Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.

Observations of the 21 cm signal face significant challenges due to bright astrophysical foregrounds that are several orders of magnitude higher than the brightness of the hydrogen line, along with various systematics. Successful 21 cm experiments require accurate calibration and foreground mitigation. Errors introduced during the calibration process such as systematics can disrupt the intrinsic frequency smoothness of the foregrounds, leading to power leakage into the Epoch of Reionisation window. Therefore, it is essential to develop strategies to effectively address these challenges. In this work, we adopt a stringent approach to identify and address suspected systematics, including malfunctioning antennas, frequency channels corrupted by radio frequency interference, and other dominant effects. We implement a statistical framework that utilises various data products from the data processing pipeline to derive specific criteria and filters. These criteria and filters are applied at intermediate stages to mitigate systematic propagation from the early stages of data processing. Our analysis focuses on observations from the Murchison Widefield Array Phase I configuration. Out of the observations processed by the pipeline, our approach selects 18%, totalling 58 h, that exhibit fewer systematic effects. The successful selection of observations with reduced systematic dominance enhances our confidence in achieving 21 cm measurements.

We synthesize sea-level science developments, priorities and practitioner needs at the end of the 10-year World Climate Research Program Grand Challenge ’Regional Sea-Level Change and Coastal Impacts’. Sea-level science and associated climate services have progressed but are unevenly distributed. There remains deep uncertainty concerning high-end and long-term sea-level projections due to indeterminate emissions, the ice sheet response and other climate tipping points. These are priorities for sea-level science. At the same time practitioners need climate services that provide localized information including median and curated high-end sea-level projections for long-term planning, together with information to address near-term pressures, including extreme sea level-related hazards and land subsidence, which can greatly exceed current rates of climate-induced sea-level rise in some populous coastal settlements. To maximise the impact of scientific knowledge, ongoing co-production between science and practitioner communities is essential. Here we report on recent progress and ways forward for the next decade.

In 2020, an outbreak of Salmonella Hadar illnesses was linked to contact with non-commercial, privately owned (backyard) poultry including live chickens, turkeys, and ducks, resulting in 848 illnesses. From late 2020 to 2021, this Salmonella Hadar strain caused an outbreak that was linked to ground turkey consumption. Core genome multilocus sequence typing (cgMLST) analysis determined that the Salmonella Hadar isolates detected during the outbreak linked to backyard poultry and the outbreak linked to ground turkey were closely related genetically (within 0–16 alleles). Epidemiological and traceback investigations were unable to determine how Salmonella Hadar detected in backyard poultry and ground turkey were linked, despite this genetic relatedness. Enhanced molecular characterization methods, such as analysis of the pangenome of Salmonella isolates, might be necessary to understand the relationship between these two outbreaks. Similarly, enhanced data collection during outbreak investigations and further research could potentially aid in determining whether these transmission vehicles are truly linked by a common source and what reservoirs exist across the poultry industries that allow Salmonella Hadar to persist. Further work combining epidemiological data collection, more detailed traceback information, and genomic analysis tools will be important for monitoring and investigating future enteric disease outbreaks.

Globally, human house types are diverse, varying in shape, size, roof type, building materials, arrangement, decoration and many other features. Here we offer the first rigorous, global evaluation of the factors that influence the construction of traditional (vernacular) houses. We apply macroecological approaches to analyse data describing house features from 1900 to 1950 across 1000 societies. Geographic, social and linguistic descriptors for each society were used to test the extent to which key architectural features may be explained by the biophysical environment, social traits, house features of neighbouring societies or cultural history. We find strong evidence that some aspects of the climate shape house architecture, including floor height, wall material and roof shape. Other features, particularly ground plan, appear to also be influenced by social attributes of societies, such as whether a society is nomadic, polygynous or politically complex. Additional variation in all house features was predicted both by the practices of neighouring societies and by a society's language family. Collectively, the findings from our analyses suggest those conditions under which traditional houses offer solutions to architects seeking to reimagine houses in light of warmer, wetter or more variable climates.

Advance consent could allow individuals at high risk of stroke to provide consent before they might become eligible for enrollment in acute stroke trials. This survey explores the acceptability of this novel technique to Canadian Research Ethics Board (REB) chairs that review acute stroke trials. Responses from 15 REB chairs showed that majority of respondents expressed comfort approving studies that adopt advance consent. There was no clear preference for advance consent over deferral of consent, although respondents expressed significant concern with broad rather than trial-specific advance consent. These findings shed light on the acceptability of advance consent to Canadian ethics regulators.

Turfgrass managers apply nonselective herbicides to control winter annual weeds during dormancy of warm-season turfgrass. Zoysiagrass subcanopies, however, retain green leaves and stems during winter dormancy, especially in warmer climates. The partially green zoysiagrass often deters the use of nonselective herbicides due to variable injury concerns in transition and southern climatic zones. This study evaluated zoysiagrass response to glyphosate and glufosinate applied at four different growing degree day (GDD)-based application timings during postdormancy transition in different locations, including Blacksburg, VA; Starkville, MS; and Virginia Beach, VA, in 2018 and 2019. GDD was calculated using a 5 C base temperature with accumulation beginning January 1 each year, and targeted application timings were 125, 200, 275, and 350 GDD5C. Zoysiagrass injury response to glyphosate and glufosinate was consistent across a broad growing region from northern Mississippi to coastal Virginia, but it varied by application timing. Glyphosate application at 125 and 200 GDD5C can be used safely for weed control during the postdormancy period of zoysiagrass, while glufosinate caused unacceptable turf injury regardless of application timing. Glyphosate and glufosinate exhibited a stepwise increase to maximum injury with increasing targeted GDD5C application timings. Glyphosate applied at 125 or 200 GDD5C did not injure zoysiagrass above a threshold of 30%, whereas glufosinate caused greater than 30% injury for 28 and 29 d when applied at 125 and 200 GDD5C, respectively. Likewise, glyphosate application at 125 or 200 GDD5C did not affect the zoysiagrass green cover area under the progress curve per day, whereas later applications reduced it. Glyphosate and glufosinate caused greater injury to zoysiagrass when applied at greater cumulative heat units and this was attributed to increasing turfgrass green leaf density, because heat unit accumulation is positively correlated with green leaf density. Accumulated heat unit-based application timing will allow practitioners to apply nonselective herbicides with reduced injury concerns.

We introduce a new approach to estimating long-term aggregate discount rates using the cross section of earnings and book values to explain current stock prices and extract expected market returns. The proposed discount rate measure is countercyclical. Shocks to it account for nearly half of historical market return variation; in contrast, shocks to other discount rate measures account for no more than 2%. It dominates other measures in explaining time-series variation in returns on duration-sorted portfolios and delivers out-of-sample predictability that exceeds that afforded by other expected return measures and predictive variables. It also performs well in international equity markets.

Advance consent presents a potential solution to the challenge of obtaining informed consent for participation in acute stroke trials. Clinicians in stroke prevention clinics are uniquely positioned to identify and seek consent from potential stroke trial participants. To assess the acceptability of advance consent to Canadian stroke clinic physicians, we performed an online survey. We obtained 58 respondents (response rate 35%): the vast majority (82%) expressed comfort with obtaining advance consent and 92% felt that doing so would not be a significant disruption to clinic workflow. These results support further study of advance consent for acute stroke trials.

Background: Clinical outcomes following childhood arterial ischaemic stroke (AIS) depend on age at the time of stroke, infarct size and location. However, other important variables including health inequity and stroke onset to arrival times remain inadequately addressed. This study reported trends in health inequity and stroke onset to arrival times along with proximity to a stroke centre in Canada. Methods: Childhood AIS patients (N=234) with stroke onset between 2004-2019 at a Level 2 (comprehensive) stroke centre were included. Measures of material deprivation included household income, education, single-parent families, and housing quality. Patients were stratified into 3 cohorts (by date of stroke onset) and postal codes were categorized as minimal, moderate, or most deprived neighbourhoods. Results: Over the 16-year period, an increasing number of patients arrived from the most deprived neighbourhoods. Although, there was no significant association between material deprivation and stroke onset to arrival time, an increasing number of patients presented within 6 hours of stroke onset (χ2 = 13.8, p = 0.008). Furthermore, most patients arrived from urban neighbourhoods. Conclusions: The faster stroke onset to arrival trend is encouraging, however, material deprivation trends are concerning. Thus, future studies exploring post-stroke outcomes should consider material deprivation, stroke onset to arrival times, and geographical proximity.

We conducted a retrospective chart review examining the demographics, clinical history, physical findings, and comorbidities of patients with influenza and patients with coronavirus disease 2019 (COVID-19). Older patients, male patients, patients reporting fever, and patients with higher body mass indexes (BMIs) were more likely to have COVID-19 than influenza.

During the 2018/19 Antarctic field season, the British Antarctic Survey (BAS) Basal conditions on Rutford Ice Stream: BEd Access, Monitoring and Ice Sheet History’ (BEAMISH) project drilled three holes through the Rutford Ice Stream, West Antarctica. At up to 2154 m, these are the deepest hot water drilled subglacial access holes yet created, enabling the recovery of sediment from the subglacial environment, and instrumenting the ice stream and its bed. The BEAMISH hot-water drill system was built on extensive experience with the BAS ice shelf hot-water drill and utilises many identical components. With up to 1 MW of heating power available, the hot water drill produces 140 L min−1 of water at 85°C to create a 300 mm diameter access hole to the base of the ice stream. New systems and processes were developed for BEAMISH to aid critical aspects of deep access drilling, most notably the creation of cavities interlinking boreholes at 230 m below the surface and enabling water recirculation throughout the deep drilling operations. The modular design of the BEAMISH drill offers many benefits in its adaptability, redundancy, and minimal logistical footprint. These design features can easily accommodate the modifications needed for future deep, clean access hole creation in the exploration of subglacial environments.

Three holes were drilled to the bed of Rutford Ice Stream, through ice up to 2154 m thick, to investigate the basal processes and conditions associated with fast ice flow and the glacial history of the West Antarctic Ice Sheet. A narrative of the drilling, measuring and sampling activities, as well as some preliminary results and initial interpretations of subglacial conditions, is given. These were the deepest subglacial access holes ever drilled using the hot-water drilling method. Samples of bed and englacial sediments were recovered, and a number of instruments were installed in the ice column and the bed. The ice–bed interface was found to be unfrozen, with an existing, well-developed subglacial hydrological system at high pressure, within ~1% of the ice overburden. The bed itself comprises soft, water-saturated sediments, consistent with previous geophysical interpretations. Englacial sediment quantity varies significantly between two locations ~2 km apart, and possibly over even shorter (~20 m) distances. Difficulties and unusual observations encountered while connecting to the subglacial hydrological system in one hole possibly resulted from the presence of a large clast embedded in the bottom of the ice.