A Genetic Analytics Approach for Risk Variant Identification to Support Intervention Strategies for People Susceptible to Polygenic Obesity and Overweigh

Obesity is a growing epidemic that has increased steadily over the past several decades. It affects significant parts of the global population and this has resulted in obesity being high on the political agenda in many countries. It represents one of the most difficult clinical and public health challenges worldwide. While eating healthy and exercising regularly are obvious ways to combat obesity, there is a need to understand the underlying genetic constructs and pathways that lead to the manifestation of obesity and their susceptibility metrics in specific individuals. In particular, the interpretation of genetic profiles will allow for the identification of Deoxyribonucleic Acid variations, known as Single Nucleotide Polymorphism, associated with traits directly linked to obesity and validated with Genome-Wide Association Studies. Using a robust data science methodology, this paper uses a subset of the TwinsUK dataset that contains genetic data from extremely obese individuals with a BMI≥40, to identify significant obesity traits for potential use in genetic screening for disease risk prediction. The approach posits a framework for methodical risk variant identification to support intervention strategies that will help mitigate long-term adverse health outcomes in people susceptible to obesity and overweight

Partisan Asymmetries in Online Political Activity

We examine partisan differences in the behavior, communication patterns and social interactions of more than 18,000 politically-active Twitter users to produce evidence that points to changing levels of partisan engagement with the American online political landscape. Analysis of a network defined by the communication activity of these users in proximity to the 2010 midterm congressional elections reveals a highly segregated, well clustered partisan community structure. Using cluster membership as a high-fidelity (87% accuracy) proxy for political affiliation, we characterize a wide range of differences in the behavior, communication and social connectivity of left- and right-leaning Twitter users. We find that in contrast to the online political dynamics of the 2008 campaign, right-leaning Twitter users exhibit greater levels of political activity, a more tightly interconnected social structure, and a communication network topology that facilitates the rapid and broad dissemination of political information.Comment: 17 pages, 10 figures, 6 table

Association Mapping Approach into Type 2 Diabetes using Biomarkers and Clinical Data

The global growth in incidence of Type 2 Diabetes (T2D) has become a major international health concern. As such, understanding the aetiology of Type 2 Diabetes is vital. This paper investigates a variety of statistical method-ologies at various level of complexity to analyse genotype data and identify bi-omarkers that show evidence of increase susceptibility to T2D and related traits. A critical overview of several selected statistical methods for population-based association mapping particularly case-control genetic association analysis is pre-sented. A discussion on a dataset accessed in this paper that includes 3435 female subjects for cases and controls with genotype information across 879071 Single Nucleotide Polymorphism (SNPs) is presented. Quality control steps into the dataset through pre-processing phase are performed to remove samples and markers that failed the quality control test. Association analysis is discussed to address which statistical method can be appropriate to the dataset. Our genetic association analysis produces promising results and indicated that Allelic asso-ciation test showed one SNP above the genome-wide significance threshold of 5×10−8 which is rs10519107 (Odds Ratio (OR)=0.7409,P−Value (P)=1.813×10−9), While, there are several SNPs above the suggestive association threshold of 5×10−6 these SNPs could worth further investigation. Furthermore, Logistic Regression analysis adjusted for multiple confounder factors indicated that none of the genotyped SNPs has passed genome-wide significance threshold of 5×10−8 . Nevertheless, four SNPs (rs10519107, rs4368343, rs6848779, rs11729955) have passed suggestive association threshold

Hmong Adults Self-Rated Oral Health: A Pilot Study

Since 1975, the Hmong refugee population in the U.S. has increased over 200%. However, little is known about their dental needs or self-rated oral health (SROH). The study aims were to: (1) describe the SROH, self-rated general health (SRGH), and use of dental/physician services; and (2) identify the factors associated with SROH among Hmong adults. A cross-sectional study design with locating sampling methodology was used. Oral health questionnaire was administered to assess SROH and SRGH, past dental and physician visits, and language preference. One hundred twenty adults aged 18–50+ were recruited and 118 had useable information. Of these, 49% rated their oral health as poor/fair and 30% rated their general health as poor/fair. Thirty-nine percent reported that they did not have a regular source of dental care, 46% rated their access to dental care as poor/fair, 43% visited a dentist and 66% visited a physician within the past 12 months. Bivariate analyses demonstrated that access to dental care, past dental visits, age and SRGH were significantly associated with SROH (P \u3c 0.05). Multivariate analyses demonstrated a strong association between access to dental care and good/excellent SROH. About half of Hmong adults rated their oral health and access to dental care as poor. Dental insurance, access to dental care, past preventive dental/physician visits and SRGH were associated with SROH

What do you do for a living? Toward a more succinct definition of health services research

This commentary discusses the need for, and the advantages of, a more concise, revised definition of the field of health services research. It argues for a definition that includes not only the topics on which health services research focuses but also the goals of health services research. A number of condensed definitions are provided for consideration

The bulk of the black hole growth since z ~ 1 occurs in a secular universe: no major merger-AGN connection

What is the relevance of major mergers and interactions as triggering mechanisms for active galactic nuclei (AGNs) activity? To answer this long-standing question, we analyze 140 XMM-Newton-selected AGN host galaxies and a matched control sample of 1264 inactive galaxies over z ~ 0.3–1.0 and M_∗ < 10^(11.7) M_⊙ with high-resolution Hubble Space Telescope/Advanced Camera for Surveys imaging from the COSMOS field. The visual analysis of their morphologies by 10 independent human classifiers yields a measure of the fraction of distorted morphologies in the AGN and control samples, i.e., quantifying the signature of recent mergers which might potentially be responsible for fueling/triggering the AGN. We find that (1) the vast majority (>85%) of the AGN host galaxies do not show strong distortions and (2) there is no significant difference in the distortion fractions between active and inactive galaxies. Our findings provide the best direct evidence that, since z ~ 1, the bulk of black hole (BH) accretion has not been triggered by major galaxy mergers, therefore arguing that the alternative mechanisms, i.e., internal secular processes and minor interactions, are the leading triggers for the episodes of major BH growth.We also exclude an alternative interpretation of our results: a substantial time lag between merging and the observability of the AGN phase could wash out the most significant merging signatures, explaining the lack of enhancement of strong distortions on the AGN hosts. We show that this alternative scenario is unlikely due to (1) recent major mergers being ruled out for the majority of sources due to the high fraction of disk-hosted AGNs, (2) the lack of a significant X-ray signal in merging inactive galaxies as a signature of a potential buried AGN, and (3) the low levels of soft X-ray obscuration for AGNs hosted by interacting galaxies, in contrast to model predictions

Obscured star formation in intermediate-density environments:A Spitzer study of the Abell 901/902 supercluster

We explore the amount of obscured star formation as a function of environment in the Abell 901/902 (A901/902) supercluster at z = 0.165 in conjunction with a field sample drawn from the A901 and CDFS fields, imaged with the Hubble Space Telescope as part of the Space Telescope A901/902 Galaxy Evolution Survey and Galaxy Evolution from Morphology and Spectral Energy Distributions (SEDs) Survey. We combine the combo-17 near-UV/optical SED with Spitzer 24 mu m photometry to estimate both the unobscured and obscured star formation in galaxies with M-* > 10(10) M-circle dot. We find that the star formation activity in massive galaxies is suppressed in dense environments, in agreement with previous studies. Yet, nearly 40% of the star-forming (SF) galaxies have red optical colors at intermediate and high densities. These red systems are not starbursting; they have star formation rates (SFRs) per unit stellar mass similar to or lower than blue SF galaxies. More than half of the red SF galaxies have low infrared-to-ultraviolet (IR-to-UV) luminosity ratios, relatively high Sersicindices, and they are equally abundant at all densities. They might be gradually quenching their star formation, possibly but not necessarily under the influence of gas-removing environmental processes. The other greater than or similar to 40% of the red SF galaxies have high IR-to-UV luminosity ratios, indicative of high dust obscuration. They have relatively high specific SFRs and are more abundant at intermediate densities. Our results indicate that while there is an overall suppression in the SF galaxy fraction with density, the small amount of star formation surviving the cluster environment is to a large extent obscured, suggesting that environmental interactions trigger a phase of obscured star formation, before complete quenching

Comparative Performance of Comorbidity Indices in Predicting Health Care-Related Behaviors and Outcomes among Medicaid Enrollees with Type 2 Diabetes

Abstract No single gold standard of comorbidity measure has been identified, and the performance of comorbidity indices vary according to the outcome of interest. The authors compared the Charlson Comorbidity Index, Elixhauser Index (EI), Chronic Disease Score (CDS), and Health-related Quality of Life Comorbidity Index (HRQL-CI) in predicting health care-related behaviors (physicians' concordance with diabetes care standards and patients' oral antidiabetic drug [OAD] adherence) and outcomes (health care utilization and expenditures) among Medicaid enrollees with type 2 diabetes. A total of 9832 diabetes patients who used OAD were identified using data from the MarketScan Medicaid database from 2003 to 2007. Predictive performance of the comorbidity index was assessed using multiple regression models controlling for patient demographics, diabetes severity, and baseline health care characteristics. Among the 4 indices, the CDS was best at predicting physician's concordance with care standards. The CDS and HRQL-CI mental index performed better than other indices as predictors of medication adherence. The EI was best at predicting health care utilization and expenditures. These results suggest that, for these low-income diabetes patients, the CDS and HRQL-CI mental index were relatively better risk-adjustment tools for health care-related behavior data evaluation and the EI was the first choice for health care utilization and expenditures data. (Population Health Management 2012;15:220?229)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98469/1/pop%2E2011%2E0037.pd

Click-chemistry mediated synthesis of OTBN-1,2,3-Triazole derivatives exhibiting STK33 inhibition with diverse anti-cancer activities

There is a continuous and pressing need to establish new brain-penetrant bioactive compounds with anti-cancer properties. To this end, a new series of 4′-((4-substituted-4,5-dihydro-1H-1,2,3-triazol-1-yl)methyl)-[1,1′-biphenyl]-2-carbonitrile (OTBN-1,2,3-triazole) derivatives were synthesized by click chemistry. The series of bioactive compounds were designed and synthesized from diverse alkynes and N3-OTBN, using copper (II) acetate monohydrate in aqueous dimethylformamide at room temperature. Besides being highly cost-effective and significantly reducing synthesis, the reaction yielded 91–98 % of the target products without the need of any additional steps or chromatographic techniques. Two analogues exhibit promising anti-cancer biological activities. Analogue 4l shows highly specific cytostatic activity against lung cancer cells, while analogue 4k exhibits pan-cancer anti-growth activity. A kinase screen suggests compound 4k has single-digit micromolar activity against kinase STK33. High STK33 RNA expression correlates strongly with poorer patient outcomes in both adult and pediatric glioma. Compound 4k potently inhibits cell proliferation, invasion, and 3D neurosphere formation in primary patient-derived glioma cell lines. The observed anti-cancer activity is enhanced in combination with specific clinically relevant small molecule inhibitors. Herein we establish a novel biochemical kinase inhibitory function for click-chemistry-derived OTBN-1,2,3-triazole analogues and further report their anti-cancer activity in vitro for the first time

Click-chemistry mediated synthesis of OTBN-1,2,3-Triazole derivatives exhibiting STK33 inhibition with diverse anti-cancer activities

There is a continuous and pressing need to establish new brain-penetrant bioactive compounds with anti-cancer properties. To this end, a new series of 4′-((4-substituted-4,5-dihydro-1H-1,2,3-triazol-1-yl)methyl)-[1,1′-biphenyl]-2-carbonitrile (OTBN-1,2,3-triazole) derivatives were synthesized by click chemistry. The series of bioactive compounds were designed and synthesized from diverse alkynes and N3-OTBN, using copper (II) acetate monohydrate in aqueous dimethylformamide at room temperature. Besides being highly cost-effective and significantly reducing synthesis, the reaction yielded 91–98 % of the target products without the need of any additional steps or chromatographic techniques. Two analogues exhibit promising anti-cancer biological activities. Analogue 4l shows highly specific cytostatic activity against lung cancer cells, while analogue 4k exhibits pan-cancer anti-growth activity. A kinase screen suggests compound 4k has single-digit micromolar activity against kinase STK33. High STK33 RNA expression correlates strongly with poorer patient outcomes in both adult and pediatric glioma. Compound 4k potently inhibits cell proliferation, invasion, and 3D neurosphere formation in primary patient-derived glioma cell lines. The observed anti-cancer activity is enhanced in combination with specific clinically relevant small molecule inhibitors. Herein we establish a novel biochemical kinase inhibitory function for click-chemistry-derived OTBN-1,2,3-triazole analogues and further report their anti-cancer activity in vitro for the first time