Fitting heavy tailed distributions: the poweRlaw package

Over the last few years, the power law distribution has been used as the data generating mechanism in many disparate fields. However, at times the techniques used to fit the power law distribution have been inappropriate. This paper describes the poweRlaw R package, which makes fitting power laws and other heavy-tailed distributions straightforward. This package contains R functions for fitting, comparing and visualising heavy tailed distributions. Overall, it provides a principled approach to power law fitting.Comment: The code for this paper can be found at https://github.com/csgillespie/poweRla

Scalable Inference for Markov Processes with Intractable Likelihoods

Bayesian inference for Markov processes has become increasingly relevant in recent years. Problems of this type often have intractable likelihoods and prior knowledge about model rate parameters is often poor. Markov Chain Monte Carlo (MCMC) techniques can lead to exact inference in such models but in practice can suffer performance issues including long burn-in periods and poor mixing. On the other hand approximate Bayesian computation techniques can allow rapid exploration of a large parameter space but yield only approximate posterior distributions. Here we consider the combined use of approximate Bayesian computation (ABC) and MCMC techniques for improved computational efficiency while retaining exact inference on parallel hardware

Ten Simple Rules for Getting Help from Online Scientific Communities

The increasing complexity of research requires scientists to work at the intersection of multiple fields and to face problems for which their formal education has not prepared them. For example, biologists with no or little background in programming are now often using complex scripts to handle the results from their experiments; vice versa, programmers wishing to enter the world of bioinformatics must know about biochemistry, genetics, and other fields. In this context, communication tools such as mailing lists, web forums, and online communities acquire increasing importance. These tools permit scientists to quickly contact people skilled in a specialized field. A question posed properly to the right online scientific community can help in solving difficult problems, often faster than screening literature or writing to publication authors. The growth of active online scientific communities, such as those listed in Table S1, demonstrates how these tools are becoming an important source of support for an increasing number of researchers. Nevertheless, making proper use of these resources is not easy. Adhering to the social norms of World Wide Web communication—loosely termed “netiquette”—is both important and non-trivial. In this article, we take inspiration from our experience on Internet-shared scientific knowledge, and from similar documents such as “Asking the Questions the Smart Way” and “Getting Answers”, to provide guidelines and suggestions on how to use online communities to solve scientific problems

Effectiveness of subnational implementation of minimum unit price for alcohol: policy appraisal modelling for local authorities in England

Aims: Evidence exists on the potential impact of national level minimum unit price (MUP) policies for alcohol. This study investigated the potential effectiveness of implementing MUP at regional and local levels compared with national implementation. Design: Evidence synthesis and computer modelling using the Sheffield Alcohol Policy Model (Local Authority version 4.0; SAPMLA). Setting: Results are produced for 23 Upper Tier Local Authorities (UTLAs) in North West England, 12 UTLAs in North East England, 15 UTLAs in Yorkshire and Humber, the nine English Government Office regions and England as a whole. Cases: Health Survey for England (HSE) data 2011–13 (n = 24 685). Measurements: Alcohol consumption, consumer spending, retailers’ revenues, hospitalizations, National Health Service costs, crimes and alcohol-attributable deaths and health inequalities. Findings: Implementing a local £0.50 MUP for alcohol in northern English regions is estimated to result in larger percentage reductions in harms than the national average. The reductions for England, North West, North East and Yorkshire and Humber regions, respectively, in annual alcohol-attributable deaths are 1024 (−10.4%), 205 (−11.4%), 121 (−17.4%) and 159 (−16.9%); for hospitalizations are 29 943 (−4.6%), 5956 (−5.5%), 3255 (−7.9%) and 4610 (−6.9%); and for crimes are 54 229 (−2.4%), 8528 (−2.5%), 4380 (−3.5%) and 8220 (−3.2%). Results vary among local authorities; for example, annual alcohol-attributable deaths estimated to change by between −8.0 and −24.8% throughout the 50 UTLAs examined. Conclusions: A minimum unit price local policy for alcohol is likely to be more effective in those regions, such as the three northern regions of England, which have higher levels of alcohol consumption and higher rates of alcohol harm than for the national average. In such regions, the minimum unit price policy would achieve larger reductions in alcohol consumption, alcohol-attributable mortality, hospitalization rates, NHS costs, crime rates and health inequalities

Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype

ims/hypothesis The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes. Methods Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with newly diagnosed or long-standing type 1 diabetes, and healthy individuals. Polychromatic flow cytometry was used to characterise the phenotypic attributes of B and T cells. Islet autoantigen-specific B cells were quantified using an enzyme-linked immunospot (ELISpot) assay and islet autoantigen-specific CD8+ T cells were quantified using peptide–HLA class I tetramers. Radioimmunoassays were used to detect islet autoantibodies. Sera were assayed for various chemokines, cytokines and soluble receptors via ELISAs. Results Islet autoantibodies were lost over time in slow progressors. Various B cell subsets expressed higher levels of CD95 in slow progressors, especially after polyclonal stimulation, compared with the corresponding B cell subsets in healthy donors (p < 0.05). The phenotypic characteristics of CD4+ and CD8+ T cells were similar in slow progressors and healthy donors. Lower frequencies of CD4+ T cells with a central memory phenotype (CD27int, CD127+, CD95int) were observed in slow progressors compared with healthy donors (mean percentage of total CD4+ T cells was 3.00% in slow progressors vs 4.67% in healthy donors, p < 0.05). Autoreactive B cell responses to proinsulin were detected at higher frequencies in slow progressors compared with healthy donors (median no. of spots was 0 in healthy donors vs 24.34 in slow progressors, p < 0.05) in an ELISpot assay. Islet autoantigen-specific CD8+ T cell responses were largely absent in slow progressors and healthy donors. Serum levels of DcR3, the decoy receptor for CD95L, were elevated in slow progressors compared with healthy donors (median was 1087 pg/ml in slow progressors vs 651 pg/ml in healthy donors, p = 0.06). Conclusions/interpretation In this study, we found that slow progression to type 1 diabetes was associated with a loss of islet autoantibodies and a distinct B cell phenotype, consistent with enhanced apoptotic regulation of peripheral autoreactivity via CD95. These phenotypic changes warrant further studies in larger cohorts to determine their functional implications