Convexity in partial cubes: the hull number

We prove that the combinatorial optimization problem of determining the hull number of a partial cube is NP-complete. This makes partial cubes the minimal graph class for which NP-completeness of this problem is known and improves some earlier results in the literature. On the other hand we provide a polynomial-time algorithm to determine the hull number of planar partial cube quadrangulations. Instances of the hull number problem for partial cubes described include poset dimension and hitting sets for interiors of curves in the plane. To obtain the above results, we investigate convexity in partial cubes and characterize these graphs in terms of their lattice of convex subgraphs, improving a theorem of Handa. Furthermore we provide a topological representation theorem for planar partial cubes, generalizing a result of Fukuda and Handa about rank three oriented matroids.Comment: 19 pages, 4 figure

Body mass index in young children and allergic disease: Gender differences in a longitudinal study

The increase in allergic diseases has occurred in parallel with the obesity epidemic, suggesting a possible association.Objective We investigated the relationship of body mass index (BMI) up to age 8 years with allergic disease within a birth cohort.Methods Children were followed from birth and were reviewed at age 3, 5 and 8 years (n=731; male 406). Parents completed questionnaires; children were weighed, measured, skin prick tested and examined.Results Increasing BMI at 3, 5 and 8 years increased the risk of current wheezing at the corresponding age (odds ratio [95% confidence interval] per standardized deviation score: age 3, 1.26 [1.04-1.53], P=0.02; age 5, 1.33 [1.06-1.67], P=0.02; age 8, 1.27 [1.0-1.62], P=0.05). The effect of BMI on wheeze at age 8 years differed between boys and girls, with a significant positive association in girls, but not in boys (P=0.04 for interaction). The effect of BMI at earlier ages on current or subsequent wheezing did not differ significantly between genders. Increasing BMI significantly increased the risk of physician-diagnosed eczema at age 5 (1.23 [1.04-1.47], P=0.02) and 8 (1.23 [1.03-1.45], P=0.02), with a significant interaction between gender and BMI at age 5 (P=0.04). There was no association between BMI and sensitization. Being overweight at age 3 years was significantly associated with late-onset wheeze (3.83 [1.51-9.75], P=0.005), persistent wheeze (4.15 [2.07-8.32],

Systolic blood pressure, chronic obstructive pulmonary disease and cardiovascular risk

\ua9 2023 Author(s) (or their employer(s)). Objective: In individuals with complex underlying health problems, the association between systolic blood pressure (SBP) and cardiovascular disease is less well recognised. The association between SBP and risk of cardiovascular events in patients with chronic obstructive pulmonary disease (COPD) was investigated. Methods: and analysis In this cohort study, 39 602 individuals with a diagnosis of COPD aged 55-90 years between 1990 and 2009 were identified from validated electronic health records (EHR) in the UK. The association between SBP and risk of cardiovascular end points (composite of ischaemic heart disease, heart failure, stroke and cardiovascular death) was analysed using a deep learning approach. Results: In the selected cohort (46.5% women, median age 69 years), 10 987 cardiovascular events were observed over a median follow-up period of 3.9 years. The association between SBP and risk of cardiovascular end points was found to be monotonic; the lowest SBP exposure group of <120 mm Hg presented nadir of risk. With respect to reference SBP (between 120 and 129 mm Hg), adjusted risk ratios for the primary outcome were 0.99 (95% CI 0.93 to 1.05) for SBP of <120 mm Hg, 1.02 (0.97 to 1.07) for SBP between 130 and 139 mm Hg, 1.07 (1.01 to 1.12) for SBP between 140 and 149 mm Hg, 1.11 (1.05 to 1.17) for SBP between 150 and 159 mm Hg and 1.16 (1.10 to 1.22) for SBP ≥160 mm Hg. Conclusion: Using deep learning for modelling EHR, we identified a monotonic association between SBP and risk of cardiovascular events in patients with COPD

Validation of risk prediction models applied to longitudinal electronic health record data for the prediction of major cardiovascular events in the presence of data shifts

\ua9 2022 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology. Aims: Deep learning has dominated predictive modelling across different fields, but in medicine it has been met with mixed reception. In clinical practice, simple, statistical models and risk scores continue to inform cardiovascular disease risk predictions. This is due in part to the knowledge gap about how deep learning models perform in practice when they are subject to dynamic data shifts; a key criterion that common internal validation procedures do not address. We evaluated the performance of a novel deep learning model, BEHRT, under data shifts and compared it with several ML-based and established risk models. Methods and results: Using linked electronic health records of 1.1 million patients across England aged at least 35 years between 1985 and 2015, we replicated three established statistical models for predicting 5-year risk of incident heart failure, stroke, and coronary heart disease. The results were compared with a widely accepted machine learning model (random forests), and a novel deep learning model (BEHRT). In addition to internal validation, we investigated how data shifts affect model discrimination and calibration. To this end, we tested the models on cohorts from (i) distinct geographical regions; (ii) different periods. Using internal validation, the deep learning models substantially outperformed the best statistical models by 6%, 8%, and 11% in heart failure, stroke, and coronary heart disease, respectively, in terms of the area under the receiver operating characteristic curve. Conclusion: The performance of all models declined as a result of data shifts; despite this, the deep learning models maintained the best performance in all risk prediction tasks. Updating the model with the latest information can improve discrimination but if the prior distribution changes, the model may remain miscalibrated

Hi-BEHRT: Hierarchical Transformer-Based Model for Accurate Prediction of Clinical Events Using Multimodal Longitudinal Electronic Health Records

\ua9 2022 IEEE. Electronic health records (EHR) represent a holistic overview of patients\u27 trajectories. Their increasing availability has fueled new hopes to leverage them and develop accurate risk prediction models for a wide range of diseases. Given the complex interrelationships of medical records and patient outcomes, deep learning models have shown clear merits in achieving this goal. However, a key limitation of current study remains their capacity in processing long sequences, and long sequence modelling and its application in the context of healthcare and EHR remains unexplored. Capturing the whole history of medical encounters is expected to lead to more accurate predictions, but the inclusion of records collected for decades and from multiple resources can inevitably exceed the receptive field of the most existing deep learning architectures. This can result in missing crucial, long-term dependencies. To address this gap, we present Hi-BEHRT, a hierarchical Transformer-based model that can significantly expand the receptive field of Transformers and extract associations from much longer sequences. Using a multimodal large-scale linked longitudinal EHR, the Hi-BEHRT exceeds the state-of-the-art deep learning models 1% to 5% for area under the receiver operating characteristic (AUROC) curve and 1% to 8% for area under the precision recall (AUPRC) curve on average, and 2% to 8% (AUROC) and 2% to 11% (AUPRC) for patients with long medical history for 5-year heart failure, diabetes, chronic kidney disease, and stroke risk prediction. Additionally, because pretraining for hierarchical Transformer is not well-established, we provide an effective end-to-end contrastive pre-training strategy for Hi-BEHRT using EHR, improving its transferability on predicting clinical events with relatively small training dataset

Using formative research to develop the healthy eating component of the CHANGE! school-based curriculum intervention

Background: Childhood obesity is a significant public health concern. Many intervention studies have attempted to combat childhood obesity, often in the absence of formative or preparatory work. This study describes the healthy eating component of the formative phase of the Children’s Health Activity and Nutrition: Get Educated! (CHANGE!) project. The aim of the present study was to gather qualitative focus group and interview data regarding healthy eating particularly in relation to enabling and influencing factors, barriers and knowledge in children and adults (parents and teachers) from schools within the CHANGE! programme to provide populationspecific evidence to inform the subsequent intervention design. Methods: Semi-structured focus group interviews were conducted with children, parents and teachers across 11 primary schools in the Wigan borough of North West England. Sixty children (N = 24 boys), 33 parents (N = 4 male) and 10 teachers (N = 4 male) participated in the study. Interview questions were structured around the PRECEDE phases of the PRECEDE-PROCEED model. Interviews were transcribed verbatim and analysed using the pen-profiling technique. Results: The pen-profiles revealed that children’s knowledge of healthy eating was generally good, specifically many children were aware that fruit and vegetable consumption was ‘healthy’ (N = 46). Adults’ knowledge was also good, including restricting fatty foods, promoting fruit and vegetable intake, and maintaining a balanced diet. The important role parents play in children’s eating behaviours and food intake was evident. The emerging themes relating to barriers to healthy eating showed that external drivers such as advertising, the preferred sensory experience of “unhealthy” foods, and food being used as a reward may play a role in preventing healthy eating. Conclusions: Data suggest that; knowledge related to diet composition was not a barrier per se to healthy eating, and education showing how to translate knowledge into behavior or action is required. The key themes that emerged through the focus groups and pen-profiling data analysis technique will be used to inform and tailor the healthy eating component of the CHANGE! intervention study. Trial registration: Current Controlled Trials ISRCTN03863885 Keywords: Nutrition, Childhood obesity, Pen-profiles, Health, School

Investigation of an intertidal area of Yaquina Head

Keywords: Zoo451; Yaquina Head; Distribution; Alaria marginata; Hedophyllum sessile; Endocladia muricata; Microcladia borealis; Spongomorpha coalita; Balanus glandula; Anthopleura xanthogrammica; Strongylocentrotus purpuratus; Acmaea digitalis; Mytilus californianus; Petrolisthes cinctipes; Polycipes polymerus; Cyanoplax dentiens; Katharina tunicata; Littorina scutulata; Mopalia ciliata; Pisaster ochraceus; Pugettia productus; Tonicella lineata; Pollicipes polymeru

Blood pressure and risk of venous thromboembolism: a cohort analysis of 5.5 million UK adults and Mendelian randomization studies

\ua9 The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. Aims Evidence for the effect of elevated blood pressure (BP) on the risk of venous thromboembolism (VTE) has been conflicting. We sought to assess the association between systolic BP and the risk of VTE. Methods and results Three complementary studies comprising an observational cohort analysis, a one-sample and two-sample Mendelian randomization were conducted using data from 5 588 280 patients registered in the Clinical Practice Research Datalink (CPRD) dataset and 432 173 UK Biobank participants with valid genetic data. Summary statistics of International Network on Venous Thrombosis genome-wide association meta-analysis was used for two-sample Mendelian randomization. The primary outcome was the first occurrence of VTE event, identified from hospital discharge reports, death registers, and/or primary care records. In the CPRD cohort, 104 017(1.9%) patients had a first diagnosis of VTE during the 9.6-year follow-up. Each 20 mmHg increase in systolic BP was associated with a 7% lower risk of VTE [hazard ratio: 0.93, 95% confidence interval (CI): (0.92–0.94)]. Statistically significant interactions were found for sex and body mass index, but not for age and subtype of VTE (pulmonary embolism and deep venous thrombosis). Mendelian randomization studies provided strong evidence for the association between systolic BP and VTE, both in the one-sample [odds ratio (OR): 0.69, (95% CI: 0.57–0.83)] and two-sample analyses [OR: 0.80, 95% CI: (0.70–0.92)]. Conclusion We found an increased risk of VTE with lower BP, and this association was independently confirmed in two Mendelian randomization analyses. The benefits of BP reduction are likely to outweigh the harms in most patient groups, but in people with predisposing factors for VTE, further BP reduction should be made cautiously

Genetic susceptibility, elevated blood pressure, and risk of atrial fibrillation: a Mendelian randomization study

BACKGROUND: Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual’s genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk. METHODS: First, causality of association was assessed through two-sample Mendelian randomization, using data from two independent genome-wide association studies that included a population of one million Europeans in total. Second, the UK Biobank data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with major BP-lowering drug classes on AF risk was predicted through genetic variants in genes encode the therapeutic targets of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists. RESULTS: The two-sample Mendelian randomization analysis indicated that, on average, exposure to a higher systolic BP increased the risk of AF by 19% (odds ratio per each 10-mmHg [OR] 1.19 [1.12 to 1.27]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF. The comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers, and calcium channel blockers) suggested similar average effects for the prevention of atrial fibrillation and coronary heart disease. CONCLUSIONS: The effect of elevated BP on the risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility risk for AF