Fidelity of SNP array genotyping using Epstein Barr virus-transformed B-lymphocyte cell lines: Implications for genome-wide association studies

Background: As availability of primary cells can be limited for genetic studies of human disease, lymphoblastoid cell lines (LCL) are common sources of genomic DNA. LCL are created in a transformation process that entails in vitro infection of human B-lymphocytes with the Epstein-Barr Virus (EBV). Methodology/Principal Findings: To test for genotypic errors potentially induced by the Epstein-Barr Virus transformation process, we compared single nucleotide polymorphism (SNP) genotype calls in peripheral blood mononuclear cells (PBMC) and LCL from the same individuals. The average mismatch rate across 19 comparisons was 0.12% for SNPs with a population call rate of at least 95%, and 0.03% at SNPs with a call rate of at least 99%. Mismatch rates were not correlated across genotype subarrays run on all sample pairs. Conclusions/Significance: Genotypic discrepancies found in PBMC and LCL pairs were not significantly different than control pairs, and were not correlated across subarrays. These results suggest that mismatch rates are minimal with stringent quality control, and that most genotypic discrepancies are due to technical artifacts rather than the EBV transformation process. Thus, LCL likely constitute a reliable DNA source for host genotype analysis. © 2009 Herbeck et al

Staphylococcus aureus in the oral cavity: a three-year retrospective analysis of clinical laboratory data

OBJECTIVE: A retrospective analysis of laboratory data to investigate the isolation of Staphylococcus aureus from the oral cavity and facial area in specimens submitted to a regional diagnostic oral microbiology laboratory. METHODS: A hand search of laboratory records for a three-year period (1998-2000) was performed for specimens submitted to the regional diagnostic oral microbiology laboratory based at Glasgow Dental Hospital and School. Data were collected from forms where S. aureus was isolated. These data included demographics, referral source, specimen type, methicillin susceptibility and clinical details. RESULTS: For the period 1998-2000, there were 5,005 specimens submitted to the laboratory. S. aureus was isolated from 1,017 specimens, of which 967 (95%) were sensitive to methicillin (MSSA) and 50 (5%) were resistant to methicillin (MRSA). The 1,017 specimens were provided from 615 patients. MRSA was isolated from 37 (6%) of patients. There was an increasing incidence of S. aureus with age, particularly in the greater than 70 years age group. The most common specimen from which MSSA was isolated was an oral rinse (38%) whilst for MRSA isolates this was a tongue swab (28%). The clinical condition most commonly reported for MSSA isolates was angular cheilitis (22%). Erythema, swelling, pain or burning of the oral mucosa was the clinical condition most commonly reported for MRSA isolates (16%). Patients from whom the MSSA isolates were recovered were most commonly (55%) seen in the oral medicine clinic at the dental hospital, whilst patients with MRSA were more commonly seen in primary care settings such as nursing homes, hospices and general dental practice (51%). CONCLUSION: In line with more recent surveys, this retrospective study suggests that S. aureus may be a more frequent isolate from the oral cavity than hitherto suspected. A small proportion of the S. aureus isolates were MRSA. There were insufficient data available to determine whether the S. aureus isolates were colonising or infecting the oral cavity. However, the role of S. aureus in several diseases of the oral mucosa merits further investigation

Lorentz Violation in Warped Extra Dimensions

Higher dimensional theories which address some of the problematic issues of the Standard Model(SM) naturally involve some form of $D=4+n$-dimensional Lorentz invariance violation (LIV). In such models the fundamental physics which leads to, e.g., field localization, orbifolding, the existence of brane terms and the compactification process all can introduce LIV in the higher dimensional theory while still preserving 4-d Lorentz invariance. In this paper, attempting to capture some of this physics, we extend our previous analysis of LIV in 5-d UED-type models to those with 5-d warped extra dimensions. To be specific, we employ the 5-d analog of the SM Extension of Kostelecky et. al. ~which incorporates a complete set of operators arising from spontaneous LIV. We show that while the response of the bulk scalar, fermion and gauge fields to the addition of LIV operators in warped models is qualitatively similar to what happens in the flat 5-d UED case, the gravity sector of these models reacts very differently than in flat space. Specifically, we show that LIV in this warped case leads to a non-zero bulk mass for the 5-d graviton and so the would-be zero mode, which we identify as the usual 4-d graviton, must necessarily become massive. The origin of this mass term is the simultaneous existence of the constant non-zero $AdS_5$ curvature and the loss of general co-ordinate invariance via LIV in the 5-d theory. Thus warped 5-d models with LIV in the gravity sector are not phenomenologically viable.Comment: 14 pages, 4 figs; discussion added, algebra repaire

Association between free testosterone levels and anal human papillomavirus Types 16/18 infections in a cohort of men who have sex with men

Background Human papillomavirus (HPV) types 16 and 18 cause invasive cervical cancer and most invasive anal cancers (IACs). Overall, IAC rates are highest among men who have sex with men (MSM), especially MSM with HIV infection. Testosterone is prescribed for men showing hypogonadism and HIV-related wasting. While there are direct and indirect physiological effects of testosterone in males, its role in anal HPV16/18 infections in men is unknown. Methods Free testosterone (FT) was measured in serum from 340 Multicenter AIDS Cohort Study (MACS) participants who were tested for anal HPV16/18-DNA approximately 36 months later. The effect of log10-transformed current FT level on anal HPV16/18 prevalence was modeled using Poisson regression with robust error variance. Multivariate models controlled for other HPV types, cumulative years of exogenous testosterone use, race, age, lifetime number of receptive anal intercourse partnerships, body mass index, tobacco smoking, HIV-infection and CD4+ T-cell counts among HIV-infected, and blood draw timing. Results Participants were, on average, 60 (+5.4) years of age, White (86%), and HIV-uninfected (56%); Twenty-four percent tested positive for anal HPV16 and/or 18-DNA (HPV16 prevalence= 17.1%, HPV18=9.1%). In adjusted analysis, each half-log10 increase of FT was associated with a 1.9-fold (95% Confidence Interval: 1.11, 3.24) higher HPV16/18 prevalence. Additionally, other Group 1 high-risk HPVs were associated with a 1.56-fold (1.03, 2.37) higher HPV16/18 prevalence. Traditional risk factors for HPV16/18 infection (age, tobacco smoking; lifetime number of sexual partners, including the number of receptive anal intercourse partnerships within 24 months preceding HPV testing) were poorly correlated with one another and not statistically significantly associated with higher prevalence of HPV16/ 18 infection in unadjusted and adjusted analyses. Conclusions Higher free testosterone was associated with increased HPV16/18 prevalence measured approximately three years later, independent of sexual behavior and other potential confounders. The mechanisms underlying this association remain unclear and warrant further study

PCB-containing wood floor finish is a likely source of elevated PCBs in residents' blood, household air and dust: a case study of exposure

© 2008 Rudel et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Field Evaluation of Calypte’s AWARE™ Blood Serum Plasma (BSP) and Oral Mucosal Transudate (OMT) Rapid Tests for Detecting Antibodies to HIV-1 and 2 in Plasma and Oral Fluid

As programs to prevent and care for HIV-infected persons are scaled-up in Africa, there is the need for continuous evaluation of the performance of test kits that could best support these programs. The present study evaluated the sensitivity, specificity, ease of use, and cost of AWARE ™ Blood Serum Plasma (BSP) and Oral Mucosal Transudate (OMT) Rapid HIV-1/2 test kits using real-time and archived samples of HIV-infected persons from Cameroon. Matched whole blood and OMT specimens were collected prospectively from HIV-positive and HIV-negative persons from different regions of Cameroon and tested using the AWARE ™ BSP and OMT test kits, respectively. These results were compared to the gold standard that included a combination of Determine HIV-1/2 and Enzygnost HIV-1/2. The BSP Rapid test kit was further evaluated using well characterized panels of HIV-2 and HIV-1 group O samples. Cost and end-user analysis of the OMT test kit was done by comparing its actual cost, consumables, safety, bench time and manipulation with other test kits. Of the 732 matched samples, 412 (56.3%) and 320 (43.7%) were from females and males, respectively. Of these samples, 23 (3.1%) gave discordant results between Determine HIV-1/2 and Enzygnost HIV1/2 and were excluded from the analysis. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the AWARE™ BSP were 100%. The AWARE™ OMT had 98.8% sensitivity, 98.9% specificity, 98.0% PPV and 99.4% NPV. The results of a well-characterized archived panel of HIV-2 (n=7) and HIV-1 group O (n=3) samples using the AWARE™ BSP Rapid test kit gave 100% concordance. Total per patient cost of the AWARE OMT rapid test kit was US$4.72 compared to a mean cost of US$7.33 ± 0.11 for the other test kits. Both the AWARE™ BSP and OMT Rapid test kits demonstrated high sensitivities and specificities on all samples tested and were well adapted for use in resource-constrained settings with high HIV heterogeneity such as Cameroon. The AWARE ™ HIV-1/2 OMT Rapid test kit appears to be the cheapest, safest and easiest to use compared with other available test kits

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

The effect on mental health of a large scale psychosocial intervention for survivors of mass violence: A quasi-experimental study in Rwanda

Background: War has serious and prolonged mental health consequences. It is argued that post-emergency mental health interventions should not only focus on psychological factors but also address the social environment. No controlled trials of such interventions exist. We studied the effect on mental health of a large scale p