Generation and measurement of nonstationary random processes technical note no. 3

Generation and measurement of nonstationary stochastic processes related to Monte Carlo studies with analog compute

Competing reproductive and physiological investments in an all‑female lizard, the Colorado checkered whiptail

Organisms in the wild have to allocate limited resources towards competing functions such as reproduction, growth, and self-maintenance. These competing investments create significant changes in physiological activity, and we still know little about the relationship between physiological activity and reproductive investment in natura. We investigated trade-offs between physiological activity and reproductive investment in the parthenogenetic Colorado checkered whiptail, Aspidoscelis neotesselata, across three different sites at the US Army Fort Carson Military Installation near Colorado Springs, CO, through-out the reproductive season in 2018 and 2019. We measured clutch size and reproductive activity and quantified plasma corticosterone (CORT), reactive oxygen metabolites (ROMs), and bacterial killing ability (BKA) to examine how energy-mobilizing hormones, oxidative stress, and immunity change in light of reproductive investment across different sub-populations. Circulating CORT increased with reproductive investment across all sub-populations, and increased clutch size led to a decrease in BKA in one sub-population, suggesting that habitat and nutritional availability may mediate this relationship. Oxidative stress, CORT, and innate immunity were not correlated with the exception of a trade-off between ROMs and BKA. This indicates individuals that have a better capacity to fight-off pathogens suffered increased reactive oxygen metabolites across all sub-populations, independently of habitat characteristics, which has important implications for A. neotesselata conservation

Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes

Aims/hypothesis: We investigated whether biochemical cardiovascular risk factors and/or markers of subclinical cardiovascular disease were associated with the development of reduced renal function in people with type 2 diabetes. Methods: A cohort of 1066 Scottish men and women aged 60–74 years with type 2 diabetes from the Edinburgh Type 2 Diabetes Study were followed up for a median of 6.7 years. New-onset reduced renal function was defined as two eGFRs <60 ml−1 min−1 (1.73 m)−2 at least 3 months apart with a > 25% decline from baseline eGFR. Ankle brachial pressure index (ABI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) were measured at baseline. Pulse wave velocity (PWV) and carotid intima media thickness were measured 1 year into follow-up. Data were analysed using Cox proportional hazards models. Results: A total of 119 participants developed reduced renal function during follow-up. ABI, PWV, NT-proBNP and hsTnT were all associated with onset of decline in renal function following adjustment for age and sex. These associations were attenuated after adjustment for additional diabetes renal disease risk factors (systolic BP, baseline eGFR, albumin:creatinine ratio and smoking pack-years), with the exception of hsTnT which remained independently associated (HR 1.51 [95% CI 1.22, 1.87]). Inclusion of hsTnT in a predictive model improved the continuous net reclassification index by 0.165 (0.008, 0.286). Conclusions/interpretation: Our findings demonstrate an association between hsTnT, a marker of subclinical cardiac ischaemia, and subsequent renal function decline. Further research is required to establish the predictive value of hsTnT and response to intervention

Additively Manufactured RCS for Small Satellites and Landers

After a fifty year absence, NASA’s return to the lunar surface under the Artemis Program – for long term human exploration and utilization – is driving commercial and academic opportunities for small satellite and small lander platforms (e.g., Commercial Lunar Payload Services program – CLPS). Bipropellant thrusters are a reliable, low risk, and flight proven method for the propulsion and attitude control that is required for complex maneuvers such entry, descent, and landing (EDL) or in-space proximity operations. However, due to the increasingly competitive commercial spaceflight market in the last decade, satellite subsystems must also be affordable to buy their way into the final mission design and engineering solution. Therefore starting in 2019, and based off prior satellite integration work, Aerojet Rocketdyne (AR) undertook an advanced propulsion development effort to combine modern metal additive manufacturing (AM) techniques with thrust scalable hypergolic MON-25 propulsion technology to create a high performance and fully integrated (i.e., multiple thrusters integrated into a single package) reaction control system (RCS) at a fraction of the production cost when compared to the heritage designs that are assembled from individual thrusters. The point-of-departure for the RCS design comes from a new line of additively manufactured thrusters that stably burn volatile MON-25 oxidizer with monomethylhydrazine (MMH) fuel at thrust levels of 5 lbf and 100 lbf. Cost at the subsystem level is lowered by the AM integration of parts and functions which reduces the build of materials, touch labor, and assembly time. In addition, AM allows the design to be adaptable to changing requirements such as the number of thrusters, orientation, and thrust level. Cost at the satellite level is reduced by leveraging MON-25’s lower freezing point of -55 °C (compared to traditional dinitrogen tetroxide oxidizer) to minimize mass, thermal, and power requirements while operating in deep-space environments. In addition, thruster operation at the equal volume mixture ratio for MMH/MON-25 allows for a modular approach to tank design and a predictable center of gravity during maneuvering. This paper provides an overview of the ISE-5 and the ISE-100 MON-25 thruster technology that powers the integrated designs as well as the development progress of the AM RCS concept itself. This includes reduction to practice activities such as proof-of-concept AM material test demonstrators and water flow test units

Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3):protocol for a randomised double-blind trial in patients with essential hypertension

INTRODUCTION: Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K(+)-depletion. We hypothesised that a K(+)-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K(+)-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide.METHODS AND ANALYSIS: This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25-50 mg, amiloride 10-20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18-79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate &lt;45 mL/min, abnormal plasma K(+), clinic SBP &gt;200 mm Hg or DBP &gt;120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators.ETHICS AND DISSEMINATION: PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal.TRIAL REGISTRATION NUMBERS: Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973.</p