127 research outputs found
Experimental study of negative photoconductivity in n-PbTe(Ga) epitaxial films
We report on low-temperature photoconductivity (PC) in n-PbTe(Ga) epitaxial
films prepared by the hot-wall technique on -BaF_2 substrates. Variation
of the substrate temperature allowed us to change the resistivity of the films
from 10^8 down to 10_{-2} Ohm x cm at 4.2 K. The resistivity reduction is
associated with a slight excess of Ga concentration, disturbing the Fermi level
pinning within the energy gap of n-PbTe(Ga). PC has been measured under
continuous and pulse illumination in the temperature range 4.2-300 K. For films
of low resistivity, the photoresponse is composed of negative and positive
parts. Recombination processes for both effects are characterized by
nonexponential kinetics depending on the illumination pulse duration and
intensity. Analysis of the PC transient proves that the negative
photoconductivity cannot be explained in terms of nonequilibrium charge
carriers spatial separation of due to band modulation. Experimental results are
interpreted assuming the mixed valence of Ga in lead telluride and the
formation of centers with a negative correlation energy. Specifics of the PC
process is determined by the energy levels attributed to donor Ga III, acceptor
Ga I, and neutral Ga II states with respect to the crystal surrounding. The
energy level corresponding to the metastable state Ga II is supposed to occur
above the conduction band bottom, providing fast recombination rates for the
negative PC. The superposition of negative and positive PC is considered to be
dependent on the ratio of the densities of states corresponding to the donor
and acceptor impurity centers.Comment: 7 pages, 4 figure
Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial
BACKGROUND
Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH.
METHODS
In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6.
FINDINGS
Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group).
INTERPRETATION
Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.
FUNDING
Intercept Pharmaceuticals
Latitudinal variation in sugar maple fine root respiration
A changing global climate may impact the respiration of fine roots. While many models adjust fine root respiration as temperature increases, the influence of soil nutrient availability and the possibility that root respiration may be adapted to local climate are often not addressed. Rates of fine root respiration were measured in four sugar maple (Acer saccharum Marsh.) forests located along a latitudinal gradient in Michigan. Root respiration was measured as O2 consumption at temperatures ranging from 6 to 24°C on excised fine root samples in early September, October, and November of 1994. Root respiration increased exponentially with temperature with an average Q10 of 2.7; there were no differences in Q10 among sites. However, there were differences among sites in mean respiration rate at a given temperature. This site effect did not indicate ecotypic adaptation to local climate, but rather reflected fine root N concentration. Respiration at a given temperature was consistently higher in roots with higher N concentrations, and higher root N concentrations always occurred at sites having greater N mineralization rates. Results suggest increases in soil temperature could significantly alter root respiration C flux at these sites, as could changes in site N availability associated with chronic N deposition or altered N mineralization resulting from global climate change
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