HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study.

BACKGROUND AND OBJECTIVES: There is a need for local anesthetics that provide consistent analgesia through 72 hours after surgery. This study evaluates the use of HTX-011 (bupivacaine and meloxicam in Biochronomerpolymer technology), an extended-release, dual-acting local anesthetic, in reducing both postoperative pain over 72 hours and postoperative opioid use when compared with bupivacaine hydrochloride (HCl) and saline placebo. Inclusion of low-dose meloxicam in HTX-011 is designed to reduce local inflammation caused by surgery, potentiating the analgesic effect of bupivacaine. Previously, significant synergy has been observed with bupivacaine and meloxicam with both given locally together. METHODS: EPOCH 1 was a randomized, double-blind, placebo-controlled and active-controlled phase III study in subjects undergoing a primary unilateral, distal, first metatarsal bunionectomy in which subjects received either a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl or saline placebo. RESULTS: A total of 412 subjects were dosed. The results for the primary and all four key secondary endpoints were statistically significant in favor of HTX-011. HTX-011 demonstrated superior, sustained pain reduction through 72 hours, significantly reduced opioid consumption and resulted in significantly more opioid-free subjects compared with saline placebo and bupivacaine HCl. Safety was similar across groups with fewer opioid-related adverse events observed in the HTX-011 group. CONCLUSIONS: HTX-011 demonstrated significant reduction in postoperative pain through 72 hours with significant reduction in opioid consumption and a significant increase in the proportion of opioid-free subjects compared with saline placebo and the most widely used local anesthetic, bupivacaine HCl. TRIAL REGISTRATION NUMBER: NCT03295721

Shape of initial portion of boundary of supersonic axisymmetric free jets at large jet pressure ratios

Calculations have been made of the initial portion of the boundary of axisymmetric free jets exhausting at large pressure ratios from a conically divergent nozzle having a jet exit Mach number of 2.5 and a semidivergence angle of 15 degrees. The results of the calculations indicate the size and shape of the jet to be expected at large pressure ratios, the effects of ratio of specific heats, and the large initial inclinations of the boundary that are likely to be encountered by hypersonic vehicles at high altitude

Spin symmetry breaking in bilayer quantum Hall systems

Based on the construction of generalized Halperin wave functions, we predict the possible existence of a large class of broken spin symmetry states in bilayer quantum Hall structures, generalizing the recently suggested canted antiferromgnetic phase to many fractional fillings. We develop the appropriate Chern-Simons theory, and establish explicitly that the low-lying neutral excitation is a Goldstone mode and that the charged excitations are bimerons with continuously tunable (through the canted antiferromagnetic order parameter) electric charge on the individual merons.Comment: 4 page

Highly Abundant Proteins Favor More Stable 3D Structures in Yeast

AbstractTo understand the variation of protein sequences in nature, we need to reckon with evolutionary constraints that are biophysical, cellular, and ecological. Here, we show that under the global selection against protein misfolding, there exists a scaling among protein folding stability, protein cellular abundance, and effective population size. The specific scaling implies that the several-orders-of-magnitude range of protein abundances in the cell should leave imprints on extant protein structures, a prediction that is supported by our structural analysis of the yeast proteome

Spatial variations in Chlorophyll a, C, N, and P in a Louisiana estuary from 1994 to 2016

Intense sampling of an estuary can reveal relative spatial changes that are significant irrespective of whether or not the estuary is eutrophic, micro- or meso-tidal, disturbed, or restored. This waterscape\u27 perspective is analogous to a landscape perspective. We collected monthly water samples in the Barataria Basin watershed from 1994 to 2016 at 37 stations along a 129km transect from 1km offshore to a freshwater stream. The average Chlorophyll a (Chl) concentration from 267 trips was supported from both nitrogen-fixing cyanobacteria in a freshwater lake and partially from nutrients in seaward sources. Estuarine salinity was correlated with the discharge of the nearby Mississippi River. The main form of N was as organic nitrogen, not inorganic forms that recycle quickly, making changes in inorganic nitrogen concentration an unreliable indicator of net denitrification or uptake. The total nitrogen (TN) and total phosphorus (TP) concentrations declined with dilution towards the coast, but not because of denitrification. The phytoplankton standing biomass reflected the TN:TP ratio in the water column and there was a significant rise in the variability of Chl concentration at 2-6psu, which was otherwise unremarkably constant. These waterscape patterns and cautionary interpretations may be common to other estuaries

Peak chlorophyll a concentrations in the lower Mississippi River from 1997 to 2018

Large and turbid rivers have varying temperatures, light conditions, nutrient availability, and nutrient ratios that may affect phytoplankton communities and occur within a changing world of point and nonpoint source nutrient loadings. We investigated how these physical and chemical factors affect Chlorophyll a (Chl a) concentrations in the Mississippi River, the largest river in North America, by sampling 878 times from February 1997 to December 2018 near its terminus at Baton Rouge, Louisiana. We hypothesized that nutrient concentrations and ratios were significant factors limiting phytoplankton biomass accumulations in this turbid river. The Chl a concentrations were in the poor water quality category when above 20 mu g Chl a L-1 12% of the time. Two percent of the samples were \u3e 40 mu g Chl a L-1 and occurred on declining discharges. Results from graphical analysis and a principal component regression analysis showed that the highest Chl a values were constrained to when dissolved silicate: dissolved inorganic nitrogen (DIN) molar ratios \u3c 1 : 1 and dissolved DIN : phosphate molar ratios \u3c 16 : 1, which is when the phytoplankton community likely consists of non-siliceous phytoplankton. Increasing light conditions and reducing turbulence, which happens when river water is diverted into calmer and shallower waters, will create a phytoplankton bloom-perhaps becoming a harmful algal bloom-as has happened previously