12 research outputs found
Photoisomerization and Photocyclization of 5-Styryloxazole
This paper describes the competition of the relaxation processes (fluorescence, isomerization and cyclization) of 5-styryloxazole in the first excited singlet state. The study is carried out under mild conditions and in the first stage of irradiation to compare the photobehaviour with that reported in a previous work on preparative scale. The quantum yields of the radiative and reactive deactivation are compared with those of the analogous compounds containing pentatomic heteroaryl groups
Ertugliflozin and Slope of Chronic eGFR: Prespecified Analyses from the Randomized VERTIS CV Trial
Background and objectives A reduction in the rate of eGFR decline, with preservation of $0.75 ml/min per 1.73 m2
per year, has been proposed as a surrogate for kidney disease progression. We report results from prespecified
analyses assessing effects of ertugliflozin versus placebo on eGFR slope from the eValuation of ERTugliflozin
effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881).
Design, setting, participants, & measurements Patients with type 2 diabetes mellitus and established
atherosclerotic cardiovascular disease were randomized to placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg
(1:1:1). The analyses compared the effect of ertugliflozin (pooled doses, n55499) versus placebo (n52747) on eGFR
slope per week and per year by random coefficient models. Study periods (weeks 0–6 and weeks 6–52) and total
and chronic slopes (week 0 or week 6 to weeks 104, 156, 208, and 260) were modeled separately and by baseline
kidney status.
Results In the overall population, for weeks 0–6, the least squares mean eGFR slopes (ml/min per 1.73 m2 per week
[95% confidence interval (95% CI)]) were 20.07 (20.16 to 0.03) and 20.54 (20.61 to 20.48) for the placebo and
ertugliflozin groups, respectively; the difference was 20.47 (20.59 to 20.36). During weeks 6–52, least squares
mean eGFR slopes (ml/min per 1.73 m2 per year [95% CI]) were 20.12 (20.70 to 0.46) and 1.62 (1.21 to 2.02) for the
placebo and ertugliflozin groups, respectively; the difference was 1.74 (1.03 to 2.45). For weeks 6–156, least squares
mean eGFR slopes (ml/min per 1.73 m2 per year [95% CI]) were 21.51 (21.70 to 21.32) and 20.32 (20.45 to 20.19)
for the placebo and ertugliflozin groups, respectively; the difference was 1.19 (0.95 to 1.42). During weeks 0–156, the
placebo-adjusted difference in least squares mean slope was 1.06 (0.85 to 1.27). These findings were consistent by
baseline kidney status.
Conclusions Ertugliflozin has a favorable placebo-adjusted eGFR slope .0.75 ml/min per 1.73 m2 per year,
documenting the kidney function preservation underlying the clinical benefits of ertugliflozin on kidney disease
progression in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease.
Clinical Trial registry name and registration number: US National Library of Medicine, ClinicalTrials.gov
NCT01986881. Date of trial registration: November 13, 2013
Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial
Aims/hypothesis In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time
to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared
with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data
from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881).
Methods Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin
5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney
composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline,
renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine
with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio
(UACR) and eGFR over time was assessed.
Results A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite
outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event
rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66
(0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were
−16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in
UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and
Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups.
Conclusions/interpretation Among individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for
the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR.
Trial registration ClinicalTrials.gov NCT0198688
Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes
BACKGROUND
The cardiovascular effects of ertugliflozin, an inhibitor of sodium–glucose cotransporter 2, have not been established.
METHODS
In a multicenter, double-blind trial, we randomly assigned patients with type 2 diabetes and atherosclerotic cardiovascular disease to receive 5 mg or 15 mg of ertugliflozin or placebo once daily. With the data from the two ertugliflozin dose
groups pooled for analysis, the primary objective was to show the noninferiority of
ertugliflozin to placebo with respect to the primary outcome, major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The noninferiority margin was 1.3 (upper
boundary of a 95.6% confidence interval for the hazard ratio [ertugliflozin vs. placebo] for major adverse cardiovascular events). The first key secondary outcome was
a composite of death from cardiovascular causes or hospitalization for heart failure.
RESULTS
A total of 8246 patients underwent randomization and were followed for a mean
of 3.5 years. Among 8238 patients who received at least one dose of ertugliflozin
or placebo, a major adverse cardiovascular event occurred in 653 of 5493 patients
(11.9%) in the ertugliflozin group and in 327 of 2745 patients (11.9%) in the placebo group (hazard ratio, 0.97; 95.6% confidence interval [CI], 0.85 to 1.11;
P<0.001 for noninferiority). Death from cardiovascular causes or hospitalization
for heart failure occurred in 444 of 5499 patients (8.1%) in the ertugliflozin group
and in 250 of 2747 patients (9.1%) in the placebo group (hazard ratio, 0.88; 95.8% CI,
0.75 to 1.03; P=0.11 for superiority). The hazard ratio for death from cardiovascular causes was 0.92 (95.8% CI, 0.77 to 1.11), and the hazard ratio for death from
renal causes, renal replacement therapy, or doubling of the serum creatinine level
was 0.81 (95.8% CI, 0.63 to 1.04). Amputations were performed in 54 patients (2.0%)
who received the 5-mg dose of ertugliflozin and in 57 patients (2.1%) who received
the 15-mg dose, as compared with 45 patients (1.6%) who received placebo.
CONCLUSIONS
Among patients with type 2 diabetes and atherosclerotic cardiovascular disease,
ertugliflozin was noninferior to placebo with respect to major adverse cardiovascular
events. (Funded by Merck Sharp & Dohme and Pfizer; VERTIS CV ClinicalTrials.gov
number, NCT01986881.)
Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial (VERTIS-CV)
Background Ertugliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), approved in the United States and
European Union to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). The VERTIS cardiovascular (CV)
outcomes trial (NCT01986881) has a primary objective to demonstrate non-inferiority of ertugliflozin versus placebo on major
adverse CV events: time to the first event of CV death, nonfatal myocardial infarction, or nonfatal stroke. Secondary objectives
are to demonstrate superiority of ertugliflozin versus placebo on time to: 1) the composite outcome of CV death or
hospitalization for heart failure (HF); 2) CV death; and 3) the composite outcome of renal death, dialysis/transplant, or
doubling of serum creatinine from baseline.
Methods Patients ≥40 years old with T2DM (HbA1c 7.0–10.5%) and established atherosclerotic cardiovascular disease
(ASCVD) of the coronary, cerebral, and/or peripheral arterial systems, were randomized 1:1:1 to once daily double-blind
placebo, ertugliflozin 5 mg or 15 mg added to existing therapy.
Results 8246 patients were randomized and 8238 received at least 1 dose of investigational product. Mean age was
64.4 years, 11.0% were ≥75 years old, and mean diabetes duration was 12.9 years with screening HbA1c of 8.3%. At entry,
coronary artery disease, cerebrovascular disease, and peripheral arterial disease were present in 76.3%, 23.1%, and 18.8%
of patients, respectively. HF was present in 23.1%, and Stage 3 kidney disease in 21.6% of patients.
Conclusion The results from the VERTIS-CV trial will define the CV and renal safety and efficacy of ertugliflozin in patients
with T2DM and ASCVD. (Am Heart J 2018;206:11-23.
Моделювання моментів, обумовлених дією атмосферної турбулентності на крило літака
We have used Diederich’s theory of wingspan average correlation functions to obtain analytical expressions for the local spectral density of aircraft wing moments induced by horizontal and vertical wind gusts. We have assumed that the correlation functions of atmospheric turbulence belong to the Bullen family which includes both partial cases of known Dryden’s model as well as von Karman’s model.На основе метода усредненных по размаху крыла корреляционных функций Дидериха получены аналитические выражения для локальных спектральных плотностей моментов крыла самолета, обусловленных горизонтальными и вертикальными порывами ветра. Допущено, что корреляционные функции атмосферной турбулентности относятся к семейству Буллена, которое включает как частные случаи известные модели турбулентности Драйдена и фон Кармана.На основі методу усереднених за розмахом крила кореляційних функцій Дідеріха отримано аналітичні вирази для локальних спектральних щільностей моментів крила літака, обумовлених горизонтальними і вертикальними поривами вітру. Припущено, що кореляційні функції атмосферної турбулентності належать до сім’ї Булена, яка включає як частинні випадки відомі моделі турбулентності Драйдена і фон Кармана
Study of Motivations for Systematic Exercises of Physical Exercises of Mature Women of Mature Age
Дані теоретичного дослідження приставлені питанню вивчення мотивів до занять фізичними вправами. У статті розкрито суть питання напрямку занять фітнесом на організм жінок. У статті проаналізовано й узагальнено питання вивчення мотивів до систематичних занять фізичними вправами жінок зрілого віку.The data of the theoretical research are attached to the question of studying the motives for physical exercises. The article reveals the essence of the issue of the direction of fitness classes for women. The article analyzes and generalizes the study of motives for regular physical exercise of mature women
Electrospray sample injection for single-particle imaging with x-ray lasers
The possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization. Here, we show that, with our electrospray injector, we can decrease the size of aerosol droplets and demonstrate virtually contaminant-free sample delivery of organelles, small virions, and proteins. The results presented here, together with the increased performance of next-generation x-ray lasers, constitute an important stepping stone toward the ultimate goal of protein structure determination from imaging at room temperature and high temporal resolution