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Innovative, responsible data use is a critical need in the global response to the coronavirus disease-2019 (COVID-19) pandemic. Yet potentially impactful data are often unavailable to those who could utilize it, particularly in data-poor settings, posing a serious barrier to effective pandemic mitigation. Data challenges, a public call-to-action for innovative data use projects, can identify and address these specific barriers. To understand gaps and progress relevant to effective data use in this context, this study thematically analyses three sets of qualitative data focused on/based in low/middle-income countries: (a) a survey of innovators responding to a data challenge, (b) a survey of organizers of data challenges, and (c) a focus group discussion with professionals using COVID-19 data for evidence-based decision-making. Data quality and accessibility and human resources/institutional capacity were frequently reported limitations to effective data use among innovators. New fit-for-purpose tools and the expansion of partnerships were the most frequently noted areas of progress. Discussion participants identified building capacity for external/national actors to understand the needs of local communities can address a lack of partnerships while de-siloing information. A synthesis of themes demonstrated that gaps, progress, and needs commonly identified by these groups are relevant beyond COVID-19, highlighting the importance of a healthy data ecosystem to address emerging threats. This is supported by data holders prioritizing the availability and accessibility of their data without causing harm; funders and policymakers committed to integrating innovations with existing physical, data, and policy infrastructure; and innovators designing sustainable, multi-use solutions based on principles of good data governance.
Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One possible mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes is via associations with brain structure. This study aimed to elucidate the associations between childhood trauma and brain structure across two large, independent community cohorts.
The two samples comprised (i) a subsample of Generation Scotland (n=1,024); and (ii) individuals from UK Biobank (n=27,202). This comprised n=28,226 for mega-analysis. MRI scans were processed using Free Surfer, providing cortical, subcortical, and global brain metrics. Regression models were used to determine associations between childhood trauma measures and brain metrics and psychiatric phenotypes.
Childhood trauma associated with lifetime depression across cohorts (OR 1.06 GS, 1.23 UKB), and related to early onset and recurrent course within both samples. There was evidence for associations between childhood trauma and structural brain metrics. This included reduced global brain volume, and reduced cortical surface area with highest effects in the frontal (β=−0.0385, SE=0.0048, p(FDR)=5.43x10−15) and parietal lobes (β=−0.0387, SE=0.005, p(FDR)=1.56x10−14). At a regional level the ventral diencephalon (VDc) displayed significant associations with childhood trauma measures across both cohorts and at mega-analysis (β=−0.0232, SE=0.0039, p(FDR)=2.91x10−8). There were also associations with reduced hippocampus, thalamus, and nucleus accumbens volumes.
Associations between childhood trauma and reduced global and regional brain volumes were found, across two independent UK cohorts, and at mega-analysis. This provides robust evidence for a lasting effect of childhood adversity on brain structure.
Field studies were conducted in Alabama in 2016 and 2017 to determine the effect of postemergence applications of glufosinate alone and glufosinate applied with S-metolachlor, using two different nozzle types, on LibertyLink®, XtendFlex®, and WideStrike® cotton growth and yield. Two applications of glufosinate at 0.6 kg ha−1, and glufosinate with S-metolachlor at 1.39 kg ha−1 were applied to each cotton cultivar at the four-leaf and eight-leaf growth stages using a flatfan and Turbo TeeJet Induction® nozzle. Visual estimates of cotton injury were evaluated after each application, as well as yield. No differences in yield within each cotton cultivar were observed for either year. Visible injury was higher for WideStrike cotton than LibertyLink or XtendFlex cultivars. On average, glufosinate applied with S-metolachlor resulted in greater injury than glufosinate applied alone. In LibertyLink cotton, applications made with TTI nozzles resulted in greater injury than flatfan nozzles. However, cotton injury was transient and did not affect cotton yields. These data indicate that applications of glufosinate and glufosinate applied with S-metolachlor, at 0.6 kg ha−1 and 1.39 kg ha−1, respectively, with either a flatfan or TTI nozzle, can have no detrimental effect on cotton growth or yield.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding about the remaining options to achieve the Paris Agreement goals, through overcoming political barriers to carbon pricing, taking into account non-CO2 factors, a well-designed implementation of demand-side and nature-based solutions, resilience building of ecosystems and the recognition that climate change mitigation costs can be justified by benefits to the health of humans and nature alone. We consider new insights about what to expect if we fail to include a new dimension of fire extremes and the prospect of cascading climate tipping elements.
A synthesis is made of 10 topics within climate research, where there have been significant advances since January 2020. The insights are based on input from an international open call with broad disciplinary scope. Findings include: (1) the options to still keep global warming below 1.5 °C; (2) the impact of non-CO2 factors in global warming; (3) a new dimension of fire extremes forced by climate change; (4) the increasing pressure on interconnected climate tipping elements; (5) the dimensions of climate justice; (6) political challenges impeding the effectiveness of carbon pricing; (7) demand-side solutions as vehicles of climate mitigation; (8) the potentials and caveats of nature-based solutions; (9) how building resilience of marine ecosystems is possible; and (10) that the costs of climate change mitigation policies can be more than justified by the benefits to the health of humans and nature.
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How do we limit global warming to 1.5 °C and why is it crucial? See highlights of latest climate science.
The COVID-19 pandemic has disrupted lives and livelihoods, and people already experiencing mental ill health may have been especially vulnerable.
Quantify mental health inequalities in disruptions to healthcare, economic activity and housing.
We examined data from 59 482 participants in 12 UK longitudinal studies with data collected before and during the COVID-19 pandemic. Within each study, we estimated the association between psychological distress assessed pre-pandemic and disruptions since the start of the pandemic to healthcare (medication access, procedures or appointments), economic activity (employment, income or working hours) and housing (change of address or household composition). Estimates were pooled across studies.
Across the analysed data-sets, 28% to 77% of participants experienced at least one disruption, with 2.3–33.2% experiencing disruptions in two or more domains. We found 1 s.d. higher pre-pandemic psychological distress was associated with (a) increased odds of any healthcare disruptions (odds ratio (OR) 1.30, 95% CI 1.20–1.40), with fully adjusted odds ratios ranging from 1.24 (95% CI 1.09–1.41) for disruption to procedures to 1.33 (95% CI 1.20–1.49) for disruptions to prescriptions or medication access; (b) loss of employment (odds ratio 1.13, 95% CI 1.06–1.21) and income (OR 1.12, 95% CI 1.06 –1.19), and reductions in working hours/furlough (odds ratio 1.05, 95% CI 1.00–1.09) and (c) increased likelihood of experiencing a disruption in at least two domains (OR 1.25, 95% CI 1.18–1.32) or in one domain (OR 1.11, 95% CI 1.07–1.16), relative to no disruption. There were no associations with housing disruptions (OR 1.00, 95% CI 0.97–1.03).
People experiencing psychological distress pre-pandemic were more likely to experience healthcare and economic disruptions, and clusters of disruptions across multiple domains during the pandemic. Failing to address these disruptions risks further widening mental health inequalities.
Nicolaides–Baraitser syndrome is a rare, neuro-developmental disorder caused by heterozygous pathogenic variants in the SMARCA2 gene, involved with chromatin regulation. Cardinal features include intellectual disability, short stature, microcephaly, triangular facies, sparse hair, brachydactyly, prominent interphalangeal joints and seizures. Genetic testing demonstrated a loss within SMARCA2 at 9p24.3 inclusive of basepairs 2094861_2141830 (hg19) in our patient. This case highlights a child with Nicolaides–Baraiter syndrome, a SMARCA2 gene deletion and a novel association of hypertrophic obstructive cardiomyopathy.
The COVID-19 global pandemic has had considerable health impact, including sub-Saharan Africa. In Malawi, a resource-limited setting in Africa, gaining access to data to inform the COVID-19 response is challenging. Information on adherence to physical distancing guidelines and reducing contacts are nonexistent, but critical to understanding and communicating risk, as well as allocating scarce resources. We present a case study which leverages aggregated call detail records into a daily data pipeline which summarize population density and mobility in an easy-to-use dashboard for public health officials and emergency operations. From March to April 2021, we have aggregated 6-billion calls and text messages and continue to process 12 million more daily. These data are summarized into reports which describe, quantify, and locate mass gatherings and travel between subdistricts. These reports are accessible via web dashboards for policymakers within the Ministry of Health and Emergency Operations Center to inform COVID-19 response efforts and resource allocation.
16p12.2 microdeletion has been associated with congenital heart defects and developmental delay. In this case, we describe the rare association between tetralogy of Fallot with an absent pulmonary valve a right-sided aortic arch and a retro-aortic innominate vein associated with a 16p12.2 microdeletion and epilepsy.
Self-harm is a major international public health concern and is especially prevalent among prisoners. In this editorial, we explore recent trends in prisoner self-harm during the coronavirus lockdown, and consider strategies for improving the prevention and management of self-harm in prisons as we emerge from the pandemic.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Anecdotal evidence suggests the use of bolus tube feeding is increasing in the long-term home enteral tube feed (HETF) patients. A cross-sectional survey to assess the prevalence of bolus tube feeding and to characterise these patients was undertaken. Dietitians from ten centres across the UK collected data on all adult HETF patients on the dietetic caseload receiving bolus tube feeding (n 604, 60 % male, age 58 years). Demographic data, reasons for tube and bolus feeding, tube and equipment types, feeding method and patients’ complete tube feeding regimens were recorded. Over a third of patients receiving HETF used bolus feeding (37 %). Patients were long-term tube fed (4·1 years tube feeding, 3·5 years bolus tube feeding), living at home (71 %) and sedentary (70 %). The majority were head and neck cancer patients (22 %) who were significantly more active (79 %) and lived at home (97 %), while those with cerebral palsy (12 %) were typically younger (age 31 years) but sedentary (94 %). Most patients used bolus feeding as their sole feeding method (46 %), because it was quick and easy to use, as a top-up to oral diet or to mimic mealtimes. Importantly, oral nutritional supplements (ONS) were used for bolus feeding in 85 % of patients, with 51 % of these being compact-style ONS (2·4 kcal (10·0 kJ)/ml, 125 ml). This survey shows that bolus tube feeding is common among UK HETF patients, is used by a wide variety of patient groups and can be adapted to meet the needs of a variety of patients, clinical conditions, nutritional requirements and lifestyles.
Use of the herbicide atrazine (ATR) is banned in the European Union; yet, it is still widely used in the USA and Australia. ATR is known to alter testosterone and oestrogen production and thus reproductive characteristics in numerous species. In this proof of concept study, we examined the effect of ATR exposure, at a supra-environmental dose (5 mg/kg bw/day), beginning on E9.5 in utero, prior to sexual differentiation of the reproductive tissues, until 26 weeks of age, on the development of the mouse penis. Notably, this is the first study to specifically investigate whether ATR can affect penis characteristics. We show that ATR exposure, beginning in utero, causes a shortening (demasculinisation) of penis structures and increases the incidence of hypospadias in mice. These data indicate the need for further studies of ATR on human reproductive development and fertility, especially considering its continued and widespread use.
There is increasing evidence to support integration of simulation into medical training; however, no national emergency medicine (EM) simulation curriculum exists. Using Delphi methodology, we aimed to identify and establish content validity for adult EM curricular content best suited for simulation-based training, to inform national postgraduate EM training.
A national panel of experts in EM simulation iteratively rated potential curricular topics, on a 4-point scale, to determine those best suited for simulation-based training. After each round, responses were analyzed. Topics scoring <2/4 were removed and remaining topics were resent to the panel for further ratings until consensus was achieved, defined as Cronbach α ≥ 0.95. At conclusion of the Delphi process, topics rated ≥ 3.5/4 were considered “core” curricular topics, while those rated 3.0-3.5 were considered “extended” curricular topics.
Forty-five experts from 13 Canadian centres participated. Two hundred eighty potential curricular topics, in 29 domains, were generated from a systematic literature review, relevant educational documents and Delphi panellists. Three rounds of surveys were completed before consensus was achieved, with response rates ranging from 93-100%. Twenty-eight topics, in eight domains, reached consensus as “core” curricular topics. Thirty-five additional topics, in 14 domains, reached consensus as “extended” curricular topics.
Delphi methodology allowed for achievement of expert consensus and content validation of EM curricular content best suited for simulation-based training. These results provide a foundation for improved integration of simulation into postgraduate EM training and can be used to inform a national simulation curriculum to supplement clinical training and optimize learning.
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
This article explores the case of a musician performing pro-Zapatista revolutionary songs in a restaurant in a city in southern Mexico which has undergone rapid gentrification since the turn of the century. It highlights the particular set of constraints on, and possibilities for, musical creativity that emerged in an urban setting in which space was increasingly ordered around the accumulation of rents. Exploring relationships between commercial strategy and musical detail, it examines tensions arising around the performance of a revolutionary body of song in such a setting. To conclude, and drawing on the recent work of Anna Tsing, it introduces the notion of musical ‘salvage’ to make sense of the relationship between protest and commerce. Recognizing the incompleteness of revolutionary songs’ translation into the rapidly gentrifying context of San Cristóbal, it is argued here, may help to underline performer agency and creativity.
Significant increases in excess all-cause mortality, particularly in the elderly, were observed during the winter of 2014/15 in England. With influenza A(H3N2) the dominant circulating influenza A subtype, this paper determines the contribution of influenza to this excess controlling for weather. A standardised multivariable Poisson regression model was employed with weekly all-cause deaths the dependent variable for the period 2008–2015. Adjusting for extreme temperature, a total of 26 542 (95% CI 25 301–27 804) deaths in 65+ and 1942 (95% CI 1834–2052) in 15–64-year-olds were associated with influenza from week 40, 2014 to week 20, 2015. This is compatible with the circulation of influenza A(H3N2). It is the largest estimated number of influenza-related deaths in England since prior to 2008/09. The findings highlight the potential health impact of influenza and the important role of the annual influenza vaccination programme that is required to protect the population including the elderly, who are vulnerable to a severe outcome.
OBJECTIVES/SPECIFIC AIMS: Key factors causing irreproducibility of research include those related to inappropriate study design methodologies and statistical analysis. In modern statistical practice irreproducibility could arise due to statistical (false discoveries, p-hacking, overuse/misuse of p-values, low power, poor experimental design) and computational (data, code and software management) issues. These require understanding the processes and workflows practiced by an organization, and the development and use of metrics to quantify reproducibility. METHODS/STUDY POPULATION: Within the Foundation of Discovery – Population Health Research, Center for Clinical and Translational Science, University of Utah, we are undertaking a project to streamline the study design and statistical analysis workflows and processes. As a first step we met with key stakeholders to understand the current practices by eliciting example statistical projects, and then developed process information models for different types of statistical needs using Lucidchart. We then reviewed these with the Foundation’s leadership and the Standards Committee to come up with ideal workflows and model, and defined key measurement points (such as those around study design, analysis plan, final report, requirements for quality checks, and double coding) for assessing reproducibility. As next steps we are using our finding to embed analytical and infrastructural approaches within the statisticians’ workflows. This will include data and code dissemination platforms such as Box, Bitbucket, and GitHub, documentation platforms such as Confluence, and workflow tracking platforms such as Jira. These tools will simplify and automate the capture of communications as a statistician work through a project. Data-intensive process will use process-workflow management platforms such as Activiti, Pegasus, and Taverna. RESULTS/ANTICIPATED RESULTS: These strategies for sharing and publishing study protocols, data, code, and results across the spectrum, active collaboration with the research team, automation of key steps, along with decision support. DISCUSSION/SIGNIFICANCE OF IMPACT: This analysis of statistical methods and process and computational methods to automate them ensure quality of statistical methods and reproducibility of research.
OBJECTIVES/SPECIFIC AIMS: The objective of this research is to determine under what conditions endpoints based on estimated glomerular filtration rate (eGFR) slope or on relatively small declines in eGFR provide valid and useful surrogate endpoints for pivotal clinical trials in chronic kidney disease (CKD) patients. METHODS/STUDY POPULATION: We consider 2 classes of surrogate endpoints. The first class includes endpoints defined by the average rate of change in eGFR during defined portions of the follow-up period of the trial, following initiation of the randomized treatment interventions. The second class includes composite endpoints defined by the time from randomization until the occurrence of a designated decline in eGFR or kidney failure. The true clinical endpoint is considered to be the time from randomization until kidney failure, irrespective of the trajectory in eGFR measurements prior to kidney failure. We apply statistical simulation to determine conditions under which alternative endpoints within the 2 classes are (1) valid surrogate endpoints, in the sense of preserving a low probability of rejecting the null hypothesis of no treatment effect on the surrogate endpoint when there is no treatment effect on the clinical endpoints and are also (2) useful surrogate endpoints, in the sense of providing increased statistical power that allows significant reductions in sample size and/or duration of follow-up. Input parameters for the simulations include (a) characteristics of the joint distribution of the longitudinal eGFR measurements and the time to occurrence of renal failure, (b) characteristics of the short-term and long-term effects of the treatment, and (c) design parameters, including the duration of accrual and follow-up and the spacing of eGFR measurements during the follow-up period. We use joint analyses of 19 treatment comparisons across 13 previous clinical trials of CKD patients to guide the selection of input parameters for the simulations. We apply longitudinal mixed effects models for analysis of endpoints based on eGFR slope, and Cox regression for analyses of the composite time-to-event endpoints. RESULTS/ANTICIPATED RESULTS: We have previously shown that surrogate endpoints defined by eGFR declines of 30% or 40% can provide valid and useful alternative endpoints in CKD clinical trials for interventions that do not produce short-term effects on eGFR which differ from the longer-term effects of the interventions. Other factors influencing the validity and utility of these endpoints include the average baseline eGFR, the mean rate of change in eGFR, and the extent to which the size of the treatment effect depends on the patient’s underling rate of eGFR decline. We will extend these results by presenting preliminary results describing conditions under which outcomes based on eGFR slope provide valid and useful alternatives to the clinical endpoint of time until occurrence of kidney failure. DISCUSSION/SIGNIFICANCE OF IMPACT: The statistical simulation strategy described in this research can be used during the design of clinical trials of chronic kidney disease to assist in the selection of endpoints that maximize savings in sample size and duration of follow-up while retaining a low risk of producing a false positive conclusion in the absence of a true effect of the treatment on the time until kidney failure.
Intensive archaeobotanical investigations at Çatalhöyük have created a unique opportunity to explore change and continuity in plant use through the ca 1,500-year Neolithic to early Chalcolithic sequence of an early established farming community. The combination of crops and herd animals in the earliest (Aceramic) part of the sequence reflects a distinct and diverse central Anatolian ‘package’ at the end of the eighth millennium cal. BC. Here we report evidence for near continual adjustment of cropping regimes through time at Çatalhöyük, featuring recruitment of minor crops or crop contaminants to become major staples. We use panarchy theory to frame an understanding of Çatalhöyük's long-term sustainability, arguing that its resilience was a function of three key factors: its diverse initial crop spectrum, which acted as an archive for later innovations; its modular social structure, enabling small-scale experimentation and innovation in cropping at the household level; and its agglomerated social morphology, allowing successful developments to be scaled up across the wider community. This case study in long-term sustainability through flexible, changeable cropping strategies is significant not only for understanding so-called boom and bust cycles elsewhere but also for informing wider agro-ecological understanding of sustainable development in central Anatolia and beyond.