Haplotype Variety Analysis of Human Populations: an Application to HapMap Data

We undertake a study to investigate the haplotype variety of distinct human populations. We use a natural measure of haplotype variety, the total number of haplotypes (TNH) present that reflects the number of haplotypes with nonzero frequencies estimated from the data at hand for each selection of multiple loci. For the analysis of real human populations, we use the haplotype data of the Denver Chinese, Tuscan Italians, Luhya Kenyans, and Gujarati Indians from release III of the HapMap database. Moreover, we show that the TNH statistic is biased in small sample data scenarios such as the HapMap and implement a nested simulation study to estimate and remove such bias. We perform a preliminary analysis of means and variances of the population allele frequencies in the four populations. Lastly, we implement a generalized linear model to detect and quantify the differences in haplotype structures of these populations. Our results show that all populations possess significantly different adjusted average TNH values. Our findings extend previous results based on alternative statistical approaches and demonstrate the existence of pronounced differences in the haplotype variety of the analyzed populations even after controlling for haplotype span as well as all allele frequencies and their two-way interactions

Integrating Prevention of Mother-to-Child HIV Transmission Programs to Improve Uptake: A Systematic Review

BACKGROUND: We performed a systematic review to assess the effect of integrated perinatal prevention of mother-to-child transmission of HIV interventions compared to non- or partially integrated services on the uptake in low- and middle-income countries. METHODS: We searched for experimental, quasi-experimental and controlled observational studies in any language from 21 databases and grey literature sources. RESULTS: Out of 28 654 citations retrieved, five studies met our inclusion criteria. A cluster randomized controlled trial reported higher probability of nevirapine uptake at the labor wards implementing HIV testing and structured nevirapine adherence assessment (RRR 1.37, bootstrapped 95% CI, 1.04-1.77). A stepped wedge design study showed marked improvement in antiretroviral therapy (ART) enrolment (44.4% versus 25.3%, p<0.001) and initiation (32.9% versus 14.4%, p<0.001) in integrated care, but the median gestational age of ART initiation (27.1 versus 27.7 weeks, p = 0.4), ART duration (10.8 versus 10.0 weeks, p = 0.3) or 90 days ART retention (87.8% versus 91.3%, p = 0.3) did not differ significantly. A cohort study reported no significant difference either in the ART coverage (55% versus 48% versus 47%, p = 0.29) or eight weeks of ART duration before the delivery (50% versus 42% versus 52%; p = 0.96) between integrated, proximal and distal partially integrated care. Two before and after studies assessed the impact of integration on HIV testing uptake in antenatal care. The first study reported that significantly more women received information on PMTCT (92% versus 77%, p<0.001), were tested (76% versus 62%, p<0.001) and learned their HIV status (66% versus 55%, p<0.001) after integration. The second study also reported significant increase in HIV testing uptake after integration (98.8% versus 52.6%, p<0.001). CONCLUSION: Limited, non-generalizable evidence supports the effectiveness of integrated PMTCT programs. More research measuring coverage and other relevant outcomes is urgently needed to inform the design of services delivering PMTCT programs

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Mechanoreceptors Found in a Posterior Cruciate Ligament From a Well-Functioning Total Knee Arthroplasty Retrieval

Histologic analysis of the posterior cruciate ligament has been reported in the normal and osteoarthritic knee but not after cruciate-retaining (CR) total knee arthroplasty (TKA). Retention of the posterior cruciate ligament during TKA has been debated as to whether it is beneficial in stability and function. If the presence of mechanoreceptors is shown to be maintained in CR TKA, then there may be an argument for retention. This case report used a retrieval of a well-functioning TKA specimen that had a CR TKA. To prove the presence of mechanoreceptors within the ligament, immunohistochemistry techniques using S100 protein and neurofilament protein were used. This specimen had pacini and lamellar type of mechanoreceptors present on immunohistochemistry analysis. The presence or retention of mechanoreceptors and innervations of the ligament may indicate an advantage when retained during TKA. © 2011 Elsevier Inc

APOE, MAPT, and COMT and Parkinson's Disease Susceptibility and Cognitive Symptom Progression.

BackgroundCognitive decline is well recognized in Parkinson's disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), and microtubule-associated protein tau (MAPT) are of interest related to their contributions to cognitive decline or dementia in PD.ObjectiveHere, we investigate whether APOE, COMT, or MAPT influence the rate of cognitive decline in PD patients.MethodsWe relied on 634 PD patients and 879 controls to examine gene-PD susceptibility associations, and nested longitudinal cohort of 246 patients from the case-control study, which followed patients on average 5 years and 7.5 years into disease. We repeatedly assessed cognitive symptom progression with the MMSE and conducted a full neuropsychological battery on a subset of 183 cognitively normal patients. We used repeated-measures regression analyses to assess longitudinal associations between genotypes and cognitive progression scores.ResultsThe MAPT H1 haplotype was associated with PD susceptibility. APOE 4 carriers (ɛ4+) (p = 0.03) and possibly COMT Met/Met (p = 0.06) carriers exhibited faster annual decline on the MMSE. Additionally, APOEɛ4+ carriers showed faster decline in many of the neuropsychological test scores. No such differences in neuropsychological outcomes were seen for the COMT genotypes.ConclusionThis work supports a growing set of research identifying overlapping etiology and pathology between synucleinopathies, such as PD, Alzheimer's disease, and tauopathies, especially in the context of cognitive dysfunction in PD. We provide support for the argument that APOE ɛ4+ and COMT Met/Met genotypes can be used as predictors of faster cognitive decline in PD

Feminized behavior and brain gene expression in a novel mouse model of Klinefelter Syndrome.

Klinefelter Syndrome (KS) is the most common sex chromosome aneuploidy in men and is characterized by the presence of an additional X chromosome (XXY). In some Klinefelter males, certain traits may be feminized or shifted from the male-typical pattern towards a more female-typical one. Among them might be partner choice, one of the most sexually dimorphic traits in the animal kingdom. We investigated the extent of feminization in XXY male mice (XXYM) in partner preference and gene expression in the bed nucleus of the stria terminalis/preoptic area and the striatum in mice from the Sex Chromosome Trisomy model. We tested for partner preference using a three-chambered apparatus in which the test mouse was free to choose between stimulus animals of either sex. We found that partner preference in XXYM was feminized. These differences were likely due to interactions of the additional X chromosome with the Y. We also discovered genes that differed in expression in XXYM versus XYM. Some of these genes are feminized in their expression pattern. Lastly, we also identified genes that differed only between XXYM versus XYM and not XXM versus XYM. Genes that are both feminized and unique to XXYM versus XYM represent strong candidates for dissecting the molecular pathways responsible for phenotypes present in KS/XXYM but not XXM. In sum, our results demonstrated that investigating behavioral and molecular feminization in XXY males can provide crucial information about the pathophysiology of KS and may aid our understanding of sex differences in brain and behavior

Shared_Methylation_Sites

File containing the methylation frequency for each individual at all shares sites (24,205