A primary breast cancer with distinct foci of estrogen receptor-alpha positive and negative cells derived from the same clonal origin as revealed by whole exome sequencing

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Background/purpose: Tumor heterogeneity is a now well-recognized phenomenon that can affect the classification, prognosis and treatment of human cancers. Heterogeneity is often described in primary breast cancers based upon histologic subtypes, hormone- and HER2-receptor status, and immunolabeling for various markers, which can be seen within a single tumor as mixed cellular populations, or as separate discrete foci. Experimental design/methods: Here, we present a case report of a patient’s primary breast cancer that had two separate but adjacent histologic components, one that was estrogen receptor (ER) positive, and the other ER negative. Each component was subjected to whole exome sequencing and compared for gene identity to determine clonal origin. Results: Using prior bioinformatic tools, we demonstrated that both the ER positive and negative components shared many variants, including passenger and driver alterations. Copy number variations also supported the two components were derived from a single common clone. Conclusions: These analyses strongly suggest that the two ER components of this patient’s breast cancer were derived from the same clonal origin. Our results have implications for the evolution of breast cancers with mixed histologies, and how they might be best managed for optimal therapy

Identifying sources, pathways and risk drivers in ecosystems of Japanese Encephalitis in an epidemic-prone north Indian district

Japanese Encephalitis (JE) has caused repeated outbreaks in endemic pockets of India. This study was conducted in Kushinagar, a highly endemic district, to understand the human-animal-ecosystem interactions, and the drivers that influence disease transmission. Utilizing the ecosystems approach, a cross-sectional, descriptive study, employing mixed methods design was employed. Four villages (two with pig-rearing and two without) were randomly selected from a high, a medium and a low burden (based on case counts) block of Kushinagar. Children, pigs and vectors were sampled from these villages. A qualitative arm was incorporated to explain the findings from the quantitative surveys. All human serum samples were screened for JE-specific IgM using MAC ELISA and negative samples for JE RNA by rRT-PCR in peripheral blood mononuclear cells. In pigs, IgG ELISA and rRT-PCR for viral RNA were used. Of the 242 children tested, 24 tested positive by either rRT-PCR or MAC ELISA; in pigs, 38 out of the 51 pigs were positive. Of the known vectors, Culex vishnui was most commonly isolated across all biotopes. Analysis of 15 blood meals revealed human blood in 10 samples. Univariable analysis showed that gender, religion, lack of indoor residual spraying of insecticides in the past year, indoor vector density (all species), and not being vaccinated against JE in children were significantly associated with JE positivity. In multivariate analysis, only male gender remained as a significant risk factor. Based on previous estimates of symptomatic: asymptomatic cases of JE, we estimate that there should have been 618 cases from Kushinagar, although only 139 were reported. Vaccination of children and vector control measures emerged as major control activities; they had very poor coverage in the studied villages. In addition, lack of awareness about the cause of JE, lack of faith in the conventional medical healthcare system and multiple referral levels causing delay in diagnosis and treatment emerged as factors likely to result in adverse clinical outcomes

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

Mobile evaporite enhances the cycle of physical–chemical erosion in badlands

Chemical weathering driven by physical erosion is a natural process that strongly affects chemical and solid matter budgets at the Earth's surface. However, the influence of extreme climatic erosion on chemical weathering dynamics is poorly understood. Badland landscapes formed in highly erodible substrates have the potential to respond to individual events on scales that are rapid enough for direct observation. Here, we assess the geochemical and grain-size composition of suspended sediment and riverine chemistry measurements collected from two catchments during the 2017 Nesat and Haitang typhoons in southwestern (SW) Taiwan. During the typhoons, the Na+ concentration covaried with suspended sediment concentration (SSC), which we attributed to sodium-induced deflocculation. Evaporite weathering at peak rainfall is succeeded by peak silicate weathering at maximum discharge. Overall, our observations suggest that initial weathering of near-surface evaporite enhances the physical erosion of silicate rock during extreme rainfall events.</p

The precordial electrocardiogram

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32574/1/0000703.pd

The effectiveness of health appraisal processes currently in addressing health and wellbeing during spatial plan appraisal: a systematic review

<p>Abstract</p> <p>Background</p> <p>Spatial planning affects the built environment, which in turn has the potential to have a significant impact on health, for good or ill. One way of ensuring that spatial plans take due account of health is through the inclusion of health considerations in the statutory and non statutory appraisal processes linked to plan-making processes.</p> <p>Methods</p> <p>A systematic review to identify evaluation studies of appraisals or assessments of plans where health issues were considered from 1987 to 2010.</p> <p>Results</p> <p>A total of 6161 citations were identified: 6069 from electronic databases, 57 fromwebsite searches, with a further 35 citations from grey literature, of which 20 met the inclusion criteria. These 20 citations reported on a total of 135 different case studies: 11 UK HIA; 11 non UK high income countries HIA, 5 UK SEA or other integrated appraisal; 108 non UK high income SEA or other integrated appraisal. All studies were in English. No relevant studies were identified reporting on low or middle income countries.</p> <p>The studies were limited by potential bias (no independent evaluation, with those undertaking the appraisal also responsible for reporting outcomes), lack of detail and a lack of triangulation of results. Health impact assessments generally covered the four specified health domains (physical activity, mental health and wellbeing, environmental health issues such as pollution and noise, injury) more comprehensively than SEA or other integrated appraisals, although mental health and wellbeing was an underdeveloped area. There was no evidence available on the incorporation of health in Sustainability Appraisal, limited evidence that the recommendations from any type of appraisal were implemented, and almost no evidence that the recommendations had led to the anticipated outcomes or improvements in health postulated.</p> <p>Conclusion</p> <p>Research is needed to assess (i) the degree to which statutory plan appraisal processes (SA in the UK) incorporate health; (ii) whether recommendations arising from health appraisal translate into the development process and (iii) whether outcomes are as anticipated.</p

Helminth and Intestinal Protozoa Infections, Multiparasitism and Risk Factors in Champasack Province, Lao People's Democratic Republic

Multiparsitism is a general public health concern in tropical countries, and is of particular importance in the Mekong River basin of Southeast Asia. Here, we report results obtained from an in-depth study of hepato-biliary and intestinal multiparasitism and associated risk factors in three settings of the most southern province of Lao People's Democratic Republic. Multiple species intestinal parasite infections were very common: more than 80% of the study participants harbored at least two and up to seven different intestinal parasites concurrently. Of particular concerns are the high prevalence of the liver fluke Opisthorchis viverrini (64.1%) and the moderate prevalence of the blood fluke Schistosoma mekongi (24.2%), as these fluke infections are responsible for severe hepato-biliary morbidity, including the bile duct cancer cholangiocarcinoma. Hookworm was the most common nematode infection (76.8%). We conclude that given the very high prevalence rates of parasite infections and the extent of multiparasitism, regular deworming is warranted and that this intervention should be coupled with health education and improved assess to clean water and adequate sanitation to consolidate morbidity control and ensure long-term sustainability

Evidence for a useful life of more than three years for a polyester-based long-lasting insecticidal mosquito net in Western Uganda

<p>Abstract</p> <p>Background</p> <p>Long-lasting insecticidal nets (LLIN) are now standard for the prevention of malaria. However, only products with recommendation for public use from the World Health Organization should be used and this evaluation includes the assessment of net effectiveness after three years of field use. Results for one of the polyester-based products, Interceptor^®is presented.</p> <p>Methods</p> <p>In five villages, 190 LLIN and 90 nets conventionally treated with the insecticide alpha-cypermethrin at 25 mg/m²were distributed randomly and used by the families. Following a baseline household survey a net survey was carried out every six months to capture use, washing habits and physical condition of the nets. Randomly selected nets were collected after 6, 12, 24, 36 and 42 months and tested for remaining insecticide content and ability to knock-down and kill malaria transmitting mosquitoes.</p> <p>Results</p> <p>During the three and a half years of observation only 16 nets were lost to follow-up resulting in an estimated attrition rate of 12% after three and 20/% after 3.5 years. Nets were used regularly and washed on average 1.5 times per year. After three and a half years 29% of the nets were still in good condition while 13% were seriously torn with no difference between the LLIN and control nets. The conventionally treated nets quickly lost insecticide and after 24 months only 7% of the original dose remained (1.6 mg/m²). Baseline median concentration of alpha-cypermethrin for LLIN was 194.5 mg/m²or 97% of the target dose with between and within net variation of 11% and 4% respectively (relative standard deviation). On the LLIN 73.8 mg/m²alpha-cypermethrin remained after three years of use and 56.2 mg/m²after three and a half and 94% and 81% of the LLIN still had > 15 mg/m²left respectively. Optimal effectiveness in bio-assays (≥95% 60 minute knock-down or ≥ 80% 24 hour mortality) was found in 83% of the sampled LLIN after three and 71% after three and a half years.</p> <p>Conclusions</p> <p>Under conditions in Western Uganda the tested long-lasting insecticidal net Interceptor^®fulfilled the criteria for phase III of WHO evaluations and, based on preliminary criteria of the useful life, this product is estimated to last on average between three and four years.</p