44 research outputs found
Charging Induced Emission of Neutral Atoms from NaCl Nanocube Corners
Detachment of neutral cations/anions from solid alkali halides can in
principle be provoked by donating/subtracting electrons to the surface of
alkali halide crystals, but generally constitutes a very endothermic process.
However, the amount of energy required for emission is smaller for atoms
located in less favorable positions, such as surface steps and kinks. For a
corner ion in an alkali halide cube the binding is the weakest, so it should be
easier to remove that atom, once it is neutralized. We carried out first
principles density functional calculations and simulations of neutral and
charged NaCl nanocubes, to establish the energetics of extraction of
neutralized corner ions. Following hole donation (electron removal) we find
that detachment of neutral Cl corner atoms will require a limited energy of
about 0.8 eV. Conversely, following the donation of an excess electron to the
cube, a neutral Na atom is extractable from the corner at the lower cost of
about 0.6 eV. Since the cube electron affinity level (close to that a NaCl(100)
surface state, which we also determine) is estimated to lie about 1.8 eV below
vacuum, the overall energy balance upon donation to the nanocube of a zero
energy electron from vacuum will be exothermic. The atomic and electronic
structure of the NaCl(100) surface, and of the nanocube Na and Cl corner
vacancies are obtained and analyzed as a byproduct.Comment: 16 pages, 2 table, 7 figure
Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
Background:
Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.
Methods:
We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.
Findings:
Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group.
Interpretation:
In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes.
Funding:
GlaxoSmithKline
Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial
Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials.
Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.
Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.
Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
Mellin Transform for Monomial Functions of the Solution to the General Polynomial System
In the present paper we give the calculation of Mellin transform for the monomial function of the vector-solution to the general polynomial system. We essentially use linearization of the system. In scalar case it defines bijective change of variables. In case of the system of equations we weaken requirements on the mapping given by the linearization: it is proper and its degree is equal to one.В настоящей статье вычисляется преобразование Меллина мономиальной функции решения общей полиномиальной системы. При этом существенно используется линеаризация системы, которая в скалярном случае определяет биективную замену переменной. В случае системы уравнений требования к линеаризации ослаблены: она определяет собственное отображение, степень которого равна единице
On the Set of Convergence for Mellin-Barnes Integral Representing Solutions to the Tetranomial Algebraic Equation
В работе дано детальное описание множества сходимости интеграла Меллина-Барнса, представляющего решения тетраномиального алгебраического уравнения.In the present paper we give the detailed description of the set of convergence for Mellin-Barnes integral
representing solutions to the tetranomial algebraic equation
Adaptation of mathematical educational content in e-learning resources
Modern trends in the world electronic educational system development determine the necessity of adaptive learning intellectual environments and resources’ development and implementation. An upcoming trend in improvement the quality of studying mathematical disciplines is the development and application of adaptive electronic educational resources. However, the development and application experience of adaptive technologies in higher education is currently extremely limited and does not imply the usage flexibility. Adaptive educational resources in the electronic environment are electronic educational resources that provide the student with a personal educational space, filled with educational content that “adapts” to the individual characteristics of the students and provides them with the necessary information.This article focuses on the mathematical educational content adaptation algorithms development and their implementation in the e-learning system. The peculiarity of the proposed algorithms is the possibility of their application and distribution for adaptive e-learning resources construction. The novelty of the proposed approach is the three-step content organization of the adaptive algorithms for the educational content: “introductory adaptation of content”, “the current adaptation of content”, “estimative and a corrective adaptation”. For each stage of the proposed system, mathematical algorithms for educational content adaptation in adaptive e-learning resources are presented.Due to the high level of abstraction and complexity perception of mathematical disciplines, educational content is represented in the various editions of presentation that correspond to the levels of assimilation of the course material. Adaptation consists in the selection of the optimal edition of the material that best matches the individual characteristics of the student. The introduction of a three-step content organization of the adaptive algorithms for the educational content in the adaptive e-learning resource made it possible to implement individual educational paths in the electronic environment. For each student it was formed a personal space of mathematical educational content that “adapts” to its level of mastering the material, which contributed to improving the quality of the educational process in mathematical disciplines.In this paper, the methods of mathematical modeling and logicalgnosiological analysis, the theory of graphs and hypergraphs, system analysis, dynamic processes and systems control theory, complex systems design and imitation modelling methods were used.Approbation of the proposed algorithms for the educational content organization of adaptation in the adaptive electronic learning resource for the discipline “Discrete mathematics” showed the productivity of the proposed approach in the teaching process. The obtained results could be used for adaptive electronic educational resources construction in other educational institutions of higher education.Further development of the proposed approach involves the development of a formal model of the educational content adaptation, including control rules, based on the expert evaluation methods and the fuzzy-set theory
On the Set of Convergence for Mellin-Barnes Integral Representing Solutions to the Tetranomial Algebraic Equation
В работе дано детальное описание множества сходимости интеграла Меллина-Барнса, представляющего решения тетраномиального алгебраического уравнения.In the present paper we give the detailed description of the set of convergence for Mellin-Barnes integral
representing solutions to the tetranomial algebraic equation
Mellin Transform for Monomial Functions of the Solution to the General Polynomial System
In the present paper we give the calculation of Mellin transform for the monomial function of the vector-solution to the general polynomial system. We essentially use linearization of the system. In scalar case it defines bijective change of variables. In case of the system of equations we weaken requirements on the mapping given by the linearization: it is proper and its degree is equal to one.В настоящей статье вычисляется преобразование Меллина мономиальной функции решения общей полиномиальной системы. При этом существенно используется линеаризация системы, которая в скалярном случае определяет биективную замену переменной. В случае системы уравнений требования к линеаризации ослаблены: она определяет собственное отображение, степень которого равна единице