24 research outputs found
Simulation of high-speed interaction between impactor and layered-spaced design involving explosive
In this paper we present calculating and experimental study of high-speed interaction between explosive content, protected by layered-spaced design, and the cermet impactor in wide speed range. An experimental technique and mathematical model of during the behavior of explosives, protected by layer-spaced design, by with high-speed impact. The process of the interaction between the cermet impactor and element of the protective design is customized and depends on the materials of the interacting bodies, the speed and angle of impact
Experimental and theoretical research of the interaction between high-strength supercavitation impactors and monolithic barriers in water
The article describes experimental and theoretical research of the interaction between supercavitating impactors and underwater aluminum alloy and steel barriers. Strong alloys are used for making impactors. An experimental research technique based on a high-velocity hydro-ballistic complex was developed. Mathematical simulation of the collision the impactor and barrier is based on the continuum mechanics inclusive of the deformation and destruction of interacting bodies. Calculated and experimental data on the ultimate penetration thickness of barriers made of aluminum alloy D16T and steel for the developed supercavitating impactor are obtained
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
Glomerular matrix metalloproteinases and their regulators in the pathogenesis of lupus nephritis
Lupus nephritis is a major contributor to morbidity and mortality in
systemic lupus erythematosus, but little is known about the
pathogenic processes that underlie the progressive decay in renal
function. A common finding in lupus nephritis is thickening of
glomerular basement membranes associated with immune complex
deposition. It has been speculated that alterations in the synthesis
or degradation of membrane components might contribute to such
changes, and thereby to initiation and progression of nephritis
through facilitation of immune complex deposition. Matrix metalloproteinases
(MMPs) are enzymes that are intimately involved in the
turnover of major glomerular basement membrane constituents,
including collagen IV and laminins. Alterations in the expression
and activity of MMPs have been described in a number of renal
diseases, suggesting their relevance to the pathogenesis of various
glomerulopathies. The same is true for their natural inhibitors, the
tissue inhibitor of metalloproteinase family. Recent data from our
group have identified an increase in proteolytic activity within the
glomerulus coinciding with the development of proteinuria in the
(NXB×NZW)F1 mouse model of systemic lupus erythematosus.
Here we review current understanding of MMP/tissue inhibitor of
metalloproteinase function within the kidney, and discuss their
possible involvement in the development and progression of lupus
nephritis
Metabolomics to Diagnose Oxidative Stress in Perinatal Asphyxia: Towards a Non-Invasive Approach
There is a need for feasible and non-invasive diagnostics in perinatal asphyxia. Metabolomics is the study of small molecular weight products of cellular metabolism that may, directly and indirectly, reflect the level of oxidative stress. Saliva analysis is a novel approach that has a yet unexplored potential in metabolomics in perinatal asphyxia. The aim of this review was to give an overview of metabolomics studies of oxidative stress in perinatal asphyxia, particularly searching for studies analyzing non-invasively collected biofluids including saliva. We searched the databases PubMed/Medline and included 11 original human and 4 animal studies. In perinatal asphyxia, whole blood, plasma, and urine are the most frequently used biofluids used for metabolomics analyses. Although changes in oxidative stress-related salivary metabolites have been reported in adults, the utility of this approach in perinatal asphyxia has not yet been explored. Human and animal studies indicate that, in addition to antioxidant enzymes, succinate and hypoxanthine, as well acylcarnitines may have discriminatory diagnostic and prognostic properties in perinatal asphyxia. Researchers may utilize the accumulating evidence of discriminatory metabolic patterns in perinatal asphyxia to develop bedside methods to measure oxidative stress metabolites in perinatal asphyxia. Although only supported by indirect evidence, saliva might be a candidate biofluid for such point-of-care diagnostics
Simulation of high-speed interaction between impactor and layered-spaced design involving explosive
In this paper we present calculating and experimental study of high-speed interaction between explosive content, protected by layered-spaced design, and the cermet impactor in wide speed range. An experimental technique and mathematical model of during the behavior of explosives, protected by layer-spaced design, by with high-speed impact. The process of the interaction between the cermet impactor and element of the protective design is customized and depends on the materials of the interacting bodies, the speed and angle of impact
Experimental and theoretical research of the interaction between high-strength supercavitation impactors and monolithic barriers in water
The article describes experimental and theoretical research of the interaction between supercavitating impactors and underwater aluminum alloy and steel barriers. Strong alloys are used for making impactors. An experimental research technique based on a high-velocity hydro-ballistic complex was developed. Mathematical simulation of the collision the impactor and barrier is based on the continuum mechanics inclusive of the deformation and destruction of interacting bodies. Calculated and experimental data on the ultimate penetration thickness of barriers made of aluminum alloy D16T and steel for the developed supercavitating impactor are obtained