Development of a GEM-TPC prototype

The use of GEM foils for the amplification stage of a TPC instead of a con- ventional MWPC allows one to bypass the necessity of gating, as the backdrift is suppressed thanks to the asymmetric field configuration. This way, a novel continuously running TPC, which represents one option for the PANDA central tracker, can be realized. A medium sized prototype with a diameter of 300 mm and a length of 600 mm will be tested inside the FOPI spectrometer at GSI using a carbon or lithium beam at intermediate energies (E = 1-3AGeV). This detector test under realistic experimental conditions should allow us to verify the spatial resolution for single tracks and the reconstruction capability for displaced vertexes. A series of physics measurement implying pion beams is scheduled with the FOPI spectrometer together with the GEM-TPC as well.Comment: 5 pages, 4 figures, Proceedings for 11th ICATTP conference in como (italy

Development and validation of a prognostic model for the early identification of COVID-19 patients at risk of developing common long COVID symptoms

Background: The coronavirus disease 2019 (COVID-19) pandemic demands reliable prognostic models for estimating the risk of long COVID. We developed and validated a prediction model to estimate the probability of known common long COVID symptoms at least 60 days after acute COVID-19. Methods: The prognostic model was built based on data from a multicentre prospective Swiss cohort study. Included were adult patients diagnosed with COVID-19 between February and December 2020 and treated as outpatients, at ward or intensive/intermediate care unit. Perceived long-term health impairments, including reduced exercise tolerance/reduced resilience, shortness of breath and/or tiredness (REST), were assessed after a follow-up time between 60 and 425 days. The data set was split into a derivation and a geographical validation cohort. Predictors were selected out of twelve candidate predictors based on three methods, namely the augmented backward elimination (ABE) method, the adaptive best-subset selection (ABESS) method and model-based recursive partitioning (MBRP) approach. Model performance was assessed with the scaled Brier score, concordance c statistic and calibration plot. The final prognostic model was determined based on best model performance. Results: In total, 2799 patients were included in the analysis, of which 1588 patients were in the derivation cohort and 1211 patients in the validation cohort. The REST prevalence was similar between the cohorts with 21.6% (n = 343) in the derivation cohort and 22.1% (n = 268) in the validation cohort. The same predictors were selected with the ABE and ABESS approach. The final prognostic model was based on the ABE and ABESS selected predictors. The corresponding scaled Brier score in the validation cohort was 18.74%, model discrimination was 0.78 (95% CI: 0.75 to 0.81), calibration slope was 0.92 (95% CI: 0.78 to 1.06) and calibration intercept was -0.06 (95% CI: -0.22 to 0.09). Conclusion: The proposed model was validated to identify COVID-19-infected patients at high risk for REST symptoms. Before implementing the prognostic model in daily clinical practice, the conduct of an impact study is recommended. Keywords: Clinical prediction model; Long COVID; Prognostic factors; Stratified medicin

The Added Value of Large-Eddy and Storm-Resolving Models for Simulating Clouds and Precipitation

More than one hundred days were simulated over very large domains with fine (0.156 km to 2.5 km) grid spacing for realistic conditions to test the hypothesis that storm (kilometer) and large-eddy (hectometer) resolving simulations would provide an improved representation of clouds and precipitation in atmospheric simulations. At scales that resolve convective storms (storm-resolving for short), the vertical velocity variance becomes resolved and a better physical basis is achieved for representing clouds and precipitation. Similarly to past studies we found an improved representation of precipitation at kilometer scales, as compared to models with parameterized convection. The main precipitation features (location, diurnal cycle and spatial propagation) are well captured already at kilometer scales, and refining resolution to hectometer scales does not substantially change the simulations in these respects. It does, however, lead to a reduction in the precipitation on the time-scales considered – most notably over the ocean in the tropics. Changes in the distribution of precipitation, with less frequent extremes are also found in simulations incorporating hectometer scales. Hectometer scales appear to be more important for the representation of clouds, and make it possible to capture many important aspects of the cloud field, from the vertical distribution of cloud cover, to the distribution of cloud sizes, and to the diel (daily) cycle. Qualitative improvements, particularly in the ability to differentiate cumulus from stratiform clouds, are seen when one reduces the grid spacing from kilometer to hectometer scales. At the hectometer scale new challenges arise, but the similarity of observed and simulated scales, and the more direct connection between the circulation and the unconstrained degrees of freedom make these challenges less daunting. This quality, combined with already improved simulation as compared to more parameterized models, underpins our conviction that the use and further development of storm-resolving models offers exciting opportunities for advancing understanding of climate and climate change

Don’t Forget about the Children – Latent Food Insecurity in Rural Cambodia

Despite encouraging developments in overall undernourishment figures our analysis of rural Cambodian households reveals very high malnutrition in children. In this paper we use a novel panel data set from Stung Treng in Cambodia which allows to compare different household food security indicators with each other and individual level anthropometric data of children under five. While the large majority of households appear to be food secure according to the Food Consumption Score (FCS) and the Household Hunger Scale (HHS), the Household Food Insecurity Access Scale (HFIAS) and the Coping Strategies Index (CSI) classify less than four percent of the households in Stung Treng as food secure. Stunting and underweight measures for children show that between 38 to 45 percent of children under five are classified as undernourished. Analyzing the influence of household characteristics on these different measures for food security we find that the FCS is largely driven by household characteristics and livelihood strategy choices whereas the anthropometrics show little or zero correlation. Household wealth, inequality, and the prevalence of shocks however, has a strong influence on both measures. Individual and mother specific characteristics are vital to explain child malnutrition

Targeting prohibitins at the cell surface prevents Th17-mediated autoimmunity.

T helper (Th)17 cells represent a unique subset of CD4(+) T cells and are vital for clearance of extracellular pathogens including bacteria and fungi. However, Th17 cells are also involved in orchestrating autoimmunity. By employing quantitative surface proteomics, we found that the evolutionarily conserved prohibitins (PHB1/2) are highly expressed on the surface of both murine and human Th17 cells. Increased expression of PHBs at the cell surface contributed to enhanced CRAF/MAPK activation in Th17 cells. Targeting surface-expressed PHBs on Th17 cells with ligands such as Vi polysaccharide (Typhim vaccine) inhibited CRAF-MAPK pathway, reduced interleukin (IL)-17 expression and ameliorated disease pathology with an increase in FOXP3(+)-expressing Tregs in an animal model for multiple sclerosis (MS). Interestingly, we detected a CD4(+) T cell population with high PHB1 surface expression in blood samples from MS patients in comparison with age- and sex-matched healthy subjects. Our observations suggest a pivotal role for the PHB-CRAF-MAPK signalling axis in regulating the polarization and pathogenicity of Th17 cells and unveil druggable targets in autoimmune disorders such as MS

Targeting prohibitins at the cell surface prevents Th17‐mediated autoimmunity

T helper (Th)17 cells represent a unique subset of CD4+ T cells and are vital for clearance of extracellular pathogens including bacteria and fungi. However, Th17 cells are also involved in orchestrating autoimmunity. By employing quantitative surface proteomics, we found that the evolutionarily conserved prohibitins (PHB1/2) are highly expressed on the surface of both murine and human Th17 cells. Increased expression of PHBs at the cell surface contributed to enhanced CRAF/MAPK activation in Th17 cells. Targeting surface‐expressed PHBs on Th17 cells with ligands such as Vi polysaccharide (Typhim vaccine) inhibited CRAF‐MAPK pathway, reduced interleukin (IL)‐17 expression and ameliorated disease pathology with an increase in FOXP3+‐expressing Tregs in an animal model for multiple sclerosis (MS). Interestingly, we detected a CD4+ T cell population with high PHB1 surface expression in blood samples from MS patients in comparison with age‐ and sex‐matched healthy subjects. Our observations suggest a pivotal role for the PHB‐CRAF‐MAPK signalling axis in regulating the polarization and pathogenicity of Th17 cells and unveil druggable targets in autoimmune disorders such as MS

Human neurons carrying FMR1 unmethylated full mutations require large CGG repeat expansions for silencing and display neurodegenerative features

In Fragile X Syndrome (FXS), unmethylated full mutation (UFM) individuals carry a CGG expansion greater than 200 repeats in the FMR1 gene but lack the disease causing DNA methylation mediated silencing. Here, we show that hypomethylation of the FMR1 promoter is maintained in induced pluripotent stem cells (iPSCs) derived from two UFM individuals. However, we identify a subset of iPSC clones with large CGG expansions that silence FMR1. Furthermore, we demonstrate that de-novo silencing occurs upon expansion of CGG repeats. The silencing status of FMR1 is stable during neuronal differentiation. This indicates that UFM stem cells do not undergo developmental silencing as described for FXS. We also show that the expression of large unmethylated CGG repeats has direct phenotypic consequences resulting in neurodegenerative features. Our data suggest that UFM individuals do not lack the ability to silence FMR1 but require a higher CGG repeat size than the one described for FXS patients

The Added Value of Large-Eddy and Storm-Resolving Models for Simulating Clouds and Precipitation

More than one hundred days were simulated over very large domains with fine (0.156 km to 2.5 km) grid spacing for realistic conditions to test the hypothesis that storm (kilometer) and large-eddy (hectometer) resolving simulations would provide an improved representation of clouds and precipitation in atmospheric simulations. At scales that resolve convective storms (storm-resolving for short), the vertical velocity variance becomes resolved and a better physical basis is achieved for representing clouds and precipitation. Similarly to past studies we found an improved representation of precipitation at kilometer scales, as compared to models with parameterized convection. The main precipitation features (location, diurnal cycle and spatial propagation) are well captured already at kilometer scales, and refining resolution to hectometer scales does not substantially change the simu-lations in these respects. It does, however, lead to a reduction in the precipitation on the time-scales considered – most notably over the ocean in the tropics. Changes in the distribution of precipitation, with less frequent extremes are also found in simulations incorporating hectometer scales. Hectometer scales appear to be more important for the representation of clouds, and make it possible to capture many important aspects of the cloud field, from the vertical distribution of cloud cover, to the distribution of cloud sizes, and to the diel (daily) cycle. Qualitative improvements, particularly in the ability to differentiate cumulus from stratiform clouds, are seen when one reduces the grid spacing from kilometer to hectometer scales. At the hectometer scale new challenges arise, but the similarity of observed and simulated scales, and the more direct connection between the circula-tion and the unconstrained degrees of freedom make these challenges less daunting. This quality, combined with already improved simulation as compared to more parameterized models, underpins our conviction that the use and further development of storm-resolving models offers exciting opportunities for advancing understanding of climate and climate change

Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

Background Women are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Aim We assessed the impact of sex and gender on PASC in a Swiss population. Method Our multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030). Conclusion Specific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident