Psychological counselling interventions to improve perceived quality of life and counter anxiety and depression in pulmonary-arterial-hypertension patients. a clinical trial

Introduction: Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease, frequently associated with a worsening of perceived quality of life as well as anxiety and depression symptomatology. Psychological counselling helps the patient understand the diagnosis and prevent the onset of psychopathologies. This study evaluates the effect of counselling sessions on anxiety and depression as well as the impact on self-reported quality of life in patients with PAH. Methods: Patients with a diagnosis of PAH were recruited at the Monaldi Hospital (Naples). An EQ-5D 3L questionnaire was administered to all patients at baseline (pre-session), three months (post-session) after the last session to patients who received psychological counselling (experimental group, EG) and after the first questionnaire to patients who did not (control group, CG). The EQ-5D index and EQ-VAS score were analysed in both groups. Results: A sample of 50 patients with a PAH diagnosis was evaluated; among them 6% had mild PAH, 66% moderate PAH, and 28% severe PAH. The majority (53%) did not receive psychological counselling. All patients showed no significant difference in EQ-5D index (P > 0.05), EQ-VAS score (P > 0.05), and the anxiety/depression dimension (P>.05) at baseline. However, between pre- and post-session evaluations, the analysis showed a significant change in the EQ-VAS score (P = 0.00) and the anxiety/depression dimension (P = 0.02) in the EG. In the CG, there was a similar change in the anxiety/depression dimension (P = 0.00) but not in the EQ-VAS score (P = 0.05) in CG. The z-test revealed significant intergroup relations, showing that the EG had a 37% increase in perceived quality of life and a 9% reduction in anxiety and depression, while a 12% reduction was observed for the CG’s perceived quality of life and a 44% increase in anxiety and depression. Discussion and Conclusions: This study showed that patients with PAH who received psychological support improved their health-related quality of life by reducing anxiety and depression symptomatology. Our findings highlight the impact of psychological support in the treatment of patients with PAH

The Impact of Crystal Light Yield Non-Proportionality on a Typical Calorimetric Space Experiment: Beam Test Measurements and Monte Carlo Simulations

Calorimetric space experiments were employed for the direct measurements of cosmic-ray spectra above the TeV region. According to several theoretical models and recent measurements, relevant features in both electron and nucleus fluxes are expected. Unfortunately, sizable disagreements among the current results of different space calorimeters exist. In order to improve the accuracy of future experiments, it is fundamental to understand the reasons of these discrepancies, especially since they are not compatible with the quoted experimental errors. A few articles of different collaborations suggest that a systematic error of a few percentage points related to the energy-scale calibration could explain these differences. In this work, we analyze the impact of the nonproportionality of the light yield of scintillating crystals on the energy scale of typical calorimeters. Space calorimeters are usually calibrated by employing minimal ionizing particles (MIPs), e.g., nonshowering proton or helium nuclei, which feature different ionization density distributions with respect to particles included in showers. By using the experimental data obtained by the CaloCube collaboration and a minimalist model of the light yield as a function of the ionization density, several scintillating crystals (BGO, CsI(Tl), LYSO, YAP, YAG and BaF2) are characterized. Then, the response of a few crystals is implemented inside the Monte Carlo simulation of a space calorimeter to check the energy deposited by electromagnetic and hadronic showers. The results of this work show that the energy scale obtained by MIP calibration could be affected by sizable systematic errors if the nonproportionality of scintillation light is not properly taken into account

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

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

Coupling environmental transition and social prosperity: a scenario-analysis of the Italian case

This paper investigates the social and structural conditions grounding the feasibility of green growth policies. It takes the proposal of a Green New Deal as a reference and assesses i) whether green investments and innovation will be able to ensure the promised social prosperity and ii) what kind of social policies are able to compensate for the risk of increasing inequality. For this purpose, we develop a dynamic macrosimulation model of the Italian economy which explores the social and structural effects of the Italian integrated policy plan for energy and climate. We find that green growth alone will not result in better societal conditions and needs to be compensated with social policies to reduce inequality. Hence, we select two social policies, namely a basic income programme and a working time reduction policy, that are expected to deliver similar results in terms of redistribution and compare their environmental outcomes in terms of CO2 emissions. Our scenario analysis shows that working time reduction leads to an increase in employment and a parallel decrease in aggregate demand that cause both a reduction in emissions and inequality. On the other hand, the basic income programme reduces inequality by sustaining aggregate demand, which in turn reduces the positive environmental effects of the energy plan