Upadacitinib treatment improves symptoms of bowel urgency and abdominal pain, and correlates with quality of life improvements in patients with moderate to severe ulcerative colitis

Bowel urgency and abdominal pain are impactful, yet underappreciated ulcerative colitis symptoms and not commonly assessed in clinical trials. We evaluated how these symptoms may improve with upadacitinib treatment and correlate with clinical and health-related quality of life (HRQOL) outcomes in the phase 2b U-ACHIEVE study. Patients aged 18-75 years with moderately to severely active ulcerative colitis were randomised to receive placebo or upadacitinib (7.5, 15, 30, or 45 mg QD). Bowel urgency and abdominal pain were evaluated at baseline and Weeks 2, 4, 6, and 8. Week 8 correlations were evaluated between bowel urgency/abdominal pain with clinical (Mayo subscores, and high-sensitivity C-reactive protein and faecal calprotectin measurements) and HRQOL outcomes (Inflammatory Bowel Disease Questionnaire and 36-Item Short Form Health Survey scores). A greater proportion of patients (N = 250) reported no bowel urgency and less abdominal pain with upadacitinib treatment compared to placebo, with improvements observed as early as 2 weeks. At Week 8, patients receiving the 45-mg QD dose had the greatest improvements versus placebo, with 46% reporting no bowel urgency (vs 9%; P =0.001) and 38% reporting no abdominal pain (vs 13%; P = 0.015). At Week 8, moderate correlations were found between bowel urgency or abdominal pain and most clinical and HRQOL outcomes. Induction treatment with upadacitinib demonstrated significant reductions in bowel urgency and abdominal pain compared to placebo. These symptoms also correlate to clinical and HRQOL outcomes, supporting their use to monitor disease severity and other treatment outcomes

An interferon-free antiviral regimen for HCV after liver transplantation.

Background Hepatitis C virus (HCV) infection is the leading indication for liver transplantation worldwide, and interferon-containing regimens are associated with low response rates owing to treatment-limiting toxic effects in immunosuppressed liver-transplant recipients. We evaluated the interferon-free regimen of the NS5A inhibitor ombitasvir coformulated with the ritonavir-boosted protease inhibitor ABT-450 (ABT-450/r), the nonnucleoside NS5B polymerase inhibitor dasabuvir, and ribavirin in liver-transplant recipients with recurrent HCV genotype 1 infection. Methods We enrolled 34 liver-transplant recipients with no fibrosis or mild fibrosis, who received ombitasvir-ABT-450/r (at a once-daily dose of 25 mg of ombitasvir, 150 mg of ABT-450, and 100 mg of ritonavir), dasabuvir (250 mg twice daily), and ribavirin for 24 weeks. Selection of the initial ribavirin dose and subsequent dose modifications for anemia were at the investigator's discretion. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment. Results Of the 34 study participants, 33 had a sustained virologic response at post-treatment weeks 12 and 24, for a rate of 97% (95% confidence interval, 85 to 100). The most common adverse events were fatigue, headache, and cough. Five patients (15%) required erythropoietin; no patient required blood transfusion. One patient discontinued the study drugs owing to adverse events after week 18 but had a sustained virologic response. Blood levels of calcineurin inhibitors were monitored, and dosages were modified to maintain therapeutic levels; no episode of graft rejection was observed during the study. Conclusions Treatment with the multitargeted regimen of ombitasvir-ABT-450/r and dasabuvir with ribavirin was associated with a low rate of serious adverse events and a high rate of sustained virologic response among liver-transplant recipients with recurrent HCV genotype 1 infection, a historically difficult-to-treat populatio

Bayesian phylogenetic model selection and applications

The Bayes factor is commonly used for comparing different evolutionary rate models and different topologies in phylogeny. It is crucial to develop efficient Monte Carlo methods for estimating the marginal likelihoods in the Bayes factor. The Monte Carlo methods currently advocated in the phylogenetic literature include the harmonic mean (HM) method and the thermodynamic integration or path sampling (PS) method. However, these two methods may not be able to provide accurate estimates of the marginal likelihoods due to the complexity of the phylogenetic models. In this research work, we develop several new Monte Carlo methods including stepping stone (SS) method and bridge stepping stone (BSS) method, as well as better choices of the path parameter to overcome the limitations of current available methods. In addition to Bayes factor, we also investigate other attractive model comparison criteria, such as deviance information criterion (DIC) and conditional predictive ordinate (CPO) to compare different models and examine sensitivity of priors in phylogenetics. We further extend the SS method to other statistical applications. One of such applications is to compute marginal likelihoods of regression models for binary response data with different links, including logit, complementary log-log, and generalized t links. The marginal likelihoods are used for guiding the choice of links.

Development and implementation of a viscoplastic model for air plasma sprayed thermal barrier coatings

Thermal barrier coatings (TBCs) are widely used in gas turbines to reduce the temperature in hot components, which allow a combination of increased part life and improved system performance. Experiments have shown that plasma sprayed ceramic coatings exhibit large tension-compression flow stress asymmetry and rate-dependent deformation behaviors. While in recent years there has been extensive activity in the analytical and numerical simulation of TBC behaviors, none of the research has focused on the realistic behavior of TBCs mentioned above. Instead, simple elastic and a few elastic-plastic models have been used. The purpose of this study is to investigate and implement a realistic viscoplastic model for a plasma sprayed ceramic TBC. Temperature-dependent material constants in the model are found for a specific material using a novel approach based on genetic algorithm. A finite element simulation of a plasma sprayed TBC system represented as a three-layer structure with an interface asperity is presented. The validity of results obtained using simpler and more convenient nonlinear constitutive models for the TBC is assessed by comparison. It is shown that elastic residual stresses at room temperature never become large enough to propagate asperity size scale cracks based on linear elastic fracture mechanics. Failure may need to be described in terms of volumetric damage associated with exceeding the limit stress of the TBC.

Data from: Posterior predictive Bayesian phylogenetic model selection

We present two distinctly different posterior predictive approaches to Bayesian phylogenetic model selection, and illustrate these methods using examples from green algal protein-coding cpDNA sequences and flowering plant rDNA sequences. The Gelfand-Ghosh (GG) approach allows dissection of an overall measure of model fit into components due to posterior predictive variance (Pm) and goodness-of-fit (Gm), which distinguishes this method from the posterior predictive P-value approach. The conditional predictive ordinate (CPO) method provides a site-specific measure of model fit useful for exploratory analyses and can be combined over sites yielding the log pseudomarginal likelihood (LPML), which is useful as an overall measure of model fit. CPO provides a useful cross-validation approach that is computationally efficient, requiring only a sample from the posterior distribution (no additional simulation is required). Both GG and CPO add new perspectives to Bayesian phylogenetic model selection based on the predictive abilities of models, and complement the perspective provided by the marginal likelihood (including Bayes Factor comparisons) based solely on the fit of competing models to observed data

Surgical Treatment and Prognosis for Patients with Synchronous Multiple Primary Lung Adenocarcinomas

Background and objective With the popularization of high-resolution computed tomography (HRCT), there is a rising trend of the detection of multiple primary lung cancers (MPLC). Adenocarcinomas is the major pathological type of MPLC. At present, reports on MPLC are relatively common, but few study focused on synchronous multiple primary lung adenocarcinomas (SMPLA). We carried out this study in an attempt to enhance our understanding about SMPLA. Methods Data from 38 patients undergoing surgery for SMPLA in our institution frrom December 2012 and July 2016 were retrospectively collected. Results Among the 38 patients, 12 patients were male, 26 patients were female, with a median age of 58 (ranging from 39 to 73). Surgical outcomes verified 29 patients with 2 tumors and 9 patients with more than 2 tumors. There were 26 patients with tumors in ipsilateral lung while 12 patients in contralateral lung. Eight patients underwent one-stage surgical treatment for contralateral tumors with mean postoperative hospitalization of 10 days. The gene detection results of 5 patients showed different epidermal growth factor receptor (EGFR) mutations can be found in one patient’s different tumors. The 1-year and 3-year overall survival (OS) rate were 96.6% and 74.2%. Larger maximal tumor dimension (P<0.001), advanced pT stage (P=0.003), lymph nodes metastases positive (P=0.001), advanced TNM stage (P=0.022) and postoperative adjuvant chemoradiotherapy (P=0.009) were correlated with poor OS. Conclusion Multiple lung malignant lesions should not be taken as metastasis for granted and the possibility of MPLC also should be considered. Mutational status of EGFR could be used as a clinical reference to diagnose patients with SMPLA

sphaero-4gene

Extracted from: http://treebase.org/ study id 1166