Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries

Objective To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. Study design In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 24(0/7) to 31(6/7) weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed. Results For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany. Conclusions In most countries, mortality decreased whereas BPD increased for neonates born very preterm

Influence of shielding gases on preheat produced in surface coatings incorporating SiC particulates into microalloy steel using TIG technique

The use of a tungsten inert gas (TIG) welding torch has resulted in the development of an economical route for surface engineering of alloys, giving similar results to the more expensive high power laser. Due to the preheating generated by both techniques, the extent of the temperature rise is sufficient to produce significant changes to the melt dimensions, microstructure and properties between the first and last tracks melted during the coating of a complete surface. The present study examines if similar changes can occur between the start and finish locations of a single track of 50 mm length. The results show that for a TIG melted surface of a microalloy steel substrate, with or without incorporating preplaced SiC particles, in either argon or argon-helium environments, a maximum temperature of 375°C developed in the second third of the track. Even over this short distance, a hardness decrease of >300 Hv was recorded in the re-solidified SiC coated substrate melt zone, microstructure of a cast iron with cracks were observed. Also porosity was found in all the tracks, with and without preplaced SiC powders

Vitamin D receptor agonist paricalcitol plus gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer

Background: Patients(pts) with metastatic pancreatic cancer (PC) have a median survival of less than one year even with use of multiagent chemotherapy programs. Pancreatic tumors are composed of multiple cell types and a dense extracellular matrix that may support cancer cell proliferation and impede chemotherapy delivery. Cancer-associated fibroblasts (CAF’s) in the tumor microenvironment secrete pro-inflammatory factors and components of the extracellular matrix. In PC laboratory models, engagement of the vitamin D receptor (VDR) by VDR agonists shifts CAFs toward a more quiescent phenotype with reduced tumor growth and improved chemotherapy penetration (Sherman. Cell, 2014). Paricalcitol is a synthetic VDR agonist used in patients with secondary hyperparathyroidism due to chronic kidney disease. A prior pilot study evaluated IV paricalcitol with gemcitabine (G) and nab-paclitaxel (A) before surgical resection in patients with resectable PC (NCT02030860). Methods: Pts with previously-untreated metastatic PC will be enrolled in a two-stage study consisting of a safety run-in and a randomized phase 2 study (NCT03520790). In the run-in stage, 36 pts will be randomized 1:1:1 to G (1000 mg/m2) and A (125 mg/m2) given 3 weeks on and 1 week off plus: (a) paricalcitol 25mcg IV thrice weekly, (b) paricalcitol 16mcg oral daily, or (c) placebo oral daily. Grade 3/4 hypercalcemia or genitourinary stones will be considered dose limiting toxicities.Pts will undergo paired pre- and on-treatment tumor biopsies to examine pharmacodynamic (PD) markers by bulk and single cell RNA sequencing and multiplex immunofluoresence.Assuming safety and supportive PD assessments, the phase 2 study will randomize an additional 76 pts to two treatment arms with GA plus: (a) paricalcitol or (b) placebo.Paricalcitol formulation (IV or oral) will be determined based on data from the run-in stage.The primary endpoint of the phase 2 study is overall survival, with a total of 100 pts needed to identify a hazard ratio of 0.6 with 80% power and one-sided alpha of 0.10.Secondary endpoints include safety, response rate, and progression free survival.Trial funding provided by SU2C, CRUK,Lustgarten Foundation, and AACR. Clinical trial information: NCT03520790

Long wave length oscillations and the GALLEX solar neutrino signal

The recently reported solar neutrino signal in the $^{71}$Ga GALLEX detector adds a new dimension to the solar neutrino puzzle, complementing the previously known signals in $^{37}$Cl and water-Cherenkov detectors. Possible explanations for this new signal in terms of matter-enhanced neutrino oscillations (MSW effect) are already awaiting in the literature. We point out here that long-wavelength vacuum oscillations can furnish an alternative explanation of all three signals simultaneously; such solutions give neutrino spectra with distinctive energy dependence and seasonal time dependence. %This is a Revtex file, which is Latex-based but depends upon inputting the %Revtex style files distributed by APS/Physical Review. For more information, %contact Peggy Sutherland at [email protected], phone (516) 349-7800 ext 674Comment: 11 pages, 3 figures available by conventional mail or fax, MAD/PH/70