Influence of Continuous Casting Speeds on Cast Microstructure and Mechanical Properties of an ADC14 Alloy

To improve the mechanical properties of the casting alloys, various attempts have been made to use alternative casting technologies. The Ohno continuous casting (OCC) process is a unidirectional solidification method, which leads to high-quality cast samples. In this study, the Al-Si-Cu-Mg alloy was cast at casting speeds of 1 mm/s, 2 mm/s, and 3 mm/s, by the OCC process. The aim of this study is to investigate the effects of the casting process parameters, such as casting speeds and cooling conditions, on the crystallization characteristics and mechanical properties of OCC-Al-Si-Cu-Mg alloy. Particularly, secondary dendrite arms spacing of alpha-Al dendrites in OCC samples significantly decreases with increasing casting speed. Moreover, the mean tensile strength of the samples, produced at the highest casting speed of 4.0 mm/s, is significantly higher than that for the samples produced at a casting speed of 1.0 mm/s

Germline genes hypomethylation and expression define a molecular signature in peripheral blood of ICF patients: implications for diagnosis and etiology.

International audienceBACKGROUND: Immunodeficiency Centromeric Instability and Facial anomalies (ICF) is a rare autosomal recessive disease characterized by reduction in serum immunoglobulins with severe recurrent infections, facial dysmorphism, and more variable symptoms including mental retardation. ICF is directly related to a genomic methylation defect that mainly affects juxtacentromeric heterochromatin regions of certain chromosomes, leading to chromosomal rearrangements that constitute a hallmark of this syndrome upon cytogenetic testing. Mutations in the de novo DNA methyltransferase DNMT3B, the protein ZBTB24 of unknown function, or loci that remain to be identified, lie at its origin. Despite unifying features, common or distinguishing molecular signatures are still missing for this disease. METHOD: We used the molecular signature that we identified in a mouse model for ICF1 to establish transcriptional biomarkers to facilitate diagnosis and understanding of etiology of the disease. We assayed the expression and methylation status of a set of genes whose expression is normally restricted to germ cells, directly in whole blood samples and epithelial cells of ICF patients. RESULTS: We report that DNA hypomethylation and expression of MAEL and SYCE1 represent robust biomarkers, easily testable directly from uncultured cells to diagnose the most prevalent sub-type of the syndrome. In addition, we identified the first unifying molecular signatures for ICF patients. Of importance, we validated the use of our biomarkers to diagnose a baby born to a family with a sick child. Finally, our analysis revealed unsuspected complex molecular signatures in two ICF patients suggestive of a novel genetic etiology for the disease. CONCLUSIONS: Early diagnosis of ICF syndrome is crucial since early immunoglobulin supplementation can improve the course of disease. However, ICF is probably underdiagnosed, especially in patients that present with incomplete phenotype or born to families with no affected relatives. The specific and robust biomarkers identified in this study could be introduced into routine clinical immunology or neurology departments to facilitate testing of patients with suspected ICF syndrome. In addition, as exemplified by two patients with a combination of molecular defects never described before, our data support the search for new types of mutations at the origin of ICF syndrome

Swelling behavior of butyl and chloroprene rubber composites with poly (sodium acrylate) showing high water-uptake

金沢大学理工研究域フロンティア工学系Water‐swellable rubber (WSR) comprises super absorbent polymer (SAP) embedded in a rubber matrix and has been commonly used as sealants and caulks, in which high water uptake and sufficient mechanical strength are required. In this work, we investigated the swelling behavior and mechanical properties of rubber composites comprising SAP powders. A reinforcement effect is caused by the SAP particles, which are described using a modified Guth–Gold equation up to the semi‐dilute region. The complex modulus shows upper deviation at high SAP content owing to network formation between SAP particles. The swelling force of the WSR is explained by the amount of SAP particles in the surface layer of the matrix up to the semi‐dilute region. The formation of the SAP network leads to an appreciable increase in the swelling force of WSR, as SAP particles embedded in the matrix also contribute to the swelling of WSR. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48535.Embargo Period 12 month

Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure:Rationale for and design of the EMPA-AHF trial

Aims: The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. Methods: The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate &lt;60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of &lt;300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. Conclusion: The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.</p

Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure:Rationale for and design of the EMPA-AHF trial

Aims: The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. Methods: The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate &lt;60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of &lt;300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. Conclusion: The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.</p

Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure:Rationale for and design of the EMPA-AHF trial

Aims: The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. Methods: The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate &lt;60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of &lt;300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. Conclusion: The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.</p

Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure:Rationale for and design of the EMPA-AHF trial

Aims: The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. Methods: The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate &lt;60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of &lt;300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. Conclusion: The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.</p

Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure:Rationale for and design of the EMPA-AHF trial

Aims: The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. Methods: The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate &lt;60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of &lt;300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. Conclusion: The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.</p

Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure:Rationale for and design of the EMPA-AHF trial

Aims: The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. Methods: The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate &lt;60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of &lt;300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. Conclusion: The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.</p