Glycosylated hemoglobin, but not advanced glycation end products, predicts severity of coronary artery disease in patients with or without diabetes.

Background:The association between coronary artery disease (CAD) and diabetes mellitus (DM) is strong but the physiologic mechanisms responsible for this association remain unclear. Patients with DM exhibit high circulating levels of glycated proteins and lipoproteins called advanced glycation end products (AGEs) which have been implicated in the development of oxidative damage to vascular endothelium. We examined the relationships between the presence and extent of CAD and AGEs in patients undergoing elective coronary artery catheterization in an urban teaching hospital. Methods:Patients with possible CAD (n = 364) were recruited prior to elective cardiac catheterization (52% male, 48% diabetic). Regression and correlation analyses were used to examine the relationship between serum AGE concentrations, soluble AGE receptor (sRAGE) concentration, HbA1c, LDL and the presence of obstructive CAD along with the burden of CAD measured by SYNTAX and SYNTAX II scores. Results:AGE and sRAGE levels did not significantly correlate with any of the studied coronary artery disease parameters. HbA1c showed positive correlation with both SYNTAX and SYNTAX II scores in patients with and without diabetes. Conclusion:In this cross-sectional study of patients with possible CAD, serum AGEs and sRAGE concentrations did not correlate with SYNTAX or SYNTAX II scores regardless of diabetic status. HbA1C correlated positively with the SYNTAX and SYNTAX II scores in both diabetic and non-diabetic populations

Major merging history in CANDELS. I. Evolution of the incidence of massive galaxy–galaxy pairs from z = 3 to z ∼ 0

The rate of major galaxy–galaxy merging is theoretically predicted to steadily increase with redshift during the peak epoch of massive galaxy development (1 ≤ z ≤ 3). We use close-pair statistics to objectively study the incidence of massive galaxies (stellar M1 > 2 × 1010 M⊙) hosting major companions (1 ≤ M1/M2 ≤ 4; i.e. 4:1) companions at z > 1. We show that these evolutionary trends are statistically robust to changes in companion proximity. We find disagreements between published results are resolved when selection criteria are closely matched. If we compute merger rates using constant fraction-to-rate conversion factors (Cmerg,pair = 0.6 and Tobs,pair = 0.65 Gyr), we find that MR rates disagree with theoretical predictions at z > 1.5. Instead, if we use an evolving Tobs,pair(z) ∝ (1 + z)−2 from Snyder et al., our MR-based rates agree with theory at 0 < z < 3. Our analysis underscores the need for detailed calibration of Cmerg,pair and Tobs,pair as a function of redshift, mass, and companion selection criteria to better constrain the empirical major merger history

CANDELS multi-wavelength catalogs: source identification and photometry in the CANDELS COSMOS survey field

We present a multi-wavelength photometric catalog in the COSMOS field as part of the observations by the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey. The catalog is based on Hubble Space Telescope Wide Field Camera 3 (HST/WFC3) and Advanced Camera for Surveys observations of the COSMOS field (centered at R.A.: 10h00m28s, Decl.:+02h12m21s). The final catalog has 38671 sources with photometric data in 42 bands from UV to the infrared (~0.3-8 μm). This includes broadband photometry from HST, CFHT, Subaru, the Visible and Infrared Survey Telescope for Astronomy, and Spitzer Space Telescope in the visible, near-infrared, and infrared bands along with intermediate- and narrowband photometry from Subaru and medium-band data from Mayall NEWFIRM. Source detection was conducted in the WFC3 F160W band (at 1.6 μm) and photometry is generated using the Template FITting algorithm. We further present a catalog of the physical properties of sources as identified in the HST F160W band and measured from the multi-band photometry by fitting the observed spectral energy distributions of sources against templates

Recent Progress in the Use of Glucagon and Glucagon Receptor Antagonists in the Treatment of Diabetes Mellitus

Glucagon is an important pancreatic hormone, released into blood circulation by alpha cells of the islet of Langerhans. Glucagon induces gluconeogenesis and glycogenolysis in hepatocytes, leading to an increase in hepatic glucose production and subsequently hyperglycemia in susceptible individuals. Hyperglucagonemia is a constant feature in patients with T2DM. A number of bioactive agents that can block glucagon receptor have been identified. These glucagon receptor antagonists can reduce the hyperglycemia associated with exogenous glucagon administration in normal as well as diabetic subjects. Glucagon receptor antagonists include isoserine and beta-alanine derivatives, bicyclic 19-residue peptide BI-32169, Des-His1-[Glu9] glucagon amide and related compounds, 5-hydroxyalkyl-4-phenylpyridines, N-[3-cano-6- (1,1 dimethylpropyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]-2-ethylbutamide, Skyrin and NNC 250926. The absorption, dosage, catabolism, excretion and medicinal chemistry of these agents are the subject of this review. It emphasizes the role of glucagon in glucose homeostasis and how it could be applied as a novel tool for the management of diabetes mellitus by blocking its receptors with either monoclonal antibodies, peptide and non-peptide antagonists or gene knockout techniques

How to discuss gene therapy for haemophilia? A patient and physician perspective

Gene therapy has the potential to revolutionise treatment for patients with haemophilia and is close to entering clinical practice. While factor concentrates have improved outcomes, individuals still face a lifetime of injections, pain, progressive joint damage, the potential for inhibitor development and impaired quality of life. Recently published studies in adeno‐associated viral (AAV) vector‐mediated gene therapy have demonstrated improvement in endogenous factor levels over sustained periods, significant reduction in annualised bleed rates, lower exogenous factor usage and thus far a positive safety profile. In making the shared decision to proceed with gene therapy for haemophilia, physicians should make it clear that research is ongoing and that there are remaining evidence gaps, such as long‐term safety profiles and duration of treatment effect. The eligibility criteria for gene therapy trials mean that key patient groups may be excluded, eg children/adolescents, those with liver or kidney dysfunction and those with a prior history of factor inhibitors or pre‐existing neutralising AAV antibodies. Gene therapy offers a life‐changing opportunity for patients to reduce their bleeding risk while also reducing or abrogating the need for exogenous factor administration. Given the expanding evidence base, both physicians and patients will need sources of clear and reliable information to be able to discuss and judge the risks and benefits of treatment