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

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

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

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

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

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

Veterans Affairs Health System and Mental Health Treatment Retention among Patients with Serious Mental Illness: Evaluating Accessibility and Availability Barriers

We examine the impact of two dimensions of access—geographic accessibility and availability—on VA health system and mental health treatment retention among patients with serious mental illness (SMI). Methods . Among 156,631 patients in the Veterans Affairs (VA) health care system with schizophrenia or bipolar disorder in fiscal year 1998 (FY98), we used Cox proportional hazards regression to model time to first 12-month gap in health system utilization, and in mental health services utilization, by the end of FY02. Geographic accessibility was operationalized as straight-line distance to nearest VA service site or VA psychiatric service site, respectively. Service availability was assessed using county-level VA hospital beds and non-VA beds per 1,000 county residents. Patients who died without a prior gap in care were censored. Results . There were 32, 943 patients (21 percent) with a 12-month gap in health system utilization; 65,386 (42 percent) had a 12-month gap in mental health services utilization. Gaps in VA health system utilization were more likely if patients were younger, nonwhite, unmarried, homeless, nonservice-connected, if they had bipolar disorder, less medical morbidity, an inpatient stay in FY98, or if they lived farther from care or in a county with fewer VA inpatient beds. Similar relationships were observed for mental health, however being older, female, and having greater morbidity were associated with increased risks of gaps, and number of VA beds was not significant. Conclusions . Geographic accessibility and resource availability measures were associated with long-term continuity of care among patients with SMI. Increased distance from providers was associated with greater risks of 12-month gaps in health system and mental health services utilization. Lower VA inpatient bed availability was associated with increased risks of gaps in health system utilization. Study findings may inform efforts to improve treatment retention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73433/1/j.1475-6773.2006.00642.x.pd

Redrawing Boundaries: WITNESS and the Politics of Citizen Videos

This article engages with several pressing issues revolving around ‘citizen witnessing’, with specific reference to the human rights advocacy group, WITNESS. In the course of tracing WITNESS’ development over the past two decades, it offers an evaluative assessment of the challenges its members have faced in promoting a grassroots, citizen-centred approach to video reportage. More specifically, this advocacy is informed by an ethical commitment to advancing human rights causes by equipping citizens in crisis situations with cameras, and the training to use them, so that they might bear witness to the plight of others. In so doing, this article argues, WITNESS offers a tactical reformulation of the guiding tenets of peace journalism, one with considerable potential for recasting anew its strategic priorities