Mapping the evidence of novel plant-based foods: a systematic review of nutritional, health, and environmental impacts in high-income countries.

CONTEXT: Shifting from current dietary patterns to diets rich in plant-based (PB) foods and lower in animal-based foods (ABFs) is generally regarded as a suitable strategy to improve nutritional health and reduce environmental impacts. Despite the recent growth in supply of and demand for novel plant-based foods (NPBFs), a comprehensive overview is lacking. OBJECTIVES: This review provides a synthesis of available evidence, highlights challenges, and informs public health and environmental strategies for purposeful political decision-making by systematically searching, analyzing, and summarizing the available literature. DATA SOURCES: Five peer-reviewed databases and grey literature sources were rigorously searched for publications. DATA EXTRACTION: Study characteristics meeting the inclusion criteria regarding NPBF nutrient composition and health and environmental outcomes in high-income countries were extracted. DATA ANALYSIS: Fifty-seven peer-reviewed and 36 grey literature sources were identified; these were published in 2016-2022. NPBFs typically have substantially lower environmental impacts than ABFs, but the nutritional contents are complex and vary considerably across brands, product type, and main primary ingredient. In the limited evidence on the health impacts, shifts from ABFs to PB meats were associated with positive health outcomes. However, results were mixed for PB drinks, with links to micronutrient deficiencies. CONCLUSION: If carefully selected, certain NPBFs have the potential to be healthier and nutrient-rich alternatives to ABFs and typically have smaller environmental footprints. More disaggregated categorization of various types of NPBFs would be a helpful step in guiding consumers and key stakeholders to make informed decisions. To enable informed policymaking on the inclusion of NPBFs in dietary transitions as part of a wider net-zero and health strategy, future priorities should include nutritional food standards, labelling, and subdivisions or categorizations of NPBFs, as well as short- and long-term health studies evaluating dietary shifts from ABFs to NPBFs and standardized environmental impact assessments, ideally from independent funders.

Patient-reported outcomes in integrated health and social care: A scoping review.

Background: Patient-reported outcomes (PROs) have potential to support integrated health and social care research and practice; however, evidence of their utilisation has not been synthesised. Objective: To identify PRO measures utilised in integrated care and adult social care research and practice and to chart the evidence of implementation factors influencing their uptake. Design: Scoping review of peer-reviewed literature. Data sources: Six databases (01 January 2010 to 19 May 2023). Study selection: Articles reporting PRO use with adults (18+ years) in integrated care or social care settings. Review methods: We screened articles against pre-specified eligibility criteria; 36 studies (23%) were extracted in duplicate for verification. We summarised the data using thematic analysis and descriptive statistics. Results: We identified 159 articles reporting on 216 PRO measures deployed in a social care or integrated care setting. Most articles used PRO measures as research tools. Eight (5.0%) articles used PRO measures as an intervention. Articles focused on community-dwelling participants (35.8%) or long-term care home residents (23.9%), with three articles (1.9%) focussing on integrated care settings. Stakeholders viewed PROs as feasible and acceptable, with benefits for care planning, health and wellbeing monitoring as well as quality assurance. Patient-reported outcome measure selection, administration and PRO data management were perceived implementation barriers. Conclusion: This scoping review showed increasing utilisation of PROs in adult social care and integrated care. Further research is needed to optimise PROs for care planning, design effective training resources and develop policies and service delivery models that prioritise secure, ethical management of PRO data.

Genomic surveillance of SARS-CoV-2 using long-range PCR primers.

Introduction: Whole Genome Sequencing (WGS) of the SARS-CoV-2 virus is crucial in the surveillance of the COVID-19 pandemic. Several primer schemes have been developed to sequence nearly all of the ~30,000 nucleotide SARS-CoV-2 genome, using a multiplex PCR approach to amplify cDNA copies of the viral genomic RNA. Midnight primers and ARTIC V4.1 primers are the most popular primer schemes that can amplify segments of SARS-CoV-2 (400 bp and 1200 bp, respectively) tiled across the viral RNA genome. Mutations within primer binding sites and primer-primer interactions can result in amplicon dropouts and coverage bias, yielding low-quality genomes with 'Ns' inserted in the missing amplicon regions, causing inaccurate lineage assignments, and making it challenging to monitor lineage-specific mutations in Variants of Concern (VoCs). Methods: In this study we used a set of seven long-range PCR primer pairs to sequence clinical isolates of SARS-CoV-2 on Oxford Nanopore sequencer. These long-range primers generate seven amplicons approximately 4500 bp that covered whole genome of SARS-CoV-2. One of these regions includes the full-length S-gene by using a set of flanking primers. We also evaluated the performance of these long-range primers with Midnight primers by sequencing 94 clinical isolates in a Nanopore flow cell. Results and discussion: Using a small set of long-range primers to sequence SARS-CoV-2 genomes reduces the possibility of amplicon dropout and coverage bias. The key finding of this study is that long range primers can be used in single-molecule sequencing of RNA viruses in surveillance of emerging variants. We also show that by designing primers flanking the S-gene, we can obtain reliable identification of SARS-CoV-2 variants.

Implementation of climate adaptation in the public health sector in Europe: qualitative thematic analysis.

BACKGROUND: Adaptation, to reduce the health impacts of climate change, is driven by political action, public support and events (extreme weather). National adaptation policies or strategies are limited in addressing human health risks and implementation of adaptation in the public health community is not well understood. AIM: To identify key issues in climate change adaptation implementation for public health in Europe. METHODS: Key informant interviews with decision-makers in international, national and local city governments in 19 European countries. Participants were recruited if a senior decision-maker working in public health, environmental health or climate adaptation. INTERVIEWS ADDRESSED: Barriers and levers for adaptation, policy alignment, networks and evidence needs. RESULTS: Thirty-two interviews were completed between June and October 2021 with 4 international, 5 national and 23 city/local government stakeholders. Respondents reported inadequate resources (funding, training and personnel) for health-adaptation implementation and the marginal role of health in adaptation policy. A clear mandate to act was key for implementation and resource allocation. Limited cross-departmental collaboration and poor understanding of the role of public health in climate policy were barriers to implementation. CONCLUSIONS: Across Europe, progress is varied in implementation of climate adaptation in public health planning. Providing appropriate resources, training, knowledge mobilization and supporting cross-departmental collaboration and multi-level governance will facilitate adaptation to protect human health.

The impact of COVID-19 on PRO development, collection and implementation: views of UK and Ireland professionals.

BACKGROUND: PROs are valuable tools in clinical care to capture patients' perspectives of their health, symptoms and quality of life. However the COVID-19 pandemic has had profound impacts on all aspects of life, in particular healthcare and research. This study explores the views of UK and Irish health professionals, third sector and pharmaceutical industry representatives and academic researchers on the impact of COVID-19 on PRO collection, use and development in clinical practice. METHODS: A volunteer sample took part in a 10 question cross sectional qualitative survey, on the impact of COVID-19, administered online via Qualtrics. Demographic data was descriptively analysed, and the qualitative free text response data was subject to thematic analysis and summarised within the Strengths, Weaknesses, Opportunities and Threats (SWOT) framework. RESULTS: Forty nine participants took part located in a range of UK settings and professions. Participants highlighted staff strengths during the pandemic including colleagues' flexibility and ability to work collaboratively and the adoption of novel communication tools. Weaknesses were a lack of staff capacity to continue or start PRO projects and insufficient digital infrastructure to continue studies online. Opportunities included the added interest in PROs as useful outcomes, the value of electronic PROs for staff and patients particularly in relation to integration into systems and the electronic patient records. However, these opportunities came with an understanding that digital exclusion may be an issue for patient groups. Threats identified included that the majority of PRO research was stopped or delayed and funding streams were cut. CONCLUSIONS: Although most PRO research was on hold during the pandemic, the consensus from participants was that PROs as meaningful outcomes were valued more than ever. From the opportunities afforded by the pandemic the development of electronic PROs and their integration into electronic patient record systems and clinical practice could be a lasting legacy from the COVID-19 pandemic.

I'm not burned out. This is how I write notes.

Objectives: We describe an automated transcription system that addresses many documentation problems and fits within scheduled clinical hours. Materials and methods: During visits, the provider listens to the patient while maintaining eye contact and making brief notes on paper. Immediately after the visit conclusion and before the next, the provider makes a short voice recording on a smartphone which is transmitted to the system. The system uses a public domain general language model, and a hypertuned provider-specific language model that is iteratively refined as each produced note is edited by the physician, followed by final automated processing steps to add any templated text to the note. Results: The provider leaves the clinic having completed all voice files, median duration 3.4 minutes. Created notes are formatted as preferred and are a median of 363 words (range 125-1175). Discussion: This approach permits documentation to occur almost entirely within scheduled clinic hours, without copy-forward errors, and without interference with patient-provider interaction. Conclusion: Though no documentation method is likely to appeal to all, this approach may appeal to many physicians and avoid many current problems with documentation.

Considerations for patient and public involvement and engagement in health research.

Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.

Genomic Surveillance of SARS-CoV-2 Using Long-Range PCR Primers.

Whole Genome Sequencing (WGS) of the SARS-CoV-2 virus is crucial in the surveillance of the COVID-19 pandemic. Several primer schemes have been developed to sequence the ~30,000 nucleotide SARS-CoV-2 genome that use a multiplex PCR approach to amplify cDNA copies of the viral genomic RNA. Midnight primers and ARTIC V4.1 primers are the most popular primer schemes that can amplify segments of SARS-CoV-2 (400 bp and 1200 bp, respectively) tiled across the viral RNA genome. Mutations within primer binding sites and primer-primer interactions can result in amplicon dropouts and coverage bias, yielding low-quality genomes with 'Ns' inserted in the missing amplicon regions, causing inaccurate lineage assignments, and making it challenging to monitor lineage-specific mutations in Variants of Concern (VoCs). This study uses seven long-range PCR primers with an amplicon size of ~4500 bp to tile across the complete SARS-CoV-2 genome. One of these regions includes the full-length S-gene by using a set of flanking primers. Using a small set of long-range primers to sequence SARS-CoV-2 genomes reduces the possibility of amplicon dropout and coverage bias.

Lasting impairments following transient ischemic attack and minor stroke: a systematic review protocol.

Introduction: The focus on medical management and secondary prevention following Transient Ischemic Attack (TIA) and minor stroke is well-established. Evidence is emerging that people with TIA and minor stroke can experience lasting impairments as fatigue, depression, anxiety, cognitive impairment, and communication difficulties. These impairments are often underrecognized and inconsistently treated. Research in this area is developing rapidly and an updated systematic review is required to evaluate new evidence as it emerges. This living systematic review aims to describe the prevalence of lasting impairments and how they affect the lives of people with TIA and minor stroke. Furthermore, we will explore whether there are differences in impairments experienced by people with TIA compared to minor stroke. Methods: Systematic searches of PubMed, EMBASE, CINAHL, PsycINFO, Cochrane Libraries will be undertaken. The protocol will follow the Cochrane living systematic review guideline with an update annually. A team of interdisciplinary reviewers will independently screen search results, identify relevant studies based on the defined criteria, conduct quality assessments, and extract data. This systematic review will include quantitative studies on people with TIA and/or minor stroke that report on outcomes in relation to fatigue, cognitive and communication impairments, depression, anxiety, quality of life, return to work/education, or social participation. Where possible, findings will be grouped for TIA and minor stroke and collated according to the time that follow-up occurred (short-term < 3 months, medium-term 3-12 months, and long-term > 12 months). Sub-group analysis on TIA and minor stroke will be performed based on results from the included studies. Data from individual studies will be pooled to perform meta-analysis where possible. Reporting will follow the Preferred Reporting Items for Systematic review and Meta-Analysis Protocol (PRISMA-P) guideline. Perspectives: This living systematic review will collate the latest knowledge on lasting impairments and how these affect the lives of people with TIA and minor stroke. It will seek to guide and support future research on impairments emphasizing distinctions between TIA and minor stroke. Finally, this evidence will allow healthcare professionals to improve follow-up care for people with TIA and minor stroke by supporting them to identify and address lasting impairments.

Younger and Rural Children are More Likely to be Hospitalized for SARS-CoV-2 Infections.

Purpose: To identify characteristics of SARS-CoV-2 infection that are associated with hospitalization in children initially evaluated in a Pediatric Emergency Department (ED). Methods: We identified cases of SARS-CoV-2 positive patients seen in the Arkansas Children's Hospital (ACH) ED or hospitalized between May 27, 2020, and April 28, 2022 using ICD-10 codes within the Pediatric Hospital Information System (PHIS) Database. We compared infection waves for differences in patient characteristics, and used logistic regressions to examine which characteristics led to a higher chance of hospitalization. Findings: We included 681 pre-Delta cases, 673 Delta cases, and 970 Omicron cases. Almost 17% of patients were admitted to the hospital. Compared to Omicron infected children, pre-Delta and Delta infected children were twice as likely to be hospitalized (OR=2.2 and 2.0, respectively; p<0.0001). Infants less than 1 year of age were >3 times as likely to be hospitalized than children ages 5-14 years regardless of wave (OR=3.42; 95%CI=2.36-4.94). Rural children were almost 3 times as likely than urban children to be hospitalized across all waves (OR=2.73; 95%CI=1.97-3.78). Finally, those with a complex condition had nearly a 15-fold increase in odds of admission (OR=14.6; 95%CI=10.6-20.0). Conclusions: Children diagnosed during the pre-Delta or Delta waves were more likely to be hospitalized than those diagnosed during the Omicron wave. Younger and rural patients were more likely to be hospitalized regardless of wave. We suspect lower vaccination rates and larger distances from medical care influenced higher hospitalization rates.

Symptoms and signs of lung cancer prior to diagnosis: case-control study using electronic health records from ambulatory care within a large US-based tertiary care centre.

OBJECTIVE: Lung cancer is the most common cause of cancer-related death in the USA. While most patients are diagnosed following symptomatic presentation, no studies have compared symptoms and physical examination signs at or prior to diagnosis from electronic health records (EHRs) in the USA. We aimed to identify symptoms and signs in patients prior to diagnosis in EHR data. DESIGN: Case-control study. SETTING: Ambulatory care clinics at a large tertiary care academic health centre in the USA. PARTICIPANTS, OUTCOMES: We studied 698 primary lung cancer cases in adults diagnosed between 1 January 2012 and 31 December 2019, and 6841 controls matched by age, sex, smoking status and type of clinic. Coded and free-text data from the EHR were extracted from 2 years prior to diagnosis date for cases and index date for controls. Univariate and multivariable conditional logistic regression were used to identify symptoms and signs associated with lung cancer at time of diagnosis, and 1, 3, 6 and 12 months before the diagnosis/index dates. RESULTS: Eleven symptoms and signs recorded during the study period were associated with a significantly higher chance of being a lung cancer case in multivariable analyses. Of these, seven were significantly associated with lung cancer 6 months prior to diagnosis: haemoptysis (OR 3.2, 95% CI 1.9 to 5.3), cough (OR 3.1, 95% CI 2.4 to 4.0), chest crackles or wheeze (OR 3.1, 95% CI 2.3 to 4.1), bone pain (OR 2.7, 95% CI 2.1 to 3.6), back pain (OR 2.5, 95% CI 1.9 to 3.2), weight loss (OR 2.1, 95% CI 1.5 to 2.8) and fatigue (OR 1.6, 95% CI 1.3 to 2.1). CONCLUSIONS: Patients diagnosed with lung cancer appear to have symptoms and signs recorded in the EHR that distinguish them from similar matched patients in ambulatory care, often 6 months or more before diagnosis. These findings suggest opportunities to improve the diagnostic process for lung cancer.

Dehydrated Drosophila melanogaster track a water plume in tethered flight.

Perception of sensory stimuli can be modulated by changes in internal state to drive contextually appropriate behavior. For example, dehydration is a threat to terrestrial animals, especially to Drosophila melanogaster due to their large surface area to volume ratio, particularly under the energy demands of flight. While hydrated D. melanogaster avoid water cues, while walking, dehydration leads to water-seeking behavior. We show that in tethered flight, hydrated flies ignore a water stimulus, whereas dehydrated flies track a water plume. Antennal occlusions eliminate odor and water plume tracking, whereas inactivation of moist sensing neurons in the antennae disrupts water tracking only upon starvation and dehydration. Elimination of the olfactory coreceptor eradicates odor tracking while leaving water-seeking behavior intact in dehydrated flies. Our results suggest that while similar hygrosensory receptors may be used for walking and in-flight hygrotaxis, the temporal dynamics of modulating the perception of water vary with behavioral state.

Co-production of a feasibility trial of pacing interventions for Long COVID.

BACKGROUND: The high incidence of COVID-19 globally has led to a large prevalence of Long COVID but there is a lack of evidence-based treatments. There is a need to evaluate existing treatments for symptoms associated with Long COVID. However, there is first a need to evaluate the feasibility of undertaking randomised controlled trials of interventions for the condition. We aimed to co-produce a feasibility study of non-pharmacological interventions to support people with Long COVID. METHODS: A consensus workshop on research prioritisation was conducted with patients and other stakeholders. This was followed by the co-production of the feasibility trial with a group of patient partners, which included the design of the study, the selection of interventions, and the production of dissemination strategies. RESULTS: The consensus workshop was attended by 23 stakeholders, including six patients. The consensus from the workshop was to develop a clinical trial platform that focused on testing different pacing interventions and resources. For the co-production of the feasibility trial, patient partners selected three pacing resources to evaluate (video, mobile application, and book) and co-designed feasibility study processes, study materials and undertook usability testing of the digital trial platform. CONCLUSION: In conclusion, this paper reports the principles and process used to co-produce a feasibility study of pacing interventions for Long COVID. Co-production was effective and influenced important aspects of the study.

The World Health Organisation defines Long COVID as a condition which impacts people 3 months after they first had COVID-19. Some of the symptoms that characterise Long COVID symptoms include fatigue, breathlessness and brain fog. These symptoms have a major impact on people's health and quality of life. Today, over 2 million people in the United Kingdom suffer from Long COVID and there is a lack of drugs and non-drugs treatment. However, some non-drugs treatments which aim to manage fatigue in other conditions, such as pacing, could be used with people with Long COVID. In this paper, we report how we co-produced a study which tested whether or not it is feasible for people who have Long COVID to use a pacing resource and report their symptoms using an electronic platform. After a meeting to review existing non-drugs treatments, the research team and a group of patient partners agreed on co-developing a clinical trial platform to test different pacing resources. The research team then met with the patient partners twice a week to co-design the study during which people with Long COVID will use the pacing resources and report their symptoms. They also co-designed the study documents and how to report its results. Co-producing a study with patient partners was effective and influenced important aspects of the study.

Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.

BACKGROUND: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS. METHODS: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively. FINDINGS: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients. INTERPRETATION: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS. REGISTRATION: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.

Impact on mortality of pathways to net zero greenhouse gas emissions in England and Wales: a multisectoral modelling study.

BACKGROUND: The UK is legally committed to reduce its greenhouse gas emissions to net zero by 2050. We aimed to understand the potential impact on population health of two pathways for achieving this target through the integrated effects of six actions in four sectors. METHODS: In this multisectoral modelling study we assessed the impact on population health in England and Wales of six policy actions relating to electricity generation, transport, home energy, active travel, and diets relative to a baseline scenario in which climate actions, exposures, and behaviours were held constant at 2020 levels under two scenarios: the UK Climate Change Committee's Balanced Pathway of technological and behavioural measures; and its Widespread Engagement Pathway, which assumes more substantial changes to consumer behaviours. We quantified the impacts of each policy action on mortality using a life table comprising all exposures, behaviours, and health outcomes in a single model. FINDINGS: Both scenarios are predicted to result in substantial reductions in mortality by 2050. The Widespread Engagement Pathway achieves a slightly greater reduction in outdoor fine particulate matter air pollution of 3·2 µg/m3 (33%) and, under assumptions of appropriate ventilation, a greater improvement in indoor air pollution (a decrease in indoor-generated fine particulate matter from 9·4 µg/m3 to 4·6 µg/m3) and winter temperatures (increasing from 17·8°C to 18·1°C), as well as appreciably greater changes in levels of active travel (27% increase in metabolic equivalent hours per week of walking and cycling) by 2050. Additionally, the greater reduction in red meat consumption (50% compared with 35% under the Balanced Pathway) by 2050 results in greater consumption of fruits (17-18 g/day), vegetables (22-23 g/day), and legumes (5-7 g/day). Combined actions under the Balanced Pathway result in more than 2 million cumulative life-years gained over 2021-50; the estimated gain under the Widespread Engagement Pathway is greater, corresponding to nearly 2·5 million life-years gained by 2050 and 13·7 million life-years gained by 2100. INTERPRETATION: Reaching net zero greenhouse gas emissions is likely to lead to substantial benefits for public health in England and Wales, with the cumulative net benefits being correspondingly greater with a pathway that entails faster and more ambitious changes, especially in physical activity and diets. FUNDING: National Institute for Health Research and the Wellcome Trust.

How Timely Is Diagnosis of Lung Cancer? Cohort Study of Individuals with Lung Cancer Presenting in Ambulatory Care in the United States.

The diagnosis of lung cancer in ambulatory settings is often challenging due to non-specific clinical presentation, but there are currently no clinical quality measures (CQMs) in the United States used to identify areas for practice improvement in diagnosis. We describe the pre-diagnostic time intervals among a retrospective cohort of 711 patients identified with primary lung cancer from 2012-2019 from ambulatory care clinics in Seattle, Washington USA. Electronic health record data were extracted for two years prior to diagnosis, and Natural Language Processing (NLP) applied to identify symptoms/signs from free text clinical fields. Time points were defined for initial symptomatic presentation, chest imaging, specialist consultation, diagnostic confirmation, and treatment initiation. Median and interquartile ranges (IQR) were calculated for intervals spanning these time points. The mean age of the cohort was 67.3 years, 54.1% had Stage III or IV disease and the majority were diagnosed after clinical presentation (94.5%) rather than screening (5.5%). Median intervals from first recorded symptoms/signs to diagnosis was 570 days (IQR 273-691), from chest CT or chest X-ray imaging to diagnosis 43 days (IQR 11-240), specialist consultation to diagnosis 72 days (IQR 13-456), and from diagnosis to treatment initiation 7 days (IQR 0-36). Symptoms/signs associated with lung cancer can be identified over a year prior to diagnosis using NLP, highlighting the need for CQMs to improve timeliness of diagnosis.

A regionally coherent ecological fingerprint of climate change, evidenced from natural history collections.

Climate change has dramatic impacts on ecological systems, affecting a range of ecological factors including phenology, species abundance, diversity, and distribution. The breadth of climate change impacts on ecological systems leads to the occurrence of fingerprints of climate change. However, climate fingerprints are usually identified across broad geographical scales and are potentially influenced by publication biases. In this study, we used natural history collections spanning over 250 years, to quantify a range of ecological responses to climate change, including phenology, abundance, diversity, and distributions, across a range of taxa, including vertebrates, invertebrates, plants, and fungi, within a single region, Central Norway. We tested the hypotheses that ecological responses to climate change are apparent and coherent at a regional scale, that longer time series show stronger trends over time and in relation to temperature, and that ecological responses change in trajectory at the same time as shifts in temperature. We identified a clear regional coherence in climate signal, with decreasing abundances of limnic zooplankton (on average by 7691 individuals m-3 °C-1) and boreal forest breeding birds (on average by 1.94 territories km-2 °C-1), and earlier plant flowering phenology (on average 2 days °C-1) for every degree of temperature increase. In contrast, regional-scale species distributions and species diversity were largely stable. Surprisingly, the effect size of ecological response did not increase with study duration, and shifts in responses did not occur at the same time as shifts in temperature. This may be as the long-term studies include both periods of warming and temperature stability, and that ecological responses lag behind warming. Our findings demonstrate a regional climate fingerprint across a long timescale. We contend that natural history collections provide a unique window on a broad spectrum of ecological responses at timescales beyond most ecological monitoring programs. Natural history collections are thus an essential source for long-term ecological research.

Stroke and TIA Survivors' Perceptions of the COVID-19 Vaccine and Influences on Its Uptake: Cross Sectional Survey.

BACKGROUND: People who have experienced a stroke or transient ischaemic attack (TIA) have greater risks of complications from COVID-19. Therefore, vaccine uptake in this vulnerable population is important. To prevent vaccine hesitancy and maximise compliance, we need to better understand individuals' views on the vaccine. OBJECTIVES: We aimed to explore perspectives of the COVID-19 vaccine and influences on its uptake from people who have experienced a stroke or TIA. METHOD: A cross-sectional, electronic survey comprising multiple choice and free text questions. Convenience sampling was used to recruit people who have experienced a stroke/TIA in the UK/Ireland. RESULTS: The survey was completed by 377 stroke/TIA survivors. 87% (328/377) had either received the first vaccine dose or were booked to have it. The vaccine was declined by 2% (7/377) and 3% (11/377) had been offered the vaccine but not yet taken it up. 8% (30/377) had not been offered the vaccine despite being eligible. Some people expressed concerns around the safety of the vaccine (particularly risk of blood clots and stroke) and some were hesitant to have the second vaccine. Societal and personal benefits were motivations for vaccine uptake. There was uncertainty and lack of information about risk of COVID-19 related complications specifically for people who have experienced a stroke or TIA. CONCLUSION: Despite high uptake of the first vaccine, some people with stroke and TIA have legitimate concerns and information needs that should be addressed. Our findings can be used to identify targets for behaviour change to improve vaccine uptake specific to stroke/TIA patients.

Dominant effects of the histone mutant H3-L61R on Spt16-gene interactions in budding yeast.

Recent studies have unveiled an association between an L61R substitution within the human histone H3.3 protein and the presentation of neurodevelopmental disorders in two patients. In both cases, the mutation responsible for this substitution is encoded by one allele of the H3F3A gene and, if this mutation is indeed responsible for the disease phenotypes, it must act in a dominant fashion since the genomes of these patients also harbour three other alleles encoding wild-type histone H3.3. In our previous work in yeast, we have shown that most amino acid substitutions at H3-L61 cause an accumulation of the Spt16 component of the yFACT histone chaperone complex at the 3' end of transcribed genes, a defect we have attributed to impaired yFACT dissociation from chromatin following transcription. In those studies, however, the H3-L61R mutant had not been tested since it does not sustain viability when expressed as the sole source of histone H3 in cells. In the present work, we show that H3-L61R impairs proper Spt16 dissociation from genes when co-expressed with wild-type histone H3 in haploid cells as well as in diploid cells that express the mutant protein from one of four histone H3-encoding alleles. These results, combined with other studies linking loss of function mutations in human Spt16 and neurodevelopmental disorders, provide a possible molecular mechanism underlying the neurodevelopmental disorders seen in patients expressing the histone H3.3 L61R mutant.