Fixed-Form Variational Posterior Approximation through Stochastic Linear Regression

We propose a general algorithm for approximating nonstandard Bayesian posterior distributions. The algorithm minimizes the Kullback-Leibler divergence of an approximating distribution to the intractable posterior distribution. Our method can be used to approximate any posterior distribution, provided that it is given in closed form up to the proportionality constant. The approximation can be any distribution in the exponential family or any mixture of such distributions, which means that it can be made arbitrarily precise. Several examples illustrate the speed and accuracy of our approximation method in practice

Decades of Delay: EPA Leadership Still Lacking in Protecting America's Great River

This report demonstrates the continuing failure of EPA's voluntary approach and the continuing and growing threats of unregulated nitrogen and phosphorus pollution. EPA has the power and the duty to act to require reasonable, common-sense regulations to address the growing scourge of nutrient pollution, and it should do so. Once again, MRC calls upon EPA to remedy this state of affairs, specifically recommending that EPA:Develop numeric phosphorus criteria for each of the eight states that have yet to adopt them, and numeric nitrogen criteria for all 10 states.Require states to assess their waters for nitrogen and phosphorus pollution and to prioritize TMDL development and implementation planning accordingly.Increase oversight of the state NPDES programs to ensure that both narrative and numeric nutrient criteria are implemented through limits in permits, including the use of Water Quality Based Effluent Limits (WQBELs) where appropriate.Disapprove TMDLs that lacking reasonable assurance that nonpoint source reductions are likely to occur and lack monitoring and timelines to ensure that planned reductions actually take place. Further, EPA needs to provide oversight to ensure consistency among EPA Regions in TMDL review and approval (especially in Regions 4 and 6.)Ensure that states' Nutrient Reduction Strategies contain implementation plans detailing point and nonpoint source reductions needed, responsible parties, funding mechanisms, milestones, measurement metrics, and reasonable timelines.Require states under Section 319 of the Clean Water Act to identify programs and practices for controlling nonpoint sources of pollution to the maximum extent possible

Making the journey with me : a qualitative study of experiences of a bespoke mental health smoking cessation intervention for service users with serious mental illness

BACKGROUND: Smoking is one of the major modifiable risk factors contributing to early mortality for people with serious mental illness. However, only a minority of service users access smoking cessation interventions and there are concerns about the appropriateness of generic stop-smoking services for this group. The SCIMITAR (Smoking Cessation Intervention for Severe Mental Ill-Health Trial) feasibility study explored the effectiveness of a bespoke smoking cessation intervention delivered by mental health workers. This paper reports on the nested qualitative study within the trial. METHODS: Qualitative semi-structured interviews were conducted with 13 service users receiving the intervention and 3 of the MHSCPs (mental health smoking cessation practitioners) delivering the intervention. Topic guides explored the perceived acceptability of the intervention particularly in contrast to generic stop-smoking services, and perceptions of the implementation of the intervention in practice. Transcripts were analysed using the Constant Comparative Method. RESULTS: Generic services were reported to be inappropriate for this group, due to concerns over stigma and a lack of support from health professionals. The bespoke intervention was perceived positively, with both practitioners and service users emphasising the benefits of flexibility and personalisation in delivery. The mental health background of the practitioners was considered valuable not only due to their increased understanding of the service users' illness but also due to the more collaborative relationship style they employed. Challenges involved delays in liaising with general practitioners and patient struggles with organisation and motivation, however the MHSCP was considered to be well placed to address these problems. CONCLUSION: The bespoke smoking cessation intervention was acceptable to service users and the both service users and practitioners reported the value of a protected mental health worker role for delivering smoking cessation to this group. The results have wider implications for understanding how to achieve integrated and personalised care for this high-risk population and further underscore the need for sensitised smoking cessation support for people with serious mental illness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79497236 . Registered 3(rd) July 2009

Recombination rate and protein evolution in yeast

<p>Abstract</p> <p>Background</p> <p>Theory and artificial selection experiments show that recombination can promote adaptation by enhancing the efficacy of natural selection, but the extent to which recombination affects levels of adaptation across the genome is still an open question. Because patterns of molecular evolution reflect long-term processes of mutation and selection in nature, interactions between recombination rate and genetic differentiation between species can be used to test the benefits of recombination. However, this approach faces a major difficulty: different evolutionary processes (i.e. negative versus positive selection) produce opposing relationships between recombination rate and genetic divergence, and obscure patterns predicted by individual benefits of recombination.</p> <p>Results</p> <p>We use a combination of polymorphism and genomic data from the yeast <it>Saccharomyces cerevisiae </it>to infer the relative importance of nearly-neutral (i.e. slightly deleterious) evolution in different gene categories. For genes with high opportunities for slightly deleterious substitution, recombination substantially reduces the rate of molecular evolution, whereas divergence in genes with little opportunity for slightly deleterious substitution is not strongly affected by recombination.</p> <p>Conclusion</p> <p>These patterns indicate that adaptation throughout the genome can be strongly influenced by each gene's recombinational environment, and suggest substantial long-term fitness benefits of enhanced purifying selection associated with sexual recombination.</p

Graphic Interlude

This graphic interlude features a selection of photographs of artworks which can illustrate the topic of this issue: “The Cultures and Politics of Leisure in the British Isles and the United States”.Cet interlude iconographique comporte une sélection de photographies d’œuvres d’art illustrant à leur manière le thème de ce numéro: « Les cultures et politiques de loisirs dans les Îles britanniques et les États-Unis »

Structural characterization of toxic oligomers that are kinetically trapped during alpha-synuclein fibril formation

This is the author accepted manuscript. The final version is avialble via PNAS at http://www.pnas.org/content/112/16/E1994.long#ack-1.We describe the isolation and detailed structural characterization of stable toxic oligomers of α-synuclein that have accumulated during the process of amyloid formation. Our approach has allowed us to identify distinct subgroups of oligomers and to probe their molecular architectures by using cryo-electron microscopy (cryoEM) image reconstruction techniques. Although the oligomers exist in a range of sizes, with different extents and nature of β-sheet content and exposed hydrophobicity, they all possess a hollow cylindrical architecture with similarities to certain types of amyloid fibril, suggesting that the accumulation of at least some forms of amyloid oligomers is likely to be a consequence of very slow rates of rearrangement of their β-sheet structures. Our findings reveal the inherent multiplicity of the process of protein misfolding and the key role the β-sheet geometry acquired in the early stages of the self-assembly process plays in dictating the kinetic stability and the pathological nature of individual oligomeric species.We thank Dr. Katherine Stott, from the Biophysics Facility, Department of Biochemistry, University of Cambridge, for her assistance in using these facilities. This work was supported by the Agency for Science, Technology and Research, Singapore (S.W.C.), the “La Caixa” foundation (S.D.), Wellcome/MRC (Medical Research Council) Parkinson’s Disease Consortium Grant WT089698 (to E.D. and N.W.W.), National Institute for Health Research Biomedical Research Centres funding at University College London (to N.W.W.), the BBSRC through Grants BB/H003843/1 (to M.O.) and BB/E019927/1 (to C.M.D.), the Spanish Ministry of Economy and Competitiveness through Grants SAF 2012-39720 (to C.R.), BFU2013-44202 (to J.M.V.), and BIO2011-28941-C03-03 (to C.A. and G.R.), the Spanish Ministry of Health with cofunding by The European Regional Development Fund through Grant CP10/00527 (to C.R.), the Madrid Regional Government through Grant S2013/MIT-2807 (to J.M.V.), Parkinson’s UK through Grant H-0903 (to T.G.), the Wellcome Trust, the Leverhulme Trust, the European Commission through project LSHM-CT-2006-037525 (to C.M.D.), the Medical Research Council through Grant MRC G1002272 (to E.J.D.-G. and C.M.D.), and the Engineering and Physical Sciences Research Council (C.M.D.). A.Y.A. was a Parkinson’s UK Senior Research Fellow. N.C. is a Royal Society Research Fellow and also acknowledges financial support by the Human Frontier Science Program from Long-Term Fellowship LT000795/2009

Knowledge infrastructure and research agendas for quotidian Anthropocenes: Critical localism with planetary scope

The Anthropocene requires the development of new forms of knowledge and supporting sociotechnical infrastructure. While there have been calls for both interdisciplinary and community-engaged approaches, there remains a need to develop, test, and sustain modes of Anthropocene knowledge production that effectively link people working at different scales, in different sites, with many different types of expertise. In this Perspectives piece, we describe one such approach to Anthropocene knowledge production, centered in short-term Field Campuses that bring together community actors in cultural institutions, media, and government agencies with external academic researchers, bringing cultural analysis into the work of characterizing and responding to the Anthropocene. We argue that it is important to build public knowledge infrastructure that allows people to visualize and address many intersecting scales and systems (ecological, atmospheric, economic, technological, social, cultural, etc.) that shape the Anthropocene at the local level