249 research outputs found
cegpy: Modelling with Chain Event Graphs in Python
Chain event graphs (CEGs) are a recent family of probabilistic graphical
models that generalise the popular Bayesian networks (BNs) family. Crucially,
unlike BNs, a CEG is able to embed, within its graph and its statistical model,
asymmetries exhibited by a process. These asymmetries might be in the
conditional independence relationships or in the structure of the graph and its
underlying event space. Structural asymmetries are common in many domains, and
can occur naturally (e.g. a defendant vs prosecutor's version of events) or by
design (e.g. a public health intervention). However, there currently exists no
software that allows a user to leverage the theoretical developments of the CEG
model family in modelling processes with structural asymmetries. This paper
introduces cegpy, the first Python package for learning and analysing complex
processes using CEGs. The key feature of cegpy is that it is the first CEG
package in any programming language that can model processes with symmetric as
well as asymmetric structures. cegpy contains an implementation of Bayesian
model selection and probability propagation algorithms for CEGs. We illustrate
the functionality of cegpy using a structurally asymmetric dataset
A study of the efficacy and cost-effectiveness of MRSA screening and monitoring on surgical wards using a new, rapid molecular test (EMMS)
<p>Abstract</p> <p>Background</p> <p>MRSA is a significant contributor to prolonged hospital stay, poor clinical outcome and increased healthcare costs amongst surgical patients. A PCR test has been developed for rapid detection of MRSA in nasal swabs. The aims of this study are (1) to estimate the effectiveness of screening using this rapid PCR tests vs culture in reducing MRSA cross-infection rates; (2) to compare the cost of each testing strategy, including subsequent health care costs; and (3) to model different policies for the early identification and control of MRSA infection in surgical patients.</p> <p>Methods/Design</p> <p>The study is a prospective two-period cross-over study set in 7 surgical wards covering different surgical specialities. A total of 10,000 patients > 18 years will be tested over 16 months. The only difference between the two study periods is the method used for the detection of MRSA in each ward (rapid v conventional culture), with all other infection control practices remaining consistent between the arms. The study has been designed to complement routine practice in the NHS. Outcomes are MRSA cross-infection rates (primary outcome) and need for antibiotic therapy and MRSA-related morbidity. Parallel economic and modelling studies are being conducted to aid in the interpretation of the results and to evaluate the cost-effectiveness of the rapid PCR screening strategy.</p> <p>Discussion</p> <p>This paper highlights the design, methods and operational aspects of a study evaluating rapid MRSA screening in the surgical ward setting.</p
Genetic regulation of glucoraphanin accumulation in Beneforté® broccoli
Diets rich in broccoli (Brassica oleracea var italica) have been associated with maintenance of cardiovascular health and reduction in risk of cancer. These health benefits have been
attributed to glucoraphanin that specifically accumulates in broccoli. The development of broccoli with enhanced concentrations of glucoraphanin may deliver greater health benefits.
Three high-glucoraphanin F1 broccoli hybrids were developed in independent programmes through genome introgression from the wild species Brassica villosa. Glucoraphanin and other metabolites were quantified in experimental field trials. Global SNP analyses quantified the differential extent of B. villosa introgression
The high-glucoraphanin broccoli hybrids contained 2.5–3 times the glucoraphanin content of standard hybrids due to enhanced sulphate assimilation and modifications in sulphur partitioning between sulphur-containing metabolites. All of the high-glucoraphanin hybrids possessed an introgressed B. villosa segment which contained a B. villosa Myb28 allele. Myb28
expression was increased in all of the high-glucoraphanin hybrids. Two high-glucoraphanin hybrids have been commercialised as Beneforte broccoli.
The study illustrates the translation of research on glucosinolate genetics from Arabidopsis to broccoli, the use of wild Brassica species to develop cultivars with potential consumer benefits, and the development of cultivars with contrasting concentrations of glucoraphanin for use in blinded human intervention studie
Developing a social mobilisation intervention for salt reduction: participatory action research in Bombali district, Sierra Leone
From Springer Nature via Jisc Publications RouterHistory: received 2023-01-08, accepted 2023-09-01, registration 2023-09-04, epub 2023-09-12, online 2023-09-12, collection 2023-12Acknowledgements: Thanks to all the stakeholders in the social mobilisation teams and focus group discussion members from the communities of Binkolo, Maforay, Makarie and Masongbo.Publication status: PublishedFunder: UK National Institute for Health Research; Grant(s): 16/136/100Sophie Witter - ORCID: 0000-0002-7656-6188 https://orcid.org/0000-0002-7656-6188Background: High salt intake is a major risk factor for hypertension, which in turn contributes to cardiovascular diseases, the major cause of death from non communicable diseases (NCDs). Research is limited on social mobilisation interventions to tackle NCDs, including in fragile health settings such as Sierra Leone. Methods: Participatory action research methods were used to develop a social mobilisation intervention for salt reduction in Bombali District, Sierra Leone. A team of 20 local stakeholders were recruited to develop and deliver the intervention. Stakeholder workshop reports and interviews were used to record outcomes, enablers, and barriers to the intervention. Focus group discussions were used to observe knowledge, attitudes, and behaviours of community members pre- and post- the intervention. Results: Stakeholders showed enthusiasm and were well engaged in the social mobilisation process around salt reduction. They developed radio jingles, radio show talks, organised community awareness raising meetings, school sensitisation outreaches, and door to door engagements. Stakeholders reported benefiting personally through developing their own skills and confidence in communication and felt positive about their role in educating their community. The interventions led to reported increased awareness of risks of high salt intake and NCDs, resulting in a reduction of salt use in the community, leading to perceived health gains. However, salt reduction was also met with some resistance due to social factors. Local community structures were also reactivated to work on the interventions and connect the community to the local health facility, which saw an increase in patients having their blood pressure checked. The comparison villages also experienced an increase in awareness and perceived reductions in salt intake behaviours. This was as messages had cascaded via the radio and initial focus group discussions. The social mobilisation stakeholders also agreed on future activities that could continue at no or low cost. Conclusion: Social mobilisation interventions can provide low-cost strategies to tackle NCDs in fragile settings such as Sierra Leone through the utilisation of community structures. However, more research is required to ascertain the key enablers for replicability and if such successes can be sustained over a longer follow up period.This study/project is funded by the UK National Institute for Health Research (NIHR) [NIHR Global Health Research programme (project reference 16/136/100)/NIHR Research Unit on Health in Situations of Fragility]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funder played no role in the study design, data collection, analysis, interpretation, or in writing the manuscript.pubpu
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Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases.
PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the noncoding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity, and magnetic resonance image changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, probably missed owing to failure of alignment.ConclusionThese cases illustrate potential pitfalls of WES/NGS testing and the importance of phenotype-guided molecular testing in yielding diagnoses
Trait analysis reveals DOG1 determines initial depth of seed dormancy, but not changes during dormancy cycling that result in seedling emergence timing.
Seedling emergence timing is crucial in competitive plant communities and so contributes to species fitness. To understand the mechanistic basis of variation in seedling emergence timing, we exploited the contrasting behaviour of two Arabidopsis ecotypes; Cape Verde island (Cvi) and Burren (Bur-0). We used RNAseq analysis of RNA from exhumed seeds and quantitative trait loci (QTL) analyses on a mapping population from crossing the Cvi and Bur-0 ecotypes. We determined genome-wide expression patterns over an annual dormancy cycle in both ecotypes identifying nine major clusters based on the seasonal timing of gene expression, and variation in behaviour between them. QTL were identified for depth of seed dormancy and Seedling Emergence Timing (SET). Both analyses showed a key role for DOG1 in determining depth of dormancy, but did not support a direct role for DOG1 in generating altered seasonal patterns of seedling emergence. The principle QTL determining Seedling Emergence Timing (SET1: dormancy cycling) is physically close on chromosome 5, but distinct from DOG1. We show that SET1 and two other SET QTLs each contain a candidate gene (AHG1, ANAC60, PDF1 respectively) closely associated to DOG1 and abscisic acid signalling and suggest a model for the control of SET in the field
The incidence and prevalence of systemic lupus erythematosus in the UK, 1999–2012
Objectives: To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in the UK over the period 1999–2012.
Methods: A retrospective cohort study using the Clinical Practice Research Datalink (CPRD). The incidence was calculated per 100 000 person-years and the prevalence was calculated per 100 000 people for the period 1999–2012 and stratified by year, age group, gender, region and ethnicity. Three definitions of SLE were explored: (1) systemic lupus, (2) a fully comprehensive definition of lupus including cutaneous only lupus and (3) requiring supporting evidence of SLE in the medical record.
Results: Using our primary definition of SLE, the incidence during the study period was 4.91/100 000 person-years (95% CI 4.73 to 5.09), with an annual 1.8% decline (p<0.001). In contrast, the prevalence increased from 64.99/100 000 in 1999 (95% CI 62.04 to 67.93) (0.065%) to 97.04/100 000 in 2012 (95% CI 94.18 to 99.90) (0.097%). SLE was six times more common in women. The peak age of incidence was 50–59 years. There was regional variation in both incidence and prevalence. People of Black Caribbean ethnicity had the highest incidence and prevalence. Alternative definitions of SLE increased (definition 2) or decreased (definition 3) estimates of incidence and prevalence, but similar trends were found.
Conclusions: The incidence of SLE has been declining but the prevalence has been increasing in the UK in recent years. Age, gender, region and ethnicity are risk factors for SLE. This is the first study to report ethnic differences on the incidence and prevalence of SLE using the CPRD
Addressing the threat of climate change to agriculture requires improving crop resilience to short-term abiotic stress
Climate change represents a serious threat to global agriculture, necessitating the development of more environmentally resilient crops to safeguard the future of food production. The effects of climate change are appearing to include a higher frequency of extreme weather events and increased day-to-day weather variability. As such, crops which are able to cope with short-term environmental stress, in addition to those that are tolerant to longer term stress conditions are required . It is becoming apparent that the hitherto relatively little studied process of post-stress plant recovery could be key to optimizing growth and production under fluctuating conditions with intermittent transient stress events. Developing more durable crops requires the provision of genetic resources to identify useful traits through the development of screening protocols. Such traits can then become the objective of crop breeding programmes. In this study, we discuss these issues and outline example research in leafy vegetables that is investigating resilience to short-term abiotic stress
Burden of comorbidity in systemic lupus erythematosus in the UK, 1999–2012
Objective: To estimate the comorbidity associated with systemic lupus erythematosus (SLE) in the UK during 1999–2012.
Methods: A retrospective cohort study using the UK Clinical Practice Research Datalink was conducted. Prevalent cases of SLE were matched by age, sex, and practice to 4 controls. The incidence of cardiovascular disease (CVD), stroke, end-stage renal failure (ESRF), cancer, osteoporosis, and infection were calculated per 1,000 person-years during the study period and compared to controls using Poisson regression to obtain incidence rate ratios (IRRs). IRRs were adjusted for baseline age, sex, body mass index, smoking status, alcohol intake, hypertension, hyperlipidemia, Charlson Index scores, and prednisolone use. Age- and sex-specific incidence rates were calculated.
Results: When comparing the 7,732 prevalent cases of SLE with 28,079 matched controls, the unadjusted IRR was 1.98 (95% confidence interval [95% CI] 1.69–2.31) for CVD, 1.81 (95% CI 1.49–2.19) for stroke, 7.81 (95% CI 4.68–13.05) for ESRF, 1.28 (95% CI 1.17–1.40) for cancer, 2.53 (95% CI 2.27–2.82) for osteoporosis, and 1.49 (95% CI 1.40–1.58) for infection. After adjustment, the rates remained significantly higher in cases. Men with SLE had higher rates of CVD, stroke, and cancer, whereas women had higher rates of infection and osteoporosis. Those at younger ages were at the greatest relative risk compared with controls. Cases had significantly higher Charlson Index scores at baseline.
Conclusion: People with SLE in the UK have a greater burden of comorbidity and are more likely to develop CVD, stroke, ESRF, cancer, osteoporosis, and infection than people of the same age and sex
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