A comparison of the dynamical and model-derived parameters of the pulsating eclipsing binary KIC9850387

We aim to unravel the interior mixing profile of the pulsating eclipsing binary KIC9850387 by comparing its dynamical parameters and the parameters derived through a combination of evolutionary and asteroseismic modelling. We created a grid of stellar evolutionary models using the stellar evolutionary code \textsc{mesa} and performed an isochrone-cloud (isocloud) based evolutionary modelling of the system. We then generated a grid of pulsational models using the stellar pulsation code \textsc{gyre} based on the age constraints from the evolutionary modelling. Finally, we performed asteroseismic modelling of the observed $\ell=1$ and $\ell=2$ period-spacing patterns, utilising different combinations of observational constraints, merit functions, and asteroseismic observables to obtain strong constraints on the interior properties of the primary star. Through a combination of asteroseismic modelling and dynamical constraints, we found that the system comprises two main-sequence components at an age of $1.2\pm0.1$ Gyr. We also observed that asteroseismic modelling provided stronger constraints on the interior properties than evolutionary modelling. Overall, we found high levels of interior mixing and posited that this is a result of intrinsic non-tidal mixing mechanisms due to a similar observed behaviour in single stars. We investigated the high-frequency regime of KIC9850387 and found evidence of the surface effect as well as rotational splitting in the form of a prograde-retrograde dipole g$_{1}$ mode doublet with a missing zonal mode. We find that the dynamical parameters and the parameters extracted from the asteroseismic modelling of period-spacing patterns are only barely compliant, reinforcing the need for homogeneous analyses of samples of pulsating eclipsing binaries that aim to calibrating interior mixing profiles.Comment: 21 pages, 18 figures, accepted for publication in A&

Nε-(Carboxymethyl)lysine and Coronary Atherosclerosis-Associated Low Density Lipoprotein Abnormalities in Type 2 Diabetes: Current Status

In comparison to the general population, individuals with diabetes suffer a 3- to 4-fold increased risk for developing complications of atherosclerosis and vascular insufficiency. This fact should be taken into account to develop a suitable determinant for the early detection of these complications and subsequently reduce the adverse effect of type 2 diabetes. In vitro experiments have shown that the products of glucose auto-oxidation and Amadori adducts are both potential sources of Nε-(carboxymethyl)lysine (CML). Excessive formation of CML on low density lipoprotein (LDL) has been proposed to be an important mechanism for the dyslipidemia and accelerated atherogenesis observed in patients with type 2 diabetes. It has been postulated that the uptake of CML-LDL by LDL receptors is impaired, thereby decreasing its clearance from the blood circulation. Alternatively, the uptake of these modified LDL particles by scavenger receptors on macrophages and vascular smooth muscle cells (SMCs) and by AGE receptors on endothelial cells, SMCs, and monocytes is highly enhanced and this, in turn, is centrally positioned to contribute to the pathogenesis of diabetic vascular complications especially coronary artery disease. The present review summarizes the up-to-date information on effects and mechanism of type 2 diabetes-associated coronary atherosclerosis induced by CML-LDL modification

Role of Nε-(Carboxymethyl)Lysine in the Development of Ischemic Heart Disease in Type 2 Diabetes Mellitus

This study aims to determine the levels of Nε-(carboxymethyl)lysine (CML) in patients with Type 2 diabetic patients with and without ischemic heart disease (IHD) and to find for a possible association between circulating CML and a number of clinical parameters including lipids, hemoglobin A1c (HbA1c) and malondialdehyde (MDA) in Type 2 diabetic IHD patients. Serum CML levels were measured by enzyme-linked immunosorbent assay using polyclonal anti-CML antibodies. Serum levels of CML and MDA were assessed in 60 IHD patients with Type 2 diabetes, 43 IHD patients without Type 2 diabetes, 64 Type 2 diabetics without IHD, and 80 sex- and age-matched healthy subjects. Correlations studies between CML levels and lipids, HbA1c, and lipid peroxidation were performed in Type 2 diabetes patients with and without IHD. A statistical significance was observed in the levels of serum glucose, lipids (triglyceride, total cholesterol, HDL-cholesterol), MDA, HbA1c, CML and LDL-cholesterol (p<0.05) between the groups of the study. CML levels were significantly increased in diabetic IHD patients compared with Type 2 diabetes patients but without IHD (537.1 ± 86.1 vs 449.7 ± 54.9, p<0.001). A positive correlation was observed between serum levels of CML and MDA, r = 0.338 (p = 0.008) in Type 2 diabetes patients with IHD. However, age, HbA1c and lipids had no significant influence on CML levels among diabetics (p>0.05). In conclusion, this study demonstrates the effect of both diabetes and oxidative stress on the higher levels of circulating CML. These results showed that increased serum levels of CML are associated with the development of IHD in Type 2 diabetes mellitus

Providing clinicians with a patient’s 10-year cardiovascular risk improves their statin prescribing: a true experiment using clinical vignettes

Abstract Background Statins are effective for primary prevention of cardiovascular (CV) disease, the leading cause of death in the world. Multinational guidelines emphasize CV risk as an important factor for optimal statin prescribing. However, it’s not clear how primary care providers (PCPs) use this information. The objective of this study was to determine how primary care providers use information about global CV risk for primary prevention of CV disease. Methods A double-blinded, randomized experiment using clinical vignettes mailed to office-based PCPs in the United States who were identified through the American Medical Association Physician Masterfile in June 2012. PCPs in the control group received clinical vignettes with all information on the risk factors needed to calculate CV risk. The experimental group received the same vignettes in addition to the subject’s 10-year calculated CV risk (Framingham risk score). The primary study outcome was the decision to prescribe a statin. Results Providing calculated CV risk to providers increased statin prescribing in the two high-risk cases (CV risk > 20%) by 32 percentage points (41% v. 73%; 95% CI = 23-40, p <0.001; relative risk [RR] = 1.78) and 16 percentage points (12% v. 27%, 95% CI 8.5-22.5%, p <0.001; RR = 2.25), and decreased statin prescribing in the lowest risk case (CV risk = 2% risk) by 9 percentage points [95% CI = 1.00-16.7%, p = 0.003, RR = 0.88]. Fewer than 20% of participants in each group reported routinely calculating 10-year CV risk in their patients. Conclusions Providers do not routinely calculate 10-year CV risk for their patients. In this vignette experiment, PCPs undertreated low LDL, high CV risk patients. Giving providers a patient’s calculated CV risk improved statin prescribing. Providing PCPs with accurate estimates of patient CV risk at the point of service has the potential to improve the efficiency of statin prescribing.http://deepblue.lib.umich.edu/bitstream/2027.42/134534/1/12872_2013_Article_871.pd

Multiple dimensions of excessive daytime sleepiness

Background: In this study we investigated subjective measures of sleepiness and related our findings to dimensions of affect, fatigue, emotion, mood and quality of life based on a hypothetical multidimensional model of sleepiness. Methods: Patients referred to a sleep clinic were assessed regarding their excessive daytime sleepiness (EDS), sleep complaints, routine and symptoms. Age, gender and body mass index (BMI), the Epworth Sleepiness Scale (ESS), the Stanford Sleepiness Scale (SSS), the Samn-Perelli fatigue Scale (SPS), the Global Vigor and Affect Scale (GVS and GAS, respectively), the Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and the Positive and Negative Affect Schedule (PAS and NAS, respectively) scores were recorded. Results: Fifty patients [25 male, 45.2 (18.7) years] completed the questionnaires. The ESS scores were positively correlated with SSS, SPS, HADS-A, HADS-D and NAS scores and negatively with GVS and GAS scores (P<0.05). The SPS (P<0.001) and HADS-A scores (P=0.002) were independently associated with the ESS scores (R2=0.532, adjusted R2 =0.4794, P<0.001). Conclusions: A model of sleepiness that assesses dimensions of fatigue and anxiety could explain the symptom of subjective sleepiness better than the isolated use of the ESS

Minor stroke due to large artery occlusion. When is intravenous thrombolysis not enough? Results from the SITS International Stroke Thrombolysis Register

Purpose: Beyond intravenous thrombolysis, evidence is lacking on acute treatment of minor stroke caused by large artery occlusion. To identify candidates for additional endovascular therapy, we aimed to determine the frequency of non-haemorrhagic early neurological deterioration in patients with intravenous thrombolysis-treated minor stroke caused by occlusion of large proximal and distal cerebral arteries. Secondary aims were to establish risk factors for non-haemorrhagic early neurological deterioration and report three-month outcomes in patients with and without non-haemorrhagic early neurological deterioration. Method: We analysed data from the SITS International Stroke Thrombolysis Register on 2553 patients with intravenous thrombolysis-treated minor stroke (NIH Stroke Scale scores 0–5) and available arterial occlusion data. Non-haemorrhagic early neurological deterioration was defined as an increase in NIH Stroke Scale score ≥4 at 24 h, without parenchymal hematoma on follow-up imaging within 22–36 h. Findings: The highest frequency of non-haemorrhagic early neurological deterioration was seen in 30% of patients with terminal internal carotid artery or tandem occlusions (internal carotid artery + middle cerebral artery) (adjusted odds ratio: 10.3 (95% CI 4.3–24.9), p &#60; 0.001) and 17% in extracranial carotid occlusions (adjusted odds ratio 4.3 (2.5–7.7), p &#60; 0.001) versus 3.1% in those with no occlusion. Proximal middle cerebral artery-M1 occlusions had non-haemorrhagic early neurological deterioration in 9% (adjusted odds ratio 2.1 (0.97–4.4), p = 0.06). Among patients with any occlusion and non-haemorrhagic early neurological deterioration, 77% were dead or dependent at three months. Conclusions: Patients with minor stroke caused by internal carotid artery occlusion, with or without tandem middle cerebral artery involvement, are at high risk of disabling deterioration, despite intravenous thrombolysis treatment. Acute vessel imaging contributes usefully even in minor stroke to identify and consider endovascular treatment, or intensive monitoring at a comprehensive stroke centre, for patients at high risk of neurological deterioration

The SITS-UTMOST: a registry-based prospective study in Europe investigating the impact of regulatory approval of intravenous Actilyse in the extended time window (3–4.5 h) in acute ischaemic stroke

Introduction: The SITS-UTMOST (Safe Implementation of Thrombolysis in Upper Time window Monitoring Study) was a registry-based prospective study of intravenous alteplase used in the extended time window (3–4.5 h) in acute ischaemic stroke to evaluate the impact of the approval of the extended time window on routine clinical practice. Patients and methods: Inclusion of at least 1000 patients treated within 3–4.5 h according to the licensed criteria and actively registered in the SITS-International Stroke Thrombolysis Registry was planned. Prospective data collection started 2 May 2012 and ended 2 November 2014. A historical cohort was identified for 2 years preceding May 2012. Clinical management and outcome were contrasted between patients treated within 3 h versus 3–4.5 h in the prospective cohort and between historical and prospective cohorts for the 3 h time window. Outcomes were functional independency (modified Rankin scale, mRS) 0–2, favourable outcome (mRS 0–1), and death at 3 months and symptomatic intracerebral haemorrhage (SICH) per SITS. Results: 4157 patients from 81 centres in 12 EU countries were entered prospectively (N ¼ 1118 in the 3–4.5 h, N ¼ 3039 in the 0–3 h time window) and 3454 retrospective patients in the 0–3 h time window who met the marketing approval conditions. In the prospective cohort, median arrival to treatment time was longer in the 3–4.5 h than 3 h window (79 vs. 55 min). Within the 3 h time window, treatment delays were shorter for prospective than historical patients (55 vs. 63). There was no significant difference between the 3–4.5 h versus 3 h prospective cohort with regard to percentage of reported SICH (1.6 vs. 1.7), death (11.6 vs. 11.1), functional independency (66 vs. 65) at 3 months or favourable outcome (51 vs. 50). Discussion: Main weakness is the observational design of the study. Conclusion: This study neither identified negative impact on treatment delay, nor on outcome, following extension of the approved time window to 4.5 h for use of alteplase in stroke