ORCID Profile
0000-0003-3531-0298
Current Organisations
University of Oxford
,
Infectious Diseases Data Observatory
,
British Antarctic Survey
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Publisher: Copernicus GmbH
Date: 11-2017
DOI: 10.5194/GMD-2017-268
Abstract: Abstract. An increasing number of Southern Ocean models now include Antarctic ice shelf cavities, and simulate thermodynamics at the ice-shelf/ocean interface. This adds another level of complexity to Southern Ocean simulations, as ice shelves interact directly with the ocean and indirectly with sea ice. Here we present the first published model intercomparison and evaluation of present-day ocean/sea-ice/ice-shelf interactions, as simulated by two models: a circumpolar Antarctic configuration of MetROMS (ROMS: Regional Ocean Modelling System coupled to CICE: Community Ice CodE) and the global model FESOM (Finite Element Sea-ice/ice-shelf Ocean Model), where the latter is run at two different levels of horizontal resolution. From a circumpolar Antarctic perspective, we compare and evaluate simulated ice shelf basal melting and sub-ice shelf circulation, as well as sea ice properties and Southern Ocean water mass characteristics as they influence the sub-ice shelf processes. Despite their differing numerical methods, the two models produce broadly similar results, and share similar biases in many cases. Both models reproduce many key features of observations, but struggle to reproduce others, such as the high melt rates observed in the small warm-cavity ice shelves of the Amundsen and Bellingshausen Seas. Several differences in model design show a particular influence on the simulations. For ex le, FESOM's greater topographic smoothing can alter the geometry of some ice shelf cavities enough to affect their melt rates this improves at higher resolution, since less smoothing is required. In the interior Southern Ocean, the vertical coordinate system affects the degree of water mass erosion due to spurious diapycnal mixing, with MetROMS' terrain-following coordinates leading to more erosion than FESOM's z-coordinates. Finally, increased horizontal resolution in FESOM leads to higher basal melt rates for small ice shelves, through a combination of stronger circulation and small-scale intrusions of warm water from offshore.
Publisher: Springer Science and Business Media LLC
Date: 13-09-2022
DOI: 10.1186/S13054-022-04155-1
Abstract: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI] 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI] 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI] 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI] 1.27 [1.25–1.30]). In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study therefore, no health care interventions were applied to participants, and trial registration is not applicable.
Publisher: Elsevier BV
Date: 12-2021
Publisher: F1000 Research Ltd
Date: 25-01-2022
DOI: 10.12688/WELLCOMEOPENRES.17284.1
Abstract: Background: Many available medicines have been evaluated as potential repurposed treatments for coronavirus disease 2019 (COVID-19). We summarise the registered study landscape for 32 priority pharmacological treatments identified following consultation with external experts of the COVID-19 Clinical Research Coalition. Methods: All eligible trial registry records identified by systematic searches of the World Health Organisation International Clinical Trials Registry Platform as of 26 th May 2021 were reviewed and extracted. A descriptive summary of study characteristics was performed. Results: We identified 1,314 registered studies that included at least one of the 32 priority pharmacological interventions. The majority (1,043, 79%) were randomised controlled trials (RCTs). The s le size of the RCTs identified was typically small (median (25 th , 75 th percentile) s le size = 140 patients (70, 383)), i.e. in idually powered only to show very large effects. The most extensively evaluated medicine was hydroxychloroquine (418 registered studies). Other widely studied interventions were convalescent plasma (n=208), ritonavir (n=189) usually combined with lopinavir (n=181), and azithromycin (n=147). Very few RCTs planned to recruit participants in low-income countries (n=14 1.3%). A minority of studies (348, 26%) indicated a willingness to share in idual participant data. The living systematic review data are available at iddo.cognitive.city Conclusions: There are many registered studies planning to evaluate available medicines as potential repurposed treatments of COVID-19. Most of these planned studies are small, and therefore substantially underpowered for most relevant endpoints. Very few are large enough to have any chance of providing enough convincing evidence to change policies and practices. The sharing of in idual participant data (IPD) from these studies would allow pooled IPD meta-analyses which could generate definitive conclusions, but most registered studies did not indicate that they were willing to share their data.
Publisher: Copernicus GmbH
Date: 22-12-2022
Abstract: Abstract. Ocean-driven ice loss from the West Antarctic Ice Sheet is a significant contributor to sea-level rise. Recent ocean variability in the Amundsen Sea is controlled by near-surface winds. We combine palaeoclimate reconstructions and climate model simulations to understand past and future influences on Amundsen Sea winds from anthropogenic forcing and internal climate variability. The reconstructions show strong historical wind trends. External forcing from greenhouse gases and stratospheric ozone depletion drove zonally uniform westerly wind trends centred over the deep Southern Ocean. Internally generated trends resemble a South Pacific Rossby wave train and were highly influential over the Amundsen Sea continental shelf. There was strong interannual and interdecadal variability over the Amundsen Sea, with periods of anticyclonic wind anomalies in the 1940s and 1990s, when rapid ice-sheet loss was initiated. Similar anticyclonic anomalies probably occurred prior to the 20th century but without causing the present ice loss. This suggests that ice loss may have been triggered naturally in the 1940s but failed to recover subsequently due to the increasing importance of anthropogenic forcing from greenhouse gases (since the 1960s) and ozone depletion (since the 1980s). Future projections also feature strong wind trends. Emissions mitigation influences wind trends over the deep Southern Ocean but has less influence on winds over the Amundsen Sea shelf, where internal variability creates a large and irreducible uncertainty. This suggests that strong emissions mitigation is needed to minimise ice loss this century but that the uncontrollable future influence of internal climate variability could be equally important.
Publisher: American Meteorological Society
Date: 24-07-2019
Abstract: Open-ocean polynyas in the Weddell Sea of Antarctica are the product of deep convection, which transports Warm Deep Water (WDW) to the surface and melts sea ice or prevents its formation. These polynyas occur only rarely in the observational record but are a near-permanent feature of many climate and ocean simulations. A question not previously considered is the degree to which the Weddell polynya affects the nearby Filchner–Ronne Ice Shelf (FRIS) cavity. Here we assess these effects using regional ocean model simulations of the Weddell Sea and FRIS, where deep convection is imposed with varying area, location, and duration. In these simulations, the idealized Weddell polynyas consistently cause an increase in WDW transport onto the continental shelf as a result of density changes above the shelf break. This leads to saltier, denser source waters for the FRIS cavity, which then experiences stronger circulation and increased ice shelf basal melting. It takes approximately 14 years for melt rates to return to normal after the deep convection ceases. Weddell polynyas similar to those seen in observations have a modest impact on FRIS melt rates, which is within the range of simulated interannual variability. However, polynyas that are larger or closer to the shelf break, such as those seen in many ocean models, trigger a stronger response. These results suggest that ocean models with excessive Weddell Sea convection may not be suitable boundary conditions for regional models of the Antarctic continental shelf and ice shelf cavities.
Publisher: Cold Spring Harbor Laboratory
Date: 21-03-2022
DOI: 10.1101/2022.03.18.22272601
Abstract: Acute kidney injury (AKI) is one of the most common and significant problems in patients with COVID-19. However, little is known about the incidence and impact of AKI occurring in the community or early in the hospital admission. The traditional KDIGO definition can fail to identify patients for whom hospitalization coincides with recovery of AKI as manifested by a decrease in serum creatinine (sCr). We hypothesized that an extended KDIGO definition, adapted from the International Society of Nephrology 0by25 studies, would identify more cases of AKI in patients with COVID-19 and that these may correspond to community-acquired AKI with similarly poor outcomes as previously reported in this population. All in iduals in the ISARIC cohort admitted to hospital with SARS-CoV-2 infection from February 15 th , 2020, to February 1 st , 2021, were included in the study. Data was collected and analysed for the duration of a patient’s admission. Incidence, staging and timing of AKI were evaluated using a traditional and extended KDIGO (eKDIGO) definition which incorporated a commensurate decrease in serum creatinine. Patients within eKDIGO diagnosed with AKI by a decrease in sCr were labelled as deKDIGO. Clinical characteristic and outcomes – intensive care unit (ICU) admission, invasive mechanical ventilation and in-hospital death - were compared for all three groups of patients. The relationship between eKDIGO AKI and in-hospital death was assessed using survival curves and logistic regression, adjusting for disease severity and AKI susceptibility. 75,670 patients from 54 countries were included in the final analysis cohort. Median length of admission was 12 days (IQR 7, 20). There were twice as many patients with AKI identified by eKDIGO than KDIGO (31.7 vs 16.8%). Those in the eKDIGO group had a greater proportion of stage 1 AKI (58% vs 36% in KDIGO patients). Peak AKI occurred early in the admission more frequently among eKDIGO than KDIGO patients. Compared to those without AKI, patients in the eKDIGO group had worse renal function on admission, more in-hospital complications, higher rates of ICU admission (54% vs 23%) invasive ventilation (45% vs 15%) and increased mortality (38% vs 19%). Patients in the eKDIGO group had a higher risk of in-hospital death than those without AKI (adjusted OR: 1.78, 95% confidence interval: 1.71-1.8, p-value 0.001). Mortality and rate of ICU admission were lower among deKDIGO than KDIGO patients (25% vs 50% death and 35% vs 70% ICU admission) but significantly higher when compared to patients with no AKI (25% vs 19% death and 35% vs 23% ICU admission) (all p values 5×10 −5 ). Limitations include ad hoc sCr s ling, exclusion of patients with less than two sCr measurements, and limited availability of sCr measurements prior to initiation of acute dialysis. The use of an extended KDIGO definition to diagnose AKI in this population resulted in a significantly higher incidence rate compared to traditional KDIGO criteria. These additional cases of AKI appear to be occurring in the community or early in the hospital admission and are associated with worse outcomes than those without AKI. Previous studies have shown that acute kidney injury (AKI) is a common problem among hospitalized patients with COVID-19. The current biochemical criteria used to diagnose AKI may be insufficient to capture AKI that develops in the community and is recovering by the time a patient presents to hospital. The use of an extended definition, that can identify AKI both during its development and recovery phase, may allow us to identify more patients with AKI. These patients may benefit from early management strategies to improve long term outcomes. In this study, we examined AKI incidence, severity and outcomes among a large international cohort of patients with COVID-19 using both a traditional and extended definition of AKI. We found that using the extended definition identified almost twice as many cases of AKI than the traditional definition (31.7 vs 16.8%). These additional cases of AKI were generally less severe and occurred earlier in the hospital admission. Nevertheless, they were associated with worse outcomes, including ICU admission and in-hospital death (adjusted odds ratio: 1.78, 95% confidence interval: 1.71-1.8, p-value 0.001) than those with no AKI. The current definition of AKI fails to identify a large group of patients with AKI that appears to develop in the community or early in the hospital admission. Given the finding that these cases of AKI are associated with worse admission outcomes than those without AKI, identifying and managing them in a timely manner is enormously important.
Publisher: American Meteorological Society
Date: 06-08-2013
DOI: 10.1175/JCLI-D-12-00584.1
Abstract: This paper summarizes the results of an intercomparison project with Earth System Models of Intermediate Complexity (EMICs) undertaken in support of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5). The focus is on long-term climate projections designed to 1) quantify the climate change commitment of different radiative forcing trajectories and 2) explore the extent to which climate change is reversible on human time scales. All commitment simulations follow the four representative concentration pathways (RCPs) and their extensions to year 2300. Most EMICs simulate substantial surface air temperature and thermosteric sea level rise commitment following stabilization of the atmospheric composition at year-2300 levels. The meridional overturning circulation (MOC) is weakened temporarily and recovers to near-preindustrial values in most models for RCPs 2.6–6.0. The MOC weakening is more persistent for RCP8.5. Elimination of anthropogenic CO2 emissions after 2300 results in slowly decreasing atmospheric CO2 concentrations. At year 3000 atmospheric CO2 is still at more than half its year-2300 level in all EMICs for RCPs 4.5–8.5. Surface air temperature remains constant or decreases slightly and thermosteric sea level rise continues for centuries after elimination of CO2 emissions in all EMICs. Restoration of atmospheric CO2 from RCP to preindustrial levels over 100–1000 years requires large artificial removal of CO2 from the atmosphere and does not result in the simultaneous return to preindustrial climate conditions, as surface air temperature and sea level response exhibit a substantial time lag relative to atmospheric CO2.
Publisher: BMJ
Date: 10-2022
DOI: 10.1136/BMJPO-2022-001657
Abstract: The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries. The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria. A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)). Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities.
Publisher: American Geophysical Union (AGU)
Date: 07-03-2022
DOI: 10.1029/2021GL094566
Abstract: Rapid ice loss is occurring in the Amundsen Sea sector of the West Antarctic Ice Sheet. This ice loss is assumed to be a long‐term response to oceanographic forcing, but ocean conditions in the Amundsen Sea are unknown prior to 1994. Here we present a modeling study of Amundsen Sea conditions from 1920 to 2013, using an ensemble of ice‐ocean simulations forced by climate model experiments. We find that during the early twentieth century, the Amundsen Sea likely experienced more sustained cool periods than at present. Warm periods become more dominant over the simulations (mean trend 0.33°C/century) causing an increase in ice shelf melting. The warming is likely driven by an eastward wind trend over the continental shelf break that is partly anthropogenically forced. Our simulations suggest that the Amundsen Sea responded to historical greenhouse gas forcing, and that future changes in emissions are also likely to affect the region.
Publisher: Cold Spring Harbor Laboratory
Date: 04-2021
DOI: 10.1101/2021.03.31.21254680
Abstract: With a rapidly changing evidence base, high-quality clinical management guidelines (CMGs) are key tools for aiding clinical decision making and increasing access to best available evidence-based care. A rapid review of COVID-19 CMGs found that most lacked methodological rigour, overlooked many at-risk populations, and had variations in treatment recommendations. Furthermore, social science literature highlights the complexity of implementing guidelines in local contexts where they were not developed and the resulting potential to compound health inequities. The aim of this study was to evaluate access to, inclusivity of, and implementation of Covid-19 CMGs in different settings. A cross-sectional survey of clinicians worldwide from 15 June to 20 July 2020, to explore access to and implementation of Covid-19 CMGs and treatment and supportive care recommendations provided. Data on accessibility, inclusivity, and implementation of CMGs. were analyzed by geographic location. Seventy-six clinicians, from 27 countries responded, 82% from high-income countries, 17% from low-middle income countries. Most respondents reported access to Covid-19 CMG and confidence in implementation of these. However, many respondents, particularly from LMICs reported barriers to implementation, including limited access to treatments and equipment. Only 20% of respondents reported having access to CMGs covering care for children, 25% for pregnant women and 50% for older adults ( years). Themes emerging were for CMGs to include recommendations for different at-risk populations, and settings, include supportive care guidance, be readily updated as evidence emerges, and CMG implementation supported by training, and access to treatments recommended. Our findings highlight important gaps in Covid-19 CMG development and implementation challenges during a pandemic, particularly affecting different at-risk populations and lower resourced settings., to improve access in evidence-based care recommendations during an emergency. The findings identifies an urgent need for an improved framework for CMG development, that is inclusive and adaptable to emerging evidence and considers contextual implementation support, to improve access to evidence-based care globally.
Publisher: eLife Sciences Publications, Ltd
Date: 05-10-2022
DOI: 10.7554/ELIFE.80556
Abstract: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, in idual-level data on infecting variants are typically only available for a minority of patients and settings. Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61–0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available in idual-level data on infecting variant for a subset of the study population. Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome. Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z] and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135] Laura Merson was supported by University of Oxford’s COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus and Andrea Angheben by the Italian Ministry of Health “Fondi Ricerca corrente–L1P6” to IRCCS Ospedale Sacro Cuore–Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR award CO-CIN-01), the Medical Research Council (MRC grant MC_PC_19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix.
Publisher: Springer Science and Business Media LLC
Date: 02-06-2020
DOI: 10.1186/S12916-020-01592-Z
Abstract: Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. In idual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and 37.0 weeks), small for gestational age (SGA, birthweight of 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013. Of the 22 eligible studies ( n = 5015), IPD from16 studies were shared, representing 95.0% ( n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine ( n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine ( n = 1087), artesunate-amodiaquine ( n = 775), artesunate-mefloquine ( n = 965), and dihydroartemisinin-piperaquine ( n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p 0.001). The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.
Publisher: Copernicus GmbH
Date: 16-05-2013
Abstract: Abstract. Both historical and idealized climate model experiments are performed with a variety of Earth system models of intermediate complexity (EMICs) as part of a community contribution to the Intergovernmental Panel on Climate Change Fifth Assessment Report. Historical simulations start at 850 CE and continue through to 2005. The standard simulations include changes in forcing from solar luminosity, Earth's orbital configuration, CO2, additional greenhouse gases, land use, and sulphate and volcanic aerosols. In spite of very different modelled pre-industrial global surface air temperatures, overall 20th century trends in surface air temperature and carbon uptake are reasonably well simulated when compared to observed trends. Land carbon fluxes show much more variation between models than ocean carbon fluxes, and recent land fluxes appear to be slightly underestimated. It is possible that recent modelled climate trends or climate–carbon feedbacks are overestimated resulting in too much land carbon loss or that carbon uptake due to CO2 and/or nitrogen fertilization is underestimated. Several one thousand year long, idealized, 2 × and 4 × CO2 experiments are used to quantify standard model characteristics, including transient and equilibrium climate sensitivities, and climate–carbon feedbacks. The values from EMICs generally fall within the range given by general circulation models. Seven additional historical simulations, each including a single specified forcing, are used to assess the contributions of different climate forcings to the overall climate and carbon cycle response. The response of surface air temperature is the linear sum of the in idual forcings, while the carbon cycle response shows a non-linear interaction between land-use change and CO2 forcings for some models. Finally, the preindustrial portions of the last millennium simulations are used to assess historical model carbon-climate feedbacks. Given the specified forcing, there is a tendency for the EMICs to underestimate the drop in surface air temperature and CO2 between the Medieval Climate Anomaly and the Little Ice Age estimated from palaeoclimate reconstructions. This in turn could be a result of unforced variability within the climate system, uncertainty in the reconstructions of temperature and CO2, errors in the reconstructions of forcing used to drive the models, or the incomplete representation of certain processes within the models. Given the forcing datasets used in this study, the models calculate significant land-use emissions over the pre-industrial period. This implies that land-use emissions might need to be taken into account, when making estimates of climate–carbon feedbacks from palaeoclimate reconstructions.
Publisher: Copernicus GmbH
Date: 29-04-2015
Abstract: Abstract. We analyze the source code of eight coupled climate models, selected from those that participated in the CMIP5 (Taylor et al., 2012) or EMICAR5 (Eby et al., 2013 Zickfeld et al., 2013) intercomparison projects. For each model, we sort the preprocessed code into components and subcomponents based on dependency structure. We then create software architecture diagrams that show the relative sizes of these components/subcomponents and the flow of data between them. The diagrams also illustrate several major classes of climate model design the distribution of complexity between components, which depends on historical development paths as well as the conscious goals of each institution and the sharing of components between different modeling groups. These diagrams offer insights into the similarities and differences in structure between climate models, and have the potential to be useful tools for communication between scientists, scientific institutions, and the public.
Publisher: Oxford University Press (OUP)
Date: 10-09-2022
Abstract: Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4% children: 20.4%), altered consciousness (20.9% 6.8%), myalgia (16.9% 7.6%), dysgeusia (7.4% 1.9%), anosmia (6.0% 2.2%) and seizure (1.1% 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P & 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.
Publisher: Springer Science and Business Media LLC
Date: 11-05-2015
DOI: 10.1038/NGEO2430
Publisher: American Geophysical Union (AGU)
Date: 14-12-2022
DOI: 10.1029/2022GL100646
Abstract: Warm ocean waters drive rapid ice‐shelf melting in the Amundsen Sea. The ocean heat transport toward the ice shelves is associated with the Amundsen Undercurrent, a near‐bottom current that flows eastward along the shelf break and transports warm waters onto the continental shelf via troughs. Here we use a regional ice‐ocean model to show that, on decadal time scales, the undercurrent's variability is baroclinic (depth‐dependent). Decadal ocean surface cooling in the tropical Pacific results in cyclonic wind anomalies over the Amundsen Sea. These wind anomalies drive a westward perturbation of the shelf‐break surface flow and an eastward anomaly (strengthening) of the undercurrent, leading to increased ice‐shelf melting. This contrasts with shorter time scales, for which surface current and undercurrent covary, a barotropic (depth‐independent) behavior previously assumed to apply at all time scales. This suggests that interior ocean processes mediate the decadal ice‐shelf response in the Amundsen Sea to climate forcing.
Publisher: American Geophysical Union (AGU)
Date: 10-2014
DOI: 10.1002/2014GC005474
Publisher: Elsevier BV
Date: 07-2020
Publisher: BMJ
Date: 05-2019
DOI: 10.1136/BMJOPEN-2018-027503
Abstract: Pregnant women are more vulnerable to malaria leading to adverse impact on both mothers and fetuses. However, knowledge on the efficacy and safety of antimalarials in pregnancy is limited by the paucity of randomised control trials and the lack of standardised protocols in this special subpopulation. Pooling in idual patient data (IPD) for meta-analysis could address in part these limitations to summarise accurately the currently available evidence on treatment efficacy and risk factors for treatment failure. To assess the treatment efficacy of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy, seven databases (Medline, Embase, Global Health, Cochrane Library, Scopus, Web of Science and Literatura Latino Americana em Ciências da Saúde) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrial.gov) were searched. Both interventional and observational cohort studies following up for at least 28 days will be included. IPD of the identified eligible published or unpublished studies will be sought by inviting principal investigators. Raw IPD will be shared through the web-based secure platform developed by the WorldWide Antimalarial Resistance Network using the established methodology. The primary objective is to compare the risk of PCR-corrected treatment failure among different treatments and to find the risk factors. One-stage IPD meta-analysis by Cox model with shared frailty will be conducted. A risk of bias assessment will be conducted to address the impact of unshared potential data and of the quality of in idual studies. Potential limitations include difficulty in acquiring the IPD and heterogeneity of the study designs due to the lack of standard. This IPD meta-analysis consists of secondary analyses of existing anonymous data and meets the criteria for waiver of ethics review by the Oxford Tropical Research Ethics Committee. The results of this IPD meta-analysis will be disseminated through open-access publications at peer-reviewed journals. The study results will lead to a better understanding of malaria treatment in pregnancy, which can be used for clinical decision-making and conducting further studies. CRD42018104013.
Publisher: F1000 Research Ltd
Date: 27-09-2021
DOI: 10.12688/WELLCOMEOPENRES.16984.1
Abstract: Background : With a rapidly changing evidence base, high-quality clinical management guidelines (CMGs) are key tools for aiding clinical decision making and increasing access to best available evidence-based care. A rapid review of COVID-19 CMGs found most lacked methodological rigour, overlooked at-risk populations, and varied in treatment recommendations. Furthermore, social science literature highlights the complexity of implementing guidelines in local contexts where they were not developed and the resulting potential to compound health inequities. This study aimed to evaluate access to, inclusivity of, and implementation of COVID-19 CMGs in different settings. Methods : A cross-sectional survey of clinicians worldwide was conducted from 15 th June to 20 th July 2020, to explore access to and implementation of COVID-19 CMGs, and treatment and supportive care recommendations provided. Data on accessibility, inclusivity, and implementation of CMGs were analysed by geographic location. Results : 76 clinicians from 27 countries responded: 82% from high-income countries, 17% from lower middle-income countries (LMICs). Most respondents reported access to COVID-19 CMGs and confidence in their implementation. However, many respondents, particularly from LMICs, reported barriers to implementation, including limited access to treatment and equipment. Only 20% of respondents reported having access to CMGs covering care for children, 25% for pregnant women, and 50% for older adults ( years). Identified themes were for CMGs to include recommendations for at-risk populations and settings, include supportive care guidance, and be updated as evidence emerges, and for clinicians to have training and access to recommended treatments to support implementation. Conclusion : Our findings highlight important gaps in COVID-19 CMG development and implementation challenges during a pandemic, particularly affecting at-risk populations and lower resourced settings. This study identifies an urgent need for an improved CMG development framework that is inclusive and adaptable to emerging evidence and considers contextual implementation support, to improve access to evidence-based care globally.
Publisher: Public Library of Science (PLoS)
Date: 17-03-2021
DOI: 10.1371/JOURNAL.PNTD.0009144
Abstract: Oral ivermectin is a safe broad spectrum anthelminthic used for treating several neglected tropical diseases (NTDs). Currently, ivermectin use is contraindicated in children weighing less than 15 kg, restricting access to this drug for the treatment of NTDs. Here we provide an updated systematic review of the literature and we conducted an in idual-level patient data (IPD) meta-analysis describing the safety of ivermectin in children weighing less than 15 kg. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for IPD guidelines by searching MEDLINE via PubMed, Web of Science, Ovid Embase, LILACS, Cochrane Database of Systematic Reviews, TOXLINE for all clinical trials, case series, case reports, and database entries for reports on the use of ivermectin in children weighing less than 15 kg that were published between 1 January 1980 to 25 October 2019. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42017056515. A total of 3,730 publications were identified, 97 were selected for potential inclusion, but only 17 sources describing 15 studies met the minimum criteria which consisted of known weights of children less than 15 kg linked to possible adverse events, and provided comprehensive IPD. A total of 1,088 children weighing less than 15 kg were administered oral ivermectin for one of the following indications: scabies, mass drug administration for scabies control, crusted scabies, cutaneous larva migrans, myiasis, pthiriasis, strongyloidiasis, trichuriasis, and parasitic disease of unknown origin. Overall a total of 1.4% (15/1,088) of children experienced 18 adverse events all of which were mild and self-limiting. No serious adverse events were reported. Existing limited data suggest that oral ivermectin in children weighing less than 15 kilograms is safe. Data from well-designed clinical trials are needed to provide further assurance.
Publisher: Springer Science and Business Media LLC
Date: 23-10-2023
Publisher: Copernicus GmbH
Date: 26-01-2022
Abstract: Abstract. The Regional Ocean Modeling System (ROMS), including an ice shelf component, has been applied on a circum-Antarctic domain to derive estimates of ice shelf basal melting. Significant improvements made compared to previous models of this scale are the inclusion of tides and a horizontal spatial resolution of 2 km, which is sufficient to resolve on-shelf heat transport by bathymetric troughs and eddy-scale circulation. We run the model with ocean–atmosphere–sea ice conditions from the year 2007 to represent nominal present-day climate. We force the ocean surface with buoyancy fluxes derived from sea ice concentration observations and wind stress from ERA-Interim atmospheric reanalysis. Boundary conditions are derived from the ECCO2 ocean state estimate tides are incorporated as sea surface height and barotropic currents at the open boundary. We evaluate model results using satellite-derived estimates of ice shelf melting and established compilations of ocean hydrography. The Whole Antarctic Ocean Model (WAOM v1.0) qualitatively captures the broad scale difference between warm and cold regimes as well as many of the known characteristics of regional ice–ocean interaction. We identify a cold bias for some warm-water ice shelves and a lack of high-salinity shelf water (HSSW) formation. We conclude that further calibration and development of our approach are justified. At its current state, the model is ideal for addressing specific, process-oriented questions, e.g. related to tide-driven ice shelf melting at large scales.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Elsevier BV
Date: 08-2023
Publisher: Springer Science and Business Media LLC
Date: 16-09-2022
DOI: 10.1186/S12916-022-02504-Z
Abstract: In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns. A systematic review and in idual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models. Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17–0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19–0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms. Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient in iduals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient in iduals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients. PROSPERO, CRD42019128185
Publisher: F1000 Research Ltd
Date: 02-06-2020
DOI: 10.12688/WELLCOMEOPENRES.15933.1
Abstract: Background: Since the coronavirus disease 2019 (COVID-19) outbreak was first reported in December 2019, many independent trials have been planned that aim to answer similar questions. Tools allowing researchers to review studies already underway can facilitate collaboration, cooperation and harmonisation. The Infectious Diseases Data Observatory (IDDO) has undertaken a living systematic review (LSR) to provide an open, accessible and frequently updated resource summarising characteristics of COVID-19 study registrations. Methods: Review of all eligible trial records identified by systematic searches as of 3 April 2020 and initial synthesis of clinical study characteristics were conducted. In partnership with Exaptive , an open access, cloud-based knowledge graph has been created using the results. Results: There were 728 study registrations which met eligibility criteria and were still active. Median (25 th , 75 th percentile) s le size was 130 (60, 400) for all studies and 134 (70, 300) for RCTs. Eight lower middle and low income countries were represented among the planned recruitment sites. Overall 109 pharmacological interventions or advanced therapy medicinal products covering 23 drug categories were studied. Majority (57%, 62/109) of them were planned only in one study arm, either alone or in combination with other interventions. There were 49 distinct combinations studied with 90% (44/49) of them administered in only one or two study arms. The data and interactive platform are available at iddo.cognitive.city/ . Conclusions: Baseline review highlighted that the majority of investigations in the first three months of the outbreak were small studies with unique treatment arms, likely to be unpowered to provide solid evidence. The continued work of this LSR will allow a more dependable overview of interventions tested, predict the likely strength of evidence generated, allow fast and informative filtering of relevant trials for specific user groups and provide the rapid guidance needed by investigators and funders to avoid duplication of efforts.
Publisher: Cold Spring Harbor Laboratory
Date: 25-07-2020
DOI: 10.1101/2020.07.17.20155218
Abstract: ISARIC (International Severe Acute Respiratory and emerging Infections Consortium) partnerships and outbreak preparedness initiatives enabled the rapid launch of standardised clinical data collection on COVID-19 in Jan 2020. Extensive global participation has resulted in a large, standardised collection of comprehensive clinical data from hundreds of sites across dozens of countries. Data are analysed regularly and reported publicly to inform patient care and public health response. This report, our 17th report, is a part of a series published over the past 2 years. Data have been entered for 800,459 in iduals from 1701 partner institutions and networks across 60 countries. The comprehensive analyses detailed in this report includes hospitalised in iduals of all ages for whom data collection occurred between 30 January 2020 and up to and including 5 January 2022, AND who have laboratory-confirmed SARS-COV-2 infection or clinically diagnosed COVID-19. For the 699,014 cases who meet eligibility criteria for this report, selected findings include: median age of 58 years, with an approximately equal (50/50) male:female sex distribution 29% of the cohort are at least 70 years of age, whereas 4% are 0-19 years of age the most common symptom combination in this hospitalised cohort is shortness of breath, cough, and history of fever, which has remained constant over time the five most common symptoms at admission were shortness of breath, cough, history of fever, fatigue/malaise, and altered consciousness/confusion, which is unchanged from the previous reports age-associated differences in symptoms are evident, including the frequency of altered consciousness increasing with age, and fever, respiratory and constitutional symptoms being present mostly in those 40 years and above 16% of patients with relevant data available were admitted at some point during their illness into an intensive care unit (ICU), which is slightly lower than previously reported (19%) antibiotic agents were used in 35% of patients for whom relevant data are available (669,630), a significant reduction from our previous reports (80%) which reflects a shifting proportion of data contributed by different institutions in ICU/HDU admitted patients with data available (50,560), 91% received antibiotics use of corticosteroids was reported in 24% of all patients for whom data were available (677,012) in ICU/HDU admitted patients with data available (50,646), 69% received corticosteroids outcomes are known for 632,518 patients and the overall estimated case fatality ratio (CFR) is 23.9% (95%CI 23.8-24.1), rising to 37.1% (95%CI 36.8-37.4) for patients who were admitted to ICU/HDU, demonstrating worse outcomes in those with the most severe disease To access previous versions of ISARIC COVID-19 Clinical Data Report please use the link below: esearch/covid-19-clinical-research-resources/evidence-reports/
Publisher: American Geophysical Union (AGU)
Date: 17-11-2020
DOI: 10.1029/2020GL089237
Abstract: Understanding changes in Antarctic ice shelf basal melting is a major challenge for predicting future sea level. Currently, warm Circumpolar Deep Water surrounding Antarctica has limited access to the Weddell Sea continental shelf consequently, melt rates at Filchner‐Ronne Ice Shelf are low. However, large‐scale model projections suggest that changes to the Antarctic Slope Front and the coastal circulation may enhance warm inflows within this century. We use a regional high‐resolution ice shelf cavity and ocean circulation model to explore forcing changes that may trigger this regime shift. Our results suggest two necessary conditions for supporting a sustained warm inflow into the Filchner Ice Shelf cavity: (i) an extreme relaxation of the Antarctic Slope Front density gradient and (ii) substantial freshening of the dense shelf water. We also find that the on‐shelf transport over the western Weddell Sea shelf is sensitive to the Filchner Trough overflow characteristics.
Publisher: Springer Science and Business Media LLC
Date: 30-07-2022
DOI: 10.1038/S41597-022-01534-9
Abstract: The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.
Publisher: eLife Sciences Publications, Ltd
Date: 23-11-2021
DOI: 10.7554/ELIFE.70970
Abstract: There is potentially considerable variation in the nature and duration of the care provided to hospitalised patients during an infectious disease epidemic or pandemic. Improvements in care and clinician confidence may shorten the time spent as an inpatient, or the need for admission to an intensive care unit (ICU) or high dependency unit (HDU). On the other hand, limited resources at times of high demand may lead to rationing. Nevertheless, these variables may be used as static proxies for disease severity, as outcome measures for trials, and to inform planning and logistics. We investigate these time trends in an extremely large international cohort of 142,540 patients hospitalised with COVID-19. Investigated are: time from symptom onset to hospital admission, probability of ICU/HDU admission, time from hospital admission to ICU/HDU admission, hospital case fatality ratio (hCFR) and total length of hospital stay. Time from onset to admission showed a rapid decline during the first months of the pandemic followed by peaks during August/September and December 2020. ICU/HDU admission was more frequent from June to August. The hCFR was lowest from June to August. Raw numbers for overall hospital stay showed little variation, but there is clear decline in time to discharge for ICU/HDU survivors. Our results establish that variables of these kinds have limitations when used as outcome measures in a rapidly evolving situation. This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher: Springer Science and Business Media LLC
Date: 02-2019
DOI: 10.1038/S41586-019-0889-9
Abstract: Government policies currently commit us to surface warming of three to four degrees Celsius above pre-industrial levels by 2100, which will lead to enhanced ice-sheet melt. Ice-sheet discharge was not explicitly included in Coupled Model Intercomparison Project phase 5, so effects on climate from this melt are not currently captured in the simulations most commonly used to inform governmental policy. Here we show, using simulations of the Greenland and Antarctic ice sheets constrained by satellite-based measurements of recent changes in ice mass, that increasing meltwater from Greenland will lead to substantial slowing of the Atlantic overturning circulation, and that meltwater from Antarctica will trap warm water below the sea surface, creating a positive feedback that increases Antarctic ice loss. In our simulations, future ice-sheet melt enhances global temperature variability and contributes up to 25 centimetres to sea level by 2100. However, uncertainties in the way in which future changes in ice dynamics are modelled remain, underlining the need for continued observations and comprehensive multi-model assessments.
Publisher: American Geophysical Union (AGU)
Date: 10-2014
DOI: 10.1002/2014PA002650
Publisher: Copernicus GmbH
Date: 10-04-2018
Abstract: Abstract. An increasing number of Southern Ocean models now include Antarctic ice-shelf cavities, and simulate thermodynamics at the ice-shelf/ocean interface. This adds another level of complexity to Southern Ocean simulations, as ice shelves interact directly with the ocean and indirectly with sea ice. Here, we present the first model intercomparison and evaluation of present-day ocean/sea-ice/ice-shelf interactions, as simulated by two models: a circumpolar Antarctic configuration of MetROMS (ROMS: Regional Ocean Modelling System coupled to CICE: Community Ice CodE) and the global model FESOM (Finite Element Sea-ice Ocean Model), where the latter is run at two different levels of horizontal resolution. From a circumpolar Antarctic perspective, we compare and evaluate simulated ice-shelf basal melting and sub-ice-shelf circulation, as well as sea-ice properties and Southern Ocean water mass characteristics as they influence the sub-ice-shelf processes. Despite their differing numerical methods, the two models produce broadly similar results and share similar biases in many cases. Both models reproduce many key features of observations but struggle to reproduce others, such as the high melt rates observed in the small warm-cavity ice shelves of the Amundsen and Bellingshausen seas. Several differences in model design show a particular influence on the simulations. For ex le, FESOM's greater topographic smoothing can alter the geometry of some ice-shelf cavities enough to affect their melt rates this improves at higher resolution, since less smoothing is required. In the interior Southern Ocean, the vertical coordinate system affects the degree of water mass erosion due to spurious diapycnal mixing, with MetROMS' terrain-following coordinate leading to more erosion than FESOM's z coordinate. Finally, increased horizontal resolution in FESOM leads to higher basal melt rates for small ice shelves, through a combination of stronger circulation and small-scale intrusions of warm water from offshore.
Publisher: American Meteorological Society
Date: 07-2018
Abstract: Basal melting of Antarctic ice shelves is expected to increase during the twenty-first century as the ocean warms, which will have consequences for ice sheet stability and global sea level rise. Here we present future projections of Antarctic ice shelf melting using the Finite Element Sea Ice/Ice-Shelf Ocean Model (FESOM) forced with atmospheric output from models from phase 5 of the Coupled Model Intercomparison Project (CMIP5). CMIP5 models are chosen based on their agreement with historical atmospheric reanalyses over the Southern Ocean the best-performing models are ACCESS 1.0 and the CMIP5 multimodel mean. Their output is bias-corrected for the representative concentration pathway (RCP) 4.5 and 8.5 scenarios. During the twenty-first-century simulations, total ice shelf basal mass loss increases by between 41% and 129%. Every sector of Antarctica shows increased basal melting in every scenario, with the largest increases occurring in the Amundsen Sea. The main mechanism driving this melting is an increase in warm Circumpolar Deep Water on the Antarctic continental shelf. A reduction in wintertime sea ice formation simulated during the twenty-first century stratifies the water column, allowing a warm bottom layer to develop and intrude into ice shelf cavities. This effect may be overestimated in the Amundsen Sea because of a cold bias in the present-day simulation. Other consequences of weakened sea ice formation include freshening of High Salinity Shelf Water and warming of Antarctic Bottom Water. Furthermore, freshening around the Antarctic coast in our simulations causes the Antarctic Circumpolar Current to weaken and the Antarctic Coastal Current to strengthen.
Publisher: Cold Spring Harbor Laboratory
Date: 22-06-2022
DOI: 10.1101/2022.06.22.22276764
Abstract: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, in idual-level data on infecting variants are typically only available for a minority of patients and settings. Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61 – 0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available in idual-level data on infecting variant for a subset of the study population. Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome.
Publisher: American Geophysical Union (AGU)
Date: 24-10-2012
DOI: 10.1029/2012GL053763
Publisher: Springer Science and Business Media LLC
Date: 31-03-2021
DOI: 10.1038/S41467-021-22259-0
Abstract: A potentially irreversible threshold in Antarctic ice shelf melting would be crossed if the ocean cavity beneath the large Filchner–Ronne Ice Shelf were to become flooded with warm water from the deep ocean. Previous studies have identified this possibility, but there is great uncertainty as to how easily it could occur. Here, we show, using a coupled ice sheet-ocean model forced by climate change scenarios, that any increase in ice shelf melting is likely to be preceded by an extended period of reduced melting. Climate change weakens the circulation beneath the ice shelf, leading to colder water and reduced melting. Warm water begins to intrude into the cavity when global mean surface temperatures rise by approximately 7 °C above pre-industrial, which is unlikely to occur this century. However, this result should not be considered evidence that the region is unconditionally stable. Unless global temperatures plateau, increased melting will eventually prevail.
Publisher: Springer Science and Business Media LLC
Date: 12-04-2022
DOI: 10.1186/S12936-022-04146-1
Abstract: Microscopic examination of Giemsa-stained blood films remains the reference standard for malaria parasite detection and quantification, but is undermined by difficulties in ensuring high-quality manual reading and inter-reader reliability. Automated parasite detection and quantification may address this issue. A multi-centre, observational study was conducted during 2018 and 2019 at 11 sites to assess the performance of the EasyScan Go, a microscopy device employing machine-learning-based image analysis. Sensitivity, specificity, accuracy of species detection and parasite density estimation were assessed with expert microscopy as the reference. Intra- and inter-device reliability of the device was also evaluated by comparing results from repeat reads on the same and two different devices. This study has been reported in accordance with the Standards for Reporting Diagnostic accuracy studies (STARD) checklist. In total, 2250 Giemsa-stained blood films were prepared and read independently by expert microscopists and the EasyScan Go device. The diagnostic sensitivity of EasyScan Go was 91.1% (95% CI 88.9–92.7), and specificity 75.6% (95% CI 73.1–78.0). With good quality slides sensitivity was similar (89.1%, 95%CI 86.2–91.5), but specificity increased to 85.1% (95%CI 82.6–87.4). Sensitivity increased with parasitaemia rising from 57% at 200 parasite/µL, to ≥ 90% at 200–200,000 parasite/µL. Species were identified accurately in 93% of Plasmodium falciparum s les (kappa = 0.76, 95% CI 0.69–0.83), and in 92% of Plasmodium vivax s les (kappa = 0.73, 95% CI 0.66–0.80). Parasite density estimates by the EasyScan Go were within ± 25% of the microscopic reference counts in 23% of slides. The performance of the EasyScan Go in parasite detection and species identification accuracy fulfil WHO-TDR Research Malaria Microscopy competence level 2 criteria. In terms of parasite quantification and false positive rate, it meets the level 4 WHO-TDR Research Malaria Microscopy criteria. All performance parameters were significantly affected by slide quality. Further software improvement is required to improve sensitivity at low parasitaemia and parasite density estimations. Trial registration ClinicalTrials.gov number NCT03512678.
Publisher: Elsevier BV
Date: 12-2019
Publisher: Elsevier BV
Date: 07-2023
Publisher: Cold Spring Harbor Laboratory
Date: 21-09-2021
DOI: 10.1101/2021.09.11.21263419
Abstract: Policymakers need robust data to respond to the COVID-19 pandemic. We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, the world’s largest international, standardised cohort of hospitalised patients. The dataset analysed includes COVID-19 patients hospitalised between January 2020 and May 2021. We investigated how symptoms on admission, comorbidities, risk factors, and treatments varied by age, sex, and other characteristics. We used Cox proportional hazards models to investigate associations between demographics, symptoms, comorbidities, and other factors with risk of death, admission to intensive care unit (ICU), and invasive mechanical ventilation (IMV). 439,922 patients with laboratory-confirmed (91.7%) or clinically-diagnosed (8.3%) SARS-CoV-2 infection from 49 countries were enrolled. Age (adjusted hazard ratio [HR] per 10 years 1.49 [95% CI 1.49-1.50]) and male sex (1.26 [1.24-1.28]) were associated with a higher risk of death. Rates of admission to ICU and use of IMV increased with age up to age 60, then dropped. Symptoms, comorbidities, and treatments varied by age and had varied associations with clinical outcomes. Tuberculosis was associated with an 86% higher risk of death, and HIV with an 87% higher risk of death. Case fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients. The size of our international database and the standardized data collection method makes this study a reliable and comprehensive international description of COVID-19 clinical features. This is a viable model to be applied to future epidemics. UK Foreign, Commonwealth and Development Office, the Bill & Melinda Gates Foundation and Wellcome. See acknowledgements section for funders of sites that contributed data. To identify large, international analyses of hospitalised COVID-19 patients that used standardised data collection, we conducted a systematic review of the literature from 1 Jan 2020 to 28 Apr 2020. We identified 78 studies, with data from 77,443 people (1) predominantly from China. We could not find any studies including data from low and middle-income countries. We repeated our search on 18 Aug 2021 but could not identify any further studies that met our inclusion criteria. Our study uses standardised clinical data collection to collect data from a vast number of patients across the world, including patients from low-, middle-, and high-income countries. The size of our database gives us great confidence in the accuracy of our descriptions of the global impact of COVID-19. We can confirm findings reported by smaller, country-specific studies and compare clinical data between countries. We have demonstrated that it is possible to collect large volumes of standardised clinical data during a pandemic of a novel acute respiratory infection. The results provide a valuable resource for present policymakers and future global health researchers. Presenting symptoms of SARS-CoV-2 infection in patients requiring hospitalisation are now well-described globally, with the most common being fever, cough, and shortness of breath. Other symptoms also commonly occur, including altered consciousness in older adults and gastrointestinal symptoms in younger patients, and age can influence the likelihood of a patient having symptoms that match one or more case definitions. There are geographic and temporal variations in the case fatality rate (CFR), but overall, CFR was 20.6% in this large international cohort of hospitalised patients with a median age of 60 years (IQR: 45 to 74 years).
Publisher: Springer Science and Business Media LLC
Date: 25-06-2021
DOI: 10.1007/S15010-021-01599-5
Abstract: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69% at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23 85%), older adults (≥ 70 years: 61, 62, 65 90%), and women (66, 66, 64 90% vs. men 71, 70, 67 93%, each P 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.
Publisher: Elsevier BV
Date: 08-2017
Publisher: Wiley
Date: 28-05-2020
DOI: 10.1002/ASL.984
Publisher: Public Library of Science (PLoS)
Date: 20-04-2022
DOI: 10.1371/JOURNAL.PMED.1003969
Abstract: Acute kidney injury (AKI) is one of the most common and significant problems in patients with Coronavirus Disease 2019 (COVID-19). However, little is known about the incidence and impact of AKI occurring in the community or early in the hospital admission. The traditional Kidney Disease Improving Global Outcomes (KDIGO) definition can fail to identify patients for whom hospitalisation coincides with recovery of AKI as manifested by a decrease in serum creatinine (sCr). We hypothesised that an extended KDIGO (eKDIGO) definition, adapted from the International Society of Nephrology (ISN) 0by25 studies, would identify more cases of AKI in patients with COVID-19 and that these may correspond to community-acquired AKI (CA-AKI) with similarly poor outcomes as previously reported in this population. All in iduals recruited using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)–World Health Organization (WHO) Clinical Characterisation Protocol (CCP) and admitted to 1,609 hospitals in 54 countries with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection from February 15, 2020 to February 1, 2021 were included in the study. Data were collected and analysed for the duration of a patient’s admission. Incidence, staging, and timing of AKI were evaluated using a traditional and eKDIGO definition, which incorporated a commensurate decrease in sCr. Patients within eKDIGO diagnosed with AKI by a decrease in sCr were labelled as deKDIGO. Clinical characteristics and outcomes—intensive care unit (ICU) admission, invasive mechanical ventilation, and in-hospital death—were compared for all 3 groups of patients. The relationship between eKDIGO AKI and in-hospital death was assessed using survival curves and logistic regression, adjusting for disease severity and AKI susceptibility. A total of 75,670 patients were included in the final analysis cohort. Median length of admission was 12 days (interquartile range [IQR] 7, 20). There were twice as many patients with AKI identified by eKDIGO than KDIGO (31.7% versus 16.8%). Those in the eKDIGO group had a greater proportion of stage 1 AKI (58% versus 36% in KDIGO patients). Peak AKI occurred early in the admission more frequently among eKDIGO than KDIGO patients. Compared to those without AKI, patients in the eKDIGO group had worse renal function on admission, more in-hospital complications, higher rates of ICU admission (54% versus 23%) invasive ventilation (45% versus 15%), and increased mortality (38% versus 19%). Patients in the eKDIGO group had a higher risk of in-hospital death than those without AKI (adjusted odds ratio: 1.78, 95% confidence interval: 1.71 to 1.80, p -value 0.001). Mortality and rate of ICU admission were lower among deKDIGO than KDIGO patients (25% versus 50% death and 35% versus 70% ICU admission) but significantly higher when compared to patients with no AKI (25% versus 19% death and 35% versus 23% ICU admission) (all p -values × 10 −5 ). Limitations include ad hoc sCr s ling, exclusion of patients with less than two sCr measurements, and limited availability of sCr measurements prior to initiation of acute dialysis. An extended KDIGO definition of AKI resulted in a significantly higher detection rate in this population. These additional cases of AKI occurred early in the hospital admission and were associated with worse outcomes compared to patients without AKI.
Publisher: Wiley
Date: 04-05-2023
DOI: 10.1111/AOR.14542
Abstract: Veno‐venous extracorporeal membrane oxygenation (V‐V ECMO) is a lifesaving support modality for severe respiratory failure, but its resource‐intensive nature led to significant controversy surrounding its use during the COVID‐19 pandemic. We report the performance of several ECMO mortality prediction and severity of illness scores at discriminating survival in a large COVID‐19 V‐V ECMO cohort. We validated ECMOnet, PRESET (PREdiction of Survival on ECMO Therapy‐Score), Roch, SOFA (Sequential Organ Failure Assessment), APACHE II (acute physiology and chronic health evaluation), 4C (Coronavirus Clinical Characterisation Consortium), and CURB‐65 (Confusion, Urea nitrogen, Respiratory Rate, Blood Pressure, age years) scores on the ISARIC (International Severe Acute Respiratory and emerging Infection Consortium) database. We report discrimination via Area Under the Receiver Operative Curve (AUROC) and Area under the Precision Recall Curve (AURPC) and calibration via Brier score. We included 1147 patients and scores were calculated on patients with sufficient variables. ECMO mortality scores had AUROC (0.58–0.62), AUPRC (0.62–0.74), and Brier score (0.286–0.303). Roch score had the highest accuracy (AUROC 0.62), precision (AUPRC 0.74) yet worst calibration (Brier score of 0.3) despite being calculated on the fewest patients (144). Severity of illness scores had AUROC (0.52–0.57), AURPC (0.59–0.64), and Brier Score (0.265–0.471). APACHE II had the highest accuracy (AUROC 0.58), precision (AUPRC 0.64), and best calibration (Brier score 0.26). Within a large international multicenter COVID‐19 cohort, the evaluated ECMO mortality prediction and severity of illness scores demonstrated inconsistent discrimination and calibration highlighting the need for better clinically applicable decision support tools.
Publisher: Oxford University Press (OUP)
Date: 28-02-2023
DOI: 10.1093/IJE/DYAD012
Abstract: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.
Publisher: Springer Science and Business Media LLC
Date: 17-01-2019
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Kalynn Kennon.