Salmonella enterica bacteraemia: a multi-national population-based cohort study

<p>Abstract</p> <p>Background</p> <p><it>Salmonella enterica </it>is an important emerging cause of invasive infections worldwide. However, population-based data are limited. The objective of this study was to define the occurrence of <it>S. enterica </it>bacteremia in a large international population and to evaluate temporal and regional differences.</p> <p>Methods</p> <p>We conducted population-based laboratory surveillance for all salmonella bacteremias in six regions (annual population at risk 7.7 million residents) in Finland, Australia, Denmark, and Canada during 2000-2007.</p> <p>Results</p> <p>A total of 622 cases were identified for an annual incidence of 1.02 per 100,000 population. The incidence of typhoidal (serotypes Typhi and Paratyphi) and non-typhoidal (other serotypes) disease was 0.21 and 0.81 per 100,000/year. There was major regional and moderate seasonal and year to year variability with an increased incidence observed in the latter years of the study related principally to increasing rates of non-typhoidal salmonella bacteremias. Advancing age and male gender were significant risk factors for acquiring non-typhoidal salmonella bacteremia. In contrast, typhoidal salmonella bacteremia showed a decreasing incidence with advancing age and no gender-related excess risk.</p> <p>Conclusions</p> <p><it>Salmonella enterica </it>is an important emerging pathogen and regional determinants of risk merits further investigation.</p

Rationale for and protocol of a multi-national population-based bacteremia surveillance collaborative

<p>Abstract</p> <p>Background</p> <p>Bloodstream infections are frequent causes of human illness and cause major morbidity and death. In order to best define the epidemiology of these infections and to track changes in occurrence, adverse outcome, and resistance rates over time, population based methodologies are optimal. However, few population-based surveillance systems exist worldwide, and because of differences in methodology inter-regional comparisons are limited. In this report we describe the rationale and propose first practical steps for developing an international collaborative approach to the epidemiologic study and surveillance for bacteremia.</p> <p>Findings</p> <p>The founding collaborative participants represent six regions in four countries in three continents with a combined annual surveillance population of more than 8 million residents.</p> <p>Conclusion</p> <p>Future studies from this collaborative should lead to a better understanding of the epidemiology of bloodstream infections.</p

Qualitative meta-synthesis of user experience of computerised therapy for depression and anxiety

Objective: Computerised therapies play an integral role in efforts to improve access to psychological treatment for patients with depression and anxiety. However, despite recognised problems with uptake, there has been a lack of investigation into the barriers and facilitators of engagement. We aimed to systematically review and synthesise findings from qualitative studies of computerised therapies, in order to identify factors impacting on engagement. Method: Systematic review and meta-synthesis of qualitative studies of user experiences of computer delivered therapy for depression and/or anxiety. Results: 8 studies were included in the review. All except one were of desktop based cognitive behavioural treatments. Black and minority ethnic and older participants were underrepresented, and only one study addressed users with a comorbid physical health problem. Through synthesis, we identified two key overarching concepts, regarding the need for treatments to be sensitive to the individual, and the dialectal nature of user experience, with different degrees of support and anonymity experienced as both positive and negative. We propose that these factors can be conceptually understood as the ‘non-specific’ or ‘common’ factors of computerised therapy, analogous to but distinct from the common factors of traditional face-to-face therapies. Conclusion: Experience of computerised therapy could be improved through personalisation and sensitisation of content to individual users, recognising the need for users to experience a sense of ‘self’ in the treatment which is currently absent. Exploiting the common factors of computerised therapy, through enhancing perceived connection and collaboration, could offer a way of reconciling tensions due to the dialectal nature of user experience. Future research should explore whether the findings are generalisable to other patient groups, to other delivery formats (such as mobile technology) and other treatment modalities beyond cognitive behaviour therapy. The proposed model could aid the development of enhancements to current packages to improve uptake and support engagement

Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities. [Abstract copyright: © 2023. The Author(s).

Deep Drilling in the Time Domain with DECam: Survey Characterization

This paper presents a new optical imaging survey of four deep drilling fields (DDFs), two Galactic and two extragalactic, with the Dark Energy Camera (DECam) on the 4 meter Blanco telescope at the Cerro Tololo Inter-American Observatory (CTIO). During the first year of observations in 2021, $>$4000 images covering 21 square degrees (7 DECam pointings), with $\sim$40 epochs (nights) per field and 5 to 6 images per night per filter in $g$, $r$, $i$, and/or $z$, have become publicly available (the proprietary period for this program is waived). We describe the real-time difference-image pipeline and how alerts are distributed to brokers via the same distribution system as the Zwicky Transient Facility (ZTF). In this paper, we focus on the two extragalactic deep fields (COSMOS and ELAIS-S1), characterizing the detected sources and demonstrating that the survey design is effective for probing the discovery space of faint and fast variable and transient sources. We describe and make publicly available 4413 calibrated light curves based on difference-image detection photometry of transients and variables in the extragalactic fields. We also present preliminary scientific analysis regarding Solar System small bodies, stellar flares and variables, Galactic anomaly detection, fast-rising transients and variables, supernovae, and active galactic nuclei.Comment: 22 pages, 17 figures, 2 tables. Accepted to MNRA

RNAi Screen of DAF-16/FOXO Target Genes in C. elegans Links Pathogenesis and Dauer Formation

The DAF-16/FOXO transcription factor is the major downstream output of the insulin/IGF1R signaling pathway controlling C. elegans dauer larva development and aging. To identify novel downstream genes affecting dauer formation, we used RNAi to screen candidate genes previously identified to be regulated by DAF-16. We used a sensitized genetic background [eri-1(mg366); sdf-9(m708)], which enhances both RNAi efficiency and constitutive dauer formation (Daf-c). Among 513 RNAi clones screened, 21 displayed a synthetic Daf-c (SynDaf) phenotype with sdf-9. One of these genes, srh-100, was previously identified to be SynDaf, but twenty have not previously been associated with dauer formation. Two of the latter genes, lys-1 and cpr-1, are known to participate in innate immunity and six more are predicted to do so, suggesting that the immune response may contribute to the dauer decision. Indeed, we show that two of these genes, lys-1 and clc-1, are required for normal resistance to Staphylococcus aureus. clc-1 is predicted to function in epithelial cohesion. Dauer formation exhibited by daf-8(m85), sdf-9(m708), and the wild-type N2 (at 27°C) were all enhanced by exposure to pathogenic bacteria, while not enhanced in a daf-22(m130) background. We conclude that knockdown of the genes required for proper pathogen resistance increases pathogenic infection, leading to increased dauer formation in our screen. We propose that dauer larva formation is a behavioral response to pathogens mediated by increased dauer pheromone production

The Copernicus Marine Environment Monitoring Service Ocean State Report

The Copernicus Marine Environment Monitoring Service (CMEMS) Ocean State Report (OSR) provides an annual report of the state of the global ocean and European regional seas for policy and decision-makers with the additional aim of increasing general public awareness about the status of, and changes in, the marine environment. The CMEMS OSR draws on expert analysis and provides a 3-D view (through reanalysis systems), a view from above (through remote-sensing data) and a direct view of the interior (through in situ measurements) of the global ocean and the European regional seas. The report is based on the unique CMEMS monitoring capabilities of the blue (hydrography, currents), white (sea ice) and green (e.g. Chlorophyll) marine environment. This first issue of the CMEMS OSR provides guidance on Essential Variables, large-scale changes and specific events related to the physical ocean state over the period 1993–2015. Principal findings of this first CMEMS OSR show a significant increase in global and regional sea levels, thermosteric expansion, ocean heat content, sea surface temperature and Antarctic sea ice extent and conversely a decrease in Arctic sea ice extent during the 1993–2015 period. During the year 2015 exceptionally strong large-scale changes were monitored such as, for example, a strong El Niño Southern Oscillation, a high frequency of extreme storms and sea level events in specific regions in addition to areas of high sea level and harmful algae blooms. At the same time, some areas in the Arctic Ocean experienced exceptionally low sea ice extent and temperatures below average were observed in the North Atlantic Ocean

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention