Chemical determinants of occupational hypersensitivity pneumonitis

Background: Workplace inhalational exposures to low molecular weight (LMW) chemicals cause hypersensitivity pneumonitis (HP) as well as the more common manifestation of respiratory hypersensitivity, occupational asthma (OA). Aims: To explore whether chemical causation of HP is associated with different structural and physico-chemical determinants from OA. Methods: Chemical causes of human cases of HP and OA were identified from searches of peer-reviewed literature up to the end of 2011. Each chemical was categorised according to whether or not it had been the attributed cause of at least one case of HP. The predicted asthma hazard was determined for each chemical using a previously developed quantitative structure-activity relationship (QSAR) model. The chemicals in both sets were independently and ‘blindly’ analysed by an expert in mechanistic chemistry for a qualitative prediction of protein cross-linking potential and determination of lipophilicity (log Kow). Results: Ten HP causing chemicals were identified and had a higher median QSAR predicted asthma hazard than the control group of 101 OA causing chemicals (p < 0.005). Nine of ten HP causing chemicals were predicted to be protein cross-linkers compared to 24/92 controls (p<0.0001). The distributions of log Kow indicated higher values for the HP list (median 3.47) compared to controls (median 0.81) (p < 0.05). Conclusion: These findings suggest that chemicals capable of causing HP tend to have higher predicted asthma hazard, are more lipophilic and are more likely to be protein cross-linkers than those causing OA. Key words: hypersensitivity pneumonitis, occupational chemicals, occupational respiratory disease, toxic inhalatio

An MPEG-7 scheme for semantic content modelling and filtering of digital video

Abstract Part 5 of the MPEG-7 standard specifies Multimedia Description Schemes (MDS); that is, the format multimedia content models should conform to in order to ensure interoperability across multiple platforms and applications. However, the standard does not specify how the content or the associated model may be filtered. This paper proposes an MPEG-7 scheme which can be deployed for digital video content modelling and filtering. The proposed scheme, COSMOS-7, produces rich and multi-faceted semantic content models and supports a content-based filtering approach that only analyses content relating directly to the preferred content requirements of the user. We present details of the scheme, front-end systems used for content modelling and filtering and experiences with a number of users

Integrated geophysical-petrological modeling of lithosphere-asthenosphere boundary in central Tibet using electromagnetic and seismic data

We undertake a petrologically driven approach to jointly model magnetotelluric (MT) and seismic surface wave dispersion (SW) data from central Tibet, constrained by topographic height. The approach derives realistic temperature and pressure distributions within the upper mantle and characterizes mineral assemblages of given bulk chemical compositions as well as water content. This allows us to define a bulk geophysical model of the upper mantle based on laboratory and xenolith data for the most relevant mantle mineral assemblages and to derive corresponding predicted geophysical observables. One-dimensional deep resistivity models were derived for two groups of MT stations. One group, located in the Lhasa Terrane, shows the existence of an electrically conductive upper mantle layer and shallower conductive upper mantle layer for the other group, located in the Qiangtang Terrane. The subsequent one-dimensional integrated petrological-geophysical modeling suggests a lithosphere-asthenosphere boundary (LAB) at a depth of 80¿120 km with a dry lithosphere for the Qiangtang Terrane. In contrast, for the Lhasa Terrane the LAB is located at about 180 km but the presence of a small amount of water in the lithospheric mantle (<0.02 wt%) is required to fit the longest period MT responses. Our results suggest two different lithospheric configurations beneath the southern and central Tibetan Plateau. The model for the Lhasa Terrane implies underthrusting of a moderately wet Indian plate. The model for the Qiangtang Terrane shows relatively thick and conductive crust and implies thin and dry Tibetan lithosphere.Peer Reviewe

Galaxy And Mass Assembly (GAMA) : refining the local galaxy merger rate using morphological information

KRVS acknowledges the Science and Technology Facilities Council (STFC) for providing funding for this project, as well as the Government of Catalonia for a research travel grant (ref. 2010 BE-00268) to begin this project at the University of Nottingham. PN acknowledges the support of the Royal Society through the award of a University Research Fellowship and the European Research Council, through receipt of a Starting Grant (DEGAS-259586).We use the Galaxy And Mass Assembly (GAMA) survey to measure the local Universe mass-dependent merger fraction and merger rate using galaxy pairs and the CAS (concentration, asymmetry, and smoothness) structural method, which identifies highly asymmetric merger candidate galaxies. Our goals are to determine which types of mergers produce highly asymmetrical galaxies and to provide a new measurement of the local galaxy major merger rate. We examine galaxy pairs at stellar mass limits down to M* = 108 M⊙ with mass ratios of 4:1) the lower mass companion becomes highly asymmetric, whereas the larger galaxy is much less affected. The fraction of highly asymmetric paired galaxies which have a major merger companion is highest for the most massive galaxies and drops progressively with decreasing mass. We calculate that the mass-dependent major merger fraction is fairly constant at ∼1.3–2 per cent within 109.5 < M* < 1011.5 M⊙, and increases to ∼4 per cent at lower masses. When the observability time-scales are taken into consideration, the major merger rate is found to approximately triple over the mass range we consider. The total comoving volume major merger rate over the range 108.0 < M* < 1011.5 M⊙ is (1.2 ± 0.5) × 10−3 h370 Mpc−3 Gyr−1.Publisher PDFPeer reviewe

Neogeography and seismic risk perception : a comparison between two case studies : Calabria, Southern Italy and Malta

Geography of perception aims at clarifying human behaviour by studying the concepts and images of the real world that a person elaborates on by considering the psychological and social aspects of man’s behaviour within an environment. In this context, a questionnaire was given to primary and middle school pupils in an area of Calabria (Southern Italy), which has recently been affected by an on-going seismic sequence widely felt by the local population. The same questionnaire was given to students in Malta (Central Mediterranean), an area considered to have a low-to-moderate seismic hazard, and where earthquake awareness is not culturally strong. In this way, the knowledge effectively possessed by the students (relating to age, experience and area of origin) are analysed; their analogous and differing perceptions on earthquakes in different areas are highlighted. The data collected can be used to project and create new informative tools through which students will become “geographic information volunteers” studying natural risks such as earthquakes, and augmenting the territory’s level of resilience.peer-reviewe

Quality of life is associated with chronic inflammation in schizophrenia: a cross-sectional study

International audienceInflammation may play a crucial role in the pathogenesis of schizophrenia. However, the association between chronic inflammation and health outcomes in schizophrenia remains unclear, particularly for patient-reported outcomes. The aim of this study was to investigate the relationship between quality of life (QoL) and chronic inflammation assessed using C -Reactive Protein (CRP) in patients with schizophrenia. Two hundred and fifty six patients with schizophrenia were enrolled in this study. After adjusting for key socio-demographic and clinical confounding factors, patients with high levels of CRP (>3.0 mg/l) had a lower QoL than patients with normal CRP levels (OR = 0.97, 95% CI = 0.94-0.99). An investigation of the dimensions of QoL revealed that psychological well-being, physical well-being and sentimental life were the most salient features of QoL associated with CRP. Significant associations were found between lower educational level (OR = 4.15, 95% CI = 1.55-11.07), higher body mass index (OR = 1.16, 95% CI = 1.06-1.28), higher Fagerstrom score (OR = 1.22, 95% CI = 1.01-1.47) and high levels of CRP. After replications with longitudinal approaches, the association between QoL and chronic inflammation may offer interesting interventional prospects to act both on inflammation and QoL in patients with schizophrenia

Understanding Stability of Protein-Protein Complexes

For all living organisms, macromolecular interactions facilitate most of their natural functions. Alterations to macromolecular structures through mutations, can affect the stability of their interactions, which may lead to unfavourable phenotypes and disease. Presented here, are a number of computational methods aimed at uncovering the principles behind complex stability - as described by binding affinity and dissociation rate constants. Several factors are known to govern the stability of protein-protein interactions, however, no one factor dominates, and it is the synergistic effect of a number of contributions, which amount to the affinity, and stability of a complex. The characterization of complex stability can thus be presented as a two-fold problem; modelling the individual factors and modelling the synergistic effect of the combination of such individual factors. Using machine learning as a central framework, empirical functions are designed for estimating affinity, dissociation rates and the effects of mutations on these properties. The performance of all models is in turn benchmarked on experimental data available from the literature and carefully curated datasets. Firstly, a wild-type binding free energy prediction model is designed, composed of a diverse set of stability descriptors, which account for flexibility and conformational changes undergone by the complex in question. Similarly, models for estimating the effects of mutations on binding affinity are also designed and benchmarked in a community-wide blind trial. Emphasis here is on the detection of a small subset of mutations that are able to enhance the stability of two de novo protein drugs targeting the flu virus hemagglutinin. Probing further the determinants of stability, a set of descriptors that link hotspot residues with the off-rate of a complex are designed, and applied to models predicting changes in off-rate upon mutation. Finally, the relationship between the distribution of hotspots at protein interfaces, and the rate of dissociation of such interfaces, is investigated