Household Transmission of Gastroenteritis

Transmission of infectious gastroenteritis was studied in 936 predominately Hispanic households in northern California. Among 3,916 contacts of 1,099 primary case-patients, the secondary attack rate was 8.8% (95% confidence interval 7.9–9.7); children had a 2- to 8-fold greater risk than adults. Bed-sharing among children in crowded homes is a potentially modifiable risk

Therapeutic effects of the mitochondrial ROS-redox modulator KH176 in a mammalian model of Leigh Disease

Leigh Disease is a progressive neurometabolic disorder for which a clinical effective treatment is currently still lacking. Here, we report on the therapeutic efficacy of KH176, a new chemical entity derivative of Trolox, in Ndufs4 (-/-) mice, a mammalian model for Leigh Disease. Using in vivo brain diffusion tensor imaging, we show a loss of brain microstructural coherence in Ndufs4 (-/-) mice in the cerebral cortex, external capsule and cerebral peduncle. These findings are in line with the white matter diffusivity changes described in mitochondrial disease patients. Long-term KH176 treatment retained brain microstructural coherence in the external capsule in Ndufs4 (-/-) mice and normalized the increased lipid peroxidation in this area and the cerebral cortex. Furthermore, KH176 treatment was able to significantly improve rotarod and gait performance and reduced the degeneration of retinal ganglion cells in Ndufs4 (-/-) mice. These in vivo findings show that further development of KH176 as a potential treatment for mitochondrial disorders is worthwhile to pursue. Clinical trial studies to explore the potency, safety and efficacy of KH176 are ongoing

A New Method for Morphometric Analysis of Tissue Distribution of Mobile Cells in Relation to Immobile Tissue Structures

The distribution of cells in stained tissue sections provides information that may be analyzed by means of morphometric computation. We developed an algorithm for automated analysis for the purpose of answering questions pertaining to the relative densities of wandering cells in the vicinity of comparatively immobile tissue structures such as vessels or tumors. As an example, we present the analysis of distribution of CD56-positive cells and of CXCR3-positive cells (relative densities of peri-vascular versus non-vascular cell populations) in relation to the endothelium of capillaries and venules of human parietal decidua tissue of first trimester pregnancy. In addition, the distibution of CD56-positive cells (mostly uterine NK cells) in relation to spiral arteries is analyzed. The image analysis is based on microphotographs of two-color immunohistological stainings. Discrete distances (10–50 µm) from the fixed structures were chosen for the purpose of definining the extent of neighborhood areas. For the sake of better comparison of cell distributions at different overall cell densities a model of random distribution of “cells” in relation to neighborhood areas and rest decidua of a specific sample was built. In the chosen instances, we found increased perivascular density of CD56-positive cells and of CXCR3-positive cells. In contrast, no accumulation of CD56-positive cells was found in the neighborhood of spiral arteries

Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma

HLA class I loss is a significant mechanism of immune evasion by cervical carcinoma, interfering with the development of immunotherapies and cancer vaccines. We report the systematic investigation of HLA class I and antigen processing machinery component expression and association with clinical outcome. A tissue microarray containing carcinoma lesions from 109 cervical carcinoma patients was stained for HLA class I heavy chains, β2-microglobulin, LMP2, LMP7, LMP10, TAP1, TAP2, ERAP1, tapasin, calreticulin, calnexin and ERp57. A novel staining evaluation method was used to ensure optimal accuracy and reliability of expression data, which were correlated with known clinicopathological parameters. Partial HLA class I loss was significantly associated with decreased 5-years overall survival (61% vs. 83% for normal expression; P < 0.05) and was associated with decreased 5-years disease-free survival (DFS) (65% vs. 82% for normal expression; P = 0.05). All APM components except LMP10, calnexin and calreticulin were down-regulated in a substantial number of cases and, except ERAP1, correlated significantly with HLA class I down-regulation. LMP7, TAP1 and ERAP1 loss was significantly associated with decreased overall and (except LMP7) DFS (P < 0.05 and 0.005, respectively). ERAP1 down-regulation was an independent predictor for worse overall and DFS in multivariate analysis (HR 3.08; P < 0.05 and HR 2.84; P < 0.05, respectively). HLA class I and APM component down-regulation occur frequently in cervical carcinoma, while peptide repertoire alterations due to ERAP1 loss are a major contributing factor to tumour progression and mortality

Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation

Chemotherapy plus bevacizumab is currently considered as the standard 1st line treatment of advanced colorectal cancer (ACC). Whereas GI perforation is a known side effect of bevacizumab, the development of GI ulcers has not been reported. We identified 18 patients with ACC who participated in a phase III multicentre trial which included chemotherapy and bevacizumab, who developed a GI ulcer (n = 6), perforation (n = 8) or both (n = 4). The risk of developing a symptomatic GI ulcer or perforation was 1.3% and 1.6%, respectively. Central review of the histology specimens showed ulceration and/or granulation tissue with neovascularisation. The majority (89%) of events developed early during treatment. Given these observations, as well as the relationship between VEGF and mucosal injury healing, we suggest that GI ulcers may occur as a side effect of treatment with bevacizumab and may herald perforation

Identifying placebo responders and predictors of response in osteoarthritis: a protocol for individual patient data meta-analysis

Background: The management of osteoarthritis (OA) is unsatisfactory, as most treatments are not clinically effective over placebo and most drugs have considerable side effects. On average, 75 % of the analgesic effect from OA treatments in clinical trials can be attributed to a placebo response, and this response varies greatly from patient to patient. This individual patient data (IPD) meta-analysis aims to identify placebo responders and the potential determinants of the placebo response in OA. Methods: This study is undertaken in conjunction with the OA Trial Bank, an ongoing international consortium aiming to collect IPD from randomised controlled trials (RCTs) for all treatments of OA. RCTs for each treatment of OA have been systematically searched for, and authors of the relevant trials have been contacted to request the IPD. We will use the IPD of placebo-controlled RCTs held by the OA Trial Bank for this project. The IPD in placebo groups will be used to investigate the placebo response according to the minimum clinically important difference (MCID) threshold (e.g. 20 % pain reduction). Responders to placebo will be compared with non-responders to identify predictors of response. The quality of the trials will be assessed and potential determinants will be examined using multilevel logistic regression analyses. Discussion: This study explores the varying magnitude of the placebo response and the proportion of participants that experience a clinically important placebo effect in OA RCTs. Potential determinants of the placebo response will also be investigated. These determinants may be useful for future studies as it may allow participants to be stratified into groups based on their likely response to placebo. The results of this study may also be useful for pharmaceutical companies, who could improve the design of their studies in order to separate the specific treatment from the non-specific contextual (i.e. placebo) effects

Differential branching fraction and angular analysis of the decay B0→K∗0μ+μ−

The angular distribution and differential branching fraction of the decay B 0→ K ∗0 μ + μ − are studied using a data sample, collected by the LHCb experiment in pp collisions at s√=7 TeV, corresponding to an integrated luminosity of 1.0 fb−1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions

Opposite-side flavour tagging of B mesons at the LHCb experiment

The calibration and performance of the oppositeside flavour tagging algorithms used for the measurements of time-dependent asymmetries at the LHCb experiment are described. The algorithms have been developed using simulated events and optimized and calibrated with B + →J/ψK +, B0 →J/ψK ∗0 and B0 →D ∗− μ + νμ decay modes with 0.37 fb−1 of data collected in pp collisions at √ s = 7 TeV during the 2011 physics run. The oppositeside tagging power is determined in the B + → J/ψK + channel to be (2.10 ± 0.08 ± 0.24) %, where the first uncertainty is statistical and the second is systematic

Direct comparison of [11C] choline and [18F] FET PET to detect glioma infiltration: a diagnostic accuracy study in eight patients

Background Positron emission tomography (PET) is increasingly used to guide local treatment in glioma. The purpose of this study was a direct comparison of two potential tracers for detecting glioma infiltration, O-(2-[18F]-fluoroethyl)-l-tyrosine ([18F] FET) and [11C] choline. Methods Eight consecutive patients with newly diagnosed diffuse glioma underwent dynamic [11C] choline and [18F] FET PET scans. Preceding craniotomy, multiple stereotactic biopsies were obtained from regions inside and outside PET abnormalities. Biopsies were assessed independently for tumour presence by two neuropathologists. Imaging measurements were derived at the biopsy locations from 10 to 40 min [11C] choline and 20–40, 40–60 and 60–90 min [18F] FET intervals, as standardized uptake value (SUV) and tumour-to-brain ratio (TBR). Diagnostic accuracies of both tracers were compared using receiver operating characteristic analysis and generalized linear mixed modelling with consensus histopathological assessment as reference. Results Of the 74 biopsies, 54 (73%) contained tumour. [11C] choline SUV and [18F] FET SUV and TBR at all intervals were higher in tumour than in normal samples. For [18F] FET, the diagnostic accuracy of TBR was higher than that of SUV for intervals 40–60 min (area under the curve: 0.88 versus 0.81, p = 0.026) and 60–90 min (0.90 versus 0.81, p = 0.047). The diagnostic accuracy of [18F] FET TBR 60–90 min was higher than that of [11C] choline SUV 20–40 min (0.87 versus 0.67, p = 0.005). Conclusions [18F] FET was more accurate than [11C] choline for detecting glioma infiltration. Highest accuracy was found for [18F] FET TBR for the interval 60–90 min post-injection