DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Designing user-interface of an ERP System-sales and distribution module considering usability guidelines

It is known that ERP systems are hard to implement and difficult to use for first time users. Two leading ERP systems were evaluated namely, Microsoft Dynamics Navision and SAP Business One. The good points in terms of interface design of the two ERP systems will be incorporated to a new system together with some usability guidelines. A usability test was conducted using Morae software to record the test. Test subjects identified were employees who were exposed to manual sales process but have not used any ERP system. The quality level of the current systems (SAP and NAV) in terms of task times, task completion, error rate and satisfaction were computed to help determine the issues. It si found out that most test subjects had a hard time doing the first and last task as the quality levels across the four metrics is low for the current systems. Computing for the Single usability metric of the current systems, NAV scored 1.36 while SAP scored 1.45. After the testing, the most dominant issues in the interface were the tab pane design, placement of objects and labelling. Together with the literatures, a conceptual framework was constructed that will evaluate Accessibility, Navigability, Visibility and L:anguage using usability metrics task times, task completion, error rate and satisfaction. After evaluating the usability of each system, a Single Usability Metric (SUM) was computed for the ease of assessment. Statistica was the software used in computing for the Principal Component Analysis which will produce the weights needed for SUM. In the creation of two new alternative designs, the issues found in the interface of the usability testing were not considered while the good points were integrated. Considering the design alternative, I, an increase in quality level in the first and last task is evident. The quality level in the first task of design alternative I in terms of task time increased from 11% to 65%. In the last task, the quality level increased from 7% to 50%. Considering the quality level of the design The quality levels across the different metrics in design alternative 2 further increased as compared to the current systems and design alternative 1. The SUM of the design alternative 2 is 1.60

Processes controlling silicon isotopic fractionation in a forested tropical watershed : Mule hole critical zone observatory (Southern India)

International audienceAssessing the dynamics of the silica cycle in the critical zone remains challenging, particularly within the soil, where multiple processes are involved. To improve our understanding of this cycle in the Tropics, and more specifically the role played by vegetation, we combined elemental Si mass balance with the 30 Si signatures of the compartments involved in the water-plant-rock interactions of a tropical forested watershed, Mule Hole (Southern India). To accomplish this, we analysed (1) the 30 Si values of present-day litter phytoliths from tree leaves and grass, as well as soil amorphous silica (ASi); (2) the Si isotope fractionation induced by phytolith dissolution; (3) the silicon mass balance inferred from isotopes at the soil-plant scale; and (4) the consistency between water sources and the 30 Si signatures in the ephemeral stream. The 30 Si values of present-day litter phytoliths and soil ASi vary within a narrow range of 1.10 to 1.40 ‰ for all samples, but two deep vertisol samples which likely trapped phytoliths from different vegetation growing under more humid conditions, as indicated by pollen analysis. A homogeneous signature of litter is a minimum condition for using 30 Si as a 2 proxy for the litter/phytolith source of Si. However, litter-ash dissolution experiments demonstrate that the incipient dissolution of phytoliths fractionates Si isotopes, with the preferential dissolution of 28 Si over 30 Si yielding 30 Si values as low as-1.41 ‰. Values close to the whole-sample signatures, i.e., above 1 ‰, were recovered in the solution after a few hours of water-ash interaction. At the soil-plant scale, the average 30 Si value of soil-infiltrating solutions is slightly lighter than the average phytolith signature, which suggests phytoliths as the source of soil dissolved Si. The isotopic budget of dissolved Si within the soil layer, which was obtained based on previous elemental fluxes, is imbalanced. Equilibrating the isotopic budget would imply that up to 4100 mol ha-1 yr-1 of silica is taken up by vegetation, which is almost twice as large as that initially estimated from the elemental budget. The additional Si flux taken up, and likely stored in woody stems, was estimated assuming that Si isotopes followed a steady-state model for the whole Si plant uptake and then followed a Rayleigh model once in the plants. The 30 Si value of the additional Si flux taken up should be close to 0 ‰, i.e., enriched in light Si isotopes compared to the litter. If steady-state conditions apply, the source could correspond to soil ASi dissolution or deep (saprolite) root uptake. At the outlet of the watershed, the stream exhibits low 30 Si values (0.28 to 0.71 ‰) during peak flows and high 30 Si values (1.29 to 1.61 ‰) during the recessions at the end of the rainy season. Heavy 30 Si signatures are consistent with the expected domination of seepage at the end of floods. The light 30 Si values during peak flow are slightly lower than the overland flow signature and reflect either a sampling bias of overland flow or a minor but significant contribution of another Si source within the stream, possibly the partial dissolution of phytoliths from the suspended load, with slight isotopic fractionation. This study confirms that vegetation controls the silicon cycle in this dry tropical forest. It also shows that silicon isotopes yield a better grasp of the mass balance and sources and potential mechanisms involved than the consideration of only silicon concentrations. However, this proxy still relies on working hypotheses, notably steady-state and/or Rayleigh fractionation models, which need to be confirmed in further studies

Recurrent Intragenic Duplication within the <b><i>NR5A1</i></b> Gene and Severe Proximal Hypospadias

International audienceA heterozygous intragenic duplication within the repeated area (CTGCAGCTG)×2 of the NR5A1 gene was found in a 15-year-old 46,XY DSD (disorders/differences of sex development) patient with micropenis and severe proximal hypospadias. This heterozygous duplication has already been described twice in boys with a similar phenotype, whereas a deletion of 3 amino acids at the same position in the protein SF-1 has been described in a 46,XX patient with primary ovarian failure and short stature. These data suggest that this region within the NR5A1 gene has an important role for SF-1 protein function in gonads and is a hotspot for intragenic rearrangements

Carbon dioxide emissions from the flat bottom and shallow Nam Theun 2 Reservoir: drawdown area as a neglected pathway to the atmosphere

International audienceFreshwater reservoirs are a significant source of CO2 to the atmosphere. CO2 is known to be emitted at the reservoir surface by diffusion at the air-water interface and downstream of dams or powerhouses by degassing and along the river course. In this study, we quantified total CO2 emissions from the Nam Theun 2 Reservoir (Lao PDR) in the Mekong River watershed. The study started in May 2009, less than a year after flooding and just a few months after the maximum level was first reached and lasted until the end of 2013. We tested the hypothesis that soils from the drawdown area would be a significant contributor to the total CO2 emissions. Total inorganic carbon, dissolved and particulate organic carbon and CO2 concentrations were measured in 4 pristine rivers of the Nam Theun watershed, at 9 stations in the reservoir (vertical profiles) and at 16 stations downstream of the monomictic reservoir on a weekly to monthly basis. CO2 bubbling was estimated during five field campaigns between 2009 and 2011 and on a weekly monitoring, covering water depths ranging from 0.4 to 16 m and various types of flooded ecosystems in 2012 and 2013. Three field campaigns in 2010, 2011 and 2013 were dedicated to the soils description in 21 plots and the quantification of soil CO2 emissions from the drawdown area. On this basis, we calculated total CO2 emissions from the reservoir and carbon inputs from the tributaries. We confirm the importance of the flooded stock of organic matter as a source of carbon (C) fuelling emissions. We show that the drawdown area contributes, depending on the year, from 40 to 75 % of total annual gross emissions in this flat and shallow reservoir. Since the CO2 emissions from the drawdown zone are almost constant throughout the years, the large interannual variations result from the significant decrease in diffusive fluxes and downstream emissions between 2010 and 2013. This overlooked pathway in terms of gross emissions would require an in-depth evaluation for the soil organic matter and vegetation dynamics to evaluate the actual contribution of this area in terms of net modification of gas exchange in the footprint of the reservoir, and how it could evolve in the future