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Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.
OBJECTIVES/GOALS: To introduce the new Team Science Community Toolkit, co-created by community and academic partners, and showcase its potential to empower Community Organizations (COs) in achieving equity in community-engaged research (CER). METHODS/STUDY POPULATION: In response to the challenges faced by COs in CER collaborations, qualitative interviews were conducted with CO staff from historically marginalized communities. These interviews informed the development of the Team Science Community Toolkit, a collaborative effort involving a Community Advisory Board (CAB) and Team Science experts from Northwestern University. The toolkit, designed using a community-based participatory research approach, incorporates the Science of Team Science and User-Centered Design principles. Integrated into the NIH-sponsored COALESCE website, it includes templates, checklists, and interactive tools, along with a real-world simulation, to support COs in all stages of the research process. RESULTS/ANTICIPATED RESULTS: Focus groups and usability testing involving external community experts validated the toolkit’s content and usability. Participants expressed enthusiasm and a sense of empowerment, indicating that the toolkit allows them to actively shape research processes and infuse their specific voices and needs into their partnerships. The toolkit is designed to support breaking down barriers like jargon and cultural adaptability to improve accessibility and open conversation. The impact of this Team Science focused toolkit is under evaluation. This presentation will showcase the toolkit, detail its collaborative development, and explore potential applications, ultimately offering a path to more equitable and valuable community-based research. DISCUSSION/SIGNIFICANCE: By providing COs with the resources and knowledge to participate as equal partners in research collaborations, it enhances self-advocacy, transparency, and equity. The toolkit has the potential to utilize Team Science to foster productive communication in community-academic research partnerships.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5–11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29–3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.
Growth patterns of breastfed infants show substantial inter-individual differences, partly influenced by breast milk (BM) nutritional composition. However, BM nutritional composition does not accurately indicate BM nutrient intakes. This study aimed to examine the associations between both BM intake volumes and macronutrient intakes with infant growth. Mother–infant dyads (n 94) were recruited into the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) from a single maternity hospital at birth; all infants received exclusive breast-feeding (EBF) for at least 6 weeks. Infant weight, length and skinfolds thicknesses (adiposity) were repeatedly measured from birth to 12 months. Post-feed BM samples were collected at 6 weeks to measure TAG (fat), lactose (carbohydrate) (both by 1H-NMR) and protein concentrations (Dumas method). BM intake volume was estimated from seventy infants between 4 and 6 weeks using dose-to-the-mother deuterium oxide (2H2O) turnover. In the full cohort and among sixty infants who received EBF for 3+ months, higher BM intake at 6 weeks was associated with initial faster growth between 0 and 6 weeks (β + se 3·58 + 0·47 for weight and 4·53 + 0·6 for adiposity gains, both P < 0·0001) but subsequent slower growth between 3 and 12 months (β + se − 2·27 + 0·7 for weight and −2·65 + 0·69 for adiposity gains, both P < 0·005). BM carbohydrate and protein intakes at 4–6 weeks were positively associated with early (0–6 weeks) but tended to be negatively related with later (3–12 months) adiposity gains, while BM fat intake showed no association, suggesting that carbohydrate and protein intakes may have more functional relevance to later infant growth and adiposity.
In November 2019, an outbreak of Shiga toxin-producing Escherichia coli O157:H7 was detected in South Yorkshire, England. Initial investigations established consumption of milk from a local dairy as a common exposure. A sample of pasteurised milk tested the next day failed the phosphatase test, indicating contamination of the pasteurised milk by unpasteurised (raw) milk. The dairy owner agreed to immediately cease production and initiate a recall. Inspection of the pasteuriser revealed a damaged seal on the flow divert valve. Ultimately, there were 21 confirmed cases linked to the outbreak, of which 11 (52%) were female, and 12/21 (57%) were either <15 or >65 years of age. Twelve (57%) patients were treated in hospital, and three cases developed haemolytic uraemic syndrome. Although the outbreak strain was not detected in the milk samples, it was detected in faecal samples from the cattle on the farm. Outbreaks of gastrointestinal disease caused by milk pasteurisation failures are rare in the UK. However, such outbreaks are a major public health concern as, unlike unpasteurised milk, pasteurised milk is marketed as ‘safe to drink’ and sold to a larger, and more dispersed, population. The rapid, co-ordinated multi-agency investigation initiated in response to this outbreak undoubtedly prevented further cases.
Conservation scientists are increasingly recognizing the need to evaluate the effectiveness of interventions to improve human–wildlife coexistence across different contexts. Here we assessed the long-term efficacy of the Long Shields Community Guardians programme in Zimbabwe. This community-based programme seeks to protect livestock and prevent depredation by lions Panthera leo through non-lethal means, with the ultimate aim of promoting human–lion coexistence. Using a quasi-experimental approach, we measured temporal trends in livestock depredation by lions and the prevalence of retaliatory killing of lions by farmers and wildlife managers. Farmers that were part of the Long Shields programme experienced a significant reduction in livestock loss to lions, and the annual number of lions subject to retaliatory killing by farmers dropped by 41% since the start of the programme in 2013, compared to 2008–2012, before the programme was initiated. Our findings demonstrate the Long Shields programme can be a potential model for limiting livestock depredation by lions. More broadly, our study demonstrates the effectiveness of community-based interventions to engage community members, improve livestock protection and ameliorate levels of retaliatory killing, thereby reducing human–lion conflict.
Later Cambrian and earliest Ordovician trilobites and brachiopods spanning eight horizons from five localities within the Sông Mã, Hàm Rồng and Đông Sơn formations of the Thanh Hóa province of Việt Nam, constrain the age and faunal affinities of rocks within the Sông Đà terrane, one of several suture/fault-bounded units situated between South China to the north and Indochina to the south. ‘Ghost-like’ preservation in dolomite coupled with tectonic deformation leaves many of the fossils poorly preserved, and poor exposure precludes collecting within continuously exposed stratigraphic successions. Cambrian carbonate facies pass conformably into Lower Ordovician carbonate-rich strata that also include minor siliciclastic facies, and the recovered fauna spans several uppermost Cambrian and Lower Ordovician biozones. The fauna is of equatorial Gondwanan affinity, and comparable to that from South China, North China, Sibumasu and Australia. A new species of Miaolingian ‘ptychopariid’ trilobite, Kaotaia xuanensis, is described. Detrital zircon samples from Cambrian–Ordovician rocks of the North Việt Nam and Sông Đà terranes, and from Palaeozoic samples from the Trường Sơn sector of Indochina immediately to the south, contain a predominance of ages spanning the Neoproterozoic period and have a typical equatorial Gondwanan signature. We associate the Cambrian and Tremadocian of the Sông Đà terrane with areas immediately to the north of it, including the North Việt Nam terrane and the southern parts of Yunnan and Guangxi provinces of China.
Pollen-mediated gene flow (PMGF) refers to the transfer of genetic information (alleles) from one plant to another compatible plant. With the evolution of herbicide-resistant (HR) weeds, PMGF plays an important role in the transfer of resistance alleles from HR to susceptible weeds; however, little attention is given to this topic. The objective of this work was to review reproductive biology, PMGF studies, and interspecific hybridization, as well as potential for herbicide resistance alleles to transfer in the economically important broadleaf weeds including common lambsquarters, giant ragweed, horseweed, kochia, Palmer amaranth, and waterhemp. The PMGF studies involving these species reveal that transfer of herbicide resistance alleles routinely occurs under field conditions and is influenced by several factors, such as reproductive biology, environment, and production practices. Interspecific hybridization studies within Amaranthus and Ambrosia spp. show that herbicide resistance allele transfer is possible between species of the same genus but at relatively low levels. The widespread occurrence of HR weed populations and high genetic diversity is at least partly due to PMGF, particularly in dioecious species such as Palmer amaranth and waterhemp compared with monoecious species such as common lambsquarters and horseweed. Prolific pollen production in giant ragweed contributes to PMGF. Kochia, a wind-pollinated species can efficiently disseminate herbicide resistance alleles via both PMGF and tumbleweed seed dispersal, resulting in widespread occurrence of multiple HR kochia populations. The findings from this review verify that intra- and interspecific gene flow can occur and, even at a low rate, could contribute to the rapid spread of herbicide resistance alleles. More research is needed to determine the role of PMGF in transferring multiple herbicide resistance alleles at the landscape level.
The International Personality Item Pool (IPIP) five-factor model inventories are widely used for personality research and have been translated into multiple languages. However, the extent of the psychometric assessment of translated scales is variable, often minimal. The lack of psychometric scrutiny is particularly problematic because translation is an inherently complex process. Here, we present a structural analysis of one Spanish translation of the 50-item IPIP five-factor inventory in a sample of Peruvian, non-university educated, working adults (n = 778). A global confirmatory factor analytic (CFA) model of the a priori five factors failed to fit. So too did single factor models for four of the five factors, the exception being Neuroticism. Fit was improved via use of an exploratory structural equation measurement model, but the resultant solution showed very poor theoretical coherence. So, we explored the data for systematic measurement artefacts and sought to model them to improve the psychometric properties of the scale. Specifically, the pattern of factor loadings suggested that the lack of coherence might be due to the effects of the valence of item wording (i.e., positively or negatively worded items). CFA models including five substantive factors and a series of method factors modelling shared covariance based on item wording, improved fit and coherence. This investigation suggests that unless method factors are explicitly modelled the tested Spanish translation may not be suitable for use in certain Spanish-speaking countries or samples composed of non-university educated participants. More broadly, the study has implications for many translated scales, especially when used without thorough psychometric evaluation.
In 2013, a task force was developed to discuss the future of the Canadian pediatric neurology workforce. The consensus was that there was no indication to reduce the number of training positions, but that the issue required continued surveillance. The current study provides a 5-year update on Canadian pediatric neurology workforce data.
Methods:
Names, practice types, number of weekly outpatient clinics, and dates of certification of all physicians currently practicing pediatric neurology in Canada were obtained. International data were used to compute comparisons between countries. National data sets were used to provide information about the number of residency positions available and the number of Canadian graduates per year. Models for future projections were developed based on published projected population data and trends from the past decade.
Results:
The number of pediatric neurologists practicing in Canada has increased 165% since 1994. During this period, wait times have not significantly shortened. There are regional discrepancies in access to child neurologists. The Canadian pediatric neurology workforce available to see outpatient consultations is proportionally less than that of USA. After accounting for retirements and emigrations, the number of child neurologists being added to the workforce each year is 4.9. This will result in an expected 10-year increase in Canadian pediatric neurologists from 151 to 200.
Conclusions:
Despite an increase in the number of Canadian child neurologists over the last two decades, we do not predict that there will be problems with underemployment over the next decade.
Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.
Aims
To determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis.
Method
We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum.
Results
Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD.
Conclusions
Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.
Declaration of interest
D.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.
A large number of multispectral and stereo-image data are expected to become available as part of the Global Land Ice Measurements from Space project. We investigate digital elevation model extraction, anisotropic reflectance correction and selected glacier analysis tasks that must be developed to achieve full utility of these new data. Results indicate that glaciers in the Karakoram and Nanga Parbat Himalaya, northern Pakistan, exhibit unique spectral, spatial and geomorphometric patterns that can be exploited by various models and algorithms to produce accurate information regarding glacier extent, supraglacial features and glacier geomorphology The integration of spectral, spatial and geomorphometric features, coupled with approaches for advanced pattern recognition, can help geoscientists study glacier mass balance, glacier erosion, sediment-transfer efficiency and landscape evolution.
Airborne radio-echo sounding investigations in the upper reaches of Bailey Ice Stream and Slessor Glacier, Coats Land, East Antarctica, have shown that enhanced-flow tributaries are associated with well-defined areas of relatively thicker ice, and are separated from each other by areas of relatively thinner ice. A numerical modelling study has revealed that while internal ice deformation might account for all the observed flow in inter-tributary areas and the majority in the Slessor tributaries, a significant proportion of the flow of Bailey tributary is attributable to basal motion. Further, investigations of depth-corrected basal reflection power indicate that the bed underlying both Bailey and Slessor enhanced-flow tributaries is significantly smoother than in the slower-moving inter-tributary areas. It is thus proposed that enhanced motion within Bailey tributary (and also perhaps Slessor) may be facilitated by a reduction in basal roughness, caused by the accumulation of water and/or sediments within subglacial valleys, or by the erosion and smoothing of bed obstacles.
Surveys were conducted across the northern Great Plains of Canada in 1996 and 1997 to determine the nature and occurrence of herbicide-resistant (HR) biotypes of wild oat (Avena fatua). The surveys indicated that resistance to acetyl-CoA carboxylase (ACCase) inhibitors (Group 1) occurred most frequently relative to other herbicide groups. Group 1-HR wild oat occurred in over one-half of fields surveyed in each of the three prairie provinces. Of particular concern was the relatively high incidence of multiple-group resistance in wild oat in Saskatchewan and Manitoba. In Saskatchewan, 18% of Group 1-HR populations were also resistant to acetolactate synthase inhibitors (imidazolinones), even though these herbicides were not frequently used. In Manitoba, 27% of fields surveyed had wild oat resistant to herbicides from more than one group. Four populations were resistant to all herbicides registered for use in wheat (Triticum aestivum). Depending on the nature of resistance in wild oat, alternative herbicides available for their control may substantially increase costs to the grower. The cost to growers of managing HR wild oat in Saskatchewan and Manitoba using alternative herbicides is estimated at over $4 million annually. For some HR biotypes, alternative herbicides either are not available or all have the same site of action, which restricts crop or herbicide rotation options and threatens the future sustainability of small-grain annual cropping systems where these infestations occur.
We present low-frequency spectral energy distributions of 60 known radio pulsars observed with the Murchison Widefield Array telescope. We searched the GaLactic and Extragalactic All-sky Murchison Widefield Array survey images for 200-MHz continuum radio emission at the position of all pulsars in the Australia Telescope National Facility (ATNF) pulsar catalogue. For the 60 confirmed detections, we have measured flux densities in 20 × 8 MHz bands between 72 and 231 MHz. We compare our results to existing measurements and show that the Murchison Widefield Array flux densities are in good agreement.
To describe why and how capacity-building systems for scaling up nutrition programmes should be constructed in low- and middle-income countries (LMIC).
Design
Position paper with task force recommendations based on literature review and joint experience of global nutrition programmes, public health nutrition (PHN) workforce size, organization, and pre-service and in-service training.
Setting
The review is global but the recommendations are made for LMIC scaling up multisectoral nutrition programmes.
Subjects
The multitude of PHN workers, be they in the health, agriculture, education, social welfare, or water and sanitation sector, as well as the community workers who ensure outreach and coverage of nutrition-specific and -sensitive interventions.
Results
Overnutrition and undernutrition problems affect at least half of the global population, especially those in LMIC. Programme guidance exists for undernutrition and overnutrition, and priority for scaling up multisectoral programmes for tackling undernutrition in LMIC is growing. Guidance on how to organize and scale up such programmes is scarce however, and estimates of existing PHN workforce numbers – although poor – suggest they are also inadequate. Pre-service nutrition training for a PHN workforce is mostly clinical and/or food science oriented and in-service nutrition training is largely restricted to infant and young child nutrition.
Conclusions
Unless increased priority and funding is given to building capacity for scaling up nutrition programmes in LMIC, maternal and child undernutrition rates are likely to remain high and nutrition-related non-communicable diseases to escalate. A hybrid distance learning model for PHN workforce managers’ in-service training is urgently needed in LMIC.
Background: Little knowledge exists on the availability of academic and community paediatric neurology positions. This knowledge is crucial for making workforce decisions. Our study aimed to: 1) obtain information regarding the availability of positions for paediatric neurologists in academic centres; 2) survey paediatric neurology trainees regarding their perceptions of employment issues and career plans; 3) survey practicing community paediatric neurologists 4) convene a group of paediatric neurologists to develop consensus regarding how to address these workforce issues. Methods: Surveys addressing workforce issues regarding paediatric neurology in Canada were sent to: 1) all paediatric neurology program directors in Canada (n=9) who then solicited information from division heads and from paediatric neurologists in surrounding areas; 2) paediatric neurology trainees in Canada (n=57) and; 3) community paediatric neurologists (n=27). A meeting was held with relevant stakeholders to develop a consensus on how to approach employment issues. Results: The response rate was 100% from program directors, 57.9% from residents and 44% from community paediatric neurologists. We found that the number of projected positions in academic paediatric neurology is fewer than the number of paediatric neurologists that are being trained over the next five to ten years, despite a clinical need for paediatric neurologists. Paediatric neurology residents are concerned about job availability and desire more career counselling. Conclusions: There is a current and projected clinical demand for paediatric neurologists despite a lack of academic positions. Training programs should focus on community neurology as a viable career option.