Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential. RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1 and TIG1 were highly methylated in PCa compared to BPH (p < 0.001), while SERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2a and SFN were not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level of SFN, SLIT2 and SERPINB5 distinguished low and high Gleason score cancers, e.g. SFN and SERPINB5 together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes including CDH1 previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001). Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes like RARB, HIN1, BCL2, APC and GSTP1 is warranted for diagnostic potential and SFN, SLIT2 and SERPINB5 for prognostic potential

Quantifying children's aggregate (dietary and residential) exposure and dose to permethrin: application and evaluation of EPA's probabilistic SHEDS-Multimedia model

Reliable, evaluated human exposure and dose models are important for understanding the health risks from chemicals. A case study focusing on permethrin was conducted because of this insecticide's widespread use and potential health effects. SHEDS-Multimedia was applied to estimate US population permethrin exposures for 3- to 5-year-old children from residential, dietary, and combined exposure routes, using available dietary consumption data, food residue data, residential concentrations, and exposure factors. Sensitivity and uncertainty analyses were conducted to identify key factors, pathways, and research needs. Model evaluation was conducted using duplicate diet data and biomonitoring data from multiple field studies, and comparison to other models. Key exposure variables were consumption of spinach, lettuce, and cabbage; surface-to-skin transfer efficiency; hand mouthing frequency; fraction of hand mouthed; saliva removal efficiency; fraction of house treated; and usage frequency. For children in households using residential permethrin, the non-dietary exposure route was most important, and when all households were included, dietary exposure dominated. SHEDS-Multimedia model estimates compared well to real-world measurements data; this exposure assessment tool can enhance human health risk assessments and inform children's health research. The case study provides insights into children's aggregate exposures to permethrin and lays the foundation for a future cumulative pyrethroid pesticides risk assessment

Synchrophasor-Based Islanding Detection for Distributed Generation Systems Using Systematic Principal Component Analysis Approaches

Systematic principal component analysis (PCA) methods are presented in this paper for reliable islanding detection for power systems with significant penetration of distributed generations (DGs), where synchrophasors, recorded by phasor measurement units, are used for system monitoring. Existing islanding detection methods, such as rate-of-change-of-frequency and vector shift are fast for processing local information; however, with the growth in installed capacity of DGs, they suffer from several drawbacks. Incumbent genset islanding detection cannot distinguish a system-wide disturbance from an islanding event, leading to maloperation. The problem is even more significant when the grid does not have sufficient inertia to limit frequency divergences in the system fault/stress due to the high penetration of DGs. To tackle such problems, this paper introduces PCA methods for islanding detection. A simple control chart is established for intuitive visualization of the transients. A recursive PCA scheme is proposed as a reliable extension of the PCA method to reduce the false alarms for time-varying process. To further reduce the computational burden, the approximate linear dependence condition errors are calculated to update the associated PCA model. The proposed PCA and RPCA methods are verified by detecting abnormal transients occurring in the U.K. utility network

Inclusive wealth index measuring sustainable development potentials for Chinese cities

The UN Sustainable Development Goals (SDGs) are the blueprint to achieve a better and more sustainable future. To achieve the goal, tracking progress — not just on a national level, but locally — is crucial to guide future policy development. While sustainability assessment at the national evel is quite advanced in China, similar assessments focusing at the regional or even at the city-level are currently lacking. Here, we advanced the Inclusive Wealth Index (IWI) framework, which is firstly proposed by the United Nations Development Programme, through taking water wealth into account and adjusting the variable based on data availability. Then we investigate the sustainability performance of 210 cities in China in 2016 via the advanced version of the IWI framework. The analysis makes a holistic assessment based on produced, human, and natural capital, as well as considering heterogeneities in economy, social, and environmental conditions across these cities. We find that cities clustered in the eastern parts of China are characterized by high levels of sustainability performance and increasing capacities for sustainability, largely driven by their high quality and quantity of human capital. In comparison, the western cities have a large amount of low-skilled human capital and low levels of produced capital, which determines their low sustainability performance. Cities clustered in the north are heavily dependent on low value-added products and resource-intensive industries. Furthermore, we make projections of the IWI and its three components for different cities from 2020 to 2030, referring to the index systems presented in city planning which describe the development speed of income, education, fixed asset investment, forests etc. In the future, cities in central and western clusters show considerable potential for increasing IWI per capita, whereas cities with a dominant energy sector in the north would face declining capacity for sustainability due to the exhaustion of fossil fuels and raw materials. By fully taking account of and adapting to local circumstances, we tailor-design pathways for different types of cities to grow their sustainability potentials. Those resources-dependent cities in the north could avoid the impending decline by gradually developing their human and produced capital while abandoning their resource dependency. Our study contributes to city-level sustainable development in China through the lens of per capita IWI and the potential future dynamics of changing compositions in their capital

Melanotic oncocytic metaplasia of the nasopharynx as a benign mimicker of malignant melanoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Melanotic variant of oncocytic metaplasia of the nasopharynx is an extremely rare condition.</p> <p>Case report</p> <p>A 73-year-old Japanese man presented with nasal congestion and chill. Nasoscopic examination revealed multiple black nodules around the bilateral torus tubarius. The nodules were biopsied to determine the histology. The clinical differential diagnosis was malignant melanoma or hemangioma. Microscopically, there were oncocytic plump cells with abundant brown pigmented granules showing glandular pattern. No significant atypia was found. The pigment was positive for Fontana-Masson staining, and negative for Berlin blue staining, showing that it was melanin pigment. Immunohistochemically, S100-positive HMB45-negative dendritic cells were also found.</p> <p>Conclusion</p> <p>Such a pigmented variant of benign oncocytic lesion is very rare, and only 15 cases have been reported in the English literature. As a benign mimicker of malignant melanoma, melanocytic oncocytic metaplasia should be always taken into consideration in the clinical setting.</p

Seeing Tree Structure from Vibration

Humans recognize object structure from both their appearance and motion; often, motion helps to resolve ambiguities in object structure that arise when we observe object appearance only. There are particular scenarios, however, where neither appearance nor spatial-temporal motion signals are informative: occluding twigs may look connected and have almost identical movements, though they belong to different, possibly disconnected branches. We propose to tackle this problem through spectrum analysis of motion signals, because vibrations of disconnected branches, though visually similar, often have distinctive natural frequencies. We propose a novel formulation of tree structure based on a physics-based link model, and validate its effectiveness by theoretical analysis, numerical simulation, and empirical experiments. With this formulation, we use nonparametric Bayesian inference to reconstruct tree structure from both spectral vibration signals and appearance cues. Our model performs well in recognizing hierarchical tree structure from real-world videos of trees and vessels.Comment: ECCV 2018. The first two authors contributed equally to this work. Project page: http://tree.csail.mit.edu

Reduction in Asthma Morbidity in Children as a Result of Home Remediation Aimed at Moisture Sources

OBJECTIVE: Home dampness and the presence of mold and allergens have been associated with asthma morbidity. We examined changes in asthma morbidity in children as a result of home remediation aimed at moisture sources. DESIGN: In this prospective, randomized controlled trial, symptomatic, asthmatic children (n = 62), 2–17 years of age, living in a home with indoor mold, received an asthma intervention including an action plan, education, and individualized problem solving. The remediation group also received household repairs, including reduction of water infiltration, removal of water-damaged building materials, and heating/ventilation/air-conditioning alterations. The control group received only home cleaning information. We measured children’s total and allergen-specific serum immuno-globulin E, peripheral blood eosinophil counts, and urinary cotinine. Environmental dust samples were analyzed for dust mite, cockroach, rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year. RESULTS: Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study. The remediation group had a significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent to treat) after remodeling, whereas these parameters in the control group did not significantly change. In the postremediation period, the remediation group had a lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29 vs. 11 of 33, respectively, p = 0. 003; intent to treat: 28.1% and 10.0%, respectively, p = 0.11). CONCLUSION: Construction remediation aimed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem

Acupuncture, chiropractic and osteopathy use in Australia: a national population survey

Background There have been no published national studies on the use in Australia of the manipulative therapies, acupuncture, chiropractic or osteopathy, or on matters including the purposes for which these therapies are used, treatment outcomes and the socio-demographic characteristics of users. Methods This study on the three manipulative therapies was a component of a broader investigation on the use of complementary and alternative therapies. For this we conducted a cross-sectional, population survey on a representative sample of 1,067 adults from the six states and two territories of Australia in 2005 by computer-assisted telephone interviews. The sample was recruited by random digit dialling. Results Over a 12-month period, approximately one in four adult Australians used either acupuncture (9.2%), chiropractic (16.1%) or osteopathy (4.6%) at least once. It is estimated that, adult Australians made 32.3 million visits to acupuncturists, chiropractors and osteopaths, incurring personal expenditure estimated to be A$1.58 billion in total. The most common conditions treated were back pain and related problems and over 90% of the users of each therapy considered their treatment to be very or somewhat helpful. Adverse events are reported. Nearly one fifth of users were referred to manipulative therapy practitioners by medical practitioners. Conclusion There is substantial use of manipulative therapies by adult Australians, especially for back-related problems. Treatments incur considerable personal expenditure. In general, patient experience is positive. Referral by medical practitioners is a major determinant of use of these manipulative therapies

Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation