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All sourcesNASA NTRSDOE OSTI
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Plausible Biological Mechanisms Underlying Sex Differences in Radiation-Induced Lung Cancer Risk

Some epidemiological studies suggest that women are at greater risk for radiation-induced lung cancer than men, but this observation is not consistent across all studies. A scientific committee formed by the National Council on Radiation Protection and Measurement evaluated evidence for a sex difference in lung cancer risk from radiation exposuresby reviewing animal studies and assessing the biological plausibility that such a difference might exist. The committee identified four mechanisms that could potentially result in greater radiogenic lung cancer risks for women. The first of these is that radiation exposure increases the relative risk for a molecular subtype of spontaneous lung cancer that occurs predominantly in women. The second is that is that sex chromosome or gene expression differences between men and women places women at greater risk. The third is that hormonal differences between men and women, particularly for estrogen levels, puts women at greater risk. The fourth mechanism is that sex differences in immune system function underlie a sex difference in radiation associated lung cancer risk.None of these mechanisms hasyet been proven to play a role in radiogenic lung cancer risk.

radiation↗
NASA NTRS2002

National Survey Results: Retention of Women in Collegiate Aviation

Since the numbers of women pursuing technical careers in aviation continues to remain very low, a study on retention of women was undertaken by a team of university faculty from Embry Riddle Aeronautical University, Arizona State University, and Kent State University. The study was initiated to discover the factors that influence women once they have already selected an aviation career and to ascertain what could be done to support those women who have demonstrated a serious interest in an aviation career by enrolling in a collegiate aviation program. This paper reports preliminary results of data collected in the first and second years of the study. The data was collected from surveys of 390 college students (195 women and 195 men) majoring in aviation programs in nine colleges and universities, representing widely varied geographic areas and including both two- and four-year institutions. Results revealed significant areas of concern among women in pilot training. When queried about these concerns, differences were evident in the responses of the male and female groups. These differences were expected. However, a surprising finding was that women in early stages of pilot training responded differently from women in more experienced stages, These response differences did not occur among the men surveyed. The results, therefore, suggest that women in experienced stages of training may have gone through an adaptation process and reflect more male-like attitudes about a number of objects, including social issues, confidence, family, and career.

Turney, Mary Ann↗
NASA NTRS1992

Axial and appendicular bone density predict fractures in older women

To determine whether measurement of hip and spine bone mass by dual-energy x-ray absorptiometry (DEXA) predicts fractures in women and to compare the predictive value of DEXA with that of single-photon absorptiometry (SPA) of appendicular sites, we prospectively studied 8134 nonblack women age 65 years and older who had both DEXA and SPA measurements of bone mass. A total of 208 nonspine fractures, including 37 wrist fractures, occurred during the follow-up period, which averaged 0.7 years. The risk of fracture was inversely related to bone density at all measurement sites. After adjusting for age, the relative risks per decrease of 1 standard deviation in bone density for the occurrence of any fracture was 1.40 for measurement at the proximal femur (95% confidence interval 1.20-1.63) and 1.35 (1.15-1.58) for measurement at the spine. Results were similar for all regions of the proximal femur as well as SPA measurements at the calcaneus, distal radius, and proximal radius. None of these measurements was a significantly better predictor of fractures than the others. Furthermore, measurement of the distal radius was not a better predictor of wrist fracture (relative risk 1.64: 95% CI 1.13-2.37) than other sites, such as the lumbar spine (RR 1.56; CI 1.07-2.26), the femoral neck (RR 1.65; CI 1.12-2.41), or the calcaneus (RR 1.83; CI 1.26-2.64). We conclude that the inverse relationship between bone mass and risk of fracture in older women is similar for absorptiometric measurements made at the hip, spine, and appendicular sites.

Multicenter Study↗
DOE OSTI2023

Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and nonusers

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[ 18 F]fluoro-m-tyrosine ([ 18 F]FMT), baseline D2/3 receptor binding potential using [ 11 C]raclopride, and DA release using methylphenidate-paired [ 11 C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater DA synthesis capacity than NC participants, particularly in dorsal caudate, and greater cognitive flexibility. Furthermore, across individuals, the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or DA release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women’s hormone status. Hormonal contraception (in the form of pill, shot, implant, ring, or intrauterine device) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the DA system. Findings from this study begin to address this critical gap in women’s health.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Mutations that confer resistance to broadly-neutralizing antibodies define HIV-1 variants of transmitting mothers from that of non-transmitting mothers

Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching <20,000 annual pediatric HIV cases worldwide by 2020. Prior to the widespread use of ART in the setting of pregnancy, over half of infants born to HIV-infected mothers were protected against HIV acquisition. Yet, the role of maternal immune factors in this protection against vertical transmission is still unclear, hampering the development of synergistic strategies to further reduce MTCT. It has been established that infant transmitted/founder (T/F) viruses are often resistant to maternal plasma, yet it is unknown if the neutralization resistance profile of circulating viruses predicts the maternal risk of transmission to her infant. In this study, we amplified HIV-1 envelope genes ( env ) by single genome amplification and produced representative Env variants from plasma of 19 non-transmitting mothers from the U.S. Women Infant Transmission Study (WITS), enrolled in the pre-ART era. Maternal HIV Env variants from non-transmitting mothers had similar sensitivity to autologous plasma as observed for non-transmitting variants from transmitting mothers. In contrast, infant variants were on average 30% less sensitive to paired plasma neutralization compared to non-transmitted maternal variants from both transmitting and non-transmitting mothers (p = 0.015). Importantly, a signature sequence analysis revealed that motifs enriched in env sequences from transmitting mothers were associated with broadly neutralizing antibody (bnAb) resistance. Altogether, our findings suggest that circulating maternal virus resistance to bnAb-mediated neutralization, but not autologous plasma neutralization, near the time of delivery, predicts increased MTCT risk. These results caution that enhancement of maternal plasma neutralization through passive or active vaccination during pregnancy may potentially drive the evolution of variants fit for vertical transmission.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Assessment of Demographic, Genetic, and Imaging Variables Associated With Brain Resilience and Cognitive Resilience to Pathological Tau in Patients With Alzheimer Disease

Importance: Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience). Objective: To examine the demographic (age, sex, and educational level), genetic (APOE-ε4 status), and neuroimaging (white matter hyperintensities and cortical thickness) factors associated with interindividual differences in brain and cognitive resilience to tau positron emission tomography (PET) load and to changes in global cognition over time. Design, setting, an participants: In this cross-sectional, longitudinal study, tau PET was performed from June 1, 2014, to November 30, 2017, and global cognition monitored for a mean [SD] interval of 2.0 [1.8] years at 3 dementia centers in South Korea, Sweden, and the United States. The study included amyloid-β-positive participants with mild cognitive impairment or AD dementia. Data analysis was performed from October 26, 2018, to December 11, 2019. Exposures: Standard dementia screening, cognitive testing, brain magnetic resonance imaging, amyloid-β PET and cerebrospinal fluid analysis, and flortaucipir (tau) labeled with fluor-18 (18F) PET. Main outcomes and measures: Separate linear regression models were performed between whole cortex [18F]flortaucipir uptake and cortical thickness, and standardized residuals were used to obtain a measure of brain resilience. The same procedure was performed for whole cortex [18F]flortaucipir uptake vs Mini-Mental State Examination (MMSE) as a measure of cognitive resilience. Bivariate and multivariable linear regression models were conducted with age, sex, educational level, APOE-ε4 status, white matter hyperintensity volumes, and cortical thickness as independent variables and brain and cognitive resilience measures as dependent variables. Linear mixed models were performed to examine whether changes in MMSE scores over time differed as a function of a combined brain and cognitive resilience variable. Results: A total of 260 participants (145 [55.8%] female; mean [SD] age, 69.2 [9.5] years; mean [SD] MMSE score, 21.9 [5.5]) were included in the study. In multivariable models, women (standardized β = -0.15, P = .02) and young patients (standardized β = -0.20, P = .006) had greater brain resilience to pathological tau. Higher educational level (standardized β = 0.23, P < .001) and global cortical thickness (standardized β = 0.23, P < .001) were associated with greater cognitive resilience to pathological tau. Linear mixed models indicated a significant interaction of brain resilience × cognitive resilience × time on MMSE (β [SE] = -0.235 [0.111], P = .03), with steepest slopes for individuals with both low brain and cognitive resilience. Conclusions and relevance: Results of this study suggest that women and young patients with AD have relative preservation of brain structure when exposed to neocortical pathological tau. Interindividual differences in resilience to pathological tau may be important to disease progression because participants with both low brain and cognitive resilience had the most rapid cognitive decline over time.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1999

Ethnic Differences in Physical Fitness, Blood Pressure and Blood Chemistry in Women (AGES 20-63)

This study examined the role of ethnicity on the aerobic fitness, blood pressure, and selected blood chemistry values of women. One hundred twenty-four females (mean age 41.37 +/- 9.0) were medically Examined at the NASA/Johnson Space Center occupational health clinic. Ethnic groups consisted of 23 Black (B), 18 Hispanic (H) and 83 Non-minority (NM). Each woman had a maximum Bruce treadmill stress test (RER greater than or = 1.1) and a negative ECG. Indirect calorimetry, skinfolds, self-report physical activity (NASA activity scale), seated blood pressure, and blood chemistry panel determined VO2max, percent fat, level of physical activity, blood pressure and blood chemistry values. ANOVA revealed that the groups did not differ (p greater than 0.05) in age, VO2 max, weight, percent fat, level of physical activity, total cholesterol, or HDL-C. However, significant differences (p greater than 0.05) were noted in BMI, diastolic blood pressure, and blood chemistries. BMI was 3.17 higher in H than in NM; resting diastolic pressures were 5.69 and 8.05 mmHg. lower in NM and H than in B; triglycerides were 48.07 and 37.21 mg/dl higher in H than in B and NM; hemoglobin was .814 gm/dl higher in NM than B; fasting blood sugar was 15.41 mg/dl higher in H than NM; The results of this study showed that ethnic groups differed in blood pressure and blood chemistry values but not aerobic fitness or physical activity. There was an ethnic difference in BMI but not percent fat.

Ayers, G. W.↗
DOE OSTI2025

Bayesian estimation of HIV acquisition dates for prevention trials

Accurate timing estimates of when participants acquire HIV in HIV prevention trials are necessary for determining antibody levels at acquisition. The Antibody-Mediated Prevention (AMP) Studies showed that a passively administered broadly neutralizing antibody can prevent the acquisition of HIV from a neutralization-sensitive virus. We developed a pipeline for estimating the date of detectable HIV acquisition (DDA) in AMP Study participants using diagnostic and viral sequence data. Using a Bayesian strategy that combines three streams of data (REN [rev/vpu/env/Δnef] sequence, GP [gag/Δpol] sequence, and diagnostic) where their 95% credible intervals overlap based on pre-specified criteria and decision rules. We evaluated the performance of our AMP pipeline using PacBio viral sequence data from 41 participants across two prospective acute HIV acquisition cohort studies, FRESH and RV217, with twice-weekly sampling. These cohort studies enrolled young women in South Africa and men and women in Kenya and Thailand, respectively, with a high likelihood of HIV acquisition. In evaluating performance, “true DDA” was the center of bounds between last-negative and first-positive RNA diagnostic tests (median time 4 days, range 2–7 days); bias was the mean difference between estimated and true DDA. Using diagnostic data alone yielded timing estimates with a bias of 2.4 days and root mean square error (RMSE) of 7.9 days. These results were improved using sequence + diagnostic data (bias 1.5 days, RMSE 6.9 days), as well as by restricting sequence-based estimation to samples from ≤5 weeks post-DDA (bias 0.2 days, RMSE 7.8 days).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Factors associated with treatment limitations in two Swedish intensive care units: Prevalence and patient involvement

Abstract The aim was to study the prevalence, documentation, and patient involvement in treatment limitations (TLs) in two Swedish intensive care units (ICUs). All patients admitted to the ICUs of two Swedish regional hospitals in 2019 were screened for inclusion. Exclusion criteria included postanesthesia care <24 h. Patients were identified using the Swedish Intensive Care Registry (SIR) and data were extracted from SIR and hospital charts. Uni‐ and multivariable logistic analysis was performed to investigate associations with the presence of TLs. A total of 3090 patients were admitted to the two ICUs in 2019. After exclusion, 1019 patients were included in the study. 45.5% were women and the mean age was 62.9 years. 26.5% of the patients had one or several TLs. Age (OR 1.04 per one year increase 95% confidence interval (CI) 1.02–1.05), SAPS3‐score (OR 1.08 per one unit increase 95% CI 1.06–1.09) and ICU length of stay (OR 1.11 per one day increase 95% CI 1.05–1.17) were independently associated with an increased likelihood of receiving a TL. 17% of the patients were involved in the decision‐making process and in >30% of cases neither the patient nor next‐of‐kin were informed. Women were to a larger extent involved in the decision process than men (24.5 vs. 12.5% p < .05). When the intensivist documented why a TL was established, patient autonomy was four times more commonly stated as the motivation for the TL among women compared to men (15.5% vs. 3.8% p < .05). TLs were common in two Swedish ICUs but a substantial number of patients and next‐of‐kin were not involved in the decision‐making process or informed of the decision. Women were more often than men engaged in the decision to establish a TL.

Jönsson, Nino↗
NASA NTRS1993

Materials education activities

Last year, at NEW: Update '91, a panel discussion was held to address the unique difficulties of attracting and retaining minorities and women in technical studies. Unfortunately, retention in technical majors is a problem of varying proportions for the entire student population, and must be improved in order to maintain the strength of the nation's industrial base. To investigate the cause of student attrition in technical majors, in-depth interviews of both current and former (non-graduating) engineering students at four colleges and universities in Colorado were conducted by Hewitt and Seymour. They found that there was no significant difference in the level of high school preparation and undergraduate academic performance in these two groups, despite the prevailing faculty perception that most students who switch from technical to nontechnical majors were underprepared. The majority of engineering students who changed majors reported that they were turned off by science, while one-third complained of poor teaching.

Ries, Heidi R.↗
NASA NTRS2006

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose-rate dose to the bone marrow (mean = 2.5 Gy) was consistent with the measured ERR (0.62, 95% Cl =-0.2 to 1.9). Conclusions: An extended, biologically based model for leukemia that includes HSC initiation, inactivation, proliferation, and, uniquely for leukemia, long-range HSC migration predicts, %Kith reasonable accuracy, risks for radiationinduced leukemia associated with exposure to therapeutic doses of radiation.

Shuryak, Igor↗
NASA NTRS2021

Uneven Consequences: Gendered Impacts of Shrimp Aquaculture Development on Mangrove Dependent Communities

Shrimp aquaculture is a primary driver of mangrove deforestation globally. The decline of these forests not only threatens the integrity of valuable ecosystems but can also produce detrimental impacts on mangrove-dependent communities. Ecuador is the largest producer of farmed Pacific white leg shrimp (Litopenaeus vannamei) in South America. This industry’s growth and success have come at the expense of the country’s mangrove forests. This paper analyzes the impacts of shrimp aquaculture development on a mangrove-dependent community in Esmeraldas province, Ecuador. Furthermore, this research highlights how gender and gendered norms inform the strategies adopted by different actors in response to these processes. Drawing from ethnographic and Global Positioning System data collected in situ, this study shows that women are disproportionately affected by the loss of mangrove forests. Mangrove forests have historically provided women sustenance, opportunities for income generation, and the ability to pass on cultural traditions. The establishment of the aquaculture sector also created a collapse of local livelihoods. Losing access to traditional livelihood practices pushed men into the mangroves to gather cockles, a productive activity customarily only practiced by women. This livelihood shift for men further contributes to the displacement of women from the mangrove forests. The introduction of industrial shrimp farming increased the community’s reliance on mangrove resources. The overuse of these resources is leading to a depletion of mangrove cockle populations, putting the community in a vulnerable position as both men and women are increasingly dependent on this fishery to subsist.

Gender Mangrove fisheries↗
NASA NTRS1999

EEG Analysis of the Effects of Therapeutic Cooling on the Cognitive Performance of Multiple Sclerosis Patients

The objective of this project was to determine whether a controlled period of head and torso cooling would enhance the cognitive performance of multiple sclerosis patients. Nineteen MS patients (11 men and 8 women) participated in the study. Control data were taken from nineteen healthy volunteers (12 men and 7 women). All but six of nineteen MS patients tested improved their cognitive performance, as measured by their scores on the Rao test battery. A second objective was to gain insight into the neurological effects of cooling. Visual evoked potentials (VEPs) stimulated by a reversing checkerboard pattern were recorded before and after cooling. We found that cooling selectively benefited the cognitive performance of those MS patients whose pre-cooling VEPs were abnormally shaped (which is an indication of visual pathway impairment due to demyelinization). Moreover, for female MS patients, the degree of cognitive performance improvement following cooling was correlated with a change in the shape of their VEPs toward a more normal shape following cooling.

Montgomery, Leslie D.↗
DOE OSTI2020

Application of physiologically based pharmacokinetic modeling for sertraline dosing recommendations in pregnancy

Pregnancy is a period of significant change that impacts physiological and metabolic status leading to alterations in the disposition of drugs. Uncertainty in drug dosing in pregnancy can lead to suboptimal therapy, which can contribute to disease exacerbation. A few studies show there are increased dosing requirements for antidepressants in late pregnancy; however, the quantitative data to guide dose adjustments are sparse. We aimed to develop a physiologically based pharmacokinetic (PBPK) model that allows gestational-age dependent prediction of sertraline dosing in pregnancy. A minimal physiological model with defined gut, liver, plasma, and lumped placental-fetal compartments was constructed using the ordinary differential equation solver package, ‘mrgsolve’, in R. We extracted data from the literature to parameterize the model, including sertraline physicochemical properties, in vitro metabolism studies, disposition in nonpregnant women, and physiological changes during pregnancy. The model predicted the pharmacokinetic parameters from a clinical study with eight subjects for the second trimester and six subjects for the third trimester. Based on the model, gestational-dependent changes in physiology and metabolism account for increased clearance of sertraline (up to 143% at 40 weeks gestational age), potentially leading to under-dosing of pregnant women when nonpregnancy doses are used. The PBPK model was converted to a prototype web-based interactive dosing tool to demonstrate how the output of a PBPK model may translate into optimal sertraline dosing in pregnancy. Quantitative prediction of drug exposure using PBPK modeling in pregnancy will support clinically appropriate dosing and increase the therapeutic benefit for pregnant women.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1994

Blood volume responses of men and women to bed rest

This paper reviews a series of studies that indicate that estrogens play an important role in blood volume regulation. The first study illustrates that the plasma volume (PV) of ambulatory women fluctuates during the menstrual cycle, increasing during periods of elevated estrogens. In the second study, it was shown that exogenous and endogenous elevations in blood estrogens attenuate the decrease in PV during bed rest. In the third study, the hypothesis was tested that women, who naturally have a higher blood estrogen content compared with men, will have a smaller loss of PV during bed rest. Ten men and ten women underwent a 13-day, 6 degrees head-down bed rest. Plasma volume and red cell mass (RCM) were measured before and after bed rest using 125I and 51Cr labeling, respectively. Before bed rest, the men and women had similar blood volume (BV) and PV (mL/kg body weight), but the women had a smaller (P < .01) RCM (22.2 +/- 0.9 versus 26.2 +/- 0.8 mL/kg, mean +/- SE). During bed rest, the decrease in RCM (mL/kg) was similar in men and women. However, the decrease in BV was greater in men (8.0 +/- 0.8 mL/kg versus 5.8 +/- 0.8 mL/kg), because of a greater reduction in PV (6.3 +/- 0.6 mL/kg versus 4.1 +/- 0.6 mL/kg). Because the decline in BV has been proposed to contribute to the cardiovascular deconditioning after bed rest, it is possible that women may experience less cardiac and circulatory strain on reambulation.

Review, Tutorial↗
DOE OSTI2021

Prevalence of human papillomavirus genotypes in high-grade cervical precancer and invasive cervical cancer from cancer registries before and after vaccine introduction in the United States

Background. US population-based cancer registries can be used for surveillance of human papillomavirus (HPV) types found in HPV-associated cancers. Using this framework, HPV prevalence among high-grade cervical precancers and invasive cervical cancers were compared before and after HPV vaccine availability. Methods. Archived tissue from 2 studies of cervical precancers and invasive cervical cancers diagnosed from 1993-2005 (prevaccine) were identified from 7 central cancer registries in Florida; Hawaii; Iowa; Kentucky; Louisiana; Los Angeles County, California; and Michigan; from 2014 through 2015 (postvaccine) cases were identified from 3 registries in Iowa, Kentucky, and Louisiana. HPV testing was performed using L1 consensus polymerase chain reaction analysis. HPV-type–specific prevalence was examined grouped by hierarchical attribution to vaccine types: HPV 16, 18, HPV 31, 33, 45, 52, 58, other oncogenic HPV types, and other types/HPV negative. Generalized logit models were used to compare HPV prevalence in the prevaccine study to the postvaccine study by patient age, adjusting for sampling factors. Results. A total of 676 precancers (328 prevaccine and 348 postvaccine) and 1140 invasive cervical cancers (777 prevaccine and 363 postvaccine) were typed. No differences were observed in HPV-type prevalence by patient age between the 2 studies among precancers or invasive cancers. Conclusions. The lack of reduction in vaccine-type prevalence between the 2 studies is likely explained by the low number of cases and low HPV vaccination coverage among women in the postvaccine study. Monitoring HPV-type prevalence through population-based strategies will continue to be important in evaluating the impact of the HPV vaccine.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1994

Gender- and age-related differences in heart rate dynamics: are women more complex than men?

OBJECTIVES. This study aimed to quantify the complex dynamics of beat-to-beat sinus rhythm heart rate fluctuations and to determine their differences as a function of gender and age. BACKGROUND. Recently, measures of heart rate variability and the nonlinear "complexity" of heart rate dynamics have been used as indicators of cardiovascular health. Because women have lower cardiovascular risk and greater longevity than men, we postulated that there are important gender-related differences in beat-to-beat heart rate dynamics. METHODS. We analyzed heart rate dynamics during 8-min segments of continuous electrocardiographic recording in healthy young (20 to 39 years old), middle-aged (40 to 64 years old) and elderly (65 to 90 years old) men (n = 40) and women (n = 27) while they performed spontaneous and metronomic (15 breaths/min) breathing. Relatively high (0.15 to 0.40 Hz) and low (0.01 to 0.15 Hz) frequency components of heart rate variability were computed using spectral analysis. The overall "complexity" of each heart rate time series was quantified by its approximate entropy, a measure of regularity derived from nonlinear dynamics ("chaos" theory). RESULTS. Mean heart rate did not differ between the age groups or genders. High frequency heart rate power and the high/low frequency power ratio decreased with age in both men and women (p < 0.05). The high/low frequency power ratio during spontaneous and metronomic breathing was greater in women than men (p < 0.05). Heart rate approximate entropy decreased with age and was higher in women than men (p < 0.05). CONCLUSIONS. High frequency heart rate spectral power (associated with parasympathetic activity) and the overall complexity of heart rate dynamics are higher in women than men. These complementary findings indicate the need to account for gender-as well as age-related differences in heart rate dynamics. Whether these gender differences are related to lower cardiovascular disease risk and greater longevity in women requires further study.

NASA Discipline Cardiopulmonary↗