Speciation and Extinction Drive the Appearance of Directional Range Size Evolution in Phylogenies and the Fossil Record

The appearance of directional trends in the evolution of species range sizes can arise from stochastic models and need not imply the existence of underlying trends

Investigating the maximum resolution of µXRF core scanners: a 1800 year storminess reconstruction from the Outer Hebrides

Micro x-ray fluorescence (µXRF) core scanning is capable of measuring the elemental composition of lake sediment at sub-millimetre resolution, but bioturbation and physical mixing may degrade environmental signals at such fine scales. The aim of this research is to determine the maximum possible resolution at which meaningful environmental signals may be reconstructed from lake sediments using this method. Sediment from a coastal lake in the Outer Hebrides, Scotland, has been analysed using calibrated element measurements to reconstruct storminess since AD 200. We find that a Ca/K ratio in lake-core sediments reflects the presence of fine calcium carbonate shell fragments, a constituent of sand in the catchment that is washed and blown into the lake. Variations in this ratio are significantly correlated with instrumental records of precipitation and low pressures, suggesting it is a proxy for storminess. Furthermore, identification of a c. 60-year cycle supports a climatic influence on Ca/K, as this cycle is frequently identified in reconstructions of the North Atlantic Oscillation and North Atlantic sea-surface temperature. Comparison with weather records at different resolutions and spectral analysis indicate that µXRF data from Loch Hosta can be interpreted at sub-decadal resolutions (equivalent to core depth intervals of 3–5 mm in this location). Therefore, we suggest that sub-centimetre sampling using µXRF core scanning could be beneficial in producing environmental reconstructions in many lake settings where sediments are not varved

UWE Celebrating Bristol Green Capital 2015 - Activities portfolio (supporting document for UWE Celebrating Bristol Green Capital 2015 activities catalogue)

This Activities Portfolio details projects, events and initiatives which represent the work of hundreds of UWE staff and students during Bristol's year as European Green Capital in 2015. It is the working file to accompany the UWE Green Capital 2015 Activities Catalogue

W(h)ither the academy? An exploration of the role of university social work in shaping the future of social work in Europe

A controversial proposal to pilot the training of child protection social workers through an intensive work-based route in England is being supported and funded by the UK Government. Frontline, the brainchild of a former teacher, locates social work training within local authorities (‘the agency’) rather than university social work departments (‘the academy’) and has stimulated debate amongst social work academics about their role in shaping the direction of the profession. As a contribution to this debate, this paper explores the duality of social work education, which derives its knowledge from both the academic social sciences and the experience of practice within social work agencies. While social work education has traditionally been delivered by the academy, this paper also explores whether the delivery of training in the allied professions of probation and nursing by ‘the agency’ is equally effective. Finally, this paper explores the Helsinki model which achieves a synergy of ‘academy’ and ‘agency’. It suggests that there are alternative models of social work education, practice and research which avoid dichotomies between the ‘academy’ and the ‘agency’ and enable the profession to be shaped by both social work academics and practitioners

Magnetic Resonance Imaging of Pulmonary Lesions in Guinea Pigs Infected with Mycobacterium tuberculosis

We utilized magnetic resonance imaging to visualize lesions in the lungs of guinea pigs infected by low-dose aerosol exposure to Mycobacterium tuberculosis. Lesions were prominent in such images, and colorized three-dimensional reconstructions of images revealed a very uniform distribution in the lungs. Lesion numbers after 1 month were approximately similar to the aerosol exposure algorithm, suggesting that each was established by a single bacterium. Numbers of lesions in unprotected and vaccinated animals were similar over the first month but increased thereafter in the control animals, indicating secondary lesion development. Whereas lesion sizes increased progressively in control guinea pigs, lesions remained small in BCG-vaccinated animals. A prominent feature of the disease pathology in unprotected animals was rapid and severe lymphadenopathy of the mediastinal lymph node cluster, which is paradoxical given the strong state of cellular immunity at this time. Further development of this technical approach could be very useful in tracking lesion size, number, and progression in the search for new tuberculosis vaccines

Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis

The inhibition of apoptosis of infected host cells is a well-known but poorly understood function of pathogenic mycobacteria. We show that inactivation of the secA2 gene in Mycobacterium tuberculosis, which encodes a component of a virulence-associated protein secretion system, enhanced the apoptosis of infected macrophages by diminishing secretion of mycobacterial superoxide dismutase. Deletion of secA2 markedly increased priming of antigen-specific CD8+ T cells in vivo, and vaccination of mice and guinea pigs with a secA2 mutant significantly increased resistance to M. tuberculosis challenge compared with standard M. bovis bacille Calmette-Guérin vaccination. Our results define a mechanism for a key immune evasion strategy of M. tuberculosis and provide what we believe to be a novel approach for improving mycobacterial vaccines

Assessing uncertainty in housing stock infiltration rates and associated heat loss: English and UK case studies

Strategies to reduce domestic heating loads by minimizing the infiltration of cold air through adventitious openings located in the thermal envelopes of houses are highlighted by the building codes of many countries. Consequent reductions of energy demand and CO2e emission are often unquantified by empirical evidence. Instead, a mean heating season infiltration rate is commonly inferred from an air leakage rate using a simple ratio scaled to account for the physical and environmental properties of a dwelling. The scaling does not take account of the permeability of party walls in conjoined dwellings and so cannot differentiate between the infiltration of unconditioned ambient air that requires heating, and conditioned air from adjacent dwellings that does not. A stochastic method is presented that applies a theoretical model of adventitious infiltration to predict distributions of mean infiltration rates and the associated total heat loss in any stock of dwellings during heating hours. The method is applied to the English and UK housing stocks and provides probability distribution functions of stock infiltration rates and total heat loss during the heating season for two extremes of party wall permeability. The distributions predict that up to 79% of the current English stock could require additional purpose-provided ventilation to limit negative health consequences. National models predict that fewer dwellings are under-ventilated. The distributions are also used to predict that infiltration is responsible for 3–5% of total UK energy demand, 11–15% of UK housing stock energy demand, and 10–14% of UK housing stock carbon emissions

Evidence for Oxidative Stress and Defective Antioxidant Response in Guinea Pigs with Tuberculosis

The development of granulomatous inflammation with caseous necrosis is an important but poorly understood manifestation of tuberculosis in humans and some animal models. In this study we measured the byproducts of oxidative stress in granulomatous lesions as well as the systemic antioxidant capacity of BCG vaccinated and non-vaccinated guinea pigs experimentally infected with Mycobacterium tuberculosis. In non-vaccinated guinea pigs, oxidative stress was evident within 2 weeks of infection as measured by a decrease in the serum total antioxidant capacity and blood glutathione levels accompanied by an increase in malondialdehyde, a byproduct of lipid peroxidation, within lesions. Despite a decrease in total and reduced blood glutathione concentrations, there was an increase in lesion glutathione by immunohistochemistry in response to localized oxidative stress. In addition there was an increase in the expression of the host transcription factor nuclear erythroid 2 p45-related factor 2 (Nrf2), which regulates several protein and non-proteins antioxidants, including glutathione. Despite the increase in cytoplasmic expression of Nrf2, immunohistochemical staining revealed a defect in Nrf2 nuclear translocation within granulomatous lesions as well as a decrease in the expression of the Nrf2-regulated antioxidant protein NQO1. Treating M. tuberculosis–infected guinea pigs with the antioxidant drug N-acetyl cysteine (NAC) partially restored blood glutathione concentrations and the serum total antioxidant capacity. Treatment with NAC also decreased spleen bacterial counts, as well as decreased the lung and spleen lesion burden and the severity of lesion necrosis. These data suggest that the progressive oxidative stress during experimental tuberculosis in guinea pigs is due in part to a defect in host antioxidant defenses, which, we show here, can be partially restored with antioxidant treatment. These data suggest that the therapeutic strategies that reduce oxidant-mediated tissue damage may be beneficial as an adjunct therapy in the treatment and prevention of tuberculosis in humans

Uptake and Accumulation of Oxidized Low-Density Lipoprotein during Mycobacterium tuberculosis Infection in Guinea Pigs

The typical host response to infection of humans and some animals by M. tuberculosis is the accumulation of reactive oxygen species generating inflammatory cells into discrete granulomas, which frequently develop central caseous necrosis. In previous studies we showed that infection of immunologically naïve guinea pigs with M. tuberculosis leads to localized and systemic oxidative stress that results in a significant depletion of serum total antioxidant capacity and the accumulation of malondialdehyde, a bi-product of lipid peroxidation. Here we show that in addition, the generation of excessive reactive oxygen species in vivo resulted in the accumulation of oxidized low density lipoproteins (OxLDL) in pulmonary and extrapulmonary granulomas, serum and lung macrophages collected by bronchoalveolar lavage. Macrophages from immunologically naïve guinea pigs infected with M. tuberculosis also had increased surface expression of the type 1 scavenger receptors CD36 and LOX1, which facilitate the uptake of oxidized host macromolecules including OxLDL. Vaccination of guinea pigs with Bacillus Calmette Guerin (BCG) prior to aerosol challenge reduced the bacterial burden as well as the intracellular accumulation of OxLDL and the expression of macrophage CD36 and LOX1. In vitro loading of guinea pig lung macrophages with OxLDL resulted in enhanced replication of bacilli compared to macrophages loaded with non-oxidized LDL. Overall, this study provides additional evidence of oxidative stress in M. tuberculosis infected guinea pigs and the potential role OxLDL laden macrophages have in supporting intracellular bacilli survival and persistence

nSeP: immune and metabolic biomarkers for early detection of neonatal sepsis-protocol for a prospective multicohort study

Introduction Diagnosing neonatal sepsis is heavily dependent on clinical phenotyping as culture-positive body fluid has poor sensitivity, and existing blood biomarkers have poor specificity. A combination of machine learning, statistical and deep pathway biology analyses led to the identification of a tripartite panel of biologically connected immune and metabolic markers that showed greater than 99% accuracy for detecting bacterial infection with 100% sensitivity. The cohort study described here is designed as a large-scale clinical validation of this previous work. Methods and analysis This multicentre observational study will prospectively recruit a total of 1445 newborn infants (all gestations)—1084 with suspected early—or late-onset sepsis, and 361 controls—over 4 years. A small volume of whole blood will be collected from infants with suspected sepsis at the time of presentation. This sample will be used for integrated transcriptomic, lipidomic and targeted proteomics profiling. In addition, a subset of samples will be subjected to cellular phenotype and proteomic analyses. A second sample from the same patient will be collected at 24 hours, with an opportunistic sampling for stool culture. For control infants, only one set of blood and stool sample will be collected to coincide with clinical blood sampling. Along with detailed clinical information, blood and stool samples will be analysed and the information will be used to identify and validate the efficacy of immune-metabolic networks in the diagnosis of bacterial neonatal sepsis and to identify new host biomarkers for viral sepsis