Biomedical subjects

B Rosner

Publications and source records attributed to B Rosner.

At least 19 recordsLinked to original sources

PubMed2005

Loudness predicts prominence: fundamental frequency lends little.

We explored a database covering seven dialects of British and Irish English and three different styles of speech to find acoustic correlates of prominence. We built classifiers, trained the classifiers on human prominence/nonprominence judgments, and then evaluated how well they behaved. The classifiers operate on 452 ms windows centered on syllables, using different acoustic measures. By comparing the performance of classifiers based on different measures, we can learn how prominence is expressed in speech. Contrary to textbooks and common assumption, fundamental frequency (f0) played a minor role in distinguishing prominent syllables from the rest of the utterance. Instead, speakers primarily marked prominence with patterns of loudness and duration. Two other acoustic measures that we examined also played a minor role, comparable to f0. All dialects and speaking styles studied here share a common definition of prominence. The result is robust to differences in labeling practice and the dialect of the labeler.

Acoustic Stimulation↗

PubMed2004

Thrombin generation in non-cardioembolic stroke subtypes: the Hemostatic System Activation Study.

BACKGROUND: The association between hemostatic activation, stroke mechanism, and outcome is poorly defined. The Hemostatic System Activation Study (HAS) investigators measured serial levels of prothrombin fragment F1.2, a marker of thrombin generation, in patients enrolled in the Warfarin Aspirin Recurrent Stroke Study (WARSS). METHODS: HAS enrolled 631 of the 2,206 patients in WARSS. Strokes were subtyped according to inferred mechanism. Plasma was collected for F1.2 at randomization (within 30 days of stroke), 3 months, 12 months, and 18 months. The 3 to 6 month samples in aspirin-treated patients were used for the primary analysis. RESULTS: The authors analyzed 3 to 6 month samples on 320 patients. Higher F1.2 levels were associated with older age, female sex, and hypertension. There was no difference between mean F1.2 levels in 56 cryptogenic (0.9 +/- 0.32 nmol/L) and 114 non-cryptogenic (1.13 +/- 0.74 nmol/L) patients or across specific stroke subtypes. There was an 8.8%/year (p = 0.006) increase in mean F1.2 levels. There was a trend toward higher risk of recurrent stroke or death as F1.2 levels increased in aspirin (RR: 1.30, 95% CI: 0.57 to 2.94, p = 0.53) and warfarin treated patients (RR: 1.68, 95% CI: 0.48 to 5.94, p = 0.42). F1.2 levels were reduced on average 70% in warfarin-treated patients in a dose-dependent fashion. CONCLUSION: F1.2 levels did not appear to differ by stroke subtype, suggesting that factors other than underlying stroke pathophysiology influence thrombin generation in the post-acute stroke period. F1.2 levels were suppressed by warfarin in a dose-dependent fashion. Additional research is needed to determine the predictive value of F1.2 after stroke.

Aged↗

PubMed2004

Snack food intake does not predict weight change among children and adolescents.

OBJECTIVE: To assess whether intake of snack foods was associated with weight change among children and adolescents. METHODS: Prospective study of 8,203 girls and 6,774 boys, 9-14 y of age in 1996, in an ongoing cohort study who completed at least two questionnaires between 1996 and 1999. Intake of snack foods was assessed in 1996-1998 with a validated food frequency questionnaire designed specifically for children and adolescents. The outcome measure was change in age- and gender-specific z-score of body mass index (BMI). RESULTS: Boys consumed more snack foods than girls during the entire study period. After controlling for Tanner stage of development, age, height change, activity, and inactivity, there was no relation between intake of snack foods and subsequent changes in BMI z-score among the boys (beta=-0.004), but snack foods had a weak inverse association (beta=-0.007, P<0.05) with weight change among the girls. However, the results were confounded by dieting status, which had a significant positive independent association with BMI change. After controlling for dieting status and whether the mother was overweight, the association between servings per day of snack foods and subsequent changes in BMI z-score were not significant in either gender. DISCUSSION: Our results suggest that although snack foods may have low nutritional value, they were not an important independent determinant of weight gain among children and adolescents.

Adolescent↗

PubMed2004

Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice.

Fragile X syndrome (FXS) is the most common single gene (FMR1) disorder affecting cognitive and behavioral function in humans. This syndrome is characterized by a cluster of abnormalities including lower IQ, attention deficits, impairments in adaptive behavior and increased incidence of autism. Here, we show that young males with FXS have profound deficits in prepulse inhibition (PPI), a basic marker of sensorimotor gating that has been extensively studied in rodents. Importantly, the magnitude of the PPI impairments in the fragile X children predicted the severity of their IQ, attention, adaptive behavior and autistic phenotypes. Additionally, these measures were highly correlated with each other, suggesting that a shared mechanism underlies this complex phenotypic cluster. Studies in Fmr1-knockout mice also revealed sensorimotor gating and learning abnormalities. However, PPI and learning were enhanced rather than reduced in the mutants. Therefore, these data show that mutations of the FMR1 gene impact equivalent processes in both humans and mice. However, since these phenotypic changes are opposite in direction, they also suggest that murine compensatory mechanisms following loss of FMR1 function differ from those in humans.

Acoustic Stimulation↗

PubMed2003

Association between fruit and vegetable intake and change in body mass index among a large sample of children and adolescents in the United States.

OBJECTIVE: To assess whether intake of fruits and vegetables was associated with change in body mass index (BMI) among a large sample of children and adolescents in the United States. DESIGN: Prospective cohort study of children and adolescent who were 9-14 y of age in 1996, when the study began. SUBJECTS: The subjects included 8203 girls and 6715 boys in an ongoing cohort study who completed at least two questionnaires between 1996 and 1999. MEASUREMENTS: Fruit and vegetable intake was assessed in 1996-1998 with a validated food frequency questionnaire designed specifically for children and adolescents. The outcome measure was change in age- and gender-specific z-score of BMI (kg/m(2)). Self-reported weight and height, which were used to calculate BMI, were collected annually from 1996 to 1999. RESULTS: During 3 years of follow-up, annual changes in BMI were slightly greater among the boys than the girls. After controlling for Tanner stage of development, age, height change, activity and inactivity, which are known or suspected predictors of change in BMI, among the girls there was no relation between intake of fruits, fruit juice, or vegetables (alone or combined) and subsequent changes in BMI z-score. Among the boys, intake of fruit and fruit juice was not predictive of changes in BMI, however, vegetables intake was inversely related to changes in BMI z-score (beta per serving=-0.003). However, after adjusting for caloric intake, the magnitude of the effect was diminished and no longer significant. CONCLUSION: Our results suggest that the recommendation for consumption of fruits and vegetables may be well founded, but should not be based on a beneficial effect on weight regulation.

Adolescent↗

PubMed2002

A prospective study of the relationship between body mass index and cataract extraction among US women and men.

BACKGROUND: Obesity may influence several physiologic processes involved in cataract formation such as oxidative stress, glycosylation and osmotic stress. OBJECTIVE: To examine the association between increased body mass index (BMI) and the incidence of cataract extraction. DESIGN AND SETTING: The Nurses' Health Study and the Health Professionals Follow-up Study, both prospective cohort studies of US women and men. SUBJECTS: A total of 87 682 women and 45 549 men aged 45 y and older who did not have diagnosed cataract or cancer at baseline (1980 for women, 1986 for men). MEASUREMENTS: Cataract extractions occurring between baseline and 1996, confirmed by medical records. RESULTS: During 16 y of follow-up in the women, and 10 y in the men, (1 097 997 person-y), 4430 incident cases were documented. Compared to participants with BMI less than 23 kg/m(2), those with BMI greater than or equal to 30 kg/m(2) had 36% higher risk of any type of cataract (pooled multivariate relative risk (RR), 1.36; 95% CI, 1.23-1.49) after adjusting for smoking, age and lutein/zeaxanthin intake. The association was strongest for posterior subcapsular (PSC) cataract (pooled multivariate RR, 1.99; 95% CI, 1.55-2.55). With adjustment for diabetes, the RR of obesity associated with posterior subcapsular cataract was 1.68 (95% CI, 1.30-2.17). Obesity was not significantly associated with nuclear cataract. CONCLUSION: Obesity increases the risk of developing cataract overall, and of PSC cataract in particular; the etiology of PSC cataract may be mediated at least in part by glucose intolerance and insulin resistance, even in the absence of clinical diabetes.

Aged↗

PubMed2001

Measurement error correction in nutritional epidemiology based on individual foods, with application to the relation of diet to breast cancer.

Nutrient intake is often measured with error by commonly used dietary instruments such as the food frequency questionnaire (FFQ) or 24-hour recall. More accurate assessments of true intake are obtained by using weighed diet records, in which subjects record what they eat on a real-time basis, but these records are expensive to administer. Validation studies are often performed to relate "gold standard" intake to intake according to surrogate instruments and to correct relative risk estimates obtained in the main study for measurement error. Most measurement error correction methods use validation study data at the nutrient level. However, subjects almost always report intake at the food rather than the nutrient level. In addition, the validity of measurement of different foods can vary considerably; it is relatively high for some foods (e.g., beverages) but relatively low for others (e.g., meats, vegetables). This differential validity could be incorporated into measurement error methods and potentially improve on nutrient-based measurement error methods. In this paper, the authors discuss correction methods for food-based measurement error and apply them to study the relation between FFQ intake in 1980 and incident breast cancer in 1980-1994 among approximately 89,000 women in the Nurses' Health Study, in whom approximately 3,000 incident breast cancers were observed.

Adult↗

PubMed2001

The effect of fruit and vegetable intake on risk for coronary heart disease.

BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease.

Adult↗

PubMed2001

Dietary fat and risk for advanced age-related macular degeneration.

OBJECTIVE: To evaluate the relationship between intake of total and specific types of fat and risk for advanced age-related macular degeneration (AMD), the leading cause of irreversible blindness in adults. DESIGN: A multicenter eye disease case-control study. SETTING: Five US clinical ophthalmology centers. PATIENTS: Case subjects included 349 individuals (age range, 55-80 years) with the advanced, neovascular stage of AMD diagnosed within 1 year of their enrollment into the study who resided near a participating clinical center. Control subjects included 504 individuals without AMD but with other ocular diseases. Controls were from the same geographic areas as cases and were frequency-matched to cases by age and sex. MAIN OUTCOME MEASURES: Relative risk for AMD according to level of fat intake, controlling for cigarette smoking and other risk factors. RESULTS: Higher vegetable fat consumption was associated with an elevated risk for AMD. After adjusting for age, sex, education, cigarette smoking, and other risk factors, the odds ratio (OR) was 2.22 (95% confidence interval [CI], 1.32-3.74) for persons in the highest vs those in the lowest quintiles of intake (P for trend,.007). The risk for AMD was also significantly elevated for the highest vs lowest quintiles of intake of monounsaturated (OR, 1.71) and polyunsaturated (OR, 1.86) fats (Ps for trend,.03 and.03, respectively). Higher consumption of linoleic acid was also associated with a higher risk for AMD (P for trend,.02). Higher intake of omega-3 fatty acids was associated with a lower risk for AMD among individuals consuming diets low in linoleic acid, an omega-6 fatty acid (P for trend,.05; P for continuous variable,.03). Similarly, higher frequency of fish intake tended to reduce risk for AMD when the diet was low in linoleic acid (P for trend,.05). Conversely, neither omega-3 fatty acids nor fish intake were related to risk for AMD among people with high levels of linoleic acid intake. CONCLUSION: Higher intake of specific types of fat--including vegetable, monounsaturated, and polyunsaturated fats and linoleic acid--rather than total fat intake may be associated with a greater risk for advanced AMD. Diets high in omega-3 fatty acids and fish were inversely associated with risk for AMD when intake of linoleic acid was low.

Aged↗

PubMed2001

A population-based case-control study of carotenoid and vitamin A intake and ovarian cancer (United States).

OBJECTIVE: To evaluate the association between dietary intake of carotenoids and vitamin A and the incidence of ovarian cancer. METHODS: We conducted a population-based case-control study of ovarian cancer in Massachusetts and Wisconsin. Incident cases diagnosed between 1991 and 1994 were identified through statewide tumor registries. We selected community controls at random from lists of licensed drivers and Medicare recipients; 327 cases and 3129 controls were included in the analysis. Data were collected by telephone interview, which included an abbreviated food and supplement list to quantify typical consumption of carotenoids (lutein/zeaxanthin, alpha-carotene, beta-carotene), retinol and total vitamin A at 5 years prior to diagnosis in cases, or to a comparable reference date in controls. Results were adjusted for age, state, and other risk factors. RESULTS: Participants with the highest dietary intake of lutein/zeaxanthin (> or =24,000 microg/week) experienced a 40% lower risk of ovarian cancer (95% CI = 0.36-0.99) compared to those with the lowest intake. Intake of alpha-carotene, beta-carotene, retinol and total vitamin A was unrelated to risk. Among foods, we observed non-significantly lower risks with high consumption of spinach, carrots, skim/lowfat milk and liver. CONCLUSION: These results support previous findings suggesting an inverse relationship between carotenoid intake and ovarian cancer risk.

Adult↗

PubMed2001

Sex hormone levels in premenopausal African-American women with upper and lower body fat phenotypes.

Body fat distribution may be a better marker of a hormonal pattern associated with increased breast cancer risk than obesity. This cross-sectional study of 106 healthy premenopausal African-American (AA) women compared the midfollicular phase sex hormone and sex hormone-binding globulin levels in upper body fat (UBF) and lower body fat (LBF) phenotype and obese and nonobese women. Multivariate regression analyses were used to control for various confounders, including dietary factors. UBF phenotype women had 37% (P = 0.02), 50% (P = 0.01), 52% (P = 0.007), and 50% (P = 0.009) higher levels of estradiol (E2), free E2, testosterone (T), and free T, respectively, than LBF phenotype women. Only %free T was higher in obese than in nonobese women (P = 0.02). The levels of E2, free E2, %free E2, T, and free T were higher [by 42% (P = 0.01), 68% (P = 0.001), 18% (P = 0.04), 36% (P = 0.04), and 61% (P = 0.01), respectively] and the level of sex hormone-binding globulin was lower [by 28% (P = 0.04)] in obese UBF than in nonobese LBF phenotype women. These findings support the hypothesis that body fat distribution may be a better marker of a hormonal pattern associated with increased breast cancer risk than obesity. Obese UBF phenotype AA women, in particular, have a high-risk hormonal profile. Future breast cancer studies might consider controlling for measures of obesity and body fat distribution to minimize confounding.

Adipose Tissue↗

PubMed2000

Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses' Health Study.

Because of the temporal relations between reproductive risk factors and incidence of breast cancer, the authors developed a nonlinear Poisson regression that accounts for time and summarizes risk to age 70 years. Reproductive risk factors, benign breast disease, use of postmenopausal hormones, weight, and alcohol intake were evaluated as risk factors. Among 58,520 women aged 30-55 years in 1980, followed through June 1, 1994, 1,761 incident invasive breast cancer cases were identified. All risks are multivariate adjusted. History of benign breast disease is associated with a 57% increase (95% confidence interval (CI): 43%, 73%) in cumulative risk of breast cancer by age 70 years. Use of unopposed postmenopausal estrogen from ages 50-60 years increases risk of breast cancer to age 70 by 23% (95% CI: 6%, 42%) compared with a woman who never uses hormones. Ten years of use of estrogen plus progestin increases risk to age 70 years by 67% (95% CI: 18%, 136%). Compared with never drinking alcohol, one drink per day from age 18 years increases risk to age 70 by 7% (95% CI: 0%, 13%). Use of unopposed postmenopausal hormones for 10 years significantly increases the risk of breast cancer, and the addition of progestin further increases the risk.

Adult↗

PubMed2000

Seven-year changes in alcohol consumption and subsequent risk of cardiovascular disease in men.

BACKGROUND: Few studies have examined whether changes in alcohol consumption influence future cardiovascular risk. OBJECTIVE: To examine whether 7-year changes in alcohol consumption are associated with the subsequent risk of cardiovascular disease (CVD). METHODS: We prospectively followed up 18,455 men aged 40 to 84 years from the Physicians' Health Study with no history of CVD or cancer. Alcohol consumption was reported on the baseline and the 7-year questionnaires; follow-up for this analysis began after the 7-year questionnaire (median follow-up, 5.8 years). There were 1091 CVD cases, including myocardial infarction, angina pectoris, revascularization, stroke, and CVD-related death. RESULTS: Among men initially consuming 1 drink per week or less (n=7360), those with moderate increases (>1 to <6 drinks per week) in alcohol consumption had a borderline significant (P=.05) 29% reduced risk of CVD compared with men with no changes (-1 to 1 drink per week). Among men initially consuming greater than 1 to 6 drinks per week (n=6612), those with moderate increases had a nonsignificant (P=.32) 15% decrease in CVD risk compared with men with no changes. Finally, among men initially consuming 1 drink per day or more (n=4483), those who increased intake had a 63% increased risk of CVD compared with men with no changes. CONCLUSIONS: These prospective data suggest that, among men with initially low alcohol consumption (</=1 drink per week), a subsequent moderate increase in alcohol consumption may lower their CVD risk. The possible reduction in CVD risk from increasing alcohol intake did not extend to men initially consuming greater than 1 drink per week. Given the potential risks and benefits associated with alcohol consumption, physician counseling of patients must be individualized in the context of the primary prevention of CVD.

Adult↗

PubMed2000

Two-year changes in blood pressure and subsequent risk of cardiovascular disease in men.

BACKGROUND-It is unclear whether, given a current blood pressure level, the previous 2-year change in blood pressure adds important predictive information for cardiovascular disease (CVD). METHODS AND RESULTS-We conducted a prospective cohort study of 11 150 middle-aged and older men reporting blood pressure in the Physicians' Health Study. These men had no history of CVD or antihypertensive medication use through the time of the 2-year follow-up questionnaire; after this time, follow-up for the current study began. A total of 905 incident cases of CVD (705 cases of coronary heart disease and 200 cases of stroke) occurred during a median follow-up of 10.8 years. After controlling for current blood pressure and other coronary risk factors, we found that previous 2-year changes in systolic blood pressure were not associated with the risk of CVD. A similar lack of association was found for individual end points of coronary heart disease and stroke. However, previous 2-year changes in diastolic blood pressure (DBP) may be inversely associated with the risk of CVD (linear trend, P=0.049) independent of coronary risk factors and current DBP. In subgroup analyses, previous 2-year blood pressure changes only added information in leaner men (body mass index <24.39 kg/m(2)). CONCLUSIONS-In this normotensive population of men, the prior 2-year change in DBP, but not systolic blood pressure, may add information to current levels in relation to the risk of CVD. Clinicians may need to consider the previous pattern of DBP change when considering the risk associated with the current DBP level. These data require confirmation in other studies in which blood pressure is measured.

Adult↗

PubMed2000

Blood pressure differences between blacks and whites in relation to body size among US children and adolescents.

No large national studies of ethnic differences in blood pressure among children accounting for body size differences have been published, to the authors' knowledge. This report details the similarities and differences in systolic and diastolic blood pressures between Black children and White children in the United States and examines the effects of age, sex, and body size on ethnic differences in blood pressure levels. Standardized measurements of seated systolic and diastolic pressures from eight large epidemiologic studies published between 1978 and 1991 that included measurements of 47,196 children on 68,556 occasions for systolic pressure and for 38,184 children on 52,053 occasions for diastolic pressure were used; 51 percent (24,048 children) were boys and 37 percent (17,466 children) were Black. Overall, there appear to be few substantive ethnic differences in either systolic or diastolic pressure during childhood and adolescence. The differences that were observed were small, inconsistent, and often explained by differences in body size. There was an ethnic group-body mass index (BMI) interaction that resulted in these findings that at lower levels of BMI Blacks have higher blood pressure and more hypertension than do Whites, but that at the highest levels of BMI, Whites have more hypertension (systolic or diastolic pressure) than do Blacks.

Adolescent↗

PubMed2000

Prospective study of bowel movement, laxative use, and risk of colorectal cancer among women.

The authors prospectively examined the association between bowel movement frequency, laxative use, and the risk of colorectal cancer in 84,577 women of the Nurses' Health Study living in the United States, 36-61 years of age and free of cancer in 1982. Between 1984 and 1996, 611 incident cases of colorectal cancer were documented. After controlling for age, body mass index, fiber intake, postmenopausal status and hormone use, physical activity, and use of laxatives, the relative risks associated with having bowel movements every third day or less, compared with those with bowel movements once daily, were 0.94 (95% confidence interval (CI): 0.69, 1.28) for colorectal cancer, 0.88 (95% CI: 0.62, 1.26) for colon cancer, and 1.18 (95% CI: 0.63, 2.20) for rectal cancer. Compared with women who never used laxatives, the multivariate relative risks associated with weekly to daily laxative use were 1.00 (95% CI: 0.72, 1.40) for colorectal cancer, 1.09 (95% CI: 0.76, 1.57) for colon cancer, and 0.68 (95% CI: 0.29, 1.57) for rectal cancer. These findings do not support an association between infrequent bowel movement, laxative use, and risk of colorectal cancer and indicate that simple questions directed at bowel movement frequency are unlikely to enhance our ability to predict colorectal cancer risk.

Aged↗

PubMed2000

Methods to quantify the relation between disease progression in paired eyes.

The authors compared, in the context of diabetic retinopathy, alternative methods of quantifying the extent to which disease progression in one eye increases the risk of subsequent progression in the other eye. Data were gathered on 478 US patients with insulin-dependent diabetes mellitus who participated in the 1983-1988 Sorbinil Retinopathy Trial and were followed up for a median of 41 months. During that time, diabetic retinopathy progressed in 93 right eyes and 77 left eyes. Crude incidence rates of progression for right eyes were 7.7 times higher after the left eye had progressed and, for left eyes, were 4.4 times higher after the right eye had progressed. In eye-specific proportional hazards models that adjusted for increasing rates of progression over time and for baseline risk factors, the comparable relative risks associated with progression in the other eye were 2.6 (95% confidence interval (CI): 1.5, 4.7) for right eyes and 1.4 (95% CI: 0.72, 2.9) for left eyes. Two alternative proportional hazards models that included data on both eyes and accounted for their correlation produced estimated relative risks of 1.9 (95% CI: 1.2, 2.9) and 2.7 (95% CI: 1.8, 3.5), respectively. The more complex models for joint survival integrate information on both eyes and provide more stable estimates than do separate analyses of right or left eyes.

Adult↗

PubMed2000

Bias in breast cancer analyses due to error in age at menopause.

With the use of data from the Nurses' Health Study, the authors confirm the recent argument by Pike et al. (Am J Epidemiol 1998;147:718-21) that various ways of assigning ages at menopause to women with simple hysterectomy produce relative risks for the effect of hormone replacement therapy (HRT) that are biased downward. Different methods of including women with simple hysterectomy consistently produced relative risks for the association between a 1-year increase in duration of HRT use and breast cancer that were underestimates compared with the relative risk obtained when these women were excluded from analysis. The authors used longitudinal data on recalled age at menopause to demonstrate another source of error related to age at menopause: error in recall of age at menopause that increases with time since menopause.

Adult↗