Rainfall and sentinel chicken seroconversions predict human cases of Murray Valley encephalitis in the north of Western Australia

Background Murray Valley encephalitis virus (MVEV) is a flavivirus that occurs in Australia and New Guinea. While clinical cases are uncommon, MVEV can cause severe encephalitis with high mortality. Sentinel chicken surveillance is used at many sites around Australia to provide an early warning system for risk of human infection in areas that have low population density and geographical remoteness. MVEV in Western Australia occurs in areas of low population density and geographical remoteness, resulting in logistical challenges with surveillance systems and few human cases. While epidemiological data has suggested an association between rainfall and MVEV activity in outbreak years, it has not been quantified, and the association between rainfall and sporadic cases is less clear. In this study we analysed 22 years of sentinel chicken and human case data from Western Australia in order to evaluate the effectiveness of sentinel chicken surveillance for MVEV and assess the association between rainfall and MVEV activity. Methods Sentinel chicken seroconversion, human case and rainfall data from the Kimberley and Pilbara regions of Western Australia from 1990 to 2011 were analysed using negative binomial regression. Sentinel chicken seroconversion and human cases were used as dependent variables in the model. The model was then tested against sentinel chicken and rainfall data from 2012 and 2013.Results Sentinel chicken seroconversion preceded all human cases except two in March 1993. Rainfall in the prior three months was significantly associated with both sentinel chicken seroconversion and human cases across the regions of interest. Sentinel chicken seroconversion was also predictive of human cases in the models. The model predicted sentinel chicken seroconversion in the Kimberley but not in the Pilbara, where seroconversions early in 2012 were not predicted. The latter may be due to localised MVEV activity in isolated foci at dams, which do not reflect broader virus activity in the region. Conclusions We showed that rainfall and sentinel chickens provide a useful early warning of MVEV risk to humans across endemic and epidemic areas, and that a combination of the two indicators improves the ability to assess MVEV risk and inform risk management measures

The International-Trade Network: Gravity Equations and Topological Properties

This paper begins to explore the determinants of the topological properties of the international - trade network (ITN). We fit bilateral-trade flows using a standard gravity equation to build a "residual" ITN where trade-link weights are depurated from geographical distance, size, border effects, trade agreements, and so on. We then compare the topological properties of the original and residual ITNs. We find that the residual ITN displays, unlike the original one, marked signatures of a complex system, and is characterized by a very different topological architecture. Whereas the original ITN is geographically clustered and organized around a few large-sized hubs, the residual ITN displays many small-sized but trade-oriented countries that, independently of their geographical position, either play the role of local hubs or attract large and rich countries in relatively complex trade-interaction patterns

Where to deliver? Analysis of choice of delivery location from a national survey in India

<p>Abstract</p> <p>Background</p> <p>In order to reduce maternal mortality, the Indian government has increased its commitment to institutional deliveries. We assess the determinants of home, private and public sector utilization for a delivery in a Western state.</p> <p>Methods</p> <p>Cross sectional analyses of the National Family Health Survey – 2 dataset.</p> <p>Setting</p> <p>Maharashtra state. The dataset had a sample size of 5391 ever-married females between the ages of 15 to 49 years. Data were abstracted for the most recent birth (n = 1510) and these were used in the analyses. Conceptual framework was the Andersen Behavioral Model. Multinomial logistic regression analyses was conducted to assess the association of predisposing, enabling and need factors on use of home, public or private sector for delivery.</p> <p>Results</p> <p>A majority delivered at home (n = 559, 37%); with private and public facility deliveries accounting for 32% (n = 493) and 31% (n = 454) respectively. For the choice set of home delivery versus public facility, women with higher birth order and those living in rural areas had greater odds of delivering at home, while increasing maternal age, greater media exposure, and more then three antenatal visits were associated with greater odds of delivery in a public facility. Maternal and paternal education, scheduled caste/tribe status, and media exposure were statistically significant predictors of the choice of public versus private facility delivery.</p> <p>Conclusion</p> <p>As India's economy continues to grow, the private sector will continue to expand. Given the high household expenditures on health, the government needs to facilitate insurance schemes or provide grants to prevent impoverishment. It also needs to strengthen the public sector so that it can return to its mission of being the safety net.</p

Implementation of chronic kidney disease guidelines for sodium-glucose co-transporter-2 inhibitor use in primary care in the UK: a cross-sectional study.

BACKGROUND: The cardiovascular and kidney benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in people with chronic kidney disease (CKD) are well established. The implementation of updated SGLT2 inhibitor guidelines and prescribing in the real-world CKD population remains largely unknown. METHODS: A cross-sectional study of adults with CKD registered with UK primary care practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network on the 31st December 2022 was undertaken. Pseudonymised data from electronic health records held securely within the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) were extracted. An update to a previously described ontological approach was used to identify the study population, using a combination of Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) indicating a diagnosis of CKD and laboratory confirmed CKD based on Kidney Disease: Improving Global Outcomes (KDIGO) diagnostic criteria. We examined the extent to which SGLT2 inhibitor guidelines apply to and are then implemented in adults with CKD. A logistic regression model was used to identify factors associated with SGLT2 inhibitor prescribing, reported as odds ratios (ORs) with 95% confidence intervals (CI). The four guidelines under investigation were the United Kingdom Kidney Association (UKKA) Clinical Practice Guideline SGLT2 Inhibition in Adults with Kidney Disease (October 2021), American Diabetes Association (ADA) and KDIGO Consensus Report on Diabetes Management in CKD (October 2022), National Institute for Health and Care Excellence (NICE) Guideline Type 2 Diabetes in Adults: Management (June 2022), and NICE Technology Appraisal Dapagliflozin for Treating CKD (March 2022). FINDINGS: Of 6,670,829 adults, we identified 516,491 (7.7%) with CKD, including 32.8% (n = 169,443) who had co-existing type 2 diabetes (T2D). 26.8% (n = 138,183) of the overall CKD population had a guideline directed indication for SGLT2 inhibitor treatment. A higher proportion of people with CKD and co-existing T2D were indicated for treatment, compared to those without T2D (62.8% [n = 106,468] vs. 9.1% [n = 31,715]). SGLT2 inhibitors were prescribed to 17.0% (n = 23,466) of those with an indication for treatment, and prescriptions were predominantly in those with co-existing T2D; 22.0% (n = 23,464) in those with T2D, and <0.1% (n = 2) in those without T2D. In adjusted multivariable analysis of people with CKD and T2D, females (OR 0.69, 95% CI 0.67-0.72, p <0.0001), individuals of Black ethnicity (OR 0.84, 95% CI 0.77-0.91, p <0.0001) and those of lower socio-economic status (OR 0.72, 95% CI 0.68-0.76, p <0.0001) were less likely to be prescribed an SGLT2 inhibitor. Those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 had a lower likelihood of receiving an SGLT2 inhibitor, compared to those with an eGFR ≥60 mL/min/1.73 m2 (eGFR 45-60 mL/min/1.73 m2 OR 0.65, 95% CI 0.62-0.68, p <0.0001, eGFR 30-45 mL/min/1.73 m2 OR 0.73, 95% CI 0.69-0.78, p <0.0001, eGFR 15-30 mL/min/1.73 m2 OR 0.52, 95% CI 0.46-0.60, p <0.0001, eGFR <15 mL/min/1.73 m2 OR 0.03, 95% CI 0.00-0.23, p = 0.0037, respectively). Those with albuminuria (urine albumin-to-creatinine ratio 3-30 mg/mmol) were less likely to be prescribed an SGLT2 inhibitor, compared to those without albuminuria (OR 0.78, 95% CI 0.75-0.82, p <0.0001). INTERPRETATION: SGLT2 inhibitor guidelines in CKD have not yet been successfully implemented into clinical practice, most notably in those without co-existing T2D. Individuals at higher risk of adverse outcomes are paradoxically less likely to receive SGLT2 inhibitor treatment. The timeframe between the publication of guidelines and data extraction may have been too short to observe changes in clinical practice. Enhanced efforts to embed SGLT2 inhibitors equitably into routine care for people with CKD are urgently needed, particularly in those at highest risk of adverse outcomes and in the absence of T2D. FUNDING: None

Target and reality of adjuvant endocrine therapy in postmenopausal patients with invasive breast cancer

Previous research evaluating the use of adjuvant endocrine therapy among postmenopausal breast cancer patients showed with 15–50% wide ranges of non-adherence rates. We evaluated this issue by analysing an unselected study group comprising of 325 postmenopausal women, diagnosed from 1997 to 2003 with hormonal receptor-positive invasive breast cancer. The different clinical situations that led to the discontinuation of adjuvant endocrine therapy were clearly defined and differentiated: non-adherence was not simply the act of stopping medication, but rather the manifestation of an intentional behaviour of the patient. Of the 287 patients who initiated endocrine therapy, 191 (66.6%) fully completed this treatment. Thirty-one patients (10.8%) showed non-adherence to therapy. Patients who had follow-up with a general practitioner, rather than in an oncologic unit, were more likely to be non-adherent (P=0.0088). Of 25 patients who changed medication due to therapy-related adverse effects, 20 (80%) patients fully completed the therapy after drug change. In adjuvant endocrine therapy, a lowering of the non-adherence rate to 10.8%, the lowest reported in the literature, is realistic when patients are cared for by a specialised oncologic unit focusing on the individual needs of the patients

Physical activity for people living with dementia: carer outcomes and side effects from the perspectives of professionals and family carers

Adherence to physical activity is challenging for people living with dementia, and largely dependent on carers' involvement. Carers are likely to support physical activity based on their perceived balance between benefits and potential side effects of such intervention for both patients and themselves. Professionals also have a role in terms of optimising such interventions not only for people with dementia but also their carers.publishe

Intratumor genetic heterogeneity in squamous cell carcinoma of the oral cavity

BackgroundWe sought to evaluate intratumor heterogeneity in squamous cell carcinoma of the oral cavity (OCC) and specifically determine the effect of physical separation and histologic differentiation within the same tumor.MethodsWe performed whole exome sequencing on five biopsy sites—two from well‐differentiated, two from poorly differentiated regions, and one from normal parenchyma—from five primary OCC specimens.ResultsWe found high levels of intratumor heterogeneity and, in four primary tumors, identified only 0 to 2 identical mutations in all subsites. We found that the heterogeneity inversely correlated with physical separation and that pairs of well‐differentiated samples were more similar to each other than analogous poorly differentiated specimens. Only TP53 mutations, but not other purported “driver mutations” in head and neck squamous cell carcinoma, were found in multiple biopsy sites.ConclusionThese data highlight the challenges to characterization of the mutational landscape of OCC with single site biopsy and have implications for personalized medicine.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150549/1/hed25719.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150549/2/hed25719_am.pd

A Comparison of Sodium-Glucose Co-Transporter 2 Inhibitor Kidney Outcome Trial Participants with a Real-World Chronic Kidney Disease Primary Care Population.

BACKGROUND/HYPOTHESIS: Observational studies suggest sodium-glucose co-transporter-2 (SGLT2) inhibitor kidney outcome trials are not representative of the broader population of people with chronic kidney disease (CKD). However, there are limited data on the generalisability to those without co-existing type 2 diabetes (T2D), and the representativeness of the EMPA-KIDNEY trial has not been adequately explored. We hypothesised that SGLT2 inhibitor kidney outcome trials are more representative of people with co-existing T2D than those without, and that EMPA-KIDNEY is more representative than previous trials. METHODS: A cross-sectional analysis of adults with CKD in English primary care was conducted using the Oxford-Royal College of General Practitioners Clinical Information Digital Hub. The proportions that met the eligibility criteria of SGLT2 inhibitor kidney outcome trials were determined, and their characteristics described. Logistic regression analyses were performed to identify factors associated with trial eligibility. RESULTS: Of 6,670,829 adults, 516,491 (7.7%) with CKD were identified. In the real-world CKD population, 0.9%, 2.2%, and 8.0% met the CREDENCE, DAPA-CKD, and EMPA-KIDNEY eligibility criteria, respectively. All trials were more representative of people with co-existing T2D than those without T2D. Trial participants were 9-14 years younger than the real-world CKD population, and had more advanced CKD, including higher levels of albuminuria. A higher proportion of the CREDENCE (100%), DAPA-CKD (67.6%) and EMPA-KIDNEY (44.5%) trial participants had T2D compared to the real-world CKD population (32.8%). Renin-angiotensin system inhibitors were prescribed in almost all trial participants, compared to less than half of the real-world CKD population. Females were under-represented and less likely to be eligible for the trials. CONCLUSION: SGLT2 inhibitor kidney outcome trials represent a sub-group of people with CKD at high risk of adverse kidney events. Out study highlights the importance of complementing trials with real-world studies, exploring the effectiveness of SGLT2 inhibitors in the broader population of people with CKD

Asymmetrical Gene Flow in a Hybrid Zone of Hawaiian Schiedea (Caryophyllaceae) Species with Contrasting Mating Systems

Asymmetrical gene flow, which has frequently been documented in naturally occurring hybrid zones, can result from various genetic and demographic factors. Understanding these factors is important for determining the ecological conditions that permitted hybridization and the evolutionary potential inherent in hybrids. Here, we characterized morphological, nuclear, and chloroplast variation in a putative hybrid zone between Schiedea menziesii and S. salicaria, endemic Hawaiian species with contrasting breeding systems. Schiedea menziesii is hermaphroditic with moderate selfing; S. salicaria is gynodioecious and wind-pollinated, with partially selfing hermaphrodites and largely outcrossed females. We tested three hypotheses: 1) putative hybrids were derived from natural crosses between S. menziesii and S. salicaria, 2) gene flow via pollen is unidirectional from S. salicaria to S. menziesii and 3) in the hybrid zone, traits associated with wind pollination would be favored as a result of pollen-swamping by S. salicaria. Schiedea menziesii and S. salicaria have distinct morphologies and chloroplast genomes but are less differentiated at the nuclear loci. Hybrids are most similar to S. menziesii at chloroplast loci, exhibit nuclear allele frequencies in common with both parental species, and resemble S. salicaria in pollen production and pollen size, traits important to wind pollination. Additionally, unlike S. menziesii, the hybrid zone contains many females, suggesting that the nuclear gene responsible for male sterility in S. salicaria has been transferred to hybrid plants. Continued selection of nuclear genes in the hybrid zone may result in a population that resembles S. salicaria, but retains chloroplast lineage(s) of S. menziesii