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Nucleocapsid antibody assays can be used to estimate SARS-CoV-2 infection prevalence in regions implementing spike-based COVID-19 vaccines. However, poor sensitivity of nucleocapsid antibody assays in detecting infection after vaccination has been reported. We derived a lower cutoff for identifying previous infections in a large blood donor cohort (N = 142,599) by using the Ortho VITROS Anti-SARS-CoV-2 Total-N Antibody assay, improving sensitivity while maintaining specificity >98%. We validated sensitivity in samples donated after self-reported swab-confirmed infections diagnoses. Sensitivity for first infections in unvaccinated donors was 98.1% (95% CI 98.0–98.2) and for infection after vaccination was 95.6% (95% CI 95.6–95.7) based on the standard cutoff. Regression analysis showed sensitivity was reduced in the Delta compared with Omicron period, in older donors, in asymptomatic infections,

Background/Aims To assess the cost-effectiveness of making treatment decisions for patients with ocular hypertension (OHT) based on a risk prediction (RP) tool in the United Kingdom.Methods A discrete event simulation model was constructed to compare the cost-effectiveness of an alternative care pathway in which the treatment decision was guided by a validated RP tool in secondary care against decision-making based on the standard care (SC). Individual patient sampling was used. Patients diagnosed with OHT and with an intraocular pressure of 24 mm Hg or over entered the model with a set of predefined individual characteristics related to their risk of conversion to glaucoma. These characteristics were retrieved from electronic medical records (n=5740). Different stages of glaucoma were modelled following conversion to glaucoma.Results Almost all (99%) patients were treated using the RP strategy, and less than half (47%) of the patients were treated using the SC strategy. The RP strategy produced higher cost but also higher quality-adjusted life years (QALYs) than the SC strategy. The RP strategy was cost-effective compared with the SC strategy in the base-case analysis, with an incremental cost-effectiveness ratio value of £11 522. The RP strategy had a 96% probability of being cost-effective under a £20 000 per QALY threshold.Conclusions The use of an RP tool for the management of patients with OHT is likely to be cost-effective. However, the generalisability of the result might be limited due to the high-risk nature of this cohort and the specific RP threshold used in the study.

Objective Current literature reveals an association between anthropometric measures of adiposity (AnthM) and age-related macular degeneration (AMD), but few have explored the disease association with imaging methods. This study aimed to explore the relationship between AMD status and dual-energy X-ray absorptiometry measures (DEXAMs) among a representative sample of the US population, and compare the association with AnthM.Method Using a representative sample in the National Health and Nutrition Examination Study 2005–2006 (n=1632), DEXAMs across the whole body and waist (ie, android), and relative fat distributions (eg, percentage fat, android-to-total body ratio) were analysed between no AMD (baseline) and any AMD. Bivariate analyses across AMD status were similarly performed for AnthM (ie, body mass index, waist circumference and skinfold thicknesses) and potential confounders (ie, demographics and health-related variables). Significant adiposity measures were analysed using logistic regression, adjusting for confounders.Results The participants in the sample were aged 40–69 years, were majority female (52%) and mainly Caucasian (76.5%). Bivariate analysis revealed having any AMD had positive significant associations with android-to-total fat ratio and subscapular skinfold thickness (SSFT). Other AnthM and DEXAMs were not significant. After adjusting age, gender and prescription of cholesterol-lowering medicine, only SSFT remained significantly associated.Conclusion SSFT represents an independent risk factor for AMD presence compared with other AnthM and DEXAMs. SSFT is an established method of measuring fat under the skin (ie, subcutaneous fat). Hence, subcutaneous fat may be more relevant in explaining the adiposity–AMD link due to physiological properties specific to the tissue. Limitations include the restricted age range and low numbers of participants with late AMD.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Introduction Randomised controlled trials (RCTs) conducted in care home settings address a range of health conditions impacting older people, but often include a common core of data about residents and the care home environment. These data can be used to inform service provision, but accessing these data can be challenging. Methods The Virtual International Care Home Trials Archive (VICHTA) collates care home RCTs conducted since 2010, with >100 participants, across multiple conditions, with documented eligibility criteria, initially identified from a scoping review. A Steering Committee comprising contributing trialists oversees proposed uses of fully anonymised data. We characterised available demography and outcomes to inform potential analyses. Data are accessible via application to the Virtual Trials Archives, through a secure online analysis platform. Trial recruitment is ongoing and future expansion will include international studies. Results The first phase of VICHTA includes data from six UK RCTs, with individual participant data (IPD) on 5,674 residents across 308 care homes. IPD include age, sex, dementia status, length of stay, quality of life, clinical outcome measures, medications, resource use, and care home characteristics, such as funding, case mix, and occupancy. Follow-up ranges between four and sixteen months. Conclusions VICHTA collates and makes accessible data on a complex and under-represented research population for novel analyses, and to inform design of future studies. Planned expansion to international care home RCTs will facilitate a wider range of research questions. Interested collaborators can submit trial data or request data at www.virtualtrialsarchives.org.

Abstract Background The estimand for a clinical trial is a precise definition of the treatment effect to be estimated. Traditionally, estimates of treatment effects are based on either an ITT analysis or a per-protocol analysis. However, there are important clinical questions which are not addressed by either of these analyses. For example, consider a trial where patients take a rescue medication. The ITT analysis includes data after use of rescue, while the per-protocol analysis excludes these patients altogether. Neither of these analyses addresses the important question of what the treatment effect would have been if patients did not take rescue medication. Main text Trial estimands provide a broader perspective compared to the limitations of ITT and per-protocol analysis. Trial treatment effects depend on how events occurring after treatment initiation such as use of alternative medication or discontinuation of the intervention are included in the definition. These events can be accounted for in different ways, depending on the clinical question of interest. Conclusion The estimand framework is an important step forward in improving the clarity and transparency of clinical trials. The centrality of estimands to clinical trials is currently not reflected in methods recommended by the Cochrane group or the CONSORT statement, the current standard for reporting clinical trials in medical journals. We encourage revisions to these guidelines.

Abstract Background Patients with chronic obstructive pulmonary disease (COPD) are frequently readmitted to hospital resulting in avoidable healthcare costs. Many different interventions designed to reduce hospital readmissions are reported with limited evidence for effectiveness. Greater insight into how interventions could be better designed to improve patient outcomes has been recommended. Aim To identify areas for optimisation within previously reported interventions provided to reduce COPD rehospitalisation to improve future intervention development. Methods A systematic review was conducted by searching Medline, Embase, CINAHL, PsycINFO, and CENTRAL in June 2022. Inclusion criteria were interventions provided to patients with COPD in the transition from hospital to home or community. Exclusion criteria were lack of empirical qualitative results, reviews, drug trials, and protocols. Study quality was assessed using the Critical Appraisal Skills Programme tool and results were synthesised thematically. Results A total of 2,962 studies were screened and nine studies included. Patients with COPD experience difficulties when transitioning from hospital to home. It is therefore important for interventions to facilitate a smooth transition process and give appropriate follow-up post-discharge. Additionally, interventions should be tailored for each patient, especially regarding information provided. Conclusion Very few studies specifically consider processes underpinning COPD discharge intervention implementation. There is a need to recognise that the transition itself creates problems, which require addressing, before introducing any new intervention. Patients report a preference for interventions to be individually adapted—in particular the provision of patient information. Whilst many intervention aspects were well received, feasibility testing may have enhanced acceptability. Patient and public involvement may address many of these concerns and greater use of process evaluations should enable researchers to learn from each other’s experiences. Trial registration The review was registered in PROSPERO with registration number CRD42022339523.

Abstract Single-cell approaches have revealed that the haematopoietic hierarchy is a continuum of differentiation, from stem cell to committed progenitor, marked by changes in gene expression. However, many of these approaches neglect isoform-level information and thus do not capture the extent of alternative splicing within the system. Here, we present an integrated short- and long-read single-cell RNA-seq analysis of haematopoietic stem and progenitor cells. We demonstrate that over half of genes detected in standard short-read single-cell analyses are expressed as multiple, often functionally distinct, isoforms, including many transcription factors and key cytokine receptors. We observe global and HSC-specific changes in gene expression with ageing but limited impact of ageing on isoform usage. Integrating single-cell and cell-type-specific isoform landscape in haematopoiesis thus provides a new reference for comprehensive molecular profiling of heterogeneous tissues, as well as novel insights into transcriptional complexity, cell-type-specific splicing events and consequences of ageing.

Background Adoptive cell therapy (ACT) is a promising strategy for treating cancer, yet it faces several challenges such as lack of long-term protection due to T cell exhaustion induced by chronic TCR stimulation in the tumor microenvironment. One benefit of ACT, however, is that it allows for cellular manipulations, such as deletion of the phosphotyrosine phosphatase non-receptor type 22 (PTPN22), which improves CD8+ T cell antitumor efficacy in ACT. We tested whether Ptpn22KO cytolytic T cells (CTLs) were also more effective than Ptpn22WT CTL in controlling tumors in scenarios that favor T cell exhaustion.Methods Tumor control by Ptpn22WT and Ptpn22KO CTL was assessed following adoptive transfer of low numbers of CTL to mice with subcutaneously implanted MC38 tumors. Tumor infiltrating lymphocytes were isolated for analysis of effector functions. An in vitro assay was established to compare CTL function in response to acute and chronic restimulation with antigen-pulsed tumor cells. The expression of effector and exhaustion-associated proteins by Ptpn22WT and Ptpn22KO T cells was followed over time in vitro and in vivo using the ID8 tumor model. Finally, the effect of PD-1 and TIM-3 blockade on Ptpn22KO CTL tumor control was assessed using monoclonal antibodies and CRISPR/Cas9-mediated knockout.Results Despite having improved effector function at the time of transfer, Ptpn22KO CTL became more exhausted than Ptpn22WT CTL, characterized by more rapid loss of effector functions, and earlier and higher expression of inhibitory receptors (IRs), particularly the terminal exhaustion marker TIM-3. TIM-3 expression, under the control of the transcription factor NFIL3, was induced by IL-2 signaling which was enhanced in Ptpn22KO cells. Antitumor responses of Ptpn22KO CTL were improved following PD-1 blockade in vivo, yet knockout or antibody-mediated blockade of TIM-3 did not improve but further impaired tumor control, indicating TIM-3 signaling itself did not drive the diminished function seen in Ptpn22KO CTL.Conclusions This study questions whether TIM-3 plays a role as an IR and highlights that genetic manipulation of T cells for ACT needs to balance short-term augmented effector function against the risk of T cell exhaustion in order to achieve longer-term protection.

Background Medicine prescribing, monitoring and administration in care homes can be significantly enhanced. Effective interventions to improve pharmaceutical care and resident outcomes are required. The enablement of pharmacists to prescribe provides an opportunity for pharmacist independent prescribers to assume responsibility for improving pharmaceutical care, medication-related outcomes and resident safety whilst reducing general practitioner workload. Objective(s) To determine the effectiveness and cost-effectiveness of pharmacist independent prescribing in care homes. Design Development work was undertaken through five work packages before the delivery of the definitive trial. Triads of pharmacist independent prescribers, care home and general practice with responsibility over 20 care home residents were recruited and cluster randomised to intervention or usual care for 6 months. Researchers were blinded at recruitment stage only. Recruitment of 880 residents was required to provide 80% statistical power, to show a 21% reduction in falls over 6 months, assuming 20% attrition. Randomisation was undertaken electronically at triad level, stratified by geographical area. Intention-to-treat analysis undertaken using a negative binomial model. Parameters were estimated using a generalised estimating equation approach. Costs were captured from an NHS perspective. Quality of life (EuroQol; five domain; five level) was collected by proxy to enable cost/quality-adjusted life-year estimation. A concurrent process evaluation was performed. Safety was monitored through a review of pharmacist independent prescriber activities, independent concerns reporting and review of adverse events. Participants Forty-nine triads of general practitioners, pharmacist independent prescribers and care homes were recruited with 454 residents allocated to the intervention arm and 428 to the control arm. Intervention Medication review and care planning, medication reconciliation, staff training, support with care home medication-related procedures, deprescribing and authorisation of monthly prescriptions. Main outcome measure Fall rate per person over 6 months. Results Data for 449 intervention and 427 control residents available for final analysis. The 6-month fall rate ratio in favour of intervention was 0.91 (95% confidence interval 0.66 to 1.26; p=0.58). No significant difference in secondary outcomes was identified except Drug Burden Index (rate ratio 0.83, 95% confidence interval 0.75 to 0.92; p

Objective Older people in care homes frequently experience polypharmacy, increasing the likelihood of medicine-related burden. Pharmacists working within multidisciplinary primary care teams are ideally placed to lead on medication reviews. A randomised controlled trial placed pharmacists, with independent prescribing rights (PIPs), into older people care homes. In the intervention service, PIPs worked with general practitioners (GPs) and care home staff for 6 months, to optimise medicine management at individual resident and care home level. PIP activity included stopping medicines that were no longer needed or where potential harms outweighed benefits. This analysis of qualitative data examines health and social care stakeholders’ perceptions of how the service impacted on care home medicine procedures and resident well-being.Design Pragmatic research design with secondary analysis of interviews.Setting Primary care pharmacist intervention in older people care homes in England, Scotland and Northern Ireland.Participants Recruited from intervention arm of the trial: PIPs (n=14), GPs (n=8), care home managers (n=9) and care home staff (n=6).Results There were resonances between different participant groups about potential benefits to care home residents of a medicine service provided by PIPs. There were small differences in perceptions about changes related to communication between professionals. Results are reported through three themes (1) ‘It’s a natural fit’—pharmacists undertaking medication review in care homes fitted within multidisciplinary care; (2) ‘The resident is cared for’—there were subjective improvements in residents’ well-being; (3) ‘Moving from “firefighting” to effective systems’—there was evidence of changes to care home medicine procedures.Conclusion This study suggests that pharmacist independent prescribers in primary care working within the multidisciplinary team can manage care home residents’ medicines leading to subjective improvements in residents’ well-being and medicine management procedures. Care home staff appreciated contact with a dedicated person in the GP practice.Trial registration ISRCTN 17847169

Introduction Over 50% of older adults are prescribed a medicine where the risk of harm outweighs the chances of benefit. During a hospital admission, older adults and carers expect medicines to be reviewed for appropriateness and any inappropriate medicines proactively deprescribed. While the principle of proactive deprescribing is an expectation of good prescribing practice, it is yet to become routine. The CompreHensive geriAtRician-led MEdication Review (CHARMER) study aims to develop and test a five-component behaviour change intervention to equip geriatricians and pharmacists to proactively deprescribe inappropriate medicines with older adults in hospital. This study aims to test the feasibility and acceptability of study processes and CHARMER implementation.Methods and analysis A two-arm purposive allocation feasibility study is being undertaken at four acute hospitals in England, UK (three intervention and one control). The target sample is 400 patients across all hospitals. Primary outcome measures are: (1) participant recruitment rate and (2) participant attrition rate. Secondary outcome measures are: (1) hospital readmission rate; (2) mortality rate and (3) quality of life. Quantitative data will be checked for completeness and quality, and practitioner and patient demographics descriptively analysed. We will undertake a rapid qualitative analysis on observations, interviews and study meeting minutes data. A subsequent thematic analysis will be undertaken with codes mapped to the Theoretical Domains Framework and Normalisation Process Theory. Triangulation of qualitative and quantitative data will be undertaken.Ethics and dissemination Ethics approval was obtained from Wales Research Ethics Committee 1 (IRAS ID 312494) and study approval from the Health Research Authority (22/WA/0087). Informed consent will be sought from all hospital staff involved in data collection activities and for patients involved in enhanced data collection activities. The findings of this study will be disseminated in peer-reviewed journals and conference presentations.Trial registration ISRCTN11899506.

The translational elongation factor eIF5a may have a function in T cell protein translation. Here the authors show that hypusination of eIF5a or deletion of eIF5a alters the profile of mRNA translation in T cells and that eIF5 regulates the proliferation and effector function of these T cells.

Abstract The care home staff influenza vaccination rate in England is significantly lower than the 75% World Health Organisation recommendation. This represents a substantial potential for resident harm. Barriers to staff vaccination stem from individual and organisational levels. Existing interventions address some but not all barriers and are not underpinned by behavioural science theory. This study aims to estimate the effectiveness and cost-effectiveness of a theory-informed intervention to improve care home staff vaccination rates compared to routine practice. Set in care homes with both nursing and residential focus, and a range of ownership status, only homes providing long stay care to older people with a staff vaccination rate below 40% are eligible to participate. Participation expressions of interest will be sought using a variety of approaches prior to seeking consent. The primary outcome measure is the proportion of staff vaccinated at 6 months, with secondary outcome measures being proportion vaccinated at 3 months, numbers of staff sick days, general practitioner and nurse visits to care home, care home resident hospitalisations and mortality. Based on the assumptions that the mean cluster (care home) size is 54 staff, a coefficient of variation of 0.48, control vaccination rate is 55%, intervention 75%, intra-cluster correlation coefficient of 0.2 and with 90% power, and 20% attrition, we require 39 care homes per arm. Blocked randomisation will be at the level of care home, stratified by the proportion of non-white care home staff, and implemented by Norwich Clinical Trials Unit. The intervention comprises co-designed information videos and posters, provision of in-house staff vaccination clinics, and incentive scheme and monthly data collection on trial outcomes. Beyond usual practice, the control arm will additionally contribute monthly data. Data will be collected at the start, monthly and at 6 months, and analysis will be blind to allocation. Statistical analysis will use the intention-to-treat principle with the difference in vaccination rates between groups compared using a random effect logistic regression model at the staff-level. This will be the first study to use a theory-informed intervention designed to comprehensively address identified barriers to care home staff influenza vaccination. Trial registration: ISRCTN ISRCTN22729870 . Registered on 24 August 22. Secondary identifiers: R209939, IRAS 316820, CPMS 53812.

Researchers working in the field, the places where research-relevant activity happens, are essential to recruitment and data collection in randomised controlled trials (RCTs). This study aimed to understand the nature of this often invisible work. Data were generated through an RCT of a pharmacist-led medication management service for older people in care homes. The study was conducted over three years and employed seven Research Associates (RA) working in Scotland, Northern Ireland, and England. Weekly research team meetings and Programme Management Group meetings naturally generated 129 sets of minutes. This documentary data was supplemented with two end-of-study RA debriefing meetings. Data were coded to sort the work being done in the field, then deductively explored through the lens of Normalization Process Theory to enable a greater understanding of the depth, breadth and complexity of work carried out by these trial delivery RAs. Results indicate RAs helped stakeholders and participants make sense of the research, they built relationships with participants to support retention, operationalised complex data collection procedures and reflected on their own work contexts to reach agreement on changes to trial procedures. The debrief discussions enabled RAs to explore and reflect on experiences from the field which had affected their day-to-day work. The learning from the challenges faced in facilitating care home research may be useful to inform future research team preparation for complex interventions. Scrutinising these data sources through the lens of NPT enabled us to identify RAs as linchpins in the successful conduct of a complex RCT study.

This paper discusses specific types of missile attacks the Democratic People’s Republic of Korea (DPRK) might launch in a conflict and identifies the key sources of uncertainty that US and allied political and military leaders must take into account in assessing how effective defense systems might be in stopping these attacks. A key finding is that while missile defenses might be able to blunt some kinds of attacks, the DPRK will have options for retaliatory missile attacks that can reach their targets despite the presence of defenses, and Pyongyang will know which options those are. The existence of this second set of cases is crucial for US and allied leaders to recognize if they are considering taking actions under the assumption that defenses will be effective in protecting US and allied populations.

The NANOGrav 15 yr data set shows evidence for the presence of a low-frequency gravitational-wave background (GWB). While many physical processes can source such low-frequency gravitational waves, here we analyze the signal as coming from a population of supermassive black hole (SMBH) binaries distributed throughout the Universe. We show that astrophysically motivated models of SMBH binary populations are able to reproduce both the amplitude and shape of the observed low-frequency gravitational-wave spectrum. While multiple model variations are able to reproduce the GWB spectrum at our current measurement precision, our results highlight the importance of accurately modeling binary evolution for producing realistic GWB spectra. Additionally, while reasonable parameters are able to reproduce the 15 yr observations, the implied GWB amplitude necessitates either a large number of parameters to be at the edges of expected values or a small number of parameters to be notably different from standard expectations. While we are not yet able to definitively establish the origin of the inferred GWB signal, the consistency of the signal with astrophysical expectations offers a tantalizing prospect for confirming that SMBH binaries are able to form, reach subparsec separations, and eventually coalesce. As the significance grows over time, higher-order features of the GWB spectrum will definitively determine the nature of the GWB and allow for novel constraints on SMBH populations.

The 15 yr pulsar timing data set collected by the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) shows positive evidence for the presence of a low-frequency gravitational-wave (GW) background. In this paper, we investigate potential cosmological interpretations of this signal, specifically cosmic inflation, scalar-induced GWs, first-order phase transitions, cosmic strings, and domain walls. We find that, with the exception of stable cosmic strings of field theory origin, all these models can reproduce the observed signal. When compared to the standard interpretation in terms of inspiraling supermassive black hole binaries (SMBHBs), many cosmological models seem to provide a better fit resulting in Bayes factors in the range from 10 to 100. However, these results strongly depend on modeling assumptions about the cosmic SMBHB population and, at this stage, should not be regarded as evidence for new physics. Furthermore, we identify excluded parameter regions where the predicted GW signal from cosmological sources significantly exceeds the NANOGrav signal. These parameter constraints are independent of the origin of the NANOGrav signal and illustrate how pulsar timing data provide a new way to constrain the parameter space of these models. Finally, we search for deterministic signals produced by models of ultralight dark matter (ULDM) and dark matter substructures in the Milky Way. We find no evidence for either of these signals and thus report updated constraints on these models. In the case of ULDM, these constraints outperform torsion balance and atomic clock constraints for ULDM coupled to electrons, muons, or gluons.

It is widely acknowledged that social network support plays an important role in the quality of life and illness management of breast cancer survivors. However, the factors and processes that enable and sustain such support are less well understood. This paper reports baseline findings from a prospective UK national cohort of 1,202 women with breast cancer (aged

Abstract Introduction Pharmacogenomics (PGx) testing services have been delivered through community pharmacies across the globe, though not yet in the UK. This paper is reporting a focus group study, the first stage of a participatory co-design process to increase the chance of a successful implementation of a PGx service through community pharmacy in the UK. Aim To identify the barriers and enablers to implementing a community pharmacy based PGx service in the UK. Method Three focus groups were conducted with community pharmacists (n = 10), prescribers (n = 8) and patients (n = 8) in England. The focus groups were recorded, transcribed and thematically analysed using the Braun and Clarke six phase reflexive thematic analysis approach. Results The analysis identified five themes about PGx testing in community pharmacies: (1) In- principle receptiveness, (2) Appreciation of the benefits, (3) Lack of implementation resources (4) Ambiguity about implications for implementation and (5) Interprofessional relationship challenges. Conclusion The identified enablers for implementation of a PGx service were at a macro health system strategic level; the concerns were more at a granular operational procedural level. Overall receptiveness was noted by all three participant groups, and both prescriber and pharmacist groups appreciated the potential benefits for patients and the healthcare system. Prior to implementation in the UK, there is a need to disambiguate health professional’s concerns of the guidance, resources, and knowledge required to set up and deliver the service and to resolve patient concerns about the nature of genomics.

Mutations in the non-coding RNA RMRP cause primary immunodeficiency. Robertson et al show that a disease-associated mutation in RMRP impairs pre-ribosomal RNA processing and reduces ribosome abundance, establishing this disorder as a ribosomopathy.

OBJECTIVES/GOALS: The aim of this study was to design and implement the Pharos application to map the cellular network support structure around Lake Victoria in Western Kenya. Additionally, the Pharos app was used to collect images of disease-relevant vector and plant life surrounding the study sites to train a computer vision algorithm to map disease-relevant areas. METHODS/STUDY POPULATION: Pharos was provided to a 4-person team of healthcare workers. The app was pre-loaded on both iOS and Android devices to be used during the course of normal field activity. Pharos ambiently collects network data and the team was asked to capture images of landmarks relevant to their work in schistosomiasis control. The field team traveled to 4 counties of differing schistosomiasis risk surrounding Kisumu, Kenya in autumn 2022 and will return to these areas in early spring 2023. Cell signal indicators (upload and download speed) were collected and asynchronously uploaded to a database for further analysis. Additionally, all landmark images (cell network towers, landmarks (e.g. schools, churches, public centers), plant life, vectors, and water bodies) were recorded and tagged with GPS coordinates and time stamps. RESULTS/ANTICIPATED RESULTS: Iterative development powered by small, informal, user-centered focus group discussions with the field team led to several key adaptations to the Pharos software. On the first deployment, 1,297 unique upload and download events were recorded across 3 Kenyan cell providers and 1 American provider. 1,197 data points were collected in Kenya using both Android and iOS devices using several versions of the Pharos application. 154 unique landmarks were photographed, but a distinct difference in landmark recording was observed between devices, prompting a transition to iOS-only data collection. Of the landmarks recorded, the majority (120, 77.9%) were landmarks or cell network towers, while 22.1% were water bodies, plant life, or schistosomiasis vectors. DISCUSSION/SIGNIFICANCE: For the first time, high-detail maps of cellular signal and critical schistosomiasis-related landmarks were generated. Future work on this project is focused on training computer vision algorithms using the captured images of environmental and ecological factors to isolate possible areas of human disease transmission.

Graham White’s recent book, entitled Indigenous Empowerment through Co-management: Land Claims Boards, Wildlife Management, and Environmental Regulation, is a balanced, accessible, and honest discussion of a very complex realm of Crown-Indigenous relations and institutions in Canada. The book is very well researched and clearly communicated by one of Canada’s leading experts on the topic. Co-management has been the subject of scholarly attention for many years in Canada; however, perspectives vary widely with respect to appropriateness and effectiveness. White’s book is a bold project that tackles the complexities, sensitivities, and diverse contexts head-on. It ought to be at the top of the reading list for all academics, practitioners, and government officials with an interest in modern treaties.

Abstract Brassica carinata or Ethiopian mustard, a non‐edible oilseed brassica, is a low carbon, purpose‐grown, and none‐to‐low indirect land‐use change bioenergy feedstock for the production of drop‐in sustainable aviation fuel, biodiesel, renewable diesel, and a suite of value‐added coproducts. Carinata oil converted to drop‐in fuel using an American Society for Testing and Materials approved Catalytic Hydrothermolysis process has been successfully tested in commercial and military aviation. Carinata meal, the residue after oil extraction, is a high‐protein feed supplement for livestock, poultry, and swine, and can also yield specialty products. The Southeast Partnership for Advanced Renewables from Carinata (SPARC) is a public–private partnership formed with a twofold mission: (1) Removing physical, environmental, social, and economic constraints that prevent regional intensification of carinata production as a low‐carbon feedstock for renewable fuel and coproducts and (2) demonstrating enhanced value across the entire value chain by mitigating risk to farmers and other stakeholders. The partnership's goal is to energize the US bioeconomy through sustainable agriculture and thus contribute to energy security and economic diversification. SPARC relies on a combination of cutting‐edge multidisciplinary research and active industry engagement to facilitate adoption of the crop. This involves informing stakeholders along the entire supply chain, from producers to end‐users, policymakers, influencers, and the public, about the opportunities and best practices related to carinata. This article provides context and background concerning carinata commercialization as a winter cash crop in the Southeast US for renewable fuels and bioproducts. The advances made to date in the areas of feedstock development, fuel and coproduct development, meal valorization, supply chain logistics, and stakeholder engagement are outlined.

This publication discusses several aspects of field corn production in Florida, such as economics, land preparation, hybrid selection, fertilization, irrigation, and disease management. Written by David Wright, Ian Small, Cheryl Mackowiak, Zane Grabau, Pratap Devkota, and Silvana Paula-Moraes, and published by the UF/IFAS Agronomy Department, revised August 2022.

This publication discusses camelina adaptability, stand establishment, pest and disease management, and nutrient management. Written by Ramdeo Seepaul, David Wright, Sheeja George, and Ian Small, and published by the UF/IFAS Agronomy Department, revised July 2022.

BackgroundPregnant women are active users of mobile apps for health purposes. These apps may improve self-management of health-related conditions. Up to 70% of pregnant women experience nausea and vomiting (NVP). Even mild NVP can significantly reduce quality of life (QoL), and it can become an economic burden for both the woman and society. NVP often occurs before the first maternal care visit; therefore, apps can potentially play an important role in empowering pregnant women to recognize, manage, and seek appropriate treatment for NVP, when required. ObjectiveThis study investigated whether the MinSafeStart (MSS) mobile app could impact NVP-related symptoms, QoL, and decisional conflict regarding NVP treatment. MethodsThis randomized controlled trial enrolled 268 pregnant women with NVP in Norway from 2019 to 2020. The intervention group had access to the MSS app, which could be used to track NVP symptoms and access tailored advice. NVP severity was rated with the Pregnancy Unique Quantification of Emesis (PUQE) score. The control group followed standard maternal care. We collected data on maternal baseline characteristics, NVP severity, QoL, and decisional conflict using 2 sets of online questionnaires. One set of questionnaires was completed at enrollment, and the other was completed after 2 weeks. We performed linear regression analyses to explore whether the use of the MSS app was associated with NVP severity, QoL, or decisional conflict. ResultsAmong the 268 women enrolled in the study, 192 (86.5%) completed the baseline questionnaires and were randomized to either the intervention (n=89) or control group (n=103). In the intervention group, 88 women downloaded the app, and 468 logs were recorded. In both groups, women were enrolled at a median of 8 gestational weeks. At baseline, the average PUQE scores were 4.9 and 4.7; the average QoL scores were 146 and 149; and the average DCS scores were 40 and 43 in the intervention and control groups, respectively. The app had no impact on NVP severity (aβ 0.6, 95% Cl −0.1 to 1.2), QoL (aβ −5.3, 95% Cl −12.5 to 1.9), or decisional conflict regarding NVP treatment (aβ −1.1, 95% Cl −6.2 to 4.2), compared with standard care. ConclusionsTracking NVP symptoms with the MSS app was not associated with improvements in NVP symptoms, QoL, or decisional conflict after 2 weeks, compared with standard care. Future studies should include a process evaluation to improve our understanding of how pregnant women use the app and how to optimize its utility within maternity care. Specifically, studies should focus on how digital tools might facilitate counseling and communication between pregnant women and health care providers regarding NVP management during pregnancy. Trial RegistrationClinicalTrails.gov (NCT04719286): https://www.clinicaltrials.gov/ct2/show/NCT04719286

Abstract Background Medication management in residential aged care facilities is an ongoing concern. Numerous studies have reported high rates of inappropriate prescribing and medication use in aged care facilities, which contribute to residents’ adverse health outcomes. There is a need for new models of care that enhance inter-disciplinary collaboration between residential aged care facility staff and healthcare professionals, to improve medication management. Pilot research has demonstrated the feasibility and benefits of integrating a pharmacist into the aged care facility team to improve the quality use of medicines. This protocol describes the design and methods for a cluster randomised controlled trial to evaluate the outcomes and conduct economic evaluation of a service model where on-site pharmacists are integrated into residential aged care facility healthcare teams to improve medication management. Methods Intervention aged care facilities will employ on-site pharmacists to work as part of their healthcare teams 2 to 2.5 days per week for 12 months. On-site pharmacists, in collaboration with facility nurses, prescribers, community pharmacists, residents and families will conduct medication management activities to improve the quality use of medicines. Aged care facilities in the control group will continue usual care. The target sample size is 1188 residents from a minimum of 13 aged care facilities. The primary outcome is the appropriateness of prescribing, measured by the proportion of residents who are prescribed at least one potentially inappropriate medicine according to the 2019 Beers Criteria. Secondary outcomes include hospital and emergency department presentations, fall rates, prevalence and dose of antipsychotics and benzodiazepines, Anticholinergic Cognitive Burden Score, staff influenza vaccination rate, time spent on medication rounds, appropriateness of dose form modification and completeness of resident’s allergy and adverse drug reaction documentation. A cost-consequence and cost-effectiveness analysis will be embedded in the trial. Discussion The results of this study will provide information on clinical and economic outcomes of a model that integrates on-site pharmacists into Australian residential aged care facilities. The results will provide policymakers with recommendations relevant to further implementation of this model. Trial registration ACTRN12620000430932 . Registered on 1 April 2020 with ANZCTR

Abstract Background There are a variety of approaches being used for malaria surveillance. While active and reactive case detection have been successful in localized areas of low transmission, concerns over scalability and sustainability keep the approaches from being widely accepted. Mobile health interventions are poised to address these shortcomings by automating and standardizing portions of the surveillance process. In this study, common challenges associated with current data aggregation methods have been quantified, and a web-based mobile phone application is presented to reduce the burden of reporting rapid diagnostic test (RDT) results in low-resource settings. Methods De-identified completed RDTs were collected at 14 rural health clinics as part of a malaria epidemiology study at Macha Research Trust, Macha, Zambia. Tests were imaged using the mHAT web application. Signal intensity was measured and a binary result was provided. App performance was validated by: (1) comparative limits of detection, investigated against currently used laboratory lateral flow assay readers; and, (2) receiver operating characteristic analysis comparing the application against visual inspection of RDTs by an expert. Secondary investigations included analysis of time-to-aggregation and data consistency within the existing surveillance structures established by Macha Research Trust. Results When compared to visual analysis, the mHAT app performed with 91.9% sensitivity (CI 78.7, 97.2) and specificity was 91.4% (CI 77.6, 97.0) regardless of device operating system. Additionally, an analysis of surveillance data from January 2017 through mid-February 2019 showed that while the majority of the data packets from satellite clinics contained correct data, 36% of data points required correction by verification teams. Between November 2018 and mid-February 2019, it was also found that 44.8% of data was received after the expected submission date, although most (65.1%) reports were received within 2 days. Conclusions Overall, the mHAT mobile app was observed to be sensitive and specific when compared to both currently available benchtop lateral flow readers and visual inspection. The additional benefit of automating and standardizing LFA data collection and aggregation poses a vital improvement for low-resource health facilities and could increase the accuracy and speed of data reporting in surveillance campaigns.

Sustainable aviation fuel (SAF) production from lipids is a technologically mature approach for replacing conventional fossil fuel use in the aviation sector, and there is increasing demand for such feedstocks. The oilseed Brassica carinata (known as Ethiopian mustard or simply carinata) is a promising SAF feedstock that can be grown as a supplemental cash crop over the winter fallow season of various annual crop rotations in the Southeast US, avoiding land use changes and potentially achieving some of the soil carbon sequestration and ecosystem service benefits of winter cover crops. However, carinata may require more intensive management than traditional cover crops, potentially leading to additional soil greenhouse gas (GHG) emissions through increased carbon losses from soil tillage and nitrous oxide (N2O) emissions from nitrogen fertilizer application. In this work, the 2017 version of the process-based DayCent ecosystem model was used to establish initial expectations for the total regional SAF production potential and associated soil GHG emissions when carinata is integrated as a winter crop into the existing crop rotations across its current suitability range in southern Alabama, southern Georgia, and northern Florida. Using data from academic and industry carinata field trials in the region, DayCent was calibrated to reproduce carinata yield, nitrogen response, harvest index, and biomass carbon-to-nitrogen ratio. The resulting model was then used to simulate the integration of carinata every third winter across all 2.1 Mha of actively cultivated cropland in the study area. The model predicted regional average yields of 2.9–3.0 Mg carinata seed per hectare depending on crop management assumptions. That results in the production of more than two million Mg of carinata seed annually across the study area, enough to supply approximately one billion liters of SAF. Conventional management of carinata led to only modest increases in soil carbon storage that were largely offset by additional N2O emissions. Climate-smart management via adopting no-till carinata establishment or using poultry litter as a nitrogen source resulted in a substantial net soil GHG sink (0.23–0.31 Mg CO2e ha−1 y−1, or 0.24–0.32 Mg CO2e per Mg of seed produced) at the farms where carinata is cultivated.

In Canada, comprehensive land claims agreements – often called modern treaties – between the government and Indigenous nations include provisions prescribing how disputes between treaty parties are to be resolved. Experiences with these dispute resolution mechanisms vary across treaty contexts and there is substantial variance in the terms of these treaties. To date, this dimension of modern treaty implementation has received minimal scholarly attention, despite calls for such research. Drawing on specific examples, this article sets a foundation for further research by examining the significant variation across different treaties’ dispute resolution mechanisms and commenting on key differences, similarities and other notable features. A key focus of the analysis is on the observable evolution of these mechanisms from a relatively narrow arbitration board model to a more flexible “staged approach”. The analysis suggests that the latter may provide a stronger basis for joint problem-solving and integrative bargaining, notwithstanding open questions about the extent to which such approaches are warranted in fraught Crown-Indigenous relationships in Canada. The article also discusses the conspicuous absence of dispute resolution mechanisms that accommodate, let alone require, approaches rooted in the traditional or cultural practices of Indigenous treaty parties. Observations throughout are contextualized in relation to a growing body of jurisprudence and a broader context of fast-changing federal law and policy in Canada, which may set the stage for amendments to the dispute resolution provisions of modern treaties.

Abstract Background BRIGHTLIGHT is a national evaluation of cancer services for young people aged 13–24 years in England. It is a mixed methods study with six interlinked studies aiming to answer the question: do specialist cancer services for teenagers and young adults add value? http://www.brightlightstudy.com/ . Young people have been integral to study development and management, working as co-researchers, consultants and collaborators throughout. We aimed to share results in a way that was meaningful to young people, the public, and multidisciplinary professionals. This paper reports the development of ‘There is a Light: BRIGHTLIGHT’, a theatrical interpretation of study results by young people, and offers insight into the impact on the cast, researchers and audiences. Methods The BRIGHTLIGHT team collaborated with Contact Young Company, a youth theatre group in Manchester. Twenty members of Contact Young Company and four young people with cancer worked together over an eight-week period during which BRIGHTLIGHT results were shared along with explanations of cancer, healthcare policy and models of care in interactive workshops. Through their interpretation, the cast developed the script for the performance. The impact of the process and performance on the cast was evaluated through video diaries. The research team completed reflective diaries and audiences completed a survey. Results ‘There is a Light’ contained five acts and lasted just over an hour. It played 11 performances in six cities in the United Kingdom, to approximately 1377 people. After nine performances, a 30-min talk-back between members of the cast, creative team, an expert healthcare professional, and the audience was conducted, which was attended by at least half the audience. Analysis of cast diaries identified six themes: initial anxieties; personal development; connections; cancer in young people; personal impact; interacting with professionals. The cast developed strong trusting relationships with the team. Professionals stated they felt part of the process rather than sitting on the periphery sharing results. Both professional and lay audiences described the performance as meaningful and understandable. Feedback was particularly positive from those who had experienced cancer themselves. Conclusions Using theatre to present research enabled BRIGHTLIGHT results to be accessible to a larger, more diverse audience.

Abstract Background Evidence based practice enhances service planning and delivery, clinical decision making and patient care. However, health professionals often lack the time and opportunity to access or generate evidence. Research capacity building is thus an important mechanism for improving health service delivery. This study evaluates the effectiveness of a UK-wide Nurse and Allied Health Professional musculoskeletal research internship programme in which graduates applied to undertake their internship through one of five Higher Education Institutions. The evaluation explores the experiences of interns and their mentors. Methods Sixteen new graduates completed the internship programme (September 2015 – August 2018). Twelve interns and thirteen mentors participated in the evaluation. The evaluation used qualitative asynchronous email-based interviews to explore the experiences of interns and mentors. Interpretive phenomenological analysis of coded transcripts identified principal themes. Results Early research outputs from the interns include three peer reviewed publications and 21 conference abstract presentations. Two interns were in full time research at the time of interview or had a research component in their clinical role. Nine interns in clinical posts disclosed plans to return to research in the near future. Seven themes were identified: the impact on interns’ careers; personal impact (for example, influence on self-confidence); impact on clinical practice; drivers for applying; intervention design (for example, attitudes concerning the timing and duration of the intervention); mentorship and networking (including general support provided and quality of career advice); challenges. Conclusion The internship programme is an effective model in building research capacity in musculoskeletal research for Nurses and Allied Health Professionals, influencing careers, building confidence and improving clinical practice. The internship programme has the potential to be replicable to other clinical contexts nationally and internationally.

Abstract Background Prescribing, monitoring and administration of medicines in care homes could be improved. A cluster randomised controlled trial (RCT) is ongoing to evaluate the effectiveness of an independent prescribing pharmacist assuming responsibility for medicines management in care homes compared to usual care. Aims and Objectives To conduct a mixed-methods process evaluation of the RCT, in line with Medical Research Council (MRC) process evaluation guidance, to inform interpretation of main trial findings and if the service is found to be effective and efficient, to inform subsequent implementation. Objectives 1. To describe the intervention as delivered in terms of quality, quantity, adaptations and variations across triads and time. 2. To explore the effects of individual intervention components on the primary outcomes. 3. To investigate the mechanisms of impact. 4. To describe the perceived effectiveness of relevant intervention components [including pharmacist independent prescriber (PIP) training and care home staff training] from participant [general practitioner (GP), care home, PIP and resident/relative] perspectives. 5. To describe the characteristics of GP, care home, PIP and resident participants to assess reach. 6. To estimate the extent to which intervention delivery is normalised among the intervention healthcare professionals and related practice staff. Methods A mix of quantitative (surveys, record reviews) and qualitative (interviews) approaches will be used to collect data on the extent of the delivery of detailed tasks required to implement the new service, to collect data to confirm the mechanism of impact as hypothesised in the logic model, to collect explanatory process and final outcome data, and data on contextual factors which could have facilitated or hindered effective and efficient delivery of the service. Discussion Recruitment is ongoing and the trial should complete in early 2020. The systematic and comprehensive approach that is being adopted will ensure data is captured on all aspects of the study, and allow a full understanding of the implementation of the service and the RCT findings. With so many interrelated factors involved it is important that a process evaluation is undertaken to enable us to identify which elements of the service were deemed to be effective, explain any differences seen, and identify enablers, barriers and future adaptions. Trial registration ISRCTN17847169 . Date registered: 15 December 2017.

Abstract Background The Personalised Knee Improvement Programme (P-KIP) was developed based on previously published work, with the hypothesis that surgeons would refer patients to a well-structured conservative management intervention instead of for arthroscopy (de-implementation of arthroscopy by substitution with P-KIP). This meets NICE guidelines and international recommendations but such programmes are not widely used in the UK. Our aim was to determine whether P-KIP would reduce the number of arthroscopies performed for knee osteoarthritis. Methods P-KIP is a conservative care pathway including a group education session followed by individually tailored one-to-one dietician and physiotherapy sessions. Virtual clinic follow-up is conducted three to 6 months after completion of the programme. The service began in July 2015. The number of arthroscopies saved, measured from hospital level coding data, is the primary outcome measure. Interrupted time series analysis of coding data was conducted. As a quality assurance process, patient reported outcome measures (Oxford Knee Score; Euroqol 5D) were collected at baseline and at follow up. Results Time series analysis demonstrates that the programme saved 15.4 arthroscopies a month (95% confidence interval 9–21; p

Abstract Background Prescribing, monitoring and administration of medicines in care homes could be improved. Research has identified the need for one person to assume overall responsibility for the management of medicines within each care home. and shown that a pharmacist independent prescriber service is feasible in this context. Aims and objectives To conduct a cluster randomised controlled trial to determine the effectiveness and cost-effectiveness of a pharmacist-independent prescribing service in care homes compared to usual general practitioner (GP)-led care. Objectives To perform a definitive randomised controlled trial (RCT) with an internal pilot to determine the intervention’s effectiveness and cost-effectiveness and enable modelling beyond the end of the trial. Methods This protocol is for a cluster RCT with a 3-month internal pilot to confirm that recruitment is achievable, and there are no safety concerns. The unit of randomisation is a triad comprising a pharmacist-independent prescriber (PIP) based in a GP practice with sufficient registered patients resident in one or more care homes to allow recruitment of an average of 20 participants. In the intervention group, the PIP will, in collaboration with the GP: assume responsibility for prescribing and managing residents’ medicines including medication review and pharmaceutical care planning; support systematic ordering and administration in the care home, GP practice and supplying pharmacy; train care home and GP practice staff; communicate with GP practice, care home, supplying community pharmacy and study team. The intervention will last 6 months. The primary outcome will be resident falls at 6 months. Secondary outcomes include resident health-related quality of life, falls at 3 months, medication burden, medication appropriateness, mortality and hospitalisations. A full health economic analysis will be undertaken. The target sample size is 880 residents (440) in each arm) from 44 triads. This number is sufficient to detect a decrease in fall rate from 1.5 per individual to 1.178 (relative reduction of 21%) with 80% power and an ICC of 0.05 or less. Discussion Recruitment is on-going and the trial should complete in early 2020. The trial results will have implications for the future management of residents in care homes and the ongoing implementation of independent pharmacist prescribing. Trial registration ISRCTN, ID: 17847169. Registered on 15 December 2017.

Abstract Purpose There is a recent and growing migrant population in Northern Ireland. However, rigorous research is absent regarding access to mental health care by different migrant groups. In order to address this knowledge gap, this study aimed to identify the relative use of psychotropic medication between the largest first generation migrant groups in Northern Ireland and the majority population. Methods Census (2011) data was linked to psychotropic prescriptions for the entire enumerated population of Northern Ireland using data linkage methodology through the Administrative Data Research Centre Northern Ireland (ADRC-NI). Results Lower prescription dispensation for all psychotropic medication types, particularly antidepressants (OR = 0.35, CI 95% 0.33–0.36) and anxiolytics (OR = 0.42, CI 95% 0.40–0.44), was observed for all migrant groups with the exception of migrants from Germany. Conclusions It is likely that the results reflect poorer access to services and indicate a need to improve access and the match between resources, services and the health and social care needs of migrants. Further research is required to identify barriers to accessing primary care and mental health services.

Covert audio recordings feature in the criminal justice system in a variety of guises, either on their own or accompanied by video. If legally obtained, such recordings can provide important forensic evidence. However, the quality of these potentially valuable evidential recordings is often very poor and their content indistinct, to the extent that a jury requires an accompanying transcript. At present, in many international jurisdictions, these transcriptions are produced by investigating police officers involved in the case, but transcription is a highly complex, meticulous and onerous task, and police officers are untrained and have a vested interest in the influence of the transcript on a case, which gives rise to potential inaccuracy. This paper reports the design and results of a controlled transcription experiment in which eight linguistically trained professional transcribers produced transcripts for an audio recording of a conversation between five adults in a busy restaurant. In the context of covert recordings, this recording shares many of the typical features of covert forensic recordings, including the presence of multiple speakers, background noise and use of non-specialist recording equipment. We present a detailed qualitative and quantitative comparison of the transcripts, identifying areas of agreement and disagreement in (a) speaker attribution and (b) the representation of the linguistic content. We find that disagreement between the transcriptions is frequent and various in nature; the most common causes are identified as (i) omission of speech that is included in other transcripts, (ii) variation in the representation of turns, (iii) orthographic variation seemingly motivated by phonetic similarity, and (iv) orthographic variation seemingly not motivated by phonetic similarity. We argue that the variable nature of the transcription of “challenging” audio recordings must be considered in forensic contexts and make recommendations for improving practice in the production of forensic transcriptions.

This publication presents in abbreviated form the fertilization recommendations for agronomic crops based on soil tests performed by the UF/IFAS Extension Soil Testing Laboratory (ESTL). It contains the basic information from which ESTL soil-test reports and fertilization recommendations are generated. Correction to Table 1 made 11/29/2021.

The coastline of the Ca Mau and Kien Giang provinces in the Vietnamese Mekong Delta has been severely eroded in recent decades. Pile–Rock Breakwaters (PRBWs) are among the most widely adopted structures for controlling shoreline erosion in this region. These structures are effective for wave energy dissipation, stimulating sediment accumulation, and facilitating the restoration of mangrove forests. These breakwaters are generally considered to be the best-engineering practice; however, there is currently insufficient scientific evidence with regard to specific structural design aspects. This can lead to PRBW structures being compromised when deployed in the field. This study used a physical model of a PRBW in a laboratory to investigate several design parameters, including crest width and working states (i.e., submerged, transition, and emerged), and investigated their relationship with the wave transmission coefficient, wave reflection coefficient, and wave energy dissipation. To investigate these relationships further, empirical formulas were derived for PRBWs under different sea states and crest widths to aid the design process. The results showed that the PRBW width had a significant influence on the wave energy coefficients. The findings revealed that the crest width of the breakwater was inversely proportional to the wave transmission coefficient (Kt) under the emerged state. The crest width was also proportional to the wave reduction efficiency and wave energy dissipation in both working states (i.e., the submerged and emerged states). The front wave disturbance coefficient (Kf) was found to be proportional to the wave reflection coefficient, and the wave height in front of the structure was found to increase by up to 1.4 times in the emerged state. The wave reflection coefficient requires special consideration to reduce the toe erosion in the structure. Lastly, empirical equations including linear and non-linear formulas were compared with previous studies for different classes of breakwaters. These empirical equations will be useful for understanding the wave transmission efficiency of PRBWs. The findings of this study provide important guidance for PRBW design in the coastal area of the Mekong Delta.

This publication serves as a guide to assess freeze damage and discuss management issues related to freeze damage of carinata in the southeastern United States. Written by Michael J. Mulvaney, Mahesh Bashyal, Joseph E. Iboyi, Ramdeo Seepaul, Pratap Devkota, Ian Small, and David Wright, and published by the UF/IFAS Agronomy Department, revised July 2021.

T cell engager (TCE) antibodies have emerged as promising cancer therapeutics that link cytotoxic T-cells to tumor cells by simultaneously binding to CD3E on T-cells and to a tumor-associated antigen (TAA) expressed by tumor cells. We previously reported a novel bispecific format, the IgG-like Fab x sdAb-Fc (also known as half-IG_VH-h-CH2-CH3), combining a conventional antigen-binding fragment (Fab) with a single domain antibody (sdAb). Here, we evaluated this Fab x sdAb-Fc format as a T-cell redirecting bispecific antibody (TbsAbs) by targeting mEGFR on tumor cells and mCD3E on T cells. We focused our attention specifically on the hinge design of the sdAb arm of the bispecific antibody. Our data show that a TbsAb with a shorter hinge of 23 amino acids (TbsAb.short) showed a significantly better T cell redirected tumor cell elimination than the TbsAb with a longer, classical antibody hinge of 39 amino acids (TbsAb.long). Moreover, the TbsAb.short form mediated better T cell-tumor cell aggregation and increased CD69 and CD25 expression levels on T cells more than the TbsAb.long form. Taken together, our results indicate that already minor changes in the hinge design of TbsAbs can have significant impact on the anti-tumor activity of TbsAbs and may provide a new means to improve their potency.

Preharvest estimation of cotton yield can help growers to determine their return on investment, assess weather-related damages, and adjust crop management. This publication outlines the steps to calculate a reliable estimate of cotton yield. Written by Michael J. Mulvaney, Emma Brooks, Pratap Devkota, Ethan Carter, De Broughton, Mark Mauldin, Joseph Iboyi, Mahesh Bashyal, David Wright, and Ian Small, and published by the UF/IFAS Agronomy Department, March 2021.

Abstract Background Residents in care homes are often very frail, have complex medicine regimens and are at high risk of adverse drug events. It has been recommended that one healthcare professional should assume responsibility for their medicines management. We propose that this could be a pharmacist independent prescriber (PIP). This feasibility study aimed to test and refine the service specification and proposed study processes to inform the design and outcome measures of a definitive randomised controlled trial to examine the clinical and cost effectiveness of PIPs working in care homes compared to usual care. Specific objectives included testing processes for participant identification, recruitment and consent and assessing retention rates; determining suitability of outcome measures and data collection processes from care homes and GP practices to inform selection of a primary outcome measure; assessing service and research acceptability; and testing and refining the service specification. Methods Mixed methods (routine data, questionnaires and focus groups/interviews) were used in this non-randomised open feasibility study of a 3-month PIP intervention in care homes for older people. Data were collected at baseline and 3 months. One PIP, trained in service delivery, one GP practice and up to three care homes were recruited at each of four UK locations. For ten eligible residents (≥ 65 years, on at least one regular medication) in each home, the PIP undertook management of medicines, repeat prescription authorisation, referral to other healthcare professionals and staff training. Outcomes (falls, medications, resident’s quality of life and activities of daily living, mental state and adverse events) were described at baseline and follow-up and assessed for inclusion in the main study. Participants’ views post-intervention were captured in audio-recorded focus groups and semi-structured interviews. Transcripts were thematically analysed. Results Across the four locations, 44 GP practices and 16 PIPs expressed interest in taking part; all care homes invited agreed to take part. Two thirds of residents approached consented to participate (53/86). Forty residents were recruited (mean age 84 years; 61% (24) were female), and 38 participants remained at 3 months (two died). All GP practices, PIPs and care homes were retained. The number of falls per participating resident was selected as the primary outcome, following assessment of the different outcome measures against predetermined criteria. The chosen secondary outcomes/outcome measures include total falls, drug burden index (DBI), hospitalisations, mortality, activities of daily living (Barthel (proxy)) and quality of life (ED-5Q-5 L (face-to-face and proxy)) and selected items from the STOPP/START guidance that could be assessed without need for clinical judgement. No adverse drug events were reported. The PIP service was generally well received by the majority of stakeholders (care home staff, GPS, residents, relatives and other health care professionals). PIPs reported feeling more confident implementing change following the training but reported challenges accommodating the new service within their existing workload. Conclusion Implementing a PIP service in care homes is feasible and acceptable to care home residents, staff and clinicians. Findings have informed refinements to the service specification, PIP training, recruitment to the future RCT and the choice of outcomes and outcome measures. The full RCT with internal pilot started in February 2016 and results are expected to be available in mid late 2020.

Posttraumatic epilepsy (PTE) is a major neurodegenerative disease accounting for 20% of symptomatic epilepsy cases. A long latent phase offers a potential window for prophylactic treatment strategies to prevent epilepsy onset, provided that the patients at risk can be identified. Some promising imaging biomarker candidates for posttraumatic epileptogenesis have been identified, but more are required to provide the specificity and sensitivity for accurate prediction. Experimental models and preclinical longitudinal, multimodal imaging studies allow follow-up of complex cascade of events initiated by traumatic brain injury, as well as monitoring of treatment effects. Preclinical imaging data from the posttraumatic brain are rich in information, yet examination of their specific relevance to epilepsy is lacking. Accumulating evidence from ongoing preclinical studies in TBI support insight into processes involved in epileptogenesis, e.g. inflammation and changes in functional and structural brain-wide connectivity. These efforts are likely to produce both new biomarkers and treatment targets for PTE.