Quantitative projections of a quality measure: Performance of a complex task

AbstractComplex data series that arise during interaction between humans (operators) and advanced technology in a controlled and realistic setting have been explored. The purpose is to obtain quantitative measures that reflect quality in task performance: on a ship simulator, nine crews have solved the same exercise, and detailed maneuvering histories have been logged. There are many degrees of freedom, some of them connected to the fact that the vessels may be freely moved in any direction. To compare maneuvering histories, several measures were used: the time needed to reach the position of operation, the integrated angle between the hull direction and the direction of motion, and the extent of movement when the vessel is to be manually kept in a fixed position. These measures are expected to reflect quality in performance. We have also obtained expert quality evaluations of the crews. The quantitative measures and the expert evaluations, taken together, allow a ranking of crew performance. However, except for time and integrated angle, there is no correlation between the individual measures. This may indicate that complex situations with social and man–machine interactions need complex measures of quality in task performance. In general terms, we have established a context-dependent and flexible framework with quantitative measures in contact with a social-science concept that is hard to define. This approach may be useful for other (qualitative) concepts in social science that contain important information on the society

Virtual Machining: Capabilities and Challenges of Process Simulations in the Aerospace Industry

AbstractMilling processes for the manufacturing of parts for aerospace applications can be influenced by various effects. When machining structural parts with high material removal rates, the stiffness of the machine tool can be a limiting factor because chatter vibrations. Additionally, vibrations of thin-walled structures, e. g., the blades of impellers or turbines, can lead to chatter vibrations and surface location errors. Thermo-mechanical deformations are another cause for violations of given shape tolerances. Geometric physically-based process simulations can be used to analyze milling processes with regard to these effects in order to optimize the process parameters. In this paper, an overview of several applications of a geometric physically-based simulation system for analyzing different effects during milling processes is presented. Depending on the relevant effects, process forces, the dynamic behaviour of the tool-spindle-machine system, vibrations of workpieces and fixture systems, as well as thermo-mechanical deformations are calculated

Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality

Resting heart rate is a heritable trait correlated with life span. Little is known about the genetic contribution to resting heart rate and its relationship with mortality. We performed a genome-wide association discovery and replication analysis starting with 19.9 million genetic variants and studying up to 265,046 individuals to identify 64 loci associated with resting heart rate (P < 5 × 10$^{-8}$); 46 of these were novel. We then used the genetic variants identified to study the association between resting heart rate and all-cause mortality. We observed that a genetically predicted resting heart rate increase of 5 beats per minute was associated with a 20% increase in mortality risk (hazard ratio 1.20, 95% confidence interval 1.11-1.28, P = 8.20 × 10$^{-7}$) translating to a reduction in life expectancy of 2.9 years for males and 2.6 years for females. Our findings provide evidence for shared genetic predictors of resting heart rate and all-cause mortality.This research was conducted using the UK Biobank Resource. This project is supported by the Netherlands organization for health research and development (ZonMw grant 90.700.441). S.B. is supported by the Wellcome Trust (grant 100114). P.B.M. acknowledges support from the NIHR Cardiovascular Biomedical Research Unit at Barts and the London School of Medicine and Dentistry, Queen Mary University of London. N.V. is supported by Netherlands Heart Institute and Marie Sklodowska-Curie Global Fellowship (grant 661395)

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction

Trastuzumab-associated cardiac adverse effects in the Herceptin adjuvant trial.

PURPOSE: The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. PATIENTS AND METHODS: The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF > or = 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. RESULTS: Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m(2) v 257 mg/m(2)) or epirubicin (480 mg/m(2) v 422 mg/m(2)) and had a lower screening LVEF and a higher body mass index. CONCLUSION: Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteri

Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European society of cardiology and endorsed by the European society of intensive care medicine

Patients with acute heart failure (AHF) require urgent in-hospital treatment for relief of symptoms. The main reason for hospitalization is congestion, rather than low cardiac output. Although congestion is associated with a poor prognosis, many patients are discharged with persistent signs and symptoms of congestion and/or a high left ventricular filling pressure. Available data suggest that a pre-discharge clinical assessment of congestion is often not performed, and even when it is performed, it is not done systematically because no method to assess congestion prior to discharge has been validated. Grading congestion would be helpful for initiating and following response to therapy. We have reviewed a variety of strategies to assess congestion which should be considered in the care of patients admitted with HF. We propose a combination of available measurements of congestion. Key elements in the measurement of congestion include bedside assessment, laboratory analysis, and dynamic manoeuvres. These strategies expand by suggesting a routine assessment of congestion and a pre-discharge scoring system. A point system is used to quantify the degree of congestion. This score offers a new instrument to direct both current and investigational therapies designed to optimize volume status during and after hospitalization. In conclusion, this document reviews the available methods of evaluating congestion, provides suggestions on how to properly perform these measurements, and proposes a method to quantify the amount of congestion presen

Prognostic Significance of Changes in Heart Rate Following Uptitration of Beta-Blockers in Patients with Sub-Optimally Treated Heart Failure with Reduced Ejection Fraction in Sinus Rhythm versus Atrial Fibrillation

Background: In patients with heart failure with reduced ejection fraction (HFrEF) on sub-optimal doses of beta-blockers, it is conceivable that changes in heart rate following treatment intensification might be important regardless of underlying heart rhythm. We aimed to compare the prognostic significance of both achieved heart rate and change in heart rate following beta-blocker uptitration in patients with HFrEF either in sinus rhythm (SR) or atrial fibrillation (AF). Methods: We performed a post hoc analysis of the BIOSTAT-CHF study. We evaluated 1548 patients with HFrEF (mean age 67 years, 35% AF). Median follow-up was 21 months. Patients were evaluated at baseline and at 9 months. The combined primary outcome was all-cause mortality and heart failure hospitalisation stratified by heart rhythm and heart rate at baseline. Results: Despite similar changes in heart rate and beta-blocker dose, a decrease in heart rate at 9 months was associated with reduced incidence of the primary outcome in both SR and AF patients [HR per 10 bpm decrease—SR: 0.83 (0.75–0.91), p &lt; 0.001; AF: 0.89 (0.81–0.98), p = 0.018], whereas the relationship was less strong for achieved heart rate in AF [HR per 10 bpm higher—SR: 1.26 (1.10–1.46), p = 0.001; AF: 1.08 (0.94–1.23), p = 0.18]. Achieved heart rate at 9 months was only prognostically significant in AF patients with high baseline heart rates (p for interaction 0.017 vs. low). Conclusions: Following beta-blocker uptitration, both achieved and change in heart rate were prognostically significant regardless of starting heart rate in SR, however, they were only significant in AF patients with high baseline heart rate

Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction ≤30%

Aims: Because of the prognostic importance of LV dysfunction following an AMI and the increasing use of electrical and/or mechanical interventions in patients with LV systolic dysfunction, this retrospective analysis of EPHESUS patients with LVEF ≤30% at baseline was conducted to determine the value of eplerenone in this setting. Methods and Results: In EPHESUS, 6632 patients with LVEF ≤40% and clinical heart failure (HF) post‐AMI who were receiving standard therapy were randomized to eplerenone 25 mg/day titrated to 50 mg/day or placebo for a mean follow‐up of 16 months. Treatment with eplerenone in the subgroup of patients with LVEF ≤30% ( N =2106) resulted in relative risk reductions of 21% versus placebo in both all‐cause mortality ( P =0.012) and cardiovascular (CV) mortality/CV hospitalization ( P =0.001), and 23% for CV mortality ( P =0.008). The relative risk of sudden cardiac death (SCD) was reduced 33% ( P =0.01) and HF mortality/HF hospitalization was reduced 25% ( P =0.005) with eplerenone compared with placebo. Within 30 days of randomization, eplerenone resulted in relative risk reductions of 43% for all‐cause mortality ( P =0.002), 29% for CV mortality/CV hospitalization ( P =0.006), and 58% for SCD ( P =0.008). Conclusions: Treatment with eplerenone plus standard therapy in patients with post‐AMI HF and LVEF ≤30% provided significant incremental benefits in reducing both early and late mortality and morbidity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102725/1/ejhf2005-11-008.pd