Diagnosing multiple opportunistic infections: the value of a liver biopsy

Liver function test abnormalities are prevalent in patients with HIV, and in particular advanced HIV.1 Opportunistic infections, drug hepatotoxicity and viral hepatitis co-infections are frequently encountered.2-4 We present a patient with advanced HIV and abnormal liver function tests in whom the definitive diagnosis of multiple opportunistic infections was made by liver biopsy. This case illustrates the diagnostic value of liver biopsy in our local patient population, where diagnostic uncertainty is common and empiric therapy is often the standard of care. Southern African Journal of HIV Medicine Vol. 9 (4) 2008: pp. 51-5

The unfolding low-carbon transition in the UK electricity system

The paper explores three periods in the UK electricity consumption–production system since World War II. The first two involved the development of an increasingly centralized, integrated system that provided electricity to meet growing post-war demand. It saw two major changes in governance, first to nationalization, then to privatization and liberalization. The third period started at the turn of the Century, driven by increasing evidence of the impact of fossil fuels on the Earth’s climate. The paper focuses on the drivers of change, within the UK and externally, and how they affected governance, technology deployment, and industry structure. It draws on the multi-level perspective and the concepts of governance and technological branching points to inform the analysis of each period. It shows that there is a considerable distance to travel toward a truly sustainable electricity system

A comparison of the illness beliefs of people with angina and their peers: a questionnaire study

BACKGROUND: What people believe about their illness may affect how they cope with it. It has been suggested that such beliefs stem from those commonly held within society . This study compared the beliefs held by people with angina, regarding causation and coping in angina, with the beliefs of their friends who do not suffer from angina. METHODS: Postal survey using the York Angina Beliefs Questionnaire (version 1), which elicits stress attributions and misconceived beliefs about causation and coping. This was administered to 164 people with angina and their non-cohabiting friends matched for age and sex. 132 people with angina and 94 friends completed the questionnaire. RESULTS: Peers are more likely than people with angina to believe that angina is caused by a worn out heart (p <0.01), angina is a small heart attack (p = 0.02), and that it causes permanent damage to the heart (p <0.001). Peers were also more likely to believe that people with angina should take life easy (p <0.01) and avoid exercise (p = 0.04) and excitement (p <0.01). CONCLUSIONS: The beliefs of the peer group about causation and coping in angina run counter to professional advice. Over time this may contribute to a reduction in patient concordance with risk factor reduction, and may help to create cardiac invalids

Atom gravimeters and gravitational redshift

In a recent paper, H. Mueller, A. Peters and S. Chu [A precision measurement of the gravitational redshift by the interference of matter waves, Nature 463, 926-929 (2010)] argued that atom interferometry experiments published a decade ago did in fact measure the gravitational redshift on the quantum clock operating at the very high Compton frequency associated with the rest mass of the Caesium atom. In the present Communication we show that this interpretation is incorrect.Comment: 2 pages, Brief Communication appeared in Nature (2 September 2010

Can people guess what happened to others from their reactions?

Are we able to infer what happened to a person from a brief sample of his/her behaviour? It has been proposed that mentalising skills can be used to retrodict as well as predict behaviour, that is, to determine what mental states of a target have already occurred. The current study aimed to develop a paradigm to explore these processes, which takes into account the intricacies of real-life situations in which reasoning about mental states, as embodied in behaviour, may be utilised. A novel task was devised which involved observing subtle and naturalistic reactions of others in order to determine the event that had previously taken place. Thirty-five participants viewed videos of real individuals reacting to the researcher behaving in one of four possible ways, and were asked to judge which of the four ‘scenarios’ they thought the individual was responding to. Their eye movements were recorded to establish the visual strategies used. Participants were able to deduce successfully from a small sample of behaviour which scenario had previously occurred. Surprisingly, looking at the eye region was associated with poorer identification of the scenarios, and eye movement strategy varied depending on the event experienced by the person in the video. This suggests people flexibly deploy their attention using a retrodictive mindreading process to infer events

Bistability in Apoptosis by Receptor Clustering

Apoptosis is a highly regulated cell death mechanism involved in many physiological processes. A key component of extrinsically activated apoptosis is the death receptor Fas, which, on binding to its cognate ligand FasL, oligomerize to form the death-inducing signaling complex. Motivated by recent experimental data, we propose a mathematical model of death ligand-receptor dynamics where FasL acts as a clustering agent for Fas, which form locally stable signaling platforms through proximity-induced receptor interactions. Significantly, the model exhibits hysteresis, providing an upstream mechanism for bistability and robustness. At low receptor concentrations, the bistability is contingent on the trimerism of FasL. Moreover, irreversible bistability, representing a committed cell death decision, emerges at high concentrations, which may be achieved through receptor pre-association or localization onto membrane lipid rafts. Thus, our model provides a novel theory for these observed biological phenomena within the unified context of bistability. Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our model also suggests a mechanism by which cells may function as bistable life/death switches independently of any such dynamics in their downstream components. Our results highlight the role of death receptors in deciding cell fate and add to the signal processing capabilities attributed to receptor clustering.Comment: Accepted by PLoS Comput Bio

Genetic variation in populations of the earthworm, Lumbricus rubellus, across contaminated mine sites

Background&nbsp; Populations of the earthworm, Lumbricus rubellus, are commonly found across highly contaminated former mine sites and are considered to have under-gone selection for mitigating metal toxicity. Comparison of adapted populations with those found on less contaminated soils can provide insights into ecological processes that demonstrate the long-term effects of soil contamination. Contemporary sequencing methods allow for portrayal of demographic inferences and highlight genetic variation indicative of selection at specific genes. Furthermore, the occurrence of L. rubellus lineages across the UK allows for inferences of mechanisms associated with drivers of speciation and local adaptation.&nbsp; Results&nbsp; Using RADseq, we were able to define population structure between the two lineages through the use of draft genomes for each, demonstrating an absence of admixture between lineages and that populations over extensive geographic distances form discrete populations. Between the two British lineages, we were able to provide evidence for selection near to genes associated with epigenetic and morphological functions, as well as near a gene encoding a pheromone. Earthworms inhabiting highly contaminated soils bare close genomic resemblance to those from proximal control soils. We were able to define a number of SNPs that largely segregate populations and are indicative of genes that are likely under selection for managing metal toxicity. This includes calcium and phosphate-handling mechanisms linked to lead and arsenic contaminants, respectively, while we also observed evidence for glutathione-related mechanisms, including metallothionein, across multiple populations. Population genomic end points demonstrate no consistent reduction in nucleotide diversity, or increase in inbreeding coefficient, relative to history of exposure.&nbsp; &nbsp;Conclusions&nbsp; Though we can clearly define lineage membership using genomic markers, as well as population structure between geographic localities, it is difficult to resolve markers that segregate entirely between populations in response to soil metal concentrations. This may represent a highly variable series of traits in response to the heterogenous nature of the soil environment, but ultimately demonstrates the maintenance of lineage-specific genetic variation among local populations. L. rubellus appears to provide an exemplary system for exploring drivers for speciation, with a continuum of lineages coexisting across continental Europe, while distinct lineages exist in isolation throughout the UK

Realising transition pathways for a more electric, low-carbon energy system in the United Kingdom: challenges, insights and opportunities

The United Kingdom has placed itself on a transition towards a low-carbon economy and society, through the imposition of a legally-binding goal aimed at reducing its ‘greenhouse gas’ emissions by 80% by 2050 against a 1990 baseline. A set of three low-carbon, socio-technical transition pathways were developed and analysed via an innovative collaboration between engineers, social scientists and policy analysts. The pathways focus on the power sector, including the potential for increasing use of low-carbon electricity for heating and transport, within the context of critical European Union developments and policies. Their development started from narrative storylines regarding different governance framings, drawing on interviews and workshops with stakeholders and analysis of historical analogies. The quantified UK pathways were named Market Rules, Central Co-ordination and Thousand Flowers; each reflecting a dominant logic of governance arrangements. The aim of the present contribution was to use these pathways to explore what is needed to realise a transition that successfully addresses the so-called energy policy ‘trilemma,’ i.e. the simultaneous delivery of low carbon, secure and affordable energy services. Analytical tools were developed and applied to assess the technical feasibility,social acceptability, and environmental and economic impacts of the pathways. Technological and behavioural developments were examined, alongside appropriate governance structures and regulations for these low-carbon transition pathways, as well as the roles of key energy system ‘actors’ (both large and small). An assessment of the part that could possibly be played by future demand side response was also undertaken in order to understand the factors that drive energy demand and energy-using behaviour, and reflecting growing interest in demand side response for balancing a system with high proportions of renewable generation. A set of interacting and complementary engineering and technoeconomic models or tools were then employed to analyse electricity network infrastructure investment and operational decisions to assist market design and option evaluation. This provided a basis for integrating the analysis within a whole systems framework of electricity system development, together with the evaluation of future economic benefits, costs and uncertainties. Finally, the energy and environmental performance of the different energy mixes were appraised on a‘life-cycle’ basis to determine the greenhouse gas emissions and other ecological or health burdens associated with each of the three transition pathways. Here, the challenges, insights and opportunities that have been identified over the transition towards a low-carbon future in the United Kingdom are described with the purpose of providing a valuable evidence base for developers, policy makers and other stakeholders