Variable selection with error control: Another look at stability selection

Stability Selection was recently introduced by Meinshausen and Buhlmann (2010) as a very general technique designed to improve the performance of a variable selection algorithm. It is based on aggregating the results of applying a selection procedure to subsamples of the data. We introduce a variant, called Complementary Pairs Stability Selection (CPSS), and derive bounds both on the expected number of variables included by CPSS that have low selection probability under the original procedure, and on the expected number of high selection probability variables that are excluded. These results require no (e.g. exchangeability) assumptions on the underlying model or on the quality of the original selection procedure. Under reasonable shape restrictions, the bounds can be further tightened, yielding improved error control, and therefore increasing the applicability of the methodology.This is the accepted manuscript version. The final published version is available from Wiley at http://onlinelibrary.wiley.com/doi/10.1111/j.1467-9868.2011.01034.x/abstract

Dynamic contrast enhanced CT in nodule characterization: How we review and report

Incidental indeterminate solitary pulmonary nodules (SPN) that measure less than 3 cm in size are an increasingly common finding on computed tomography (CT) worldwide. Once identified there are a number of imaging strategies that can be performed to help with nodule characterization. These include interval CT, dynamic contrast enhanced computed tomography (DCE-CT), $^{18}$F-fluorodeoxyglucose positron emission tomography-computed tomography ($^{18}$F-FDG-PET-CT). To date the most cost effective and efficient non-invasive test or combination of tests for optimal nodule characterization has yet to be determined.DCE-CT is a functional test that involves the acquisition of a dynamic series of images of a nodule before and following the administration of intravenous iodinated contrast medium. This article provides an overview of the current indications and limitations of DCE- CT in nodule characterization and a systematic approach to how to perform, analyse and interpret a DCE-CT scan.NIHR Health Technology Assessment programme (Grant ID: 09/22/117), Cambridge Biomedical Research Centre, CRUK Cambridge and Manchester Cancer Imaging Centr

Modelling high-dimensional categorical data using nonconvex fusion penalties

We propose a method for estimation in high-dimensional linear models with nominal categorical data. Our estimator, called SCOPE, fuses levels together by making their corresponding coefficients exactly equal. This is achieved using the minimax concave penalty on differences between the order statistics of the coefficients for a categorical variable, thereby clustering the coefficients. We provide an algorithm for exact and efficient computation of the global minimum of the resulting nonconvex objective in the case with a single variable with potentially many levels, and use this within a block coordinate descent procedure in the multivariate case. We show that an oracle least squares solution that exploits the unknown level fusions is a limit point of the coordinate descent with high probability, provided the true levels have a certain minimum separation; these conditions are known to be minimal in the univariate case. We demonstrate the favourable performance of SCOPE across a range of real and simulated datasets. An R package CatReg implementing SCOPE for linear models and also a version for logistic regression is available on CRAN

Patients with severe acute‐on‐chronic liver failure are disadvantaged by model for end‐stage liver disease‐based organ allocation policy

Background: Mortality for patients with acute‐on‐chronic liver failure (ACLF) may be underestimated by the model for end‐stage liver disease‐sodium (MELD‐Na) score. / Aim: To assess waitlist outcomes across varying grades of ACLF among a cohort of patients listed with a MELD‐Na score ≥35, and therefore having similar priority for liver transplantation. / Methods: We analysed the United Network for Organ Sharing (UNOS) database, years 2010‐2017. Waitlist outcomes were evaluated using Fine and Gray's competing risks regression. / Results: We identified 6342 candidates at listing with a MELD‐Na score ≥35, of whom 3122 had ACLF‐3. Extra‐hepatic organ failures were present primarily in patients with four to six organ failures. Competing risks regression revealed that candidates listed with ACLF‐3 had a significantly higher risk for 90‐day waitlist mortality (Sub‐hazard ratio (SHR) = 1.41; 95% confidence interval [CI] 1.12‐1.78) relative to patients with lower ACLF grades. Subgroup analysis of ACLF‐3 revealed that both the presence of three organ failures (SHR = 1.40, 95% CI 1.20‐1.63) or four to six organ failures at listing (SHR = 3.01; 95% CI 2.54‐3.58) was associated with increased waitlist death. Candidates with four to six organ failures also had the lowest likelihood of receiving liver transplantation (SHR = 0.61, 95% CI 0.54‐0.68). The Share 35 rule was associated with reduced 90‐day waitlist mortality among the full cohort of patients listed with ACLF‐3 and MELD‐Na score ≥35 (SHR = 0.59; 95% CI 0.49‐0.70). However, Share 35 rule implementation was not associated with reduced waitlist mortality among patients with four to six organ failures (SHR = 0.76; 95% CI 0.58‐1.02). / Conclusion: The MELD‐Na score disadvantages patients with ACLF‐3, both with and without extra‐hepatic organ failures. Incorporation of organ failures into allocation policy warrants further exploration

The Precursors and Products of Justice Climates: Group Leader Antecedents and Employee Attitudinal Consequences

Drawing on the organizational justice, organizational climate, leadership and personality, and social comparison theory literatures, we develop hypotheses about the effects of leader personality on the development of three types of justice climates (e.g., procedural, interpersonal, and informational), and the moderating effects of these climates on individual level justice- attitude relationships. Largely consistent with the theoretically-derived hypotheses, the results showed that leader (a) agreeableness was positively related to procedural, interpersonal and informational justice climates, (b) conscientiousness was positively related to a procedural justice climate, and (c) neuroticism was negatively related to all three types of justice climates. Further, consistent with social comparison theory, multilevel data analyses revealed that the relationship between individual justice perceptions and job attitudes (e.g., job satisfaction, commitment) was moderated by justice climate such that the relationships were stronger when justice climate was high

Characteristics of ischaemic stroke associated with COVID-19

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with coagulopathy causing venous and arterial thrombosis.1 2 Recent data from the pandemic epicentre in Wuhan, China, reported neurological complications in 36% of 214 patients with COVID-19; acute cerebrovascular disease (mainly ischaemic stroke) was more common among 88 patients with severe COVID-19 than those with non-severe disease (5.7% vs 0.8%).3 However, the mechanisms, phenotype and optimal management of ischaemic stroke associated with COVID-19 remain uncertain. We describe the demographic, clinical, radiological and laboratory characteristics of six consecutive patients assessed between 1st and 16th April 2020 at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK, with acute ischaemic stroke and COVID-19 (confirmed by reverse-transcriptase PCR (RT-PCR)) (table 1). All six patients had large vessel occlusion with markedly elevated D-dimer levels (≥1000μg/L). Three patients had multiterritory infarcts, two had concurrent venous thrombosis, and, in two, ischaemic strokes occurred despite therapeutic anticoagulation

Environmental life cycle assessment of wire arc additively manufactured steel structural components

Wire arc additive manufacturing (WAAM) enables the production of structural components with topologically optimised geometries thus leading to significant self-weight reductions for a given load-carrying capacity. A common question arises regarding the environmental performance of WAAM structural components in comparison with conventional steel structural components. Thus, a comparative cradle-to-gate life cycle assessment has been conducted where the environmental impact of producing a topologically optimised WAAM steel beam is compared with that of producing a conventional hot-rolled steel I-beam. The beams are 2 m long, simply-supported and loaded vertically at midspan. The impact of using either carbon steel or stainless steel is investigated. The results demonstrate that the carbon steel and stainless steel WAAM beams have 7% and 24%, respectively, lower climate change impact than the corresponding I-beams. It is concluded that WAAM can lead to lower CO2-eq. emissions than conventional hot-rolling, provided that mass reductions of the order of 50% (which are readily attainable) can be achieved by employing WAAM in conjunction with, for instance, topology optimisation. Furthermore, it is shown that the shielding gas contributes greatly to the environmental impact of WAAM, and that, by using higher deposition rates or by utilising renewable energy sources, the impact of WAAM can be reduced by more than 30%

Enhancement of lipase activity in non-aqueous media upon immobilization on multi-walled carbon nanotubes

<p>Abstract</p> <p>Background</p> <p>Immobilization of biologically active proteins on nanosized surfaces is a key process in bionanofabrication. Carbon nanotubes with their high surface areas, as well as useful electronic, thermal and mechanical properties, constitute important building blocks in the fabrication of novel functional materials.</p> <p>Results</p> <p>Lipases from <it>Candida rugosa </it>(CRL) were found to be adsorbed on the multiwalled carbon nanotubes with very high retention of their biological activity (97%). The immobilized biocatalyst showed 2.2- and 14-fold increases in the initial rates of transesterification activity in nearly anhydrous hexane and water immiscible ionic liquid [Bmim] [PF6] respectively, as compared to the lyophilized powdered enzyme. It is presumed that the interaction with the hydrophobic surface of the nanotubes resulted in conformational changes leading to the 'open lid' structure of CRL. The immobilized enzyme was found to give 64% conversion over 24 h (as opposed to 14% with free enzyme) in the formation of butylbutyrate in nearly anhydrous hexane. Similarly, with ionic liquid [Bmim] [PF6], the immobilized enzyme allowed 71% conversion as compared to 16% with the free enzyme. The immobilized lipase also showed high enantioselectivity as determined by kinetic resolution of (±) 1-phenylethanol in [Bmim] [PF6]. While free CRL gave only 5% conversion after 36 h, the immobilized enzyme resulted in 37% conversion with > 99% enantiomeric excess. TEM studies on the immobilized biocatalyst showed that the enzyme is attached to the multiwalled nanotubes.</p> <p>Conclusion</p> <p>Successful immobilization of enzymes on nanosized carriers could pave the way for reduced reactor volumes required for biotransformations, as well as having a use in the construction of miniaturized biosensensor devices.</p

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel