Search results
Found 30896 matches for
What Do Scientists Mean When They Talk About Research Animals "Volunteering"?
This paper examines discourses around "volunteering" in animal research. Through a qualitative textual analysis of the scientific literature using animals in behavioral and psychological research, we demonstrate that "voluntary" and related terms are used by scientists in a variety of distinct ways, which carry a range of ethical and political connotations. While any reference to volunteering might be assumed to imply free, unconstrained, and unpaid participation in an activity, in the animal research literature the term is often used simply to signal a lack of physical restraint, even though other human-imposed constraints are at play. Though truly voluntary behavior may be impossible, we nevertheless argue that there is a case for seeing use of the language of volunteering as an ethical or political move in which scientists aim to highlight a goal of minimizing human control, promoting animal welfare, or representing their research as ethically acceptable.
Development of START-EDI guidelines for reporting equality, diversity and inclusion in research: a study protocol.
INTRODUCTION: Acknowledging equality, diversity and inclusion (EDI) in research is not only a moral imperative but also an important step in avoiding bias and ensuring generalisability of results. This protocol describes the development of STAndards for ReporTing EDI (START-EDI) in research, which will provide a set of minimum standards to help researchers improve their consistency, completeness and transparency in EDI reporting. We anticipate that these guidelines will benefit authors, reviewers, editors, funding organisations, healthcare providers, patients and the public. METHODS AND ANALYSIS: To create START-EDI reporting guidelines, the following five stages are proposed: (i) establish a diverse, multidisciplinary Steering Committee that will lead and coordinate guideline development; (ii) a systematic review to identify the essential principles and methodological approaches for EDI to generate preliminary checklist items; (iii) conduct an international Delphi process to reach a consensus on the checklist items; (iv) finalise the reporting guidelines and create a separate explanation and elaboration document; and (v) broad dissemination and implementation of START-EDI guidelines. We will work with patient and public involvement representatives and under-served groups in research throughout the project stages. ETHICS AND DISSEMINATION: The study has received ethical approval from the Imperial College London Research Ethics Committee (study ID: 7592283). The reporting guidelines will be published in open access peer-reviewed publications and presented in international conferences, and disseminated through community networks and forums. TRIAL REGISTRATION NUMBER: The project is pre-registered within the Open Science Framework (https://osf.io/8udbq/) and the Enhancing the Quality and Transparency of Health Research Network.
Proactive and integrated consultation-liaison psychiatry for older medical inpatients: A mixed methods description of training, care provided and clinician experience in the HOME study.
OBJECTIVES: To describe the practical experience of delivering a proactive and integrated consultation-liaison (C-L) psychiatry service model (PICLP). PICLP is designed for older medical inpatients and is explicitly biopsychosocial and discharge-focused. In this paper we report: (a) observations on the training of 15 clinicians (seven senior C-L psychiatrists and eight assisting clinicians) to deliver PICLP; (b) the care they provided to 1359 patients; (c) their experiences of working in this new way. METHOD: A mixed methods observational study using quantitative and qualitative data, collected prospectively over two years as part of The HOME Study (a randomized trial comparing PICLP with usual care). RESULTS: The clinicians were successfully trained to deliver PICLP according to the service manual. They proactively assessed all patients and found that most had multiple biopsychosocial problems impeding their timely discharge from hospital. They integrated with ward teams to provide a range of interventions aimed at addressing these problems. Delivering PICLP took a modest amount of clinical time, and the clinicians experienced it as both clinically valuable and professionally rewarding. CONCLUSION: The experience of delivering PICLP highlights the special role that C-L psychiatry clinicians, working in a proactive and integrated way, can play in medical care.
Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago.
BACKGROUND: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. METHODS: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. RESULTS: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P
When research animals become pets and pets become research animals: care, death, and animal classification.
This paper explores what happens to care, and decisions about ending and extending life, when research animals become pets and pets become research animals. To do this, we draw on in-depth qualitative research on (i) rehoming of laboratory animals, (ii) veterinary clinical research, and (iii) the role of the Named Veterinary Surgeon (NVS) in UK animal research. We begin by exploring how (in theory and practice) the ethical, affective, and practical elements of care are split in the research laboratory. We then investigate arguments for and against ending and extending animal life via clinical research and rehoming, highlighting how these activities bring norms and dilemmas around animal death in the laboratory and veterinary clinic to the fore. We conclude by demonstrating the value of investigating borders between animal categories for understanding dilemmas around care and death, and for contributing to emerging literatures within geography around animal care, death, and categorisation. Key contributions of our work include highlighting: how care roles can be split; the importance of considering speculative and in-practice elements of care; the context-dependency and multiplicity of practices of killing in the veterinary clinic and laboratory; and the flexibility and changing nature of animal categories.
Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine.
Ebola virus disease (EVD) outbreaks are increasing, posing significant threats to affected communities. Effective outbreak management depends on protecting frontline health workers, a key focus of EVD vaccination strategies. IgG specific to the viral glycoprotein serves as the correlate of protection for recent vaccine licensures. Using advanced cellular and transcriptomic analyses, we examined B cell responses to the Ad26.ZEBOV, MVA-BN-Filo EVD vaccine. Our findings reveal robust plasma cell and lasting B cell memory responses post-vaccination. Machine-learning models trained on blood gene expression predicted antibody response magnitude. Notably, we identified a unique B cell receptor CDRH3 sequence post-vaccination resembling known Orthoebolavirus zairense (EBOV) glycoprotein-binding antibodies. Single-cell analyses further detailed changes in plasma cell frequency, subclass usage, and CDRH3 properties. These results highlight the predictive power of early immune responses, captured through systems immunology, in shaping vaccine-induced B cell immunity.
Reverse Shoulder Arthroplasty for Acute Trauma vs Trauma Sequalae following failed conservative management: A cohort study using data from the National Joint Registry and Hospital Episode Statistics for England.
INTRODUCTION: While the majority of proximal humerus fractures (PHFs) can be managed conservatively, for some, particularly complex 3- or 4-part fractures, management is controversial. The decision-making process can be challenging, especially in older patients when considering whether secondary surgery for failed non operative management comes with more risk than acute surgical treatment. There is limited evidence in the literature that compares the outcomes of patients having an acute reverse shoulder arthroplasty (rTSA) for trauma against those having an rTSA for trauma sequalae following failed previous conservative management. This study aims to use the National Joint Registry (NJR) and Hospital Episode Statistics (HES) for England to compare outcomes of rTSA for acute trauma against those of rTSA for trauma sequalae following failed conservative management. METHODS: NJR data from April 2012 to March 2022 was linked to HES. All patients undergoing an rTSA for acute or trauma sequalae were included. Primary outcome was revision. Secondary outcomes were non revision re-operation, mortality, medical complications within 30 & 90 days of primary procedure and length of stay. RESULTS: In the propensity matched cohorts, there were 2488 patients in the acute trauma group and 1267 patients in the trauma sequalae group. rTSA for trauma sequalae had a higher cumulative revision rate at 1,3,5,7 and 10 years and statistically significant increased risk in overall revision (HR of 2.44 (1.68-3.55 p<0.001) in comparison to acute trauma rTSA. There was no statistical difference in incidence of non-revision re-operation (p=0.17). At one year the mortality rate was 4.11% (3.38-5.00) for acute trauma and 3.07% (2.23-4.23) for trauma sequalae and this was not statistically different (HR 0.74 (0.51-1.09) p=0.13). In the acute trauma group, there was a statistically significant increase in medical complications at 30 & 90 days post procedure as well as length of stay (p<0.001). CONCLUSION: Based on this national joint registry analysis, patients are twice as likely to require a revision surgery if they undergo rTSA after conservative management has failed, compared to those who receive the procedure immediately following a proximal humerus fracture. While this may inform decision making and the consent process, given some of the limitations around registry analysis, the findings underline the importance of well-designed prospective trials in establishing the optimal timing of surgery. LEVEL OF EVIDENCE: Level III; Retrospective Cohort Comparison using Large Database; Treatment Study.
Risk of Arterial and Venous Thrombotic Events Among Patients with COVID-19: A Multi-National Collaboration of Regulatory Agencies from Canada, Europe, and United States.
PURPOSE: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. PATIENTS AND METHODS: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE. RESULTS: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09-0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99-1.04%) in the US. CONCLUSION: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability.
Chromatin-focused genetic and chemical screens identify BRPF1 as a targetable vulnerability in Taxol-resistant triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is a particularly aggressive and frequently recurring form of breast cancer, where chemotherapy is the primary treatment approach. Unfortunately, the development of resistance to chemotherapy poses a considerable challenge, restricting the already limited therapeutic alternatives for recurrent cases. Here, we generated two Taxol-resistant TNBC cell lines with a dose-escalation method to mimic chemotherapy resistance in vitro. These cells exhibited reduced growth rates, altered morphology and evasion of apoptosis. Transcriptome analysis uncovered elevated ABCB1 expression and multidrug-resistant phenotype in these resistant cells. To comprehensively investigate the key epigenetic regulators of Taxol resistance, we conducted chromatin-focused genetic and chemical screens and pinpointed Bromodomain and PHD Finger Containing 1 (BRPF1) as a novel regulator of Taxol resistance. Knockout of BRPF1, the reader protein in the MOZ-MORF histone acetyltransferase complex, but not the other complex members, sensitized resistant cells to Taxol. In addition, BRPF1 inhibitors, PFI-4 and OF-1, in combination with Taxol significantly reduced cell viability. Transcriptome analysis upon BRPF1 loss or inhibition revealed a negative impact on ribosome biogenesis-related gene sets, resulting in a global decrease in protein translation in Taxol-resistant cells. CUT&RUN-qPCR analysis demonstrated that BRPF1 directly binds to the ABCB1 promoter, enhancing its expression toward inducing a multidrug-resistant phenotype. Conversely, knockout or inhibition of BRPF1 leads to decreased ABCB1 expression. Our findings uncover a comprehensive molecular framework, highlighting the pivotal role of epigenetic reader protein BRPF1 in Taxol resistance and providing potential avenues for therapeutic intervention in TNBC.
Incidence of post-acute COVID-19 symptoms across healthcare settings in seven countries: an international retrospective cohort study using routinely-collected data.
BACKGROUND: The World Health Organisation (WHO) has identified a range of symptomatic manifestations to aid in the clinical diagnosis of post-COVID conditions, herein referred to as post-acute COVID-19 symptoms. We conducted an international network cohort study to estimate the burden of these symptoms in North American, European, and Asian populations. METHODS: A federated analysis was conducted including 10 databases from the United Kingdom, Netherlands, Norway, Estonia, Spain, France, South Korea, and the United States, between September 1st 2020 and latest data availability (which varied from December 31st 2021 to February 28th 2023), covering primary and secondary care, nationwide registries, and claims data, all mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We defined two cohorts for the main analyses: a SARS-CoV-2 infection cohort [positive polymerase chain reaction (PCR) or rapid lateral flow test (LFT) result or clinical COVID-19 diagnosis] and a general population cohort. Individuals with less than 365 days of prior history or 120 days of follow-up were excluded. We estimated incidence rates (IRs) of the 25 WHO-proposed post-acute COVID-19 symptoms, considering symptoms that occurred ≥90 and ≤365 days after index date, excluding individuals with the respective symptoms 180 days prior to the index event. Stratified analyses were conducted by age and sex. Incidence rate ratios (IRRs) were calculated comparing rates in the infected cohort versus the general population. Results from the different databases were combined using random-effects meta-analyses. FINDINGS: 3,019,408 individuals were included in the infection cohort. 1,585,160 of them were female and 1,434,248 of them male. 929,351,505 individuals were included in the general population group. 461,195,036 of them were female and 466,022,004 of them male. The 1-year IR of any post-acute COVID-19 symptom in the COVID-19 infection cohort varied significantly across databases, from 4.4 (95% CI 3.8-5.1) per 100 person-years to 103.9 (95% CI 103.2-104.7). The five most common symptoms were joint pain (from 1.6 (95% CI 1.3-1.9) to 14.3 (95% CI 14.1-14.6)), abdominal pain (from 0.3 (95% CI 0.1-0.5) to 9.9 (95% CI 9.7-10.1)), gastrointestinal issues (from 0.6 (95% CI 0.4-0.9) to 13.3 (95% CI 13.1-13.6)), cough (from 0.3 (95% CI 0.2-0.5) to 9.1 (95% CI 8.9-9.3)), and anxiety (from 0.8 (95% CI 0.6-1.2) to 11.4 (95% CI 11.2-11.6)); whereas muscle spasms (from 0.01 (95% CI 0.008-0.2) to 1.7 (95% CI 1.6-1.8)), pins and needles (from 0.05 (95% CI 0.03-0.0.9) to 1.5 (95% CI 1.4-1.6)), memory issues (from 0.03 (95% CI 0.02-0.06) to 0.8 (95% CI 0.7-0.8)), cognitive dysfunction (from 0.007 (95% CI 0.004-0.01) to 0.6 (95% CI 0.4-0.8)), and altered smell and/or taste (from 0.04 (95% CI 0.03-0.04) to 0.7 (95% CI 0.6-0.8)) were least common. Incidence rates of any post-acute COVID-19 symptoms generally increased with age, with certain symptoms peaking in middle-aged adults (anxiety, depressive disorders, headache, altered smell and taste) and others in pre-school children (gastrointestinal issues and cough). Females had higher incidence rates for most symptoms. Based on the random-effects model, the infected cohort had a higher incidence of any post-acute COVID-19 symptom than the general population, with a meta-analytic incidence rate ratio (meta-IRR) of 1.4 (1-2). A similar pattern was seen for all individual symptoms. The highest meta-IRRs were depressive disorder, 2.6 (1.7-3.9); anxiety, 2.3 (1.4-3.8); allergy, 2.1 (1.7-2.8) and sleep disorders, 2.1 (1.5-2.6). The meta-IRR for altered smell and/or taste was 1.9 (1.3-2.8). INTERPRETATION: Post-acute COVID-19 symptoms, as listed by the WHO, were commonly observed following COVID-19 infection. However, even after standardising research methods, there was significant heterogeneity in the incidence rates from different healthcare settings and geographical locations. This is the first international study of the epidemiology of post-acute COVID-19 symptoms using the WHO-listed symptoms. Its findings contibute to understand the epidemiology of this condition from a multinational approach. Limitations of this study include the lack of consensus of the post-acute COVID-19 definition, as well as the difficulty to capture the impact on daily life of the post-acute COVID-19 symptoms in the available datasets. FUNDING: This work has been funded by the European Health Data Evidence Network (EHDEN) through an Evidence Generation Fund Grant and by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC).
Treatment of systemic lupus erythematosus: Analysis of treatment patterns in adult and paediatric patients across four European countries.
OBJECTIVE: Multiple treatment options are recommended for Systemic Lupus Erythematosus (SLE) by clinical guidelines. This study aimed to explore SLE treatment patterns as there is limited real-world data of SLE medication utilisation, especially in childhood-onset SLE (cSLE). METHODS: We conducted a longitudinal cohort study using five routinely collected healthcare databases from four European countries (United Kingdom, France, Germany, and Spain). We described the characteristics of adult and paediatric patients at time of SLE diagnosis. We calculated the percentage of patients commencing SLE treatments in the first month and year after diagnosis, reported number of prescriptions, starting dose, cumulative dose, and duration of each treatment, and characterised the line of therapy. RESULTS: We characterised 11,255 patients with a first diagnosis of SLE and included 5718 in our medication utilisation analyses. The majority of adult SLE patients were female (range 80-88 %), with median age of 49 to 54 years at diagnosis. In the paediatric cohort (n = 378), 66-83 % of SLE patients were female, with median age of 12 to 16 years at diagnosis. Hydroxychloroquine and glucocorticoids were common first-line treatments in both adults and children, with second-line treatments including mycophenolate mofetil and methotrexate. Few cases of monoclonal antibody use were seen in either cohort. Initial glucocorticoid dosing in paediatric patients was often higher than in adults. CONCLUSION: Treatment choices for adult SLE patients across four European countries were in line with recent therapeutic consensus guidelines. High glucocorticoid prescriptions in paediatric patients suggests the need for steroid-sparing treatment alternatives and paediatric specific guidelines.
P035 Patient facing pharmacist reduces length of stay for paediatric short stay patients
AimTo reduce the average length of stay (LoS) of paediatric inpatients requiring discharge medication (TTO’s) on the short stay pathway (Comet).MethodsA paediatric multi-disciplinary team (MDT) used the model for improvement to identify stakeholders and key drivers for change. The Comet patient journey was mapped from A&E to discharge. Plan-Do-Study-Act (PDSA) cycles were used to reduce LoS, targeting the addition of a paediatric pharmacist to the morning ward round and use of over- label packs to facilitate nurse-led discharge for simple TTO’s required within 2 hours. Data was collected over a two week period in summer; PDSA 1 baseline data, one week prior to change; PDSA 2, one week after implementation. Baseline measurements included time taken to write, screen and dispense TTO and the average LoS. Data was collected via the electronic prescribing system (Lastword). Patients eligible for the Comet pathway were included for analysis. Results were analysed using Microsoft Excel. Ethics approval was not required for this study.ResultsPDSA one; 15 patients admitted onto the Comet pathway. 67% patients were admitted outside working hours. Six patients needed TTOs, 33% were written out of hours and all dispensed by pharmacy. Average time to writing TTO 14.6 hours (16minutes-44hhours); time to pharmacist clinical screen 19.4 hours (6 minutes – 21 hours); average time for pharmacy to dispense TTO after screening 2 hours (69–203 minutes); average LoS for all Comet patients 17.6 hours (8–44) and 26 hours (14–44) for those needing TTO’s. Post implementation 12 patients were eligible for the Comet pathway. 83% patients were admitted outside of hours. Six patients needed TTO’s, 16% were written out of hours and 33% were dispensed by the nursing team. Average time to writing TTO increased to 20.2 hours (14–26), average time to pharmacist clinical screen was reduced to 10 minutes (1–98) and average time for pharmacy to dispense TTO reduced to 57 minutes (47–74). Average LoS for Comet patients was similar to PDSA 1 at 17.7 hours (3–27) but reduced to 20.8 h0urs (5–27) for those needing TTO’s.ConclusionIncreasing patient-facing time of pharmacists to improve outcomes is recommended by the Carter report.(1)Pressures in emergency-care to free up beds for patients means we need to look for creative solutions. (2) This study found the addition of a paediatric pharmacist to the ward round increased efficiency of writing, screening and dispensing TTO’s - dramatically reducing time to screening TTO’s; and the average LoS by 5 hours. The pharmacist was aware of Comet discharges at the time of decision to discharge and was on hand to resolve medication related issues. New doctors in August could explain the increased time to writing TTO’s in the second week. Promotion of nurse-led discharge via over-label packs reduced the number of TTO’s sent to pharmacy. Limitations include2 weeks of data over summer were analysed and non-paediatric hospital activity would impact pharmacy dispensing time. Future work will test how pharmacist transcribing TTO’s on the ward round affect Los and to review pharmacist clinical interventions to assess impact on outcomes.ReferencesDepartment of Health. Carter report: Unwarranted variation: A review of operational productivity and performance in English NHS acute hospitals. 5thFebruary 2016.Royal College of Paediatrics and Child Health. Standards for Short-Stay Paediatric Assessment Units (SSPAU). March 2017.
The impact of insect herbivory on biogeochemical cycling in broadleaved forests varies with temperature.
Herbivorous insects alter biogeochemical cycling within forests, but the magnitude of these impacts, their global variation, and drivers of this variation remain poorly understood. To address this knowledge gap and help improve biogeochemical models, we established a global network of 74 plots within 40 mature, undisturbed broadleaved forests. We analyzed freshly senesced and green leaves for carbon, nitrogen, phosphorus and silica concentrations, foliar production and herbivory, and stand-level nutrient fluxes. We show more nutrient release by insect herbivores at non-outbreak levels in tropical forests than temperate and boreal forests, that these fluxes increase strongly with mean annual temperature, and that they exceed atmospheric deposition inputs in some localities. Thus, background levels of insect herbivory are sufficiently large to both alter ecosystem element cycling and influence terrestrial carbon cycling. Further, climate can affect interactions between natural populations of plants and herbivores with important consequences for global biogeochemical cycles across broadleaved forests.
Damage to tropical forests caused by cyclones is driven by wind speed but mediated by topographical exposure and tree characteristics.
Each year, an average of 45 tropical cyclones affect coastal areas and potentially impact forests. The proportion of the most intense cyclones has increased over the past four decades and is predicted to continue to do so. Yet, it remains uncertain how topographical exposure and tree characteristics can mediate the damage caused by increasing wind speed. Here, we compiled empirical data on the damage caused by 11 cyclones occurring over the past 40 years, from 74 forest plots representing tropical regions worldwide, encompassing field data for 22,176 trees and 815 species. We reconstructed the wind structure of those tropical cyclones to estimate the maximum sustained wind speed (MSW) and wind direction at the studied plots. Then, we used a causal inference framework combined with Bayesian generalised linear mixed models to understand and quantify the causal effects of MSW, topographical exposure to wind (EXP), tree size (DBH) and species wood density (ρ) on the proportion of damaged trees at the community level, and on the probability of snapping or uprooting at the tree level. The probability of snapping or uprooting at the tree level and, hence, the proportion of damaged trees at the community level, increased with increasing MSW, and with increasing EXP accentuating the damaging effects of cyclones, in particular at higher wind speeds. Higher ρ decreased the probability of snapping and to a lesser extent of uprooting. Larger trees tended to have lower probabilities of snapping but increased probabilities of uprooting. Importantly, the effect of ρ decreasing the probabilities of snapping was more marked for smaller than larger trees and was further accentuated at higher MSW. Our work emphasises how local topography, tree size and species wood density together mediate cyclone damage to tropical forests, facilitating better predictions of the impacts of such disturbances in an increasingly windier world.