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NASA NTRS2017

Sensitivity Analysis of the Bone Fracture Risk Model

Introduction: The probability of bone fracture during and after spaceflight is quantified to aid in mission planning, to determine required astronaut fitness standards and training requirements and to inform countermeasure research and design. Probability is quantified with a probabilistic modeling approach where distributions of model parameter values, instead of single deterministic values, capture the parameter variability within the astronaut population and fracture predictions are probability distributions with a mean value and an associated uncertainty. Because of this uncertainty, the model in its current state cannot discern an effect of countermeasures on fracture probability, for example between use and non-use of bisphosphonates or between spaceflight exercise performed with the Advanced Resistive Exercise Device (ARED) or on devices prior to installation of ARED on the International Space Station. This is thought to be due to the inability to measure key contributors to bone strength, for example, geometry and volumetric distributions of bone mass, with areal bone mineral density (BMD) measurement techniques. To further the applicability of model, we performed a parameter sensitivity study aimed at identifying those parameter uncertainties that most effect the model forecasts in order to determine what areas of the model needed enhancements for reducing uncertainty. Methods: The bone fracture risk model (BFxRM), originally published in (Nelson et al) is a probabilistic model that can assess the risk of astronaut bone fracture. This is accomplished by utilizing biomechanical models to assess the applied loads; utilizing models of spaceflight BMD loss in at-risk skeletal locations; quantifying bone strength through a relationship between areal BMD and bone failure load; and relating fracture risk index (FRI), the ratio of applied load to bone strength, to fracture probability. There are many factors associated with these calculations including environmental factors, factors associated with the fall event, mass and anthropometric values of the astronaut, BMD characteristics, characteristics of the relationship between BMD and bone strength and bone fracture characteristics. The uncertainty in these factors is captured through the use of parameter distributions and the fracture predictions are probability distributions with a mean value and an associated uncertainty. To determine parameter sensitivity, a correlation coefficient is found between the sample set of each model parameter and the calculated fracture probabilities. Each parameters contribution to the variance is found by squaring the correlation coefficients, dividing by the sum of the squared correlation coefficients, and multiplying by 100. Results: Sensitivity analyses of BFxRM simulations of preflight, 0 days post-flight and 365 days post-flight falls onto the hip revealed a subset of the twelve factors within the model which cause the most variation in the fracture predictions. These factors include the spring constant used in the hip biomechanical model, the midpoint FRI parameter within the equation used to convert FRI to fracture probability and preflight BMD values. Future work: Plans are underway to update the BFxRM by incorporating bone strength information from finite element models (FEM) into the bone strength portion of the BFxRM. Also, FEM bone strength information along with fracture outcome data will be incorporated into the FRI to fracture probability.

mathematical models↗

DOE OSTI2022

Post-Combat-Injury Opioid Prescription and Alcohol Use Disorder in the Military

Previous studies have identified combat exposure and combat traumatic experience as problematic drinking risk factors. Increasing evidence suggests that opioid use increases the risk of alcohol use disorder. This study investigated the association between opioid prescription use after injury and (1) alcohol use disorder and (2) severity of alcohol use disorder among deployed military servicemembers. Deidentified health records data of 9,029 deployed servicemembers from a retrospective cohort study were analyzed. Data were randomly selected from the Department of Defense Trauma Registry and included servicemembers with combat injuries during deployment in Iraq or Afghanistan (2002–2016). Pharmacy records and International Classification of Diseases, Ninth and Tenth Revision diagnosis codes were used. Three groups were identified (no opioid prescription use, nonpersistent opioid prescription use, and persistent opioid prescription use) and were compared on the basis of alcohol use disorder risk using Cox proportional hazard models. Data analyses were performed in 2021. Of the 9,029 servicemembers with combat injury, 2,262 developed alcohol use disorder (1,322 developed severe alcohol use disorder). Compared with no opioid prescription use, increased alcohol use disorder risk was associated with persistent opioid prescription use, with a hazard ratio of 1.13 (95% CI=1.02, 1.26). After covariate adjustment, increased risk remained statistically significant (hazards ratio=1.24; 95% CI=1.10, 1.39). There was no significant difference in alcohol use disorder risk between no opioid prescription use and nonpersistent opioid prescription use. The risk of severe alcohol use disorder did not vary by opioid use among servicemembers with alcohol use disorder diagnosis. Furthermore, the findings of the study suggest that the incidence of alcohol use disorder was higher among injured servicemembers with persistent opioid prescription use than among those without opioid use. If replicated in prospective studies, the findings highlight the need for clinicians to consider the current and history of alcohol use of patients in initiating treatment involving opioids.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2007

Measurement Decision Risk - The Importance of Definitions

The idea behind this presentation is how the difference in definitions can change the application. 1. Look at history, concepts, and definitions. 2. Link the test uncertainty ratio (TUR) to measurement decision risk.

Mimbs, Scott↗

NASA NTRS2007

Measurement Decision Risk - The Importance of Definitions

One of the more misunderstood areas of metrology is the Test Uncertainty Ratio (TUR) and its cousin, the Test Accuracy Ratio (TAR). There have been many definitions over the years, but why are these definitions important to a discussion on measurement decision risk? The importance lies in the clarity of communication. Problems can immediately arise in the application (or misapplication) of the definition of these terms. In other words, while it is important to understand the definitions, it is more important to understand concepts behind the definitions and to be precise in how they are applied. The objective of any measurement is a decision. Measurement Decision Risk is a way to look at the quality of a measurement and although it is not a new concept, it has generated a lot of attention since its addition as a requirement in the new U.S. National Standard, ANSI/NCSL Z540.3-2006. In addition to Measurement Decision Risk as the prime method of managing measurement risk, Z540.3 has also added, as a fall-back, an explicit definition for TUR. The impact these changes might have on calibration service providers if these requirements are levied on them has become the topic of much discussion and in some cases concern. This paper looks at the concepts behind the definitions and how they relate to Measurement Decision Risk. Using common examples, this paper will also provide a comparison of various elements of risk related to measurement science using the concepts of TAR, TUR, accuracy ratios, and Consumer Risk (False Accept Risk). The goal is to provide a better understanding of their relevance to the measurement decision process.

Mimbs, Scott M.↗

NASA NTRS2008

Measurement Decision Risk - The Importance of Definitions

One of the more misunderstood areas of metrology is the Test Uncertainty Ratio (TUR) and the Test Accuracy Ratio (TAR). There have been many definitions over the years, but why are these definitions important to a discussion on measurement decision risk? The importance lies in the clarity of communication. Problems can immediately arise in the application (or misapplication) of the definition of these terms. In other words, while it is important to understand the definitions, it is more important to understand concepts behind the definitions and to be precise in how they are applied. The objective of any measurement is a decision. Measurement Decision Risk is a way to look at the quality of a measurement, and although it is not a new concept, it has generated a lot of attention since its addition as a requirement in the new U.S. National Standard, ANSIINCSL Z540.3-2006. In addition to Measurement Decision Risk as the prime method of managing measurement risk, Z540.3 has added, as a fall-back, an explicit definition for TUR. The impact these new requirements may have on calibration service providers has become the topic of much discussion and in some cases concern. This paper will look at the concepts behind the definitions and how they relate to Measurement Decision Risk. Using common examples, this paper will also provide a comparison of various elements of risk related to measurement science using the concepts of TAR, TUR, accuracy ratios, and Consumer Risk (False Accept Risk). The goal of this paper is to provide a better understanding of their relevance to the measurement decision process.

Mimbs, Scott M.↗

DOE OSTI2020

Association Between Changes in Timing of Spring Onset and Asthma Hospitalization in Maryland

The proposed association between climate change and increased burden of allergic diseases are based on three different thematic observational studies that have linked (i) increased CO 2 concentration with higher pollen production, (ii) warmer air/surface temperatures with early spring onset and longer pollen season, and (iii) higher pollen exposure with increased risk of asthma hospitalizations. Yet empirical evidence collectively linking climate change with pollen season and asthma exacerbation is still lacking. Using satellite observations, in situ pollen monitoring data, and hospitalization records (2001-2012), here we show that changes in the timing of spring onset resulting from ongoing climate variability and change is directly related to a longer tree pollen season and increased risk of asthma hospitalization. More specifically, we observed that very early start of season (SOS) to be associated with 10% increase in risk of asthma hospitalization (Incident Rate Ratio (IRR): 1.10, 95% Confidence Interval (CI): 1.02- 1.20) while late onset of SOS to be associated with 3% increase in risk of asthma hospitalization in Maryland (IRR: 1.03, 95% CI: 0.97-1.11), however the risk in the latter case was not statistically significant. Our results serve as a wake-up call to public health and medical communities regarding the need to anticipate and adapt to the ongoing changes in the timing and severity of the spring allergy season.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2022

Nonsynonymous amino acid changes in the α-chain of complement component 5 influence longitudinal susceptibility to Plasmodium falciparum infections and severe malarial anemia in kenyan children

Background: Severe malarial anemia (SMA; Hb < 5.0 g/dl) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions such as western Kenya. Methods: We investigated the relationship between two novel complement component 5 (C5) missense mutations [rs17216529:C>T, p(Val145Ile) and rs17610:C>T, p(Ser1310Asn)] and longitudinal outcomes of malaria in a cohort of Kenyan children (under 60 mos, n = 1,546). Molecular modeling was used to investigate the impact of the amino acid transitions on the C5 protein structure. Results: Prediction of the wild-type and mutant C5 protein structures did not reveal major changes to the overall structure. However, based on the position of the variants, subtle differences could impact on the stability of C5b. The influence of the C5 genotypes/haplotypes on the number of malaria and SMA episodes over 36 months was determined by Poisson regression modeling. Genotypic analyses revealed that inheritance of the homozygous mutant (TT) for rs17216529:C>T enhanced the risk for both malaria (incidence rate ratio, IRR = 1.144, 95%CI: 1.059–1.236, p = 0.001) and SMA (IRR = 1.627, 95%CI: 1.201–2.204, p = 0.002). In the haplotypic model, carriers of TC had increased risk of malaria (IRR = 1.068, 95%CI: 1.017–1.122, p = 0.009), while carriers of both wild-type alleles (CC) were protected against SMA (IRR = 0.679, 95%CI: 0.542–0.850, p = 0.001). Conclusion: Collectively, these findings show that the selected C5 missense mutations influence the longitudinal risk of malaria and SMA in immune-naïve children exposed to holoendemic P. falciparum transmission through a mechanism that remains to be defined.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2012

Current-State Constrained Filter Bank for Wald Testing of Spacecraft Conjunctions

We propose a filter bank consisting of an ordinary current-state extended Kalman filter, and two similar but constrained filters: one is constrained by a null hypothesis that the miss distance between two conjuncting spacecraft is inside their combined hard body radius at the predicted time of closest approach, and one is constrained by an alternative complementary hypothesis. The unconstrained filter is the basis of an initial screening for close approaches of interest. Once the initial screening detects a possibly risky conjunction, the unconstrained filter also governs measurement editing for all three filters, and predicts the time of closest approach. The constrained filters operate only when conjunctions of interest occur. The computed likelihoods of the innovations of the two constrained filters form a ratio for a Wald sequential probability ratio test. The Wald test guides risk mitigation maneuver decisions based on explicit false alarm and missed detection criteria. Since only current-state Kalman filtering is required to compute the innovations for the likelihood ratio, the present approach does not require the mapping of probability density forward to the time of closest approach. Instead, the hard-body constraint manifold is mapped to the filter update time by applying a sigma-point transformation to a projection function. Although many projectors are available, we choose one based on Lambert-style differential correction of the current-state velocity. We have tested our method using a scenario based on the Magnetospheric Multi-Scale mission, scheduled for launch in late 2014. This mission involves formation flight in highly elliptical orbits of four spinning spacecraft equipped with antennas extending 120 meters tip-to-tip. Eccentricities range from 0.82 to 0.91, and close approaches generally occur in the vicinity of perigee, where rapid changes in geometry may occur. Testing the method using two 12,000-case Monte Carlo simulations, we found the method achieved a missed detection rate of 0.1%, and a false alarm rate of 2%.

Carpenter, J. Russell↗

DOE OSTI2023

Gut microbiome dynamics and associations with mortality in critically ill patients

Abstract Background Critical illness and care within the intensive care unit (ICU) leads to profound changes in the composition of the gut microbiome. The impact of such changes on the patients and their subsequent disease course remains uncertain. We hypothesized that specific changes in the gut microbiome would be more harmful than others, leading to increased mortality in critically ill patients. Methods This was a prospective cohort study of critically ill adults in the ICU. We obtained rectal swabs from 52 patients and assessed the composition the gut microbiome using 16 S rRNA gene sequencing. We followed patients throughout their ICU course and evaluated their mortality rate at 28 days following admission to the ICU. We used selbal, a machine learning method, to identify the balance of microbial taxa most closely associated with 28-day mortality. Results We found that a proportional ratio of four taxa could be used to distinguish patients with a higher risk of mortality from patients with a lower risk of mortality (p = .02). We named this binarized ratio our microbiome mortality index (MMI). Patients with a high MMI had a higher 28-day mortality compared to those with a low MMI (hazard ratio, 2.2, 95% confidence interval 1.1–4.3), and remained significant after adjustment for other ICU mortality predictors, including the presence of the acute respiratory distress syndrome (ARDS) and the Acute Physiology and Chronic Health Evaluation (APACHE II) score (hazard ratio, 2.5, 95% confidence interval 1.4–4.7). High mortality was driven by taxa from theAnaerococcus(genus) andEnterobacteriaceae(family), while lower mortality was driven byParasutterellaandCampylobacter(genera). Conclusions Dysbiosis in the gut of critically ill patients is an independent risk factor for increased mortality at 28 days after adjustment for clinically significant confounders. Gut dysbiosis may represent a potential therapeutic target for future ICU interventions.

Gastroenterology & Hepatology↗

DOE OSTI2022

Efficacy and safety of warfarin in patients with non-valvular atrial fibrillation and CKD G3–G5D

ABSTRACT Background Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3–5 (G3–G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA—the Swedish national quality registry for atrial fibrillation and anticoagulation—and the Stroke Registry. Results At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18–0.76]}, G4 [0.53 (0.38–0.74)] and G5D [0.49 (0.30–0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02–1.46)], G5 [1.52 (1.15–2.01)] and G5D [1.23 (1.00–1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4–G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4–G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Welander, Frida (ORCID:0000000311117215)↗

DOE OSTI2025

Risk of Mortality in Family Members of Men Seeking Fertility Assessment

Objective: To assess mortality in family members of men seeking fertility assessment. Subfertility serves as a biomarker for overall somatic health, and poor semen quality is associated with increased risk of hospitalization and mortality from chronic conditions. However, it is unclear if these risks extend to family members of men with low sperm count. Design: Retrospective cohort study. Subjects: Family members, up to third-degree relatives, of men in the Subfertility, Health and Assisted Reproduction and the Environment cohort who underwent a semen analysis as part of a fertility assessment 1996–2017. Relatives of men with a recorded total sperm count who lived in Utah for ≥1 year 1904–2017 were included in the analysis (N = 22,280 families). Exposure: Individuals were classified by family membership. Families were classified as relatives of azoospermic (0M), oligozoospermic (<39M), or normozoospermic (≥39M) men. The average total sperm count of the proband (male relative) with fertility assessment was also included as a continuous exposure measure. Main Outcome Measures: The main outcomes were all-cause and cause-specific mortality risk by sex, age, and degree of relation: first-, second-, and third-degree. Cox proportional hazard models were used to test the association between fertility classification and mortality, controlling for sex, race/ethnicity, and birth year. Results: A total of 666,437 relatives of men with fertility assessment (N deaths = 183,974) were included in the analysis. Relative to normozoospermia families, all-cause mortality risk increased in oligozoospermia families (hazard ratio [HR] oligozoospermia , 1.03; 95% confidence interval [CI], 1.01–1.05). Close relatives, first- (HR oligozoospermia , 1.17; 95% CI, 1.07–1.28) and second-degree relatives (HR azoospermia , 1.11; 95% CI, 1.04–1.20; HR oligozoospermia , 1.05; 95% CI,1.01–1.09), of azoospermic and oligozoospermic men had the highest all-cause and cause-specific mortality risk, including death attributed to cardiovascular disease or congenital birth conditions. Conclusion: Our results suggest that familial all-cause and cause-specific mortality risk differ by fertility phenotype. Families of azoospermic and oligozoospermic men showed significantly increased risk, particularly for close relatives. This study provides further evidence that shared genetic and/or environmental factors could influence both fertility and somatic health.

Male fertility↗

NASA NTRS1993

Joint pain and Doppler-detectable bubbles in altitude (Hypobaric) decompression

The observation that altitude decompression sickness (DCS) is associated with pain in the lower extremities is not new, although it is not a consistent finding. DCS in divers is generally in the upper body, an effect often attributed to non-loading of the body while immersed. In caisson workers, DCS is reported more in the lower extremities. Surprisingly, many researchers do not mention the location of DCS joint pain, apparently considering it to be random. This is not the case for the tissue ratios encountered in studying decompression associated with simulated EVA. In NASA/JSC tests, altitude DCS generally presented first in either the ankle, knee, or hip (83 percent = 73/88). There was a definite statistical relation between the maximum Spencer precordial Doppler Grade and the incidence of DCS in the extremity, although this is not meant to imply a casual relation between circulating gas bubbles and joint pain. The risk of DCS with Grade 4 was considerably higher than that of Grades 0 to 3. The DCS risk was independent of the 'tissue ratio.' There was a predominance of lower extremity DCS even when exercise was performed with the upper body. The reason for these locations we hypothesize to be attributed to the formation of tissue gas micronuclei from kinetic and tensile forces (stress-assisted nucleation) and are the result of the individuals ambulating in a 1g environment. Additionally, since these showers of Doppler bubbles can persist for hours, it is difficult to imagine that they are emanating solely from tendons and ligaments, the supposed site of joint pain. This follows from Henry's law linking the volume of joint tissue (the solvent) and the solubility coefficient of inert gas; there is volumetrically insufficient connective tissue to produce the prolonged release of gas bubbles. If gas bubbles are spawned and released from connective tissue, their volume is increased by those from muscle tissue. Therefore, the nexus between Doppler-detectable gas bubbles and joint-pain decompression sickness is essentially a statistical, rather than a direct, one.

Powell, Michael R.↗

NASA NTRSDate not supplied

Risk-Based Methodology for the Determination of Hall Thruster Performance Specifications

This work adapts manufacturing and metrology industry standards to create a risk-based approach for the determination of electric propulsion performance specifications. The developed process is applied to 208 total thrust measurements acquired using three different NASA Hall Effect Rocket with Magnet Shielding (HERMeS) Technology Demonstration Unit (TDU) 12.5-kW Hall thrusters in three different test facilities in order to generate thrust specifications at the 300 V/6.25 kW, 400 V/8.33 kW, 500 V/10.42 kW, and 600 V/12.5 kW operating conditions. These thrust specifications are used to perform a set of sample acceptance tests to illustrate the importance of adding additional conservatism using a parameter known of the Test Accuracy Ratio in order to control the risk to the thruster producer and consumer from false rejection and acceptance of thruster units.

HERMeS↗

NASA NTRSDate not supplied

Risk-based Methodology for the Determination of Hall Thruster Performance Specifications

HERMeS↗

DOE OSTI2020

CHRNA5 rs16969968 polymorphism is associated with lung cancer risk: A meta‐analysis

Abstract Objective To evaluate the genetic association between rs16969968 and lung cancer risk by meta‐analysis. Data source We searched eligible studies from MEDLINE, Web of Science and EMBASE up to Dec, 2017. Study selection Association studies concerning rs16969968 and lung cancer risk were included. We assessed the association strength between this polymorphism and risk of lung cancer by calculating odds ratios (OR) and 95% confidence interval (95%CI). Results A total of 26 data sets comprising 30 772 lung cancers and 90 954 controls were included. rs16969968 was found to be associated with lung cancer risk in population of European ancestry in all models (A vs. G: OR = 1.30, 95%CI 1.27‐1.33, P < 0.001; AA + GA vs. GG: OR = 1.38, 95%CI 1.33‐1.43, P < 0.001; AA vs. GG + GA: OR = 1.45, 95%CI 1.38‐1.53, P < 0.001), consistent with previous genome‐wide association study (GWAS). However, no association was observed in Asians (A vs. G: OR = 1.19. 95%CI 0.95‐1.49, P = 0.131). The minor allele A may increase the risk of lung cancer in both smokers (OR = 1.33, 95%CI 1.29‐1.39, P < 0.001) and nonsmokers (OR = 1.25, 95%CI 1.12‐1.39, P < 0.001). There was no obvious publication bias in all analyses. Conclusions Our analysis provided more evidence that rs16969968 is a susceptibility locus of lung cancer in the Caucasians and that it may be not associated with the risk in the Asians.

Zhou, Wei↗

DOE OSTI2020

Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women

Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18–24 years and other breast cancer risk factors showed that weight gain from ages 18–24 to 35–44 or to 45–54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45–54: 0.96, 95% CI: 0.95–0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45–54: 0.96, 95% CI: 0.94–0.98). Weight gain from ages 25–34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35–44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45–54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

Diabetes and hypertension are related to amyloid-beta burden in the population-based Rotterdam Study

Abstract Higher vascular disease burden increases the likelihood of developing dementia, including Alzheimer’s disease. Better understanding the association between vascular risk factors and Alzheimer’s disease pathology at the predementia stage is critical for developing effective strategies to delay cognitive decline. In this work, we estimated the impact of six vascular risk factors on the presence and severity of in vivo measured brain amyloid-beta (Aβ) plaques in participants from the population-based Rotterdam Study. Vascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, physical inactivity and smoking) were assessed 13 (2004–2008) and 7 years (2009–2014) prior to 18F-florbetaben PET (2018–2021) in 635 dementia-free participants. Vascular risk factors were associated with binary amyloid PET status or continuous PET readouts (standard uptake value ratios, SUVrs) using logistic and linear regression models, respectively, adjusted for age, sex, education, APOE4 risk allele count and time between vascular risk and PET assessment. Participants’ mean age at time of amyloid PET was 69 years (range: 60–90), 325 (51.2%) were women and 190 (29.9%) carried at least one APOE4 risk allele. The adjusted prevalence estimates of an amyloid-positive PET status markedly increased with age [12.8% (95% CI 11.6; 14) in 60–69 years versus 35% (36; 40.8) in 80–89 years age groups] and APOE4 allele count [9.7% (8.8; 10.6) in non-carriers versus 38.4% (36; 40.8) to 60.4% (54; 66.8) in carriers of one or two risk allele(s)]. Diabetes 7 years prior to PET assessment was associated with a higher risk of a positive amyloid status [odds ratio (95% CI) = 3.68 (1.76; 7.61), P < 0.001] and higher standard uptake value ratios, indicating more severe Aβ pathology [standardized beta = 0.40 (0.17; 0.64), P = 0.001]. Hypertension was associated with higher SUVr values in APOE4 carriers (mean SUVr difference of 0.09), but not in non-carriers (mean SUVr difference 0.02; P = 0.005). In contrast, hypercholesterolaemia was related to lower SUVr values in APOE4 carriers (mean SUVr difference −0.06), but not in non-carriers (mean SUVr difference 0.02). Obesity, physical inactivity and smoking were not related to amyloid PET measures. The current findings suggest a contribution of diabetes, hypertension and hypercholesterolaemia to the pathophysiology of Alzheimer’s disease in a general population of older non-demented adults. As these conditions respond well to lifestyle modification and drug treatment, further research should focus on the preventative effect of early risk management on the development of Alzheimer’s disease neuropathology.

van Arendonk, Joyce (ORCID:0000000172941633)↗

NASA NTRS1988

Variable mixture ratio performance through nitrogen augmentation

High/variable mixture ratio O2/H2 candidate engine cycles are examined for earth-to-orbit vehicle application. Engine performance and power balance information are presented for the candidate cycles relative to chamber pressure, bulk density, and mixture ratio. Included in the cycle screening are concepts where a third fluid (liquid nitrogen) is used to achieve a variable mixture ratio over the trajectory from liftoff to earth orbit. The third fluid cycles offer a very low risk, fully reusable, low operation cost alternative to high/variable mixture ratio bipropellant cycles. Variable mixture ratio engines with extendible nozzle are slightly lower performing than a single mixture ratio engine (MR = 7:1) with extendible nozzle. Dual expander engines (MR = 7:1) have slightly better performance than the single mixture ratio engine. Dual fuel dual expander engines offer a 16 percent improvement over the single mixture ratio engine.

Beichel, R.↗