Additive Beneficial Effects of Beta-Blockers to Angiotensin-Converting Enzyme Inhibitors in the Survival and Ventricular Enlargement (SAVE) Study fn1fn1This study was supported by a University-Industry grant from the Medical Research Council, Ottawa, Ontario, Canada and Bristol Myers Squibb, Montreal, Quebec, Canada.

AbstractObjectives. This study assessed whether treatment with a beta-adrenergic blocking agent in addition to the use of the angiotensin-converting enzyme (ACE) inhibitor captopril decreases cardiovascular mortality and morbidity in patients with asymptomatic left ventricular dysfunction after myocardial infarction (MI) and whether the presence of neurohumoral activation at the time of hospital discharge predicts the effects of beta-blocker treatment in these patients.Background. Both beta-blockers and ACE inhibitors have been shown to have beneficial effects in patients with left ventricular dysfunction but no overt heart failure after MI. These patients often have persistent neurohumoral activation at the time of hospital discharge, and one would expect that patients with activation of the sympathetic nervous system derive the most benefit from treatment with beta-blockers. However, beta-blockers are underutilized in this high risk group of patients, and it is unknown whether their beneficial effects are additive to those of ACE inhibitors.Methods. We performed a retrospective analysis of data from the Survival and Ventricular Enlargement (SAVE) study and its neurohumoral substudy. The relations between beta-blocker use at the time of randomization and neurohumoral activation and the subsequent development of cardiovascular events were analyzed by use of Cox proportional hazards models controlling for covariates.Results. After adjustment for baseline imbalances, beta-blocker use was associated with a significant reduction in risk of cardiovascular death (30%, 95% confidence interval [CI] 12% to 44%) and development of heart failure (21%, 95% CI 3% to 36%), but the reduction in recurrent MI (11%, 95% CI 13% to 31%) was not significant. These reductions were independent of the use of captopril. Beta-blockers were not found to have a greater effect in patients with neurohumoral activation at the time of hospital discharge.Conclusions. The beneficial effects of beta-blocker use at the time of hospital discharge in patients with asymptomatic left ventricular dysfunction after MI appear to be additive to those of captopril and other interventions known to improve prognosis. Neurohumoral activation at the time of hospital discharge fails to identify those patients who will derive the greatest benefit from treatment with beta-blockers.(J Am Coll Cardiol 1997;29:229–36

Mid-infrared VISIR and Spitzer observations of the surroundings of the magnetar SGR 1806-20

We report mid-infrared observations of SGR 1806-20 and its environment - with the highest spatial resolution in this domain to date - using ESO/VISIR in 2005 and 2006, and we retrieved Spitzer/IRAC-MIPS archival data of the same field. We aimed at studying the mid-infrared emission of the stars associated with the same cluster as SGR 1806-20, to detect variations that could be due to the high-energy activity of the magnetar through interaction with the dust. We also aimed at studying the morphology of the cloud close to the centre of the cluster. We performed broadband photometry of three stars - LBV 1806-20, a WC9 and an O/B supergiant - on our VISIR images, as well as on the IRAC data. We then built and fitted their broadband spectral energy distributions with a combination of two absorbed black bodies, representing their stellar components, as well as a possible mid-infrared excess, in order to derive their physical parameters. We show that LBV 1806-20 and the WC9 star exhibit a mid-infrared excess, likely because of the presence of circumstellar dust related to their winds. We also show that only LBV 1806-20 had a variable flux over a period of two years, variability which is due to its LBV nature rather than to a heating of the gas and dust cloud by the high-energy emission of SGR 1806-20. Finally, differences in the intrinsic absorptions of the three stars show an inhomogeneous structure of the density of the gas and dust cloud in the massive star cluster.Comment: 9 pages, 5 figures, 4 tables, accepted in A&

The extinction law in high redshift galaxies

We estimate the dust extinction laws in two intermediate redshift galaxies. The dust in the lens galaxy of LBQS1009-0252, which has an estimated lens redshift of zl~0.88, appears to be similar to that of the SMC with no significant feature at 2175 A. Only if the lens galaxy is at a redshift of zl~0.3, completely inconsistent with the galaxy colors, luminosity or location on the fundamental plane, can the data be fit with a normal Galactic extinction curve. The dust in the zl=0.68 lens galaxy for B0218+357, whose reddened image lies behind a molecular cloud, requires a very flat ultraviolet extinction curve with (formally) R(V)=12 +- 2. Both lens systems seem to have unusual extinction curves by Galactic standards.Comment: 15 pages, 3 figures. ApJ in pres

Coronary-artery bypass surgery in patients with ischemic cardiomyopathy

BACKGROUND The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear. METHODS From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years. RESULTS A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test). CONCLUSIONS In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of Health; STICH [and STICHES] ClinicalTrials.gov number, NCT00023595.

Detailed Case Studies

Wireless body area networks (WBANs) are one of the key technologies that support the development of pervasive health monitoring (remote patient monitoring systems), which has attracted more attention in recent years. These WBAN applications requires stringent security requirements as they are concerned with human lives. In the recent scenario of the corona pandemic, where most of the healthcare providers are giving online services for treatment, DDoS attacks become the major threats over the internet. This chapter particularly focusses on detection of DDoS attack using machine learning algorithms over the healthcare environment. In the process of attack detection, the dataset is preprocessed. After preprocessing the dataset, the cleaned dataset is given to the popular classification algorithms in the area of machine learning namely, AdaBoost, J48, k-NN, JRip, Random Committee and Random Forest classifiers. Those algorithms are evaluated independently and the results are recorded. Results concluded that J48 outperform with accuracy of 99.98% with CICIDS dataset and random forest outperform with accuracy of 99.917, but it takes the longest model building time. Depending on the evaluation performance the appropriate classifier is selected for further DDoS detection at real-time

Insights from the STICH trial: Change in left ventricular size after coronary artery bypass grafting with and without surgical ventricular reconstruction

ObjectiveThe present analysis of the Surgical Treatment for Ischemic Heart Failure randomized trial data examined the left ventricular volumes at baseline and 4 months after surgery to determine whether any magnitude of postoperative reduction in end-systolic volume affected survival after coronary artery bypass grafting alone compared with bypass grafting plus surgical ventricular reconstruction.MethodsOf the 1000 patients randomized, 555 underwent an operation and had a paired imaging assessment with the same modality at baseline and 4 months postoperatively. Of the remaining 455 patients, 424 either died before the 4-month study or did not have paired imaging tests and were excluded, and 21 were not considered because they had died before surgery or did not receive surgery.ResultsSurgical ventricular reconstruction resulted in improved survival compared with coronary artery bypass grafting alone when the postoperative end-systolic volume index was 70 mL/m2 or less. However, the opposite was true for patients achieving a postoperative volume index greater than 70 mL/m2. A reduction in the end-systolic volume index of 30% or more compared with baseline was an infrequent event in both treatment groups and did not produce a statistically significant survival benefit with ventricular reconstruction.ConclusionsIn patients undergoing coronary artery bypass grafting plus surgical ventricular reconstruction, a survival benefit was realized compared with bypass alone, with the achievement of a postoperative end-systolic volume index of 70 mL/m2 or less. Extensive ventricular remodeling at baseline might limit the ability of ventricular reconstruction to achieve a sufficient reduction in volume and clinical benefit

Severity of Remodeling, Myocardial Viability, and Survival in Ischemic LV Dysfunction After Surgical Revascularization

AbstractObjectivesThis study sought to test the hypothesis that end-systolic volume (ESV), as a marker of severity of left ventricular (LV) remodeling, influences the relationship between myocardial viability and survival in patients with coronary artery disease and LV systolic dysfunction.BackgroundRetrospective studies of ischemic LV dysfunction suggest that the severity of LV remodeling determines whether myocardial viability predicts improved survival with surgical compared with medical therapy, with coronary artery bypass grafting (CABG) only benefitting patients with viable myocardium who have smaller ESV. However, this has not been tested prospectively.MethodsInteractions of end-systolic volume index (ESVI), myocardial viability, and treatment with respect to survival were assessed in patients in the prospective randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial of CABG versus medical therapy who underwent viability assessment (n = 601; age 61 ± 9 years; ejection fraction ≤35%), with a median follow-up of 5.1 years. Median ESVI was 84 ml/m2. Viability was assessed by single-photon emission computed tomography or dobutamine echocardiography using pre-specified criteria.ResultsMortality was highest among patients with larger ESVI and nonviability (p < 0.001), but no interaction was observed between ESVI, viability status, and treatment assignment (p = 0.491). Specifically, the effect of CABG versus medical therapy in patients with viable myocardium and ESVI ≤84 ml/m2 (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.56 to 1.29) was no different than in patients with viability and ESVI >84 ml/m2 (HR: 0.87; 95% CI: 0.57 to 1.31). Other ESVI thresholds yielded similar results, including ESVI ≤60 ml/m2 (HR: 0.87; 95% CI: 0.44 to 1.74). ESVI and viability assessed as continuous rather than dichotomous variables yielded similar results (p = 0.562).ConclusionsAmong patients with ischemic cardiomyopathy, those with greater LV ESVI and no substantial viability had worse prognosis. However, the effect of CABG relative to medical therapy was not differentially influenced by the combination of these 2 factors. Lower ESVI did not identify patients in whom myocardial viability predicted better outcome with CABG relative to medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595

An entire exon 3 germ-line rearrangement in the BRCA2 gene: pathogenic relevance of exon 3 deletion in breast cancer predisposition

<p>Abstract</p> <p>Background</p> <p>Germ-line mutations in the <it>BRCA1 </it>and <it>BRCA2 </it>genes are major contributors to hereditary breast/ovarian cancer. Large rearrangements are less frequent in the <it>BRCA2 </it>gene than in <it>BRCA1</it>. We report, here, the first total deletion of exon 3 in the <it>BRCA2 </it>gene that was detected during screening of 2058 index cases from breast/ovarian cancer families for <it>BRCA2 </it>large rearrangements. Deletion of exon 3, which is in phase, does not alter the reading frame. Low levels of alternative transcripts lacking exon 3 (Δ3 delta3 transcript) have been reported in normal tissues, which raises the question whether deletion of exon 3 is pathogenic.</p> <p>Methods</p> <p>Large <it>BRCA2 </it>rearrangements were analysed by QMPSF (Quantitative Multiplex PCR of Short Fluorescent Fragments) or MLPA (Multiplex Ligation-Dependent Probe Amplification). The exon 3 deletion was characterized with a "zoom-in" dedicated CGH array to the <it>BRCA2 </it>gene and sequencing. To determine the effect of exon 3 deletion and assess its pathogenic effect, three methods of transcript quantification were used: fragment analysis of FAM-labelled PCR products, specific allelic expression using an intron 2 polymorphism and competitive quantitative RT-PCR.</p> <p>Results</p> <p>Large rearrangements of <it>BRCA2 </it>were detected in six index cases out of 2058 tested (3% of all deleterious <it>BRCA2 </it>mutations). This study reports the first large rearrangement of the <it>BRCA2 </it>gene that includes all of exon 3 and leads to an <it>in frame </it>deletion of exon 3 at the transcriptional level. Thirty five variants in exon 3 and junction regions of <it>BRCA2 </it>are also reported, that contribute to the interpretation of the pathogenicity of the deletion. The quantitative approaches showed that there are three classes of delta3 <it>BRCA2 </it>transcripts (low, moderate and exclusive). Exclusive expression of the delta3 transcript by the mutant allele and segregation data provide evidence for a causal effect of the exon 3 deletion.</p> <p>Conclusion</p> <p>This paper highlights that large rearrangements and total deletion of exon 3 in the <it>BRCA2 </it>gene could contribute to hereditary breast and/or ovarian cancer. In addition, our findings suggest that, to interpret the pathogenic effect of any variants of exon 3, both accurate transcript quantification and co-segregation analysis are required.</p