CHIIMP: An automated high-throughput microsatellite genotyping approach reveals greater allelic diversity in wild chimpanzees

Short tandem repeats (STRs), also known as microsatellites, are commonly used to non invasively genotype wild-living endangered species, including African apes. Until recently, capillary electrophoresis has been the method of choice to determine the length of polymorphic STR loci. However, this technique is labor intensive, difficult to compare across platforms, and notoriously imprecise. Here we developed a MiSeq-based approach and tested its performance using previously genotyped fecal samples from long-term studied chimpanzees in Gombe National Park, Tanzania. Using data from eight microsatellite loci as a reference, we designed a bioinformatics platform that converts raw MiSeq reads into locus-specific files and automatically calls alleles after filtering stutter sequences and other PCR artifacts. Applying this method to the entire Gombe population, we confirmed previously reported genotypes, but also identified 31 new alleles that had been missed due to sequence differences and size homoplasy. The new genotypes, which increased the allelic diversity and heterozygosity in Gombe by 61% and 8%, respectively, were validated by replicate amplification and pedigree analyses. This demonstrated inheritance and resolved one case of an ambiguous paternity. Using both singleplex and multiplex locus amplification, we also genotyped fecal samples from chimpanzees in the Greater Mahale Ecosystem in Tanzania, demonstrating the utility of the MiSeq-based approach for genotyping non-habituated populations and performing comparative analyses across field sites. The new automated high-throughput analysis platform (available at https://github.com/ShawHahnLab/chiimp) will allow biologists to more accurately and effectively determine wildlife population size and structure, and thus obtain information critical for conservation efforts

MRI Findings for Frozen Shoulder Evaluation: Is the Thickness of the Coracohumeral Ligament a Valuable Diagnostic Tool?

Recent studies have demonstrated that the coracohumeral ligament (CHL) is shortened and thickened in a frozen shoulder. We analyzed the rate in CHL visualization between patients with frozen shoulder and normal volunteers using Magnetic Resonance Imaging (MRI) to determine the CHL thickness in the patients with a frozen shoulder.>0.05).MR Imaging is a satisfactory method for CHL depiction, and a thickened CHL is highly suggestive of frozen shoulder

Assessment of possible impact of a health promotion program in Korea from health risk trends in a longitudinally observed cohort

BACKGROUND: Longitudinally observed cohort data can be utilized to assess the potential for health promotion and healthcare planning by comparing the estimated risk factor trends of non-intervened with that of intervened. The paper seeks (1) to estimate a natural transition (patterns of movement between states) of health risk state from a Korean cohort data using a Markov model, (2) to derive an effective and necessary health promotion strategy for the population, and (3) to project a possible impact of an intervention program on health status. METHODS: The observed transition of health risk states in a Korean employee cohort was utilized to estimate the natural flow of aggregated health risk states from eight health risk measures using Markov chain models. In addition, a reinforced transition was simulated, given that a health promotion program was implemented for the cohort, to project a possible impact on improvement of health status. An intervened risk transition was obtained based on age, gender, and baseline risk state, adjusted to match with the Korean cohort, from a simulated random sample of a US employee population, where a health intervention was in place. RESULTS: The estimated natural flow (non-intervened), following Markov chain order 2, showed a decrease in low risk state by 3.1 percentage points in the Korean population while the simulated reinforced transition (intervened) projected an increase in low risk state by 7.5 percentage points. Estimated transitions of risk states demonstrated the necessity of not only the risk reduction but also low risk maintenance. CONCLUSIONS: The frame work of Markov chain efficiently estimated the trend, and captured the tendency in the natural flow. Given only a minimally intense health promotion program, potential risk reduction and low risk maintenance was projected

Validation of a method for identifying nursing home admissions using administrative claims

<p>Abstract</p> <p>Background</p> <p>Currently there is no standard algorithm to identify whether a subject is residing in a nursing home from administrative claims. Our objective was to develop and validate an algorithm that identifies nursing home admissions at the resident-month level using the MarketScan Medicare Supplemental and Coordination of Benefit (COB) database.</p> <p>Methods</p> <p>The computer algorithms for identifying nursing home admissions were created by using provider type, place of service, and procedure codes from the 2000 – 2002 MarketScan Medicare COB database. After the algorithms were reviewed and refined, they were compared with a detailed claims review by an expert reviewer. A random sample of 150 subjects from the claims was selected and used for the validity analysis of the algorithms. Contingency table analysis, comparison of mean differences, correlations, and t-test analyses were performed. Percentage agreement, sensitivity, specificity, and Kappa statistics were analyzed.</p> <p>Results</p> <p>The computer algorithm showed strong agreement with the expert review (99.9%) for identification of the first month of nursing home residence, with high sensitivity (96.7%), specificity (100%) and a Kappa statistic of 0.97. Weighted Pearson correlation coefficient between the algorithm and the expert review was 0.97 (<it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>A reliable algorithm indicating evidence of nursing home admission was developed and validated from administrative claims data. Our algorithm can be a useful tool to identify patient transitions from and to nursing homes, as well as to screen and monitor for factors associated with nursing home admission and nursing home discharge.</p

Do pediatric hospitalizations have a unique geography?

BACKGROUND: In the U.S. small-area health services research studies are often based on the hospital service areas (HSAs) defined by the Dartmouth Atlas of Healthcare project. These areas are based on the geographic origins of Medicare Part A hospital patients, the great majority of whom are seniors. It is reasonable to question whether the geographic system so defined is appropriate for health services research for all ages, particularly for children, who have a very different system of healthcare financing and provision in the U.S. METHODS: This article assesses the need for a unique system of HSAs to support pediatric small-area analyses. It is a cross-sectional analysis of California hospital discharges for two age groups – non-newborns 0–17 years old, and seniors. The measure of interest was index of localization, which is the percentage of HSA residents hospitalized in their home HSA. Indices were computed separately for each age group, and index agreement was assessed for 219 of the state's HSAs. We examined the effect of local pediatric inpatient volume and pediatric inpatient resources on the divergence of the age group indices. We also created a new system of HSAs based solely on pediatric patient origins, and visually compared maps of the traditional and the new system. RESULTS: The mean localization index for pediatric discharges was 20 percentage points lower than for Medicare cases, indicating a poorer fit of the traditional geographic system for children. The volume of pediatric cases did not appear to be associated with the magnitude of index divergence between the two age groups. Pediatric medical and surgical case subgroups gave very similar results, and both groups differed substantially from seniors. Location of children's hospitals and local pediatric bed supply were associated with Medicare-pediatric divergence. There was little visual correspondence between the maps of traditional and pediatric-specific HSAs. CONCLUSION: Children and seniors have significantly different geographic patterns of hospitalization in California. Medicare-based HSAs may not be appropriate for all age groups and service types throughout the U.S

First experiences in the implementation of biometric technology to link data from Health and Demographic Surveillance Systems with health facility data

BACKGROUND: In developing countries, Health and Demographic Surveillance Systems (HDSSs) provide a framework for tracking demographic and health dynamics over time in a defined geographical area. Many HDSSs co-exist with facility-based data sources in the form of Health Management Information Systems (HMIS). Integrating both data sources through reliable record linkage could provide both numerator and denominator populations to estimate disease prevalence and incidence rates in the population and enable determination of accurate health service coverage. OBJECTIVE: To measure the acceptability and performance of fingerprint biometrics to identify individuals in demographic surveillance populations and those attending health care facilities serving the surveillance populations. METHODOLOGY: Two HDSS sites used fingerprint biometrics for patient and/or surveillance population participant identification. The proportion of individuals for whom a fingerprint could be successfully enrolled were characterised in terms of age and sex. RESULTS: Adult (18-65 years) fingerprint enrolment rates varied between 94.1% (95% CI 93.6-94.5) for facility-based fingerprint data collection at the Africa Centre site to 96.7% (95% CI 95.9-97.6) for population-based fingerprint data collection at the Agincourt site. Fingerprint enrolment rates in children under 1 year old (Africa Centre site) were only 55.1% (95% CI 52.7-57.4). By age 5, child fingerprint enrolment rates were comparable to those of adults. CONCLUSION: This work demonstrates the feasibility of fingerprint-based individual identification for population-based research in developing countries. Record linkage between demographic surveillance population databases and health care facility data based on biometric identification systems would allow for a more comprehensive evaluation of population health, including the ability to study health service utilisation from a population perspective, rather than the more restrictive health service perspective

Invasive behavior of ulcerative colitis-associated carcinoma is related to reduced expression of CD44 extracellular domain: comparison with sporadic colon carcinoma

<p>Abstract</p> <p>Background</p> <p>To elucidate relations of invasion of ulcerative colitis (UC)-associated carcinoma with its prognosis, the characteristics of invasive fronts were analyzed in comparison with sporadic colonic carcinomas.</p> <p>Methods</p> <p>Prognoses of 15 cases of UC-associated colonic carcinoma were compared with those of sporadic colon carcinoma cases, after which 75 cases of sporadic invasive adenocarcinoma were collected. Tumor budding was examined histologically at invasive fronts using immunohistochemistry (IHC) of pancytokeratin. Expressions of beta-catenin with mutation analysis, CD44 extracellular domain, Zo-1, occludin, matrix matalloproteinase-7, laminin-5γ2, and sialyl Lewis X (Le^X) were immunohistochemically evaluated.</p> <p>Results</p> <p>UC-associated carcinoma showed worse prognosis than sporadic colon carcinoma in all the cases, and exhibited a tendency to become more poorly differentiated when carcinoma invaded the submucosa or deeper layers than sporadic carcinoma. When the lesions were compared with sporadic carcinomas considering differentiation grade, reduced expression of CD44 extracellular domain in UC-associated carcinoma was apparent. Laminin-5γ2 and sialyl-Le^Xexpression showed a lower tendency in UC-associated carcinomas than in their sporadic counterparts. There were no differences in the numbers of tumor budding foci between the two lesion types, with no apparent relation to nuclear beta-catenin levels in IHC.</p> <p>Conclusions</p> <p>UC-associated carcinoma showed poorer differentiation when the carcinoma invaded submucosa or deeper parts, which may influence the poorer prognosis. The invasive behavior of UC-associated carcinoma is more associated with CD44 cleavage than with basement membrane disruption or sialyl-Lewis-antigen alteration.</p

Combinatorial Computational Approaches to Identify Tetracycline Derivatives as Flavivirus Inhibitors

Limited structural information of drug targets, cellular toxicity possessed by lead compounds, and large amounts of potential leads are the major issues facing the design-oriented approach of discovering new leads. In an attempt to tackle these issues, we have developed a process of virtual screening based on the observation that conformational rearrangements of the dengue virus envelope protein are essential for the mediation of viral entry into host cells via membrane fusion. Screening was based solely on the structural information of the Dengue virus envelope protein and was focused on a target site that is presumably important for the conformational rearrangements necessary for viral entry. To circumvent the issue of lead compound toxicity, we performed screening based on molecular docking using structural databases of medical compounds. To enhance the identification of hits, we further categorized and selected candidates according to their novel structural characteristics. Finally, the selected candidates were subjected to a biological validation assay to assess inhibition of Dengue virus propagation in mammalian host cells using a plaque formation assay. Among the 10 compounds examined, rolitetracycline and doxycycline significantly inhibited plaque formation, demonstrating their inhibitory effect on dengue virus propagation. Both compounds were tetracycline derivatives with IC(50)s estimated to be 67.1 µM and 55.6 µM, respectively. Their docked conformations displayed common hydrophobic interactions with critical residues that affected membrane fusion during viral entry. These interactions will therefore position the tetracyclic ring moieties of both inhibitors to bind firmly to the target and, subsequently, disrupt conformational rearrangement and block viral entry. This process can be applied to other drug targets in which conformational rearrangement is critical to function

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente