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The objective of this paper is to present the results of discussions at a workshop held as part of the International Congress of Radiation Research (Environmental Health stream) in Manchester UK, 2019. The main objective of the workshop was to provide a platform for radioecologists to engage with radiobiologists to address major questions around developing an Ecosystem approach in radioecology and radiation protection of the environment. The aim was to establish a critical framework to guide research that would permit integration of a pan-ecosystem approach into radiation protection guidelines and regulation for the environment. The conclusions were that the interaction between radioecologists and radiobiologists is useful in particular in addressing field versus laboratory issues where there are issues and challenges in designing good field experiments and a need to cross validate field data against laboratory data and vice versa. Other main conclusions were that there is a need to appreciate wider issues in ecology to design good approaches for an ecosystems approach in radioecology and that with the capture of 'Big Data', novel tools such as machine learning can now be applied to help with the complex issues involved in developing an ecosystem approach. [ABSTRACT FROM AUTHOR]

Maximising resource‐use efficiency, productivity and environmental sustainability are all fundamental requirements to raise global food production by ~70 per cent in order to feed a world population of ~9.7 billion people by 2050. Perhaps the most vital resource within our capacity to achieve this goal is our soil. Broadly, the fundamental question concerns whether or not satisfying this production demand will accelerate soil degradation, climate change, and the loss of soil carbon stocks. This paper builds upon the outputs of the UK Charity 'Food & Farming Futures' (chaired by Lord Curry of Kirkharle) virtual workshop held on 23 March 2021, entitled 'Capturing the Potential of Soil'. The event focussed on the link between soil health, primarily soil organic carbon (SOC), and agricultural productivity. Supported with commentaries by Professor Pete Smith (University of Aberdeen and Science Director of the Scottish Climate Change Centre of Expertise) and Professor Steve McGrath (Head of Sustainable Agricultural Sciences at Rothamsted Research), specific focus will be given to the research challenges within the UK's ability to improve soil health and functionality, the implementation priorities that must be held in order to improve soil management by 2050 and what the potential co‐benefits could be. These co‐benefits were scattered across environmental, economic, social and political issues, yet they may be summarised into six primary co‐benefits: developing natural capital, climate change mitigation, carbon trading, improvements in crop yield, animal performance and human health (nutrition). Additionally, the main barriers to improved soil management practices are centred on knowledge exchange‐regarding agri‐environmental techniques—whilst the most impactful solutions rely on soil monitoring, reporting and verification. [ABSTRACT FROM AUTHOR]

Deterioration of earthworks and the resultant implications for serviceability and increased occurrence of failures have a significant negative impact on transport networks both in the UK and internationally. There is evidence in the field that deterioration processes are occurring over the life of an asset, comprising cracking and loss of suction. These are weather-driven processes that occur in the absence of increased mechanical loads and can lead to failure many years after construction. To demonstrate the progressive loss in mechanical performance of clay fill due to a purely environmentally driven deterioration process, a programme of unsaturated triaxial testing was carried out. A new mechanism of soil deterioration driven by cyclic wetting and drying is proposed, based on an extensive laboratory and field experimental programme. The underlying cause for this is the micro-structural changes to the soil fabric leading to loss of suction generation capacity. In addition, cracking leads to changes in hydraulic conductivity and the movement of water into and out of the soil. The implications for slope stability assessment include the need for changeability of soil parameters and of the ground model, with changes occurring both seasonally and gradually over time. [ABSTRACT FROM AUTHOR]

Background: In recent years a large volume of clinical genomics data has become available due to rapid advances in sequencing technologies. Efficient exploitation of this genomics data requires linkage to patient phenotype profiles. Current resources providing disease-phenotype associations are not comprehensive, and they often do not have broad coverage of the disease terminologies, particularly ICD-10, which is still the primary terminology used in clinical settings. Methods: We developed two approaches to gather disease-phenotype associations. First, we used a text mining method that utilizes semantic relations in phenotype ontologies, and applies statistical methods to extract associations between diseases in ICD-10 and phenotype ontology classes from the literature. Second, we developed a semi-automatic way to collect ICD-10–phenotype associations from existing resources containing known relationships. Results: We generated four datasets. Two of them are independent datasets linking diseases to their phenotypes based on text mining and semi-automatic strategies. The remaining two datasets are generated from these datasets and cover a subset of ICD-10 classes of common diseases contained in UK Biobank. We extensively validated our text mined and semi-automatically curated datasets by: comparing them against an expert-curated validation dataset containing disease–phenotype associations, measuring their similarity to disease–phenotype associations found in public databases, and assessing how well they could be used to recover gene–disease associations using phenotype similarity. Conclusion: We find that our text mining method can produce phenotype annotations of diseases that are correct but often too general to have significant information content, or too specific to accurately reflect the typical manifestations of the sporadic disease. On the other hand, the datasets generated from integrating multiple knowledgebases are more complete (i.e., cover more of the required phenotype annotations for a given disease). We make all data freely available at https://doi.org/10.5281/zenodo.4726713. [ABSTRACT FROM AUTHOR]

Background: There is limited prospective evidence on the association between meat consumption and many common, non-cancerous health outcomes. We examined associations of meat intake with risk of 25 common conditions (other than cancer).Methods: We used data from 474,985 middle-aged adults recruited into the UK Biobank study between 2006 and 2010 and followed up until 2017 (mean follow-up 8.0 years) with available information on meat intake at baseline (collected via touchscreen questionnaire), and linked hospital admissions and mortality data. For a large sub-sample (~ 69,000), dietary intakes were re-measured three or more times using an online, 24-h recall questionnaire.Results: On average, participants who reported consuming meat regularly (three or more times per week) had more adverse health behaviours and characteristics than participants who consumed meat less regularly, and most of the positive associations observed for meat consumption and health risks were substantially attenuated after adjustment for body mass index (BMI). In multi-variable adjusted (including BMI) Cox regression models corrected for multiple testing, higher consumption of unprocessed red and processed meat combined was associated with higher risks of ischaemic heart disease (hazard ratio (HRs) per 70 g/day higher intake 1.15, 95% confidence intervals (CIs) 1.07-1.23), pneumonia (1.31, 1.18-1.44), diverticular disease (1.19, 1.11-1.28), colon polyps (1.10, 1.06-1.15), and diabetes (1.30, 1.20-1.42); results were similar for unprocessed red meat and processed meat intakes separately. Higher consumption of unprocessed red meat alone was associated with a lower risk of iron deficiency anaemia (IDA: HR per 50 g/day higher intake 0.80, 95% CIs 0.72-0.90). Higher poultry meat intake was associated with higher risks of gastro-oesophageal reflux disease (HR per 30 g/day higher intake 1.17, 95% CIs 1.09-1.26), gastritis and duodenitis (1.12, 1.05-1.18), diverticular disease (1.10, 1.04-1.17), gallbladder disease (1.11, 1.04-1.19), and diabetes (1.14, 1.07-1.21), and a lower IDA risk (0.83, 0.76-0.90).Conclusions: Higher unprocessed red meat, processed meat, and poultry meat consumption was associated with higher risks of several common conditions; higher BMI accounted for a substantial proportion of these increased risks suggesting that residual confounding or mediation by adiposity might account for some of these remaining associations. Higher unprocessed red meat and poultry meat consumption was associated with lower IDA risk. [ABSTRACT FROM AUTHOR]

Background: Red and processed meat have been consistently associated with colorectal cancer risk, but evidence for other cancer sites and for poultry intake is limited. We therefore examined associations between total, red and processed meat and poultry intake and incidence for 20 common cancers.Methods: We analyzed data from 474 996 participants (54% women) in UK Biobank. Participants were aged 37-73 years and cancer-free at baseline (2006-10). Multivariable-adjusted Cox proportional hazards models were used to determine associations between baseline meat intake and cancer incidence. Trends in risk across the baseline categories were calculated, assigning re-measured intakes from a subsample.Results: During a mean follow-up of 6.9 years, 28 955 participants were diagnosed with malignant cancer. After correction for multiple testing, red and processed meat combined, and processed meat, were each positively associated with colorectal cancer risk [hazard ratio (HR) per 70 g/day higher intake of red and processed meat 1.32, 95% confidence interval 1.14-1.53; HR per 20 g/day higher intake of processed meat 1.18, 1.03-1.31] and red meat was associated with colon cancer risk (HR per 50 g/day higher intake of red meat 1.36, 1.13-1.64). Positive associations of red meat intake with colorectal and prostate cancer, processed meat intake with rectal cancer and poultry intake with cancers of the lymphatic and haematopoietic tissues did not survive multiple testing.Conclusions: Higher intake of red and processed meat was specifically associated with a higher risk of colorectal cancer; there was little evidence that meat intake was associated with risk of other cancers. [ABSTRACT FROM AUTHOR]

Audit regulators around the world have expressed concern over market dominance by Big 4 accounting firms and the potential adverse effect it may have on the quality of audited financial statements. We use cross-country variation in the audit market structure of 42 countries to examine two separate aspects of Big 4 dominance: (1) Big 4 market concentration as a group relative to non-Big 4 auditors; and (2) concentration within the Big 4 group in which one or more of the Big 4 firms is dominant relative to the other Big 4 firms. We find that in countries where the Big 4 (as a group) conduct more listed company audits, both Big 4 and non-Big 4 clients have higher quality audited earnings compared to clients in countries with smaller Big 4 market shares. In contrast, in countries where there is a greater concentration within the Big 4 group, we find that Big 4 clients have lower quality audited earnings compared to countries with more evenly distributed market shares among the Big 4. Thus concentration within the Big 4 group appears to be detrimental to audit quality in a country and of legitimate concern to regulators and policymakers. However, Big 4 dominance per se does not appear to harm audit quality and is in fact associated with higher earnings quality, after controlling for other country characteristics that potentially affect earnings quality. [ABSTRACT FROM AUTHOR]

SUMMARY: Background: Young adults with end‐stage kidney disease (ESKD) are at a pivotal stage of life: progressing through education, seeking employment and developing relationships. We set out to explore how ESKD impacts education and employment attainment in a matched UK and USA patient cohort. Moreover, we aimed to determine if there were significant differences in reported perceptions of impact. Design: A mixed methods design combining previously validated quantitative questionnaire surveys and qualitative semi‐structured interviews. Participants: Young people with ESKD aged 18–30 years (N = 27), attending single‐centre follow‐up in Oxford, UK were matched with 27 comparable young people aged 19–30 years, under follow‐up in Denver, USA. Twelve of these patients from Denver were selected for interview. Measurements: Self‐report questionnaires surveyed patient demographics, educational and employment achievement and experiences. Questionnaire categorical data for matched pairs were analysed using Bowker's test of symmetry. Sequential flow analyses of interview content delineated perception patterns through thematic coding. Results: Sixty percent of non‐student Oxford participants were employed compared with 41% in Denver (p = 0.023). Forty‐four percent of Oxford patients compared with 52% in Denver, reported illness had made it difficult to gain employment (p = 0.88). In Oxford, 32% completed high school as their highest educational achievement, versus 68% in Denver (p = 0.22). Qualitative themes included fatigue, self‐esteem loss, social isolation and low mood. The impact of dialysis and poor understanding from educators/employers resulted in lost work time, and/or limited educational attainment. Conclusion: ESKD profoundly impacts on education and employment of young adults in the United States and United Kingdom, generating substantial barriers. Poor understanding appears prevalent amongst educators and employers. Healthcare providers must recognise these problems and invest resources towards tailored support in order to improve associated psychosocial and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Vegetarians and others who do not eat meat have been observed to have lower incidence rates than meat eaters of some chronic diseases, but it is unclear whether this translates into lower mortality. Objective: The purpose of this study was to describe mortality in vegetarians and comparable nonvegetarians in a large United Kingdom cohort. Design: The study involved a pooled analysis of data from 2 prospective studies that included 60,310 persons living in the United Kingdom, comprising 18,431 regular meat eaters (who ate meat ≥5 times/wk on average), 13,039 low (less-frequent) meat eaters, 8516 fish eaters (who ate fish but not meat), and 20,324 vegetarians (including 2228 vegans who did not eat any animal foods). Mortality by diet group for each of 18 common causes of death was estimated with the use of Cox proportional hazards models. Results: There were 5294 deaths before age 90 in >1 million y of follow-up. There was no significant difference in overall (all-cause) mortality between the diet groups: HRs in low meat eaters, fish eaters, and vegetarians compared with regular meat eaters were 0.93 (95% CI: 0.86, 1.00), 0.96 (95% CI: 0.86, 1.06), and 1.02 (95% CI: 0.94, 1.10), respectively; P-heterogeneity of risks = 0.082. There were significant differences in risk compared with regular meat eaters for deaths from circulatory disease [higher in fish eaters (HR: 1.22; 95% CI: 1.02, 1.46)]; malignant cancer [lower in fish eaters (HR: 0.82; 95% CI: 0.70, 0.97)], including pancreatic cancer [lower in low meat eaters and vegetarians (HR: 0.55; 95% CI: 0.36, 0.86 and HR: 0.48; 95% CI: 0.28, 0.82, respectively)] and cancers of the lymphatic/hematopoietic tissue [lower in vegetarians (HR: 0.50; 95% CI: 0.32, 0.79)]; respiratory disease [lower in low meat eaters (HR: 0.70; 95% CI: 0.53, 0.92)]; and all other causes [lower in low meat eaters (HR: 0.74; 95% CI: 0.56, 0.99)]. Further adjustment for body mass index left these associations largely unchanged. Conclusions: United Kingdom--based vegetarians and comparable nonvegetarians have similar all-cause mortality. Differences found for specific causes of death merit further investigation. [ABSTRACT FROM AUTHOR]

Background: Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic profiles than meat eaters. Objective: We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism between male meat eaters, fish eaters, vegetarians, and vegans from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. Design: In this cross-sectional study, concentrations of metabolites were measured by mass spectrometry in plasma from 379 men categorized according to their diet group. Differences in mean metabolite concentrations across diet groups were tested by using ANOVA, and a false discovery rate-controlling procedure was used to account for multiple testing. Principal component analysis was used to investigate patterns in metabolic profiles. Results: Concentrations of 79% of metabolites differed significantly by diet group. In the vast majority of these cases, vegans had the lowest concentration, whereas meat eaters most often had the highest concentrations of the acylcarnitines, glycerophospholipids, and sphingolipids, and fish eaters or vegetarians most often had the highest concentrations of the amino acids and a biogenic amine. A clear separation between patterns in the metabolic profiles of the 4 diet groups was seen, with vegans being noticeably different from the other groups because of lower concentrations of some glycerophospholipids and sphingolipids. Conclusions: Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of glycerophospholipids and sphingolipids in vegans. [ABSTRACT FROM AUTHOR]

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Background and purpose - There has been a recent trend towards the use of greater femoral head sizes in an attempt to improve function and enhance stability after primary hip replacement. This has been associated with the use of alternative bearings, theoretically to reduce wear and improve implant longevity. Methods - We examined the influence of these variables on patient-reported outcome measures (PROMs) for a consecutive series of primary hip replacements using National Joint Registry (NJR) and PROMs-linked data. To minimize the confounding influence of implant design factors, the single most commonly used brand in England and Wales (DePuy Corail Pinnacle) was examined. Improvement in patient hip-specific outcomes (Oxford hip score, OHS), general health outcomes (Euroqol, EQ-5D), and rates of self-reported complications (bleeding, wound problems, re-admission, and reoperation) were compared for different head sizes (28-mm, 32-mm, and 36-mm) and bearings (metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), and ceramic-on-ceramic (CoC)), adjusting for differences in case mix. Results - At a mean follow-up of 7 months, improvements in OHS and EQ5D index were similar for 28-mm and 36-mm heads. A 32-mm head was associated with poorer function (OHS: 20, 99% CI: 19-21, p = 0.002; EQ5D index: 0.39, 99% CI: 0.36-0.42, p = 0.004), although these small differences may not be of clinical importance. There were no statistically significant benefits of either CoP or CoC bearings compared to a MoP bearing. Complication rates were similar within comparisons of head sizes or bearings. Interpretation - In this short-term study, we did not find any functional benefits of larger head sizes or alternative bearings, after adjusting for other influences. We question their use in routine primary hip replacement given the lack of evidence of improved long-term survival in the literature. [ABSTRACT FROM AUTHOR]

Background Recent trials demonstrate the acceptability and short term efficacy of primary care referral to a commercial weight loss provider for weight management. Commissioners now need information on the optimal duration of intervention and the longer term outcomes and cost effectiveness of such treatment to give best value for money. Methods/Design This multicentre, randomised controlled trial with a parallel design will recruit 1200 overweight adults (BMI ⩾28 kg/m2) through their primary care provider. They will be randomised in a 2:5:5 allocation to: Brief Intervention, Commercial Programme for 12 weeks, or Commercial Programme for 52 weeks. Participants will be followed up for two years, with assessments at 0, 3, 12 and 24 months. The sequential primary research questions are whether the CP interventions achieve significantly greater weight loss from baseline to 12 months than BI, and whether CP52 achieves significantly greater weight loss from baseline to 12 months than CP12. The primary outcomes will be an intention to treat analysis of between treatment differences in body weight at 12 months. Clinical effectiveness will be also be assessed by measures of weight, fat mass, blood pressure and at each time point and biochemical risk factors at 12 months. Self-report questionnaires will collect data on psychosocial factors associated with adherence, weight-loss and weight-loss maintenance. A within-trial and long-term cost-effectiveness analysis will be conducted from an NHS perspective. Qualitative methods will be used to examine the participant experience. Discussion The current trial compares the clinical and cost effectiveness of referral to a commercial provider with a brief intervention. This trial will specifically examine whether providing longer weight-loss treatment without altering content or intensity (12 months commercial referral vs. 12 weeks) leads to greater weight loss at one year and is sustained at 2 years. It will also evaluate the relative cost-effectiveness of the three interventions. This study has direct implications for primary care practice in the UK and will provide important information to inform the decisions of practitioners and commissioners about service provision. [ABSTRACT FROM AUTHOR]

Background: Vegetarian diets might affect the risk of cancer. Objective: The objective was to describe cancer incidence in vegetarians and nonvegetarians in a large sample in the United Kingdom. Design: This was a pooled analysis of 2 prospective studies including 61,647 British men and women comprising 32,491 meat eaters, 8612 fish eaters, and 20,544 vegetarians (including 2246 vegans). Cancer incidence was followed through nationwide cancer registries. Cancer risk by vegetarian status was estimated by using multivariate Cox proportional hazards models. Results: After an average follow-up of 14.9 y, there were 4998 incident cancers: 3275 in meat eaters (10.1%), 520 in fish eaters (6.0%), and 1203 in vegetarians (5.9%). There was significant heterogeneity between dietary groups in risks of the following cancers: stomach cancer [RRs (95% CIs) compared with meat eaters: 0.62 (0.27, 1.43) in fish eaters and 0.37 (0.19, 0.69) in vegetarians; P-heterogeneity = 0.006], colorectal cancer [RRs (95% CIs): 0.66 (0.48, 0.92) in fish eaters and 1.03 (0.84, 1.26) in vegetarians; P-heterogeneity = 0.033], cancers of the lymphatic and hematopoietic tissue [RRs (95% CIs): 0.96 (0.70, 1.32) in fish eaters and 0.64 (0.49, 0.84) in vegetarians; P-heterogeneity = 0.005], multiple myeloma [RRs (95% CIs): 0.77 (0.34, 1.76) in fish eaters and 0.23 (0.09, 0.59) in vegetarians; P-heterogeneity = 0.010], and all sites combined [RRs (95% CIs): 0.88 (0.80, 0.97) in fish eaters and 0.88 (0.82, 0.95) in vegetarians; P-heterogeneity = 0.0007]. Conclusion: In this British population, the risk of some cancers is lower in fish eaters and vegetarians than in meat eaters. [ABSTRACT FROM AUTHOR]

The importance of environmental contamination in the spread of healthcare associated infections (HAI) has generated a need for high performance disinfectants. Currently chlorine-based disinfectants are the products of choice, a position reflected in UK guidance. The aim of this research was to evaluate a peracetic acid (PAA) generating disinfectant to determine if it provided a realistic alternative to commonly used chlorine-based disinfectants. The European standards framework was employed in this study and enhanced where appropriate by reducing the contact times, increasing the organic and microbial challenge, and changing the organisms involved. When tested against bacteria and spores PAA provided similar or better performance than currently employed levels of chlorine. This was particularly the case in the presence of an organic challenge or dried surface contamination. The chlorine disinfectants only demonstrated superior performance in the case of fungal spores. These results suggest that PAA generating products provide an effective alternative to chlorine-based products up to 10,000 ppm free available chlorine. These products have superior performance in situations with spore borne, surface contamination and high organic challenge. In cases where filamentous fungi are a concern, high levels of PAA (>5,000 ppm) would be required to match the performance of chlorine based disinfectants. [ABSTRACT FROM AUTHOR]

Objective Both cigarette smoking and use of exogenous hormones are associated with changes in regional distribution of body fat, but their combined effects are less investigated. We examined the interrelation between smoking, exogenous hormones and fat distribution in premenopausal and postmenopausal women. Method We used data from 20 962 women without known cardiovascular disease (CVD) who were employees of a major department store in Britain. They completed a health questionnaire and attended a clinical examination that included waist and hip circumference measurements. The cross-sectional analyses were conducted using linear regression models. Results Cigarette smoking, particularly smoking ≥20 cigarettes/day, was associated with larger waist circumference and higher waist/hip ratio (WHR) in pre- and postmenopausal women after adjusting for potential confounding factors (all P < 0·001). Premenopausal women using combined oral contraceptive (COC) and postmenopausal women using oestrogen-only hormone replacement therapy (HRT) had lower WHR than non-hormone users in both smokers and nonsmokers. However, smokers had higher WHR than nonsmokers in both groups of hormone users and nonusers. There was no significant interaction between smoking and hormone use in premenopausal and postmenopausal women ( P > 0·05). Conclusion Although exogenous hormones use was related to a more favourable fat distribution in women, smoking was associated with greater abdominal fat accumulation. [ABSTRACT FROM AUTHOR]

Summary: We undertook a service evaluation to establish how oropharyngeal dysphagia is managed in head and neck cancer patients receiving radiotherapy in the United Kingdom. A web-based survey including 23 open and closed questions was distributed to Speech and Language Therapy (SLT) teams via a national network of Royal College of Speech and Language Therapists (RCSLT) special interest groups with members involved in head and neck cancer care. Forty-six teams responded to the survey and 89% completed the questionnaire fully. Fifty percent (n =21/42) of the SLT teams reported routinely seeing patients prior to commencing radiotherapy. Baseline oromotor assessment (85.7% (n =36/42)), clinical dysphagia assessment (90.5% (n =38/42)) and information provision on the potential treatment effects on swallowing (97.6% (n =41/42)) and communication ability (85.7% (n =36/42)) were the most common components of initial evaluation. In keeping with expert opinion and emerging evidence, prophylactic swallowing exercises were administered by 71.4% (n =30/42) of teams targeting specific aspects of swallowing, although the nature, intensity and duration of programmes varied. A range of measures are used to monitor progress during treatment. Our survey highlighted that resource limitations affect service provision with some teams managing the consequences of treatment rather than proactive multidisciplinary intervention prior to and during treatment. Cancer- and treatment-related dysphagia can impact significantly on a broad range of outcomes following radiotherapy. There is variability in dysphagia service provision to patients before, during and following treatment. Comprehensive evaluation of swallowing function prior to treatment and proactive management can yield benefits for patients, inform multidisciplinary case management and support those involved in clinical trials to accurately determine treatment effects. [Copyright &y& Elsevier]

A knowledge of the limitations of automated platelet counting is essential for the effective care of thrombocytopenic patients and management of platelet stocks for transfusion. For this study, 29 external quality assessment specimen pools with platelet counts between 5 and 64 x 109/L were distributed to more than 1,100 users of 23 different hematology analyzer models. The same specimen pools were analyzed by the international reference method (IRM) for platelet counting at 3 reference centers. The IRM values were on average lower than the all-methods median values returned by the automated analyzers. The majority (~67%) of the automated analyzer results overestimated the platelet count compared with the IRM, with significant differences in 16.5% of cases. Performance differed between analyzer models. The observed differences may depend in part on the nature of the survey material and analyzer technology, but the findings have implications for the interpretation of platelet counts at levels of clinical decision making. [ABSTRACT FROM AUTHOR]

The article reports on the guidelines concerning transient loss of consciousness (TLoC), published by the National Institute for Health and Clinical Excellence (NIHCE), a health authority of Great Britain's health care system National Health Service, in August 2010. It informs that NIHCE made the guidelines for addressing inadequacies in the assessment and diagnosis of TLoC in persons who present to health care professionals. The guidelines focus on TLoC in persons of 16 years of age or more.

A unique facility for engineering and biological research has been established with the aim of improving fundamental understanding of the effects of climate change on slopes. This paper describes the building and monitoring of a full-scale embankment representative of UK infrastructure, the planting and monitoring of representative vegetation, and the construction of a system of sprinklers and covers to control climate. A summary of the results of the first experiments simulating predicted future UK climate and the response of the embankment is also presented. The information that has begun to be gathered is providing data related to the failure modes anticipated as a result of climate change and hence on the sustainability of UK infrastructure slopes. [ABSTRACT FROM AUTHOR]

The UK biological and engineering impacts of climate change on slopes (Bionics) project was funded to bring together key stake-holder and academics to research advanced procedures for maintaining serviceability and safety of strategic embankments and cuttings in addition to advancing the science base. This paper summarises some of the evidence that suggests climate change will have an effect on the behaviour of infrastructure slope sand their management, and provides an overview of future climate scenarios for the UK. It also shows how climate data have been used in numerical and physical models and full-scale tests within the Bionics project to begin to determine the magnitude and timing of the effects of climate change on infrastructure slopes. [ABSTRACT FROM AUTHOR]

Typical antipsychotics are effective in the management of schizophrenia, but are associated with troublesome adverse effects which may lead to treatment discontinuation and relapse. Long-acting depot formulations of these drugs improve patient compliance, but do not reduce the incidence of adverse effects. There is evidence to suggest that newer atypical antipsychotic drugs have a reduced propensity to induce movement disorders and are associated with a modest reduction in relapse rates. The introduction of risperidone long-acting injection (RLAI) provided clinicians with the first long-acting formulation of an atypical antipsychotic. Objective. The aim of this study was to investigate the outcomes of patients from an acute mental health trust who received RLAI during the 18-month period following its licensing in the UK in order to examine measures of clinical effectiveness, and reasons for treatment discontinuation. Methods. Data were collected retrospectively from medical notes. Results. Fifty-nine patients were included in the study, and at the time of data collection 32 (54%) had discontinued treatment. The most common reason for discontinuation was lack of effectiveness, although all of the patients who discontinued due to lack of response were treatment resistant. RLAI appeared to be well tolerated, with only 12% of patients discontinuing due to adverse effects. Thirty-eight percent of the patients treated with RLAI showed a good response as measured by discharge from inpatient setting, and of the 22 outpatients at time of data collection, five had one re-hospitalisation during the study period. Conclusion. This study concludes that RLAI appears to be well tolerated, and shows some effectiveness in the treatment of schizophrenia, but may not be effective for patients who are treatment resistant. [ABSTRACT FROM AUTHOR]

Background: In April 2004, an incentive based contract was introduced to UK primary care. An important element of the new contract is the ability to exclude individuals from quality indicators for a variety of reasons (known as 'exception reporting'). Exception of patients with stroke or TIA from the recording and achievement of quality indicators may have important consequences in terms of stroke recurrence and mortality. Methods: A cross-sectional retrospective analysis of anonymised patient data was performed using 312 Scottish primary care practices. Results: Patients recorded as unsuitable for inclusion in the contract were more likely to be female (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.36—1.68), older (>75 years:OR 3.15, 95%CI 2.69—3.69), and have dementia (OR 4.40, 95%CI 3.57—5.43) when compared to those patients without such a code. Patients were less likely to be older (>75 years:OR 0.70, 95%CI 0.56—0.87) and were more likely to be from the most deprived are as of Scotland (Quintile 5: OR 2.02, 95%CI 1.50—2.70) if they refused to attend for review or did not reply to letters asking for attendance at primary care clinics. Patients with multiple co-morbidities were more likely to have exclusions for achieving diagnostic clinical targets such as cholesterol control (3 or more co-morbidities: OR 3.37, 95%CI 2.50—4.50). Conclusion: Scottish practices have appeared to use exception reporting appropriately by excluding patients who are older or have dementia. However, younger or more socio-economically deprived patients were more likely to be recorded as having refused to attend for review or not replying to letters asking for attendance at primary care clinics. It is important for primary care practices to identify and monitor these individuals so that all patients fully benefit from the implementation of an incentive based contract and receive appropriate clinical care to prevent stroke recurrence, further disability and mortality. [ABSTRACT FROM AUTHOR]

The IMAGINE programme within the UK's National Health Service (NHS) was designed to raise the quality of information management and technology (IM&T) strategic thinking amongst participating units in what was the Trent Health Region. The national Facilitated Approach to Information Management (FAIM) initiative followed, with the intention of guiding the management team of individual NHS units in their development of their IM&T strategy. Each of these initiatives called for a means of measuring the maturity at unit level of both the IM&T endeavour and the extent of the strategic alignment between the business and IM&T strategies. This paper describes a research instrument that was developed in IMAGINE and used in FAIM to determine a unit's maturity in IM&T and IM&T strategic thinking. The research instrument is presented, together with a typical response document that summarises a unit's IM&T maturity. [ABSTRACT FROM AUTHOR]

Examines the results of the Oxford Vegetarian Study between 1980 and 1984 in Great Britain. Comparison of total- and low-density lipoprotein (LDL) concentrations of vegetarians versus meat eaters; Near similarity of total- and LDL concentration between vegetarians and fish eaters; Mortality by diet group; Mortality in relation to foods, animal fats and dietary fiber; Other aspects of health and disease.

Gives a descriptive summary of activity in what was the Trent Region of Great Britain's National Health Services. Development of IMAGINE, a program of action learning on the topic of strategic thinking in information management and technology; Description of the various phases of IMAGINE.

The article focuses on the strategic planning and management of chemical industry firm Fisons group of companies in Great Britain. The real beginning of the present Fisons group of companies can be said to lie in the amalgamation in 1929 of two agricultural fertiliser companies to form Fison Packard and Prentice. Up to the 1930s, growth had been by market penetration through horizontal integration in the fertiliser business. The company expanded in the 1930s. The most important strategic acquisition was that of the chemical industry firm Anglo-Continental Guano Works Ltd, in 1936, which effectively doubled the size of the company. Anglo-Continental was itself a large amalgamation of mainly fertiliser manufacturers and related companies. However, it also contained the Loughborough-based Genatosan company, a manufacturer of Pharmaceuticals and fine chemicals, which constituted the entry of Fisons into the Pharmaceuticals business. The next key acquisition occurred in 1947. This acquisition was important. The synergy with its current operations was such that the customers would be broadly the same as those for its fertilisers, with a common distribution channel, and there was a need to manage the concommitant R&D, in which Fisons would claim some expertise.

The article presents a discussion on those factors which condition the use firms make of human resource strategies aimed at enhancing their ability to respond flexibly to an increasingly changing environment. In particular, it focuses on the variations made by firms in their pursuit of greater levels of numerical flexibility. Numerical flexibility refers to the dimensioning of manpower, not least through the use of temporary labour relative to permanent labour, which will normally vary according to fluctuating conditions faced by firms. This contrasts with functional flexibility which regards the question of how firms deploy and redeploy their internal human resources in order to cope with changing external demands. Employees engaged in pursuits of functional flexibility are normally regarded as core employees with long-term employment status, as opposed to the more peripheral employees involved in pursuits of numerical flexibility. The latter kind of pursuits will not simply be a rational, firm-based response to market conditions, but will at least be a product of the institutional context within which firms are embedded. In order to test this, developments in Norwegian and Great Britain firms are compared.

The article presents a summary of guidance issued by the National Institute for Health and Clinical Excellence (NICE) on the management of transient loss of consciousness in people aged 16 and over. It enumerates important abnormalities in a 12 lead electrocardiogram in patients with transient loss of consciousness. It cites several factors that must be considered by physicians during the initial assessment of a patient. Clinicians are also advised to be aware of the importance of information gathering for them to have confidence to diagnose simple faints.

A recurring motto from the Tony Blair government in the UK was “Education, Education, Education.” An appropriate exhortation for the biomedical sciences would be “Standardization, Standardization, Standardization.” Inevitably, the two go hand in hand, and the challenge we face is how to encourage researchers to comply with existing or emerging standard terminologies and nomenclatures. This is both an educational and a regulatory task, one in which it is vital to succeed if we are to efficiently and accurately share and use the huge volume of data emerging in the biosciences.Journal of Investigative Dermatology (2009) 129, 1599–1601. doi:10.1038/jid.2009.81 [ABSTRACT FROM AUTHOR]

Compares analysis of predicted coronary heart disease risk in England based on Framingham study risk appraisal models published in 1991 and 2000. Methods; Results; Conclusion that coronary risk calculations with the two models were generally similar, but that a significant number of people who met criteria for drug treatment based on 1991 models would not meet the equivalent criteria based on 2000 models.

The mortality and working years lost from liver cirrhosis present a significant challenge both in the UK and globally. The recent British Association for the Study of the Liver (BASL) annual meeting highlighted the inequities present across the UK in terms of the burden of liver disease and access to specialist services. Innovative new ways of working and novel technologies are needed to address the growing demands of the specialty, while bearing in mind the need for sustainable and patient-focused interventions. [ABSTRACT FROM AUTHOR]

Prognosis and management differ between familial chylomicronaemia syndrome (FCS), a rare autosomal recessive disorder, and multifactorial chylomicronaemia syndrome (MCS) or severe mixed hyperlipidaemia. A clinical scoring tool to differentiate these conditions has been devised but not been validated in other populations. The objective of this study was to validate this score in the UK population and identify any additional factors that might improve it. A retrospective validation study was conducted using data from 151 patients comprising 75 FCS and 76 MCS patients. All participants had undergone genetic testing for genes implicated in FCS. Validation was performed by standard methods. Additional variables were identified from clinical data by logistic regression analysis. At the recommended FCS score threshold ≥10 points, the sensitivity and specificity of the score in the UK population were 96% and 75%, respectively. The receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.88 (95% CI 0.83–0.94, p < 0.001). This study identified non-European (predominantly South Asian) ethnicity, parental consanguinity, body mass index (BMI) < 25 kg/m2, and recurrent pancreatitis as additional positive predictors, while BMI >30 kg/m2 was found to be a negative predictor for FCS. However, inclusion of additional FCS predictors had no significant impact on performance of standard FCS score. Our study validates the FCS score in the UK population to distinguish FCS from MCS. While additional FCS predictors were identified, they did not improve further the score diagnostic performance. [Display omitted] • The familial chylomicronaemia syndrome (FCS) score performs well and is valid for the UK population. • The optimal cut-off for score in the UK population is at 10 points with sensitivity and specificity of 96% and 75%, respectively. • The FCS score efficiently screens for FCS in resource-limited settings, facilitating patient selection for genetic testing. • Integrating more clinical FCS predictors into the FCS score did not enhance score's performance. [ABSTRACT FROM AUTHOR]

The UK Simon Broome (SB) familial hypercholesterolaemia (FH) register previously reported 3-fold higher standardised mortality ratio for cardiovascular disease (CVD) in women compared to men from 2009 to 2015. Here we examined sex differences in CVD morbidity in FH by national linkage of the SB register with Hospital Episode Statistics (HES). Of 3553 FH individuals in the SB register (aged 20–79 years at registration), 2988 (52.5% women) had linked HES records. Standardised Morbidity Ratios (SMbR) compared to an age and sex-matched UK general practice population were calculated [95% confidence intervals] for first CVD hospitalisation in HES (a composite of coronary heart disease (CHD), myocardial infarction (MI), stable or unstable angina, stroke, TIA, peripheral vascular disease (PVD), heart failure, coronary revascularisation interventions). At registration, men had significantly (p < 0.001) higher prevalence of previous CHD (24.8% vs 17.6%), previous MI (13.2% vs 6.3%), and were commenced on lipid-lowering treatment at a younger age than women (37.5 years vs 42.3 years). The SMbR for composite CVD was 6.83 (6.33–7.37) in men and 7.55 (6.99–8.15) in women. In individuals aged 30–50 years, SMbR in women was 50% higher than in men (15.04 [12.98–17.42] vs 10.03 [9.01–11.17]). In individuals >50 years, SMbR was 33% higher in women than men (6.11 [5.57–6.70] vs 4.59 [4.08–5.15]). Excess CVD morbidity due to FH remains markedly elevated in women at all ages, but especially those aged 30–50 years. This highlights the need for earlier diagnosis and optimisation of lipid-lowering risk factor management for all FH patients, with particular attention to young women with FH. Image 1 • Males with familial hypercholesterolaemia (FH) had more cardiovascular disease (CVD) risk factors and were commenced on lipid-lowering therapy at a younger age, than females with FH. • Individuals with FH had excess rates of hospitalisations for CVD, compared to the general population of non-FH individuals. • Excess CVD morbidity due to FH was higher in women than men aged 30 years and over, but especially in those aged 30–50 years. [ABSTRACT FROM AUTHOR]

Abstract Background and aims The International Atherosclerosis Society (IAS) has proposed that patients with "severe" FH (SFH) would warrant early and more aggressive cholesterol-lowering treatment such as with PCSK9 inhibitors. SFH is diagnosed if LDL-cholesterol (LDLC) > 10 mmol/L, or LDLC >8.0 mmol/L plus one high-risk feature, or LDLC >5 mmol/L plus two high-risk features. Here we compare CHD mortality in SFH and non-SFH (NSFH) patients in the UK prospective Simon Broome Register since 1991, when statin use became routine. Methods 2929 definite or possible PFH patients (51% women) aged 20–79 years were recruited from 21 UK lipid clinics and followed prospectively between 1992 and 2016. The excess CHD standardised mortality ratio (SMR) compared to the England and Wales population was calculated (with 95% confidence intervals). Results 1982 (67.7%) patients met the SFH definition. Compared to the non-SFH, significantly (p < 0.001) more SFH patients had diagnosed CHD at baseline (24.6% vs. 17.5%), were current smokers (21.9% vs 10.2%) and had a BMI > 30 kg/m2 (14.9% vs. 7.8%). The SMR for CHD mortality was significantly (p = 0.007) higher for SFH (220 (184–261) (34,134 person years, 129 deaths observed, vs. 59 expected) compared to NSFH of 144 (98–203) (15,432 person years, 32 observed vs. 22 expected). After adjustment for traditional risk factors, the Hazard Ratio for CHD mortality in SFH vs. NSFH was 1.22 (0.80–1.87) p = 0.36, indicating that the excess risk was largely accounted for by these factors. Conclusions CHD mortality remains elevated in treated FH, especially for SFH, emphasising the importance of optimal lipid-lowering and management of other risk factors. Graphical abstract Image 1 Highlights • Patients with IAS-defined "severe" FH (SFH) are at highest risk of future CHD. • In the UK Simon Broome FH Register ∼70% meet the SFH criteria. • Those with SFH have 64% higher CHD mortality than non SFH patients. • This is explained by their higher classical risk factors including untreated LDL-C. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to analyze the impact of a structured educational intervention on the implementation of guideline-recommended pain, agitation, and delirium (PAD) assessment., Methods: This was a prospective, multinational, interventional before-after trial conducted at 12 intensive care units from 10 centers in Germany, Austria, Switzerland, and the UK. Intensive care units underwent a 6-week structured educational program, comprising online lectures, instructional videos, educational handouts, and bedside teaching. Patient-level PAD assessment data were collected in three 1-day point-prevalence assessments before (T1), 6 weeks after (T2), and 1 year after (T3) the educational program., Results: A total of 430 patients were included. The rate of patients who received all three PAD assessments changed from 55% (107/195) at T1 to 53% (68/129) at T2, but increased to 73% (77/106) at T3 (p = 0.003). The delirium screening rate increased from 64% (124/195) at T1 to 65% (84/129) at T2 and 77% (82/106) at T3 (p = 0.041). The pain assessment rate increased from 87% (170/195) at T1 to 92% (119/129) at T2 and 98% (104/106) at T3 (p = 0.005). The rate of sedation assessment showed no signficiant change. The proportion of patients who received nonpharmacological delirium prevention measures increased from 58% (114/195) at T1 to 80% (103/129) at T2 and 91% (96/106) at T3 (p < 0.001). Multivariable regression revealed that at T3, patients were more likely to receive a delirium assessment (odds ratio [OR] 2.138, 95% confidence interval [CI] 1.206-3.790; p = 0.009), sedation assessment (OR 4.131, 95% CI 1.372-12.438; p = 0.012), or all three PAD assessments (OR 2.295, 95% CI 1.349-3.903; p = 0.002) compared with T1., Conclusions: In routine care, many patients were not assessed for PAD. Assessment rates increased significantly 1 year after the intervention. Clinical trial registration ClinicalTrials.gov: NCT03553719., (© 2023. The Author(s).)

Aims: This study aimed to assess the impact of a National Reporting Indicator (NRI) on rates of reporting of suspected adverse drug reactions using the Yellow Card scheme following the introduction of the NRI in Wales (UK) in April 2014., Methods: Yellow Card reporting data for general practitioners and other reporting groups in Wales and England for the financial years 2014-15 (study period 1) and 2015-16 (study period 2) were obtained from the Medicines and Healthcare Products Regulatory Agency and compared with those for 2013-14 (pre-NRI control period)., Results: The numbers of Yellow Cards submitted by general practitioners in Wales were 271, 665 and 870 in the control period, study period 1 and study period 2, respectively. This is equivalent to an increase of 145% in study period 1 and 221% in study period 2 compared with the 12-month control period (2013-14). Corresponding increases in England were 17% and 37%, respectively (P < .001 chi-squared test). The numbers of Yellow Cards submitted by other groups in Wales were 906, 795 and 947 in each of the study periods., Conclusions: Introduction of the NRI corresponded with a significant increase in the number of Yellow Cards submitted by general practitioners in Wales. General practitioner reporting rates continued to increase year on year through to 2018-19 with the NRI still in place. No concomitant change was found in reporting rates by other groups in the health boards in Wales., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Non-alcoholic fatty liver disease (NAFLD) is common, affecting approximately 25% of the general population. The evidence base for the investigation and management of NAFLD is large and growing, but there is currently little practical guidance to support development of services and delivery of care. To address this, we produced a series of evidence-based quality standard recommendations for the management of NAFLD, with the aim of improving patient care. A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group produced the recommendations, which cover: management of people with, or at risk of, NAFLD before the gastroenterology or liver clinic; assessment and investigations in secondary care; and management in secondary care. The quality of evidence for each recommendation was evaluated by the Grading of Recommendation Assessment, Development and Evaluation tool. An anonymous modified Delphi voting process was conducted individually by each member of the group to assess the level of agreement with each statement. Statements were included when agreement was 80% or greater. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice. It is hoped that services will review their practice against our recommendations and key performance indicators and institute service development where needed to improve the care of patients with NAFLD., Competing Interests: Declaration of interests SM personal fees outside the submitted work from Gilead, Intercept, and Novo Nordisk. MJA has received fees for consultancy, advisory boards, and speaking from Novo Nordisk and Norgine. JFC has received fees for consultancy, advisory boards, and speaking from Intercept, Novo Nordisk, canNASH, and AstraZeneca. EAT has received fees for advisory boards and speaking from Falk Pharma, Intercept, Gilead, and Pfizer. AS has received fees for consultancy and speaking from Siemens. STB has received payment for advisory boards and speaking from AbbVie, Gilead, and Intercept. RJA has received honoraria for speaking and advisory board membership from Falk Pharma, Gilead, Intercept, Novartis, and Norgine. DM has received fees for consultancy from Intercept. PNB has received speaking and educational fees from Takeda. RP has received speaking fees and advisory board fees from Siemens, Norgine, Novo Nordisk, and Shionogi. AY has taken part in advisory boards and consultancy for Intercept and Novo Nordisk. HJ has received speaker fees from Intercept. WA has received fees for consultancy and lecturing from AstraZeneca, Janssen, Novo Nordisk, Gilead Science, Intercept, and Coherus and has received competitive grant funding from GSK and Gilead Science. LC has received personal fees outside the submitted work from Norgine, Intercept, and Novo Nordisk. JT has received personal fees outside the submitted work from Novartis and Poxel. QMA is coordinator of the IMI2 LITMUS consortium, which is funded by the EU Horizon 2020 programme and EFPIA. He reports research grant funding from Allergan/Tobira, AstraZeneca, GlaxoSmithKline, Glympse Bio, Novartis Pharma AG, Pfizer Ltd, and Vertex, consultancy on behalf of Newcastle University for 89Bio, Allergan/Tobira, Altimmune, AstraZeneca, Axcella, Blade, BMS, BNN Cardio, Cirius, CymaBay, EcoR1, E3Bio, Eli Lilly & Company, Galmed, Genentech, Genfit, Gilead, Grunthal, HistoIndex, Indalo, Intercept, Inventiva, IQVIA, Janssen, Madrigal, MedImmune, Medpace, Metacrine, NGMBio, North Sea Therapeutics, Novartis, Novo Nordisk A/S, PathAI, Pfizer Ltd, Poxel, ProSciento, Raptor Pharma, Roche, Servier, Terns, The Medicines Company, and Viking Therapeutics, and speaker fees from Abbott Laboratories, Allergan/Tobira, BMS, Clinical Care Options, Falk, Fishawack, Genfit SA, Gilead, Integritas Communications, Kenes, and MedScape. All other authors declared no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Patients' decisions to undergo major surgery such as orthognathic treatment are not just about how the decision is made but what influences the decision., Objectives: The primary objective of the study was to identify the key processes involved in patients' experience of decision making for orthognathic treatment., Methods: This study reports some of the findings of a larger grounded theory study. Data were collected through face-to-face interviews of patients who were seen for orthognathic treatment at a teaching hospital in the United Kingdom. Twenty-two participants were recruited (age range 18-66 y), of whom 12 (male = 2, female = 10) were 6 to 8 wk postsurgery, 6 (male = 2, female = 4) were in the decision-making stage, and 4 (male = 0, female = 4) were 1 to 2 y postsurgery. Additional data were also collected from online blogs and forums on jaw surgery. The data analysis stages of grounded theory methodology were undertaken, including open and selective coding., Results: The study identified the central role of dental care professionals (DCPs) in several underlying processes associated with decision making, including legitimating, mediating, scheduling, projecting, and supporting patients' decisions. Six categories were related to key aspects of decision making. These were awareness about their underlying dentofacial problems and treatment options available, the information available about the treatment, the temporality of when surgery would be undertaken, the motivations and expectation of patients, social support, and fear of the surgery, hospitalization, and potentially disliking their new face., Conclusion: The decision-making process for orthognathic treatment is complex, multifactorial, and heavily influenced by the role of DCPs in patient care. Understanding the magnitude of this role will enable DCPs to more clearly participate in improving patients' decision-making process. The findings of this study can inform future quantitative studies., Knowledge Transfer Statement: The results of this study can be used both for informing clinical practice around enabling decision making for orthognathic treatment and also for designing future research. The findings can better inform clinicians about the importance of their role in the patients' decision-making process for orthognathic treatment and the means to improve the patient experience. It is suggested that further research could be conducted to measure some of the key constructs identified within our grounded theory and assess how these change during the treatment process.

Purpose: The objective of this virtual study was to simulate a full cycle and assess the costs and benefits to a couple with a reciprocal translocation, using current techniques for preimplantation genetic testing and comparing reporting every chromosome with only reporting those involved in the rearrangement., Methods: A simulation was constructed for women under the age of 35 years, where vitrified-warmed embryos were transferred one at a time in a first full cycle following preimplantation genetic testing using next-generation sequencing and sampling the trophectoderm at the blastocyst stage. The effect on pregnancy outcomes (live birth, clinical miscarriage and biochemical pregnancy) was evaluated for different reporting strategies for embryo transfer to (i) report only the rearranged chromosomes and transfer embryos with a normal or balanced test result for the translocation (targeted), or (ii) report every chromosome and exclude from transfer all embryos with an abnormal test result (exclusion), or (iii) exclude only those consistent with an unbalanced translocation and/or unrelated non-mosaic whole-chromosome aneuploidy and assign those with samples consistent with a normal or balanced translocation complement and unrelated mosaic aneuploidy or segmental imbalance (embryos of uncertain reproductive potential) a lower transfer priority (ranking). The number of individual women whom might benefit by avoiding an adverse pregnancy outcome (biochemical pregnancy, clinical miscarriage) or be disadvantaged by not achieving a live birth was evaluated. The financial cost of the different reporting strategies and the time taken to complete a cycle were also considered., Results: The simulation showed that compared to only reporting the translocation chromosomes (targeted reporting), testing every chromosome and ranking embryos by test result for transfer was a cost-effective strategy to avoid an adverse pregnancy without compromising the chance of a live birth. Excluding from transfer embryos with a test result consistent with a normal or balanced translocation complement of uncertain reproductive potential was an inferior strategy because it resulted in fewer live births from a full cycle. Reporting only the translocation chromosomes was an inferior strategy because it was less effective than ranked reporting of every chromosome to avoid an adverse pregnancy. Compared to targeted reporting, the ranked and exclusion strategies marginally reduced the overall cost and time taken to complete a full cycle. The ranking strategy avoided 1 adverse pregnancy for 12 cycles started, compared to 1 in 10 for the exclusion strategy which also resulted in 1 in 22 fewer women achieving a live birth. A minority (< 10%) of couples benefited by avoiding at least 1 adverse pregnancy whilst also reducing the time and cost for a complete cycle; most (> 70% ) couples received no benefit additional to targeted reporting and had the same outcome for pregnancy, time and cost., Conclusions: The primary objective of PGT-SR for couples with a reciprocal translocation is to avoid a pregnancy with a chromosomally unbalanced product of the translocation and to reduce the risk of miscarriage, at least to that expected for couples with normal karyotypes. Trophectoderm sampling at the blastocyst stage with testing using NGS is an effective approach; however, ranking and excluding from transfer embryos with abnormal test results for unrelated chromosomes is problematical and is likely to be detrimental to achieving a live birth. Targeted reporting, where only the results of the chromosomes involved in the translocation are known, should be preferred to achieve a live birth. A best effort should be made to follow up and investigate all pregnancies following PGT-SR. Once the reproductive outcome is known (biochemical pregnancy, clinical pregnancy, live birth), the chromosomes unrelated to the rearrangement can be analysed as an experimental study. The risk/benefit of avoiding an adverse pregnancy vs reducing the chance of a healthy delivery should be a decision for each individual couple and informed by appropriate genetic counselling for their specific translocation and history., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Differences in health outcomes between meat-eaters and non-meat-eaters might relate to differences in dietary intakes between these diet groups. We assessed intakes of major protein-source foods and other food groups in six groups of meat-eaters and non-meat-eaters participating in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study. The data were from 30,239 participants who answered questions regarding their consumption of meat, fish, dairy or eggs and completed a food frequency questionnaire (FFQ) in 2010. Participants were categorized as regular meat-eaters, low meat-eaters, poultry-eaters, fish-eaters, vegetarians and vegans. FFQ foods were categorized into 45 food groups and analysis of variance was used to test for differences between age-adjusted mean intakes of each food group by diet group. Regular meat-eaters, vegetarians and vegans, respectively, consumed about a third, quarter and a fifth of their total energy intake from high protein-source foods. Compared with regular meat-eaters, low and non-meat-eaters consumed higher amounts of high-protein meat alternatives (soy, legumes, pulses, nuts, seeds) and other plant-based foods (whole grains, vegetables, fruits) and lower amounts of refined grains, fried foods, alcohol and sugar-sweetened beverages. These findings provide insight into potential nutritional explanations for differences in health outcomes between diet groups., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Background: The global prevalence of diabetes is high and rapidly increasing. Some previous studies have found that vegetarians might have a lower risk of diabetes than non-vegetarians., Objective: We examined the association between vegetarianism and risk of hospitalisation or death with diabetes in a large, prospective cohort study of British adults., Methods: The analysed cohort included participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study who were diabetes free at recruitment (1993-2001), with available dietary intake data at baseline, and linked hospital admissions and death data for diabetes over follow-up (n = 45,314). Participants were categorised as regular meat eaters (≥50 g per day: n = 15,181); low meat eaters (<50 g of meat per day: n = 7615); fish eaters (ate no meat but consumed fish: n = 7092); and vegetarians (ate no meat or fish, including vegans: n = 15,426). We used multivariable Cox proportional hazards models to assess associations between diet group and risk of diabetes., Results: Over a mean of 17.6 years of follow-up, 1224 incident cases of diabetes were recorded. Compared with regular meat eaters, the low meat eaters, fish eaters, and vegetarians were less likely to develop diabetes (hazard ratio (HR) = 0.63, 95% confidence interval (CI) 0.54-0.75; HR = 0.47, 95% CI 0.38-0.59; and HR = 0.63, 95% CI 0.54-0.74, respectively). These associations were substantially attenuated after adjusting for body mass index (BMI) (low meat eaters: HR = 0.78, 95% CI 0.66-0.92; fish eaters: HR = 0.64, 95% CI 0.51-0.80; and vegetarians: HR = 0.89, 95% CI 0.76-1.05)., Conclusions: Low meat and non-meat eaters had a lower risk of diabetes, in part because of a lower BMI.

Background and Aims: Guidelines for cholesterol-lowering medication either advocate fixed dose statin treatment without low density lipoprotein (LDL) cholesterol targets or treatment aimed at LDL cholesterol goals. The decrease in LDL cholesterol concentration determines the reduction in atherosclerotic cardiovascular disease (CVD) risk., Methods: As indices of the effectiveness of reductions in LDL cholesterol concentration achieved by the various guidelines, the number of CVD events prevented in 100 people during 10 years of treatment (N 100 ) and the number of people, who must be treated for 10 years to prevent one CVD event (NNT), were calculated taking into account both CVD risk and pretreatment LDL cholesterol concentration. That our method of calculating NNT and N 100 , could be extended to statin regimens of different intensity or of statin combined with adjunctive cholesterol-lowering medication was demonstrated by meta-analysis., Results: Reductions in LDL-cholesterol concentration are determined by the choice and dose of medication and by the pre-treatment LDL-cholesterol concentration. At similar CVD risk, whatever cholesterol-lowering strategy is adopted, people with higher pre-treatment LDL cholesterol benefit more than those with lower levels. Fixed dose statin regimens are less effective than target LDL cholesterol levels of 1.8 or 1.4 mmol/l when pre-treatment LDL-cholesterol levels exceed 4 mmol/l. However, fixed dose statin is more effective in people with lower initial LDL cholesterol. The predicted NNT and N 100 were closely related to the observed reduction in CVD risk in our meta-analysis., Conclusions: In hypercholesterolaemia, aiming for LDL cholesterol targets with statin dose titration (and when necessary adjunctive medication) is essential to optimise benefit., (Copyright © 2018. Published by Elsevier B.V.)

Background and Aims: Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded., Methods: Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction., Results: Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745., Conclusions: The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To describe the development of the Oxford WebQ, a web-based 24 h dietary assessment tool developed for repeated administration in large prospective studies; and to report the preliminary assessment of its performance for estimating nutrient intakes., Design: We developed the Oxford WebQ by repeated testing until it was sufficiently comprehensive and easy to use. For the latest version, we compared nutrient intakes from volunteers who completed both the Oxford WebQ and an interviewer-administered 24 h dietary recall on the same day., Setting: Oxford, UK., Subjects: A total of 116 men and women., Results: The WebQ took a median of 12·5 (interquartile range: 10·8-16·3) min to self-complete and nutrient intakes were estimated automatically. By contrast, the interviewer-administered 24 h dietary recall took 30 min to complete and 30 min to code. Compared with the 24 h dietary recall, the mean Spearman's correlation for the 21 nutrients obtained from the WebQ was 0·6, with the majority between 0·5 and 0·9. The mean differences in intake were less than ±10 % for all nutrients except for carotene and vitamins B12 and D. On rare occasions a food item was reported in only one assessment method, but this was not more frequent or systematically different between the methods., Conclusions: Compared with an interviewer-based 24 h dietary recall, the WebQ captures similar food items and estimates similar nutrient intakes for a single day's dietary intake. The WebQ is self-administered and nutrients are estimated automatically, providing a low-cost method for measuring dietary intake in large-scale studies.