Cryogenic carbon cycling at an Icelandic glacier

Glaciers and ice caps are recognised as an important component of the global carbon cycle. Carbon within glacial systems exists in organic and inorganic forms, across supraglacial, englacial and subglacial realms. It is often difficult to detach cryospheric carbon cycling from hydrology, with the transfer of carbon between glacial inventories relying upon meltwater flows. Classical glacial hydrology consists of distributed drainage delivering delayed flow meltwaters, throughout the accumulation season, superseded by quick flow, aerated channelized drainage during increased ablation. It is upon this template that most existing studies have addressed the dynamics of carbon within glaciated catchments. However, Icelandic glacial systems provide an opportunity to investigate the role of subglacial volcanism in driving carbon dynamics. Hydrochemical properties of Sόlheimajökull bulk meltwaters indicate untraditional redox conditions, with discharge of reduced, anoxic meltwaters in Summer, when expansion of subglacial drainage intersects the Katla geothermal zone. This unique hydrological regime generates profound effects upon the solute flux from the glacier, particularly with regard to the carbon budget. Dissolved inorganic carbon dynamics are dominated by weathering of basaltic bedrocks and accessory hydrothermal calcites, fuelled by subglacial geothermal proton supply. Widespread basal anoxia during summer facilitates methanogenesis resulting in large quantities of methane being discharged from beneath the glacier (flux range between 9,179 to 22,551 tonnes per year). Evidence suggests subglacial microbial acetoclastic methanogenesis is responsible with δ13C and δD CH4 values of ~60‰ and -320‰ respectively, supported by laboratory identification of methanogenesis in Sόlheimajökull subglacial sediments. The organic counterpart to the carbon cycle is invoked to serve as the energy source for microbial metabolism. Such direct measurements of subglacial methane have rarely been achieved at contemporary ice margins. This study therefore provides an exciting opportunity to identify methane sources and carbon cycling in areas subjected to subglacial volcanism and to consider these within the broader context of global carbon dynamics

Direct isotopic evidence of biogenic methane production and efflux from beneath a temperate glacier

The base of glaciers and ice sheets provide environments suitable for the production of methane. High pressure conditions beneath the impermeable ‘cap’ of overlying ice promote entrapment of methane reserves that can be released to the atmosphere during ice thinning and meltwater evacuation. However, contemporary glaciers and ice sheets are rarely accounted for as methane contributors through field measurements. Here, we present direct field-based evidence of methane production and release from beneath the Icelandic glacier Sólheimajökull, where geothermal activity creates sub-oxic conditions suited to methane production and preservation along the meltwater flow path. Methane production at the glacier bed (48 tonnes per day, or 39 mM CH4 m-2 day-1), and evasion to the atmosphere from the proglacial stream (41 tonnes per day, or 32 M CH4 m-2 day-1) indicates considerable production and release to the atmosphere during the summer melt season. Isotopic signatures (-60.2 ‰ to -7.6 ‰ for δ13CCH4 and -324.3 ‰ to +161.1 ‰ for DCH4), support a biogenic signature within waters emerging from the subglacial environment. Temperate glacial methane production and release may thus be a significant and hitherto unresolved contributor of a potent greenhouse gas to the atmosphere

Readmissions after general surgery: a prospective multicenter audit

Background: Readmission rates after surgical procedures are viewed as a marker of quality of care and as a driver to improve outcomes in the United Kingdom, they are not remunerated. However, readmissions are not wholly avoidable. The aim of this study was to develop a regional overview of readmissions to determine the proportion that might be avoidable and to examine predictors of readmissions at a unit level. Methods: We undertook a prospective multicenter audit of readmissions following National Health Service funded general surgical procedures in five National Health Service hospitals and three independent sector providers over a 2-wk period. Basic demographic and procedure data were captured. Readmissions to hospitals were identified through acute admissions lists. Reason for readmission was identified, and the readmission data assessed by a senior surgical doctor as to whether it was avoidable. Results: We identified 752 operations in the study period with all followed up to 30 d. The overall rate of readmissions was 4.7%, with 40% of these judged as being potentially avoidable. Pain and wound problems accounted for the vast majority of avoidable readmissions. The number of unavoidable readmissions was correlated with the workload of each center (r ¼ 0.63, P ¼ 0.06) and as with the higher (British United Provident Association) complexity of surgery (r ¼ 0.90, P ¼ 0.01). Patient and demographic factors were not associated with readmissions. Conclusions: This prospective audit describes readmission rates after general surgery. Volume and complexity of work are associated with readmission rates. A large proportion of readmissions could be reduced by attention to analgesia and outpatient arrangements for wound management

Community-powered urban stream restoration: A vision for sustainable and resilient urban ecosystems

Urban streams can provide amenities to people living in cities, but those benefits are reduced when streams become degraded, potentially even causing harm (disease, toxic compounds, etc.). Governments and institutions invest resources to improve the values and services provided by urban streams; however, the conception, development, and implementation of such projects may not include meaningful involvement of community members and other stakeholders. Consequently, project objectives may be misaligned with community desires and needs, and projects may fail to achieve their goals. In February 2020, the 5(th) Symposium on Urbanization and Stream Ecology, an interdisciplinary meeting held every 3 to 5 y, met in Austin, Texas, USA, to explore new approaches to urban stream projects, including ways to maximize the full range of potential benefits by better integrating community members into project identification and decision making. The symposium included in-depth discussion about 4 nearby field case studies, participation of multidisciplinary urban stream experts from 5 continents, and input from the Austin community. Institutional barriers to community inclusion were identified and analyzed using real-world examples, both from the case studies and from the literature, which clarified disparities in power, equity, and values. Outcomes of the symposium have been aggregated into a vision that challenges the present institutional approach to urban stream management and a set of strategies to systematically address these barriers to improve restoration solutions. Integrating community members and other stakeholders throughout the urban restoration process, and a transparent decision-making process to resolve divergent objectives, can help identify appropriate goals for realizing both the ecological and social benefits of stream restoration

Community-powered urban stream restoration: A vision for sustainable and resilient urban ecosystems

Este artículo contiene 16 páginas, 2 tablas, 3 figuras.Urban streams can provide amenities to people living in cities, but those benefits are reduced when streams become degraded, potentially even causing harm (disease, toxic compounds, etc.). Governments and institutions invest resources to improve the values and services provided by urban streams; however, the conception, development, and implementation of such projects may not include meaningful involvement of community members and other stakeholders. Consequently, project objectives may be misaligned with community desires and needs, and projects may fail to achieve their goals. In February 2020, the 5th Symposium on Urbanization and Stream Ecology, an interdisciplinary meeting held every 3 to 5 y, met in Austin, Texas, USA, to explore new approaches to urban stream projects, including ways to maximize the full range of potential benefits by better integrating community members into project identification and decision making. The symposium included in-depth discussion about 4 nearby field case studies, participation of multidisciplinary urban stream experts from 5 continents, and input from the Austin community. Institutional barriers to community inclusion were identified and analyzed using real-world examples, both from the case studies and from the literature, which clarified disparities in power, equity, and values. Outcomes of the symposium have been aggregated into a vision that challenges the present institutional approach to urban stream management and a set of strategies to systematically address these barriers to improve restoration solutions. Integrating community members and other stakeholders throughout the urban restoration process, and a transparent decision-making process to resolve divergent objectives, can help identify appropriate goals for realizing both the ecological and social benefits of stream restoration.Publication costs were covered by an award from the Society of Freshwater Science’s Endowed Publication Fund (https:// freshwater-science.org/publications/endowed-publication-fund).Peer reviewe

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

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

Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

Background: Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades. Methods: Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings: In 2019, 369 061 deaths (of which 214 337 [58%] were transport related) and 31·1 million DALYs (of which 16·2 million [52%] were transport related) among adolescents aged 10–24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34·4% (from 17·5 to 11·5 per 100 000) for transport injuries, and by 47·7% (from 15·9 to 8·3 per 100 000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80·5% to 42 774 for transport injuries and by 39·4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010–19, the rate per 100 000 of transport injury DALYs was reduced by 16·7%, from 838 in 2010 to 699 in 2019. This was a substantially slower pace of reduction compared with the 48·5% reduction between 1990 and 2010, from 1626 per 100 000 in 1990 to 838 per 100 000 in 2010. Between 2010 and 2019, the rate of unintentional injury DALYs per 100 000 also remained largely unchanged in high-SDI countries (555 in 2010 vs 554 in 2019; 0·2% reduction). The number and rate of adolescent deaths and DALYs owing to environmental heat and cold exposure increased for the high-SDI quintile during 2010–19. Interpretation: As other causes of mortality are addressed, inadequate progress in reducing transport and unintentional injury mortality as a proportion of adolescent deaths becomes apparent. The relative shift in the burden of injury from high-SDI countries to low and low–middle-SDI countries necessitates focused action, including global donor, government, and industry investment in injury prevention. The persisting burden of DALYs related to transport and unintentional injuries indicates a need to prioritise innovative measures for the primary prevention of adolescent injury. Funding: Bill & Melinda Gates Foundation

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant