Search

Recognition of the important physical and ecological roles played by large wood in channels and on floodplains has grown substantially during recent decades. Although large wood continues to be routinely removed from many river corridors worldwide, the practice of wood reintroduction has spread across the United States, the United Kingdom and western Europe, Australia, and New Zealand. The state‐of‐science regarding working with wood in rivers was discussed during a workshop held in Colorado, USA, in September 2022 with 40 participants who are scientists and practitioners from across the USA, UK, Europe, and Japan. The objectives of this paper are to present the findings from the workshop; summarize two case studies of wood in river restoration in the western United States; and provide suggestions for advancing the practice of wood in river management. We summarize the workshop results based on participant judgements and recommendations with respect to: (i) limitations and key barriers to using wood, which reflect perceptions and practicalities; (ii) gaps in the use of large wood in river management; (iii) scenarios in which wood is generally used effectively; and (iv) scenarios in which wood is generally not used effectively. The case studies illustrate the importance of the local geomorphic context, the configuration complexity of the wood, and the potential for modification of river corridor morphology to enhance desired benefits. Moving forward, we stress the importance of collaboration across disciplines and across communities of research scientists, practitioners, regulators, and potential stakeholders; accounting for stakeholder perceptions of the use of large wood; and increasing non‐scientist access to the latest state‐of‐science knowledge. [ABSTRACT FROM AUTHOR]

Objective: The Cancer Dependent Quality of Life (CancerDQoL) questionnaire asks about the impact of cancer and its treatment on individuals' quality of life (QoL). This study evaluates the psychometric properties of the CancerDQoL in a UK sample. Methods: Patients (n = 159) with a range of cancers, recruited from Barts Health NHS Trust and Barts Maggie's Centre, completed self‐administered questionnaires: CancerDQoL, EQ‐5D‐VAS (health status), EORTC‐QLQ‐C30 (predominantly health symptoms/functioning) and W‐BQ16 (well‐being). Based on the pre‐existing –DQoL template and Item Library (Bradley), the CancerDQoL includes 23 cancer‐specific life‐domain items and four overview items. Results: Exploratory factor analysis revealed a 22‐item, single‐factor solution. Internal consistency was excellent (α = 0.94). Cancer negatively impacted all life domains: 'feelings about future' had the most negative mean weighted (by importance) impact (WI) score. 'Physical abilities' WI scores were ranked 12th. CancerDQoL Average Weighted Impact (AWI) scores were more strongly correlated with the Cancer‐dependent QoL overview item than with the General QoL or General Health overview items. As expected, the EQ‐5D‐VAS and EORTC‐QLQ‐C30 correlated together more strongly than with CancerDQoL AWI scores. Conclusions: The CancerDQoL is the first individualised questionnaire measuring the impact of cancer and its treatment on QoL. The CancerDQoL AWI score is related to, but different from, measures of health status/functioning and well‐being. Eleven CancerDQoL life‐domains were more negatively impacted/important than physical abilities which is a major focus of the EQ‐5D and EORTC‐QLQ‐C30. By revealing aspects of life most impacted by cancer and its treatment, efforts can be prioritised to improve QoL for people with cancer. [ABSTRACT FROM AUTHOR]

Ethanol's anxiolytic actions contribute to increased consumption and the development of Alcohol Use Disorder (AUD). Our laboratory previously identified genetic loci contributing to the anxiolytic-like properties of ethanol in BXD recombinant inbred mice, derived from C57BL/6J (B6) and DBA/2J (D2) progenitor strains. That work identified Ninein (Nin) as a candidate gene underlying ethanol's acute anxiolytic-like properties in BXD mice. Nin has a complex exonic content with known alternative splicing events that alter cellular distribution of the NIN protein. We hypothesize that strain-specific differences in Nin alternative splicing contribute to changes in Nin gene expression and B6/D2 strain differences in ethanol anxiolysis. Using quantitative reverse-transcriptase PCR to target specific Nin splice variants, we identified isoform-specific exon expression differences between B6 and D2 mice in prefrontal cortex, nucleus accumbens and amygdala. We extended this analysis using deep RNA sequencing in B6 and D2 nucleus accumbens samples and found that total Nin expression was significantly higher in D2 mice. Furthermore, exon utilization and alternative splicing analyses identified eight differentially utilized exons and significant exon-skipping events between the strains, including three novel splicing events in the 3' end of the Nin gene that were specific to the D2 strain. Additionally, we document multiple single nucleotide polymorphisms in D2 Nin exons that are predicted to have deleterious effects on protein function. Our studies provide the first in-depth analysis of Nin alternative splicing in brain and identify a potential genetic mechanism altering Nin expression and function between B6 and D2 mice, thus possibly contributing to differences in the anxiolytic-like properties of ethanol between these strains. This work adds novel information to our understanding of genetic differences modulating ethanol actions on anxiety that may contribute to the risk for alcohol use disorder. [ABSTRACT FROM AUTHOR]

Background: Societal changes have led to greater isolation and higher levels of loneliness particularly for older generations. Loneliness is a significant public health challenge leading to increased levels of poor mental health. Depression and anxiety are also increasing in prevalence amongst children and young people. Intergenerational activities are interventions designed to bring together older and younger generations with the purpose of allowing participants to utilise their experiences and skills, and to give participants a chance to experience the pleasure and excitement that occurs with the transmission of knowledge and skills from one generation to another. Intergenerational activities are therefore potential interventions that can address the growing problems associated with loneliness and lack of wellbeing. Objectives: This systematic review aims to examine the impact of intergenerational interventions on the wellbeing and mental health in children and adolescents, and potential harmful effects. It also aims to identify areas for future research as well as key messages for service commissioners. Search Methods: We searched an evidence and gap map published in 2022 (comprehensive searches conducted July 2021 and updated June 2023) to identify randomised controlled trials of intergenerational interventions that report mental health and wellbeing outcomes for children and young people. Selection Criteria: Randomised controlled trials of intergenerational interventions that involved unrelated younger and older people with at least one skipped generation between them and reported mental health or wellbeing outcomes for children and young people were included in this review. Data Collection and Analysis: We used standard methodological procedures expected by The Campbell Collaboration. We conducted data extraction and Cochrane risk of bias assessments in EPPI reviewer. Main Results: While we identified 500 evaluations of intergenerational interventions, where the impact on participating children and/or young people was evaluated this was most often limited to assessing their impact on attitudes to aging. We identified five studies evaluating five different types of intergenerational interventions which included one‐off sessions to ones that spanned a year measuring their impact on the mental health and wellbeing of children and/or young people. The purposes of the interventions differed, which included promoting social skills, preventing harmful behaviour and promoting learning. The ages of children also varied across the five studies, with one targeting younger children, two targeting younger teenagers and two targeting older teenagers. One study included socioeconomically disadvantaged children, and in the other studies the socioeconomic backgrounds of the children and young people were not described. The outcome measures used to evaluate the interventions varied with none of the studies measuring the same outcomes. One study showed improvements in wellbeing measures, and this was an intervention delivered to children in deprived neighbourhoods, where the intervention duration was for a year allowing the development of a greater depth of relationship between the younger and older participants. Four studies found no....... The included studies were at high risk of bias therefore raising uncertainty in the reliability of the findings. Underpinning theories that supported the development of the interventions and explained the mechanisms of effect were poorly described. Authors' Conclusions: The evidence for the effectiveness of intergenerational interventions on the mental health and wellbeing of children and young people is limited and inconclusive. Few evaluations have sought to measure how intergenerational interventions impact children and young people and where this impact is measured the focus is usually limited to attitudes to aging. The evidence that has been collected is too heterogenous to allow synthesis of the findings. The underpinning theories to support their development are poorly described with no follow‐up data to ascertain if benefits are maintained. Intergenerational interventions show promise but researchers have failed to measure how they impact on the mental health and wellbeing of children and young people. This is a serious limitation of the evidence base that needs to be addressed in robust and rigorous evaluations. [ABSTRACT FROM AUTHOR]

Neutron and X-ray computed tomography (NCT and XCT, respectively) are imaging techniques that are increasingly applied in geomechanics research. They are used to non-destructively reveal different microstructural aspects of geomaterials: XCT is often used to observe/quantify differences in density or porosity, while NCT reveals the presence and distribution of hydrogenous materials such as water. The correlated use of NCT and XCT for geomechanics and geotechnics research is in its infancy. To this date, very few experiments have been carried out that combine both techniques, and none has been used to investigate geomaterial–structure interaction. This paper presents the first correlative NCT–XCT imaging study of pile installation. A scaled model pile was installed in an unsaturated intact chalk cylinder and in situ NCT and ex-situ XCT synchrotron-based imaging was applied consecutively. Chalk was used because the behaviour of displacement piles installed in this material is still subject to considerable uncertainty. Results reveal for the first time the interaction between installation-induced changes in chalk density and water distribution variations, with evidence of water displacement into the densified material in the vicinity of the installed pile. A straightforward method for correlative bulk density–moisture content determination from NCT–XCT images of geomaterials is presented and their limitations are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Binge drinking in adolescence can disrupt myelination and cause brain structural changes that persist into adulthood. Alcohol consumption at a younger age increases the susceptibility of these changes. Animal models to understand ethanol's actions on myelin and white matter show that adolescent binge ethanol can alter the developmental trajectory of oligodendrocytes, myelin structure, and myelin fiber density. Oligodendrocyte differentiation is epigenetically regulated by H3K9 trimethylation (H3K9me3). Prior studies have shown that adolescent binge ethanol dysregulates H3K9 methylation and decreases H3K9-related gene expression in the PFC. Methods: Here, we assessed ethanol-induced changes to H3K9me3 occupancy at genomic loci in the developing adolescent PFC. We further assessed ethanolinduced changes at the transcription level with qPCR time course approaches in oligodendrocyte-enriched cells to assess changes in oligodendrocyte progenitor and oligodendrocytes specifically. Results: Adolescent binge ethanol altered H3K9me3 regulation of synapticrelated genes and genes specific for glutamate and potassium channels in a sex-specific manner. In PFC tissue, we found an early change in gene expression in transcription factors associated with oligodendrocyte differentiation that may lead to the later significant decrease in myelin-related gene expression. This effect appeared stronger in males. Conclusion: Further exploration in oligodendrocyte cell enrichment time course and dose response studies could suggest lasting dysregulation of oligodendrocyte maturation at the transcriptional level. Overall, these studies suggest that binge ethanol may impede oligodendrocyte differentiation required for ongoing myelin development in the PFC by altering H3K9me3 occupancy at synaptic-related genes. We identify potential genes that may be contributing to adolescent binge ethanol-related myelin loss. [ABSTRACT FROM AUTHOR]

This article offers new insights into the important role that transdisciplinary, participatory action research approaches offer young people as a safe space to 'act' on climate change and environmental degradation. Drawing upon methodological meta‐reflections on three separate, but interlinked, projects (two UK‐based, one in Vietnam), we highlight an evolving approach that fuses knowledge, local context and emotional connection to engage action. We argue that these innovative approaches facilitate the empowerment of young people to co‐create and lead solutions, adaptations and mitigations that can make a significant impact on the climate and biodiversity crises whilst influencing policymakers and inspiring collaborative change‐making. [ABSTRACT FROM AUTHOR]

Objectives: Limited evidence exists on the policies to increase self‐isolation compliance, with no experimental evidence. This trial aimed to evaluate the effect of a home visiting intervention in the London Borough of Havering on compliance with self‐isolation guidance, relative to positive COVID‐19 cases who received no home visits. Design: Mixed method evaluation involving a two‐arm randomized controlled trial (RCT) with an implementation and process evaluation. Methods: A total of 3878 cases who tested positive for COVID‐19 were randomly allocated with equal probability to receive home visits from Havering outreach team staff (n = 1946) or to a control group (n = 1932) who did not receive home visits. Randomization was implemented through a spreadsheet consisting of random numbers generated online that was used to randomly allocate cases to treatment and control. Check‐in calls were conducted by a separate blinded contact tracing team on day six of isolation to measure successful self‐isolation compliance. The primary intention‐to‐treat (ITT) analysis was conducted on 3860 cases as 18 patients were excluded from analysis because of the missing outcome data. For the implementation and process evaluation, qualitative, semi‐structured, one‐to‐one interviews were conducted with trial participants in the treatment arm of the RCT (n = 15) and stakeholders within the London Borough of Havering's Adult Social Care and Health Team (n = 8). Qualitative data was analysed thematically using a framework approach. Results: Positive cases who were allocated to receive the home visiting intervention (n = 1933) were more likely to report successful self‐isolation compared to those allocated to the control group (n = 1927), an effect that was statistically significant (odds ratio 1.204 [95% CI: 1.052, 1.377]; absolute probability difference: 4.1 percentage points [95% CI: 1.2–6.9]). The implementation and process evaluation found that a key driver of compliance was altruistic motivation based on its perceived importance for protecting the community with some participants also reporting the potential of being caught not complying as a driving factor. Participants also reported that the intervention helped them 'feel supported', provided them with information about practical and financial support, and clarified their understanding or increased their awareness of self‐isolation and COVID‐19 guidance. No harms were reported from this trial. The trial was registered at the ISRCTN registry, number ISRCTN10030612. Conclusions: A home‐visiting intervention conducted between January and March 2022 increased the self‐isolation compliance of positive COVID‐19 cases allocated to receive home visits. The implementation and process evaluation highlighted that the intervention increased individuals' motivation to comply with guidance, and addressed some barriers associated with opportunity and capability to comply. This trial provides much‐needed evidence to inform the policy and intervention design to support public health and social measures in future outbreak scenarios. [ABSTRACT FROM AUTHOR]

Introduction: Adolescence is a critical period in cognitive and emotional development, characterized by high levels of social interaction and increases in risk-taking behavior including binge drinking. Adolescent exposure to social stress and binge ethanol have individually been associated with the development of social, emotional, and cognitive deficits, as well as increased risk for alcohol use disorder. Disruption of cortical development by early life social stress and/or binge drinking may partly underlie these enduring emotional, cognitive, and behavioral effects. The study goal is to implement a novel neighbor housing environment to identify the effects of adolescent neighbor housing and/or binge ethanol drinking on (1) a battery of emotional and cognitive tasks (2) adult ethanol drinking behavior, and (3) the nucleus accumbens and prefrontal cortex transcriptome. Methods: Adolescent male and female C57BL/6J mice were single or neighbor housed with or without access to intermittent ethanol. One cohort underwent behavioral testing during adulthood to determine social preference, expression of anxiety-like behavior, cognitive performance, and patterns of ethanol intake. The second cohort was sacrificed in late adolescence and brain tissue was used for transcriptomics analysis. Results: As adults, single housed mice displayed decreased social interaction, deficits in the novel object recognition task, and increased anxiety-like behavior, relative to neighbor-housed mice. There was no effect of housing condition on adolescent or adult ethanol consumption. Adolescent ethanol exposure did not alter adult ethanol intake. Transcriptomics analysis revealed that adolescent housing condition and ethanol exposure resulted in differential expression of genes related to synaptic plasticity in the nucleus accumbens and genes related to methylation, the extracellular matrix and inflammation in the prefrontal cortex. Discussion: The behavioral results indicate that social interaction during adolescence via the neighbor housing model may protect against emotional, social, and cognitive deficits. In addition, the transcriptomics results suggest that these behavioral alterations may be mediated in part by dysregulation of transcription in the frontal cortex or the nucleus accumbens. [ABSTRACT FROM AUTHOR]

Historically, the NHS did not routinely collect cost data, unlike many countries with private insurance markets. In 1998, for the first time the government mandated NHS trusts to submit estimates of their costs of service, known as reference costs. These have informed a wide range of health economic evaluations and important functions in the health service, such as setting prices. Reference costs are collected by progressively disaggregating budgets top-down into disease and treatment groups. Despite ongoing improvements to methods and guidance, these submissions continued to suffer a lack of accuracy and comparability, fundamentally undermining their credibility for critical functions. To overcome these issues, there was a long-held ambition to collect "patient-level" cost data. Patient-level costs are estimated with a combination of disaggregating budgets but also capturing the patient-level "causality of costs" bottom-up in the allocation of resources to patient episodes. These not only aim to capture more of the drivers of costs, but also improve consistency of reporting between providers. The change in methods may confer improvements to data quality, though judgement is still required and achieving consistency between trusts will take further work. Estimated costs may also change in important ways that may take many years to fully understand. We end on a cautionary note that patient-level cost methods may unlock potential, they alone contribute little to our understanding of the complexities involved with service quality or need, while that potential will require substantial investment to realise. Many healthcare resources cannot be attributed to individual patients so the very notion of "patient-level" costs may be misplaced. High hopes have been put in these new data, though much more work is now necessary to understand their quality, what they show and how their use will impact the system. [ABSTRACT FROM AUTHOR]

Increased extreme heat events draw attention to the potential of urban nature as a heat adaptation strategy for cities. This is reflected in multiple scientific perspective pieces, policy documents and science media publications advocating for urban greening as a cooling approach. Although attention to the dangers of heat and the benefits of urban nature is welcomed, it is vital that nature-based approaches to cooling are underpinned by diverse knowledge and a sound understanding of what nature in cities can and cannot do. We explain why an evidence-driven and cautious approach to heat adaptation through urban greening is so important, and propose three actions that urban actors can take towards effective and equitable long-term cooling through urban nature: enabling dialogue between different sectors with multiple remits; including diverse knowledge systems in planning and governance processes; and investing in long-term stewardship for the climatological and societal conditions of the coming decades. Policy and practice recommendation • Create fora for dialogue between governments, residents, civil society and developers from planning stage for green cooling; • Cooling through nature must be driven by expertise spanning diverse knowledge systems, combined with local knowledge and community needs; • Consider future climates and stewardship when planning urban cooling via nature. Science highlights • Understanding link between urban thermal environment and nature is an inter- and transdisciplinary task; • Critical need for evidence of how greening reduces heat impacts across different social and cultural contexts; • Evidence of how species perform under future climates required for stewardship of urban nature. [ABSTRACT FROM AUTHOR]

This is the protocol for a Campbell systematic review. The objectives are as follows: this systematic review will examine the impact of intergenerational interventions on the wellbeing and mental health in children and young people and will identify areas for future research as well as key messages for service commissioners. [ABSTRACT FROM AUTHOR]

While the toxicity of PARP inhibitors to cells with defects in homologous recombination (HR) is well established, other synthetic lethal interactions with PARP1/PARP2 disruption are poorly defined. To inform on these mechanisms we conducted a genome-wide screen for genes that are synthetic lethal with PARP1/2 gene disruption and identified C16orf72/HAPSTR1/TAPR1 as a novel modulator of replication-associated R-loops. C16orf72 is critical to facilitate replication fork restart, suppress DNA damage and maintain genome stability in response to replication stress. Importantly, C16orf72 and PARP1/2 function in parallel pathways to suppress DNA:RNA hybrids that accumulate at stalled replication forks. Mechanistically, this is achieved through an interaction of C16orf72 with BRCA1 and the RNA/DNA helicase Senataxin to facilitate their recruitment to RNA:DNA hybrids and confer resistance to PARP inhibitors. Together, this identifies a C16orf72/Senataxin/BRCA1-dependent pathway to suppress replication-associated R-loop accumulation, maintain genome stability and confer resistance to PARP inhibitors. Here the authors identify that C16orf72 regulates BRCA1/Senataxin to promote replication fork recovery. These proteins act together in a pathway parallel to PARP1 to suppress R-loop accumulation in response to replication stress and confer resistance to PARP inhibitors. [ABSTRACT FROM AUTHOR]

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Background: Current follow‐up models in cancer are seen to be unsustainable and inflexible, and there is growing interest in alternative models, such as patient‐initiated follow‐up (PIFU). It is therefore important to understand whether PIFU is acceptable to patients and healthcare professionals (HCPs). Methods: Standard systematic review methodology aimed at limiting bias was used for study identification (to January 2022), selection and data extraction. Thematic synthesis was undertaken for qualitative data, and survey findings were tabulated and described. Results: Nine qualitative studies and 22 surveys were included, mainly in breast and endometrial cancer. Women treated for breast or endometrial cancer and HCPs were mostly supportive of PIFU. Facilitators for PIFU included convenience, control over own health and avoidance of anxiety‐inducing clinic appointments. Barriers included loss of reassurance from scheduled visits and lack of confidence in self‐management. HCPs were supportive of PIFU but concerned about resistance to change, unsuitability of PIFU for some patients and costs. Conclusion: PIFU is viewed mostly positively by women treated for breast or endometrial cancer, and by HCPs, but further evidence is needed from a wider range of cancers, men, and more representative samples. A protocol was registered with PROSPERO (CRD42020181412). [ABSTRACT FROM AUTHOR]

Aims and method Factors influencing trainees’ decisions about choosing and remaining in higher training subspecialties have not been widely researched. We administered telephone questionnaires to higher specialist trainees in the north-east of England to ascertain what influences these decisions. Thematic analysis was employed to develop overall constructs. Results Twenty-seven trainees were interviewed, resulting in six overall constructs. These were: supervisory experiences; perceived work–life balance; career prospects; training and working environments; interest in the chosen subspecialty; and previous experience within the chosen subspecialty. Most trainees interviewed felt they had made the right specialty choice. Clinical implications This study demonstrates the particular importance of exposure to a specialty and perceptions of the supervisory experience in determining trainees’ choices of, and decisions to remain in, a particular psychiatric specialty. Factors highlighted in this study must inform training, recruitment and workforce planning in order to bolster the recruitment and retention of trainees into higher specialty training. [ABSTRACT FROM AUTHOR]

This randomized food effect study in healthy adult participants examined dispersible tablet formulations of fixed-dose combinations of dolutegravir/abacavir/lamivudine (TRIUMEQ) and dolutegravir/lamivudine (DOVATO). While adult tablet formulations of these combinations are currently approved for the treatment of human immunodeficiency virus, alternate formulations for children are urgently needed to facilitate appropriate pediatric dosing for patients who may have difficulty swallowing a conventional tablet. This study compared the effect of a high-fat, high-calorie meal on the pharmacokinetics, safety, and tolerability of dispersible tablet (DT) formulations of the two-drug and three-drug regimens, with administration under fasting conditions. Both the two-drug and three-drug dispersible tablet formulations, administered under fasting conditions and following a high-fat, high-calorie meal, were well tolerated in healthy participants. There were no clinically relevant differences in drug exposure for either regimen when administered with a high-fat meal as compared to under fasting conditions. Safety observations were similar for both treatments, either in the fed or fasted state. Both TRIUMEQ DT and DOVATO DT formulations can be administer with or without food. [ABSTRACT FROM AUTHOR]

Adolescence is marked in part by the ongoing development of the prefrontal cortex (PFC). Binge ethanol use during this critical stage in neurodevelopment induces significant structural changes to the PFC, as well as cognitive and behavioral deficits that can last into adulthood. Previous studies showed that adolescent binge ethanol causes lasting deficits in working memory, decreases in the expression of chromatin remodeling genes responsible for the methylation of histone 3 lysine 36 (H3K36), and global decreases in H3K36 in the PFC. H3K36me3 is present within the coding region of actively-transcribed genes, and safeguards against aberrant, cryptic transcription by RNA Polymerase II. We hypothesize that altered methylation of H3K36 could play a role in adolescent binge ethanol-induced memory deficits. To investigate this at the molecular level, ethanol (4g/kg, i.g.) or water was administered intermittently to adolescent mice. RNA-and ChIP-sequencing were then performed within the same tissue to determine gene expression changes and identify genes and loci where H3K36me3 was disrupted by ethanol. We further assessed ethanolinduced changes at the transcription level with differential exon-use and cryptic transcription analysis - a hallmark of decreased H3K36me3. Here, we found ethanolinduced changes to the gene expression and H3K36me3-regulation of synapticrelated genes in all our analyses. Notably, H3K36me3 was differentially trimethylated between ethanol and control conditions at synaptic-related genes, and Snap25 and Cplx1 showed evidence of cryptic transcription in males and females treated with ethanol during adolescence. Our results provide preliminary evidence that ethanol-induced changes to H3K36me3 during adolescent neurodevelopment may be linked to synaptic dysregulation at the transcriptional level, which may explain the reported ethanol-induced changes to PFC synaptic function. [ABSTRACT FROM AUTHOR]

Background: Opportunities for social connection between generations in the UK have diminished over the last few decades because of changes in the way that we live and work. The decline in communal spaces such as libraries, youth clubs and community centres mean that there are fewer opportunities to meet and mix socially with other generations outside our own families. Increased working hours, improved technology, changes in family patterns, relationship breakdowns within families and migration are also believed to be contributory factors to generation segregation. There are many potential economic, social and political impacts of generations living separate and parallel lives, for example, higher health and social care costs, an undermining of trust between generations reduced social capital, a reliance on the media to form understanding of others' viewpoints and higher levels of anxiety and loneliness. Intergenerational programmes and activities can take many forms and are delivered in many settings. Evidence suggests that intergenerational activity can have a positive impact on participants, for example, in reducing loneliness and exclusion for both older people and children and young people, improving mental health, increasing mutual understanding and addressing important issues such as ageism, housing and care. There are currently no other EGMs that exist that address this type of intervention; however, it would complement existing EGMs addressing child welfare. Objectives: To identify, appraise and bring together the evidence on the use of intergenerational practice, to answer the following specific research questions: What is the volume, nature and diversity of research on, and evaluation of, intergenerational practice and learning?What approaches have been used to deliver intergenerational activities and programmes that may be relevant to providing such services during and in the subsequent recovery from the COVID‐19 pandemic?What promising intergenerational activities and programmes have been developed and are being used but have not yet been subject to formal evaluation? Search Methods: We searched MEDLINE (via OvidSp), EMBASE (via OvidSp), PsycINFO (via OvidSp), CINAHL (via EBSCOHost), Social Policy and Practice (via OvidSp), Health Management Information Consortium (via OvidSp), Ageline (via EBSCOhost), ASSIA (via ProQuest), Social Science Citations Index (via Web of Science), ERIC (via EBSCOhost), Community Care Inform Children, Research in Practice for Children, ChildData (via Social Policy and Practice), the Campbell Library, the Cochrane Database of Systematic Reviews and the CENTRAL database between 22 and 30 July 2021. We searched for additional grey literature via the Conference Proceedings Citation Index (via Web of Science) and ProQuest Dissertation & Theses Global and via relevant organisation websites, for example, Age UK, Age International, the Centre for Ageing Better, Barnado's, Children's Commission, UNICEF, Generations Working Together, the Intergenerational Foundation, Linking Generations and The Beth Johnson Foundation) and the Ottawa initiative called Older Adults and Students for Intergenerational support. Selection Criteria: Any intervention that brings older and younger people together with the purpose of interacting to achieve positive health and/or social and/or educational outcomes from any study design including systematic reviews, randomised controlled studies, observational studies, surveys and qualitative studies are included. The titles and abstracts, and later full texts, of records identified by the search methods were screened against inclusion criteria by two independent reviewers. Data Collection and Analysis: Data extraction was undertaken by one reviewer and checked by a second with any inconsistencies identified and resolved through discussion. The data extraction tool was developed on EPPI reviewer and was modified and tested through stakeholder and advisor consultation, and piloting of the process. The tool was informed by the research question and the structure of the map. We did not undertake quality appraisal of the included studies. Main Results: Our searches identified 12,056 references, after screening 500 research articles were included in the evidence gap map conducted across 27 countries. We identified 26 systematic reviews, 236 quantitative comparative studies (of which 38 were randomised controlled trials), 227 were qualitative studies (or had a qualitative element), 105 were observational studies (or had elements of observational methods) and 82 used a mixed methods approach. The outcomes reported in the research cover mental health (n = 73), physical health (n = 62), attainment and knowledge (n = 165), agency (n = 174), mental wellbeing (n = 224), loneliness and social isolation (n = 54), attitudes towards the other generation (n = 283), intergenerational interactions (n = 196), peer interactions (n = 30) and health promotion (n = 23) and including mutual outcomes such as the impact on community (n = 37) and perceptions on the sense of community (n = 43). Gaps in the evidence that were identified include: research that reports on mutual, societal and community outcomes of intergenerational interventions; more research on interventions classified as levels 1–4 and level 7 on the Intergenerational Engagement Scale, mental health, loneliness, social isolation, peer interactions, physical health and health promotion outcomes in children and young people; health promotion in older people; outcomes centred on care giver wellbeing, mental health and attitudes; economic outcomes; process outcomes and adverse or unexpected outcomes. Authors' Conclusions: Whilst a substantional amount of research on intergenerational interventions has been identified in this EGM, as well as the gaps identified above, there is a need to explore promising interventions not yet formally evaluated. Research on this topic is gradually increasing, and systematic reviews will be important to determine how and why interventions are or are not beneficial. However, the primary research needs to build more cohesively so that the findings can be comparable and avoid research waste. The EGM presented here will nevertheless be a useful resource for decision‐makers allowing them to explore the evidence with regard to the different interventions that may be relevant to their population needs and the settings or resources available to them. [ABSTRACT FROM AUTHOR]

Tumor mutational burden (TMB) has recently been approved as an agnostic biomarker for immune checkpoint inhibitors. However, methods for TMB testing have not yet been standardized. The International Quality Network for Pathology (IQNPath) organized a pilot external quality assessment (EQA) scheme for TMB testing. The aim of this program was the validation of the materials and the procedures for the EQA of this complex biomarker. Five formalin-fixed paraffin-embedded (FFPE) cell lines were selected to mimic the various TMB values observed in clinical practice. The FFPE samples were tested with the FoundationOne CDx (F1CDx) assay as the reference test and three commercially available targeted sequencing panels. Following this internal validation, the five cell lines were sent to 29 laboratories selected on the basis of a previous survey. Nineteen of the 23 laboratories that submitted results (82.6%) used targeted sequencing for TMB estimation. Only two laboratories performed whole exome sequencing (WES) and two assessed TMB by clinical exome. A high variability in the reported TMB values was observed. The variability was higher for samples with the highest TMB value according to the F1CDx test. However, good reproducibility of the TMB score was shown by laboratories using the same panel. The majority of laboratories did not indicate a TMB cut-off value for clinical interpretation. In conclusion, this pilot EQA scheme suggests that it is feasible to run such an EQA program for TMB assessment. However, the results of our pilot highlight the numerous challenges for the standardization of this test. [ABSTRACT FROM AUTHOR]

Astrochemical models treat dust surfaces as ice covered. We investigate the effects of implementing increased bare dust binding energies of CO and S-bearing species on the chemistry in the outflows of asymptotic giant branch (AGB) stars. We demonstrate the potential for improving agreement with observations in the outflow of IK Tau. Increasing the binding energies to measured and computationally derived values in high mass-loss AGB outflows increased the production of daughter species. Switching from a high binding energy on bare dust to weaker binding to ice, the gas phase abundance increased at a radius in agreement with observations of IK Tau, suggesting that displacement of bound species could contribute to this observational puzzle. Using a strong binding to bare dust, a gas phase increase was not observed, however parent species concentrations had to be increased by around a factor of four to explain observed concentrations. [ABSTRACT FROM AUTHOR]

Alcohol use disorder is a major cause of morbidity, which requires newer treatment approaches. We previously showed in a randomized clinical trial that alcohol craving and consumption reduces after fecal transplantation. Here, to determine if this could be transmitted through microbial transfer, germ-free male C57BL/6 mice received stool or sterile supernatants collected from the trial participants pre-/post-fecal transplant. We found that mice colonized with post-fecal transplant stool but not supernatants reduced ethanol acceptance, intake and preference versus pre-fecal transplant colonized mice. Microbial taxa that were higher in post-fecal transplant humans were also associated with lower murine alcohol intake and preference. A majority of the differentially expressed genes (immune response, inflammation, oxidative stress response, and epithelial cell proliferation) occurred in the intestine rather than the liver and prefrontal cortex. These findings suggest a potential for therapeutically targeting gut microbiota and the microbial-intestinal interface to alter gut-liver-brain axis and reduce alcohol consumption in humans. Gut microbiota composition is altered in patients with alcohol use disorder, and fecal microbiota transplant reduced alcohol craving in patients with alcohol use disorder and liver cirrhosis in a phase 1 clinical trial. Here the authors used stool samples collected in the trial to report that this phenotype is transmissible via microbial transfer to germ free mice, as assessed by reduced ethanol acceptance, intake and preference. [ABSTRACT FROM AUTHOR]

Background: Quality of life (QoL) is an important measure of disease burden and general health perception. The relationship between early chronic kidney disease (CKD) and QoL remains poorly understood. The Oxford Renal Study (OxRen) cohort comprises 1063 adults aged ≥60 years from UK primary care practices screened for early CKD, grouped according to existing or screen-detected CKD diagnoses, or biochemistry results indicative of reduced renal function (referred to as transient estimated glomerular filtration rate (eGFR) reduction). Objectives: This study aimed to compare QoL in participants known to have CKD at recruitment to those identified as having CKD through a screening programme. Methods: Health profile data and multi-attribute utility scores were reported for two generic questionnaires: 5-level EuroQol-5 Dimension (EQ-5D-5L) and ICEpop CAPability measure for Adults (ICECAP-A). QoL was compared between patients with existing and screen-detected CKD; those with transient eGFR reduction served as the reference group in univariable and multivariable linear regression. Results: Mean and standard deviation utility scores were not significantly different between the subgroups for EQ-5D-5L (screen-detected:0.785±0.156, n = 480, transient:0.779±0.157, n = 261, existing CKD:0.763±0.171, n = 322, p = 0.216) or ICECAP-A (screen-detected:0.909±0.094, transient:0.904±0.110, existing CKD:0.894±0.115, p = 0.200). Age, smoking status, and number of comorbidities were identified as independent predictors of QoL in this cohort. Conclusion: QoL of participants with existing CKD diagnoses was not significantly different from those with screen-detected CKD or transient eGFR reduction and was similar to UK mean scores for the same age, suggesting that patient burden of early CKD is minor. Moreover, CKD-related comorbidities contribute more significantly to disease burden in earlier stages of CKD than renal function per se. Larger prospective studies are required to define the relationship between QoL and CKD progression more precisely. These data also confirm the essentially asymptomatic nature of CKD, implying that routine screening or case finding are required to diagnose it. [ABSTRACT FROM AUTHOR]

A persistent problem in UK hospitals is that of delayed discharges, where patients who are fit for discharge continue to occupy beds whilst awaiting care packages from Social Care. Integrated Care Systems (ICSs) in which Health and Social Care collaborate are now a major NHS initiative, the thinking being that such spending will have direct cost savings to health by freeing up expensive beds. The premise of this paper is that the benefits to health of assisting Social Care could also reduce a number of serious indirect costs and provide wide-ranging benefits to hospital patients, staff and budgets. This is accomplished by reducing the congestion arising from the use of many painful internal coping strategies and unintended consequences, which hospitals have to resort to when constrained by a lack of discharge solutions. The paper explores new and novel ways of using generic systems archetypes to create a hypothesis linking general Integrated Care Systems to congestion reduction throughout hospitals. Rather than use archetypes individually, they are applied here collectively in tandem. These are named 'cascaded archetypes', where the unintended consequence of one archetype becomes the driver for the next and are useful where fundamental solutions to problems are difficult to implement and unintended consequences must be dealt with. [ABSTRACT FROM AUTHOR]

Background: Safety netting in primary care may help diagnose cancer earlier, but it is unclear what the format and content of an acceptable safety-netting intervention would be. This project aimed to co-design a safety-netting intervention with and for primary care patients and staff.Aim: This work sought to address how a safety-netting intervention would be implemented in practice; and, if and how a safety-netting intervention would be acceptable to all stakeholders.Design and Setting: Patient representatives, GPs, and nurse practitioners were invited to a series of co-design workshops. Patients who had and had not received a diagnosis of cancer and primary care practices took part in separate focus groups.Method: Three workshops using creative co-design processes developed the format and content of the intervention prototype. The COM-B Framework underpinned five focus groups to establish views on capability, opportunity, and motivation to use the intervention to assist with prototype refinement.Results: Workshops and focus groups suggested the intervention format and content should incorporate visual and written communication specifying clear timelines for monitoring symptoms and when to present back; be available in paper and electronic forms linked to existing computer systems; and be able to be delivered within a 10-minute consultation. Intervention use themes included 'building confidence through partnership', 'using familiar and current procedures and systems', and 'seeing value'.Conclusion: The Shared Safety Net Action Plan (SSNAP) - a safety-netting intervention to assist the timely diagnosis of cancer in primary care, was successfully co-designed with and for patients and primary care staff. [ABSTRACT FROM AUTHOR]

This is the protocol for a Campbell systematic review. The objectives are as follows: identify, appraise and bring together the evidence on the use of intergenerational practice. [ABSTRACT FROM AUTHOR]

Objective: To determine the potential cost savings resulting from the introduction of routine early medical abortion (EMA) at home by telemedicine in the UK. Design: A costing study. Setting: The UK. Population: Women in 2020 undergoing EMA provided by three independent abortion providers and two National Health Service (NHS) abortion clinics. Methods: Computation of the costs of each abortion procedure and of managing failed or incomplete abortion and haemorrhage requiring blood transfusion. Main outcome measures: Cost savings. Results: Overall estimated cost savings are £15.80 per abortion undertaken by independent abortion providers, representing a saving to the NHS of over £3 million per year. Limited data from NHS services resulted in an estimated average saving of £188.84 per abortion. Conclusions: Were telemedicine EMA to become routine, an increase in the number of women eligible for medical rather than surgical abortion, and a reduction in adverse events resulting from earlier abortion, could result in significant cost savings. Early medical abortion at home using telemedicine could save the NHS £3 million per year. Early medical abortion at home using telemedicine could save the NHS £3 million per year. [ABSTRACT FROM AUTHOR]

The aim of the Being Warm Being Happy project was to understand and characterise fuel poverty and energy vulnerability from the perspective of adults with learning disabilities. Undertaken in community settings in South Yorkshire, UK, the study adopted an inclusive research approach, with three members of a self-advocacy organisation who have learning disabilities and/or autism working alongside academics as co-researchers. The study incorporated home temperature and humidity measurements and qualitative individual interviews. Ten households, all of which included an adult with learning disabilities participated in the research. Framework analysis identified four interrelated themes influencing decisions about energy use and payment method. First, energy need varied according to health status. Energy need was also influenced by the size, tenure and age of the participant's home. Second, emotions, attitudes and values, in particular a sense of control impacted upon energy use. Third, knowledge and previous experience could help or hinder participants keeping warm. Factors included prior first-hand experiences of support from self-advocacy organisations, energy companies and local authorities and the influence of parents' views and practices. Finally, concerns about affordability and challenges accessing the energy market also had an important impact on experiences and decisions. The research contributes to the limited evidence base about the nature and experience of fuel poverty amongst adults with learning disabilities highlighting the extent to which the existing energy system puts them at a disadvantage and the resourcefulness and resilience of many adults with learning disabilities when facing these challenges. [ABSTRACT FROM AUTHOR]

Adolescence is a critical developmental period characterized by enhanced social interactions, ongoing development of the frontal cortex and maturation of synaptic connections throughout the brain. Adolescents spend more time interacting with peers than any other age group and display heightened reward sensitivity, impulsivity and diminished inhibitory self-control, which contribute to increased risky behaviors, including the initiation and progression of alcohol use. Compared to adults, adolescents are less susceptible to the negative effects of ethanol, but are more susceptible to the negative effects of stress, particularly social stress. Juvenile exposure to social isolation or binge ethanol disrupts synaptic connections, dendritic spine morphology, and myelin remodeling in the frontal cortex. These structural effects may underlie the behavioral and cognitive deficits seen later in life, including social and memory deficits, increased anxiety-like behavior and risk for alcohol use disorders (AUD). Although the alcohol and social stress fields are actively investigating the mechanisms through which these effects occur, significant gaps in our understanding exist, particularly in the intersection of the two fields. This review will highlight the areas of convergence and divergence in the fields of adolescent social stress and ethanol exposure. We will focus on how ethanol exposure or social isolation stress can impact the development of the frontal cortex and lead to lasting behavioral changes in adulthood. We call attention to the need for more mechanistic studies and the inclusion of the evaluation of sex differences in these molecular, structural, and behavioral responses. [ABSTRACT FROM AUTHOR]

The article describes the 0-19 Research Network Yorkshire and the Humber (Y&H) developed over eight years that resonates and reflects the nursing research vision in practice for 0 to 19 practitioners. Topics discussed include evidence that demonstrates research conducted alongside practice that improves the quality of care provided, background to the research network , and personal awards as a direct result of the 0-19 Network.

Objective: Accurate automated segmentation of cartilage should provide rapid reliable outcomes for both epidemiological studies and clinical trials. We aimed to assess the precision and responsiveness of cartilage thickness measured with careful manual segmentation or a novel automated technique.Methods: Agreement of automated segmentation was assessed against 2 manual segmentation datasets: 379 magnetic resonance images manually segmented in-house (training set), and 582 from the Osteoarthritis Initiative with data available at 0, 1, and 2 years (biomarkers set). Agreement of mean thickness was assessed using Bland-Altman plots, and change with pairwise Student t test in the central medial femur (cMF) and tibia regions (cMT). Repeatability was assessed on a set of 19 knees imaged twice on the same day. Responsiveness was assessed using standardized response means (SRM).Results: Agreement of manual versus automated methods was excellent with no meaningful systematic bias (training set: cMF bias 0.1 mm, 95% CI ± 0.35; biomarkers set: bias 0.1 mm ± 0.4). The smallest detectable difference for cMF was 0.13 mm (coefficient of variation 3.1%), and for cMT 0.16 mm(2.65%). Reported change using manual segmentations in the cMF region at 1 year was -0.031 mm (95% CI -0.022, -0.039), p < 10-4, SRM -0.31 (-0.23, -0.38); and at 2 years was -0.071 (-0.058, -0.085), p < 10-4, SRM -0.43 (-0.36, -0.49). Reported change using automated segmentations in the cMF at 1 year was -0.059 (-0.047, -0.071), p < 10-4, SRM -0.41 (-0.34, -0.48); and at 2 years was -0.14 (-0.123, -0.157, p < 10-4, SRM -0.67 (-0.6, -0.72).Conclusion: A novel cartilage segmentation method provides highly accurate and repeatable measures with cartilage thickness measurements comparable to those of careful manual segmentation, but with improved responsiveness. [ABSTRACT FROM AUTHOR]

While tumour mutation burden (TMB) is emerging as a possible biomarker for immune-checkpoint inhibitors (ICI), methods for testing have not been standardised as yet. In April 2019, the International Quality Network for Pathology (IQN Path) launched a survey to assess the current practice of TMB testing. Of the 127 laboratories that replied, 69 (54.3%) had already introduced TMB analysis for research purposes and/or clinical applications. Fifty laboratories (72.5%) used targeted sequencing, although a number of different panels were employed. Most laboratories tested formalin-fixed paraffin-embedded material (94.2%), while 18/69 (26%) tested also cell-free DNA. Fifty-five laboratories used both single nucleotide variants and indels for TMB calculation; 20 centers included only non-synonymous variants. In conclusion, the data from this survey indicate that multiple global laboratories were capable of rapidly introducing routine clinical TMB testing. However, the variability of testing methods raises concerns about the reproducibility of results among centers. [ABSTRACT FROM AUTHOR]

Background: Ivermectin is widely used in human and animal medicine to treat and prevent parasite nematode infections. It has been suggested that its mode of action requires the host immune system, as it is difficult to reproduce its clinical efficacy in vitro. We therefore studied the effects of a single dose of ivermectin (Stromectol®—0.15 mg/kg) on cytokine levels and immune cell gene expression in human volunteers. This dose reduces bloodstream microfilariae rapidly and for several months when given in mass drug administration programmes. Methods: Healthy volunteers with no travel history to endemic regions were given 3–4 tablets, depending on their weight, of either ivermectin or a placebo. Blood samples were drawn immediately prior to administration, 4 h and 24 h afterwards, and complete blood counts performed. Serum levels of 41 cytokines and chemokines were measured using Luminex® and expression levels of 770 myeloid-cell-related genes determined using the NanoString nCounter®. Cytokine levels at 4 h and 24 h post-treatment were compared to the levels pre-treatment using simple t tests to determine if any individual results required further investigation, taking p = < 0.05 as the level of significance. NanoString data were analysed on the proprietary software, nSolver™. Results: No significant differences were observed in complete blood counts or cytokine levels at either time point between people given ivermectin versus placebo. Only three genes showed a significant change in expression in peripheral blood mononuclear cells 4 h after ivermectin was given; there were no significant changes 24 h after drug administration or in polymorphonuclear cells at either time point. Leukocytes isolated from those participants given ivermectin showed no difference in their ability to kill Brugia malayi microfilariae in vitro. Conclusions: Overall, our data do not support a direct effect of ivermectin, when given at the dose used in current filarial elimination programmes, on the human immune system. Trial registration ClinicalTrials.gov NCT03459794 Registered 9th March 2018, Retrospectively registered https://clinicaltrials.gov/ct2/show/NCT03459794?term=NCT03459794&draw=2&rank=1. [ABSTRACT FROM AUTHOR]

Pharmacokinetics, safety, and tolerability of abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg were assessed in this phase 1, single‐arm, open‐label, single‐dose study in fasted healthy male (n = 4) and female (n = 8) participants of Japanese heritage. Participants received a single dose of abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg after an 8‐hour fast, with safety assessments and blood samples for pharmacokinetic parameters collected through 72 hours after dosing. Geometric mean maximum plasma concentrations were 5.22 μg/mL (time to maximum concentration [tmax], 1.01 hours) for abacavir, 4.13 μg/mL (tmax, 3.50 hours) for dolutegravir, and 3.35 μg/mL (tmax, 2.98 hours) for lamivudine. Geometric mean area under the concentration‐time curve values were 18.20, 71.60, and 16.60 μg • h/mL for abacavir, dolutegravir, and lamivudine, respectively. No adverse events were reported, and no clinically significant findings were observed in laboratory values, physical examinations, or 12‐lead electrocardiographic parameters. Single‐tablet administration of abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg was well tolerated in Japanese participants. Exposure to abacavir and lamivudine was comparable with that seen in previous studies. A modest increase in exposure to dolutegravir vs previous clinical studies was observed but is not expected to impact the clinical management of HIV‐1 or increase the risk for adverse events. [ABSTRACT FROM AUTHOR]

Background: Ivermectin is widely used in human and animal medicine to treat and prevent parasite nematode infections. It has been suggested that its mode of action requires the host immune system, as it is difficult to reproduce its clinical efficacy in vitro. We therefore studied the effects of a single dose of ivermectin (Stromectol®—0.15 mg/kg) on cytokine levels and immune cell gene expression in human volunteers. This dose reduces bloodstream microfilariae rapidly and for several months when given in mass drug administration programmes. Methods: Healthy volunteers with no travel history to endemic regions were given 3–4 tablets, depending on their weight, of either ivermectin or a placebo. Blood samples were drawn immediately prior to administration, 4 h and 24 h afterwards, and complete blood counts performed. Serum levels of 41 cytokines and chemokines were measured using Luminex® and expression levels of 770 myeloid-cell-related genes determined using the NanoString nCounter®. Cytokine levels at 4 h and 24 h post-treatment were compared to the levels pre-treatment using simple t tests to determine if any individual results required further investigation, taking p = < 0.05 as the level of significance. NanoString data were analysed on the proprietary software, nSolver™. Results: No significant differences were observed in complete blood counts or cytokine levels at either time point between people given ivermectin versus placebo. Only three genes showed a significant change in expression in peripheral blood mononuclear cells 4 h after ivermectin was given; there were no significant changes 24 h after drug administration or in polymorphonuclear cells at either time point. Leukocytes isolated from those participants given ivermectin showed no difference in their ability to kill Brugia malayi microfilariae in vitro. Conclusions: Overall, our data do not support a direct effect of ivermectin, when given at the dose used in current filarial elimination programmes, on the human immune system. Trial registration ClinicalTrials.gov NCT03459794 Registered 9th March 2018, Retrospectively registered https://clinicaltrials.gov/ct2/show/NCT03459794?term=NCT03459794&draw=2&rank=1. [ABSTRACT FROM AUTHOR]

Background: The Obstetric Anal Sphincter Injury (OASI) Care Bundle comprises four primary and secondary prevention practices that target the rising rates of severe perineal tearing during childbirth, which can have severe debilitating consequences for women. The OASI Care Bundle was implemented in 16 maternity units in Britain in the OASI1 project (2017-2018), which demonstrated the care bundle's effectiveness in reducing OASI rates. In OASI2, the care bundle will be scaled up to 20 additional National Health Service (NHS) maternity units in a hybrid effectiveness-implementation study that will examine the effectiveness of strategies used to introduce, implement and sustain the care bundle.Methods: OASI2 is a two-arm cluster-randomised control trial (C-RCT) of maternity units in England, Scotland and Wales, with an additional non-randomised study arm. C-RCT arm 1 (peer support, n = 10 units) will be supported by 'buddy' units to implement the OASI Care Bundle. C-RCT arm 2 (lean implementation, n = 10 units) will implement without external support. The additional study arm (sustainability, n = 10 units) will include some original OASI1 units to evaluate the care bundle's sustainability and OASI rates over time, from before OASI1 and through the end of OASI2. Units in all three study arms will receive an Implementation Toolkit with training resources and implementation support. The C-RCT arms will be compared in terms of OASI rate reduction (primary effectiveness outcome) and clinicians' adoption of the care bundle (primary implementation outcome). Clinical data will be collated from maternity information systems; implementation data will be collected through validated surveys with women and clinicians, supplemented by qualitative methods. Descriptive statistics and regression modelling will be used for analysis. Emergent themes from the qualitative data will be assessed using framework analysis.Discussion: OASI2 will study the impact of various implementation strategies used to introduce and sustain the OASI Care Bundle, and how these strategies affect the bundle's clinical effectiveness. The study will generate insights into how to effectively scale-up and sustain uptake and coverage of similar interventions in maternity units. A locally adaptable 'implementation blueprint' will be produced to inform development of future guidelines to prevent perineal trauma.Trial Registration: ISRCTN26523605. [ABSTRACT FROM AUTHOR]

Context: Reconnecting fragmented habitat is a major challenge in biodiversity conservation. It is especially important in landscapes that have undergone significant change through agriculture and forestry conversion. This is particularly prevalent within heathland regions across Western Europe where remaining fragments are significantly isolated in intensely managed landscapes. Objectives: This study examines to what extent forest trackways can facilitate connectivity between open patches, and how invertebrate dispersal ability (terrestrial or aerial) influences functional landscape connectivity. We also investigate a range of management scenarios to examine the efficacy of landscape management plans to facilitate connectivity for vulnerable invertebrate communities. Methods: We develop the Path-Cost Index (PCI) that combines multiple environmental factors to quantify species-specific habitat suitability within forestry trackways. The PCI generates dispersal cost values for resistance-based connectivity models that represent specific forest environments and species/guild responses. We demonstrate the use of this index through the modelling of least-cost pathways for heathland invertebrates and test management scenarios (clustered and contiguous habitat improvements) developed to support heathland biodiversity. Results: The plantation landscape provided significant barriers for vulnerable heathland invertebrate guilds. Landscape metrics indicate that management plans incorporating contiguous corridors would provide significantly greater improvements over clustered corridors for target invertebrate guilds in our study landscape. Conclusion: The PCI presented in this study delivered easily definable resistance costs allowing comparative assessment of landscape enhancements plans. The PCI can be easily adapted to other linear features and landscapes, affording a low-cost tool to assist the evaluation of management plans and biological networks. [ABSTRACT FROM AUTHOR]

In personalized medicine, predictive biomarker testing is the basis for an appropriate choice of therapy for patients with cancer. An important tool for laboratories to ensure accurate results is participation in external quality assurance (EQA) programs. Several providers offer predictive EQA programs for different cancer types, test methods, and sample types. In 2013, a guideline was published on the requirements for organizing high-quality EQA programs in molecular pathology. Now, after six years, steps were taken to further harmonize these EQA programs as an initiative by IQNPath ABSL, an umbrella organization founded by various EQA providers. This revision is based on current knowledge, adds recommendations for programs developed for predictive biomarkers by in situ methodologies (immunohistochemistry and in situ hybridization), and emphasized transparency and an evidence-based approach. In addition, this updated version also has the aim to give an overview of current practices from various EQA providers. [ABSTRACT FROM AUTHOR]

Molecular rotor‐based fluorophores (RBFs) have been widely used in many fields. However, the lack of control of their viscosity sensitivity limits their application. Herein, this problem is resolved by chemically installing extended π‐rich alternating carbon‐carbon linkages between the rotational electron donors and acceptors of RBFs. The data reveal that the length of the linkage strongly influences the viscosity sensitivity, likely resulting from varying height of the energy barriers between the fluorescent planar and the dark twisted configurations. Three RBF derivatives that span a wide range of viscosity sensitivities were designed. These RBFs demonstrated, through a dual‐color imaging strategy, that they can differentiate misfolded protein oligomers and insoluble aggregates, both in test tubes and live cells. Beyond RBFs, it is envisioned that this chemical mechanism might be generally applicable to a wide range of photoisomerizable and aggregation‐induced emission fluorophores. [ABSTRACT FROM AUTHOR]

Molecular rotor‐based fluorophores (RBFs) have been widely used in many fields. However, the lack of control of their viscosity sensitivity limits their application. Herein, this problem is resolved by chemically installing extended π‐rich alternating carbon‐carbon linkages between the rotational electron donors and acceptors of RBFs. The data reveal that the length of the linkage strongly influences the viscosity sensitivity, likely resulting from varying height of the energy barriers between the fluorescent planar and the dark twisted configurations. Three RBF derivatives that span a wide range of viscosity sensitivities were designed. These RBFs demonstrated, through a dual‐color imaging strategy, that they can differentiate misfolded protein oligomers and insoluble aggregates, both in test tubes and live cells. Beyond RBFs, it is envisioned that this chemical mechanism might be generally applicable to a wide range of photoisomerizable and aggregation‐induced emission fluorophores. [ABSTRACT FROM AUTHOR]