Quantification of Persistence of Escherichia coli O157:H7 in Contrasting Soils

Persistence of Escherichia coli (E. coli) O157:H7 in the environment is a major concern to vegetable and fruit growers where farms and livestock production are in close proximity. The objectives were to determine the effects of preplant fumigation treatment on the survival of E. coli O157:H7 in two soils and the effects of indigenous bacterial populations on the survival of this pathogen. Real-time PCR and plate counts were used to quantify the survival of E. coli O157:H7 in two contrasting soils after fumigation with methyl bromide (MeBr) and methyl iodide (MeI). Ten days after fumigation, E. coli O157:H7 counts were significantly lower (P = .0001) in fumigated soils than in the non-fumigated. Direct comparison between MeBr and MeI within each soil indicated that these two fumigants showed similar impacts on E. coli O157:H7 survival. Microbial species diversity as determined by DGGE was significantly higher in clay soil than sandy soil and this resulted in higher initial decline in population in clay soil than in sandy soil. This study shows that if soil is contaminated with E. coli O157:H7, fumigation alone may not eliminate the pathogen, but may cause decrease in microbial diversity which may enhance the survival of the pathogen

Quantification of Persistence of Escherichia coli O157:H7 in Contrasting Soils

Persistence of Escherichia coli (E. coli) O157:H7 in the environment is a major concern to vegetable and fruit growers where farms and livestock production are in close proximity. The objectives were to determine the effects of preplant fumigation treatment on the survival of E. coli O157:H7 in two soils and the effects of indigenous bacterial populations on the survival of this pathogen. Real-time PCR and plate counts were used to quantify the survival of E. coli O157:H7 in two contrasting soils after fumigation with methyl bromide (MeBr) and methyl iodide (MeI). Ten days after fumigation, E. coli O157:H7 counts were significantly lower (P = .0001) in fumigated soils than in the non-fumigated. Direct comparison between MeBr and MeI within each soil indicated that these two fumigants showed similar impacts on E. coli O157:H7 survival. Microbial species diversity as determined by DGGE was significantly higher in clay soil than sandy soil and this resulted in higher initial decline in population in clay soil than in sandy soil. This study shows that if soil is contaminated with E. coli O157:H7, fumigation alone may not eliminate the pathogen, but may cause decrease in microbial diversity which may enhance the survival of the pathogen

Readiness for Delivering Digital Health at Scale: Lessons From a Longitudinal Qualitative Evaluation of a National Digital Health Innovation Program in the United Kingdom

Background: Digital health has the potential to support care delivery for chronic illness. Despite positive evidence from localized implementations, new technologies have proven slow to become accepted, integrated, and routinized at scale.Objective: The aim of our study was to examine barriers and facilitators to implementation of digital health at scale through the evaluation of a £37m national digital health program: ‟Delivering Assisted Living Lifestyles at Scale” (dallas) from 2012-2015.Methods: The study was a longitudinal qualitative, multi-stakeholder, implementation study. The methods included interviews (n=125) with key implementers, focus groups with consumers and patients (n=7), project meetings (n=12), field work or observation in the communities (n=16), health professional survey responses (n=48), and cross program documentary evidence on implementation (n=215). We used a sociological theory called normalization process theory (NPT) and a longitudinal (3 years) qualitative framework analysis approach. This work did not study a single intervention or population. Instead, we evaluated the processes (of designing and delivering digital health), and our outcomes were the identified barriers and facilitators to delivering and mainstreaming services and products within the mixed sector digital health ecosystem.Results: We identified three main levels of issues influencing readiness for digital health: macro (market, infrastructure, policy), meso (organizational), and micro (professional or public). Factors hindering implementation included: lack of information technology (IT) infrastructure, uncertainty around information governance, lack of incentives to prioritize interoperability, lack of precedence on accountability within the commercial sector, and a market perceived as difficult to navigate. Factors enabling implementation were: clinical endorsement, champions who promoted digital health, and public and professional willingness.Conclusions: Although there is receptiveness to digital health, barriers to mainstreaming remain. Our findings suggest greater investment in national and local infrastructure, implementation of guidelines for the safe and transparent use and assessment of digital health, incentivization of interoperability, and investment in upskilling of professionals and the public would help support the normalization of digital health. These findings will enable researchers, health care practitioners, and policy makers to understand the current landscape and the actions required in order to prepare the market and accelerate uptake, and use of digital health and wellness services in context and at scale

The Chief Scientist Office cardiovascular and pulmonary imaging in SARS Coronavirus disease-19 (CISCO-19) study

Background: COVID-19 is typically a primary respiratory illness with multisystem involvement. The prevalence and clinical significance of cardiovascular and multisystem involvement in COVID-19 remain unclear. Methods: This is a prospective, observational, multicentre, longitudinal, cohort study with minimal selection criteria and a near-consecutive approach to screening. Patients who have received hospital care for COVID-19 will be enrolled within 28 days of discharge. Myocardial injury will be diagnosed according to the peak troponin I in relation to the upper reference limit (URL, 99th centile) (Abbott Architect troponin I assay; sex-specific URL, male: >34 ng/L; female: >16 ng/L). Multisystem, multimodality imaging will be undertaken during the convalescent phase at 28 days post-discharge (Visit 2). Imaging of the heart, lung, and kidneys will include multiparametric, stress perfusion, cardiovascular magnetic resonance imaging, and computed tomography coronary angiography. Health and well-being will be assessed in the longer term. The primary outcome is the proportion of patients with a diagnosis of myocardial inflammation. Conclusion: CISCO-19 will provide detailed insights into cardiovascular and multisystem involvement of COVID-19. Our study will inform the rationale and design of novel therapeutic and management strategies for affected patients

SurgiCal Obesity Treatment Study (SCOTS) : a prospective, observational cohort study on health and socioeconomic burden in treatment-seeking individuals with severe obesity in Scotland, UK

Objectives: There is a lack of evidence to inform the delivery and follow-up of bariatric surgery for people with severe obesity. The SurgiCal Obesity Treatment Study (SCOTS) is a national longitudinal cohort of people undergoing bariatric surgery. Here, we describe characteristics of the recruited SCOTS cohort, and the relationship between health and socioeconomic status with body mass index (BMI) and age. Participants/Methods: 445 participants scheduled for bariatric surgery at any of 14 centres in Scotland, UK, were recruited between 2013 and 2016 for this longitudinal cohort study (1 withdrawal); 249 completed health-related preoperative patient-reported outcome measures. Regression models were used to estimate the effect of a 10-unit increase in age or BMI, adjusting for sex, smoking and socioeconomic status. Results: Mean age was 46 years and median BMI was 47 kg/m2. For each 10 kg/m2 higher BMI, there was a change of −5.2 (95% CI −6.9 to –3.5; p<0.0001) in Rand 12-item Short Form Survey Physical Component Summary (SF-12 PCS), −0.1 (95% CI −0.2 to –0.1; p<0.0001) in EuroQoL 5-level EQ-5D version index score and 14.2 (95% CI 10.7 to 17.7; p<0.0001) in Impact of Weight on Quality of Life-Lite Physical Function Score. We observed a 3.1 times higher use of specialist aids and equipment at home (OR: 3.1, 95% CI 1.9 to 5.0; p<0.0001). Broadly, similar results were seen for each 10-year higher age, including a change of −2.1 (95% CI −3.7 to –0.5; p<0.01) in SF-12 PCS. Conclusions: A higher BMI combined with older age is associated with poor physical functioning and quality of life in people seeking bariatric surgery treatment. Policy-makers must consider the health and care needs of these individuals and invest to provide increased access to effective weight management. Trial registration number: ISRCTN47072588

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Socioeconomic deprivation and illness trajectory in the Scottish population after COVID-19 hospitalization

Background The associations between deprivation and illness trajectory after hospitalisation for coronavirus disease-19 (COVID-19) are uncertain. Methods A prospective, multicentre cohort study was conducted on post-COVID-19 patients, enrolled either in-hospital or shortly post-discharge. Two evaluations were carried out: an initial assessment and a follow-up at 28–60 days post-discharge. The study encompassed research blood tests, patient-reported outcome measures, and multisystem imaging (including chest computed tomography (CT) with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging). Primary and secondary outcomes were analysed in relation to socioeconomic status, using the Scottish Index of Multiple Deprivation (SIMD). The EQ-5D-5L, Brief Illness Perception Questionnaire (BIPQ), Patient Health Questionnaire-4 (PHQ-4) for Anxiety and Depression, and the Duke Activity Status Index (DASI) were used to assess health status. Results Of the 252 enrolled patients (mean age 55.0 ± 12.0 years; 40% female; 23% with diabetes), deprivation status was linked with increased BMI and diabetes prevalence. 186 (74%) returned for the follow-up. Within this group, findings indicated associations between deprivation and lung abnormalities (p = 0.0085), coronary artery disease (p = 0.0128), and renal inflammation (p = 0.0421). Furthermore, patients with higher deprivation exhibited worse scores in health-related quality of life (EQ-5D-5L, p = 0.0084), illness perception (BIPQ, p = 0.0004), anxiety and depression levels (PHQ-4, p = 0.0038), and diminished physical activity (DASI, p = 0.002). At the 3-month mark, those with greater deprivation showed a higher frequency of referrals to secondary care due to ongoing COVID-19 symptoms (p = 0.0438). However, clinical outcomes were not influenced by deprivation. Conclusions In a post-hospital COVID-19 population, socioeconomic deprivation was associated with impaired health status and secondary care episodes. Deprivation influences illness trajectory after COVID-19