Estimation of Directional Stability Derivatives at Small Angles and Subsonic and Supersonic Speeds

Methods are presented for estimating the directional stability derivative increments contributed by the stabilizing surfaces of subsonic and supersonic aircraft. These methods are strictly applicable at zero angle of attack and small angles of sideslip. The procedure of totaling the incremental coefficients to obtain an estimation of the total empennage side-force and yawing-moment coefficient derivatives is also shown, together with numerical examples. A correlation is presented between estimated and experimental incremental coefficients which indicates that the methods of this report generally estimate the increment of side force gained by the addition of a panel to within +/-10 percent of the experimental value while the yawing-moment increment is generally estimated to within +/-20 percent. This is true for both subsonic and supersonic Mach numbers. An example application of the methods to one of the problems in directional stability, that of minimizing the effect of Mach number on the side-force coefficient derivative of the empennage, is discussed

An automated Internet application to help patients with bipolar disorder track social rhythm stabilization.

This column describes a pilot study of a fully automated, Internet-based program that provides a key element of interpersonal and social rhythm therapy, a form of psychotherapy shown to be effective in the treatment of bipolar disorder when combined with mood-stabilizing medication. Participants (N=64) recorded the time they completed activities of daily living and their mood at the time of each entry. After 90 days they demonstrated a 31% increase in social rhythm stability and a small, though statistically significant, decrease in symptoms of abnormal mood. Internet-based programs can enhance access to a best practice in the management of bipolar disorder

Three-Dimensional Orbits of Earth Satellites, Including Effects of Earth Oblateness and Atmospheric Rotation

The principal purpose of the present paper is to present sets of equations which may be used for calculating complete trajectories of earth satellites from outer space to the ground under the influence of air drag and gravity, including oblateness effects, and to apply these to several examples of entry trajectories starting from a circular orbit. Equations of motion, based on an "instantaneous ellipse" technique, with polar angle as independent variable, were found suitable for automatic computation of orbits in which the trajectory consists of a number of revolutions. This method is suitable as long as the trajectory does not become nearly vertical. In the terminal phase of the trajectories, which are nearly vertical, equations of motion in spherical polar coordinates with time as the independent variable were found to be more suitable. In the first illustrative example the effects of the oblateness component of the earth's gravitational field and of atmospheric rotation were studied for equatorial orbits. The satellites were launched into circular orbits at a height of 120 miles, an altitude sufficiently high that a number of revolutions could be studied. The importance of the oblateness component of the earth's gravitational field is shown by the fact that a satellite launched at circular orbital speed, neglecting oblateness, has a perigee some 67,000 feet lower when oblateness forces are included in the equations of motion than when they are not included. Also, the loss in altitude per revolution is double that of a satellite following an orbit not subject to oblateness. The effect of atmospheric rotation on the loss of altitude per revolution was small. As might be surmised, the regression of the line of nodes as predicted by celestial mechanics is unchanged when drag is included. It is clear that the inclination of the orbital plane to the equator will be relatively unaffected by drag for no atmospheric rotation since the drag lies in the orbital plane in this case. With the inclusion of atmospheric rotation it was found that the inclination of the plane changed about one-millionth of a radian per revolution. Thus the prediction of the position of the orbital plane of an earth satellite is not complicated by the introduction of drag. The line of apsides, which without drag but with oblateness moves slowly in space, tends to move with the satellite when drag is included in the calculations. As a results, the usual linearized solutions based on oblateness alone must be basically altered when drag is included to take into account the rapid movement of the line of apsides. In the second illustrative example the final revolution was calculated to impact for a number of trajectories in an orbital plane inclined at 650 to the equator. Of particular interest is the large effect the oblateness gravitational field and atmospheric rotation can have on the impact point. For a value of CDA/m of unity, and for an initial downward angle at 80 miles altitude of 0.01 radian, such as might be utilized for manned re-entry, oblateness had an influence of about 300 miles in the impact point, and atmospheric rotation had about a 150-mile influence

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)