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Children with neurodevelopmental diagnoses often experience discrimination from their peers at school. This may result from a lack of understanding, and intolerance of differences in their thinking, communication and social interactions. Learning About Neurodiversity at School (LEANS) is a teaching programme designed to educate primary school children about the concept of neurodiversity. The LEANS programme was created by a neurodiverse team, using participatory methods. In the current study, we evaluated whether the wider neurodiverse community endorsed the planned design generated by our participatory approach. Respondents (n = 111) rated their support for key elements of the planned LEANS content, via an online survey. Participants were majority neurodivergent (70%), 98% of whom reported moderate-to-high familiarity with neurodiversity concepts. Over 90% of respondents expressed support for the planned content presented, and 73% of respondents endorsed the draft neurodiversity definition provided. A small number of respondents provided open-ended comments giving further detail on their views. Overall, the LEANS programme plan received a high level of support from this independent, neurodiversity-aware sample -- demonstrating the potential of small-group participatory methods to generate wider community support. The completed resource is now available as a free online download.

The approach that students take in their studies at university is critical not only for their academic success but is equally important in life-long learning for their career and professional development. Heutagogy is the study of self-determined learning and it is important that we appraise how students in higher education are developing their metacognitive awareness in how they learn and study effectively. Cognitive science is an interdisciplinary research area that involves the scientific study of the human mind. It helps provide new knowledge in relation to areas such as memory, problem solving, knowledge transfer and understanding of complex topics. Cognitive science has demonstrated that re-testing oneself on material when learning, enhances and promotes greater retention of knowledge compared to re-reading the material. Learning that is distributed or spaced out over multiple study sessions also allows for greater retention of knowledge in the longer-term compared to 'cramming' of information. To evaluate the use of effective study approaches and habits across three different levels of study in an undergraduate pharmacy programme, a survey study was employed. A paper-based survey was completed by first-, second- and third-year undergraduate pharmacy students (n=192) during class sessions. Although there was some evidence of metacognitive awareness such as using testing (retrieval practice) with practice problems; across all years, suboptimal study approaches such as rereading, copying notes and cramming were endorsed. A schedule of deadlines shaped the organisation of study and time management for most students. Self-testing was predominantly used to test learning rather than an approach used during learning. There was evidence of a difference between the cohorts in relation to decisions for prioritizing studying, returning to review course material and re-reading. The evidence from this study demonstrates that learners would require training on metacognitive awareness and effective study strategies to enable their self-determined learning capabilities to evolve. The linear progression through a programme of study alone will not achieve this. There is a need to embed and emphasize effective strategies for learning into curricula and for faculty to utilise metacognitive awareness in their teaching.

The approach that students take in their studies at university is critical not only for their academic success but is equally important in life-long learning for their career and professional development. Cognitive science has demonstrated that retesting oneself on material when learning enhances and promotes greater retention of knowledge compared to rereading the material. Learning that is spaced out over multiple study sessions also allows for greater retention of knowledge in the longer-term compared to "cramming" of information. A survey study with first- and second-year undergraduate students (n = 135) at a university in Spain and in the U.K. was carried out to investigate the study strategies and habits prevalent in these cohorts and to explore the extent of their metacognitive awareness. It was found that most students endorsed self-testing but also suboptimal study methods such as rereading, copying notes, and cramming. There was evidence of differences between the U.K. and Spain in relation to decisions for prioritizing studying, returning to review course material, and time of study. A key conclusion is the need to embed and emphasize effective strategies for learning into curricula and for faculty to have metacognitive awareness in their teaching.

The COVID-19 pandemic has focused attention to online delivery of teaching and assessment within the higher education sector. This article will reflect on the laboratory assessment of chemistry to undergraduate students on a pharmaceutical science program in the UK. With students prohibited from accessing laboratory environments, associated assessments focused on the interpretation of data and simulating the experience of viewing data produced elsewhere. Aspects to promote the assessment of process skills were included, and it was found that the use of data sets for individual interpretation helped to mitigate "oversharing". A purposeful community of inquiry requires further consideration to maximize opportunities for peer collaborative discussions that occur within the laboratory environment.

Integrated care systems join up health and care services, so that people have the support they need, in the right place, at the right time. The aims include improving outcomes in healthcare, tackling inequalities in access and enhancing productivity and value for money. This is needed for neuroscience care as the traditional delivery of neuroscience care is inefficient, outdated and expensive, and can involve complex referral pathways and long waiting times. In preparation for the formation of the integrated care system (ICS), a novel innovative collaboration across multiple NHS trusts developed across North Central London in 2021. We developed a model where neuroscience specialists engage in collaborative care with clinicians outside the specialist hospital setting. Pivotal to the pathway is a multidisciplinary meeting, and collaborative working enables joint clinical reviews, diagnostics and medication initiation. This innovative collaboration has already significantly improved access, addressed inequalities due to borough variation and enhanced the delivery and quality of neuroscience care in our ICS. It is a translatable model that can be adapted to suit other regions in the UK. It fulfils many of the objectives of the integrated care system and these benefits are seen without the need for significantly more resource. [ABSTRACT FROM AUTHOR]

Purpose: To compare the performance of multiple international guidelines in selecting patients for head CT prior to lumbar puncture (LP) in suspected meningitis, focusing on identification of potential contraindications to immediate LP. Methods: Retrospective study of 196 patients with suspected meningitis presenting to an emergency department between March 2013 and March 2023 and undergoing head CT prior to LP. UK Joint Specialist Society Guidelines (UK), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Infectious Diseases Society of America (IDSA) guidelines were evaluated by cross-referencing imaging criteria with clinical characteristics present at time of presentation. Sensitivity of each guideline for recommending neuroimaging in cases with brain shift on CT was evaluated, along with the number of normal studies and incidental or spurious findings. Results: 2/196 (1%) patients had abnormal CTs with evidence of brain shift, while 14/196 (7%) had other abnormalities on CT without brain shift. UK, ESCMID and IDSA guidelines recommended imaging in 10%, 14% and 33% of cases respectively. All three guidelines recommended imaging pre-LP in 2/2 (100%) cases with brain shift. IDSA guidelines recommended more CT studies with normal findings (59 vs 16 and 24 for UK and ESCMID guidelines respectively) and CT abnormalities without brain shift (4 vs 1 and 2 respectively) than the other guidelines. Conclusion: UK, ESCMID and IDSA guidelines are all effective at identifying the small cohort of patients who benefit from a head CT prior to LP. Following the more selective UK/ESCMID guidelines limits the number of normal studies and incidental or spurious CT findings. [ABSTRACT FROM AUTHOR]

Heme oxygenase 1 is a key enzyme in the management of heme in humans. A GT(n) repeat length in the heme oxygenase 1 gene (HMOX1) has been widely associated with a variety of phenotypes, including susceptibility to and outcomes in diabetes, cancer, infections, and neonatal jaundice. However, studies have generally been small and results inconsistent. In this study, we imputed the GT(n) repeat length in participants from 2 UK cohort studies (the UK Biobank study (n  = 463,005; recruited in 2006–2010) and the Avon Longitudinal Study of Parents and Children (ALSPAC; n  = 937; recruited in 1990–1991)), with the reliability of imputation tested in other cohorts (1000 Genomes Project, Human Genome Diversity Project, and Personal Genome Project UK). Subsequently, we measured the relationship between repeat length and previously identified associations (diabetes, chronic obstructive pulmonary disease, pneumonia, and infection-related mortality in the UK Biobank; neonatal jaundice in ALSPAC) and performed a phenomewide association study in the UK Biobank. Despite high-quality imputation (correlation between true repeat length and imputed repeat length > 0.9 in test cohorts), clinical associations were not identified in either the phenomewide association study or specific association studies. These findings were robust to definitions of repeat length and sensitivity analyses. Despite multiple smaller studies identifying associations across a variety of clinical settings, we could not replicate or identify any relevant phenotypic associations with the HMOX1 GT(n) repeat. [ABSTRACT FROM AUTHOR]

Using current research and real-life scenarios to motivate students to understand chemistry principles is a key strategy in learning and teaching. An illustration of psychoactive drugs referred to as "legal highs" used in the U.K. and Europe is presented to highlight key chemistry principles and relate the importance of chemistry research in healthcare. Specific topics include stereochemistry, 1 H NMR characterization, organic synthesis, and functional groups, which can be used in chemistry curricula for high school students and also in higher education programs. A contextualized example focused on mephedrone is used during an interpretative spectroscopy exercise in a second-year bioscience program. Student evaluations on the use of this case study approach were very positive. This topic on psychoactive drugs integrates chemistry in social and legal issues relating to patient safety. It highlights public awareness of "legal highs" and the generalized perception that "natural products" are safe and nontoxic.

Background: Acquired brain injury (ABI) and other chronic conditions are placing unprecedented pressure on healthcare systems. In the UK, 1.3 million people live with the effects of brain injury, costing the UK economy approximately £15 billion per year. As a result, there is an urgent need to adapt existing healthcare delivery to meet increasing current and future demands. A focus on wellbeing may provide an innovative opportunity to reduce the pressure on healthcare services while also supporting patients to live more meaningful lives. The overarching aims of the study are as follows: (1) evaluate the feasibility of conducting a positive psychotherapy intervention for individuals with ABI and (2) ascertain under what conditions such an intervention would merit a fully powered randomised controlled trial (RCT) compared to a standard control group (TAU). Methods and analysis: A randomised, two-arm feasibility trial involving allocation of patients to either a treatment group (positive psychotherapy) or control group (treatment as usual) group, according to a 1:1 ratio. A total of 60 participants at three sites will be recruited including 20 participants at each site. Assessments will be conducted at baseline, on completion of the 8-week intervention and 3 months following completion. These will include a range of questionnaire-based measures, psychophysiology and qualitative outcomes focusing on feasibility outcomes and participant experience. This study has been approved by the Wales Research Ethics Committee (IRAS project ID: 271,251, REC reference: 19/WA/0336). Discussion: This study will be the first to examine the feasibility of an innovative, holistic positive psychotherapy intervention for people living with ABI, focused on individual, collective and planetary wellbeing, and will enable us to determine whether to proceed to a full randomised controlled trial. Trial registration: ISRCTN12690685, registered 11th November 2020. [ABSTRACT FROM AUTHOR]

Patients in the UK who suffer an out-of-hospital cardiac arrest are treated with cardiopulmonary resuscitation in the pre-hospital environment. Current survival outcomes are low in out-of-hospital cardiac arrest. Extracorporeal cardiopulmonary resuscitation is a technique which is offered to patients in specialised centres which provides better blood flow and oxygen delivery than conventional chest compressions. Shortening the interval between cardiac arrest and restoration of circulation is associated with improved outcomes in extracorporeal cardiopulmonary resuscitation. Delivering extracorporeal cardiopulmonary resuscitation in the pre-hospital environment can shorten this interval, improving outcomes in out-of-hospital cardiac arrest. This article will review recently published studies and summarise studies currently being undertaken in pre-hospital extracorporeal cardiopulmonary resuscitation. It will also discuss the potential application of a pre-hospital extracorporeal cardiopulmonary resuscitation programme in the North East of England. [ABSTRACT FROM AUTHOR]

This paper examines whether monetary policy pass-through to mortgage interest rates affects household fertility decisions. Our empirical strategy exploits variation in households' eligibility for a rate adjustment, coupled with the large reductions in the monetary policy rate that occurred during the Great Recession in the U.K. and U.S. We estimate that each one percentage point drop in the policy rate increased birth rates amongst households eligible for a rate adjustment by 3%. Our results provide new evidence on the nature of monetary policy transmission to households and suggest a new mechanism via which mortgage contract structures can affect both aggregate demand and supply. [ABSTRACT FROM AUTHOR]

Background: Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations. Methods: Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK). Representativeness was assessed by comparing the AdDIT cohort's distribution of deprivation quintiles with that of the local paediatric type 1 diabetes population (regional), and the broader type 1 diabetes population for which the trial's intervention was targeted (national). Results: Recruited study cohorts from each country had higher proportions of participants with higher SES, and significant underrepresentation of lower SES, in relation to their national references. The socioeconomic make-up in Australia mirrored that of the regional population (p = 0.99). For Canada, the 2nd least deprived (p = 0.001) and the most deprived quintiles (p < 0.001) were over- and under-represented relative to the regional reference, while the UK featured higher regional and national SES bias with over-representation and under-representation from the least-deprived and most-deprived quintiles (p < 0.0001). Conclusions: Significant national differences in trial participation of low SES participants were observed, highlighting limitations in access to clinical research and the importance of reporting sociodemographic representation in diabetes clinical trials. Trial registration: NCT01581476. Registered on 20 April 2012. [ABSTRACT FROM AUTHOR]

Mendelian randomization (MR) is a widely used method that exploits the unique properties of germline genetic variation to strengthen causal inference in relationships between exposures and outcomes. Nonlinear MR allows estimation of the shape of these relationships. In a previous paper, the authors applied linear and nonlinear MR to estimate the effect of BMI on mortality in UK Biobank, providing evidence for a J‐shaped association. However, it is now clear that there are problems with widely used nonlinear MR methods, which draws attention to the likely erroneous nature of the conclusions regarding the shapes of several explored relationships. Here, the authors explore the utility and likely biases of these nonlinear MR methods with the use of a negative control design. Although there remains good evidence for a causal effect of higher BMI increasing the risk of mortality, the pattern of this association across different levels of BMI requires further characterization. [ABSTRACT FROM AUTHOR]

Background: Risk-based screening for lung cancer is currently being considered in several countries; however, the optimal approach to determine eligibility remains unclear. Ensemble machine learning could support the development of highly parsimonious prediction models that maintain the performance of more complex models while maximising simplicity and generalisability, supporting the widespread adoption of personalised screening. In this work, we aimed to develop and validate ensemble machine learning models to determine eligibility for risk-based lung cancer screening. Methods and findings: For model development, we used data from 216,714 ever-smokers recruited between 2006 and 2010 to the UK Biobank prospective cohort and 26,616 high-risk ever-smokers recruited between 2002 and 2004 to the control arm of the US National Lung Screening (NLST) randomised controlled trial. The NLST trial randomised high-risk smokers from 33 US centres with at least a 30 pack-year smoking history and fewer than 15 quit-years to annual CT or chest radiography screening for lung cancer. We externally validated our models among 49,593 participants in the chest radiography arm and all 80,659 ever-smoking participants in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial. The PLCO trial, recruiting from 1993 to 2001, analysed the impact of chest radiography or no chest radiography for lung cancer screening. We primarily validated in the PLCO chest radiography arm such that we could benchmark against comparator models developed within the PLCO control arm. Models were developed to predict the risk of 2 outcomes within 5 years from baseline: diagnosis of lung cancer and death from lung cancer. We assessed model discrimination (area under the receiver operating curve, AUC), calibration (calibration curves and expected/observed ratio), overall performance (Brier scores), and net benefit with decision curve analysis. Models predicting lung cancer death (UCL-D) and incidence (UCL-I) using 3 variables—age, smoking duration, and pack-years—achieved or exceeded parity in discrimination, overall performance, and net benefit with comparators currently in use, despite requiring only one-quarter of the predictors. In external validation in the PLCO trial, UCL-D had an AUC of 0.803 (95% CI: 0.783, 0.824) and was well calibrated with an expected/observed (E/O) ratio of 1.05 (95% CI: 0.95, 1.19). UCL-I had an AUC of 0.787 (95% CI: 0.771, 0.802), an E/O ratio of 1.0 (95% CI: 0.92, 1.07). The sensitivity of UCL-D was 85.5% and UCL-I was 83.9%, at 5-year risk thresholds of 0.68% and 1.17%, respectively, 7.9% and 6.2% higher than the USPSTF-2021 criteria at the same specificity. The main limitation of this study is that the models have not been validated outside of UK and US cohorts. Conclusions: We present parsimonious ensemble machine learning models to predict the risk of lung cancer in ever-smokers, demonstrating a novel approach that could simplify the implementation of risk-based lung cancer screening in multiple settings. Thomas Callender and colleagues present a development and validation study using parsimonious ensemble machine learning models to assess eligibility for lung cancer screening. Author summary: Why was this study done?: Screening and disease prevention programmes are increasingly bespoke; however, their simultaneous delivery at a population-scale presents considerable challenges. Lung cancer is the most common cause of cancer death worldwide, with poor survival in the absence of early detection. Screening for lung cancer among those at high-risk could reduce lung cancer-specific mortality by 20% to 24% among those screened, but the ideal way to determine if someone is high-risk remains uncertain and existing approaches are resource intensive. What did the researchers do and find?: We used data from the UK Biobank and US National Lung Screening Trial to develop novel, parsimonious models, to simplify the prediction of lung cancer risk and selection to lung cancer screening programmes. Using ensemble machine learning and 3 predictors—age, smoking duration, and pack-years—we found our models achieved or exceeded parity in performance with leading comparators despite requiring one-third of the variables. Our models were externally validated in the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and benchmarked against models that are either in use or have performed strongly in previous analyses. What do these findings mean?: Risk assessment for lung cancer screening can be simplified without reducing performance, potentially improving the uptake and effectiveness of national lung cancer screening programmes, and therefore contributing to reducing deaths from lung cancer. Future research should focus on the application of this modelling approach to other conditions such as cardiovascular disease, diabetes, and chronic kidney disease to support the implementation at scale of multiple concurrent risk-stratified prevention and early detection programmes for major causes of morbidity and mortality. This study has key limitations as it is based on past data from the US and UK, so prospective evaluation in different countries and regions should be considered. [ABSTRACT FROM AUTHOR]

Target trial emulation applies design principles from randomised controlled trials to the analysis of observational data for causal inference and is increasingly used within human epidemiology. Veterinary electronic clinical records represent a potentially valuable source of information to estimate real-world causal effects for companion animal species. This study employed the target trial framework to evaluate the usefulness on veterinary observational data. Acute diarrhoea in dogs was used as a clinical exemplar. Inclusion required dogs aged ≥ 3 months and < 10 years, presenting for veterinary primary care with acute diarrhoea during 2019. Treatment strategies were: 1. antimicrobial prescription compared to no antimicrobial prescription and 2. gastrointestinal nutraceutical prescription compared to no gastrointestinal nutraceutical prescription. The primary outcome was clinical resolution (defined as no revisit with ongoing diarrhoea within 30 days from the date of first presentation). Informed from a directed acyclic graph, data on the following covariates were collected: age, breed, bodyweight, insurance status, comorbidities, vomiting, reduced appetite, haematochezia, pyrexia, duration, additional treatment prescription and veterinary group. Inverse probability of treatment weighting was used to balance covariates between the treatment groups for each of the two target trials. The risk difference (RD) of 0.4% (95% CI -4.5% to 5.3%) was non-significant for clinical resolution in dogs treated with antimicrobials compared with dogs not treated with antimicrobials. The risk difference (RD) of 0.3% (95% CI -4.5% to 5.0%) was non-significant for clinical resolution in dogs treated with gastrointestinal nutraceuticals compared with dogs not treated with gastrointestinal nutraceuticals. This study successfully applied the target trial framework to veterinary observational data. The findings show that antimicrobial or gastrointestinal prescription at first presentation of acute diarrhoea in dogs causes no difference in clinical resolution. The findings support the recommendation for veterinary professionals to limit antimicrobial use for acute diarrhoea in dogs. [ABSTRACT FROM AUTHOR]

In May 2022, a cluster of mpox cases were detected in the UK that could not be traced to recent travel history from an endemic region. Over the coming months, the outbreak grew, with over 3000 total cases reported in the UK, and similar outbreaks occurring worldwide. These outbreaks appeared linked to sexual contact networks between gay, bisexual and other men who have sex with men. Following the COVID-19 pandemic, local health systems were strained, and therefore effective surveillance for mpox was essential for managing public health policy. However, the mpox outbreak in the UK was characterised by substantial delays in the reporting of the symptom onset date and specimen collection date for confirmed positive cases. These delays led to substantial backfilling in the epidemic curve, making it challenging to interpret the epidemic trajectory in real-time. Many nowcasting models exist to tackle this challenge in epidemiological data, but these lacked sufficient flexibility. We have developed a nowcasting model using generalised additive models that makes novel use of individual-level patient data to correct the mpox epidemic curve in England. The aim of this model is to correct for backfilling in the epidemic curve and provide real-time characteristics of the state of the epidemic, including the real-time growth rate. This model benefited from close collaboration with individuals involved in collecting and processing the data, enabling temporal changes in the reporting structure to be built into the model, which improved the robustness of the nowcasts generated. The resulting model accurately captured the true shape of the epidemic curve in real time. Author summary: During 2022, outbreaks of mpox, the disease caused by the monkeypox virus, occurred simultaneously in multiple non-endemic countries, including England. These outbreaks were distinct from historic outbreaks with a majority of cases in gay, bisexual and other men who have sex with men and in individuals without recent travel histories to endemic countries. To inform public health policy, understanding the number of new cases and growth rate of the outbreak in real-time is essential. However, the outbreak was characterised by long delays from individuals developing symptoms (or getting a test) and being reported as a positive case. This creates a biased picture of the outbreak, where observed real-time cases underestimates the true extent of the outbreak. We developed a mathematical model that accounts for these reporting delays to estimate the true shape of the epidemic curve in real-time. The modelled outputs are able to accurately capture the true shape of the epidemic, and provide improved real-time insight over the raw data. This model was used continuously throughout the outbreak response in the UK to provide insight to the incident management team at the UK Health Security Agency. [ABSTRACT FROM AUTHOR]

We investigate whether the dynamic response of aggregate consumption to monetary policy depends on the distribution of household debt relative to income. Using U.K. loan-level microdata, we propose a novel approach to isolate the fraction of households with a limited ability to smooth consumption. By exploiting time and cross-sectional variation, we show that consumption responds more to monetary policy when the share of highly indebted households is large, but find no state contingency with respect to the overall level of debt-to-income. Our results highlight the role of household heterogeneity for understanding monetary transmission to aggregate consumption. [ABSTRACT FROM AUTHOR]

Following pretraining with everyday objects, 14 children aged from 1 to 4 years were trained, for each of three pairs of different arbitrary wooden shapes (Set 1), to select one stimulus in response to the spoken word /zog/, and the other to /vek/. When given a test for the corresponding tacts ("zog" and "vek"), 10 children passed, showing that they had learned common names for the stimuli, and 4 failed. All children were trained to clap to one stimulus of Pair 1 and wave to the other. All those who named showed either transfer of the novel functions to the remaining two pairs of stimuli in Test 1, or novel function comprehension for all three pairs in Test 2, or both. Three of these children next participated in, and passed, category match-to-sample tests. In contrast, all 4 children who had learned only listener behavior failed both the category transfer and category match-to-sample tests. When 3 of them were next trained to name the stimuli, they passed the category transfer and (for the 2 subjects tested) category match-to-sample tests. Three children were next trained on the common listener relations with another set of arbitrary stimuli (Set 2); all succeeded on the tact and category tests with the Set 2 stimuli. Taken together with the findings from the other studies in the series, the present experiment shows that (a) common listener training also establishes the corresponding names in some but not all children, and (b) only children who learn common names categorize; all those who learn only listener behavior fail. This is good evidence in support of the naming account of categorization. (Contains 3 tables and 4 figures.)

Following pretraining with everyday objects, 10 children aged from 1 to 4 years were given common vocal tact training with a set of three pairs of arbitrary stimuli of differing shapes; Set 1. Nine children learned to tact one stimulus as "zog" and the other as "vek" in each pair, and all passed subsequent pairwise tests for the corresponding listener behavior to each listener stimulus (i.e., /zog/ and /vek/, respectively). The children were next trained to clap to one stimulus of Pair 1 and wave to the other, and all then showed name-consistent transfer of these behaviors to the stimuli of Pair 2 and Pair 3. Seven children also were given a test of listener responding to experimenter-modeled clap and wave gestures, respectively, which they all passed. Four of the children next participated in a category match-to-sample test for the Set 1 stimuli; all 4 passed. For each pair of two additional six-stimuli sets, Set 2 and Set 3, 3 children were trained to wave to one stimulus and to clap to the other. For each set, all 3 children showed perfect transfer of the vocal tacts trained to Set 1, and of listener behavior both to the auditory stimuli /zog/ and /vek/ and to experimenter-modeled clap and wave gestures. They also sorted the stimuli perfectly in category match-to-sample tests for Set 2, Sets 1 and 2 combined, Set 3, and Sets 1, 2, and 3 combined. The results show that even in very young children, naming is a powerful means of generating new category relations among as many as 18 arbitrary stimuli. (Contains 2 tables and 3 figures.)

Lung cancer is the second most common cancer in incidence and the leading cause of cancer deaths worldwide. Meanwhile, lung cancer screening with low-dose CT can reduce mortality. The UK National Screening Committee recommended targeted lung cancer screening on Sept 29, 2022, and asked for more modelling work to be done to help refine the recommendation. This study aims to develop and validate a risk prediction model—the CanPredict (lung) model—for lung cancer screening in the UK and compare the model performance against seven other risk prediction models. For this retrospective, population-based, cohort study, we used linked electronic health records from two English primary care databases: QResearch (Jan 1, 2005–March 31, 2020) and Clinical Practice Research Datalink (CPRD) Gold (Jan 1, 2004–Jan 1, 2015). The primary study outcome was an incident diagnosis of lung cancer. We used a Cox proportional-hazards model in the derivation cohort (12·99 million individuals aged 25–84 years from the QResearch database) to develop the CanPredict (lung) model in men and women. We used discrimination measures (Harrell's C statistic, D statistic, and the explained variation in time to diagnosis of lung cancer [R2 D ]) and calibration plots to evaluate model performance by sex and ethnicity, using data from QResearch (4·14 million people for internal validation) and CPRD (2·54 million for external validation). Seven models for predicting lung cancer risk (Liverpool Lung Project [LLP] v2 , LLP v3 , Lung Cancer Risk Assessment Tool [LCRAT], Prostate, Lung, Colorectal, and Ovarian [PLCO] M2012 , PLCO M2014 , Pittsburgh, and Bach) were selected to compare their model performance with the CanPredict (lung) model using two approaches: (1) in ever-smokers aged 55–74 years (the population recommended for lung cancer screening in the UK), and (2) in the populations for each model determined by that model's eligibility criteria. There were 73 380 incident lung cancer cases in the QResearch derivation cohort, 22 838 cases in the QResearch internal validation cohort, and 16 145 cases in the CPRD external validation cohort during follow-up. The predictors in the final model included sociodemographic characteristics (age, sex, ethnicity, Townsend score), lifestyle factors (BMI, smoking and alcohol status), comorbidities, family history of lung cancer, and personal history of other cancers. Some predictors were different between the models for women and men, but model performance was similar between sexes. The CanPredict (lung) model showed excellent discrimination and calibration in both internal and external validation of the full model, by sex and ethnicity. The model explained 65% of the variation in time to diagnosis of lung cancer R2 D in both sexes in the QResearch validation cohort and 59% of the R2 D in both sexes in the CPRD validation cohort. Harrell's C statistics were 0·90 in the QResearch (validation) cohort and 0·87 in the CPRD cohort, and the D statistics were 2·8 in the QResearch (validation) cohort and 2·4 in the CPRD cohort. Compared with seven other lung cancer prediction models, the CanPredict (lung) model had the best performance in discrimination, calibration, and net benefit across three prediction horizons (5, 6, and 10 years) in the two approaches. The CanPredict (lung) model also had higher sensitivity than the current UK recommended models (LLP v2 and PLCO M2012), as it identified more lung cancer cases than those models by screening the same amount of individuals at high risk. The CanPredict (lung) model was developed, and internally and externally validated, using data from 19·67 million people from two English primary care databases. Our model has potential utility for risk stratification of the UK primary care population and selection of individuals at high risk of lung cancer for targeted screening. If our model is recommended to be implemented in primary care, each individual's risk can be calculated using information in the primary care electronic health records, and people at high risk can be identified for the lung cancer screening programme. Innovate UK (UK Research and Innovation). For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Beginning in May 2022, Mpox virus spread rapidly in high-income countries through close human-to-human contact primarily amongst communities of gay, bisexual and men who have sex with men (GBMSM). Behavioural change arising from increased knowledge and health warnings may have reduced the rate of transmission and modified Vaccinia-based vaccination is likely to be an effective longer-term intervention. We investigate the UK epidemic presenting 26-week projections using a stochastic discrete-population transmission model which includes GBMSM status, rate of formation of new sexual partnerships, and clique partitioning of the population. The Mpox cases peaked in mid-July; our analysis is that the decline was due to decreased transmission rate per infected individual and infection-induced immunity among GBMSM, especially those with the highest rate of new partners. Vaccination did not cause Mpox incidence to turn over, however, we predict that a rebound in cases due to behaviour reversion was prevented by high-risk group-targeted vaccination. An outbreak of Mpox in the UK began in May 2022 and peaked in July. In this modelling study, the authors show that the decline in cases was likely due to behavioural changes among high-risk populations, whilst vaccination could prevent a rebound. [ABSTRACT FROM AUTHOR]

Comparative case study of factors related to operation of school-level financial management in five UK community/foundation schools and five US charter schools. Uses on-site interviews with UK head teachers and bursars and US directors and business officials. Explores four themes and related conclusions: control, evolution, shared leadership, and public probity. (Contains 31 references.) (PKP)

ERAP2 is an aminopeptidase involved in immunological antigen presentation. Genotype data in human samples from before and after the Black Death, an epidemic due to Yersinia pestis , have marked changes in allele frequency of the single-nucleotide polymorphism (SNP) rs2549794, with the T allele suggested to be deleterious during this period, while ERAP2 is also implicated in autoimmune diseases. This study explored the association between variation at ERAP2 and (1) infection, (2) autoimmune disease, and (3) parental longevity. Genome-wide association studies (GWASs) of these outcomes were identified in contemporary cohorts (UK Biobank, FinnGen, and GenOMICC). Effect estimates were extracted for rs2549794 and rs2248374, a haplotype tagging SNP. Additionally, cis expression and protein quantitative trait loci (QTLs) for ERAP2 were used in Mendelian randomization (MR) analyses. Consistent with decreased survival in the Black Death, the T allele of rs2549794 showed evidence of association with respiratory infection (odds ratio; OR for pneumonia 1.03; 95% CI 1.01–1.05). Effect estimates were larger for more severe phenotypes (OR for critical care admission with pneumonia 1.08; 95% CI 1.02–1.14). In contrast, opposing effects were identified for Crohn disease (OR 0.86; 95% CI 0.82–0.90). This allele was shown to associate with decreased ERAP2 expression and protein levels, independent of haplotype. MR analyses suggest that ERAP2 expression may be mediating disease associations. Decreased ERAP2 expression is associated with severe respiratory infection with an opposing association with autoimmune diseases. These data support the hypothesis of balancing selection at this locus driven by autoimmune and infectious disease. The T allele at the ERAP2 SNP rs2549794 has been suggested as deleterious during the Black Death. We have found that the T allele is associated with increased risk of respiratory infection, with opposing effects for Crohn disease, supporting the hypothesis of balancing selection driven by autoimune and infectious disease. [ABSTRACT FROM AUTHOR]

Background: Mortality prediction is critical on long-term kidney replacement therapy (KRT), both for individual treatment decisions and resource planning. Many mortality prediction models already exist, but as a major shortcoming most of them have only been validated internally. This leaves reliability and usefulness of these models in other KRT populations, especially foreign, unknown. Previously two models were constructed for one- and two-year mortality prediction of Finnish patients starting long-term dialysis. These models are here internationally validated in KRT populations of the Dutch NECOSAD Study and the UK Renal Registry (UKRR). Methods: We validated the models externally on 2051 NECOSAD patients and on two UKRR patient cohorts (5328 and 45493 patients). We performed multiple imputation for missing data, used c-statistic (AUC) to assess discrimination, and evaluated calibration by plotting average estimated probability of death against observed risk of death. Results: Both prediction models performed well in the NECOSAD population (AUC 0.79 for the one-year model and 0.78 for the two-year model). In the UKRR populations, performance was slightly weaker (AUCs: 0.73 and 0.74). These are to be compared to the earlier external validation in a Finnish cohort (AUCs: 0.77 and 0.74). In all tested populations, our models performed better for PD than HD patients. Level of death risk (i.e., calibration) was well estimated by the one-year model in all cohorts but was somewhat overestimated by the two-year model. Conclusions: Our prediction models showed good performance not only in the Finnish but in foreign KRT populations as well. Compared to the other existing models, the current models have equal or better performance and fewer variables, thus increasing models' usability. The models are easily accessible on the web. These results encourage implementing the models into clinical decision-making widely among European KRT populations. [ABSTRACT FROM AUTHOR]

Background: Driving cessation can be one of the adjustments made following a diagnosis of dementia. Little is known about the views and opinions of people living with dementia about this. The study aimed to gather a broad idea of the expectations, impacts and the process of driving cessation from the perspective of those living with dementia. Methods: 138 people with dementia and 91 relatives/friends (on behalf of an individual with dementia) took part in an online questionnaire. Results: People living with dementia reported stopping driving following diagnosis can have negative psychological impacts particularly in relation to; feelings of isolation, depression, loss of freedom and feeling life isn't worth living. Age, gender and choice in the driving cessation process were related to the degree of negative experiences. Conclusions: The difficulties reported by people with dementia suggest a need to provide more structured post diagnostic support to aid decision making of driving continuation or cessation; with the view to reducing associated distress and enabling people with dementia to continue to live a meaningful life. Key points: Stopping driving following a diagnosis of dementia can have significant negative psychological impacts on the person with dementia.Male gender, young age and being unable to work increases the risk of negative psychological impacts.Supporting people with dementia to make their own informed decisions may help the adjustment process to stopping driving.Post diagnostic support should include support for those affected by stopping driving.Driving assessments were found to be supportive. It is essential these remain available as a means to support safe decision‐making surrounding continuing or stopping driving. [ABSTRACT FROM AUTHOR]

Background: Sepsis is characterised by dysregulated, life-threatening immune responses, which are thought to be driven by cytokines such as interleukin 6 (IL-6). Genetic variants in IL6R known to down-regulate IL-6 signalling are associated with improved Coronavirus Disease 2019 (COVID-19) outcomes, a finding later confirmed in randomised trials of IL-6 receptor antagonists (IL6RAs). We hypothesised that blockade of IL6R could also improve outcomes in sepsis. Methods and findings: We performed a mendelian randomisation (MR) analysis using single nucleotide polymorphisms (SNPs) in and near IL6R to evaluate the likely causal effects of IL6R blockade on sepsis (primary outcome), sepsis severity, other infections, and COVID-19 (secondary outcomes). We weighted SNPs by their effect on CRP and combined results across them in inverse variance weighted meta-analysis, proxying the effect of IL6RA. Our outcomes were measured in UK Biobank, FinnGen, the COVID-19 Host Genetics Initiative (HGI), and the GenOSept and GainS consortium. We performed several sensitivity analyses to test assumptions of our methods, including utilising variants around CRP and gp130 in a similar analysis. In the UK Biobank cohort (N = 486,484, including 11,643 with sepsis), IL6R blockade was associated with a decreased risk of our primary outcome, sepsis (odds ratio (OR) = 0.80; 95% confidence interval (CI) 0.66 to 0.96, per unit of natural log-transformed CRP decrease). The size of this effect increased with severity, with larger effects on 28-day sepsis mortality (OR = 0.74; 95% CI 0.47 to 1.15); critical care admission with sepsis (OR = 0.48, 95% CI 0.30 to 0.78) and critical care death with sepsis (OR = 0.37, 95% CI 0.14 to 0.98). Similar associations were seen with severe respiratory infection: OR for pneumonia in critical care 0.69 (95% CI 0.49 to 0.97) and for sepsis survival in critical care (OR = 0.22; 95% CI 0.04 to 1.31) in the GainS and GenOSept consortium, although this result had a large degree of imprecision. We also confirm the previously reported protective effect of IL6R blockade on severe COVID-19 (OR = 0.69, 95% CI 0.57 to 0.84) in the COVID-19 HGI, which was of similar magnitude to that seen in sepsis. Sensitivity analyses did not alter our primary results. These results are subject to the limitations and assumptions of MR, which in this case reflects interpretation of these SNP effects as causally acting through blockade of IL6R, and reflect lifetime exposure to IL6R blockade, rather than the effect of therapeutic IL6R blockade. Conclusions: IL6R blockade is causally associated with reduced incidence of sepsis. Similar but imprecisely estimated results supported a causal effect also on sepsis related mortality and critical care admission with sepsis. These effects are comparable in size to the effect seen in severe COVID-19, where IL-6 receptor antagonists were shown to improve survival. These data suggest that a randomised trial of IL-6 receptor antagonists in sepsis should be considered. In a Mendelian randomisation analysis, Fergus Hamilton and colleagues test the hypothesis that blockade of interleukin-6 signalling could improve outcomes in sepsis. Author summary: Why was this study done?: Inhibition of the cytokine interleukin 6 (IL-6) using drugs such as tocilizumab, which bind to the IL-6 receptor, has been shown to reduce mortality in critically unwell patients with Coronavirus Disease 2019 (COVID-19). It is currently unknown whether IL-6 inhibition might have similar benefits in other, severe infections, such as bacterial sepsis. Genetic analyses (mendelian randomisation (MR)) have previously predicted the success of IL-6 inhibition in COVID-19 and other conditions. What did the researchers find?: In a large, UK cohort (N = 485,825, including 11,643 with sepsis), genetic variation acting as a proxy (or natural experiment) for IL6R blockade was associated with a reduced odds of sepsis (odds ratio (OR) 0.80; 95% confidence interval (CI) 0.66 to 0.96) in MR analyses. Effects were consistent in secondary cohorts and when using differing definitions of sepsis, with effect sizes generally larger in more severe phenotypes. The effect estimates on sepsis were similar in magnitude to those seen in severe COVID-19 (OR 0.69, 95% CI 0.57 to 0.84), where IL-6 blockade is currently recommended. What do the findings mean?: Within the limitations and assumptions of MR, these findings support the consideration of IL-6 inhibition in randomised controlled trials in sepsis. More broadly, these findings support the potentially pathological role of IL-6 in severe infection. [ABSTRACT FROM AUTHOR]

Background: The UK's living-donor kidney transplant (LDKT) activity falls behind that of many other countries internationally, with less than 20% of those eligible receiving a LDKT each year. Certain individuals with kidney disease in the UK appear to be particularly disadvantaged in accessing a LDKT; the most socioeconomically deprived people with kidney disease are 60% less likely to receive a LDKT than the least deprived. Improving equity in living-donor kidney transplantation has been highlighted as an international research priority. Methods: This feasibility trial was designed to determine the feasibility of delivery and acceptability of a multicomponent intervention designed to improve access to living-donor kidney transplantation. The intervention comprises three main components: (i) a meeting between a home educator and the transplant candidate for a dedicated discussion about living-donor kidney transplantation, living kidney donation and potential donors; (ii) a standardized letter from a healthcare professional to a candidate's potential donors and (iii) a home-based education and family engagement session including two home educators, the transplant candidate and their family. The primary objectives are to establish the feasibility (i) of delivering the developed intervention in existing care pathways and (ii) of undertaking a randomised controlled trial of the intervention. A mixed-methods parallel process evaluation will investigate the acceptability, implementation and mechanisms of impact of the intervention. The trial is based at two UK hospitals: a transplanting hospital and a non-transplanting referral hospital. Individuals are eligible if they are ≥ 18 years old, are active on the kidney transplant waiting list or have been referred for transplant listing and do not have a potential living-donor undergoing surgical assessment. Randomisation will be undertaken with concealed allocation. Participants will be randomly allocated 1:1 to (i) the intervention or (ii) usual care, stratified by site to ensure a balance in terms of local differences. Minimisation will be used to ensure balance in sex, age group and socioeconomic strata, with probability weighting of 0.8 in order to reduce predictability. The primary outcomes are recruitment (% of those eligible and invited who consent to randomisation) and retention (% of participants completing follow-up). Discussion: Findings will inform the design of a future fully powered, randomised controlled trial to formally evaluate the effectiveness of the intervention at improving equitable access to living-donor kidney transplantation. Trial registration: ISRCTN Registry ISRCTN10989132 Applied 30/10/20. [ABSTRACT FROM AUTHOR]

Objective: Patients with otitis externa (OE) are commonly referred to acute ENT services after failed treatment in community. This case series analyses the prevalence and management of OE in a UK ENT rapid access clinic (RAC) prior to and following the national lockdown imposed in March 2020. Materials and Methods: Retrospective case review of all patients referred with OE to the RAC between January 2019 and March 2021 with comparison of the cohorts before and after 1st March 2020. Data anaylsed included demographics, treatment methods, rates of admission, microbiological swab and CT results and rates of necrotising otitis externa (NOE). Results: There were 239 new referrals over the total study period. The rate of referral dropped from 12.1/month to 5.8/month following the March 2020 lockdown. There were no significant differences in rates of severe infection or NOE before and after the lockdown. The most common organisms grown were Pseudomonas aeruginosa, Candida, and Staphylococcus aureus. Conclusions: There was a considerable reduction in acute referrals for OE to this centre in the year following the March 2020 lockdown. There was no significant change in disease severity or management trends. [ABSTRACT FROM AUTHOR]

Background Kidney disease registries typically report populations incident to kidney replacement therapy (KRT) after excluding reversible disease. Registry-based audit and quality assurance is thus based on populations depleted of those with the highest early mortality. It is now mandatory for UK kidney units to report all recipients of dialysis, both acute and chronic. This work presents 90-day survival and recovery outcomes for all reported adults. Methods Seventy adult centres reporting to the UK Renal Registry were included. Those assessed as underreporting death and recovery were excluded. Survival was evaluated using a Kaplan–Meier estimator. Cox regression was used to describe hazard ratios (HRs) for age, sex and acute/chronic dialysis coding on day 1. Analysis of all-cause 90-day mortality with recovery as a competing risk is presented. Results Twenty-four centres were assessed as underreporting, with rates of death/recovery below the 99.7th centile. Of 5784 dialysis starters in the remaining 46 centres, 2163 (37.4%) were coded as receiving acute dialysis on day 1. Ninety days after starting, 3860 (66.7%) of all starters were receiving KRT, 1157 (20.0%) were alive having stopped, 716 (12.4%) were dead and 51 (0.9%) were lost to follow-up. Mortality was higher among those coded as receiving acute dialysis on day 1 (HR 4.88, P < 0.001). The sub-HR for recovery among those coded as receiving acute compared with chronic dialysis was 56.14 (P < 0.001). Conclusions Death and recovery rates are substantially higher than reported in conventional incident populations. This work highlights a vulnerable subgroup of patients largely overlooked by most national quality assurance systems. [ABSTRACT FROM AUTHOR]

The Ionising Radiation (Medical Exposure) Regulations require employers to appoint suitable medical physics experts (MPE) for nuclear medicine services, and they also define the areas where MPEs are required to provide advice and specify matters that they must contribute towards. Applications for employer licences under IR(ME)R require employers to specify the level of MPE support available and if this is provided by onsite MPEs or remotely. Assessment of these applications by the Administration of Radioactive Substances Advisory Committee (ARSAC) has highlighted variability in the levels of MPE support being provided for similar services across the UK. A working party including representatives from IPEM, ARSAC, BIR and BNMS was formed and has produced these recommendations on MPE support. Nuclear medicine services were divided into seven broad categories and MPE support for each category has been considered. However, some services that differ from the scenarios provided in this guidance may require different levels of MPE support. Positron emission tomography (PET)/CT and gamma camera imaging have been considered separately here, although it is recognised that both PET/CT and gamma cameras are often sited within the same department in many centres. The separation has been done for pragmatic purposes, as there are felt to be sufficient differences in the MPE role requirements. This guidance sets out recommendations for MPE support, and broader physics support, to run a safe nuclear medicine service and defines the responsibilities of these staff for a range of clinical nuclear medicine services. The recommendations on MPE support made are advice, but will assist employers in meeting regulatory requirements. [ABSTRACT FROM AUTHOR]

Background: People living with a long-term condition, such as chronic kidney disease (CKD), often suffer from multiple symptoms simultaneously, making symptom management challenging. This study aimed to identify symptom clusters in adults with CKD across treatment groups and investigate their association with people's ability to perform their usual activities. Methods: We conducted a secondary analysis of both cross-sectional and longitudinal data collected as part of a national service improvement programme in 14 kidney centres in England, UK. This data included symptom severity (17 items, POS-S Renal) and the extent to which people had problems performing their usual activities (single item, EQ-5D-5L). We categorised data by treatment group: haemodialysis (n = 1,462), transplantation (n = 866), peritoneal dialysis (n = 127), or CKD without kidney replacement therapy (CKD non-KRT; n = 684). We used principal component analysis to identify symptom clusters per treatment group, and proportional odds models to assess the association between clusters and usual activities. Results: Overall, clusters related to: lack of energy and mobility; gastrointestinal; skin; and mental health. Across groups, the 'lack of energy and mobility' clusters were associated with having problems with usual activities, with odds ratios (OR) ranging between 1.24 (95% confidence interval [CI], 1.21–1.57) for haemodialysis and 1.56 for peritoneal dialysis (95% CI, 1.28–1.90). This association was confirmed longitudinally in haemodialysis (n = 399) and transplant (n = 249) subgroups. Implications: Our findings suggest that healthcare professionals should consider routinely assessing symptoms in the 'lack of energy & mobility' cluster in all people with CKD, regardless of whether they volunteer this information; not addressing these symptoms is likely to be related to them having problems with performing usual activities. Future studies should explore why symptoms within clusters commonly co-occur and how they interrelate. This will inform the development of cluster-level symptom management interventions with enhanced potential to improve outcomes for people with CKD. [ABSTRACT FROM AUTHOR]

Background: Little is known about the clinical demographics of and access to transplantation for Chinese diaspora populations with kidney disease. Methods: The UK Renal Registry provided data on adults with ethnicity recorded as 'Chinese' or 'White' starting Kidney Replacement Therapy (KRT) 1/1/97-31/12/17. Baseline characteristics were compared between Chinese and White patients. Multivariable logistic regression models were used to investigate the relationships between Chinese ethnicity and i) being listed for deceased-donor transplantation at start of KRT, ii) being listed 2 years after start of KRT, iii) pre-emptive kidney transplantation, iv) kidney transplantation 3 years after start of KRT, and v) living-donor kidney transplantation (LDKT). Results: UK Chinese patients were younger at start of KRT (61.6 vs 65.6 years, p <0.001) and had more diabetic kidney disease (29% vs 20%, p<0.001) and glomerulonephritis (21% vs 13%, p<0.001) than White patients. We found evidence of interaction between ethnicity and sex. Compared to UK White men, UK Chinese men had lower odds of pre-emptive transplant (aOR 0.28, 95% CI [0.10–0.76]) and transplant within 3 years of KRT start (aOR 0.65, [95% CI 0.49–0.87], P = 0.004). UK White women and Chinese women had the same likelihood of pre-emptive transplant (aOR 0.78, 95% CI [0.38–1.61]), or transplant within 3 years of KRT start (aOR 0.94, 95% CI [0.60–1.46]). Both UK Chinese men and women had markedly lower odds of LDKT compared to Whites aOR 0.34 [95% CI 0.21–0.53]. Conclusions: UK Chinese are less likely to receive a LDKT. UK Chinese men have lower odds of accessing pre-emptive wait-listing and transplantation. Understanding whether these disparities reflect modifiable barriers will help ensure equitable access to transplantation. [ABSTRACT FROM AUTHOR]

Background: Prospective cohort studies are challenging to deliver, with one of the main difficulties lying in retention of participants. The need to socially distance during the COVID-19 pandemic has added to this challenge. The pre-COVID-19 adaptation of the European Quality (EQUAL) study in the UK to a remote form of follow-up for efficiency provides lessons for those who are considering changing their study design.Methods: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced chronic kidney disease. Initially, patients were invited to complete a questionnaire (SF-36, Dialysis Symptom Index and Renal Treatment Satisfaction Questionnaire) at research clinics every 3-6 months, known as "traditional follow-up" (TFU). In 2018, all living patients were invited to switch to "efficient follow-up" (EFU), which used an abbreviated questionnaire consisting of SF-12 and Dialysis Symptom Index. These were administered centrally by post. Response rates were calculated using returned questionnaires as a proportion of surviving invitees, and error rates presented as the average percentage of unanswered questions or unclear answers, of total questions in returned questionnaires. Response and error rates were calculated 6-monthly in TFU to allow comparisons with EFU.Results: Of the 504 patients initially recruited, 236 were still alive at the time of conversion to EFU; 111 of these (47%) consented to the change in follow-up. In those who consented, median TFU was 34 months, ranging from 0 to 42 months. Their response rates fell steadily from 88% (98/111) at month 0 of TFU, to 20% (3/15) at month 42. The response rate for the first EFU questionnaire was 60% (59/99) of those alive from TFU. With this improvement in response rates, the first EFU also lowered errors to baseline levels seen in early follow-up, after having almost trebled throughout traditional follow-up.Conclusions: Overall, this study demonstrates that administration of shorter follow-up questionnaires by post rather than in person does not negatively impact patient response or error rates. These results may be reassuring for researchers who are trying to limit face-to-face contact with patients during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Avoidance of unnecessary antimicrobial administration is a key tenet of antimicrobial stewardship; knowing the optimal duration of therapy obviates over-treatment. However, little research has been performed to establish course lengths for common canine infections. In clinical practice, antimicrobial therapy is frequently prescribed in dogs presenting lower urinary tract signs (haematuria, pollakiuria and dysuria/stranguria). The proposed length of treatment in International Consensus guidelines has decreased with each iteration, but these recommendations remain arbitrary and largely extrapolated from experience in people. Methods: The objective of this prospective, multi-centre study is to find the shortest course duration that is non-inferior to the standard duration of 7 days of amoxicillin/clavulanate in terms of clinical outcomes for female dogs with lower urinary tract signs consistent with a urinary tract infection. An electronic data capture platform will be used by participating veterinarians working in clinical practice in the United Kingdom. Eligible dogs must be female, aged between 6 months and 10 years and have lower urinary tract signs of up to seven days' duration. Enrolment will be offered in cases where the case clinician intends to prescribe antimicrobial therapy. Automatic pseudo-randomisation to treatment group will be based on the day of presentation (Monday-Friday); all antimicrobial courses will be completed on the Sunday after presentation generating different treatment durations. Follow-up data will be collected 1, 8 and 22–26 days after completion of the antimicrobial course to ensure effective safety netting, and to monitor short-term outcome and recurrence rates. Informed owner consent will be obtained in all cases. The study is approved by the Ethical Review Board of the University of Nottingham and has an Animal Test Certificate from the Veterinary Medicine's Directorate. Discussion: This study has been designed to mirror current standards of clinical management; conclusions should therefore, be widely applicable and guide practising veterinarians in their antimicrobial decision-making process. A duration-response curve will be created allowing determination of the optimal treatment duration for the management of female dogs with lower urinary tract signs. It is hoped that these results will contribute valuable information to improve future antimicrobial stewardship as part of a wider one-health perspective. [ABSTRACT FROM AUTHOR]

Context: There have been dramatic global declines in pollinating insects. A common land management intervention to support wild pollinators is to plant non-crop flowering plants ('pollinator planting'). However, there are limited data on which species or spatial arrangement of planting provide maximum benefit to wild pollinators. Objectives: Here we investigate which flowering species and locations are visited by free-foraging Bombus terrestris (buff-tailed bumblebees) in species-rich semi-natural grassland and woodland. Methods: Two study nests of buff-tailed bumblebees were established in Wytham Woods, UK. Pollen analogue pigments were sprayed on open flowers in the study area over a period of two months, with unique colours used to identify separate sections of the study area. Pollen load analysis was used to identify forage species and foraging locations. Results: Bumblebees showed low flower constancy, visiting five flower species per trip on average, and as a group the sampled bumblebees visited 36 of the 49 plant species identified in study area surveys. Many individuals foraged in multiple, spatially-discrete locations during single trips. Conclusions: The positive relationship between floral diversity and pollen load species diversity, and the positive relationship between site floral diversity and frequency of visitation, suggest behavioural strategies that maximize the diversity of flower species visited, in line with the energetic costs and benefits hypothesis. This supports recommendations for pollinator plantings with high species diversity, potentially spread across many small forage areas across the landscape. [ABSTRACT FROM AUTHOR]

A living-donor kidney transplant (LDKT) is one of the best treatments for kidney failure. The UK's LDKT activity falls behind that of many other countries, and there is evidence of socioeconomic inequity in access. We aimed to develop a UK-specific multicomponent intervention to support eligible individuals to access a LDKT. The intervention was designed to support those who are socioeconomically-deprived and currently disadvantaged, by targeting mediators of inequity identified in earlier work. We identified three existing interventions in the literature which target these mediators: a) the Norway model (healthcare practitioners contact patients' family with information about kidney donation), b) a home education model, and c) a Transplant candidate advocate model. We undertook intervention development using the Person-Based Approach (PBA). We performed in-depth qualitative interviews with people with advanced kidney disease (n = 13), their family members (n = 4), and renal and transplant healthcare practitioners (n = 15), analysed using thematic analysis. We investigated participant views on each proposed intervention component. We drafted intervention resources and revised these in light of comments from qualitative 'think-aloud' interviews. Four general themes were identified: i) Perceived cultural and societal norms; ii) Influence of family on decision-making; iii) Resource limitation, and iv) Evidence of effectiveness. For each intervention discussed, we identified three themes: for the Norway model: i) Overcoming communication barriers and assumptions; ii) Request from an official third party, and iii) Risk of coercion; for the home education model: i) Intragroup dynamics; ii) Avoidance of hospital, and iii) Burdens on participants; and for the transplant candidate advocates model: i) Vested interest of advocates; ii) Time commitment, and iii) Risk of misinformation. We used these results to develop a multicomponent intervention which comprises components from existing interventions that have been adapted to increase acceptability and engagement in a UK population. This will be evaluated in a future randomised controlled trial. [ABSTRACT FROM AUTHOR]

Shared decision making in advanced chronic kidney disease (CKD) requires unbiased information on survival and person-centred outcomes known to matter to patients: quality of life, symptom burden and support from family and healthcare professionals. To date, when deciding between dialysis and conservative care, patients have had to rely on evidence from small observational studies. Clinicians recognize that like is not being compared with like in these studies, and interpret the results differently. Furthermore, support differs considerably between renal units. What patients choose therefore depends on which renal unit they attend. To address this, a programme of work has been underway in the UK. After reports on survival and symptoms from a small number of renal units, a national, mixed-methods study—the Conservative Kidney Management Assessment of Practice Patterns Study—mapped out conservative care practices and attitudes in the UK. This led to the Prepare for Kidney Care study, a randomized controlled trial comparing preparation for dialysis versus preparation for conservative care. Although powered to detect a positivist 0.345 difference in quality-adjusted life years between the two treatments, this trial also takes a realist approach with a range of person-centred secondary outcomes and embedded qualitative research. To understand generalizability, it is nested in an observational cohort study, which is nested in a CKD registry. Challenges to recruitment and retention have been rapidly identified and addressed using an established embedded mixed methods approach—the QuinteT recruitment intervention. This review considers the background to and progress with recruitment to the trial. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance of a novel convolutional neural network (CNN) for the classification of typical perifissural nodules (PFN).Methods: Chest CT data from two centers in the UK and The Netherlands (1668 unique nodules, 1260 individuals) were collected. Pulmonary nodules were classified into subtypes, including "typical PFNs" on-site, and were reviewed by a central clinician. The dataset was divided into a training/cross-validation set of 1557 nodules (1103 individuals) and a test set of 196 nodules (158 individuals). For the test set, three radiologically trained readers classified the nodules into three nodule categories: typical PFN, atypical PFN, and non-PFN. The consensus of the three readers was used as reference to evaluate the performance of the PFN-CNN. Typical PFNs were considered as positive results, and atypical PFNs and non-PFNs were grouped as negative results. PFN-CNN performance was evaluated using the ROC curve, confusion matrix, and Cohen's kappa.Results: Internal validation yielded a mean AUC of 91.9% (95% CI 90.6-92.9) with 78.7% sensitivity and 90.4% specificity. For the test set, the reader consensus rated 45/196 (23%) of nodules as typical PFN. The classifier-reader agreement (k = 0.62-0.75) was similar to the inter-reader agreement (k = 0.64-0.79). Area under the ROC curve was 95.8% (95% CI 93.3-98.4), with a sensitivity of 95.6% (95% CI 84.9-99.5), and specificity of 88.1% (95% CI 81.8-92.8).Conclusion: The PFN-CNN showed excellent performance in classifying typical PFNs. Its agreement with radiologically trained readers is within the range of inter-reader agreement. Thus, the CNN-based system has potential in clinical and screening settings to rule out perifissural nodules and increase reader efficiency.Key Points: • Agreement between the PFN-CNN and radiologically trained readers is within the range of inter-reader agreement. • The CNN model for the classification of typical PFNs achieved an AUC of 95.8% (95% CI 93.3-98.4) with 95.6% (95% CI 84.9-99.5) sensitivity and 88.1% (95% CI 81.8-92.8) specificity compared to the consensus of three readers. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to describe the outcome and management of all children who have presented with haemorrhagic stroke (HS) secondary to an arteriovenous malformation (AVM) at a single UK centre over a 13-year period. Methods: All children with HS managed at our institution (2005–2018) were identified and those with underlying AVMs were studied. Clinical and imaging data were obtained from medical records. Outcome was scored using the Recovery and Recurrence Questionnaire. Results: Ninety-three children (median age 8.8 years; 56 males; 8 neonates) presented with both global and focal features (28 had Glasgow Coma Score < 8). Haemorrhage was intraparenchymal in 72; prior risk factors present in 14. An underlying vascular lesion was identified in 68/93, most commonly AVM (n = 48). A systemic cause was found in 10, cerebral venous thrombosis in three, and 9 remain unidentified despite neuroradiological investigation. Median follow-up was 2.4 years, six died, and one was lost to follow-up. Outcome was rated as good in 60/86. Of the 48 AVMs, 3 were Spetzler-Martin (SM) grade 1, 21 SM 2, 21 SM3 and 3 SM4. One patient was treated conservatively as the AVM was too high risk to treat. At follow-up, 19 with AVM were angiographically cured, all with low SM grade and with the use of a single modality in 9 cases (all low SM grade). Conclusion: Although children with acute HS are extremely unwell at presentation, supportive care results in a good outcome in the majority. Complete obliteration for childhood AVMs is challenging even with low-grade lesions with multimodal treatment. [ABSTRACT FROM AUTHOR]

Background: Lymphopenia (reduced lymphocyte count) during infections, such as pneumonia, is common and is associated with increased mortality. Little is known about the relationship between lymphocyte count before developing infections and mortality risk.Aim: To identify whether patients with lymphopenia who develop pneumonia have increased risk of death.Design and Setting: A cohort study set in the Clinical Practice Research Datalink (CPRD) linked to national death records, in primary care. This database is representative of the UK population and is extracted from routine records.Method: Patients aged >50 years with a pneumonia diagnosis were included from January 1998 until January 2019. The relationship between lymphocyte count and mortality was measured, using a time-to-event (multivariable Cox regression) approach, adjusted for age, sex, social factors, and potential causes of lymphopenia. The primary analysis used the most recent test before pneumonia. The primary outcome was 28-day, all-cause mortality.Results: A total of 40 909 participants with pneumonia were included, with 28 556 having had a lymphocyte count test before pneumonia (median time between test and diagnosis was 677 days). When lymphocyte count was categorised (0-1 × 109 cells/L, 1-2 × 109 cells/L, 2-3 × 109 cells/L, >3 × 109 cells/L, never tested), both 28-day and 1-year mortality varied significantly: 14%, 9.2%, 6.5%, 6.1%, and 25%, respectively, for 28-day mortality, and 41%, 29%, 22%, 20%, and 52% for 1-year mortality. In multivariable Cox regression, lower lymphocyte count was consistently associated with increased hazard of death.Conclusion: Lymphopenia is an independent predictor of mortality in primary care pneumonia. Even low-normal lymphopenia (1-2 × 109 cells/L) is associated with an increase in short- and long-term mortality compared with higher counts. [ABSTRACT FROM AUTHOR]

As urban populations grow, it is increasingly important to accurately characterize flood risk in cities and built up areas. Global digital elevation models (GDEMs) have recently enabled flood risk analysis at broad scale and worldwide, but their accuracy and its impact on modeled flood risk in cities has not been fully investigated. We compare flood extents, hydrographs, depths, and impacts between hydrodynamic simulations, using five spaceborne GDEM products and an airborne LIDAR product. Benchmark observations of a historical flood event in Carlisle (UK) were used to assess the accuracy of each simulation. GDEM simulations are shown to perform significantly less accurately than the airborne LIDAR‐based simulations. No DEM outperforms the others across all metrics; the MERIT DEM is the best predictor of flood extent, but TanDEM‐X performs best for discharge. However, the impacts of flooding from GDEM simulations are consistently overestimated, 2 to 3 times higher than those from LIDAR simulations. Until a high resolution, accurate, global DEM is available, multiple products should be used concurrently to enable the full uncertainty range to be quantified and communicated, to ensure flood risk management decisions are not misinformed. Key Points: Flood models using five global DEMs are worse at predicting flood extents, hydrographs, and floodplain depths than a model using LIDARGlobal DEM flood models consistently overestimate the impacts of flooding in a city by 2–3 times compared to a model using LIDARNo single global DEM performs best across all validation metrics, so multiple DEMs should be used to capture uncertainties in flood risk [ABSTRACT FROM AUTHOR]

Purpose: Global rates of caesarean section (CS) rates have increased rapidly in recent years. This is a growing public health concern as it has been proposed that CS may impact cognitive outcomes in childhood. However, the evidence for this association is limited and inconsistent. Therefore, the aim of this study was to investigate the relationship between obstetric mode of delivery and longitudinal cognitive outcomes in childhood.Methods: We examined this question using data from a longitudinal cohort study of 8845 participants from the Millennium Cohort Study, a nationally representative UK cohort, who completed a range of verbal and visual-spatial cognitive assessments at ages 3, 5, 7 and 11 years.Results: We found a statistically significant association between planned CS and visual-spatial cognitive delay in the pattern construction assessment at age 5 (OR 1.31, 95% CI 0.99-1.72) and age 7 (OR 1.42, 95% CI 1.12-1.81). Additionally planned CS was also associated with increased odds of "early childhood delay" (OR 1.70, 95% CI 1.15-2.50) and borderline increased odds of "persistent delay" (OR 1.37, 95% CI 0.99-1.89) in visual-spatial cognitive tests. Mode of delivery was not associated with verbal ability or with patterns of delay at any age point in verbal cognitive tests.Conclusion: We have reported a small association between planned CS and visual-spatial cognitive delay in childhood. However, while this result should be interpreted with caution, it highlights the need to further explore this potential relationship and the causal basis of such an association. [ABSTRACT FROM AUTHOR]

Background: Estimation of the risk of malignancy in pulmonary nodules detected by CT is central in clinical management. The use of artificial intelligence (AI) offers an opportunity to improve risk prediction. Here we compare the performance of an AI algorithm, the lung cancer prediction convolutional neural network (LCP-CNN), with that of the Brock University model, recommended in UK guidelines.Methods: A dataset of incidentally detected pulmonary nodules measuring 5-15 mm was collected retrospectively from three UK hospitals for use in a validation study. Ground truth diagnosis for each nodule was based on histology (required for any cancer), resolution, stability or (for pulmonary lymph nodes only) expert opinion. There were 1397 nodules in 1187 patients, of which 234 nodules in 229 (19.3%) patients were cancer. Model discrimination and performance statistics at predefined score thresholds were compared between the Brock model and the LCP-CNN.Results: The area under the curve for LCP-CNN was 89.6% (95% CI 87.6 to 91.5), compared with 86.8% (95% CI 84.3 to 89.1) for the Brock model (p≤0.005). Using the LCP-CNN, we found that 24.5% of nodules scored below the lowest cancer nodule score, compared with 10.9% using the Brock score. Using the predefined thresholds, we found that the LCP-CNN gave one false negative (0.4% of cancers), whereas the Brock model gave six (2.5%), while specificity statistics were similar between the two models.Conclusion: The LCP-CNN score has better discrimination and allows a larger proportion of benign nodules to be identified without missing cancers than the Brock model. This has the potential to substantially reduce the proportion of surveillance CT scans required and thus save significant resources. [ABSTRACT FROM AUTHOR]

Previous research has shown that riots spread across multiple locations, but has not explained underlying psychological processes. We examined rioting in three locations during the August 2011 disorders in England to test a social identity model of riot diffusion. We triangulated multiple sources to construct a narrative of events; and we analysed interviews with 68 participants to examine experiences. In line with the model, we found evidence for two pathways of influence: "cognitive" and "strategic". For some participants, previous rioting was highly self‐relevant, and shared identity was the basis of their subsequent involvement. For others, previous rioting was empowering because it demonstrated the vulnerability of a common enemy (the police). In each location, interaction dynamics mediated the link between initial perceptions and collective action. The utility of this social identity approach is that it is able to account for both the boundaries and the sequence of urban riot diffusion. [ABSTRACT FROM AUTHOR]

The rising demand for health and social care, and around the clock monitoring services, is increasing and are unsustainable under current care provisions. Consequently, a safe and independent living environment is hard to achieve; yet the detection of sudden or worsening changes in a patient's condition is vital for early intervention. The use of smart technologies in primary care delivery is increasing significantly. However, substantial research gaps remain in non-invasive and cost effective monitoring technologies. The inability to learn the unique characteristics of patients and their conditions seriously limits the effectiveness of most current solutions. The smart metering infrastructure provides new possibilities for a variety of applications that are unachievable using the traditional energy grid. By 2020, UK energy suppliers will install 50 million smart meters, therefore, providing access to a highly accurate sensing network. Each smart meter records the electrical load for a given property at 30 minute intervals. This granular data captures detailed habits and routines through the occupant's interactions with electrical devices, enabling the detection and identification of alterations in behaviour. The research presented in this paper explores how this data could be used to achieve a safe living environment for people living with progressive neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: The associations between pregnancy hypertensive disorders and common cardiovascular disorders have not been investigated at scale in a contemporaneous population. We aimed to investigate the association between preeclampsia, hypertensive disorders of pregnancy, and subsequent diagnosis of 12 different cardiovascular disorders.Methods: We used linked electronic health records from 1997 to 2016 to recreate a UK population-based cohort of 1.3 million women, mean age at delivery 28 years, with nearly 1.9 million completed pregnancies. We used multivariable Cox models to determine the associations between hypertensive disorders of pregnancy, and preeclampsia alone (term and preterm), with 12 cardiovascular disorders in addition to chronic hypertension. We estimated the cumulative incidence of a composite end point of any cardiovascular disorder according to preeclampsia exposure.Results: During the 20-year study period, 18 624 incident cardiovascular disorders were observed, 65% of which had occurred in women under 40 years. Compared to women without hypertension in pregnancy, women who had 1 or more pregnancies affected by preeclampsia had a hazard ratio of 1.9 (95% confidence interval 1.53-2.35) for any stroke, 1.67 (1.54-1.81) for cardiac atherosclerotic events, 1.82 (1.34-2.46) for peripheral events, 2.13 (1.64-2.76) for heart failure, 1.73 (1.38-2.16) for atrial fibrillation, 2.12 (1.49-2.99) for cardiovascular deaths, and 4.47 (4.32-4.62) for chronic hypertension. Differences in cumulative incidence curves, according to preeclampsia status, were apparent within 1 year of the first index pregnancy. Similar patterns of association were observed for hypertensive disorders of pregnancy, while preterm preeclampsia conferred slightly further elevated risks.Conclusions: Hypertensive disorders of pregnancy, including preeclampsia, have a similar pattern of increased risk across all 12 cardiovascular disorders and chronic hypertension, and the impact was evident soon after pregnancy. Hypertensive disorders of pregnancy should be considered as a natural screening tool for cardiovascular events, enabling cardiovascular risk prevention through national initiatives. [ABSTRACT FROM AUTHOR]

Background: One-stop clinics provide comprehensive diagnostic testing in one outpatient appointment. They could benefit patients with conditions, such as cancer, whose outcomes are improved by early diagnosis, and bring efficiency savings for health systems.Objective: To assess the use and outcomes of one-stop clinics for symptoms where cancer is a possible diagnosis.Design and Setting: Systematic review of studies reporting use and outcomes of one-stop clinics in primary care patients.Method: We searched MEDLINE, Embase, and Cochrane Library for studies assessing one-stop clinics for adults referred after presenting to primary care with any symptom that could be indicative of cancer. Study selection was carried out independently in duplicate with disagreements resolved through discussion.Results: Twenty-nine studies were identified, most were conducted in the UK and observational in design. Few included a comparison arm. A pooled comparison of the cancer conversion rate of one-stop and multi-stop clinics was only possible for breast symptoms, and we found no significant difference. One-stop clinics were associated with significant reductions in the interval from referral to testing (15 versus 75 days) and more patients diagnosed on the same day (79% versus 25%) compared to multi-stop pathways. The majority of patients and GPs found one-stop clinics to be acceptable.Conclusion: This review found one-stop clinics were associated with reduced time from referral to testing, increased same day diagnoses, and were acceptable to patients and GPs. Our conclusions are limited by high levels of heterogeneity, scarcity of comparator groups, and the overwhelmingly observational nature of included studies. [ABSTRACT FROM AUTHOR]

Background Improvement in long-term renal allograft survival is impeded by incomplete or erroneous coding of causes of allograft loss. This study reports 13-year trends in causes of graft failure across the UK. Methods National Health Service Blood and Transplant (NHSBT) and UK Renal Registry data were linked to describe UK kidney patients transplanted in 2000–13. NHSBT graft failure categories were used, with 'other' recoded when free text was available. Adjusted analyses examined the influence of age, ethnicity and donor type on causes of graft failure. Results In 22 730 recipients, 5389 (23.7%) grafts failed within a median follow-up of 5 years. The two most frequent causes were death with a functioning graft (40.8%) and alloimmune pathology (25.0%). Graft survival was higher in recipients who were younger (mean 47.3 versus 50.7 years), received a pre-emptive transplant (20.2% versus 10.4%), spent less time on dialysis (median 1.6 versus 2.4 years) and received a living donor transplant (36.3% versus 22.2%), with no differences by sex, ethnicity or human leucocyte antigen mismatch. Allograft failure within 2 years of transplantation fell from 12.5% (2000–4) to 9.8% (2009–13). Surgical- and alloimmune-related failures decreased over time while death with a functioning graft became more common. Age, ethnicity and donor type were factors in recurrent primary disease and alloimmune pathology. Conclusions Since 2000 there have been reductions in surgical and alloimmune graft failures in the UK. However, graft failure codes need to be revised if they are to remain useful and effective in epidemiological and quality improvement trials. [ABSTRACT FROM AUTHOR]