Perinatal Risk Factors and Later Social, Thought, and Attention Problems after Perinatal Stroke

Objective. Survivors of perinatal stroke may be at risk for behavioral problems. Perinatal risk factors that might increase the likelihood of later behavior problems have not been identified. The goal of this study was to explore whether perinatal factors might contribute to behavior problems after perinatal stroke. Methods. 79 children with unilateral perinatal stroke were studied. Perinatal factors included gender, gestational age, neonatal seizures, instrumented delivery, fetal distress, acute birth problems, birth weight, and time of diagnosis. Subjects with evidence of hypoxic ischemic encephalopathy were excluded. Parents completed the Achenbach Child Behavior Checklist (CBCL) (Achenbach 1985). The CBCL yields T-scores in several symptom scales. We focused on Social, Thought, and Attention Problems scates. Results. Gestational age and the presence of uteroplacental insufficiency were associated with significant differences on the Thought Problems scale; Attention Problems scores approached significance for these variables. Fetal distress, neonatal seizures, or neonatal diagnosis was associated with 25–30% incidence of clinically significant T-scores on Social, Thought, and Attention Problems scales. Conclusions. Several perinatal factors were associated with a high incidence of social, thought, and behavior problems in children with perinatal stroke. These findings may be useful in anticipatory guidance to parents and physicians caring for these children

Parallelization and Visual Analysis of Multidimensional Fields: Application to Ozone Production, Destruction, and Transport in Three Dimensions

The three-dimensional, spectral transport model used in the current project was first successfully integrated over climatological time scales by Dr. Guang Ping Lou for the simulation of atmospheric N2O using the United Kingdom Meteorological Office (UKMO) 4-dimensional, assimilated wind and temperature data set. A non-parallel, FORTRAN version of this integration using a fairly simple N2O chemistry package containing only photo-chemical reactions was used to verify our initial parallel model results. The integrations reproduced the gross features of the observed stratospheric climatological N2O distributions but also simulated the structure of the stratospheric Antarctic vortex and its evolution. Subsequently, Dr. Thomas Kindler, who produced much of the parallel version of our model, enlarged the N2O model chemistry package to include N2O reactions involving O(D-1) and also introduced assimilated wind data from NASA as well as UKMO. Initially, transport calculations without chemistry were run using Carbon-14 as a non-reactive tracer gas with the result that large differences in the transport properties of the two assimilated wind data sets were apparent from the resultant Carbon-14 distributions. Subsequent calculations for N2O, including its chemistry, with the two input winds data sets with verification from UARS satellite observations have refined the transport differences between the two such that the model's steering capabilities could be used to infer the correct climatological vertical velocity fields required to support the N2O observations. During this process, it was also discovered that both the NASA and the UKMO data contained spurious values in some of the higher frequency wave components, leading to incorrect local transport calculations and ultimately affecting the large scale properties of the model's N2O distributions, particularly at tropical latitudes. Subsequent model runs with wind data that had been filtered to remove some of the high frequency components produced much more realistic N2O distributions. During the past few months, the UKMO wind data base for a complete two-year period was processed into spectral form for model use. This new version of the input transport data base now includes complete temperature fields as well as the necessary wind data. This was done to facilitate advanced chemical calculations in the parallel model which often depend upon temperature. Additional UKMO data is being added as it becomes available

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update

Background: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. Methods: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. Results: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still’s disease, Castleman’s disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. Conclusions: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers

A Parallel Spectral Model for Atmospheric Transport Processes

This paper describes a parallel implementation of a grand challenge problem: global atmospheric modeling. The novel contributions of our work include: (1) a detailed investigation of opportunities for parallelism in atmospheric transport based on spectral solution methods, (2) the experimental evaluation of overheads arising from load imbalances and data movement for alternative parallelization methods, and (3) the development of a parallel code that can be monitored and steered interactively based on output data visualizations and animations of program functionality or performance. Code parallelization takes advantage of the relative independence of computations at different levels in the earth's atmosphere, resulting in parallelism of up to 40 processors, each independently performing computations for different atmospheric levels and requiring few communications between different levels across model time steps. Next, additional parallelism is attained within each level by taking adva..

A Parallel Spectral Model for Atmospheric Transport Processes

This paper describes a parallel implementation of a grand challenge problem: global atmospheric modeling. The novel contributions of our work include: (1) a detailed investigation of opportunities for parallelism in atmospheric transport based on spectral solution methods, (2) the experimental evaluation of overheads arising from load imbalances and data movement for alternative parallelization methods, and (3) the development of a parallel code that can be monitored and steered interactively based on output data visualizations and animations of program functionality or performance. Code parallelization takes advantage of the relative independence of computations at different levels in the earth's atmosphere, resulting in parallelism of up to 40 processors, each independently performing computations for different atmospheric levels and requiring few communications between different levels across model time steps. Next, additional parallelism is attained within each level by taking advantage of the natural parallelism offered by the spectral computations being performed (eg., taking advantage of independently computable terms in equations). Performance measurements are performed on a 64-node KSR2 supercomputer. However, the parallel code has been ported to several shared memory parallel machines, including SGI multiprocessors

Perinatal Risk Factors and Later Social, Thought, and Attention Problems after Perinatal Stroke

Objective. Survivors of perinatal stroke may be at risk for behavioral problems. Perinatal risk factors that might increase the likelihood of later behavior problems have not been identified. The goal of this study was to explore whether perinatal factors might contribute to behavior problems after perinatal stroke. Methods. 79 children with unilateral perinatal stroke were studied. Perinatal factors included gender, gestational age, neonatal seizures, instrumented delivery, fetal distress, acute birth problems, birth weight, and time of diagnosis. Subjects with evidence of hypoxic ischemic encephalopathy were excluded. Parents completed the Achenbach Child Behavior Checklist (CBCL