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Objective: Although nursing home (NH) residents make up a large and growing proportion of Americans with diabetes mellitus, little is known about how glucose-lowering medications are used in this population. We sought to examine glucose-lowering medication use in Veterans Affairs (VA) NH residents with diabetes between 2005 and 2011. Research Design and Methods: Retrospective cohort study, using linked laboratory, pharmacy, administrative, and NH Minimum Dataset (MDS) 2.0 databases in 123 VA NHs. A total of 9431 long-stay (>90 days) VA NH residents older than 65 followed for 52,313 person-quarters. We identified receipt of glucose-lowering medications, including insulin, metformin, sulfonylureas, thiazolidinediones, and others (alpha-glucosidase inhibitors, meglitinides, glucagonlike peptide-1 analogs, dipeptidyl peptidase-4 inhibitors and amylin analogs) per quarter. Results: The rates of sulfonylurea use in long-stay NH residents dropped dramatically from 24% in 2005 to 12% in 2011 (P

The present study explores the ability of intracellular bacteria within the renal-inter-renal tissue of the winter skate Leucoraja ocellata to metabolize steroids and contribute to the synthesis of the novel elasmobranch corticosteroid, 1α-hydroxycorticosterone (1α- OH-B). Despite the rarity of C1 hydroxylation noted in the original identification of 1α- OH-B, literature provides evidence for steroid C1 hydroxylation by micro-organisms. Eight ureolytic bacterial isolates were identified in the renal-inter-renal tissue of L. ocellata, the latter being the site of 1α- OH-B synthesis. From incubations of bacterial isolates with known amounts of potential 1α- OH-B precursors, one isolate UM008 of the genus Rhodococcus was seen to metabolize corticosteroids and produce novel products via HPLC analysis. Cations Zn2+ and Fe3+ altered metabolism of certain steroid precursors, suggesting inhibition of Rhodococcus steroid catabolism. Genome sequencing of UM008 identified strong sequence and structural homology to that of Rhodococcus erythropolis PR4. A complete enzymatic pathway for steroid-ring oxidation as documented within other Actinobacteria was identified within the UM008 genome. This study highlights the potential role of Rhodococcus bacteria in steroid metabolism and proposes a novel alternative pathway for 1α- OH-B synthesis, suggesting a unique form of mutualism between intracellular bacteria and their elasmobranch host. [ABSTRACT FROM AUTHOR]

We identify and analyse practices and management regimes around burial and handling of ashes across eight case study towns within six Northern European countries. We analyse management of cemeteries and crematoria gardens, majority practices and provision for minority communities, including various burial types, cremated remains, the re-use of graves, and costs for interments. Comparative data is drawn from analysis of national and local regulations, interviews with stakeholders, and observations at cemeteries and crematoria gardens. The findings show significant variation in national and local regulations and practices for burial and cremation particularly around the re-use of graves, handling of ashes and costs for grave space and cremation. We identify the opportunities and constraints of these variations in terms of accessibility, diversity and equality; and argue for national directions to avoid unequal treatment within nations. Furthermore, we stress the importance of a liberal and inclusive management of European cemeteries and crematoria gardens., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Epithelioid haemangioendothelioma (EHE) is an ultra-rare malignant vascular tumour with a prevalence of 1 per 1,000,000. It is typically molecularly characterised by a WWTR1::CAMTA1 gene fusion in approximately 90% of cases, or a YAP1::TFE3 gene fusion in approximately 10% of cases. EHE cases are typically refractory to therapies, and no anticancer agents are reimbursed for EHE in Australia., Methods: We report a cohort of nine EHE cases with comprehensive histologic and molecular profiling from the Walter and Eliza Hall Institute of Medical Research Stafford Fox Rare Cancer Program (WEHI-SFRCP) collated via nation-wide referral to the Australian Rare Cancer (ARC) Portal. The diagnoses of EHE were confirmed by histopathological and immunohistochemical (IHC) examination. Molecular profiling was performed using the TruSight Oncology 500 assay, the TruSight RNA fusion panel, whole genome sequencing (WGS), or whole exome sequencing (WES)., Results: Molecular analysis of RNA, DNA or both was possible in seven of nine cases. The WWTR1::CAMTA1 fusion was identified in five cases. The YAP1::TFE3 fusion was identified in one case, demonstrating unique morphology compared to cases with the more common WWTR1::CAMTA1 fusion. All tumours expressed typical endothelial markers CD31, ERG, and CD34 and were negative for pan-cytokeratin. Cases with a WWTR1::CAMTA1 fusion displayed high expression of CAMTA1 and the single case with a YAP1::TFE3 fusion displayed high expression of TFE3. Survival was highly variable and unrelated to molecular profile., Conclusions: This cohort of EHE cases provides molecular and histopathological characterisation and matching clinical information that emphasises the molecular patterns and variable clinical outcomes and adds to our knowledge of this ultra-rare cancer. Such information from multiple studies will advance our understanding, potentially improving treatment options.

Social capital is considered important for resilience across social levels, including communities, yet insights are scattered across disciplines. This meta-synthesis of 187 studies examines conceptual and empirical understandings of how social capital relates to resilience, identifying implications for community resilience and climate change practice. Different conceptualisations are highlighted, yet also limited focus on underlying dimensions of social capital and proactive types of resilience for engaging with the complex climate change challenge. Empirical insights show that structural and socio-cultural aspects of social capital, multiple other factors and formal actors are all important for shaping the role of social capital for guiding resilience outcomes. Thus, finding ways to work with these different elements is important. Greater attention on how and why outcomes emerge, interactions between factors, approaches of formal actors and different socio-cultural dimensions will advance understandings about how to nurture social capital for resilience in the context of climate change., (© 2022. The Author(s).)

Resilience-informed water quality management embraces the growing environmental challenges and provides greater accuracy by unpacking the systems' characteristics in response to failure conditions in order to identify more effective opportunities for intervention. Assessing the resilience of water quality requires complex analysis of influential parameters which can be challenging, time consuming and costly to compute. It may also require building detailed conceptual and/or physically process-based models that are difficult to build, calibrate and validate. This study utilises Artificial Neural Network (ANN) to develop a novel application to predict water quality resilience to simplify resilience evaluation. The Fuzzy Analytic Hierarchy Process method is used to rank water basins based on their level of resilience and to identify the ones that demand prompt restoration strategies. The commonly used 'magnitude * duration of being in failure state' quantification method has been used to formulate and evaluate resilience. A 17-years long water quality dataset from the 22 water basins in the State of São Paulo, Brazil, was used to train and test the ANN model. The overall agreement between the measured and simulated WQI resilience values is satisfactory and hence, can be used by planners and decision makers for improved water management. Moreover, comparative analyses show similarities and differences between the 'level of criticalities' reported in each zone by Environment Agency of the state of São Paulo (CETESB) and by the resilience model in this study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The necessity of incorporating a resilience-informed approach into urban planning and its decision-making is felt now more than any time previously, particularly in low and middle income countries. In order to achieve a successful transition to sustainable, resilient and cost-effective cities, there is a growing attention given to more effective integration of nature-based solutions, such as Sustainable Drainage Systems (SuDS), with other urban components. The experience of SuDS integration with urban planning, in developed cities, has proven to be an effective strategy with a wide range of advantages and lower costs. The effective design and implementation of SuDS requires a multi-objective approach by which all four pillars of SuDS design (i.e., water quality, water quantity, amenity and biodiversity) are considered in connection to other urban, social, and economic aspects and constraints. This study develops a resilience-driven multi-objective optimisation model aiming to provide a Pareto-front of optimised solutions for effective incorporation of SuDS into (peri)urban planning, applied to a case study in Brazil. This model adopts the SuDS's two pillars of water quality and water quantity as the optimisation objectives with its level of spatial distribution as decision variables. Also, an improved quality of life index (iQoL) is developed to re-evaluate the optimal engineering solutions to encompass the amenity and biodiversity pillars of SuDS. Rain barrels, green roofs, bio-retention tanks, vegetation grass swales and permeable pavements are the suitable SuDS options identified in this study. The findings show that the most resilient solutions are costly but this does not guarantee higher iQoL values. Bio-retention tanks and grass swales play effective roles in promotion of water quality resilience but this comes with considerable increase in costs. Permeable pavements and green roofs are effective strategies when flood resilience is a priority. Rain barrel is a preferred solution due to the dominance of residential areas in the study area and the lower cost of this option., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

AbstractThe etiologic agent of yaws, Treponema pallidum subsp. pertenue , causes a multistage infection transmitted by nonsexual contact with the exudates from active lesions. Bone lesions in the form of osteoperiostitis are common and occur in numerous bones simultaneously in early stages. Although a multinational eradication campaign with mass administration of intramuscular benzathine benzylpenicillin in the 1950s greatly reduced its global incidence, a resurgence of yaws has occurred since around 2000 in western and central Africa and the Pacific Islands. The finding that a single oral dose of azithromycin (30 mg/kg) was as effective as benzathine benzylpenicillin prompted renewed interest by World Health Organization in 2012 toward eradication of this infection by 2020. We previously reported the excellent response to benzathine benzylpenicillin therapy for yaws osteoperiostitis. Herein, we document a confirmed case of yaws with osteoperiostitis successfully treated with single-dose azithromycin and discuss the pathology of yaws periostitis and comment on the implications of this in light of the new campaign toward yaws eradication.

Background: To explore the perspectives of nursing home (NH) residents with diabetes and their doctors regarding the burdens of living with diabetes and diabetes treatments., Methods: Qualitative study of nursing home residents aged 65 and older with diabetes (n = 14) and nursing home physicians (n = 9) at a Department of Veterans Affairs nursing home (known as the Community Living Center). A semi-structured interview was used to elicit nursing home residents' and physicians' perspectives on the burden of diabetes and diabetes treatments. Transcripts were analyzed using constant comparative methods., Results: The mean age of the nursing home residents was 74; Most (93%) were male and 50% self-identified themselves as white. The mean age of nursing home physicians was 39 and 55% were geriatricians. Dietary restrictions, loss of independence and fingersticks/insulin were noted to be the most burdensome aspects of diabetes. Nursing home residents with a more positive outlook were generally more engaged in their care, while nursing home residents with a more pessimistic outlook were less engaged, allowing their physicians to assume complete control of their care. While physicians noted the potential negative impact of dietary restrictions, nursing home residents' comments suggest that physicians underestimate the burden of dietary restrictions., Conclusions: Veterans Affairs nursing home residents were substantially burdened by their diabetes treatments, especially dietary restrictions and fingerstick monitoring. Since there is little evidence that dietary restrictions improve outcomes, fewer dietary restrictions may be appropriate and lead to lower treatment burdens for nursing home residents with diabetes.

One of the primary aims of synthetic biology is to (re)design metabolic pathways towards the production of desired chemicals. The fast pace of developments in molecular biology increasingly makes it possible to experimentally redesign existing pathways and implement de novo ones in microbes or using in vitro platforms. For such experimental studies, the bottleneck is shifting from implementation of pathways towards their initial design. Here, we present an online tool called 'Metabolic Tinker', which aims to guide the design of synthetic metabolic pathways between any two desired compounds. Given two user-defined 'target' and 'source' compounds, Metabolic Tinker searches for thermodynamically feasible paths in the entire known metabolic universe using a tailored heuristic search strategy. Compared with similar graph-based search tools, Metabolic Tinker returns a larger number of possible paths owing to its broad search base and fast heuristic, and provides for the first time thermodynamic feasibility information for the discovered paths. Metabolic Tinker is available as a web service at http://osslab.ex.ac.uk/tinker.aspx. The same website also provides the source code for Metabolic Tinker, allowing it to be developed further or run on personal machines for specific applications.

In recent years an increasing number of real-world many-dimensional optimisation problems have been identified across the spectrum of research fields. Many popular evolutionary algorithms use non-dominance as a measure for selecting solutions for future generations. The process of sorting populations into non-dominated fronts is usually the controlling order of computational complexity and can be expensive for large populations or for a high number of objectives. This paper presents two novel methods for non-dominated sorting: deductive sort and climbing sort. The two new methods are compared to the fast non-dominated sort of NSGA-II and the non-dominated rank sort of the omni-optimizer. The results demonstrate the improved efficiencies of the deductive sort and the reductions in comparisons that can be made when applying inferred dominance relationships defined in this paper.

Collagenous ileitis (CI), characterized by subepithelial collagen deposition in the terminal ileum, is an uncommon condition. The few cases reported to date have been associated with collagenous colitis (CC) or lymphocytic colitis. Thirteen cases of CI retrieved over a 9-year period were retrospectively studied. There were 7 female and 6 male patients, with an age range of 39 to 72 years (mean, 64 y). Two groups were identified: (1) CI associated with collagenous or lymphocytic disease elsewhere in the gastrointestinal tract and (2) CI as an isolated process. Diarrhea was the presenting symptom in 11 cases. Most patients had no regular medication use. Subepithelial collagen thickness ranged from 15 to 100 μm (mean, 32 μm) and involved 5% to 80% of the subepithelial region of the submitted biopsies. Six cases had >25 intraepithelial lymphocytes (IELs)/100 epithelial cells, and villous blunting was observed in 11 cases. Chronic inflammation of the lamina propria was present in 9 cases, and focal neutrophil infiltration was identified in 3 cases. In biopsies taken from other sites, 7 of 13 colonic biopsies showed CC, 4 of 9 gastric biopsies showed collagenous gastritis, and 2 of 10 duodenal biopsies were abnormal with collagenous sprue (n=1) and partial villous atrophy and increased IELs (n=1) (both celiac disease related). Resolution of the subepithelial collagen deposition was found in the 1 case in which follow-up of terminal ileal biopsies were taken. There was partial or complete resolution of symptoms in 6 of 9 patients for whom follow-up information was available.

Objectives: To assess the radical prostatectomy findings in patients with a minute focus of adenocarcinoma on prostate needle biopsy in current practice in Australia., Methods: A total of 58 patients with a 0.5-mm focus or less of Gleason score 6 adenocarcinoma on needle biopsy who had been treated by radical prostatectomy were selected. At each biopsy, 6 to 20 cores (mean 11, median 13) were taken. Significant tumors were those with a Gleason score of 6 or more and tumor volume of 0.5 cm3 or larger., Results: The 58 patients (mean age 50 years, median 58, range 44 to 69) had a mean prostate-specific antigen (PSA) level of 6.9 ng/mL (range 0.7 to 16, median 6). Of the 58 men, 48 (82.75%) had pathologically significant tumor, with 8 (13.8%) showing extraprostatic extension. No statistically significant association was found between significant carcinoma and age, mean PSA level, PSA density greater than 0.15, prior negative biopsy, coexistent atypical glands, or the number of tissue cores per biopsy. A prostate weight greater than 40 g correlated significantly with insignificant cancer on both univariate (P = 0.03) and multivariate (P = 0.02) analyses. In 14 (29.2%) of 48 patients with significant tumor, the largest cancer focus in the radical prostatectomy was anterior, lateral, or anterolateral. In patients without atypical glands, 37 (78.72%) of 47 had significant carcinoma, a risk not significantly lower than that of the entire group., Conclusions: The results of our study have shown that in populations without PSA screening, a minute focus of prostate cancer on needle biopsy, even with extended biopsy cores, does not mean insignificant carcinoma in most cases. Patients with larger glands had a greater chance of insignificant cancer.