Expanding access to coronary artery bypass surgery: who stands to gain

OBJECTIVE--To determine the perceptions of general practitioners (GPs) about the benefits of coronary artery bypass surgery, in terms of gains in life expectancy, for different groups of patients. DESIGN--A questionnaire survey of all GPs in Northern Ireland. SETTING--A survey conducted collaboratively by the departments of public health medicine in each of the four health boards in the province, serving a total population of 1.5 million. MAIN OUTCOME MEASURES--The median and mean gain in life expectancy perceived by groups of doctors for smoking and non-smoking male and female 55 year old patients. The percentage of 50 year old and 70 year old non-smoking patients considered likely to have their lives extended with bypass surgery. Differences were assessed using the Mann-Whitney U test for unpaired samples and the Wilcoxon signed rank tests for paired. RESULTS--541 GPs replied (response rate 56%). The median (and mean) perceived gain in life expectancy after cardiac surgery for non-smoking 55 year old subjects was 120 (104) months for men and 120 (112) months for women (z = 6.42; P < 0.0001; Wilcoxon signed rank test). For male and female smokers of the same age, the perceived gains were 48 (47) and 60 (52) months respectively (z = 6.72; P < 0.0001; Wilcoxon signed ranks test), both figures being significantly different than for non-smokers. The median (and mean) percentage of patients that the doctors considered would have their lives extended by bypass surgery was 70 (64) of every 100 "young" patients and 40 (42) of every 100 "old" patients, (z = 16.2; P < 0.0001). CONCLUSIONS--These results point to a significant overestimation of the benefits of coronary artery bypass surgery by GPs in Northern Ireland and to a need to develop guidelines for referral

Dynamical Friction in dE Globular Cluster Systems

The dynamical friction timescale for globular clusters to sink to the center of a dwarf elliptical galaxy (dE) is significantly less than a Hubble time if the halos have King-model or isothermal profiles and the globular clusters formed with the same radial density profile as the underlying stellar population. We examine the summed radial distribution of the entire globular cluster systems and the bright globular cluster candidates in 51 Virgo and Fornax Cluster dEs for evidence of dynamical friction processes. We find that the summed distribution of the entire globular cluster population closely follows the exponential profile of the underlying stellar population. However, there is a deficit of bright clusters within the central regions of dEs (excluding the nuclei), perhaps due to the orbital decay of these massive clusters into the dE cores. We also predict the magnitude of each dE's nucleus assuming the nuclei form via dynamical friction. The observed trend of decreasing nuclear luminosity with decreasing dE luminosity is much stronger than predicted if the nuclei formed via simple dynamical friction processes. We find that the bright dE nuclei could have been formed from the merger of orbitally decayed massive clusters, but the faint nuclei are several magnitudes fainter than expected. These faint nuclei are found primarily in M_V > -14 dEs which have high globular cluster specific frequencies and extended globular cluster systems. In these galaxies, supernovae-driven winds, high central dark matter densities, extended dark matter halos, the formation of new star clusters, or tidal interactions may act to prevent dynamical friction from collapsing the entire globular cluster population into a single bright nucleus.Comment: 15 pages, 2 tables, 7 figures; to appear in the Astrophysical Journal, April 20, 200

Design of a DSO-TSO balancing market coordination scheme for decentralised energy

The proliferation of distributed generation and the electrification of heat and transport pose significant challenges to distribution system operators (DSOs) and transmission system operators (TSOs). These challenges include the choice between network upgrades or operating increasingly constrained networks, with a reliance on the flexibility of distributed energy resources (DERs). This study presents a novel market-based coordination scheme, which allows both the DSO and TSO to access DER flexibility, while respecting distribution system limits. The DSO's objective in this work is to minimise the cost incurred by DSO adjustments to DERs, required to ensure stable distribution network operation. The methodology presented has the advantages of being compatible with existing TSO balancing market operation, and scalable enough to include multiple DSO markets coordinating with the TSO. The approach is demonstrated on a section of Great Britain distribution network, using high DER growth scenario data for the year 2030. The case studies demonstrate the proposed DSO market mechanism to maintain thermal and voltage limits during periods of peak demand and DER output. The DSO is given priority in using DERs to solve distribution network constraints, however, significant flexibility remains for the TSO even during periods of peak demand and maximum export

Intervention with citrus flavonoids reverses obesity and improves metabolic syndrome and atherosclerosis in obese Ldlr \u3csup\u3e/\u3c/sup\u3e mice

Copyright © 2018 Burke et al. Obesity and its associated metabolic dysfunction and cardiovascular disease risk represent a leading cause of adult morbidity worldwide. Currently available pharmacological therapies for obesity have had limited success in reversing existing obesity and metabolic dysregulation. Previous prevention studies demonstrated that the citrus flavonoids, naringenin and nobiletin, protect against obesity and metabolic dysfunction in Ldlr/ mice fed a high-fat cholesterol-containing (HFHC) diet. However, their effects in an intervention model are unknown. In this report, we show that, in Ldlr/ mice with diet-induced obesity, citrus flavonoid supplementation to a HFHC diet reversed existing obesity and adipocyte size and number through enhanced energy expenditure and increased hepatic fatty acid oxidation. Caloric intake was unaffected and no evidence of white adipose tissue browning was observed. Reversal of adiposity was accompanied by improvements in hyperlipidemia, insulin sensitivity, hepatic steatosis, and a modest reduction in blood monocytes. Together, this resulted in atherosclerotic lesions that were unchanged in size, but characterized by reduced macrophage content, consistent with a more stable plaque phenotype. These studies further suggest potential therapeutic utility of citrus flavonoids, especially in the context of existing obesity, metabolic dysfunction, and cardiovascular disease

Isostructurality of quinoxaline crystal phases: The interplay of weak hydrogen bonds and halogen bonding

YesTailoring the physical properties of molecular crystals though the construction of solid solutions requires the existence of isostructural crystals. Simple substitutions of a given molecular framework can give a range of different crystal structures. A set of quinoxaline derivatives, C8H4N2(C6H4X)2,Q3,3′X2, has been investigated (X = F, Cl, Br, I and Me) where kinetic factors generated a set of isostructural crystals for the lighter halogens (F, Cl, Br) alone. Computational analysis shows that the stabilising interactions are maximal for Cl, while DSC studies demonstrate the existence of more stable polymorphs for both F and Br containing systems. Steric factors appear to have a lower contribution than the balance of weaker hydrogen and halogen bonding shown by the Me and I containing systems displaying different packing driven by CH⋯N/CH⋯π bonds and I⋯I bonds respectively

Complete mitochondrial genomes and nuclear ribosomal RNA operons of two species of Diplostomum (Platyhelminthes: Trematoda): a molecular resource for taxonomy and molecular epidemiology of important fish pathogens

© 2015 Brabec et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Association of early postresuscitation hypotension with survival to discharge after targeted temperature management for pediatric out-of-hospital cardiac arrest secondary analysis of a randomized clinical trial

© 2017 American Medical Association. All rights reserved. IMPORTANCE Out-of-hospital cardiac arrest (OHCA) occurs in more than 6000 children each year in the United States, with survival rates of less than 10% and severe neurologic morbidity in many survivors. Post-cardiac arrest hypotension can occur, but its frequency and association with survival have not been well described duringtargeted temperature management. OBJECTIVE To determine whether hypotension is associated with survival to discharge in children and adolescents after resuscitation from OHCA. DESIGN, SETTING, AND PARTICIPANTS This post hoc secondary analysis of the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) trial included 292 pediatric patients older than 48 hours and younger than 18 years treated in 36 pediatric intensive care units from September 1,2009, through December 31,2012. Participants underwent therapeutic hypothermia (33.0°C) vs therapeutic normothermia (36.8°C) for 48 hours. All participants had hourly systolic blood pressure measurements documented during the initial 6 hours of temperature intervention. Hourly blood pressures beginning at the time of temperature intervention (time 0) were normalized for age, sex, and height. Early hypotension was defined as a systolic blood pressure less than the fifth percentile during the first 6 hours after temperature intervention. With use of forward stepwise logistic regression, covariates of interest (age, sex, initial cardiac rhythm, any preexisting condition, estimated duration of cardiopulmonary resuscitation [CPR], primary cause of cardiac arrest, temperature intervention group, night or weekend cardiac arrest, witnessed status, and bystander CPR) were evaluated in the final model. Data were analyzed from February 5,2016, through June 13,2017. EXPOSURES Hypotension. MAIN OUTCOMES AND MEASURE Survival to hospital discharge. RESULTS Of 292children (194 boys [66.4%] and 98 girls [33.6%]; medianage, 23.0 months [interquartile range, 5.0-105.0 months]), 78 (26.7%) had at least 1 episode of early hypotension. No difference was observed between the therapeutic hypothermia and therapeutic normothermia groups in the prevalence of hypotension during induction and maintenance (73 of 153 [47.7%] vs 72 of 139 [51.8%]; P = .50) orre warming (35 of 118 [29.7%] vs 19 of 95 [20.0%]; P = .10) during the first 72 hours. Participants who had early hypotension were less likely to survive to hospital discharge (20 of 78 [25.6%] vs 93 of 214 [43.5%]; adjusted odds ratio, 0.39; 95% CI, 0.20-0.74). CONCLUSIONS AND RELEVANCE In this post hoc secondary analysis of the THAPCA trial, 26.7% of participants had hypotension within 6 hours after temperature intervention. Early post-cardiac arrest hypotension was associated with lower odds of discharge survival, even after adjusting for covariates of interest

Peroxisome proliferator-activated receptor δ agonist GW1516 attenuates diet-induced aortic inflammation, insulin resistance, and atherosclerosis in low-density lipoprotein receptor knockout mice

OBJECTIVE - The peroxisome proliferator-activated receptor (PPAR) δ regulates systemic lipid homeostasis and inflammation. However, the ability of PPARδ agonists to improve the pathology of pre-established lesions and whether PPARδ activation is atheroprotective in the setting of insulin resistance have not been reported. Here, we examine whether intervention with a selective PPARδ agonist corrects metabolic dysregulation and attenuates aortic inflammation and atherosclerosis. APPROACH AND RESULTS - Low-density lipoprotein receptor knockout mice were fed a chow or a high-fat, high-cholesterol (HFHC) diet (42% fat, 0.2% cholesterol) for 4 weeks. For a further 8 weeks, the HFHC group was fed either HFHC or HFHC plus GW1516 (3 mg/kg per day). GW1516 significantly attenuated pre-established fasting hyperlipidemia, hyperglycemia, and hyperinsulinemia, as well as glucose and insulin intolerance. GW1516 intervention markedly reduced aortic sinus lesions and lesion macrophages, whereas smooth muscle α-actin was unchanged and collagen deposition enhanced. In aortae, GW1516 increased the expression of the PPARδ-specific gene Adfp but not PPARα- or γ-specific genes. GW1516 intervention decreased the expression of aortic proinflammatory M1 cytokines, increased the expression of the anti-inflammatory M2 cytokine Arg1, and attenuated the iNos/Arg1 ratio. Enhanced mitogen-activated protein kinase signaling, known to induce inflammatory cytokine expression in vitro, was enhanced in aortae of HFHC-fed mice. Furthermore, the HFHC diet impaired aortic insulin signaling through Akt and forkhead box O1, which was associated with elevated endoplasmic reticulum stress markers CCAAT-enhancer-binding protein homologous protein and 78kDa glucose regulated protein. GW1516 intervention normalized mitogen-activated protein kinase activation, insulin signaling, and endoplasmic reticulum stress. CONCLUSIONS - Intervention with a PPARδ agonist inhibits aortic inflammation and attenuates the progression of pre-established atherosclerosis. © 2013 American Heart Association, Inc