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OBJECTIVES/SPECIFIC AIMS: To understand the mechanisms of how a non-antimicrobial can reshape a commensal microbe community to cure a ubiquitous human disease. METHODS/STUDY POPULATION: Whole genome sequencing of bacterial isolates, metabolomic investigations of previously collected skin microbe isolates from patients, and structural investigations of a protein from these skin microbes. RESULTS/ANTICIPATED RESULTS: Metabolic pathways associated with adaptation to a changing skin microenvironment, novel antimicrobial characterization, and a structural understanding of a novel nutrient acquisition protein. DISCUSSION/SIGNIFICANCE OF IMPACT: Multiple angles of this investigation are poised to improve current non-antimicrobial dermatologic treatments and they have the potential to impact microbe-related diseases in other human microenvironments.
OBJECTIVES/SPECIFIC AIMS: By combining clinical knowledge of hoarding disorder (HD) with qualitative methods from cultural anthropology, we hope to build a patient-centered approach that will allow us to better understand the clinician perspectives on patient motivations and explanatory models of individuals with HD, and improve treatment outcomes. We describe the ways that these methodologies are productively merged in this project as a result of TL1 collaboration, and present a preliminary picture of methodological and theoretical issues uncovered as part of this processes. We further describe the analytical methods used for this project, and explore issues raised through the combination of psychological and anthropological data and insights. METHODS/STUDY POPULATION: This study represents an attempt to combine the qualitative methodologies of cultural anthropology with the clinical knowledge of psychology and psychiatry in order to better understand gaps between provider and patient beliefs and knowledge about hoarding disorder. This study will present preliminary methodological issues arising from interviews with hoarding experts. RESULTS/ANTICIPATED RESULTS: This study will discuss preliminary issues including shared language, strengths and limitations of both disciplines, and factors for consideration when combining these disparate methodologies. It will close with recommendations for consideration when moving forward with similar collaborations. DISCUSSION/SIGNIFICANCE OF IMPACT: This project seeks to unite psychological and social factors that may contribute to the lived experience of individuals with HD in order to better understand the way that HD is manifested. It also unites disparate methodologies to provide us with a more holistic and complete picture of the experience of HD. While HD has been studied within psychiatry, it has never been assessed using the qualitative methods of anthropology. These methods provide the possibility of expanding knowledge about the ways that this disorder is experienced by individuals and their families, and potentially impacted by shared beliefs and cultures. Furthermore, qualitative data of this nature provides a patient perspective on the experience of HD as a psychiatric illness. This patient perspective can be used to better inform treatment, improve patient outcomes, and to allow providers and researchers to gain a fuller understanding of this complex population.
In the Euclidean plane a curve C has a one-parameter family of parallel involutes and a unique evolute C* which coincides with the locus of the centres of the osculating circles of C. If is parallel to C, C* is also the evolute of . We will study parallel curves in n-dimensional Euclidean space and obtain generalizations of the properties given above.
We will study parallel curves in n-dimensional Euclidean space and obtain generalizations of the properties given above.
Recovery Colleges are opening internationally. The evaluation focus has been on outcomes for Recovery College students who use mental health services. However, benefits may also arise for: staff who attend or co-deliver courses; the mental health and social care service hosting the Recovery College; and wider society. A theory-based change model characterising how Recovery Colleges impact at these higher levels is needed for formal evaluation of their impact, and to inform future Recovery College development. The aim of this study was to develop a stratified theory identifying candidate mechanisms of action and outcomes (impact) for Recovery Colleges at staff, services and societal levels.
Inductive thematic analysis of 44 publications identified in a systematised review was supplemented by collaborative analysis involving a lived experience advisory panel to develop a preliminary theoretical framework. This was refined through semi-structured interviews with 33 Recovery College stakeholders (service user students, peer/non-peer trainers, managers, community partners, clinicians) in three sites in England.
Candidate mechanisms of action and outcomes were identified at staff, services and societal levels. At the staff level, experiencing new relationships may change attitudes and associated professional practice. Identified outcomes for staff included: experiencing and valuing co-production; changed perceptions of service users; and increased passion and job motivation. At the services level, Recovery Colleges often develop somewhat separately from their host system, reducing the reach of the college into the host organisation but allowing development of an alternative culture giving experiential learning opportunities to staff around co-production and the role of a peer workforce. At the societal level, partnering with community-based agencies gave other members of the public opportunities for learning alongside people with mental health problems and enabled community agencies to work with people they might not have otherwise. Recovery Colleges also gave opportunities to beneficially impact on community attitudes.
This study is the first to characterise the mechanisms of action and impact of Recovery Colleges on mental health staff, mental health and social care services, and wider society. The findings suggest that a certain distance is needed in the relationship between the Recovery College and its host organisation if a genuine cultural alternative is to be created. Different strategies are needed depending on what level of impact is intended, and this study can inform decision-making about mechanisms to prioritise. Future research into Recovery Colleges should include contextual evaluation of these higher level impacts, and investigate effectiveness and harms.
To determine the prevalence of Clostridium difficile colonization among patients who meet the 2017 IDSA/SHEA C. difficile infection (CDI) Clinical Guideline Update criteria for the preferred patient population for C. difficile testing.
Tertiary-care hospital in St. Louis, Missouri.
Patients whose diarrheal stool samples were submitted to the hospital’s clinical microbiology laboratory for C. difficile testing (toxin EIA) from August 2014 to September 2016.
Electronic and manual chart review were used to determine whether patients tested for C. difficile toxin had clinically significant diarrhea and/or any alternate cause for diarrhea. Toxigenic C. difficile culture was performed on all stool specimens from patients with clinically significant diarrhea and no known alternate cause for their diarrhea.
A total of 8,931 patients with stool specimens submitted were evaluated: 570 stool specimens were EIA positive (+) and 8,361 stool specimens were EIA negative (−). Among the EIA+stool specimens, 107 (19% of total) were deemed eligible for culture. Among the EIA− stool specimens, 515 (6%) were eligible for culture. One EIA+stool specimen (1%) was toxigenic culture negative. Among the EIA− stool specimens that underwent culture, toxigenic C. difficile was isolated from 63 (12%).
Most patients tested for C. difficile do not have clinically significant diarrhea and/or potential alternate causes for diarrhea. The prevalence of toxigenic C. difficile colonization among EIA− patients who met the IDSA/SHEA CDI guideline criteria for preferred patient population for C. difficile testing was 12%.
The predictions of mean-field electrodynamics can now be probed using direct numerical simulations of random flows and magnetic fields. When modelling astrophysical magnetohydrodynamics, it is important to verify that such simulations are in agreement with observations. One of the main challenges in this area is to identify robust quantitative measures to compare structures found in simulations with those inferred from astrophysical observations. A similar challenge is to compare quantitatively results from different simulations. Topological data analysis offers a range of techniques, including the Betti numbers and persistence diagrams, that can be used to facilitate such a comparison. After describing these tools, we first apply them to synthetic random fields and demonstrate that, when the data are standardized in a straightforward manner, some topological measures are insensitive to either large-scale trends or the resolution of the data. Focusing upon one particular astrophysical example, we apply topological data analysis to H i observations of the turbulent interstellar medium (ISM) in the Milky Way and to recent magnetohydrodynamic simulations of the random, strongly compressible ISM. We stress that these topological techniques are generic and could be applied to any complex, multi-dimensional random field.
The Greenland ice sheet (GrIS) subglacial hydrological system may undergo a seasonal evolution, with significant geophysical and biogeochemical implications. We present results from a new isotope-mixing model to quantify the relative contributions of surface snow, glacial ice and delayed flow to the bulk meltwater discharge from a small (∼5 km2) land-terminating GrIS outlet glacier during melt onset (May) and at peak melt (July). We use radioactive (222Rn) and stable isotopes (18O, deuterium) to differentiate the water source contributions. Atmospherically derived 7Be further constrains meltwater transit time from the glacier surface to the ice margin. We show that (1) 222Rn is a promising tracer for glacial waters stored at the bed and (2) a quantitative chemical mixing model can be constructed by combining 222Rn and the stable water isotopes. Applying this model to the bulk subglacial outflow from our study area, we find a constant delayed-flow (stored) component from melt onset through peak melt. This component is diluted first by snowmelt and then by increasing glacial ice melt as the season progresses. Results from this pilot study are consistent with the hypothesis that subglacial drainage beneath land-terminating sections of the GrIS undergoes a seasonal evolution from a distributed to a channelized system.
The livestock sector is one of the fastest growing subsectors of the agricultural economy and, while it makes a major contribution to global food supply and economic development, it also consumes significant amounts of natural resources and alters the environment. In order to improve our understanding of the global environmental impact of livestock supply chains, the Food and Agriculture Organization of the United Nations has developed the Global Livestock Environmental Assessment Model (GLEAM). The purpose of this paper is to provide a review of GLEAM. Specifically, it explains the model architecture, methods and functionality, that is the types of analysis that the model can perform. The model focuses primarily on the quantification of greenhouse gases emissions arising from the production of the 11 main livestock commodities. The model inputs and outputs are managed and produced as raster data sets, with spatial resolution of 0.05 decimal degrees. The Global Livestock Environmental Assessment Model v1.0 consists of five distinct modules: (a) the Herd Module; (b) the Manure Module; (c) the Feed Module; (d) the System Module; (e) the Allocation Module. In terms of the modelling approach, GLEAM has several advantages. For example spatial information on livestock distributions and crops yields enables rations to be derived that reflect the local availability of feed resources in developing countries. The Global Livestock Environmental Assessment Model also contains a herd model that enables livestock statistics to be disaggregated and variation in livestock performance and management to be captured. Priorities for future development of GLEAM include: improving data quality and the methods used to perform emissions calculations; extending the scope of the model to include selected additional environmental impacts and to enable predictive modelling; and improving the utility of GLEAM output.
In 1975 F. J. Kerr and P. F. Bowers of the University of Maryland made a full coverage survey of the neutral hydrogen in the southern hemisphere between ±10° latitude from 240° to 350° in longitude. This survey taken with the CSIRO 18 meter telescope is still in the reduction stage but when completed it will provide an ideal complement to the full ±10° coverage of the northern sky by H. Weaver and D. R. W. Williams (1973). The possibility of a unified analysis of the outer region of the Galaxy has inspired this present study. The plan here is to use the ±10° Weaver-Williams survey in the region 10° < ℓ < 130°; the ±30° extension to this survey (H. Weaver and D. R. W. Williams, 1974) in the region 115° < ℓ < 245° and finally the Kerr-Bowers survey, 240° < ℓ < 350°. Since the latter survey is incompletely reduced at this time we have only used profiles at 5° intervals in longitude and thereby have produced a preliminary determination of the plane in the southern hemisphere. The northern hemisphere determination is complete.
Recent regulatory initiatives in the United States of America and Europe have transformed the paediatric clinical trials landscape by significantly increasing capital investment and paediatric trial volume. The purpose of this manuscript was to review the impact of these initiatives on the paediatric cardiovascular trials landscape when compared with other paediatric sub-specialties. We also evaluate factors that may have contributed to the success or failure of recent major paediatric cardiovascular trials so as to inform the optimal design and conduct of future trials in the field.
Paediatricians recognize that using the time-dependent community-acquired vs. hospital-acquired bloodstream infection (BSI) dichotomy to guide empirical treatment no longer distinguishes between causative pathogens due to the emergence of healthcare-associated BSIs. However, paediatric epidemiological evidence of the aetiology of BSIs in relation to hospital admission in England is lacking. For 12 common BSI-causing pathogens in England, timing of laboratory reports of positive paediatric (3 months to 5 years) bacterial blood isolates were linked to in-patient hospital data and plotted in relation to hospital admission. The majority (88·6%) of linked pathogens were isolated <2 days after hospital admission, including pathogens widely regarded as hospital acquired: Enterococcus spp. (67·2%) and Klebsiella spp. (88·9%). Neisseria meningitidis, Streptococcus pneumoniae, group A streptococcus and Salmonella spp. were unlikely to cause hospital-acquired BSI. Pathogens commonly associated with hospital-acquired BSI are being isolated <2 days after hospital admission alongside pathogens commonly associated with community-acquired BSI. We confirm that timing of blood samples alone does not differentiate between bacterial pathogens. Additional factors including clinical patient characteristics and healthcare contact should be considered to help predict the causative pathogen and guide empirical antibiotic therapy.
This study builds on existing research on the prevalence and consequences of mental illness discrimination by investigating and quantifying the relationships between experienced discrimination and costs of healthcare and leisure activities/social participation among secondary mental health service users in England.
We use data from the Mental Illness-Related Investigations on Discrimination (MIRIAD) study (n = 202) and a subsample of the Viewpoint study (n = 190). We examine experiences of discrimination due to mental illness in the domains of personal relationships, community activities, and health care, and how such experienced discrimination relates to patterns of service use and engagement in leisure activities.
Our findings show that the cost of health services used for individuals who reported previous experiences of discrimination in a healthcare setting was almost twice as high as for those who did not report any discrimination during the last 12 months (Relative Risk: 1.73; 95% Confidence Interval (CI): 1.39, 2.17) and this was maintained after controlling for symptoms and functioning. Experienced discrimination in healthcare (Relative Risk: 0.83; 95% CI: 0.81, 0.84) or in relationships (Relative Risk: 0.89; 95% CI: 0.87, 0.91), however, was associated with lower participation in, and hence lower costs of, leisure activities. Individuals who reported any discrimination in a healthcare setting had, on average, £434 higher costs associated with health service use while reported discrimination in the community was associated with increased leisure costs of £32.
These findings make an important initial step towards understanding the magnitude of the costs of mental health-related discrimination.
To explore the role of psychiatric admission, diagnosis and reported unfair treatment in the relationship between ethnicity and mistrust of mental health services.
The Mental Illness-Related Investigations on Discrimination (MIRIAD) study was a cross-sectional study of 202 individuals using secondary mental health services in South London. Two structural equation models were estimated, one using Admission (whether admitted to hospital for psychiatric treatment in the past 5 years) and one using involuntary admission to hospital in the past 5 years.
Increased mistrust was directly associated with the latent variable ‘unfair treatment by mental health services and staff’ and with Black or mixed ethnicity in both models. Those with a diagnosis of schizophrenia spectrum (as compared to depression and bipolar disorder) had a lower average score on the latent variable, suggesting that on average they reported less unfair treatment. We found evidence of increased reporting of unfair treatment by those who had an admission in the past 5 years, had experienced involuntary admission, and for people of Black of mixed Black and White ethnicity.
Neither prevalence of schizophrenia spectrum nor rates of hospital admission explained the greater mistrust of mental health services found among people of Black and mixed Black and White ethnicity compared with White ethnicity. Rather, people of Black and mixed Black and white ethnicity may be more likely to experience unfair treatment, generating mistrust; furthermore, this group is more likely to express mistrust even after accounting for reporting of unfair treatment by mental health services and staff.
The excavation of a large circular dished earthwork near Carnforth,
North Lancashire, in 1982, has revealed a substantial Bronze Age funerary
monument. The earliest structure was a sub-rectangular enclosure of
limestone boulders dated to c. 1740–1640 BC cal. and
associated with parts of two poorly preserved inhumation burials lying on
the previously cleared ground surface. Both burials were accompanied by
typologically early metalwork. The central inhumation was associated with
a flat axe and dagger, suggesting an individual of high status as well as
providing an important link between the early stages of development of
both bronze types. The subsequent overlying cairn of smaller stones
included eleven fairly discrete concentrations of inhumed bone, and seven
of cremated bone and pottery. All this material was extremely
fragmentary, and was probably derived from later re-use of the
Duchenne muscular dystrophy (DMD) is a severe muscle disease that affects afflicted males from a young age, and the mdx mouse is an animal model of this disease. Although new drugs are in development, it is also essential to assess potential dietary therapies that could assist in the management of DMD. In the present study, we compared two diets, high-MUFA diet v. high-PUFA diet, in mdx mice. To generate the high-PUFA diet, a portion of dietary MUFA (oleic acid) was replaced with the dietary essential n-3 PUFA α-linolenic acid (ALA). We sought to determine whether ALA, compared with oleic acid, was beneficial in mdx mice. Consumption of the high-PUFA diet resulted in significantly higher n-3 PUFA content and reduced arachidonic acid content in skeletal muscle phospholipids (PL), while the high-MUFA diet led to higher oleate content in PL. Mdx mice on the high-MUFA diet exhibited 2-fold lower serum creatine kinase activity than those on the high-PUFA diet (P< 0·05) as well as a lower body fat percentage (P< 0·05), but no significant difference in skeletal muscle histopathology results. There was no significant difference between the dietary groups with regard to phosphorylated p65 (an inflammatory marker) in skeletal muscle. In conclusion, alteration of PL fatty acid (FA) composition by the high-PUFA diet made mdx muscle more susceptible to sarcolemmal leakiness, while the high-MUFA diet exhibited a more favourable impact. These results may be important for designing dietary treatments for DMD patients, and future work on dietary FA profiles, such as comparing other FA classes and dose effects, is needed.