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Soybean is an essential protein and oilseed crop, but environmental factors, such as photoperiod and altitude, highly influence its growth. Poor adaptability of soybean cultivars may result in a significant decrease in seed yield due to disruption of flowering or maturity. It is, therefore, vital to select cultivars adapted to specific regions of the world. Global climate change, causing increasing temperature and associated water deficit stress, may further challenge sustainable soybean production worldwide. Therefore, it is necessary to understand genetic responses in soybeans induced by environmental variables. This review highlights previous research showing how several quantitative trait loci (QTLs) activated by photo-thermal responses affected soybean flowering. We discuss cytogenetic stocks, including chromosome segment substitution lines, and their role in introgressing novel genes from wild soybeans. A review of genes showing responses to various environmental variables that affect soybean adaptability is also ensued, with putative functions suggested. These include gene response regulation to temperature and heat stress, identified via genetic mapping, and emerged as tools for developing adapted soybean cultivars. [ABSTRACT FROM AUTHOR]

Objectives: To describe the operational model, epidemiology and outcomes of COVID-19 cases managed by the first decentralised Victorian Public Health Unit (PHU) in the Barwon South-West (BSW) region in 2020., Methods: The Barwon Health team used a clinician-led, locally-based interprofessional model of care, combining clinical care and monitoring, contact tracing and public health measures., Results: From 7th March to 5th October 2020, 575 confirmed COVID-19 cases (82 in Wave 1; 493 in Wave 2) were identified in residents of the BSW region. Overall, 4.7% were admitted to local hospitals (0.7% to intensive care units) and 1.7% died. COVID-19 incidence in the region was 129 cases/100,000. Wave 2 in the region featured community transmission in high-risk settings and among culturally and linguistically diverse and mobile populations. Within 3 months of the initial local case in Wave 2, SARS-COV-2 was eliminated from the community., Conclusions: A local interprofessional model of care was key to the containment of community transmission and complex outbreaks with the elimination of COVID-19 in the community., Implications for Public Health: Key successes and learnings from the BSW PHU contributed to the improvement of statewide systems and responses and provided an impetus for the implementation of a decentralised public health model for Victoria., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Not being in employment, education, or training (NEET) is associated with poor health (physical and mental) and social exclusion. We investigated whether England's statutory school readiness measure conducted at 4-5 years provides a risk signal for NEET in late adolescence., Methods: We identified 8,118 individuals with school readiness measures at 4-5 years and NEET records at 16-17 years using Connected Bradford, a bank of linked routinely collected datasets. Children were categorised as 'school ready' if they reached a 'Good Level of Development' on the Early Years Foundation Stage Profile. We used probit regression and structural equation modelling to investigate the relationship between school readiness and NEET status and whether it primarily relates to academic attainment., Results: School readiness was significantly associated with NEET status. A larger proportion of young people who were not school ready were later NEET (11%) compared to those who were school ready (4%). Most of this effect was attributable to shared relationships with academic attainment, but there was also a direct effect. Measures of deprivation and Special Educational Needs were also strong predictors of NEET status., Conclusions: NEET risk factors occur early in life. School readiness measures could be used as early indicators of risk, with interventions targeted to prevent the long-term physical and mental health problems associated with NEET, especially in disadvantaged areas. Primary schools are therefore well placed to be public health partners in early intervention strategies., (© 2024. The Author(s).)

Human sensorimotor decision making has a tendency to get 'stuck in a rut', being biased towards selecting a previously implemented action structure (hysteresis). Existing explanations propose this is the consequence of an agent efficiently modifying an existing plan, rather than creating a new plan from scratch. Instead, we propose that hysteresis is an emergent property of a system learning from the consequences of its actions. To examine this, 152 participants moved a cursor to a target on a tablet device while avoiding an obstacle. Hysteresis was observed when the obstacle moved sequentially across the screen between trials, whereby the participant continued moving around the same side of the obstacle despite it now requiring a larger movement than the alternative. Two further experiments ( n = 20) showed an attenuation when time and resource constraints were eased. We created a simple computational model capturing probabilistic estimate updating that showed the same patterns of results. This provides, to our knowledge, the first computational demonstration of how sensorimotor decision making can get 'stuck in a rut' through the updating of the probability estimates associated with actions., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Objectives: Patients with previously treated microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) tumours have limited chemotherapeutic treatment options. Pembrolizumab received approval from the EMA in 2022 for the treatment of colorectal, endometrial, gastric, small intestine, and biliary MSI-H/dMMR tumour types. This approval was supported by data from the KEYNOTE-164 and KEYNOTE-158 clinical trials. This study evaluated the cost-effectiveness of pembrolizumab compared with standard of care (SoC) for previously treated MSI-H/dMMR solid tumours in line with the approved EMA label from a UK healthcare payer perspective., Methods: A multi-tumour partitioned survival model was built consisting of pre-progression, progressed disease, and dead health states. Pembrolizumab survival outcomes were extrapolated using Bayesian hierarchical models (BHMs) fitted to pooled data from KEYNOTE-164 and KEYNOTE-158. Comparator outcomes were informed by published sources. Tumour sites were modelled independently and then combined, weighted by tumour site distribution. A SoC comparator was used to formulate the overall cost-effectiveness result with pembrolizumab as the intervention. SoC comprised a weighted average of the comparators by tumour site based on market share. Drug acquisition, administration, adverse events, monitoring, subsequent treatment, end-of-life costs, and testing costs were included. Sensitivity and scenario analyses were performed, including modelling pembrolizumab efficacy using standard parametric survival models., Results: Pembrolizumab, at list price, was associated with £129,469 in total costs, 8.30 LYs, and 3.88 QALYs across the pooled tumour sites. SoC was associated with £28,222 in total costs, 1.14 LYs, and 0.72 QALYs across the pooled tumour sites. This yields an incremental cost-effectiveness ratio (ICER) of £32,085 per QALY. Results were robust to sensitivity and scenario analyses., Conclusions: This model demonstrates pembrolizumab provides a valuable new alternative therapy for UK patients with MSH-H/dMMR cancer at the cost of £32,085 per QALY, with confidential discounts anticipated to improve cost-effectiveness further.

Consumer virtual reality (VR) systems are increasingly being deployed in research to study sensorimotor behaviors, but properties of such systems require verification before being used as scientific tools. The 'motion-to-photon' latency (the lag between a user making a movement and the movement being displayed within the display) is a particularly important metric as temporal delays can degrade sensorimotor performance. Extant approaches to quantifying this measure have involved the use of bespoke software and hardware and produce a single measure of latency and ignore the effect of the motion prediction algorithms used in modern VR systems. This reduces confidence in the generalizability of the results. We developed a novel, system-independent, high-speed camera-based latency measurement technique to co-register real and virtual controller movements, allowing assessment of how latencies change through a movement. We applied this technique to measure the motion-to-photon latency of controller movements in the HTC Vive, Oculus Rift, Oculus Rift S, and Valve Index, using the Unity game engine and SteamVR. For the start of a sudden movement, all measured headsets had mean latencies between 21 and 42 ms. Once motion prediction could account for the inherent delays, the latency was functionally reduced to 2-13 ms, and our technique revealed that this reduction occurs within ~25-58 ms of movement onset. Our findings indicate that sudden accelerations (e.g., movement onset, impacts, and direction changes) will increase latencies and lower spatial accuracy. Our technique allows researchers to measure these factors and determine the impact on their experimental design before collecting sensorimotor data from VR systems., (© 2022. The Author(s).)

Video games present a unique opportunity to study motor skill. First-person shooter (FPS) games have particular utility because they require visually guided hand movements that are similar to widely studied planar reaching tasks. However, there is a need to ensure the tasks are equivalent if FPS games are to yield their potential as a powerful scientific tool for investigating sensorimotor control. Specifically, research is needed to ensure that differences in visual feedback of a movement do not affect motor learning between the two contexts. In traditional tasks, a movement will translate a cursor across a static background, whereas FPS games use movements to pan and tilt the view of the environment. To this end, we designed an online experiment where participants used their mouse or trackpad to shoot targets in both visual contexts. Kinematic analysis showed player movements were nearly identical between contexts, with highly correlated spatial and temporal metrics. This similarity suggests a shared internal model based on comparing predicted and observed displacement vectors rather than primary sensory feedback. A second experiment, modeled on FPS-style aim-trainer games, found movements exhibited classic invariant features described within the sensorimotor literature. We found the spatial metrics tested were significant predictors of overall task performance. More broadly, these results show that FPS games offer a novel, engaging, and compelling environment to study sensorimotor skill, providing the same precise kinematic metrics as traditional planar reaching tasks., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Antimicrobial resistance (AMR) is a growing threat to global health. With pathogenic bacteria inevitably becoming more resistant to existing antimicrobials, mortality and costs due to AMR will significantly increase over the next few decades if adequate action is not taken. A major challenge in addressing AMR is the lack of financial incentives for manufacturers to invest in developing new antimicrobials. This is partly because current approaches in health technology assessment (HTA) and standard modeling methods fail to capture the full value of antimicrobials., Aim: We explore recent reimbursement and payment frameworks, particularly pull incentives, aimed to address the market failures in antimicrobials. We focus on the "subscription-style" payment model recently used in the UK and discuss the learnings for other European countries., Methods: A pragmatic literature review was conducted to identify recent initiatives and frameworks between 2012 and 2021, across seven European markets. The National Institute for Health and Care Excellence (NICE) technology appraisals for cefiderocol and for ceftazidime with avibactam were reviewed to evaluate how the new UK model has been applied in practice and identify the key challenges., Conclusion: The UK and Sweden are the first European countries to pilot the feasibility of implementing pull incentives through fully and partially delinked payment models, respectively. The NICE appraisals highlighted the complexity and large areas of uncertainty of modeling antimicrobials. If HTA and value-based pricing are part of the future in tackling the market failure in AMR, European-level efforts may be needed to overcome some of the key challenges., Competing Interests: All authors are employed by Lumanity. Lumanity was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (© 2023 Schurer, Patel, van Keep, Horgan, Matthijsse and Madin-Warburton.)

Background: Parkinson's disease is a progressive neurodegenerative disease, which significantly impacts patients' quality of life and is associated with high treatment and direct healthcare costs. In England, levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of levodopa-responsive advanced Parkinson's disease with troublesome motor fluctuations when available combinations of medicinal products are unsatisfactory., Objective: We aimed to determine the cost effectiveness of LCIG compared to the standard of care for patients with advanced Parkinson's disease in England, using real-world data., Methods: A Markov model was adapted from previous published studies, using the perspective of the English National Health System and Personal and Social Services to evaluate the cost effectiveness of LCIG compared to standard of care in patients with advanced Parkinson's disease over a 20-year time horizon. The model comprised 25 health states, defined by a combination of the Hoehn and Yahr scale, and waking time spent in OFF-time. The base case considered an initial cohort of patients with an Hoehn and Yahr score of ≥ 3, and > 4 h OFF-time. Standard of care comprised standard oral therapies, and a proportion of patients were assumed to be treated with subcutaneous apomorphine infusion or injection in addition to oral therapies. Efficacy inputs were based on LCIG clinical trials where possible. Resource use and utility values were based on results of a large-scale observational study, and costs were derived from the latest published UK data, valued at 2017 prices. The EuroQol five-dimensions-3-level (EQ-5D-3L) instrument was used to measure utilities. Costs and quality-adjusted life-years were discounted at 3.5%. Both deterministic and probabilistic sensitivity analyses were conducted., Results: Total costs and quality-adjusted life-years gained for LCIG vs standard of care were £586,832 vs £554,022, and 2.82 vs 1.43, respectively. The incremental cost-effectiveness ratio for LCIG compared to standard of care was £23,649/quality-adjusted life-year. Results were sensitive to the healthcare resource utilisation based on real-world data, and long-term efficacy of LCIG., Conclusions: The base-case incremental cost-effectiveness ratio was estimated to be within the acceptable thresholds for cost effectiveness considered for England., (© 2022. Crown.)

Prolonged drought due to climate change has negatively impacted amphibians in southern California, U.S.A. Due to the severity and length of the current drought, agencies and researchers had growing concern for the persistence of the arroyo toad ( Anaxyrus californicus ), an endangered endemic amphibian in this region. Range-wide surveys for this species had not been conducted for at least 20 years. In 2017-2020, we conducted collaborative surveys for arroyo toads at historical locations. We surveyed 88 of the 115 total sites having historical records and confirmed that the arroyo toad is currently extant in at least 61 of 88 sites and 20 of 25 historically occupied watersheds. We did not detect toads at almost a third of the surveyed sites but did detect toads at 18 of 19 specific sites delineated in the 1999 Recovery Plan to meet one of four downlisting criteria. Arroyo toads are estimated to live 7-8 years, making populations susceptible to prolonged drought. Drought is estimated to increase in frequency and duration with climate change. Mitigation strategies for drought impacts, invasive aquatic species, altered flow regimes, and other anthropogenic effects could be the most beneficial strategies for toad conservation and may also provide simultaneous benefits to several other native species that share the same habitat., Competing Interests: None., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)