Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Fungal systematics and evolution : FUSE 6

Fungal Systematics and Evolution (FUSE) is one of the journal series to address the “fusion” between morphological data and molecular phylogenetic data and to describe new fungal taxa and interesting observations. This paper is the 6th contribution in the FUSE series—presenting one new genus, twelve new species, twelve new country records, and three new combinations. The new genus is: Pseudozeugandromyces (Laboulbeniomycetes, Laboulbeniales). The new species are: Albatrellopsis flettioides from Pakistan, Aureoboletus garciae from Mexico, Entomophila canadense from Canada, E. frigidum from Sweden, E. porphyroleucum from Vietnam, Erythrophylloporus flammans from Vietnam, Marasmiellus boreoorientalis from Kamchatka Peninsula in the Russian Far East, Marasmiellus longistipes from Pakistan, Pseudozeugandromyces tachypori on Tachyporus pusillus (Coleoptera, Staphylinidae) from Belgium, Robillarda sohagensis from Egypt, Trechispora hondurensis from Honduras, and Tricholoma kenanii from Turkey. The new records are: Arthrorhynchus eucampsipodae on Eucampsipoda africanum (Diptera, Nycteribiidae) from Rwanda and South Africa, and on Nycteribia vexata (Diptera, Nycteribiidae) from Bulgaria; A. nycteribiae on Eucampsipoda africanum from South Africa, on Penicillidia conspicua (Diptera, Nycteribiidae) from Bulgaria (the first undoubtful country record), and on Penicillidia pachymela from Tanzania; Calvatia lilacina from Pakistan; Entoloma shangdongense from Pakistan; Erysiphe quercicola on Ziziphus jujuba (Rosales, Rhamnaceae) and E. urticae on Urtica dioica (Rosales, Urticaceae) from Pakistan; Fanniomyces ceratophorus on Fannia canicularis (Diptera, Faniidae) from the Netherlands; Marasmiellus biformis and M. subnuda from Pakistan; Morchella anatolica from Turkey; Ophiocordyceps ditmarii on Vespula vulgaris (Hymenoptera, Vespidae) from Austria; and Parvacoccum pini on Pinus cembra (Pinales, Pinaceae) from Austria. The new combinations are: Appendiculina gregaria, A. scaptomyzae, and Marasmiellus rodhallii. Analysis of an LSU dataset of Arthrorhynchus including isolates of A. eucampsipodae from Eucampsipoda africanum and Nycteribia spp. hosts, revealed that this taxon is a complex of multiple species segregated by host genus. Analysis of an SSU–LSU dataset of Laboulbeniomycetes sequences revealed support for the recognition of four monophyletic genera within Stigmatomyces sensu lato: Appendiculina, Fanniomyces, Gloeandromyces, and Stigmatomyces sensu stricto. Finally, phylogenetic analyses of Rhytismataceae based on ITS–LSU ribosomal DNA resulted in a close relationship of Parvacoccum pini with Coccomyces strobi.http://www.sydowia.at/index.htmpm2021Medical Virolog

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades

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

Mobile Communication & Accessibility for Blind Users

Abstract-Throughout the world, legislations accessibility guidelines have been adopted. However, the technical solutions that have been proposed mainly focus to provide support when users access the Web applications through desktop interfaces. Recent technological evolutions in mobile devices can provide a number of interesting and fruitful opportunities for disabled people in order to improve the quality of their life and social interactions. We need to identify solutions for disabled users when they are on the move and they want to carry out important social activities (such as visiting museums). For these reasons we believe that emerging mobile technologies should introduce represent new opportunities for all, especially for users with special needs. In this regard, research should better investigate on how mobile devices, such as PDAs or smart phones, can be used to aid in daily life of blind users. To better understand the accessibility issues experienced by users of current mobile devices, we will engage in qualitative observations and interviews with mobile device users having disabilities. Our analysis will explore the types of mobile devices currently used by people with disabilities, common accessibility issues that these people encounter, and adaptation strategies that they use to overcome accessibility issues. We are also considering focus groups and diary studies to cover additional mobile accessibility corners. We will analyze a framework of accessible interaction techniques that can be used to increase the accessibility of mainstream mobile devices. This framework will be designed by qualitative investigation and participatory design for mobile device users having disabilities, and will be implemented as user-installable software for current and future mobile devices

An experimental multi-instrumental approach to understand the size effect on the damage propagation of plain-woven CFRP composites under shear loading

Damage propagation and failure mechanisms in woven carbon fiber composites are complex due to their anisotropic nature and are affected by the percentage of constituents of the composite materials named fiber, matrix, and void. The “size effect” that relies on these parameters can be influenced by the volume fraction percentages of these constituents and composite manufacturing parameters. This research introduces a multi-instrumental structural health monitoring approach to understand damage progression due to the size effect under the Iosipescu configuration. Acoustic emission (AE) signals are classified via a K-means clustering algorithm to distinguish the damage activities based on their frequencies. It is shown that both size effect and void content are relatable based on cumulative AE energy jumps attributed to the accumulation of micro-damages inside these laminates. The thermal variations observed by passive infrared thermography are associated with the nonlinear response of the shear behavior. The outcomes of the thermal analysis are depicted to show the relationship between damage progress and laminate thickness. The digital image correlation analysis is performed to measure the full-field strain measurement during the testing. The correspondence of material thickness with elastic shear behavior is investigated via a comparison of shear strain maps

Geochemistry and Petrogenesis of the Wadhrai Granite Stock of the Malani Igneous Suite in Nagar Parkar Area, SE Pakistan

The Wadhrai granite stock is a part of the Nagar Parkar Igneous Complex, an extension of the Neoproterozoic Malani Igneous Suite of western Rajasthan. It is occupied by a petrographically uniform granite comprising perthite, plagioclase, quartz, with small quantities of biotite, opaque oxides, titanite, and secondary minerals. The rocks are sparingly porphyritic and contain dykes of microgranite, aplite, and rare pegmatite. In the south-central part, parallel sheets and swarms of mafic dykes, and in the western part very fine-grained felsic sheets intrude the body. The granite is metaluminous to peraluminous and characterized by high silica (73–76 wt%), and alkalis (7–9 wt%), and low CaO (0.15–1.4 wt%), MgO (0.15–0.38 wt%), Th (7–12 ppm), and U (1–2 ppm). On geochemical discriminant diagrams, it classifies mostly as A-type (with rather high Y/Nb (8.6 to 2.4, average 5.2) and low Nb/Ga and Ce (typical of A2-type), but sparingly as I-type. Chondrite-normalized patterns show enrichment in LREE over HREE, and small negative Eu anomalies, whereas mantle-normalized spidergrams display higher LILE over HFSE, distinct troughs for Nb, Sr, P, Ti, and spikes for La, Ce, Nd, Sm and Tb. The granite magma was possibly derived from a tonalite-granodiorite-dominated crustal source. Based on the above-mentioned geochemical evidence, it is interpreted that the source rocks of the magma of the Wadhrai granite likely developed initially in a continental margin subduction setting and underwent partial melting in a continental extensional environment