349 research outputs found
Lies, damned lies and storytelling: an exploration of the contribution of principalsâ anecdotes to research, teaching and learning about the management of schools and colleges
This article investigates the extent to which story telling can be an acceptable and effective presentation of experience which facilitates research, teaching and learning in education management. Stories, written by school principals about real events which influenced their practice, are interspersed with discussion first, on the art of storytellers and how their magic can be distinguished from that of actors and of management gurus. Secondly, story telling is suggested as a method of research since it records authoritative experience, can lead to categorisation. is documentary in source, recreates the past from participant observation and offers easy access to data. Thirdly, storytelling is an effective teaching method, stimulating imagination, offering learning stimuli from varying sources, linking teacher and taught through shared experiences, allowing relaxation in the learning process and opening up opportunities for frank exchanges of feelings. The three stories included in the article offer the reader the chance to test the ideas presented
Listen to Nice
In describing Humphrey Jenningsâ wartime documentary propaganda film, 'Listen to Britain' (1942), a film with an overtly poetic sensibility and dominantly musical soundtrack, John Corner asserts that âthrough listening to
Britain, we are enabled to properly look at it'. This idea of sound leading our attention to the images has underpinned much of the collaborative
work between composer and sound designer, Geoffrey Cox, and documentary filmmaker, Keith Marley. It is in this context that the article will analyse an extract of A Film About Nice (Marley and Cox 2010), a contemporary
re-imagining of Jean Vigoâs silent documentary, 'A propos de Nice' (1930). Reference will be made throughout to the historical context, and the filmic and theoretical influences that have informed the way music and creative sound design have been used to place emphasis on hearing a place, as much as seeing it
Bidirectional Mendelian randomisation analysis of the relationship between circulating vitamin D concentration and colorectal cancer risk
Epidemiological evidence is consistent with a protective effect of vitamin D against colorectal cancer (CRC), but the observed strong associations are open to confounders and potential reverse causation. Previous Mendelian randomisation (MR) studies were limited by poor genetic instruments and inadequate statistical power. Moreover, whether genetically higher CRC risk can influence vitamin D level, namely the reverse causation, still remains unknown. Herein, we report the first bidirectional MR study. We employed 110 newly identified genetic variants as proxies for vitamin D to obtain unconfounded effect estimates on CRC risk in 26â397 CRC cases and 41â481 controls of European ancestry. To test for reserve causation, we estimated effects of 115 CRC-risk variants on vitamin D level among 417â580 participants from the UK Biobank. The causal association was estimated using the random-effect inverse-variance weighted (IVW) method. We found no significant causal effect of vitamin D on CRC risk [IVW estimate odds ratio: 0.97, 95% confidence interval (CI) = 0.88-1.07, P = .565]. Similarly, no significant reverse causal association was identified between genetically increased CRC risk and vitamin D levels (IVW estimate β: -0.002, 95% CI = -0.008 to 0.004, P = .543). Stratified analysis by tumour sites did not identify significant causal associations in either direction between vitamin D and colon or rectal cancer. Despite the improved statistical power of this study, we found no evidence of causal association of either direction between circulating vitamin D and CRC risk. Significant associations reported by observational studies may be primarily driven by unidentified confounders
Phenome-wide association study (PheWAS) of colorectal cancer risk SNP effects on health outcomes in UK Biobank
BACKGROUND: Associations between colorectal cancer (CRC) and other health outcomes have been reported, but these may be subject to biases, or due to limitations of observational studies. METHODS: We set out to determine whether genetic predisposition to CRC is also associated with the risk of other phenotypes. Under the phenome-wide association study (PheWAS) and tree-structured phenotypic model (TreeWAS), we studied 334,385 unrelated White British individuals (excluding CRC patients) from the UK Biobank cohort. We generated a polygenic risk score (PRS) from CRC genome-wide association studies as a measure of CRC risk. We performed sensitivity analyses to test the robustness of the results and searched the Danish Disease Trajectory Browser (DTB) to replicate the observed associations. RESULTS: Eight PheWAS phenotypes and 21 TreeWAS nodes were associated with CRC genetic predisposition by PheWAS and TreeWAS, respectively. The PheWAS detected associations were from neoplasms and digestive system disease group (e.g. benign neoplasm of colon, anal and rectal polyp and diverticular disease). The results from the TreeWAS corroborated the results from the PheWAS. These results were replicated in the observational data within the DTB. CONCLUSIONS: We show that benign colorectal neoplasms share genetic aetiology with CRC using PheWAS and TreeWAS methods. Additionally, CRC genetic predisposition is associated with diverticular disease
Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas
BackgroundLow penetrance genetic variants, primarily single nucleotide polymorphisms, have substantial influence on colorectal cancer (CRC) susceptibility. Most CRCs develop from colorectal adenomas (CRA). Here we report the first comprehensive field synopsis that catalogues all genetic association studies on CRA, with a parallel online database [http://www.chs.med.ed.ac.uk/CRAgene/].MethodsWe performed a systematic review, reviewing 9750 titles, and then extracted data from 130 publications reporting on 181 polymorphisms in 74 genes. We conducted meta-analyses to derive summary effect estimates for 37 polymorphisms in 26 genes. We applied the Venice criteria and Bayesian False Discovery Probability (BFDP) to assess the levels of the credibility of associations.ResultsWe considered the association with the rs6983267 variant at 8q24 as 'highly credible', reaching genome-wide statistical significance in at least one meta-analysis model. We identified 'less credible' associations (higher heterogeneity, lower statistical power, BFDP > 0.02) with a further four variants of four independent genes: MTHFR c.677C>T p.A222V (rs1801133), TP53 c.215C>G p.R72P (rs1042522), NQO1 c.559C>T p.P187S (rs1800566), and NAT1 alleles imputed as fast acetylator genotypes. For the remaining 32 variants of 22 genes for which positive associations with CRA risk have been previously reported, the meta-analyses revealed no credible evidence to support these as true associations.ConclusionsThe limited number of credible associations between low penetrance genetic variants and CRA reflects the lower volume of evidence and associated lack of statistical power to detect associations of the magnitude typically observed for genetic variants and chronic diseases. The CRA gene database provides context for CRA genetic association data and will help inform future research directions
COVID-19 trajectories among 57 million adults in England:a cohort study using electronic health records
Background: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. Methods: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. Findings: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12¡7% during the study period. Of 7 244 925 individuals, 460 737 (6¡4%) were admitted to hospital and 158 020 (2¡2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10¡6%) were admitted to the intensive care unit (ICU), 69 090 (15¡0%) received non-invasive ventilation, and 25 928 (5¡6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30¡4%] of 77 202 patients) than wave 2 (44 220 [23¡1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50¡7%] of 5063 patients). 15 486 (9¡8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6¡9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. Interpretation: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. Funding: British Heart Foundation Data Science Centre, led by Health Data Research UK.</p
COVID-19 trajectories among 57 million adults in England:a cohort study using electronic health records
Background: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. Methods: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. Findings: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12¡7% during the study period. Of 7 244 925 individuals, 460 737 (6¡4%) were admitted to hospital and 158 020 (2¡2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10¡6%) were admitted to the intensive care unit (ICU), 69 090 (15¡0%) received non-invasive ventilation, and 25 928 (5¡6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30¡4%] of 77 202 patients) than wave 2 (44 220 [23¡1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50¡7%] of 5063 patients). 15 486 (9¡8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6¡9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. Interpretation: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. Funding: British Heart Foundation Data Science Centre, led by Health Data Research UK.</p
Exploring causality in the association between circulating 25-hydroxyvitamin D and colorectal cancer risk:a large Mendelian randomisation study
Background: Whilst observational studies establish that lower plasma 25-hydroxyvitamin D (25-OHD) levels are associated with higher risk of colorectal cancer (CRC), establishing causality has proven challenging. Since vitamin D is modifiable, these observations have substantial clinical and public health implications. Indeed, many health agencies already recommend supplemental vitamin D. Here, we explore causality in a large Mendelian randomisation (MR) study using an improved genetic instrument for circulating 25-OHD. Methods: We developed a weighted genetic score for circulating 25-OHD using six genetic variants that we recently reported to be associated with circulating 25-OHD in a large genome-wide association study (GWAS) meta-analysis. Using this score as instrumental variable in MR analyses, we sought to determine whether circulating 25-OHD is causally linked with CRC risk We conducted MR analysis using individual-level data from 10,725 CRC cases and 30,794 controls (Scotland, UK Biobank and Croatia). We then applied estimates from meta-analysis of 11 GWAS of CRC risk (18,967 cases; 48,168 controls) in a summary statistics MR approach. Results: The new genetic score for 25-OHD was strongly associated with measured plasma 25-OHD levels in 2821 healthy Scottish controls (P = 1.47 x 10(-11)), improving upon previous genetic instruments (F-statistic 46.0 vs. 13.0). However, individual-level MR revealed no association between 25-OHD score and CRC risk (OR 1.03/unit log-transformed circulating 25-OHD, 95% CI 0.51-2.07, P= 0.93). Similarly, we found no evidence for a causal relationship between 25-OHD and CRC risk using summary statistics MR analysis (OR 0.91, 95% CI 0.69-1.19, P= 0.48). Conclusions: Despite the scale of this study and employing an improved score capturing more of the genetic contribution to circulating 25-OHD, we found no evidence for a causal relationship between circulating 25-OHD and CRC risk Although the magnitude of effect for vitamin D suggested by observational studies can confidently be excluded, smaller effects sizes and non-linear relationships remain plausible. Circulating vitamin D may be a CRC biomarker, but a causal effect on CRC risk remains unproven
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