Normalized Power Prior Bayesian Analysis

The elicitation of power prior distributions is based on the availability of historical data, and is realized by raising the likelihood function of the historical data to a fractional power. However, an arbitrary positive constant before the like- lihood function of the historical data could change the inferential results when one uses the original power prior. This raises a question that which likelihood function should be used, one from raw data, or one from a su±cient-statistics. We propose a normalized power prior that can better utilize the power parameter in quantifying the heterogeneity between current and historical data. Furthermore, when the power parameter is random, the optimality of the normalized power priors is shown in the sense of maximizing Shannon's mutual information. Some comparisons between the original and the normalized power prior approaches are made and a water-quality monitoring data is used to show that the normalized power prior is more sensible.Bayesian analysis, historical data, normalized power prior, power prior, prior elicitation, Shannon's mutual information.

Saxagliptin in combination with Metformin or Sulfonylurea achieved HbA1c goals

Diabetes affects over 1.2 million people in Australia. Saxagliptin (SAXA) is a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor. Three 24-week phase 3 studies assessed efficacy and safety of SAXA as add-on to Metformin (MET), as initial combination therapy with MET, or as add-on to the sulfonylurea (SU) glyburide (GLY) in patients (pts) with type 2 diabetes (T2D) and inadequate glycaemic control. In the add-on to MET study, 743 pts inadequately controlled on MET alone (HbA1c 7.0%–10.0%; mean baseline (BL) HbA1c 8.0%; mean T2D duration 6.5 yrs) were randomised to SAXA or placebo (PBO) with ongoing dose of MET. In the initial combination study, 1306 drug naïve pts (HbA1c8.0%–12.0%; mean BL HbA1c 9.5%; mean T2D duration 1.7 yrs) were randomised to SAXA + MET, SAXA + PBO, or MET + PBO. In the add-on to SU study, 768 pts inadequately controlled on SU alone (HbA 1c7.5%–10.0%; mean BL HbA1c 8.4%; mean T2D duration 6.9 yrs) were randomised to SAXA or uptitrated GLY + PBO in addition to open-label GLY. Efficacy analyses used ANCOVA model. The proportion of patients reaching HbA1c goals used Fisher exact test. HbA1c goals were predefined for each study. In all three studies, statistically significantly greater proportions of SAXA-treated pts achieved HbA1c goals of <7.0% and ≤6.5% vs. control at 24 wks (Table). Twice as many pts treated with SAXA added to MET or GLY achieved the HbA1c goal of <7% and ≤6.5% relative to control at 24 wks. For all three studies, the frequency of adverse events (AEs) was generally similar for SAXA vs. control (Table). SAXA 5 mg + MET as either add-on or initial combination therapy, and SAXA 5 mg + SU significantly improved glycaemic control, was well tolerated and achieved predefined HbA1c goals vs. control in more patients

β-cell stimulation by saxagliptin in patients with type 2 diabetes

Diabetes is Australia’s fastest growing chronic disease with approximately 890,000 patients currently diagnosed with diabetes.1By 2031 it is predicted that 3.3 million Australians will have type 2 diabetes2thus increasing the demand for prevention strategies and an emphasis on early diagnosis and treatment. Saxagliptin (SAXA) is a potent, selective DPP-4 inhibitor, specifically designed for extended inhibition of the DPP-4 enzyme. DPP-4 inactivates incretins that stimulate glucose-dependent insulin secretion and inhibit glucagon secretion. A proposed MOA of SAXA involves protecting incretins from DPP-4 degradation, thus improving β-cell response. This randomised, parallel-group, double-blind, PBO-controlled study (CV181-041) assessed SAXA’s effect on β-cell function by intravenous hyperglycaemic clamp (IV HC) in T2DM patients. Patients were assessed at baseline (BL) and wk 12 in the fasting state (0-180min, IV HC) and after stimulating incretin secretion by orally ingesting 75g glucose (180-480min, IV-oral HC). HC infusions were adjusted to maintain plasma glucose at 280mg/dL. Insulin secretion was calculated by C-peptide deconvolution. Primary endpoint was %Δfrom BL in total insulin secretion (%Δinsulin) during IV-oral HC (180-480min). Secondary endpoint was %Δinsulin during IV HC (120-180min). Patients were drug-naïve with T2DM aged 43-69yrs with BL A1C range 5.9%-8.1%. Twenty patients received SAXA 5mg od; 16 received PBO. After 12 wks, SAXA significantly increased %Δinsulin from BL during IV-oral HC (adj% difference of 18.5% vs PBO, p=.035). In the fasting state during IV HC SAXA significantly increased %Δinsulin from BL (adj% difference of 27.9% vs PBO, p=.020). At wk 12 insulin secretion increased from BL with SAXA but not with PBO (Fig). Glucagon AUC during IV-oral HC also improved from BL with SAXA, (adj% difference of –21.8% vs PBO, p=.031). SAXA was generally safe and well-tolerated. In conclusion, SAXA improved pancreatic β-cell function in the postprandial and fasting states and decreased postprandial glucagon concentration

Challenges and support needs in psychological and physical health among pilots: a qualitative study

IntroductionPhysical and mental health problems among pilots affect their working state and impact flight safety. Although pilots’ physical and mental health problems have become increasingly prominent, their health has not been taken seriously. This study aimed to clarify challenges and support needs related to psychological and physical health among pilots to inform development of a more scientific and comprehensive physical and mental health system for civil aviation pilots.MethodsThis qualitative study recruited pilots from nine civil aviation companies. Focus group interviews via an online conference platform were conducted in August 2022. Colaizzi analysis was used to derive themes from the data and explore pilots’ experiences, challenges, and support needs.ResultsThe main sub-themes capturing pilots’ psychological and physical health challenges were: (1) imbalance between family life and work; (2) pressure from assessment and physical examination eligibility requirements; (3) pressure from worries about being infected with COVID-19; (4) nutrition deficiency during working hours; (5) changes in eating habits because of the COVID-19 pandemic; (6) sleep deprivation; (7) occupational diseases; (8) lack of support from the company in coping with stress; (9) pilots’ yearly examination standards; (10) support with sports equipment; (11) respecting planned rest time; and (12) isolation periods.DiscussionThe interviewed pilots experienced major psychological pressure from various sources, and their physical health condition was concerning. We offer several suggestions that could be addressed to improve pilots’ physical and mental health. However, more research is needed to compare standard health measures for pilots around the world in order to improve their physical and mental health and contribute to overall aviation safety

A de novo Genome of a Chinese Radish Cultivar

AbstractHere, we report a high-quality draft genome of a Chinese radish (Raphanus sativus) cultivar. This draft contains 387.73Mb of assembled scaffolds, 83.93% of the scaffolds were anchored onto nine pseudochromosomes and 95.09% of 43 240 protein-coding genes were functionally annotated. 184.75Mb (47.65%) of repeat sequences was identified in the assembled genome. By comparative analyses of the radish genome against 10 other plant genomes, 2 275 genes in 780 gene families were found unique to R. sativus. This genome is a good reference for genomic study and of great value for genetic improvement of radish

Spectroscopie rovibronique et rotationnelle de molécules réactives

LILLE1-BU (590092102) / SudocSudocFranceF

Once-daily saxagliptin added to metformin provides sustained glycaemic control and is well tolerated over 102 weeks in patients with type 2 diabetes

Diabetes is Australia’s fastest growing chronic disease with approximately 890,000 patients currently diagnosed with diabetes.1By 2031 it is predicted that 3.3 million Australians will have type 2 diabetes mellitus,2thus increasing the demand for treatment. Saxagliptin (SAXA) is a potent selective DPP-4 inhibitor designed for extended inhibition of the DPP-4 enzyme. The long-term efficacy and safety of SAXA added to metformin were assessed in patients with T2D and inadequate glycaemic control (A1C ≥7.0% −≤10.0%) on metformin alone. For the double-blind (DB) short-term (ST) treatment period 743 patients (baseline [BL] A1C 8.0%) were randomized and treated 1:1:1:1 to SAXA 2.5, 5, 10 mg or placebo od + stable metformin dose (1500−2500mg/d) for 24 weeks. Patients who met pre-specified glycaemic rescue criteria during ST treatment period received open-label pioglitazone 15-45 mg + blinded study medication and entered the DB 42-month long-term extension (LTE). Patients completing ST treatment period without rescue were also eligible to enter the 42mo LTE; pioglitazone rescue therapy was also available during the LTE based on prespecified glycaemic criteria. At 102 weeks placebo-subtracted A1C changes from BL (n/N) were -0.62, -0.72, and -0.52 for SAXA 2.5, 5, and 10mg, respectively. The proportion of patients (n/N) discontinued for lack of glycaemic control or rescued for meeting prespecified glycaemic criteria was lower for SAXA. SAXA + metformin was generally well tolerated; AE frequency was 89.6%, 78.0%, and 86.7% for SAXA 2.5, 5, and 10 mg vs. 78.8% for placebo + metformin. Proportion of patients with hypoglycaemia events (all) was 10.4%, 8.9%, and 11.0% for SAXA 2.5, 5, and 10mg vs. 10.1% for placebo + metformin and confirmed hypoglycaemia was infrequent. In summary, in patients with T2D inadequately controlled on metformin alone SAXA added to metformin provided sustained clinically meaningful glycaemic improvements over 102 weeks vs. control and was generally well tolerated with no increase in hypoglycaemia or weight