Determining the significance of associations between two series of discrete events : bootstrap methods /

We review and develop techniques to determine associations between series of discrete events. The bootstrap, a nonparametric statistical method, allows the determination of the significance of associations with minimal assumptions about the underlying processes. We find the key requirement for this method: one of the series must be widely spaced in time to guarantee the theoretical applicability of the bootstrap. If this condition is met, the calculated significance passes a reasonableness test. We conclude with some potential future extensions and caveats on the applicability of these methods. The techniques presented have been implemented in a Python-based software toolkit

The SpacePy space science package at 12 years

For over a decade, the SpacePy project has contributed open-source solutions for the production and analysis of heliophysics data and simulation results. Here we introduce SpacePy's functionality for the scientific user and present relevant design principles. We examine recent advances and the future of SpacePy in the broader scientific Python ecosystem, concluding with some of the work that has used SpacePy.Comment: 14 pages, 3 figures, accepted for publication in Frontiers in Astronomy and Space Science

Model Evaluation Guidelines for Geomagnetic Index Predictions

Geomagnetic indices are convenient quantities that distill the complicated physics of some region or aspect of near‐Earth space into a single parameter. Most of the best‐known indices are calculated from ground‐based magnetometer data sets, such as Dst, SYM‐H, Kp, AE, AL, and PC. Many models have been created that predict the values of these indices, often using solar wind measurements upstream from Earth as the input variables to the calculation. This document reviews the current state of models that predict geomagnetic indices and the methods used to assess their ability to reproduce the target index time series. These existing methods are synthesized into a baseline collection of metrics for benchmarking a new or updated geomagnetic index prediction model. These methods fall into two categories: (1) fit performance metrics such as root‐mean‐square error and mean absolute error that are applied to a time series comparison of model output and observations and (2) event detection performance metrics such as Heidke Skill Score and probability of detection that are derived from a contingency table that compares model and observation values exceeding (or not) a threshold value. A few examples of codes being used with this set of metrics are presented, and other aspects of metrics assessment best practices, limitations, and uncertainties are discussed, including several caveats to consider when using geomagnetic indices.Plain Language SummaryOne aspect of space weather is a magnetic signature across the surface of the Earth. The creation of this signal involves nonlinear interactions of electromagnetic forces on charged particles and can therefore be difficult to predict. The perturbations that space storms and other activity causes in some observation sets, however, are fairly regular in their pattern. Some of these measurements have been compiled together into a single value, a geomagnetic index. Several such indices exist, providing a global estimate of the activity in different parts of geospace. Models have been developed to predict the time series of these indices, and various statistical methods are used to assess their performance at reproducing the original index. Existing studies of geomagnetic indices, however, use different approaches to quantify the performance of the model. This document defines a standardized set of statistical analyses as a baseline set of comparison tools that are recommended to assess geomagnetic index prediction models. It also discusses best practices, limitations, uncertainties, and caveats to consider when conducting a model assessment.Key PointsWe review existing practices for assessing geomagnetic index prediction models and recommend a “standard set” of metricsAlong with fit performance metrics that use all data‐model pairs in their formulas, event detection performance metrics are recommendedOther aspects of metrics assessment best practices, limitations, uncertainties, and geomagnetic index caveats are also discussedPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147764/1/swe20790_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147764/2/swe20790.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147764/3/swe20790-sup-0001-2018SW002067-SI.pd

An analysis of potential barriers and enablers to regulating the television marketing of unhealthy foods to children at the state government level in Australia

Background In Australia there have been many calls for government action to halt the effects of unhealthy food marketing on children\u27s health, yet implementation has not occurred. The attitudes of those involved in the policy-making process towards regulatory intervention governing unhealthy food marketing are not well understood. The objective of this research was to understand the perceptions of senior representatives from Australian state and territory governments, statutory authorities and non-government organisations regarding the feasibility of state-level government regulation of television marketing of unhealthy food to children in Australia.Method Data from in-depth semi-structured interviews with senior representatives from state and territory government departments, statutory authorities and non-government organisations (n=22) were analysed to determine participants\u27 views about regulation of television marketing of unhealthy food to children at the state government level. Data were analysed using content and thematic analyses.Results Regulation of television marketing of unhealthy food to children was supported as a strategy for obesity prevention. Barriers to implementing regulation at the state level were: the perception that regulation of television advertising is a Commonwealth, not state/territory, responsibility; the power of the food industry and; the need for clear evidence that demonstrates the effectiveness of regulation. Evidence of community support for regulation was also cited as an important factor in determining feasibility.Conclusions The regulation of unhealthy food marketing to children is perceived to be a feasible strategy for obesity prevention however barriers to implementation at the state level exist. Those involved in state-level policy making generally indicated a preference for Commonwealth-led regulation. This research suggests that implementation of regulation of the television marketing of unhealthy food to children should ideally occur under the direction of the Commonwealth government. However, given that regulation is technically feasible at the state level, in the absence of Commonwealth action, states/territories could act independently. The relevance of our findings is likely to extend beyond Australia as unhealthy food marketing to children is a global issue.<br /

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

A philosophical analysis of the evidence-based medicine debate

BACKGROUND: The term "evidence-based medicine" (or EBM) was introduced about ten years ago, and there has been considerable debate about the value of EBM. However, this debate has sometimes been obscured by a lack of conceptual clarity concerning the nature and status of EBM. DISCUSSION: First, we note that EBM proponents have obscured the current debate by defining EBM in an overly broad, indeed almost vacuous, manner; we offer a clearer account of EBM and its relation to the alternative approaches to medicine. Second, while EBM proponents commonly cite the philosophical work of Thomas Kuhn and claim that EBM is a Kuhnian 'paradigm shift,' we argue that such claims are seriously mistaken and unduly polarize the EBM debate. Third, we suggest that it is much more fruitful to understand the relationship between EBM and its alternatives in light of a different philosophical metaphor: W.V. Quine's metaphor of the web of belief. Seen in this way, we argue that EBM is an approach to medical practice that is indeed importantly different from the alternatives. SUMMARY: We can have a more productive debate about the value of EBM by being clearer about the nature of EBM and its relationship to alternative approaches to medicine

In vivo cholinergic basal forebrain atrophy predicts cognitive decline in de novo Parkinson’s disease

Cognitive impairments are a prevalent and disabling non-motor complication of Parkinson’s disease, but with variable expression and progression. The onset of serious cognitive decline occurs alongside substantial cholinergic denervation, but imprecision of previously available techniques for in vivo measurement of cholinergic degeneration limit their use as predictive cognitive biomarkers. However, recent developments in stereotactic mapping of the cholinergic basal forebrain have been found useful for predicting cognitive decline in prodromal stages of Alzheimer’s disease. These methods have not yet been applied to longitudinal Parkinson’s disease data. In a large sample of people with de novo Parkinson’s disease (n = 168), retrieved from the Parkinson’s Progressive Markers Initiative database, we measured cholinergic basal forebrain volumes, using morphometric analysis of T1-weighted images in combination with a detailed stereotactic atlas of the cholinergic basal forebrain nuclei. Using a binary classification procedure, we defined patients with reduced basal forebrain volumes (relative to age) at baseline, based on volumes measured in a normative sample (n = 76). Additionally, relationships between the basal forebrain volumes at baseline, risk of later cognitive decline, and scores on up to 5 years of annual cognitive assessments were assessed with regression, survival analysis and linear mixed modelling. In patients, smaller volumes in a region corresponding to the nucleus basalis of Meynert were associated with greater change in global cognitive, but not motor scores after 2 years. Using the binary classification procedure, patients classified as having smaller than expected volumes of the nucleus basalis of Meynert had ∼3.5-fold greater risk of being categorized as mildly cognitively impaired over a period of up to 5 years of follow-up (hazard ratio = 3.51). Finally, linear mixed modelling analysis of domain-specific cognitive scores revealed that patients classified as having smaller than expected nucleus basalis volumes showed more severe and rapid decline over up to 5 years on tests of memory and semantic fluency, but not on tests of executive function. Thus, we provide the first evidence that volumetric measurement of the nucleus basalis of Meynert can predict early cognitive decline. Our methods therefore provide the opportunity for multiple-modality biomarker models to include a cholinergic biomarker, which is currently lacking for the prediction of cognitive deterioration in Parkinson’s disease. Additionally, finding dissociated relationships between nucleus basalis status and domain-specific cognitive decline has implications for understanding the neural basis of heterogeneity of Parkinson’s disease-related cognitive decline