81 research outputs found

    Mean field variational Bayesian inference for support vector machine classification

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    A mean field variational Bayes approach to support vector machines (SVMs) using the latent variable representation on Polson & Scott (2012) is presented. This representation allows circumvention of many of the shortcomings associated with classical SVMs including automatic penalty parameter selection, the ability to handle dependent samples, missing data and variable selection. We demonstrate on simulated and real datasets that our approach is easily extendable to non-standard situations and outperforms the classical SVM approach whilst remaining computationally efficient.Comment: 18 pages, 4 figure

    On semiparametric regression and data mining

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    Semiparametric regression is playing an increasingly large role in the analysis of datasets exhibiting various complications (Ruppert, Wand & Carroll, 2003). In particular semiparametric regression a plays prominent role in the area of data mining where such complications are numerous (Hastie, Tibshirani & Friedman, 2001). In this thesis we develop fast, interpretable methods addressing many of the difficulties associated with data mining applications including: model selection, missing value analysis, outliers and heteroscedastic noise. We focus on function estimation using penalised splines via mixed model methodology (Wahba 1990; Speed 1991; Ruppert et al. 2003). In dealing with the difficulties associated with data mining applications many of the models we consider deviate from typical normality assumptions. These models lead to likelihoods involving analytically intractable integrals. Thus, in keeping with the aim of speed, we seek analytic approximations to such integrals which are typically faster than numeric alternatives. These analytic approximations not only include popular penalised quasi-likelihood (PQL) approximations (Breslow & Clayton, 1993) but variational approximations. Originating in physics, variational approximations are a relatively new class of approximations (to statistics) which are simple, fast, flexible and effective. They have recently been applied to statistical problems in machine learning where they are rapidly gaining popularity (Jordan, Ghahramani, Jaakkola & Sau11999; Corduneanu & Bishop, 2001; Ueda & Ghahramani, 2002; Bishop & Winn, 2003; Winn & Bishop 2005). We develop variational approximations to: generalized linear mixed models (GLMMs); Bayesian GLMMs; simple missing values models; and for outlier and heteroscedastic noise models, which are, to the best of our knowledge, new. These methods are quite effective and extremely fast, with fitting taking minutes if not seconds on a typical 2008 computer. We also make a contribution to variational methods themselves. Variational approximations often underestimate the variance of posterior densities in Bayesian models (Humphreys & Titterington, 2000; Consonni & Marin, 2004; Wang & Titterington, 2005). We develop grid-based variational posterior approximations. These approximations combine a sequence of variational posterior approximations, can be extremely accurate and are reasonably fast

    Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality

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    Background More than 50 interventions have been used to treat hidradenitis suppurativa (HS) and so therapy decisions can be challenging. Objectives To summarise and appraise randomised controlled trial (RCT) evidence for HS interventions in adults. Materials and methods Searches were conducted in MEDLINE, EMBASE, CENTRAL, LILACS, five trials registers and abstracts from eight dermatology conferences until 13 August 2015. Two review authors independently assessed study eligibility, extracted data and assessed methodological quality. Primary outcomes were quality of life and adverse effects of the interventions. Results Twelve trials, from 1983 to 2015, investigating 15 different interventions met our inclusion criteria. Median trial duration was 16 weeks and the median number of participants was 27. Adalimumab 40mg weekly improved the Dermatology Life Quality Index by 4.0 points, which equates to the minimal clinically important difference for the scale, compared to placebo (95% confidence interval (CI) -6.5 to -1.5 points). Evidence quality was reduced to ‘moderate’ because results are based on only a single study. Adalimumab 40mg every other week was ineffective in a meta-analysis of two studies comprising 124 participants. Infliximab 5mg/kg improved DLQI score by 8.4 points after eight weeks in a moderate quality study completed by 33 of 38 participants. Etanercept 50mg twice weekly was ineffective. Inclusion of a gentamicin sponge prior to primary closure did not improve outcomes. Other interventions including topical and oral antibiotics, were investigated by relatively small studies, preventing treatment recommendations due to imprecision. Conclusions More, larger RCTs are required to investigate most HS interventions, particularly oral treatments and surgical therapy. Moderate quality evidence suggests that adalimumab given weekly and infliximab are effective whereas adalimumab every other week is ineffective

    Corporate governance and financial constraints on strategic turnarounds

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    The paper extends the Robbins and Pearce (1992) two-stage turnaround response model to include governance factors. In addition to the retrenchment and recovery, the paper proposes the addition of a realignment stage, referring specifically to the re-alignment of expectations of principal and agent groups. The realignment stage imposes a threshold that must be crossed before the retrenchment and hence recovery stage can be entered. Crossing this threshold is problematic to the extent that the interests of governance-stakeholder groups diverge in a crisis situation. The severity of the crisis impacts on the bases of strategy contingent asset valuation leading to the fragmentation of stakeholder interests. In some cases the consequence may be that management are prevented from carrying out turnarounds by governance constraints. The paper uses a case study to illustrate these dynamics, and like the Robbins and Pearce study, it focuses on the textile industry. A longitudinal approach is used to show the impact of the removal of governance constraints. The empirical evidence suggests that such financial constraints become less serious to the extent that there is a functioning market for corporate control. Building on governance research and turnaround literature, the paper also outlines the general case necessary and sufficient conditions for successful turnarounds

    Climate change and water in the UK: past changes and future prospects

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    Climate change is expected to modify rainfall, temperature and catchment hydrological responses across the world, and adapting to these water-related changes is a pressing challenge. This paper reviews the impact of anthropogenic climate change on water in the UK and looks at projections of future change. The natural variability of the UK climate makes change hard to detect; only historical increases in air temperature can be attributed to anthropogenic climate forcing, but over the last 50 years more winter rainfall has been falling in intense events. Future changes in rainfall and evapotranspiration could lead to changed flow regimes and impacts on water quality, aquatic ecosystems and water availability. Summer flows may decrease on average, but floods may become larger and more frequent. River and lake water quality may decline as a result of higher water temperatures, lower river flows and increased algal blooms in summer, and because of higher flows in the winter. In communicating this important work, researchers should pay particular attention to explaining confidence and uncertainty clearly. Much of the relevant research is either global or highly localized: decision-makers would benefit from more studies that address water and climate change at a spatial and temporal scale appropriate for the decisions they mak

    Microneedle Array Design Determines the Induction of Protective Memory CD8+ T Cell Responses Induced by a Recombinant Live Malaria Vaccine in Mice

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    BACKGROUND: Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8(+) T cell responses to a malaria antigen induced by a live vaccine. METHODOLOGY AND FINDINGS: Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8(+) T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes

    Climate change and water in the UK : past changes and future prospects: a climate change report card for water: Working technical paper

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    Climate change is expected to modify rainfall, temperatures and catchment hydrological responses across the world, and adapting to these water-related changes is a pressing challenge. This paper reviews the impact of climate change on water in the UK and looks at projections of future change. The natural variability of the UK climate makes change hard to detect; only historical increases in air temperature can be attributed to climate change, but over the last fifty years more winter rainfall has been falling in intense events. Future changes in rainfall and evapotranspiration could lead to changed flow regimes and impacts on water quality, aquatic ecosystems and the water available for use by people. Summer flows may decrease on average, but floods may become larger and more frequent. Water quality may decline as a result of higher water temperatures, lower river flows and increased algal blooms. Water demand may increase in response to higher summer temperatures, placing additional pressure on water resources. These changes affect many parts of everyday life, emphasising the importance of long-term adaptation that takes these possible changes into account
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