Reconstructing Rawls has one overarching goal: to reclaim Rawls for the Enlightenment—more specifically, the Prussian Enlightenment. Rawls’s so-called political turn in the 1980s, motivated by a ...newfound interest in pluralism and the accommodation of difference, has been unhealthy for autonomy-based liberalism and has led liberalism more broadly toward cultural relativism, be it in the guise of liberal multiculturalism or critiques of cosmopolitan distributive-justice theories. Robert Taylor believes that it is time to redeem A Theory of Justice’s implicit promise of a universalistic, comprehensive Kantian liberalism. Reconstructing Rawls on Kantian foundations leads to some unorthodox conclusions about justice as fairness, to be sure: for example, it yields a more civic-humanist reading of the priority of political liberty, a more Marxist reading of the priority of fair equality of opportunity, and a more ascetic or antimaterialist reading of the difference principle. It nonetheless leaves us with a theory that is still recognizably Rawlsian and reveals a previously untraveled road out of Theory—a road very different from the one Rawls himself ultimately followed.
The unprecedented volume and rate of transient events that will be discovered by the Large Synoptic Survey Telescope (LSST) demand that the astronomical community update its follow-up paradigm. ...Alert-brokers-automated software system to sift through, characterize, annotate, and prioritize events for follow-up-will be critical tools for managing alert streams in the LSST era. The Arizona-NOAO Temporal Analysis and Response to Events System (ANTARES) is one such broker. In this work, we develop a machine learning pipeline to characterize and classify variable and transient sources only using the available multiband optical photometry. We describe three illustrative stages of the pipeline, serving the three goals of early, intermediate, and retrospective classification of alerts. The first takes the form of variable versus transient categorization, the second a multiclass typing of the combined variable and transient data set, and the third a purity-driven subtyping of a transient class. Although several similar algorithms have proven themselves in simulations, we validate their performance on real observations for the first time. We quantitatively evaluate our pipeline on sparse, unevenly sampled, heteroskedastic data from various existing observational campaigns, and demonstrate very competitive classification performance. We describe our progress toward adapting the pipeline developed in this work into a real-time broker working on live alert streams from time-domain surveys.
Abstract Background Data prior to 2011 suggest that a low percentage of patients hospitalized for acute coronary syndromes filled high-intensity statin prescriptions upon discharge. Black-box ...warnings, generic availability of atorvastatin, and updated guidelines may have resulted in a change in high-intensity statin use. Objectives The aim of this study was to examine trends and predictors of high-intensity statin use following hospital discharge for myocardial infarction (MI) between 2011 and 2014. Methods Secular trends in high-intensity statin use following hospital discharge for MI were analyzed among patients 19 to 64 years of age with commercial health insurance in the MarketScan database (n = 42,893) and 66 to 75 years of age with U.S. government health insurance through Medicare (n = 75,096). Patients filling statin prescriptions within 30 days of discharge were included. High-intensity statins included atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg. Results The percentage of beneficiaries whose first statin prescriptions filled following hospital discharge for MI were for high-intensity doses increased from 33.5% in January through March 2011 to 71.7% in October through November 2014 in MarketScan and from 24.8% to 57.5% in Medicare. Increases in high-intensity statin use following hospital discharge occurred over this period among patients initiating treatment (30.6% to 72.0% in MarketScan and 21.1% to 58.8% in Medicare) and those taking low- or moderate-intensity statins prior to hospitalization (from 27.8% to 62.3% in MarketScan and from 12.6% to 45.1% in Medicare). In 2014, factors associated with filling high-intensity statin prescriptions included male sex, filling beta-blocker and antiplatelet agent prescriptions, and attending cardiac rehabilitation within 30 days following discharge. Conclusions The use of high-intensity statins following hospitalization for MI increased progressively from 2011 through 2014.
Enhancers are modular regulatory elements that are central to the spatial and temporal regulation of gene expression. Bidirectional transcription initiating at enhancers has been proposed to mark ...active enhancers and as such has been utilized to experimentally identify active enhancers de novo.
Here, we show that bidirectional transcription initiation is a pervasive feature of accessible chromatin, including at enhancers, promoters, and other DNase hypersensitive regions not marked with canonical histone modification profiles. Transcription is less predictive for enhancer activity than epigenetic modifications such as H3K4me1 or the accessibility of DNA when measured both in enhancer assays and at endogenous loci. The stability of enhancer initiated transcripts does not influence measures of enhancer activity and we cannot detect evidence of purifying selection on the resulting enhancer RNAs within the human population.
Our results indicate that bidirectional transcription initiation from accessible chromatin is not sufficient for, nor specific to, enhancer activity. Transcription initiating at enhancers may be a frequent by-product of promiscuous RNA polymerase initiation at accessible chromatin and is unlikely to generally play a functional role in enhancer activity.
Statins are highly effective for preventing cardiovascular events by reducing low-density lipoprotein cholesterol (LDL-C). However, many patients taking statins report muscle-related symptoms that ...prevent the use of guideline recommended doses. Patients with reported intolerance to statins have a high risk of cardiovascular events. Clinical strategies that optimize cardiovascular risk reduction through LDL-C lowering need to be applied in patients experiencing intolerable side effects that they attribute to statins. In this paper, the authors review definitions of statin intolerance, propose algorithms to better define statin intolerance, and describe approaches to optimize cardiovascular risk reduction among individuals reporting statin-associated muscle symptoms.
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Writing a college-application essay has become a rite of passage for high-school seniors in the United States, one whose importance has expanded over time due to an increasingly competitive ...admissions process. Various commentators have noted the disturbing evolution of these essays over the years, with an ever-greater emphasis placed on obstacles overcome and traumas survived. How have we gotten to the point where college-application essays are all too frequently competitive-victimhood displays? Colleges have an understandable interest in the disadvantages their applicants may have suffered, but this interest – and the awareness of it among both applicants and their advisors – has led to a ‘race to the bottom’: in order to thrive (or even survive) in a particular competitive context, participants are forced to continuously lower relevant standards in a game of one-upmanship. With college essays, the competition is among high-school seniors for admission, the one-upmanship is an ever-escalating effort to persuade admission committees of one’s greater disadvantage, and the relevant standards being lowered are honesty, privacy, and dignity – or so I shall argue. As we will see, this particular race to the bottom imposes unequal costs on certain groups and has implications stretching well beyond collegiate admissions.
Promoters are sites of transcription initiation that harbour a high concentration of phenotype-associated genetic variation. The evolutionary gain and loss of promoters between species (collectively, ...termed turnover) is pervasive across mammalian genomes and may play a prominent role in driving human phenotypic diversity.
We classified human promoters by their evolutionary history during the divergence of mouse and human lineages from a common ancestor. This defined conserved, human-inserted and mouse-deleted promoters, and a class of functional-turnover promoters that align between species but are only active in humans. We show that promoters of all evolutionary categories are hotspots for substitution and often, insertion mutations. Loci with a history of insertion and deletion continue that mode of evolution within contemporary humans. The presence of an evolutionary volatile promoter within a gene is associated with increased expression variance between individuals, but only in the case of human-inserted and mouse-deleted promoters does that correspond to an enrichment of promoter-proximal genetic effects. Despite the enrichment of these molecular quantitative trait loci (QTL) at evolutionarily volatile promoters, this does not translate into a corresponding enrichment of phenotypic traits mapping to these loci.
Promoter turnover is pervasive in the human genome, and these promoters are rich in molecularly quantifiable but phenotypically inconsequential variation in gene expression. However, since evolutionarily volatile promoters show evidence of selection, coupled with high mutation rates and enrichment of QTLs, this implicates them as a source of evolutionary innovation and phenotypic variation, albeit with a high background of selectively neutral expression variation.
Paradoxical reactions are immune-mediated exacerbations of disease triggered by tuberculosis treatment. Paradoxical reactions involving the central nervous system may be life threatening. Infliximab ...(tumor necrosis factor antibody) profoundly inhibits cellular immune responses to Mycobacterium tuberculosis. We describe a case in which infliximab was used to control steroid-resistant tuberculosis paradoxical reaction involving the central nervous system.
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