Social and spatial heterogeneity in psychosis proneness in a multilevel case-prodrome-control study

To test whether spatial and social neighbourhood patterning of people at ultra-high risk (UHR) of psychosis differs from first-episode psychosis (FEP) participants or controls and to determine whether exposure to different social environments is evident before disorder onset

The incidence of healthcare use, ill health and mortality in adults with intellectual disabilities and mealtime support needs

This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1111/jir.12167/full.Background\ud Adults with intellectual disabilities (ID) experience a wide range of eating, drinking and/or swallowing (EDS) problems, for which they receive diverse mealtime support interventions. Previous research has estimated that dysphagia (difficulty swallowing) affects 8% of all adults with ID and that 15% require some form of mealtime support. People with ID (whether they require mealtime support or not) also experience a greater burden of ill-health and die younger than their peers in the general population with no ID.\ud \ud Methods\ud Using an exploratory, population-based cohort study design, we set out to explore health-related outcomes in adults with ID who receive mealtime support for any eating, drinking or swallowing problem, by establishing the annual incidence of healthcare use, EDS-related ill-health, and all-cause mortality. This study was conducted in two counties in the East of England.\ud \ud Results\ud In 2009, 142 adults with mild to profound ID and a need for any type of mealtime support were recruited for a baseline survey. At follow-up one year later, 127 individuals were alive; eight had died; and seven could not be contacted. Almost all participants had one or more GP consultations each year (85-95%) and, in the first year, 20% reportedly had one or more emergency hospitalisations. Although their annual number of GP visits was broadly comparable to that of the general population, one-fifth of this population?s primary healthcare use was directly attributable to EDS-related ill-health. Respiratory infections were the most common cause of morbidity, and the immediate cause of all eight deaths, while concerns about nutrition and dehydration were surprisingly minor. Our participants had a high annual incidence of death (5%) and, with a standardised mortality ratio of 267, their observed mortality was more than twice that expected in the general population of adults with ID (not selected because of mealtime support for EDS problems).\ud \ud Conclusions\ud All Annual Health Checks now offered to adults with ID should include questions about respiratory infections and EDS functioning, in order to focus attention on EDS problems in this population. This has the potential to reduce life-threatening illness

Evaluation of Xpert® MTB/RIF and ustar easyNAT™ TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania : a prospective descriptive study

Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB-endemic setting in Tanzania.; Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania. Fine needle aspirates of lymph nodes were analysed using acid-fast bacilli microscopy, liquid TB culture, cytology, Xpert MTB/RIF and EasyNAT. Latent class analysis and comparison against a composite reference standard comprising "culture and/or cytology" was done, to assess the performance of Xpert MTB/RIF and EasyNAT for the diagnosis of TB lymphadenitis.; Seventy-nine children were recruited; 4 were excluded from analysis. Against a composite reference standard of culture and/or cytology, Xpert MTB/RIF and EasyNAT had a sensitivity and specificity of 58 % and 93 %; and 19 % and 100 % respectively. Relative to latent class definitions, cytology had a sensitivity of 100 % and specificity of 94.7 %.; Combining clinical assessment, cytology and Xpert MTB/RIF may allow for a rapid and accurate diagnosis of childhood TB lymphadenitis. Larger diagnostic evaluation studies are recommended to validate these findings and on Xpert MTB/RIF to assess its use as a solitary initial test for TB lymphadenitis in children

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Retinal blood vessels extraction using probabilistic modelling

© 2014 Kaba et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.The analysis of retinal blood vessels plays an important role in detecting and treating retinal diseases. In this review, we present an automated method to segment blood vessels of fundus retinal image. The proposed method could be used to support a non-intrusive diagnosis in modern ophthalmology for early detection of retinal diseases, treatment evaluation or clinical study. This study combines the bias correction and an adaptive histogram equalisation to enhance the appearance of the blood vessels. Then the blood vessels are extracted using probabilistic modelling that is optimised by the expectation maximisation algorithm. The method is evaluated on fundus retinal images of STARE and DRIVE datasets. The experimental results are compared with some recently published methods of retinal blood vessels segmentation. The experimental results show that our method achieved the best overall performance and it is comparable to the performance of human experts.The Department of Information Systems, Computing and Mathematics, Brunel University

Applications of Direct Injection Soft Chemical Ionisation-Mass Spectrometry for the Detection of Pre-blast Smokeless Powder Organic Additives

Analysis of smokeless powders is of interest from forensics and security perspectives. This article reports the detection of smokeless powder organic additives (in their pre-detonation condition), namely the stabiliser diphenylamine and its derivatives 2-nitrodiphenylamine and 4-nitrodiphenylamine, and the additives (used both as stabilisers and plasticisers) methyl centralite and ethyl centralite, by means of swab sampling followed by thermal desorption and direct injection soft chemical ionisation-mass spectrometry. Investigations on the product ions resulting from the reactions of the reagent ions H3O+ and O2+ with additives as a function of reduced electric field are reported. The method was comprehensively evaluated in terms of linearity, sensitivity and precision. For H3O+, the limits of detection (LoD) are in the range of 41-88 pg of additive, for which the accuracy varied between 1.5 and 3.2%, precision varied between 3.7 and 7.3% and linearity showed R20.9991. For O2+, LoD are in the range of 72 to 1.4 ng, with an accuracy of between 2.8 and 4.9% and a precision between 4.5 and 8.6% and R20.9914. The validated methodology was applied to the analysis of commercial pre-blast gun powders from different manufacturers.(VLID)4826148Accepted versio

The host dark matter haloes of [O II] emitters at 0.5 < z < 1.5

Emission line galaxies (ELGs) are used in several ongoing and upcoming surveys (SDSS-IV/eBOSS, DESI) as tracers of the dark matter distribution. Using a new galaxy formation model, we explore the characteristics of [OII] emitters, which dominate optical ELG selections at z ≃ 1. Model [OII] emitters at 0.5 < z < 1.5 are selected to mimic the DEEP2, VVDS, eBOSS and DESI surveys. The luminosity functions of model [OII] emitters are in reasonable agreement with observations. The selected [OII] emitters are hosted by haloes with Mhalo ≥ 1010.3h−1M⊙, with ∼90 per cent of them being central star-forming galaxies. The predicted mean halo occupation distributions of [OII] emitters have a shape typical of that inferred for star-forming galaxies, with the contribution from central galaxies, ⟨N⟩[OII]cen⁠, being far from the canonical step function. The ⟨N⟩[OII]cen can be described as the sum of an asymmetric Gaussian for discs and a step function for spheroids, which plateau below unity. The model [OII] emitters have a clustering bias close to unity, which is below the expectations for eBOSS and DESI ELGs. At z ∼ 1, a comparison with observed g-band-selected galaxy, which is expected to be dominated by [OII] emitters, indicates that our model produces too few [OII] emitters that are satellite galaxies. This suggests the need to revise our modelling of hot gas stripping in satellite galaxies

Prognostic Value of [18F]-Fluoro-Deoxy-Glucose PET/CT, S100 or MIA for Assessment of Cancer-Associated Mortality in Patients with High Risk Melanoma

PURPOSE: To assess the prognostic value of FDG PET/CT compared to the tumor markers S100B and melanoma inhibitory activity (MIA) in patients with high risk melanoma. METHODS: Retrospective study in 125 consecutive patients with high risk melanoma that underwent FDG PET/CT for re-staging. Diagnostic accuracy and prognostic value was determined for FDG PET/CT as well as for S100B and MIA. As standard of reference, cytological, histological, PET/CT or MRI follow-up findings as well as clinical follow-up were used. RESULTS: Of 125 patients, FDG PET/CT was positive in 62 patients. 37 (29.6%) patients had elevated S100B (>100 pg/ml) and 24 (20.2%) had elevated MIA (>10 pg/ml) values. Overall specificities for FDG PET/CT, S100B and MIA were 96.8% (95% CI, 89.1% to 99.1%), 85.7% (75.0% to 92.3%), and 95.2% (86.9% to 98.4%), corresponding sensitivities were 96.8% (89.0% to 99.1%), 45.2% (33.4% to 55.5%), and 36.1% (25.2% to 48.6%), respectively. The negative predictive values (NPV) for PET/CT, S100B, and MIA were 96.8% (89.1% to 99.1%), 61.4% (50.9% to 70.9%), and 60.6% (50.8% to 69.7%). The positive predictive values (PPV) were 96.7% (89.0% to 99.1%), 75.7% (59.9% to 86.6%), and 88.0% (70.0% to 95.8%). Patients with elevated S100B- or MIA values or PET/CT positive findings showed a significantly (p<0.001 each, univariate Cox regression models) higher risk of melanoma associated death which was increased 4.2-, 6.5- or 17.2-fold, respectively. CONCLUSION: PET/CT has a higher prognostic power in the assessment of cancer-associated mortality in melanoma patients compared with S100 and MIA

Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows

We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows. Finally, we discuss several major problems, including the occurrence of drug-resistant mutations, drug promiscuity, and the design of dual-effect inhibitors.Fil: Goncearenco, Alexander. National Institutes of Health; Estados UnidosFil: Li, Minghui. Soochow University; China. National Institutes of Health; Estados UnidosFil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Shoemaker, Benjamin A. National Institutes of Health; Estados UnidosFil: Panchenko, Anna R. National Institutes of Health; Estados Unido