69 research outputs found

    Cryptic multiple hypotheses testing in linear models: overestimated effect sizes and the winner's curse

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    Fitting generalised linear models (GLMs) with more than one predictor has become the standard method of analysis in evolutionary and behavioural research. Often, GLMs are used for exploratory data analysis, where one starts with a complex full model including interaction terms and then simplifies by removing non-significant terms. While this approach can be useful, it is problematic if significant effects are interpreted as if they arose from a single a priori hypothesis test. This is because model selection involves cryptic multiple hypothesis testing, a fact that has only rarely been acknowledged or quantified. We show that the probability of finding at least one ‘significant’ effect is high, even if all null hypotheses are true (e.g. 40% when starting with four predictors and their two-way interactions). This probability is close to theoretical expectations when the sample size (N) is large relative to the number of predictors including interactions (k). In contrast, type I error rates strongly exceed even those expectations when model simplification is applied to models that are over-fitted before simplification (low N/k ratio). The increase in false-positive results arises primarily from an overestimation of effect sizes among significant predictors, leading to upward-biased effect sizes that often cannot be reproduced in follow-up studies (‘the winner's curse’). Despite having their own problems, full model tests and P value adjustments can be used as a guide to how frequently type I errors arise by sampling variation alone. We favour the presentation of full models, since they best reflect the range of predictors investigated and ensure a balanced representation also of non-significant results

    Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

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    <p>Abstract</p> <p>Background</p> <p>In the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events.</p> <p>Methods/Design</p> <p>The Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction (EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years.</p> <p>Discussion</p> <p>The ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome.</p> <p>Trial registration</p> <p>trialregister.nl NTR1108.</p

    Silicon optical modulators

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    Optical technology is poised to revolutionize short-reach interconnects. The leading candidate technology is silicon photonics, and the workhorse of such an interconnect is the optical modulator. Modulators have been improved dramatically in recent years, with a notable increase in bandwidth from the megahertz to the multigigahertz regime in just over half a decade. However, the demands of optical interconnects are significant, and many questions remain unanswered as to whether silicon can meet the required performance metrics. Minimizing metrics such as the device footprint and energy requirement per bit, while also maximizing bandwidth and modulation depth, is non-trivial. All of this must be achieved within an acceptable thermal tolerance and optical spectral width using CMOS-compatible fabrication processes. This Review discusses the techniques that have been (and will continue to be) used to implement silicon optical modulators, as well as providing an outlook for these devices and the candidate solutions of the future

    Hand, hip and knee osteoarthritis in a Norwegian population-based study - The MUST protocol

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    A revision of the deep-water octopus genus Scaeurgus (Cephalopoda : Octopodidae) with description of three new species from the southwest Pacific Ocean

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    Deep-water trawl surveys on seamounts around New Caledonia yielded 62 specimens of the little-known genus, Scaeurgus. Members of this genus of octopuses typically occur at depths of 200-500 m in temperate and tropical latitudes worldwide. Prior to this study, Scaeurgus was considered to contain one to two species. The new material from New Caledonia contained a surprising diversity of Scaeurgus species from a small area: three distinct new species are described and limited material of a further two taxa is reported. A pygmy member of this genus is reported for the first time. Distributions of these new taxa are consistent with reports of high endemism on the seamount systems in this region. Fifty-eight of the 62 specimens were collected from seamounts, with four of the five taxa unique to a single seamount
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