Host genotype and genetic diversity shape the evolution of a novel bacterial infection

Pathogens continue to emerge from increased contact with novel host species. Whilst these hosts can represent distinct environments for pathogens, the impacts of host genetic background on how a pathogen evolves post-emergence are unclear. In a novel interaction, we experimentally evolved a pathogen (Staphylococcus aureus) in populations of wild nematodes (Caenorhabditis elegans) to test whether host genotype and genetic diversity affect pathogen evolution. After ten rounds of selection, we found that pathogen virulence evolved to vary across host genotypes, with differences in host metal ion acquisition detected as a possible driver of increased host exploitation. Diverse host populations selected for the highest levels of pathogen virulence, but infectivity was constrained, unlike in host monocultures. We hypothesise that population heterogeneity might pool together individuals that contribute disproportionately to the spread of infection or to enhanced virulence. The genomes of evolved populations were sequenced, and it was revealed that pathogens selected in distantly-related host genotypes diverged more than those in closely-related host genotypes. S. aureus nevertheless maintained a broad host range. Our study provides unique empirical insight into the evolutionary dynamics that could occur in other novel infections of wildlife and humans

Regional Climate Trends and Scenarios for the U.S. National Climate Assessment Part 4. Climate of the U.S. Great Plains

This document is one of series of regional climate descriptions designed to provide input that can be used in the development of the National Climate Assessment (NCA). As part of a sustained assessment approach, it is intended that these documents will be updated as new and well-vetted model results are available and as new climate scenario needs become clear. It is also hoped that these documents (and associated data and resources) are of direct benefit to decision makers and communities seeking to use this information in developing adaptation plans. There are nine reports in this series, one each for eight regions defined by the NCA, and one for the contiguous U.S. The eight NCA regions are the Northeast, Southeast, Midwest, Great Plains, Northwest, Southwest, Alaska, and Hawai‘i/Pacific Islands. These documents include a description of the observed historical climate conditions for each region and a set of climate scenarios as plausible futures – these components are described in more detail below. While the datasets and simulations in these regional climate documents are not, by themselves, new, (they have been previously published in various sources), these documents represent a more complete and targeted synthesis of historical and plausible future climate conditions around the specific regions of the NCA. There are two components of these descriptions. One component is a description of the historical climate conditions in the region. The other component is a description of the climate conditions associated with two future pathways of greenhouse gas emissions

Health Center Data Warehouses: Opportunities and Challenges for Quality Improvement

This Policy Research Brief reports on a pilot effort to leverage the growing presence of health center data warehouses to advance health care quality improvement through data sharing and exchange. This project builds on a partnership between the Michigan Primary Care Association and The George Washington University\u27s Geiger Gibson/RCHN Community Health Foundation Research Collaborative that centers on developing approaches to using existing health center data for quality improvement

The Implementation Playbook: Study protocol for the development and feasibility evaluation of a digital tool for effective implementation of evidence-based innovations

BACKGROUND: Evidence-based innovations can improve health outcomes, but only if successfully implemented. Implementation can be complex, highly susceptible to failure, costly and resource intensive. Internationally, there is an urgent need to improve the implementation of effective innovations. Successful implementation is best guided by implementation science, but organizations lack implementation know-how and have difficulty applying it. Implementation support is typically shared in static, non-interactive, overly academic guides and is rarely evaluated. In-person implementation facilitation is often soft-funded, costly, and scarce. This study seeks to improve effective implementation by (1) developing a first-in-kind digital tool to guide pragmatic, empirically based and self-directed implementation planning in real-time; and (2) exploring the tool\u27s feasibility in six health organizations implementing different innovations. METHODS: Ideation emerged from a paper-based resource, The Implementation Game©, and a revision called The Implementation Roadmap©; both integrate core implementation components from evidence, models and frameworks to guide structured, explicit, and pragmatic planning. Prior funding also generated user personas and high-level product requirements. This study will design, develop, and evaluate the feasibility of a digital tool called The Implementation Playbook©. In Phase 1, user-centred design and usability testing will inform tool content, visual interface, and functions to produce a minimum viable product. Phase 2 will explore the Playbook\u27s feasibility in six purposefully selected health organizations sampled for maximum variation. Organizations will use the Playbook for up to 24 months to implement an innovation of their choosing. Mixed methods will gather: (i) field notes from implementation team check-in meetings; (ii) interviews with implementation teams about their experience using the tool; (iii) user free-form content entered into the tool as teams work through implementation planning; (iv) Organizational Readiness for Implementing Change questionnaire; (v) System Usability Scale; and (vi) tool metrics on how users progressed through activities and the time required to do so. DISCUSSION: Effective implementation of evidence-based innovations is essential for optimal health. We seek to develop a prototype digital tool and demonstrate its feasibility and usefulness across organizations implementing different innovations. This technology could fill a significant need globally, be highly scalable, and potentially valid for diverse organizations implementing various innovations

The fossil insect assemblage associated with the Toarcian (Lower Jurassic) oceanic anoxic event from Alderton Hill, Gloucestershire, UK

Extreme global warming and environmental changes associated with the Toarcian (Lower Jurassic) Oceanic Anoxic Event (T-OAE, ∼183 Mya) profoundly impacted marine organisms and terrestrial plants. Despite the exceptionally elevated abundances of fossil insects from strata of this age, only assemblages from Germany and Luxembourg have been studied in detail. Here, we focus on the insect assemblage found in strata recording the T-OAE at Alderton Hill, Gloucestershire, UK, where <15% of specimens have previously been described. We located all known fossil insects (n = 370) from Alderton Hill, and used these to create the first comprehensive taxonomic and taphonomic analysis of the entire assemblage. We show that a diverse palaeoentomofaunal assemblage is preserved, comprising 12 orders, 21 families, 23 genera and 21 species. Fossil disarticulation is consistent with insect decay studies. The number of orders is comparable with present-day assemblages from similar latitudes (30°-40°N), including the Azores, and suggests that the palaeoentomofauna reflects a life assemblage. At Alderton, Hemiptera, Coleoptera and Orthoptera are the commonest (56.1%) orders. The high abundance of Hemiptera (22.1%) and Orthoptera (13.4%) indicates well-vegetated islands, while floral changes related to the T-OAE may be responsible for hemipteran diversification. Predatory insects are relatively abundant (∼10% of the total assemblage) and we hypothesise that the co-occurrence of fish and insects within the T-OAE represents a jubilee-like event. The marginally higher proportion of sclerotised taxa compared to present-day insect assemblages possibly indicates adaptation to environmental conditions or taphonomic bias. The coeval palaeoentomofauna from Strawberry Bank, Somerset is less diverse (9 orders, 12 families, 6 genera, 3 species) and is taphonomically biased. The Alderton Hill palaeoentomofauna is interpreted to be the bestpreserved and most representative insect assemblage from Toarcian strata in the UK. This study provides an essential first step towards understanding the likely influence of the TOAE on insects

Hybrid Polypyrrole and Polydopamine Nanosheets for Precise Raman/Photoacoustic Imaging and Photothermal Therapy

The development of near-infrared light (NIR)-responsive conductive polymers provides a useful theranostic platform for malignant tumours by maximizing spatial resolution with deep tissue penetration for diagnosis and photothermal therapy. Herein, we demonstrated the self-assembly of ultrathin two-dimensional (2D) polypyrrole nanosheets utilizing dopamine as a capping agent and a monolayer of octadecylamine as a template. The 2D polypyrrole-polydopamine nanostructure (DPPy) had tunable size distribution which showed strong absorption in the first and second near-infrared windows, enabling photoacoustic imaging and photothermal therapy. The hybrid double-layer was demonstrated to increase Raman intensity for 3D Raman imaging (up to two orders of magnitude enhancement and spatial resolution up to 1 μm). The acidic environment drove reversible doping of polypyrrole, which could be detected by Raman spectroscopy. The combined properties of the nanosheets could substantially enhance performance in dual-mode Raman and photoacoustic guided photothermal therapy, as shown by the 69% light to heat conversion efficiency and higher cytotoxicity against cancer spheroids. These pH-responsive features highlight the potential of 2D conductive polymers for applications in accurate, highly efficient theranostics. This article is protected by copyright. All rights reserved

Within- and between-host dynamics of producer and non-producer pathogens

For infections to be maintained in a population, pathogens must compete to colonise hosts and transmit between them. Within the host, much research has been conducted into pathogeni interactions, yet less is known about whether within-host interactions can affect between-host transmission. In this study, we use an experimental approach to investigate within-and-between host dynamics using the pathogen Pseudomonas aeruginosa and the host Caenorhabditis elegans. Within-host interactions often involve the production of goods, that are beneficial to all the pathogens in the local environment but susceptible to exploitation by non-producers. We exposed the nematode host to ‘producer’ and two ‘non-producer’ bacterial strains (specifically for siderophore production and quorum sensing), in single infections and coinfections, to investigate within-host colonisation. Subsequently, we introduced infected nematodes to pathogen-naive populations, to allow natural pathogen transmission between hosts. We find that producer pathogens are consistently better at colonising hosts and transmitting between them than non-producers during coinfection and single infection. Non-producers were poor at colonising hosts and between-host transmission, even when coinfecting with producers. Understanding pathogen dynamics across these multiple levels will ultimately help us to predict and control the spread of infections and contribute to explanations for the persistence of cooperative genotypes in natural populations

Trends in kidney function testing in UK primary care since the introduction of the Quality and Outcomes Framework:a retrospective cohort study using CPRD

Objectives: To characterise serum creatinine and urinary protein testing in UK general practices from 2005 to 2013 and to examine how the frequency of testing varies across demographic factors, with the presence of chronic conditions and with the prescribing of drugs for which kidney function monitoring is recommended. Design: Retrospective open cohort study. Setting: Routinely collected data from 630 UK general practices contributing to the Clinical Practice Research Datalink. Participants: 4 573 275 patients aged over 18 years registered at up-to-standard practices between 1 April 2005 and 31 March 2013. At study entry, no patients were kidney transplant donors or recipients, pregnant or on dialysis. Primary outcome measures: The rate of serum creatinine and urinary protein testing per year and the percentage of patients with isolated and repeated testing per year. Results: The rate of serum creatinine testing increased linearly across all age groups. The rate of proteinuria testing increased sharply in the 2009–2010 financial year but only for patients aged 60 years or over. For patients with established chronic kidney disease (CKD), creatinine testing increased rapidly in 2006–2007 and 2007–2008, and proteinuria testing in 2009–2010, reflecting the introduction of Quality and Outcomes Framework indicators. In adjusted analyses, CKD Read codes were associated with up to a twofold increase in the rate of serum creatinine testing, while other chronic conditions and potentially nephrotoxic drugs were associated with up to a sixfold increase. Regional variation in serum creatinine testing reflected country boundaries. Conclusions: Over a nine-year period, there have been increases in the numbers of patients having kidney function tests annually and in the frequency of testing. Changes in the recommended management of CKD in primary care were the primary determinant, and increases persist even after controlling for demographic and patient-level factors. Future studies should address whether increased testing has led to better outcomes.</p

Systematic review and metaanalysis comparing the bias and accuracy of the modification of diet in renal disease and chronic kidney disease epidemiology collaboration equations in community-based population

BACKGROUND The majority of patients with chronic kidney disease are diagnosed and monitored in primary care. Glomerular filtration rate (GFR) is a key marker of renal function, but direct measurement is invasive; in routine practice, equations are used for estimated GFR (eGFR) from serum creatinine. We systematically assessed bias and accuracy of commonly used eGFR equations in populations relevant to primary care. CONTENT MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing measured GFR (mGFR) with eGFR in adult populations comparable to primary care and reporting both the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on standardized creatinine measurements. We pooled data on mean bias (difference between eGFR and mGFR) and on mean accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse-variance weighted metaanalysis. We included 48 studies of 26875 patients that reported data on bias and/or accuracy. Metaanalysis of within-study comparisons in which both formulae were tested on the same patient cohorts using isotope dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1–3.2; 30 studies; I2 = 74.4%) and a higher mean accuracy of CKD-EPI of 2.7% (1.6–3.8; 47 studies; I2 = 55.5%). Metaregression showed that in both equations bias and accuracy favored the CKD-EPI equation at higher mGFR values. SUMMARY Both equations underestimated mGFR, but CKD-EPI gave more accurate estimates of GFR

Exploring interprofessional collaboration and attitudes of health sciences librarians

Objective: This study assessed health sciences librarians’ attitudes toward interprofessional collaboration using the Interdisciplinary Education Perception Scale (IEPS) and gathered information on their involvement with interprofessional activities. Methods: The authors sent a survey to librarians in the Medical Library Association’s (MLA’s) Interprofessional Education Special Interest Group and Research Section consisting of the IEPS and questions about their prior and current experiences with interprofessional practice and education (IPE). We compared mean IEPS scores between each MLA group and several other demographic factors to assess differences in attitudes. We also compared librarians’ IEPS scores with those of previously published health professional students’ IEPS scores and thematically analyzed two open-ended questions. Results: Health sciences librarians’ scores on the IEPS indicated positive attitudes toward IPE. There were no statistically significant differences between any group. Health sciences librarians’ mean IEPS score was similar to the mean score of health professions students from a prior study. The most commonly reported interprofessional activity was teaching or facilitating learning activities for health professions students; fewer served on committees or engaged in non-curricular activities such as grand rounds and book clubs. Conclusion: Health sciences librarians in this study reported positive attitudes toward IPE, in line with the majority of other previously studied health professionals. Years of experience, previous health professional careers, and experience supporting IPE as a librarian had little bearing on the responses to the survey. This suggests that health sciences librarians have positive attitudes toward IPE, regardless of whether they directly support IPE programs or participate in interprofessional activities