Aspects of yaw control design of an aircraft with distributed electric propulsion.

Distributed electric propulsion (DEP) offers new options in aircraft design. Besides the optimization of the wing, another area of optimization is the vertical tail plane (VTP) and yaw control. The large number of engines significantly relaxes the one-engine-inoperative (OEI) case during take-off, which is mostly the sizing case for the VTP. This offers the possibility to reduce the VTP and rudder size to a certain amount. Also, the dynamics of electric motors offer the possibility to use differential thrust for yaw control. This can compensate at least some of the reduced rudder effectiveness coming from the smaller VTP size. In the framework of the German nationally funded project SynergIE, different aircraft designs of a hybrid-electric regional aircraft were investigated. Three aircraft concepts with 2, 6 and 12 propellers were designed in the project, for which reasonable minimum VTP sizes were investigated. For the 12-propeller aircraft, the investigations showed that the VTP could be reduced by 50%, still allowing the compensation of OEI during take-off and the generation of sideslip angle during crosswind operations. This reduction in VTP size results in a reduction of the block fuel by about 4%. For the 12-engine aircraft, a 6-degrees-of-freedom simulation model was developed including flight control laws for yaw control using the rudder and differential thrust. Virtual flight tests were performed in a full-flight simulator. The tests generally showed a good agreement with the theoretical results from the handling quality analysis but also outlined deficiencies in aircraft handling at low speed with full flaps. The use of a flight simulator at this early stage of aircraft design has proven to be a useful tool to investigate such unconventional designs.

Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?

AIMS: The DoUble-blind Atorvastatin AmLodipine (DUAAL) trial investigated whether atorvastatin decreases ischaemia by a vascular benefit, independent of low-density lipoprotein cholesterol lowering, in patients with coronary artery disease (CAD), both alone and in combination with the traditional anti-anginal therapy, amlodipine. METHODS AND RESULTS: Randomized, double-blind, parallel-group, multicountry trial (2 weeks run-in and 24 weeks active therapy) comparing three treatments: amlodipine, atorvastatin, and amlodipine + atorvastatin; in 311 patients (78% male; mean age 62 years) with stable angina (≥ 2 attacks/week), CAD history, ≥ 3 transient myocardial ischaemia (TMI) episodes, and/or ≥ 15 min ischaemia on 48 h ambulatory electrocardiographic (AECG) monitoring. Efficacy variables were change in TMI by AECG, exercise ischaemia, angina diary data, and inflammatory biomarkers at Week 26. There was a comparable, highly significant decrease in TMI with amlodipine and atorvastatin, but no additional benefit for the combination. More than 50% of patients became TMI-free in all three groups and this was accompanied by a comparable, marked reduction in angina and nitroglycerin consumption. High-sensitivity C-reactive protein fell by 40% in patients receiving atorvastatin but there was no change with amlodipine. Adverse events were comparable among groups. CONCLUSION: Atorvastatin was as potent an anti-ischaemic agent as amlodipine. Future studies of combination therapies will be instructive. CLINICAL TRIAL REGISTRATION INFORMATION: National clinical trial number: NCT00159718, protocol number A0531031 listed on http://clinicaltrials.gov/.

Neurobiological differences in mental rotation and instrument interpretation in airline pilots.

Airline pilots and similar professions require reliable spatial cognition abilities, such as mental imagery of static and moving three-dimensional objects in space. A well-known task to investigate these skills is the Shepard and Metzler mental rotation task (SMT), which is also frequently used during pre-assessment of pilot candidates. Despite the intuitive relationship between real-life spatial cognition and SMT, several studies have challenged its predictive value. Here we report on a novel instrument interpretation task (IIT) based on a realistic attitude indicator used in modern aircrafts that was designed to bridge the gap between the abstract SMT and a cockpit environment. We investigated 18 professional airline pilots using fMRI. No significant correlation was found between SMT and IIT task accuracies. Contrasting both tasks revealed higher activation in the fusiform gyrus, angular gyrus, and medial precuneus for IIT, whereas SMT elicited significantly stronger activation in pre- and supplementary motor areas, as well as lateral precuneus and superior parietal lobe. Our results show that SMT skills per se are not sufficient to predict task accuracy during (close to) real-life instrument interpretation. While there is a substantial overlap of activation across the task conditions, we found that there are important differences between instrument interpretation and non-aviation based mental rotation.

Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease: a longitudinal analysis of the PREVENT study.

OBJECTIVES: The objective of this study was to test the predictive value of an oxidative stress biomarker in 634 patients from the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT). BACKGROUND: Oxidative stress contributes to mechanisms of atherosclerosis and plaque instability. Biomarkers of oxidation, such as malondialdehyde (MDA), may represent independent indicators of risk for patients with stable coronary artery disease (CAD). METHODS: Serum MDA levels were measured as thiobarbituric acid reactive substances (TBARS) in 634 patients with documented CAD using reverse-phase high-performance liquid chromatography and spectrophotometric approaches. RESULTS: During the three-year study, there were 51 major vascular events such as fatal/nonfatal myocardial infarction, 149 hospitalizations for nonfatal vascular events, and 139 patients underwent a major vascular procedure. At baseline, patients with TBARS levels in the highest quartile had a relative risk (RR) of 3.30 (95% confidence interval [CI] 1.47 to 7.42; p = 0.038) for major vascular events, RR of 4.10 (95% CI 2.55 to 6.60; p < 0.0001) for nonfatal vascular events, and RR of 3.84 (95% CI 2.56 to 5.76; p < 0.0001) for major vascular procedures. The effect of TBARS on events and procedures was also seen in a multivariate model adjusted for inflammatory markers (C-reactive protein, soluble intercellular adhesion molecule-1, interleukin-6), and other risk factors (age, low-density lipoprotein, high-density lipoprotein, total cholesterol, triglycerides, body mass index, and blood pressure). This analysis showed an independent effect of TBARS on major vascular events (p = 0.0149), nonfatal vascular events (p < 0.0001), major vascular procedures (p < 0.001), and all vascular events and procedures (p < 0.0001). CONCLUSIONS: Serum levels of TBARS were strongly predictive of cardiovascular events in patients with stable CAD, independently of traditional risk factors and inflammatory markers.

Impact of atorvastatin among older and younger patients in the Anglo-Scandinavian Cardiac Outcomes Trial Lipid-Lowering Arm.

OBJECTIVE: Older patients experience higher rates of cardiovascular disease than younger patients, but may be undertreated with statins due to doubts about efficacy and safety. The Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial allowed an evaluation of the efficacy and safety of atorvastatin among older (≥ 65 years) and younger (<65 years) patients with hypertension. METHODS: A total of 10 305 patients with hypertension, at least three other cardiovascular risk factors, total cholesterol concentrations of 251 mg/dl or less, and no known coronary heart disease (CHD) were randomized to receive atorvastatin 10 mg or placebo. The primary endpoint was a composite of nonfatal myocardial infarction and fatal CHD. RESULTS: There were 4445 patients in the older group (mean 71 years) and 5860 patients (mean 57 years) in the younger group. Among those taking placebo, the older group experienced a higher rate of primary endpoints than the younger group (11.7 vs. 7.6 events per 1000 patient years, respectively). After a median follow-up of 3.3 years, the primary endpoint was reduced by a similar proportion in both older and younger patients (37 vs. 33%, respectively). Although older patients reported more serious adverse events than younger patients, there were no significant differences between atorvastatin and placebo within each age group. CONCLUSION: Atorvastatin reduced the risk of major cardiovascular events to a similar relative extent in both older and younger patients with treated hypertension. However, given that event rates were higher in older patients, the absolute benefits of atorvastatin were greater for older than younger patients.

Impact of amlodipine-based therapy among older and younger patients in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA).

OBJECTIVES: Older patients experience higher rates of cardiovascular disease than younger patients, but studies have suggested that relative risk reductions due to antihypertensive therapy are lower in older than younger patients. The Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) allowed an evaluation of the efficacy and safety of an amlodipine versus an atenolol-based antihypertensive regimen among older (≥ 65 years) and younger (<65 years) patients. METHODS: In ASCOT-BPLA 19 257 patients (8137 aged ≥ 65 years and 11 020 <65 years) were randomly assigned to receive amlodipine or atenolol-based antihypertensive therapy. The primary endpoint (nonfatal myocardial infarction and fatal coronary heart disease) and seven secondary endpoints were consistent with the original trial design. RESULTS: All cardiovascular endpoints evaluated favoured the amlodipine-based regimen, significantly so in seven of the 16 age-stratified endpoints. Compared with the atenolol-based regimen, the amlodipine-based regimen reduced the relative risk of cardiovascular events by 17% in older and 15% in younger patients (P < 0.01). Overall, older patients experienced more cardiovascular events [n = 1625 (20%)] than younger patients [n = 1339 (12%)]. Discontinuations due to serious adverse events were low in both age groups and less frequent in the amlodipine-based versus atenolol-based regimen: 0.6 versus 1.1% among older patients and 0.4 versus 0.8% among younger patients. CONCLUSIONS: The amlodipine-based regimen reduced the relative risk of cardiovascular events more effectively than the atenolol-based regimen in both older and younger patients. However, because event rates were higher among older patients, the absolute benefits were greater for older compared with younger patients.

Urapidil, a dual-acting antihypertensive agent: Current usage considerations.

Despite the availability of a wide range of effective blood pressure (BP)-lowering agents, a substantial proportion of patients with hypertension fail to achieve target BP levels. The majority of patients with hypertension need a combination of two or more drugs to achieve BP targets and choice of second-line or subsequent-line therapy is an important consideration in hypertension management. Alpha-1-adrenoreceptor antagonists (alpha-blockers) have a BP-lowering effect broadly similar to the other antihypertensive drug classes and are effective as add-on therapy in patients with inadequately controlled hypertension. Alpha-blockers may also have therapeutic benefits that go beyond BP control, including improvements in lipid profile and glucose metabolism, as well as reducing the symptoms of benign prostatic hyperplasia. Urapidil has an alpha-blocking effect but, unlike other alpha-blockers, also has a central sympatholytic effect mediated via stimulation of serotonin 5HT(1A) receptors in the central nervous system. Several studies have suggested that oral urapidil is effective and well tolerated when used as second-line therapy in patients with BP inadequately controlled with other agents. Urapidil has also been shown to improve glucose and lipid metabolism in hypertensive patients with concomitant diabetes and/or hyperlipidemia. Intravenous urapidil is effective in the treatment of hypertensive crises, perioperative hypertension, and pre-eclampsia and may have a potential role in the management of acute stroke. In this review, the use of alpha-blockers in hypertension is discussed, with particular focus on urapidil for the lowering of BP in a variety of clinical settings.

Circulating lipid hydroperoxides predict cardiovascular events in patients with stable coronary artery disease: the PREVENT study.

OBJECTIVES: This study was designed to determine the predictive value of lipid hydroperoxide (LOOH) levels for adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD). BACKGROUND: Oxidative modification of circulating lipids contributes to inflammation and endothelial dysfunction, which are hallmark features of atherosclerosis. A serum biomarker of oxidation is LOOH, which is a primary product of fatty acid peroxidation. METHODS: Serum LOOH levels were measured and correlated with clinical events over a 3-year period in 634 patients with angiographic evidence of CAD. RESULTS: Baseline LOOH levels in the highest quartile were associated with hazard ratios of 3.24 (95% confidence interval [CI] 1.86 to 5.65; p = 0.0001) for nonfatal vascular events (n = 149), 1.80 (95% CI 1.13 to 2.88; p = 0.014) for major vascular procedures (n = 139), and 2.23 (95% CI 1.44 to 3.44; p = 0.0003) for all vascular events and procedures. Baseline LOOH levels correlated with serum levels of soluble intercellular adhesion molecule-1 (p = 0.001) and thiobarbituric acid reactive substances (p = 0.001) as well as the mean percent change in stenosis for large segments >50% stenosed (p = 0.048). A multivariate proportional hazards model, adjusted for traditional risk factors and inflammatory markers, showed an independent effect of LOOH on nonfatal vascular events, vascular procedures, and all events or procedures. Amlodipine treatment was associated with reduced cardiovascular events and changes in LOOH levels compared with placebo. CONCLUSIONS: Elevated LOOH levels were predictive of nonfatal vascular events and procedures in patients with stable CAD, independent of traditional risk factors and inflammatory markers.