Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

Foliar-applied postemergence applications of glufosinate are often applied to glufosinate-resistant crops to provide nonselective weed control without significant crop injury. Rainfall, air temperature, solar radiation, and relative humidity near the time of application have been reported to affect glufosinate efficacy. However, previous research may have not captured the full range of weather variability to which glufosinate may be exposed to prior to or following application. Additionally, climate models suggest more extreme weather will become the norm, further expanding this weather range glufosinate can be exposed to. The objective of this research was to quantify the probability of successful weed control (efficacy ≥85%) with glufosinate applied to some key weed species across a broad range of weather conditions. A database of >10,000 North American herbicide evaluation trials was used in this study. The database was filtered to include treatments with a single POST application of glufosinate applied to waterhemp (Amaranthus tuburculatus (Moq.) J. D. Sauer), morningglory species (Ipomoea spp.), and/or giant foxtail (Setaria faberi Herm.) <15cm in height. These species were chosen because they are well represented in the database and listed as common and troublesome weed species in both corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] (Van Wychen 2020, 2022). Individual random forest models were created. Low rainfall (≤20 mm) over the five days prior to glufosinate application was detrimental to the probability of successful control of A. tuburculatus and S. faberi. Lower relative humidity (≤70%) and solar radiation (≤23 MJ m-1 day-1) the day of application reduced the probability of successful weed control in most cases. Additionally, the probability of successful control decreased for all species when average air temperature over the first five days after application was ≤25C. As climate continues to change and become more variable, the risk of unacceptable control of several common species with glufosinate is likely to increase.

This paper analyzes the sum score based (SSB) formulation of the Rasch model, where items and sum scores of persons are considered as factors in a logit model. After reviewing the evolution leading to the equality between their maximum likelihood estimates, the SSB model is then discussed from the point of view of pseudo-likelihood and of misspecified models. This is then employed to provide new insights into the origin of the known inconsistency of the difficulty parameter estimates in the Rasch model. The main results consist of exact relationships between the estimated standard errors for both models; and, for the ability parameters, an upper bound for the estimated standard errors of the Rasch model in terms of those for the SSB model, which are more easily available.

Foliar-applied postemergence herbicides are a critical component of corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] weed management programs in North America. Rainfall and air temperature around the time of application may affect the efficacy of herbicides applied postemergence in corn or soybean production fields. However, previous research utilized a limited number of site-years and may not capture the range of rainfall and air temperatures that these herbicides are exposed to throughout North America. The objective of this research was to model the probability of achieving successful weed control (≥85%) with commonly applied postemergence herbicides across a broad range of environments. A large database of more than 10,000 individual herbicide evaluation field trials conducted throughout North America was used in this study. The database was filtered to include only trials with a single postemergence application of fomesafen, glyphosate, mesotrione, or fomesafen + glyphosate. Waterhemp [Amaranthus tuberculatus (Moq.) Sauer], morningglory species (Ipomoea spp.), and giant foxtail (Setaria faberi Herrm.) were the weeds of focus. Separate random forest models were created for each weed species by herbicide combination. The probability of successful weed control deteriorated when the average air temperature within the first 10 d after application was <19 or >25 C for most of the herbicide by weed species models. Additionally, drier conditions before postemergence herbicide application reduced the probability of successful control for several of the herbicide by weed species models. As air temperatures increase and rainfall becomes more variable, weed control with many of the commonly used postemergence herbicides is likely to become less reliable.

Ice rises hold valuable records revealing the ice dynamics and climatic history of Antarctic coastal areas from the Last Glacial Maximum to today. This history is often reconstructed from isochrone radar stratigraphy and simulations focusing on Raymond arch evolution beneath the divides. However, this relies on complex ice-flow models where many parameters are unconstrained by observations. Our study explores quad-polarimetric, phase-coherent radar data to enhance understanding near ice divides and domes, using Hammarryggen Ice Rise (HIR) as a case study. Analysing a 5 km profile intersecting the dome, we derive vertical strain rates and ice-fabric properties. These align with ice core data near the summit, increasing confidence in tracing signatures from the dome to the flanks. The Raymond effect is evident, correlating with surface strain rates and radar stratigraphy. Stability is inferred over millennia for the saddle connecting HIR to the mainland, but dome ice-fabric appears relatively young compared to 2D model predictions. In a broader context, quad-polarimetric measurements provide valuable insights into ice-flow models, particularly for anisotropic rheology. Including quad-polarimetric data advances our ability to reconstruct past ice flow dynamics and climatic history in ice rises.

The developmental origins of health and disease hypothesis have highlighted the link between early life environment and long-term health outcomes in offspring. For example, maternal protein restriction during pregnancy and lactation can result in adverse metabolic and cognitive outcomes in offspring postnatal. Hence, in the present study, we assess whether an isocaloric low-protein diet (ILPD) affects the fatty acid profile in breast milk, the hippocampal synaptophysin (Syn) ratio, and the oxidative stress markers in the neonatal stage of male and female offspring. The aim of this work was to assess the effect of an ILPD on the fatty acid profile in breast milk, quantified the hippocampal synaptophysin (Syn) ratio and oxidative stress markers in neonatal stage of male and female offspring. Female Wistar rats were fed with either a control diet or an ILPD during gestation to day 10 of lactation. Oxidative stress markers were assessed in serum and liver. All quantifications were done at postnatal day 10. The results showed: ILPD led to decreases of 38.5% and 17.4% in breast milk volume and polyunsaturated fatty acids content. Significant decreases of hippocampal Syn ratio in male offspring (decreases of 98% in hippocampal CA1 pyramidal and CA1 oriens, 83%, stratum pyramidal in CA3, 80%, stratum lucidum in CA3, and 81% stratum oriens in CA3). Male offspring showed an increase in pro-oxidant status in serum and liver. Thus, the data suggest that male offspring are more vulnerable than females to an ILPD during gestation and lactation.

Declining labor force participation of older men throughout the 20th century and recent increases in participation have generated substantial interest in understanding the effect of public pensions on retirement. The National Bureau of Economic Research's International Social Security (ISS) Project, a long-term collaboration among researchers in a dozen developed countries, has explored this and related questions. The project employs a harmonized approach to conduct within-country analyses that are combined for meaningful cross-country comparisons. The key lesson is that the choices of policy makers affect the incentive to work at older ages and these incentives have important effects on retirement behavior.

Background: The Uganda Ministry of Health (MoH) and implementing partners instituted an infection prevention and control (IPC) response strategy during the Uganda SVD outbreak in 2022 that involved rapid enhancement of screening capacity at HCFs. Rapid scale-up of screening for infectious diseases, such as SVD, is critical for early identification and triage of suspected or confirmed cases in HCFs. We describe the rapid deployment of a multimodal IPC strategy implemented in response to the SVD outbreak and the resulting impact on screening measures at HCFs. Methods: We implemented a multimodal IPC strategy in HCFs from five high risk districts to improve screening practices from November 2022–January 2023. The strategy included training health workers (HCWs) identified as IPC mentors; establishing screening areas; and providing screening supplies and communication materials. The three-day training utilized an MoH standardized training package with didactic and practice sessions. The mentors then cascaded screening information and skills to other HCWs through onsite trainings and mentorships and established screening areas. Baseline and endline (3 months after baseline) cross-sectional assessments were conducted using the MoH IPC Assessment Tool adapted from the WHO Ebola IPC Scorecard. The five main screening parameters assessed included presence of ≥ 1 meter distance between screener and the person screened, availability of a functional handwashing facility and infrared thermometer, correct record of each person’s temperature, and appropriate referral process for those suspected of having SVD to holding areas. IPC capacity was measured through the summation of each of these parameter results and calculated as an overall percentage. IBM SPSS Statistics 20 software was used for data analysis and a paired t-test done to determine any significant findings between mean scores (percentage) at baseline and endpoint. Results: A total of 296 IPC mentors were trained, screening information was cascaded to 3,899 HCWs, and screening areas were established in 1,135 HCFs. Based on the screening results from the MoH IPC assessment tool, capacity improved from 44% (SD=37) at baseline to 67% (SD=34) at endpoint. Screening capacity improved from baseline to endpoint among level II and public HCFs from 33% (SD=35) to 60% (SD=35) (p < 0 .05) and from 54% (SD=38) to 76% (SD=31) (p < 0 .05), respectively. Conclusion: Rapid implementation of a multimodal IPC strategy was successful in enhancing screening capacity across Uganda’s HCFs during a SVD response, which is critical for early identification of infected patients to interrupt transmission. This multimodal approach should be recommended for future response actions.

Observations of glacier melt and runoff are of fundamental interest in the study of glaciers and their interactions with their environment. Considerable recent interest has developed around distributed acoustic sensing (DAS), a sensing technique which utilizes Rayleigh backscatter in fiber optic cables to measure the seismo-acoustic wavefield in high spatial and temporal resolution. Here, we present data from a month-long, 9 km DAS deployment extending through the ablation and accumulation zones on Rhonegletscher, Switzerland, during the 2020 melt season. While testing several types of machine learning (ML) models, we establish a regression problem, using the DAS data as the dependent variable, to infer the glacier discharge observed at a proglacial stream gauge. We also compare two predictive models that only depend on meteorological station data. We find that the seismo-acoustic wavefield recorded by DAS can be utilized to infer proglacial discharge. Models using DAS data outperform the two models trained on meteorological data with mean absolute errors of 0.64, 2.25 and 2.72 m3 s−1, respectively. This study demonstrates the ability of in situ glacier DAS to be used for quantifying proglacial discharge and points the way to a new approach to measuring glacier runoff.

Changing practice patterns caused by the pandemic have created an urgent need for guidance in prescribing stimulants using telepsychiatry for attention-deficit hyperactivity disorder (ADHD). A notable spike in the prescribing of stimulants accompanied the suspension of the Ryan Haight Act, allowing the prescribing of stimulants without a face-to-face meeting. Competing forces both for and against prescribing ADHD stimulants by telepsychiatry have emerged, requiring guidelines to balance these factors. On the one hand, factors weighing in favor of increasing the availability of treatment for ADHD via telepsychiatry include enhanced access to care, reduction in the large number of untreated cases, and prevention of the known adverse outcomes of untreated ADHD. On the other hand, factors in favor of limiting telepsychiatry for ADHD include mitigating the possibility of exploiting telepsychiatry for profit or for misuse, abuse, and diversion of stimulants. This Expert Consensus Group has developed numerous specific guidelines and advocates for some flexibility in allowing telepsychiatry evaluations and treatment without an in-person evaluation to continue. These guidelines also recognize the need to give greater scrutiny to certain subpopulations, such as young adults without a prior diagnosis or treatment of ADHD who request immediate-release stimulants, which should increase the suspicion of possible medication diversion, misuse, or abuse. In such cases, nonstimulants, controlled-release stimulants, or psychosocial interventions should be prioritized. We encourage the use of outside informants to support the history, the use of rating scales, and having access to a hybrid model of both in-person and remote treatment.

Although the practice of human sacrifice in the British Iron Age is mentioned by multiple authors, both ancient and modern, physical proof of such activity in the archaeological record is comparatively rare. At Winterborne Kingston, in Dorset, the skeletal remains of a young adult female found face down near the base of a cylindrical storage pit provides clear evidence of violent death in the later Iron Age. Analysis of the skeleton suggests an individual who led a hard-working life and who, having suffered an act of violence a few weeks before death, was killed, possibly with her hands tied, by a blade incision to the neck. Placement of the body further suggests that killing was enacted within the pit, execution as spectacle forming the final act in a larger ceremony involving the creation of an animal bone stack or platform.

Equine strongylid parasites are ubiquitous around the world and are main targets of parasite control programmes. In recent years, automated fecal egg counting systems based on image analysis have become available allowing for collection and analysis of large-scale egg count data. This study aimed to evaluate equine strongylid fecal egg count (FEC) data generated with an automated system over three years in the US with specific attention to seasonal and regional trends in egg count magnitude and sampling activity. Five US regions were defined; North East, South East, North Central, South Central and West. The data set included state, region and zip code for each FEC. The number of FECs falling in each of the following categories were recorded: (1) 0 eggs per gram (EPG), (2) 1 ⩽ 200 EPG, (3) 201 ⩽ 500 EPG and (4) >500 EPG. The data included 58 329 FECs. A fixed effects model was constructed fitting the number of samples analysed per month, year and region, and a mixed effects model was constructed to fit the number of FECs falling in each of the 4 egg count categories defined above. The overall proportion of horses responsible for 80% of the total FEC output was 18.1%, and this was consistent across years, months and all regions except West, where the proportion was closer to 12%. Statistical analyses showed significant seasonal trends and regional differences of sampling frequency and FEC category. The data demonstrated that veterinarians tended to follow a biphasic pattern when monitoring strongylid FECs in horses, regardless of location.

OBJECTIVES/GOALS: Adoption of the Observational Medical Outcomes Partnership (OMOP) common data model promises to transform large-scale observational health research. However, there are diverse challenges for operationalizing OMOP in terms of interoperability and technical skills among coordinating centers throughout the US. METHODS/STUDY POPULATION: A team from the Critical Path Institute (C-Path) collaborated with the informatics team members at Johns Hopkins to provide technical support to participating sites as part of the Extract, Transform, and Load (ETL) process linking existing concepts to OMOP concepts. Health systems met regularly via teleconference to review challenges and progress in ETL process. Sites were responsible for performing the local ETL process with assistance and securely provisioning de-identified data as part of the CURE ID program. RESULTS/ANTICIPATED RESULTS: More than twenty health systems participated in the CURE ID effort.Laboratory measures, basic demographics, disease diagnoses and problem list were more easily mapped to OMOP concepts by CURE ID partner institutions. Outcomes, social determinants of health, medical devices, and specific treatments were less easily characterized as part of the project. Concepts within the medical record presented very different technical challenges in terms of representation. There is a lack of standardization in OMOP implementation even among centers using the same electronic medical health record. Readiness to adopt OMOP varied across the institutions who participated. Health systems achieved variable level of coverage using OMOP medical concepts as part of the initiative. DISCUSSION/SIGNIFICANCE: Adoption of OMOP involves local stakeholder knowledge and implementation. Variable complexity of health concepts contributed to variable coverage. Documentation and support require extensive time and effort. Open-source software can be technically challenging. Interoperability of secure data systems presents unique problems.