Multicenter, randomized trial of a bionic pancreas in type 1 diabetes

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P\u3c0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P\u3c0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. CONCLUSIONS: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.)

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Recent trends in the use of electrical neuromodulation in Parkinson's disease

Purpose of Review: This review aims to survey recent trends in electrical forms of neuromodulation, with a specific application to Parkinson’s disease (PD). Emerging trends are identified, highlighting synergies in state-of-the-art neuromodulation strategies, with directions for future improvements in stimulation efficacy suggested. Recent Findings: Deep brain stimulation remains the most common and effective form of electrical stimulation for the treatment of PD. Evidence suggests that transcranial direct current stimulation (tDCS) most likely impacts the motor symptoms of the disease, with the most prominent results relating to rehabilitation. However, utility is limited due to its weak effects and high variability, with medication state a key confound for efficacy level. Recent innovations in transcranial alternating current stimulation (tACS) offer new areas for investigation. Summary: Our understanding of the mechanistic foundations of electrical current stimulation is advancing and as it does so, trends emerge which steer future clinical trials towards greater efficacy

Short and Long-Term Productivity Comparison of Hydraulic Fracturing Fluid Systems in East Texas Cotton Valley Formation

The aim of most hydraulic fracturing treatment is to design and implement the best stimulation strategies that help to increase the short and long-term productivity of the stimulated reservoir section. This can be achieved by selecting the best treatment fluid types that are compatible with the formation to achieve the best combination of fracture geometry and well\u27s productivity. The main objective of this study is to investigate the short and long-term wells\u27 productivity for the different types of hydraulic fracturing treatment fluids in the East Texas Basin Cotton Valley formation. Two hundred and sixty one Cotton Valley wells were identified and selected for this study. All the wells were horizontal and hydraulically fractured that were completed after 2012. The wells were classified based on the type of hydraulic fracturing fluid into four major groups: gel, water, cross-linked gel, and hybrid fracs. The hydraulic fracturing chemicals were obtained from FracFocus public record database. FracFocus data were processed then combined with production and completion data obtained from DrillingInfo database. Several data workflows were developed to classify the treatment fluid types based on the chemical ingredients of each fracturing treatment. The productivity in this paper is reported in terms of equivalent barrel of oil which converts every 6 MCF of gas into 1 equivalent barrel of oil. This paper investigates the Cotton Valley initial production (BOE/Day), cumulative 6 months, 1 year, 2 years, and 5 years and compares the productivity for each type of hydraulic fracturing fluids. This work also provides several insights about the wells performance as a function to stimulation parameters such as the amount of pumped proppant, the volume of pumped water, and the length of the perforated horizontal lateral. The normalized production and stimulation parameters to the perforated lateral are also discussed in this paper. This study discusses several data processing workflows that will help to illustrate the procedures to extract data from FracFocus and DrillingInfo. It provides an understanding of the hydraulic fracturing fluid types\u27 occurrence and measures the effect of stimulation and completion parameters on the short and long-term productivity

ConvKN at SemEval-2016 task 3: Answer and question selection for question answering on Arabic and English fora

We describe our system, ConvKN, participating to the SemEval-2016 Task 3 "Community Question Answering". The task targeted the reranking of questions and comments in real-life web fora both in English and Arabic. ConvKN combines convolutional tree kernels with convolutional neural networks and additional manually designed features including text similarity and thread specific features. For the first time, we applied tree kernels to syntactic trees of Arabic sentences for a reranking task. Our approaches obtained the second best results in three out of four tasks. The only task we performed averagely is the one where we did not use tree kernels in our classifier

ConvKN at SemEval-2016 task 3: Answer and question selection for question answering on Arabic and English fora

We describe our system, ConvKN, participating to the SemEval-2016 Task 3 "Community Question Answering". The task targeted the reranking of questions and comments in real-life web fora both in English and Arabic. ConvKN combines convolutional tree kernels with convolutional neural networks and additional manually designed features including text similarity and thread specific features. For the first time, we applied tree kernels to syntactic trees of Arabic sentences for a reranking task. Our approaches obtained the second best results in three out of four tasks. The only task we performed averagely is the one where we did not use tree kernels in our classifier

Non-pylori Helicobacteraceae in the upper digestive tract of asymptomatic venezuelan subjects: Detection of helicobacter cetorum-like and candidatus Wolinella africanus-like DNA

Background: The spectrum of human non-pylori Helicobacter infections is expanding, with species such as H. heilmannii and H. felis occasionally being associated with gastritis. However, the existence of non-pylori Helicobacter colonization in asymptomatic subjects has not been evaluated. The aim of this study was to investigate whether Helicobacter species other than pylori are present in the upper digestive tract of asymptomatic human subjects. Materials and methods: A Helicobacteraceae-specific semi-nested polymerase chain reaction (PCR) assay was used to detect Helicobacter-like organisms in the upper digestive tract of 91 Venezuelan volunteers (aged 18-68 years, 41 females, 50 males). Species were identified by denaturing gradient gel electrophoresis analysis and sequencing of the PCR products. Results: We detected DNA sharing 99-100% sequence identity in over 300-400 bp with the 16S rRNA genes of H. pylori, H. cetorum, and Candidatus Wolinella africanus in 76%, 16%, and 15% of the subjects, respectively. Multiple colonization was documented in 10% of the subjects: H. cetorum and Candidatus W. africanus (4%), H. pylori and Candidatus W. africanus (4%), and H. pylori and H. cetorum (2%). Conclusions: Our results suggest that non-pylori Helicobacteraceae colonization is relatively common in the Venezuelan asymptomatic population. This is the first report documenting the presence of H. cetorum DNA in the human upper digestive tract, and the second report of the recently discovered Candidatus W. africanus

Analysis of ERCC1 and ERCC2 gene variants in osteosarcoma, colorectal and breast cancer

CONACYT [SALUD 2011-C01-162100