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R G Ziegler

Publications and source records attributed to R G Ziegler.

At least 19 recordsLinked to original sources
PubMed2002

Does place of birth influence endogenous hormone levels in Asian-American women?

In 1983-87, we conducted a population-based case-control study of breast cancer in Asian women living in California and Hawaii, in which migration history (a composite of the subject's place of birth, usual residence in Asia (urban/rural), length of time living in the West, and grandparents' place of birth) was associated with a six-fold risk gradient that paralleled the historical differences in incidence rates between the US and Asian countries. This provided the opportunity to determine whether endogenous hormones vary with migration history in Asian-American women. Plasma obtained from 316 premenopausal and 177 naturally premenopausal study controls was measured for levels of estrone (E1), estradiol (E2), estrone sulphate (E1S), androstenedione (A), testosterone (T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), progesterone (PROG) and sex hormone-binding globulin (SHBG). Levels of the oestrogens and sex hormone-binding globulin did not differ significantly between Asian- and Western-born women, although among premenopausal women, those least westernised had the lowest levels of E1, E2, and E1S. Androgen levels, particularly DHEA, were lower in women born in the West. Among premenopausal women, age-adjusted geometric mean levels of DHEA were 16.5 and 13.8 nmol l(-1) in Asian- and Western-born women respectively; in postmenopausal women these values were 11.8 and 9.2 nmol l(-1), (P<0.001) respectively. Among postmenopausal women, androgens tended to be highest among the least westernised women and declined as the degree of westernisation increased. Our findings suggest that aspects of hormone metabolism play a role in population differences in breast cancer incidence.

Adult↗
PubMed2002

Serum lycopene, other serum carotenoids, and risk of prostate cancer in US Blacks and Whites.

Epidemiologic studies investigating the relation between individual carotenoids and risk of prostate cancer have produced inconsistent results. To further explore these associations and to search for reasons prostate cancer incidence is over 50% higher in US Blacks than Whites, the authors analyzed the serum levels of individual carotenoids in 209 cases and 228 controls in a US multicenter, population-based case-control study (1986-1989) that included comparable numbers of Black men and White men aged 40-79 years. Lycopene was inversely associated with prostate cancer risk (comparing highest with lowest quartiles, odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.36, 1.15; test for trend, p = 0.09), particularly for aggressive disease (comparing extreme quartiles, OR = 0.37, 95% CI: 0.15, 0.94; test for trend, p = 0.04). Other carotenoids were positively associated with risk. For all carotenoids, patterns were similar for Blacks and Whites. However, in both the controls and the Third National Health and Nutrition Examination Survey, serum lycopene concentrations were significantly lower in Blacks than in Whites, raising the possibility that differences in lycopene exposure may contribute to the racial disparity in incidence. In conclusion, the results, though not statistically significant, suggest that serum lycopene is inversely related to prostate cancer risk in US Blacks and Whites.

Adult↗
PubMed2001

Is shorter always better? Relative importance of questionnaire length and cognitive ease on response rates and data quality for two dietary questionnaires.

In this study, the authors sought to determine the effects of length and clarity on response rates and data quality for two food frequency questionnaires (FFQs): the newly developed 36-page Diet History Questionnaire (DHQ), designed to be cognitively easier for respondents, and a 16-page FFQ developed earlier for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The PLCO Trial is a 23-year randomized controlled clinical trial begun in 1992. The sample for this substudy, which was conducted from January to April of 1998, consisted of 900 control and 450 screened PLCO participants aged 55-74 years. Controls received either the DHQ or the PLCO FFQ by mail. Screenees, who had previously completed the PLCO FFQ at baseline, were administered the DHQ. Among controls, the response rate for both FFQs was 82%. Average amounts of time needed by controls to complete the DHQ and the PLCO FFQ were 68 minutes and 39 minutes, respectively. Percentages of missing or uninterpretable responses were similar between instruments for questions on frequency of intake but were approximately 3 and 9 percentage points lower (p < or = 0.001) in the DHQ for questions on portion size and use of vitamin/mineral supplements, respectively. Among screenees, response rates for the DHQ and the PLCO FFQ were 84% and 89%, respectively, and analyses of questions on portion size and supplement use showed few differences. These data indicated that the shorter FFQ was not better from the perspective of response rate and data quality, and that clarity and ease of administration may compensate for questionnaire length.

Aged↗
PubMed2001

Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women.

OBJECTIVES: To explore the relationship between serum homocysteine, a sensitive biomarker for folate inadequacy and problems in one-carbon metabolism, and invasive cervical cancer. METHODS: A large case-control study was conducted in five US areas with up to two community controls, obtained by random-digit dialing, individually matched to each case. Cervical cancer risk factors were assessed through at-home interview. Blood was drawn at least 6 months after completion of cancer treatment from 51% and 68% of interviewed cases and controls. Serum homocysteine was measured by high-performance liquid chromatography, and exposure to human papillomavirus (HPV) type 16, the most prevalent oncogenic type, was assessed using an enzyme-linked immunosorbent assay. Cases with advanced cancer and/or receiving chemotherapy were excluded, leaving 183 cases and 540 controls. RESULTS: Invasive cervical cancer risk was substantially elevated for women in the upper three homocysteine quartiles (> 6.31 micromol/L); multivariate-adjusted odds ratios ranged from 2.4 to 3.2 (all 95% CIs excluded 1.0). A trend was apparent and significant (p = 0.01). When cases were compared with HPV-16 seropositive controls only, odds ratios were comparable. CONCLUSIONS: Serum homocysteine was strongly and significantly predictive of invasive cervical cancer risk. This association could reflect folate, B12 and/or B6 inadequacy, or genetic polymorphisms affecting one-carbon metabolism.

Adult↗
PubMed2001

Low serum and red blood cell folate are moderately, but nonsignificantly associated with increased risk of invasive cervical cancer in U.S. women.

Previous observational epidemiologic studies of folate and cervical cancer, as well as folate supplementation trials for cervical dysplasia, have produced mixed results. We examined the relationship between serum and RBC folate and incident invasive cervical cancer in a large, multicenter, community-based case-control study. Detailed in-person interviews were conducted, and blood was drawn at least 6 mo after completion of cancer treatment from 51% of cases and 68% of controls who were interviewed. Blood folate was measured with both microbiologic and radiobinding assays. Included in the final analyses were 183 cases and 540 controls. Logistic regression was used to control for all accepted risk factors, including age, sexual behavior, smoking, oral contraceptive use, Papanicolaou smear history and human papillomavirus (HPV)-16 serology. For all four folate measures, the geometric mean in cases was lower than in controls (e.g., 11.6 vs. 13.0 nmol/L, P < 0.01 for the serum radiobinding assay). Folate measures using microbiologic and radiobinding assays were correlated (serum: r = 0.90; RBC: r = 0.77). For serum folate, multivariate-adjusted odds ratios (OR) in the lowest vs. highest quartile were 1.3 [95% confidence interval (CI) = 0.8--2.9] and 1.6 (0.9--2.9), using the microbiologic and radiobinding assays, respectively. For RBC folate, comparable OR were 1.2 (0.6--2.2) and 1.5 (0.8--2.7). Similar risks were obtained when restricting analyses to subjects with a history of HPV infection. Thus, low serum and RBC folate were each moderately, but nonsignificantly, associated with increased invasive cervical cancer risk. These findings support a role for one-carbon metabolism in the etiology of cervical cancer.

Adenocarcinoma↗
PubMed2001

Insulin-like growth factors and prostate cancer: a population-based case-control study in China.

Insulin-like growth factors (IGFs) have potent mitogenic and antiapoptotic effects on prostate epithelial cells. Through modulation of IGF bioactivity and other mechanisms, IGF-binding proteins (IGFBPs) also have growth-regulatory effects on prostate cells. Recently, IGF-I and IGFBP-3 have been implicated in prostate cancer risk among Western populations. To assess whether IGF-I, IGF-II, IGFBP-1, or IGFBP-3 are also associated with prostate cancer in a low-risk population, we measured plasma levels of these factors among 128 newly diagnosed prostate cancer cases and 306 randomly selected population controls in Shanghai, China. Relative to the lowest quartile of IGF-I levels, men in the highest quartile had a 2.6-fold higher prostate cancer risk, with a significant trend [odds ratio (OR) = 2.63; 95% confidence interval (95% CI) = 1.19-5.79; P(trend) = 0.01]. In contrast, men in the highest quartile of IGFBP-3 levels had a 46% decreased risk relative to the lowest quartile (OR = 0.54; 95% CI = 0.26-1.15; P(trend) = 0.08). A similar but less distinct result was observed for IGFBP-1 (OR = 0.60; 95% CI = 0.31-1.17; P(trend) = 0.25). Men in the highest quartile for the IGF-I:IGFBP-3 molar ratio (an indirect measure of free IGF-I) had a 2.5-fold higher risk compared with the lowest quartile (OR = 2.51; 95% CI = 1.32-4.75, P(trend) < 0.001). These associations were more pronounced after adjustment for serum 5alpha-androstane-3alpha,17beta-diol glucuronide and sex hormone-binding globulin levels. There was no significant association with IGF-II levels. Our findings in a low-risk population provide evidence that IGF-I, IGFBP-3, and IGFBP-1 are determinants of prostate cancer and indicate that additional studies are needed to evaluate their effects on ethnic and geographic incidence differentials and to elucidate carcinogenic mechanisms.

Aged↗
PubMed2000

Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women.

BACKGROUND: Diets high in fruits and vegetables have been shown to be associated with a lower risk of lung cancer. beta-Carotene was hypothesized to be largely responsible for the apparent protective effect, but this hypothesis was not supported by clinical trials. METHODS: We examined the association between lung cancer risk and fruit and vegetable consumption in 77 283 women in the Nurses' Health Study and 47 778 men in the Health Professionals' Follow-up Study. Diet was assessed with the use of a food-frequency questionnaire that included 15 fruits and 23 vegetables. We used logistic regression models to estimate relative risks (RRs) of lung cancer within each cohort. All statistical tests were two-sided. RESULTS: We documented 519 lung cancer cases among the women and 274 among the men. Total fruit and vegetable consumption was associated with a modestly lower risk of lung cancer among the women but not among the men. The RR for the highest versus lowest quintile of intake was 0.79 (95% confidence interval [CI] = 0.59-1.06) among the women and 1.12 (95% CI = 0.74-1.69) among the men after adjustment for smoking status, quantity of cigarettes smoked per day, time since quitting smoking, and age at initiation of smoking. However, total fruit and vegetable consumption was associated with a lower risk of lung cancer among never smokers in the combined cohorts, although the reduction was not statistically significant (RR = 0.63; 95% CI = 0.35-1.12 in the highest tertile). CONCLUSION: Higher fruit and vegetable intakes were associated with lower risks of lung cancer in women but not in men. It is possible that the inverse association among the women remained confounded by unmeasured smoking characteristics, although fruits and vegetables were protective in both men and women who never smoked.

Adult↗
PubMed2000

Etiologic and early marker studies in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial.

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which is randomizing 74,000 screening arm participants (37,000 men, 37,000 women; ages 55-74) and an equal number of nonscreened controls, is a unique setting for the investigation of the etiology of cancer and other diseases and for the evaluation of potential molecular markers of early disease. At entry, baseline information is collected by questionnaire on dietary intake, tobacco and alcohol use, reproductive history (for women), family history of cancer, use of selected drugs, and other selected risk factors. Blood samples collected at the baseline screening exam are aliquoted to serum, plasma, red blood cell, and buffy coat fractions. At the next two annual screening visits, serum samples are collected. At the third annual reexamination, cryopreserved whole blood is obtained, in addition to serum, plasma, red blood cell, and buffy coat fractions. At the fourth and fifth years, serum, plasma, and buffy coat are collected. All blood samples are shipped to a central repository for long-term storage at -70 degrees C. Dietary questionnaires and buccal cells for DNA analysis are obtained from nonscreened controls. Cancer cases are identified through annual follow-up questionnaires, and all deaths are identified through vital status tracing mechanisms. Procedures are being developed to obtain archival pathologic material for selected cases of cancer and related diseases. Initial investigations are focusing on the etiology of colorectal cancer and on the operative characteristics of tests for the early detection of colorectal and prostate cancer.

Aged↗
PubMed2000

The coordinated psychosocial and neurologic care of children with seizures and their families.

SUMMARY: As the medical and surgical management of epilepsy continues to advance, issues associated with the quality of life of patients and their families can be addressed. Whenever associated with other handicaps, such as learning disabilities, attentional or behavioral disorders, and problems in psychological adjustment, dual-diagnosis issues must be identified. To provide comprehensive care for children with epilepsy, a team approach to psychosocial assessment and treatment must be provided and coordinated with neurologic care. When the age-related needs in the life stage of the individual and family are identified, the best possible adaptation of the patient and his or her family can be supported.

Adolescent↗
PubMed2000

Eating frequency and risk of colorectal cancer.

Case-control studies have found elevated risk of colorectal cancer with higher eating frequency. The present analyses, the first to examine this association using prospectively collected information, utilized nationally representative data from the Epidemiologic Follow-Up Study of the First National Health and Nutrition Examination Survey (NHEFS). The study population included 9,978 subjects followed from 1982-84 to 1992. Colorectal cancer cases (n = 141) were identified by self-report, hospital records, and death certificates. Interviews conducted in 1982-84 provided information on meal and snack frequencies and covariates of interest. Relative risk (RR) of colorectal cancer and 95% confidence intervals (CI) were estimated using Cox proportional hazards models adjusted for age, gender, and race and energy, alcohol, total fat, and fiber intake. Compared with those eating < 3 times/day, those eating 3-4 times/day had an RR of 0.66 (95% CI = 0.42-1.03) and those eating > 4 times/day had an RR of 0.74 (95% CI = 0.41-1.32). The association was due to decreased risk with more meals rather than more snacks per day. Given limitations of previous studies as well as the possibility of a protective effect of higher eating frequency through improved glycemic control, the present findings suggest that the influence of eating frequency on colorectal cancer risk is more complex than has been previously supposed and merits additional study.

Adult↗
PubMed2000

A new ELISA kit for measuring urinary 2-hydroxyestrone, 16alpha-hydroxyestrone, and their ratio: reproducibility, validity, and assay performance after freeze-thaw cycling and preservation by boric acid.

There is considerable controversy regarding the role of estrogen metabolites in breast cancer risk, fueled in part by the development of a rapid ELISA that is suitable for large scale investigations. An earlier version of the ELISA could detect values of the 2-hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha-OHE1) metabolites as low as 2 ng/ml and produce consistent results in premenopausal urines. However, reproducibility was problematic in postmenopausal urines where concentrations of these compounds are much lower. In response to our concern, a new ELISA was developed with a sensitivity of 0.625 ng/ml, which we evaluated using the same pre- and postmenopausal urine samples analyzed in the earlier ELISA. In this report, we present findings on the new kit with regard to reproducibility of the 2-OHE1 and 16alpha-OHE1 measurements, comparability of results with gas chromatography-mass spectroscopy values, and with regard to the stability of the metabolites after repeated freeze-thaw cycles and after preservation by boric acid. For the most part, we found the new ELISA to be reproducible, with assay coefficients of variation ranging from 10 to 20%, and intraclass correlation coefficients (ICCs) ranging from 80 to 95% in both the pre- and postmenopausal urines. ELISA results for 16alpha-OHE1 differed from 1 day (i.e., batch) to the next, and the absolute values of the metabolites obtained by the ELISA were consistently lower than but well correlated with those obtained by gas chromatography-mass spectroscopy. Values of the 2-OHE1:16alpha-OHE1 ratio also differed between the methods, but because the range of values was not large, the magnitude of these differences was not as great. For the ratio, the correlation between methods was excellent, and the ICCs were high for both groups of women. After preservation by boric acid, values of the ratio varied according to acid concentration but not in a linear fashion. Ratio values were similar in urine samples exposed to four different freeze-thaw cycle treatments, although values for all treatments were consistently lower in one batch. Because batch-to-batch variability was not negligible, it is advisable that matched cases and controls be analyzed in the same batch. Provided this is done, the relatively low assay coefficient of variation and high ICC demonstrate that the new ELISA kit can reliably measure the 2-OHE1:16alpha-OHE1 ratio and detect small case-control differences in large population-based studies, where rapid and relatively easy laboratory methods are critical.

Boric Acids↗
PubMed2000

Reproducibility studies and interlaboratory concordance for androgen assays in female plasma.

We conducted studies to determine the magnitude and sources of variability in androgen assay results and to identify laboratories capable of performing such assays for large epidemiological studies. We studied androstanediol (ADIOL), androstanediol glucuronide (ADIOL G), androstenedione (ADION), androsterone glucuronide (ANDRO G), androsterone sulfate (ANDRO S), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA S), dihydrotestosterone (DHT), and testosterone (TESTO). A single sample of plasma was obtained from five postmenopausal women, five premenopausal women in the midfollicular phase of the menstrual cycle, and five women in the midluteal phase, divided into aliquots, and stored at -70 degrees. Four sets of two coded aliquots from each woman were then sent to participating labs for analysis at monthly intervals over 4 months. Using the logarithm of assay measurements, we estimated the components of variance and three measures of reproducibility. The usual coefficient of variation is a function of the components that are under the control of the laboratory. The intraclass correlation between measurements for a given individual is the proportion of the total variability that is associated with individuals. The minimum detectable relative difference is important to evaluate study feasibility. Results suggest that a single sample of ADIOL G, DHEA, DHEA S, and ANDRO G (with two lab replicates per sample) can be used to discriminate reliably among women in a given menstrual phase or menopausal status. The results for DHT, TESTO, ADION, and ANDRO S are more problematic and suggest that the present measurement techniques should be used with care, especially with midluteal phase women. The results for ADIOL suggest that this assay is not yet ready for use in epidemiological studies.

Adult↗
PubMed1999

Breast cancer and oral contraceptive use in Asian-American women.

Breast cancer incidence has historically been 4-7 times higher in the United States than in Asia. A previous study by the authors in Asian-American women demonstrated a substantial increase in breast cancer risk in women who migrated from Asia to the United States, with the risk almost doubling during the first decade after migration. Increased use of oral contraceptives soon after migration to the United States could possibly explain this rapid rise in risk. In a population-based case-control study of Chinese, Filipino, and Japanese-American women, aged 20-55 years, who lived in San Francisco-Oakland, California; Los Angeles, California; and Oahu, Hawaii during 1983-1987, 597 cases (70% of those eligible) and 966 controls (75%) were interviewed. Controls were matched to cases on age, ethnicity, and area of residence. Oral contraceptive (OC) use increased with time since migration; 15.0% of Asian-born women who had been in the West <8 years, 33.4% of Asian-born women who had been in the West > or =8 years, and 49.6% of Asian women born in the West had ever used OCs. However, duration of OC use (adjusted for age, ethnicity, study area, years since migration, education, family history of breast cancer and age at first full-term birth) was not associated with increased risk of breast cancer. Moreover, neither OC use before age 25 years nor before first full-term birth was associated with increased risk. Results were unchanged when restricted to women under age 45 years or under age 40 years. After adjustment for duration of OC use, women who had been in the United States > or =8 years were still at almost twice the risk of breast cancer compared with women who had been in the United States 2-7 years. This study suggests that OC use cannot explain the elevated risk observed in Asian women who migrated to the United States > or =7 years ago.

Adult↗
PubMed1999

Alcohol and prostate cancer in the NHANES I epidemiologic follow-up study. First National Health and Nutrition Examination Survey of the United States.

PURPOSE: We prospectively investigated the association between alcohol consumption and prostate cancer in the Epidemiologic Follow-up Study (NHEFS) of the first National Health and Nutrition Examination Survey (NHANES I). METHODS: There were two cohorts: 1) Cohort I, followed from baseline (1971-75) through 1992, included 5766 men ages 25-74 years (median follow-up = 17 years); and 2) Cohort II, followed from the first follow-up round for Cohort I (1982-84) through 1992, included the 3868 men in Cohort I free of prostate cancer in 1982-84 (median follow-up = 9 years). Alcohol consumption was assessed at baseline as usual consumption, and at follow-up as usual consumption and as distant past consumption at the ages of 25, 35, 45, and 55. RESULTS: There were 252 incident cases of prostate cancer. Consistent with most previous studies, we found no significant associations between usual total alcohol consumption and prostate cancer in Cohorts I or II [p = non significant (NS)], except for a significant inverse association at the heaviest level of drinking in Cohort II [relative risk (RR) = 0.23, 95% confidence interval (CI) = 0.06-0.95]. Further study of heavy drinkers in Cohort II revealed significant inverse associations between distant past heavy drinking (defined as > 25 drinks/week) and prostate cancer at age 25 (RR = 0.20, 95% CI = 0.06-0.63), age 35 (RR = 0.30, 95% CI = 0.12-0.77), and age 45 (RR = 0.39, 95% CI = 0.17-0.93), but not at age 55 (RR = 0.43, 95% CI = 0.17-1.10). CONCLUSIONS: These results suggest that it may be important to consider distant past alcohol consumption in etiologic studies of prostate cancer. However, our results were based on small numbers of cases who were heavy drinkers and require replication.

Adult↗
PubMed1999

Do we facilitate the scientific process and the development of dietary guidance when findings from single studies are publicized? An American Society for Nutritional Sciences controversy session report.

This American Society for Nutritional Sciences Controversy Session presented at the 1997 Experimental Biology meeting considered whether publicity of findings from single studies facilitates or hampers the scientific process and the development of scientifically sound dietary guidance. In a 1995 survey, 78% of primary household shoppers believed it "very likely" or "somewhat likely" that in the next 5 y experts would have a completely different idea about which foods were healthy and which were not. This skepticism is fueled by the media's emphasis on reporting new and often controversial findings about food and nutrition. Media efforts are reinforced by the fact that some scientific journals regularly publicize newly published research findings. As a consequence, journalists frequently mediate scientific debate in a public forum-debate that previously was conducted among knowledgeable peers. Tight deadlines often make it difficult for reporters to thoroughly investigate findings publicized in press releases. Headlines can make results from single studies appear important, even when results are inconclusive. Finally, scientists and public policymakers have limited opportunity for making timely comments in response to an issue reported in the media. Nevertheless, the public has a right to be informed about health-related research findings to help them make decisions about their diets. The media are a valuable resource for educating the public and maintaining public interest in the importance of diet in overall health status. Nutrition scientists should be more involved in helping the media accurately convey diet and health messages.

Attitude to Health↗
PubMed1999

Reproducibility and validity of radioimmunoassays for urinary hormones and metabolites in pre- and postmenopausal women.

The reproducibility of RIAs of circulating sex hormones has been evaluated as part of recent epidemiological investigations, but none seem to have addressed the reproducibility or validity of RIAs for urinary hormones or their metabolites. As part of a case-control study of breast cancer in Asian-American women, 12-h overnight urine samples were obtained, and a methodological study was conducted to identify laboratories capable of assaying urinary hormones. For the reproducibility component of this study, two laboratories with extensive experience in hormone assays measured urinary estrone, estradiol, estriol, pregnanediol glucuronide, and estrone glucuronide using samples from 15 women (5 midfollicular, 5 midluteal, and 5 postmenopausal). Variance estimates from these measurements were used to calculate the laboratory variability (coefficient of variation) and to assess the magnitude of the biological variability among the women in relation to the total variability (intraclass correlation coefficient). For the validity component, urinary estrone, estradiol, and estriol levels were measured in the same samples by gas chromatography-mass spectroscopy in the laboratory of Dr. Herman Adlercreutz (University of Helsinki, Helsinki, Finland). We found that the degree of assay reproducibility differed between the laboratories, but that laboratory variability was usually low compared with the range of hormone values among women, particularly for the estrogens. Values for estrone and estradiol were well correlated among all of the laboratories. For estriol, the RIAs tended to overestimate levels compared with gas chromatography-mass spectroscopy. In one laboratory, assays for pregnanediol glucuronide and estrone glucuronide were consistently reproduced; in the other, the reproducibility of the RIA for pregnanediol glucuronide was problematic, and estrone glucuronide was not measured. Despite some limitations, urinary hormones and their metabolites can be reliably measured by current RIAs in large investigations attempting to link hormone level to disease risk and may be particularly advantageous for studies of postmenopausal women, where serum concentrations of estrone and estradiol are low and assay measurements are not as dependable.

Adult↗