Viral diversity and prevalence gradients in North American Pacific Coast grasslands

Host-pathogen interactions may be governed by the number of pathogens coexisting within an individual host (i.e., coinfection) and among different hosts, although most sampling in natural systems focuses on the prevalence of single pathogens and/or single hosts. We measured the prevalence of four barley and cereal yellow dwarf viruses (B/CYDVs) in three grass species at 26 natural grasslands along a 2000-km latitudinal gradient in the western United States and Canada. B/CYDVs are aphid-vectored RNA viruses that cause one of the most prevalent of all plant diseases worldwide. Pathogen prevalence and coinfection were uncorrelated, suggesting that different forces likely drive them. Coinfection, the number of viruses in a single infected host (alpha diversity), did not differ among host species but increased roughly twofold across our latitudinal transect. This increase in coinfection corresponded with a decline in among-host pathogen turnover (beta diversity), suggesting that B/CYDVs in northern populations experience less transmission limitation than in southern populations. In contrast to pathogen diversity, pathogen prevalence was a function of host identity as well as biotic and abiotic environmental conditions. Prevalence declined with precipitation and increased with soil nitrate concentration, an important limiting nutrient for hosts and vectors of B/CYDVs. This work demonstrates the need for further studies of processes governing coinfection, and the utility of applying theory developed to explain diversity in communities of free-living organisms to pathogen systems

Effectiveness of a structured, framework-based approach to implementation: the Researching Effective Approaches to Cleaning in Hospitals (REACH) Trial

BACKGROUND: Implementing sustainable practice change in hospital cleaning has proven to be an ongoing challenge in reducing healthcare associated infections. The purpose of this study was to develop a reliable framework-based approach to implement and quantitatively evaluate the implementation of evidence-based practice change in hospital cleaning. DESIGN/METHODS: The Researching Effective Approaches to Cleaning in Hospitals (REACH) trial was a pragmatic, stepped-wedge randomised trial of an environmental cleaning bundle implemented in 11 Australian hospitals from 2016 to 2017. Using a structured multi-step approach, we adapted the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to support rigorous and tailored implementation of the cleaning bundle intervention in eleven diverse and complex settings. To evaluate the effectiveness of this strategy we examined post-intervention cleaning bundle alignment calculated as a score (an implementation measure) and cleaning performance audit data collected using ultraviolet (UV) gel markers (an outcome measure). RESULTS: We successfully implemented the bundle and observed improvements in cleaning practice and performance, regardless of hospital size, intervention duration and contextual issues such as staff and organisational readiness at baseline. There was a positive association between bundle alignment scores and cleaning performance at baseline. This diminished over the duration of the intervention, as hospitals with lower baseline scores were able to implement practice change successfully. CONCLUSION: Using a structured framework-based approach allows for pragmatic and successful implementation of clinical trials across diverse settings, and assists with quantitative evaluation of practice change. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12615000325505, registered on 4 September 2015

Improving Delivery of Secondary Prophylaxis for Rheumatic Heart Disease in a High-Burden Setting: Outcome of a Stepped-Wedge, Community, Randomized Trial

BACKGROUND Health system strengthening is needed to improve delivery of secondary prophylaxis against rheumatic heart disease. METHODS AND RESULTS We undertook a stepped-wedge, randomized trial in northern Australia. Five pairs of Indigenous community clinics entered the study at 3-month steps. Study phases comprised a 12 month baseline phase, 3 month transition phase, 12 month intensive phase and a 3- to 12-month maintenance phase. Clinics received a multicomponent intervention supporting activities to improve penicillin delivery, aligned with the chronic care model, with continuous quality-improvement feedback on adherence. The primary outcome was the proportion receiving ≥80% of scheduled penicillin injections. Secondary outcomes included "days at risk" of acute rheumatic fever recurrence related to late penicillin and acute rheumatic fever recurrence rates. Overall, 304 patients requiring prophylaxis were eligible. The proportion receiving ≥80% of scheduled injections during baseline was 141 of 304 (46%)-higher than anticipated. No effect attributable to the study was evident: in the intensive phase, 126 of 304 (41%) received ≥80% of scheduled injections (odds ratio compared with baseline: 0.78; 95% confidence interval, 0.54-1.11). There was modest improvement in the maintenance phase among high-adhering patients (43% received ≥90% of injections versus 30% [baseline] and 28% [intensive], P<0.001). Also, the proportion of days at risk in the whole cohort decreased in the maintenance phase (0.28 versus 0.32 [baseline] and 0.34 [intensive], P=0.001). Acute rheumatic fever recurrence rates did not differ between study sites during the intensive phase and the whole jurisdiction (3.0 versus 3.5 recurrences per 100 patient-years, P=0.65). CONCLUSIONS This strategy did not improve adherence to rheumatic heart disease secondary prophylaxis within the study time frame. Longer term primary care strengthening strategies are needed. CLINICAL TRIAL REGISTRATION URL: www.anzctr.org.au. Unique identifier: ACTRN12613000223730

Qualitative Evaluation of a Complex Intervention to Improve Rheumatic Heart Disease Secondary Prophylaxis

BACKGROUND Rheumatic heart disease is a high-burden condition in Australian Aboriginal communities. We evaluated a stepped-wedge, community, randomized trial at 10 Aboriginal communities from 2013 to 2015. A multifaceted intervention was implemented using quality improvement and chronic care model approaches to improve delivery of penicillin prophylaxis for rheumatic heart disease. The trial did not improve penicillin adherence. This mixed-methods evaluation, designed a priori, aimed to determine the association between methodological approaches and outcomes. METHODS AND RESULTS An evaluation framework was developed to measure the success of project implementation and of the underlying program theory. The program theory posited that penicillin delivery would be improved through activities implemented at clinics that addressed elements of the chronic care model. Qualitative data were derived from interviews with health-center staff, informants, and clients; participant observation; and project officer reports. Quantitative data comprised numbers and types of "action items," which were developed by participating clinic staff with project officers to improve delivery of penicillin injections. Interview data from 121 health-center staff, 22 informants, and 72 clients revealed barriers to achieving the trial's aims, including project-level factors (short trial duration), implementation factors (types of activities implemented), and contextual factors (high staff turnover and the complex sociocultural environment). Insufficient actions were implemented addressing "self-management support" and "community linkage" streams of the chronic care model. Increased momentum was evident in later stages of the study. CONCLUSIONS The program theory underpinning the study was sound. The limited impact made by the study on adherence was attributable to complex implementation challenges.This study was funded by the Australian National Health and Medical Research Council (NHMRC) project grant 1027040 and Center of Research Excellence 1080401 and by the Wesfarmers Center for Vaccines and Infectious Diseases at Telethon Kids Institute. Ralph and Maguire are supported by NHMRC fellowships (1142011 and 1046563, respectively)

Non-random biodiversity loss underlies predictable increases in viral disease prevalence

Disease dilution (reduced disease prevalence with increasing biodiversity) has been described for many different pathogens. Although the mechanisms causing this phenomenon remain unclear, the disassembly of communities to predictable subsets of species, which can be caused by changing climate, land use, or invasive species, underlie one important hypothesis. In this case, infection prevalence will reflect the competence of the remaining hosts. To test this hypothesis, we measured local host species abundance and prevalence of four generalist aphid-vectored pathogens (barley and cereal yellow dwarf viruses) in a ubiquitous annual grass host at ten sites spanning 2000 kilometers along the North American West Coast. In lab and field trials, we measured viral infection, and aphid fecundity and feeding preference on several host species. Virus prevalence increased as local host richness declined. Community disassembly was non random: ubiquitous hosts dominating species-poor assemblages were among the most competent for vector production and virus transmission. This suggests that non-random biodiversity loss led to increased virus prevalence. Because diversity loss is occurring globally in response to anthropogenic changes, such work can inform medical, agricultural, and veterinary disease research by providing insights into the dynamics of pathogens nested within a complex web of environmental forces.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The article is copyrighted by the author(s) and published by The Royal Society. It can be found at: http://rsif.royalsocietypublishing.org/.KEYWORDS: Vector-borne pathogen, Bromus hordeaceus, Rhopalosiphum padi (Aphididae), Disease dilution, Nestedness, Barley and cereal yellow dwarf viruses (B/CYDVs, Luteoviridae

Direct and Interactive Effects of Enemies and Mutualists on Plant Performance: A Meta-Analysis

Plants engage in multiple, simultaneous interactions with other species; some (enemies) reduce and others (mutualists) enhance plant performance. Moreover, effects of different species may not be independent of one another; for example, enemies may compete, reducing their negative impact on a plant. The magnitudes of positive and negative effects, as well as the frequency of interactive effects and whether they tend to enhance or depress plant performance, have never been comprehensively assessed across the many published studies on plant–enemy and plant–mutualist interactions. We performed a meta-analysis of experiments in which two enemies, two mutualists, or an enemy and a mutualist were manipulated factorially. Specifically, we performed a factorial meta-analysis using the log response ratio. We found that the magnitude of (negative) enemy effects was greater than that of (positive) mutualist effects in isolation, but in the presence of other species, the two effects were of comparable magnitude. Hence studies evaluating single-species effects of mutualists may underestimate the true effects found in natural settings, where multiple interactions are the norm and indirect effects are possible. Enemies did not on average influence the effects on plant performance of other enemies, nor did mutualists influence the effects of mutualists. However, these averages mask significant and large, but positive or negative, interactions in individual studies. In contrast, mutualists ameliorated the negative effects of enemies in a manner that benefited plants; this overall effect was driven by interactions between pathogens and belowground mutualists (bacteria and mycorrhizal fungi). The high frequency of significant interactive effects suggests a widespread potential for diffuse rather than pairwise coevolutionary interactions between plants and their enemies and mutualists. Pollinators and mycorrhizal fungi enhanced plant performance more than did bacterial mutualists. In the greenhouse (but not the field), pathogens reduced plant performance more than did herbivores, pathogens were more damaging to herbaceous than to woody plants, and herbivores were more damaging to crop than to non-crop plants (suggesting evolutionary change in plants or herbivores following crop domestication). We discuss how observed differences in effect size might be confounded with methodological differences among studies

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

A comparison of welfare outcomes for weaner and mature Bos indicus bulls surgically or tension ban castrated with or without analgesia: 2. responses related to stress, health and productivity

Tension banding castration of cattle is gaining favour because it is relatively simple to perform and is promoted by retailers of the banders as a humane castration method. Two experiments were conducted, under tropical conditions using Bos indicus bulls comparing tension banding (Band) and surgical (Surgical) castration of weaner (7-10 months old) and mature (22-25 months old) bulls with and without pain management (NSAID (ketoprofen) or saline injected intramuscularly immediately prior to castration). Welfare outcomes were assessed using a range of measures; this paper reports on some physiological, morbidity and productivity-related responses to augment the behavioural responses reported in an accompanying paper. Blood samples were taken on the day of castration (day 0) at the time of restraint (0. min) and 30. min (weaners) or 40. min (mature bulls), 2. h, and 7. h; and days 1, 2, 3, 7, 14, 21 and 28 post-castration. Plasmas from day 0 were assayed for cortisol, creatine kinase, total protein and packed cell volume. Plasmas from the other samples were assayed for cortisol and haptoglobin (plus the 0. min sample). Liveweights were recorded approximately weekly to 6 weeks and at 2 and 3 months post-castration. Castration sites were checked at these same times to 2 months post-castration to score the extent of healing and presence of sepsis. Cortisol concentrations (mean. ±. s.e. nmol/L) were significantly (

Corruption and the Composition of Public Expenditures: Evidence from OECD Countries

This paper analyzes how corruption affects the composition of public expenditures. First, a two-stage rent-seeking model with endogenous rent-setting is derived that captures both "political corruption" and "bureaucratic corruption". The model illustrates how asymmetries between industries in the degree of competition and in the difficulty of concealing bribery may influence the allocation of public spending. The theoretical implications are tested with a panel dataset for 26 OECD countries over the 1996 - 2008 period. The results suggest that the shares of spending on health and environmental protection increase, while the shares of spending on social protection and recreation, culture and religion decline with higher levels of corruption. The significance of these distortions is robust to a variety of specifications such as fixed effects, random effects, seemingly unrelated regressions, the inclusion of additional controls, and the use of alternative corruption indicators

human cytochrome P450 2E1導入ヒト肝癌細胞株(HLE/2E1)の樹立と薬物毒性に対する特徴

C1 - Journal Articles RefereedMutations in RAD51D have been associated with an increased risk of hereditary ovarian cancer and although they have been observed in the context of breast and ovarian cancer families, the association with breast cancer is unclear. The aim of this current study was to validate the reported association of RAD51D with ovarian cancer and assess for an association with breast cancer. We screened for RAD51D mutations in BRCA1/2 mutation-negative index cases from 1,060 familial breast and/or ovarian cancer families (including 741 affected by breast cancer only) and in 245 unselected ovarian cancer cases. Exons containing novel non-synonymous variants were screened in 466 controls. Two overtly deleterious RAD51D mutations were identified among the unselected ovarian cancers cases (0.82%) but none were detected among the 1,060 families. Our data provide additional evidence that RAD51D mutations are enriched among ovarian cancer patients, but are extremely rare among familial breast cancer patients