantify the rates of some of the most relevant, yet still uncertain physical and chemical processes. To this end RECONCILE used a broad approach of laboratory experiments, two field missions in the Arctic winter 2009/10 employing the high altitude research aircraft M55-Geophysica and an extensive match ozone sonde campaign, as well as microphysical and chemical transport modelling and data assimilation. Some of the main outcomes of RECONCILE are as follows: (1) vortex meteorology: the 2009/10 Arctic winter was unusually cold at stratospheric levels during the six-week period from mid-December 2009 until the end of January 2010, with reduced transport and mixing across the polar vortex edge; polar vortex stability and how it is influenced by dynamic processes in the troposphere has led to unprecedented, synoptic-scale stratospheric regions with temperatures below the frost point; in these regions stratospheric ice clouds have been observed, extending over >106km2 during more than 3 weeks. (2) Particle microphysics: heterogeneous nucleation of nitric acid trihydrate (NAT) particles in the absence of ice has been unambiguously demonstrated; conversely, the synoptic scale ice clouds also appear to nucleate heterogeneously; a variety of possible heterogeneous nuclei has been characterised by chemical analysis of the non-volatile fraction of the background aerosol; substantial formation of solid particles and denitrification via their sedimentation has been observed and model parameterizations have been improved. (3) Chemistry: strong evidence has been found for significant chlorine activation not only on polar stratospheric clouds (PSCs) but also on cold binary aerosol; laboratory experiments and field data on the ClOOCl photolysis rate and other kinetic parameters have been shown to be consistent with an adequate degree of certainty; no evidence has been found that would support the existence of yet unknown chemical mechanisms making a significant contribution to polar ozone loss. (4) Global modelling: results from process studies have been implemented in a prognostic chemistry climate model (CCM); simulations with improved parameterisations of processes relevant for polar ozone depletion are evaluated against satellite data and other long term records using data assimilation and detrended fluctuation analysis. Finally, measurements and process studies within RECONCILE were also applied to the winter 2010/11, when special meteorological conditions led to the highest chemical ozone loss ever observed in the Arctic. In addition to quantifying the 2010/11 ozone loss and to understand its causes including possible connections to climate change, its impacts were addressed, such as changes in surface ultraviolet (UV) radiation in the densely populated northern mid-latitudes.
The international research project RECONCILE has addressed central questions regarding polar ozone depletion, with the objective to quantify some of the most relevant yet still uncertain physical and chemical processes and thereby improve prognostic modelling capabilities to realistically predict the response of the ozone layer to climate change. This overview paper outlines the scope and the general approach of RECONCILE, and it provides a summary of observations and modelling in 2010 and 2011 that have generated an in many respects unprecedented dataset to study processes in the Arctic winter stratosphere. Principally, it summarises important outcomes of RECONCILE including (i) better constraints and enhanced consistency on the set of parameters governing catalytic ozone destruction cycles, (ii) a better understanding of the role of cold binary aerosols in heterogeneous chlorine activation, (iii) an improved scheme of polar stratospheric cloud (PSC) processes that includes heterogeneous nucleation of nitric acid trihydrate (NAT) and ice on non-volatile background aerosol leading to better model parameterisations with respect to denitrification, and (iv) long transient simulations with a chemistry-climate model (CCM) updated based on the results of RECONCILE that better reproduce past ozone trends in Antarctica and are deemed to produce more reliable predictions of future ozone trends. The process studies and the global simulations conducted in RECONCILE show that in the Arctic, ozone depletion uncertainties in the chemical and microphysical processes are now clearly smaller than the sensitivity to dynamic variability.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p–Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
Objective: In light of the ongoing COVID-19 pandemic and the associated hospitalization of an overwhelming number of ventilator-dependent patients, medical and/or ethical patient triage paradigms have become essential. While guidelines on the allocation of scarce resources do exist, such work within the subdisciplines of intensive care (e.g., neurocritical care) remains limited.
Methods: A 16-item questionnaire was developed that sought to explore/quantify the expert opinions of German neurointensivists with regard to triage decisions. The anonymous survey was conducted via a web-based platform and in total, 96 members of the Initiative of German Neurointensive Trial Engagement (IGNITE)-study group were contacted via e-mail. The IGNITE consortium consists of an interdisciplinary panel of specialists with expertise in neuro-critical care (i.e., anesthetists, neurologists and neurosurgeons).
Results: Fifty members of the IGNITE consortium responded to the questionnaire; in total the respondents were in charge of more than 500 Neuro ICU beds throughout Germany. Common determinants reported which affected triage decisions included known patient wishes (98%), the state of health before admission (96%), SOFA-score (85%) and patient age (69%). Interestingly, other principles of allocation, such as a treatment of “youngest first” (61%) and members of the healthcare sector (50%) were also noted. While these were the most accepted parameters affecting the triage of patients, a “first-come, first-served” principle appeared to be more accepted than a lottery for the allocation of ICU beds which contradicts much of what has been reported within the literature. The respondents also felt that at least one neurointensivist should serve on any interdisciplinary triage team.
Conclusions: The data gathered in the context of this survey reveal the estimation/perception of triage algorithms among neurointensive care specialists facing COVID-19. Further, it is apparent that German neurointensivists strongly feel that they should be involved in any triage decisions at an institutional level given the unique resources needed to treat patients within the Neuro ICU.
Given the ongoing global SARS-CoV-2-vaccination efforts, clinical awareness needs to be raised regarding the possibility of an increased incidence of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia in patients with intracerebral hemorrhage (ICH) secondary to cerebral sinus and vein thrombosis (CVT) requiring (emergency) neurosurgical treatment in the context of vaccine-induced immune thrombotic thrombocytopenia (VITT). Only recently, an association of vaccinations and cerebral sinus and vein thrombosis has been described. In a number of cases, neurosurgical treatment is warranted for these patients and special considerations are warranted when addressing the perioperative coagulation. We, herein, describe the past management of patients with VITT and established a literature-guided algorithm for the treatment of patients when addressing the impaired coagulation in these patients. Increasing insights addressing the pathophysiology of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia guide physicians in developing an interdisciplinary algorithm taking into account the special considerations of this disease.
Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new VH1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC50 = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505SOSIP.664 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.