lpEdit: an editor to facilitate reproducible analysis via literate programming

ArticleCopyright 2013 Adam J Richards et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited .There is evidence to suggest that a surprising proportion of published experiments in science are difficult if not impossible to reproduce. The concepts of data sharing, leaving an audit trail and extensive documentation are fundamental to reproducible research, whether it is in the laboratory or as part of an analysis. In this work, we introduce a tool for documentation that aims to make analyses more reproducible in the general scientific community. The application, lpEdit, is a cross-platform editor, written with PyQt4, that enables a broad range of scientists to carry out the analytic component of their work in a reproducible manner—through the use of literate programming. Literate programming mixes code and prose to produce a final report that reads like an article or book. lpEdit targets researchers getting started with statistics or programming, so the hurdles associated with setting up a proper pipeline are kept to a minimum and the learning burden is reduced through the use of templates and documentation. The documentation for lpEdit is centered around learning by example, and accordingly we use several increasingly involved examples to demonstrate the software’s capabilities. We first consider applications of lpEdit to process analyses mixing R and Python code with the LATEX documentation system. Finally, we illustrate the use of lpEdit to conduct a reproducible functional analysis of high-throughput sequencing data, using the transcriptome of the butterfly species Pieris brassica

Can restenosis after coronary angioplasty be predicted from clinical variables?

AbstractObjectives. The purpose of this study was to determine whether variables shown to correlate with restenosis in one group (learning group) could be shown to predict recurrent stenosis in a second group (validation group).Background. Restenosis remains a critical limitation after percutaneous transluminal coronary angioplasty. Although several clinical variables have been shown to correlate with restenosis, there are few data concerning attempts to predict recurrent stenosis.Methods. The source of data was the clinical data bese at Emory University. Patients who had had previous coronary surgery and patients who underwent coronary angioplasty in the setting of acute myocardial Infarction were excluded. A total of 4,006 patients with angiographic restudy after successful angioplisty were identified. They were classified into a learning group of 2,500 patients and a validation group of 1,506 patients. The correlates of restenosis in the learning group were determined by stepwise logistic regression, and a model was developed to predict the probability of restenosis and was tested in the validation group. By using various cut points for the predicted probability of restenosis, a receiver operating characteristic curve was created. Goodness of fit of the model was evaluated by comparing average predicted probabilities with average observed probabilities within subgroups on the basis of risk level determined by linear regression analysis.Results. In the learning group 1,145 patients had restenosis and 1,355 did not. Correlates of restenosis were severe angina, severe diameter stenosis before angioplasty, left anterior descending coronary artery dilation, diabetes, greater diameter stenosis after angioplasty, hypertension, absence of an intimal tear, eccentric morphology and older patient age. The model derived from the learing group was used to predict restenosis in the validation group. By varying the cut point for the predicted probability of restenosis above which restenosis is diagnosed and below which it is not, a receiver operating characteristic curve was created. The curve was close to the line of identity, reflecting a poor predictive ability. However, the model was shown to fit well with the predicted probability of restenosis correlating well with the observed probability (r = 0.98, p = 0.0001).Conclusions. Clinical variables provide limited ability to predict definitively whether a particular patient will have restenosis. However, the current model may be used to predict the probability of restenosis, with some uncertainty, at least in well characterized patients who have already had angioplasy

Relationship Between Characteristics of Medications and Drug-Induced Liver Disease Phenotype and Outcome

Background & Aims: It is not known if specific characteristics of medication are associated with type of drug-induced liver injury (DILI) or outcome. We examined the relationships among select characteristics of medications and DILI phenotype and outcome. Methods: We analyzed 383 cases of DILI caused by a single orally administered prescription agent from the DILI Network Prospective Study with causalities of definite, highly likely, or probable. Relationship of daily dosage (≥ 50 mg vs. ≤ 49 mg), preponderance of hepatic metabolism (≥50% vs <50%), or Biopharmaceutics Drug Disposition Classification System (BDDCS) class (1–4, based on solubility and metabolism of the drug) were compared with clinical characteristics and outcomes. Results: Compared to cases of DILI in the <50 mg/day group, those associated with daily dosages ≥50 mg had shorter latency (median 38 days vs 56 days; P=.03) and a different biochemical pattern of liver injury (P=.04); no differences in pattern of injury, recovery, severity, or outcome were observed. Patients with DILI caused by medications with or without preponderant hepatic metabolism did not differ in clinical characteristics or outcomes. Compared to other classes of BDDCS, DILI caused by BDDCS class 1 medications had significantly longer latency (P<.001) and greater proportion of hepatocellular injury (P=.001). However, peak liver biochemical values and patients’ time to recovery, disease severity, and outcomes did not differ among the 4 BDDCS classes. Conclusions: Characteristics of medications (dosage, hepatic metabolism, and solubility) are associated with features of DILI such as latency and pattern of liver injury, but not with recovery, severity, or outcome

Features of Autoimmune Hepatitis in Patients With Drug-induced Liver Injury

BACKGROUND & AIMS: Drug-induced liver injury (DILI) has features similar to those of other liver diseases including autoimmune hepatitis (AIH). We aimed to characterize the clinical and autoimmune features of liver injury caused by nitrofurantoin, minocycline, methyldopa, or hydralazine. METHODS: We analyzed data from 88 cases of DILI attributed to nitrofurantoin, minocycline, methyldopa, or hydralazine included in the Drug-Induced Liver Injury Network prospective study from 2004 through 2014. Sera were collected from patients at baseline and follow-up examination and tested for levels of immunoglobulin G (IgG), antibodies to nuclear antigen (ANA), smooth muscle (SMA), and soluble liver antigen (SLA). An autoimmune score was derived on the basis of increases in levels of IgG, ANA, SMA, and SLA (assigned values of 0, 1+, or 2+). AIH-associated HLA-DRB1*03:01 and HLA-DRB1*04:01 allele frequencies were compared with those of the general population (controls). RESULTS: Of the 88 cases, 80 were women (91%), 74% had hepatocellular injury, and 25% had severe injury. At the onset of DILI, 39% of cases had increased levels of IgG, 72% had increased levels of ANA, 60% had increased levels of SMA, and none had increases in SLA. A phenotype of autoimmunity (autoimmune score ≥2) was observed in 82% of cases attributed to nitrofurantoin and 73% of cases attributed to minocycline (73%) but only 55% of cases attributed to methyldopa and 43% of cases attributed to hydralazine (P = .16 for nitrofurantoin and minocycline vs methyldopa and hydralazine). We observed a decrease in numbers of serum samples positive for ANA (P = .01) or SMA (P < .001) and in autoimmune scores (P < .001) between DILI onset and follow-up. Similar percentages of patients with DILI had HLA-DRB1*03:01 (15%) and HLA-DRB1*04:01 (9%) as controls (12% and 9%, respectively). CONCLUSIONS: In analysis of data from the DILIN prospective study, we found that most cases of DILI attributed to nitrofurantoin or minocycline and about half of cases that were due to methyldopa and hydralazine have a phenotype of autoimmunity similar to AIH. These features decrease with recovery of the injury and are not associated with the typical HLA alleles found in patients with idiopathic AIH

Cryo-EM structure of the fully assembled elongator complex

Transfer RNA (tRNA) molecules are essential to decode messenger RNA codons during protein synthesis. All known tRNAs are heavily modified at multiple positions through post-transcriptional addition of chemical groups. Modifications in the tRNA anticodons are directly influencing ribosome decoding and dynamics during translation elongation and are crucial for maintaining proteome integrity. In eukaryotes, wobble uridines are modified by Elongator, a large and highly conserved macromolecular complex. Elongator consists of two subcomplexes, namely Elp123 containing the enzymatically active Elp3 subunit and the associated Elp456 hetero-hexamer. The structure of the fully assembled complex and the function of the Elp456 subcomplex have remained elusive. Here, we show the cryo-electron microscopy structure of yeast Elongator at an overall resolution of 4.3 Å. We validate the obtained structure by complementary mutational analyses in vitro and in vivo. In addition, we determined various structures of the murine Elongator complex, including the fully assembled mouse Elongator complex at 5.9 Å resolution. Our results confirm the structural conservation of Elongator and its intermediates among eukaryotes. Furthermore, we complement our analyses with the biochemical characterization of the assembled human Elongator. Our results provide the molecular basis for the assembly of Elongator and its tRNA modification activity in eukaryotes

Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial

Background: There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study. Methods/Design: STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI) or Health Education Intervention Augmentation (HEI). Both groups will receive TAU (i.e., usual care). The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual) sessions, although other participants may be exercising at the same time. Following the 12-week acute phase, participants will begin a 6-month continuation phase during which time they will attend one weekly supervised DEI or HEI session

Caracterización de la fibrilación auricular y riesgo tromboembólico en pacientes del Hospital León Cuervo Rubio

Introduction: among cardiac pathologies, atrial fibrillation is related to a high incidence of thromboembolic diseases. Objective: to clinically and epidemiologically characterize atrial fibrillation and thromboembolic risk in patients attended at the León Cuervo Rubio Hospital in Pinar del Río between 2017 and 2019. Methods: an observational, descriptive, cross-sectional, descriptive study was conducted on patients with atrial fibrillation attended at the León Cuervo Rubio Hospital in Pinar del Río from 2017 to 2019. The study universe consisted of 198 patients diagnosed with atrial arrhythmias in that hospital, the sample was constituted by 68 patients who met the inclusion and exclusion criteria. Results: female sex predominated (58.8%). The most representative age group was 75 to 85 years old (45.5 %). Some type of heart disease associated with atrial fibrillation was present in 69.1% of patients. Persistent atrial fibrillation predominated (35.2%). Palpitations predominated as symptoms of atrial fibrillation (91.1%). Most patients with atrial fibrillation were in the moderate thromboembolic risk category (66.1%). Conclusions: the predominant sex was female, the most affected age group was over 85 years, ischemic heart disease was the most prevalent history, persistent atrial fibrillation was the most frequent, palpitations were the main symptom, and according to the thromboembolic risk category, most patients were at moderate risk.Introducción: dentro de las patologías cardiacas, la fibrilación auricular se relaciona con una alta incidencia de enfermedades tromboembólicas. Objetivo: caracterizar clínica y epidemiológicamente la fibrilación auricular y el riesgo tromboembólico en pacientes atendidos en el Hospital León Cuervo Rubio de Pinar del Río entre 2017 y 2019. Método: se realizó un estudio observacional, descriptivo, de corte transversal a pacientes con fibrilación auricular atendidos en el Hospital León Cuervo Rubio de Pinar del Río de 2017 a 2019. El universo de estudio estuvo conformado por 198 pacientes con diagnóstico de arritmias auriculares en dicho hospital, la muestra quedó constituida por 68 pacientes que cumplieron con los criterios de inclusión y exclusión. Resultados: predominó el sexo femenino (58,8 %). El grupo etario más representativo fue el de 75 a 85 años (45,5 %). El 69,1 % presentaban algún tipo de cardiopatía asociada a la fibrilación auricular. Predominó la fibrilación auricular de tipo persistente (35,2 %). Predominaron las palpitaciones como síntomas de la fibrilación auricular (91,1 %). La mayoría de los pacientes con fibrilación auricular estaban en la categoría de riesgo tromboembólico moderado (66,1 %). Conclusiones: el sexo que predominó fue el femenino, el grupo etáreo más afectado fue el de más de 85 años, la cardiopatía isquémica fue el antecedente de mayor prevalencia, la fibrilación auricular de tipo persistente fue la más frecuente, las palpitaciones constituyeron el síntoma principal y según la categoría de riesgo tromboembólico la mayoría de los pacientes presentaban riesgo moderado

Twisted bialgebroids versus bialgebroids from Drinfeld twist

Bialgebroids (resp. Hopf algebroids) are bialgebras (Hopf algebras) over noncommutative rings. Drinfeld twist techniques are particularly useful in the (deformation) quantization of Lie algebras as well as underlying module algebras (=quantum spaces). Smash product construction combines these two into the new algebra which, in fact, does not depend on the twist. However, we can turn it into bialgebroid in the twist dependent way. Alternatively, one can use Drinfeld twist techniques in a category of bialgebroids. We show that both techniques indicated in the title: twisting of a bialgebroid or constructing a bialgebroid from the twisted bialgebra give rise to the same result in the case of normalized cocycle twist. This can be useful for better description of a quantum deformed phase space. We argue that within this bialgebroid framework one can justify the use of deformed coordinates (i.e. spacetime noncommutativity) which are frequently postulated in order to explain quantum gravity effects.Comment: 13 pages, version accepted for publicatio

Outcomes of Anatomical versus Functional Testing for Coronary Artery Disease

BACKGROUND: Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care. METHODS: We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure. RESULTS: The mean age of the patients was 60.8±8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3±21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P = 0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P = 0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001). CONCLUSIONS: In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung, and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550.

Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study.</p> <p>Methods/Design</p> <p>STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI) or Health Education Intervention Augmentation (HEI). Both groups will receive TAU (i.e., usual care). The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual) sessions, although other participants may be exercising at the same time. Following the 12-week acute phase, participants will begin a 6-month continuation phase during which time they will attend one weekly supervised DEI or HEI session.</p> <p>Clinical Trials Registry</p> <p>ClinicalTrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01141608">NCT01141608</a></p> <p><url>http://clinicaltrials.gov/ct2/show/NCT01141608?term=Stimulant+Reduction+Intervention+using+Dosed+Exercise&rank=1</url></p