Carol Rubin

Aflatoxin contamination of commercial maize products during an outbreak of acute aflatoxicosis in eastern and central Kenya.

In April 2004, one of the largest aflatoxicosis outbreaks occurred in rural Kenya, resulting in 317 cases and 125 deaths. Aflatoxin-contaminated homegrown maize was the source of the outbreak, but the extent of regional contamination and status of maize in commercial markets (market maize) were unknown. We conducted a cross-sectional survey to assess the extent of market maize contamination and evaluate the relationship between market maize aflatoxin and the aflatoxicosis outbreak. We surveyed 65 markets and 243 maize vendors and collected 350 maize products in the most affected districts. Fifty-five percent of maize products had aflatoxin levels greater than the Kenyan regulatory limit of 20 ppb, 35% had levels > 100 ppb, and 7% had levels > 1,000 ppb. Makueni, the district with the most aflatoxicosis case-patients, had significantly higher market maize aflatoxin than did Thika, the study district with fewest case-patients (geometric mean aflatoxin = 52.91 ppb vs. 7.52 ppb, p = 0.0004). Maize obtained from local farms in the affected area was significantly more likely to have aflatoxin levels > 20 ppb compared with maize bought from other regions of Kenya or other countries (odds ratio = 2.71; 95% confidence interval, 1.12–6.59). Contaminated homegrown maize bought from local farms in the affected area entered the distribution system, resulting in widespread aflatoxin contamination of market maize. Contaminated market maize, purchased by farmers after their homegrown supplies are exhausted, may represent a source of continued exposure to aflatoxin. Efforts to successfully interrupt exposure to aflatoxin during an outbreak must consider the potential role of the market system in sustaining exposure.

Heat-related mortality during a 1999 heat wave in Chicago.

BACKGROUND During the summer of 1999, Chicagos second deadliest heat wave of the decade resulted in at least 80 deaths. The high mortality, exceeded only by a 1995 heat wave, provided the opportunity to investigate the risks associated with heat-related deaths and to examine the effectiveness of targeted heat-relieving interventions. METHODS We conducted a case-control study to determine risk factors for heat-related death. We collected demographic, health, and behavior information for 63 case patients and 77 neighborhood-and-age-matched control subjects and generated odds ratios (ORs) for each potential risk factor. RESULTS Fifty-three percent of the case patients were aged <65 years, and psychiatric illness was almost twice as common in the younger than the older age group. In the multivariate analysis, the strongest risk factors for heat-related death were living alone (OR=8.1; 95% confidence interval [CI], 1.4-48.1) and not leaving home daily (OR=5.8; 95% CI, 1.5-22.0). The strongest protective factor was a working air conditioner (OR=0.2; 95% CI, 0.1-0.7). Over half (53%) of the 80 decedents were seen or spoken to on the day of or day before their deaths. CONCLUSIONS A working air conditioner is the strongest protective factor against heat-related death. The relatively younger age of case patients in 1999 may be due to post-1995 interventions that focused on the elderly of Chicago. However, social isolation and advanced age remain important risk factors. Individual social contacts and educational messages targeted toward at-risk populations during heat waves may decrease the number of deaths in these groups.

Genetic variation in LIN28B is associated with the timing of puberty

The timing of puberty is highly variable. We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 × 10−8). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08–0.16; P = 2.8 × 10−10; combined P = 3.6 × 10−16). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 × 10−7; N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing, as the first genetic determinant regulating the timing of human pubertal growth and development.

Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl.

Accidental contamination of the Michigan food chain with polybrominated biphenyls (PBBs) led to the exposure of more than 4,000 individuals in 1973. Because PBB exposure is suspected to disrupt endocrine function, we assessed pubertal development in females 5–24 years of age (N = 327) who were exposed to PBB in utero and, in many cases, through breastfeeding. We estimated in utero PBB exposure using maternal serum PBB measurements taken after exposure (1976–1979) and extrapolated to time of pregnancy using a model of PBB decay. We found that breastfed girls exposed to high levels of PBB in utero (≥7 parts per billion) had an earlier age at menarche (mean age = 11.6 years) than breastfed girls exposed to lower levels of PBB in utero (mean age = 12.2–12.6 years) or girls who were not breastfed (mean age = 12.7 years). This association persisted after adjustment for potential confounders (menarche ratio = 3.4, 95% confidence interval = 1.3–9.0). Perinatal PBB exposure was associated with earlier pubic hair stage in breastfed girls, but little association was found with breast development. The associations observed here lend support to the hypothesis that pubertal events may be affected by pre- and postnatal exposure to organohalogens.

Case-control study of an acute aflatoxicosis outbreak, Kenya, 2004

Objectives: During January–June 2004, an aflatoxicosis outbreak in eastern Kenya resulted in 317 cases and 125 deaths. We conducted a case–control study to identify risk factors for contamination of implicated maize and, for the first time, quantitated biomarkers associated with acute aflatoxicosis. Design: We administered questionnaires regarding maize storage and consumption and obtained maize and blood samples from participants. Participants: We recruited 40 case-patients with aflatoxicosis and 80 randomly selected controls to participate in this study. Evaluations/Measurements: We analyzed maize for total aflatoxins and serum for aflatoxin B1–lysine albumin adducts and hepatitis B surface antigen. We used regression and survival analyses to explore the relationship between aflatoxins, maize consumption, hepatitis B surface antigen, and case status. Results: Homegrown (not commercial) maize kernels from case households had higher concentrations of aflatoxins than did kernels from control households [geometric mean (GM) = 354.53 ppb vs. 44.14 ppb; p = 0.04]. Serum adduct concentrations were associated with time from jaundice to death [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 1.04–1.6]. Case patients had positive hepatitis B titers [odds ratio (OR) = 9.8; 95% CI, 1.5–63.1] more often than controls. Case patients stored wet maize (OR = 3.5; 95% CI, 1.2–10.3) inside their homes (OR = 12.0; 95% CI, 1.5–95.7) rather than in granaries more often than did controls. Conclusion: Aflatoxin concentrations in maize, serum aflatoxin B1–lysine adduct concentrations, and positive hepatitis B surface antigen titers were all associated with case status. Relevance: The novel methods and risk factors described may help health officials prevent future outbreaks of aflatoxicosis.

The Effect of the 1995 Heat Wave in Chicago on All-Cause and Cause-Specific Mortality

OBJECTIVES We sought to reexamine the effects of the 1995 Chicago heat wave on all-cause and cause-specific mortality, including mortality displacement, using advanced time-series analysis methods. METHODS We used Poisson regression with penalized regression splines to model excess mortality and mortality displacement over a 50-day period centered on the day in which the heat wave temperature peaked, adjusting for meteorological and other variables. We controlled for temporal trends by using daily mortality data during 1993-1997. We estimated relative risks (RRs) with reference to the first day of the 50-day period. RESULTS We estimated that there were 692 excess deaths from June 21, 1995, to August 10, 1995; 26% of these deaths were owing to mortality displacement. RR for all-cause mortality on the day with peak mortality was 1.74 (95% confidence interval=1.67, 1.81). Risk of heat-related death was significantly higher among Blacks, and mortality displacement was substantially lower. CONCLUSIONS The 1995 Chicago heat wave substantially effected all-cause and cause-specific mortality, but mortality displacement was limited. Mortality risks and displacement affected Blacks disproportionally. Appropriately targeted interventions may have a tangible effect on life expectancy.

Earlier Mother's Age at Menarche Predicts Rapid Infancy Growth and Childhood Obesity

Background Early menarche tends to be preceded by rapid infancy weight gain and is associated with increased childhood and adult obesity risk. As age at menarche is a heritable trait, we hypothesised that age at menarche in the mother may in turn predict her childrens early growth and obesity risk. Methods and Findings We tested associations between mothers age at menarche, mothers adult body size and obesity risk, and her childrens growth and obesity risk in 6,009 children from the UK population-based Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort who had growth and fat mass at age 9 y measured by dual-energy X-ray absorptiometry. A subgroup of 914 children also had detailed infancy and childhood growth data. In the mothers, earlier menarche was associated with shorter adult height (by 0.64 cm/y), increased weight (0.92 kg/y), and body mass index (BMI, 0.51 kg/m2/y; all p < 0.001). In contrast, in her children, earlier mothers menarche predicted taller height at 9 y (by 0.41 cm/y) and greater weight (0.80 kg/y), BMI (0.29 kg/m2/y), and fat mass index (0.22 kg/m2/year; all p < 0.001). Children in the earliest mothers menarche quintile (≤11 y) were more obese than the oldest quintile (≥15 y) (OR, 2.15, 95% CI 1.46 to 3.17; p < 0.001, adjusted for mothers education and BMI). In the subgroup, children in the earliest quintile showed faster gains in weight (p < 0.001) and height (p < 0.001) only from birth to 2 y, but not from 2 to 9 y (p = 0.3–0.8). Conclusions Earlier age at menarche may be a transgenerational marker of a faster growth tempo, characterised by rapid weight gain and growth, particularly during infancy, and leading to taller childhood stature, but likely earlier maturation and therefore shorter adult stature. This growth pattern confers increased childhood and adult obesity risks.

Heat-related death and mental illness during the 1999 Cincinnati heat wave.

During a 1999 heat wave in Cincinnati, Ohio, the Hamilton County Coroner reported 18 heat-related deaths. The Centers for Disease Control and Prevention and the Cincinnati Department of Health conducted a case–control study using surrogate case information and first-person control information to identify risk factors for mortality during the heat wave. Surrogate data were supplemented by systematic death scene investigation reports and comprehensive toxicologic screens, important sources of data that are routinely collected by the Hamilton County Coroner’s Office. The study included 17 case subjects and 34 controls from the decedents’ neighborhood. Among 17 case subjects, 8 (47.1%) had mental illness (odds ratio [OR], 14.0; 95% confidence interval [CI], 1.8–633). There was a suggestion of an interaction between age and mental health. A working air-conditioner was the strongest protective factor (OR, 0.03; 95% CI, 0–0.2). Toxicologic screening indicated that case subjects with reported mental illness and a prescription for psychotropic drugs may not have been medication compliant. Three decedents lived in group homes for people with mental illness, indicating that opportunities for prevention may have been missed. Systematic death investigations, including toxicologic screening, provide valuable information about the circumstances of heat-related death, particularly the role of medication compliance as a risk factor. Prevention programs during heat waves should target people with mental illness, especially those who take psychotropic medication.

Stature and pubertal stage assessment in American boys: the 1988-1994 Third National Health and Nutrition Examination Survey.

PURPOSE To describe current stature and pubertal development in North American boys, and to compare these measures with measures observed approximately 30 years ago. METHODS We analyzed data (i.e., height, weight, and Tanner Stage) from the Third National Health and Nutrition Examination Survey (NHANES III), conducted between 1988-1994, and compared it to the National Health Examination Survey, Cycles II and III (HES II/III), conducted from 1963-1965 and 1966-1970. The surveys included physical examination and questionnaire components, employed cross-sectional designs, and are nationally representative. We used logistic regression to calculate median age at onset of pubertal stages. RESULTS NHANES III included 2481 boys aged 8 to 18 years. HES II comprised 3010 boys aged 8-11 years and HES III comprised 3514 boys aged 12-17 years. The mean heights of the oldest boys in both surveys did not differ significantly; however, at younger ages, boys in the more recent survey were taller (average height difference among those aged 8-14 years was 2.0 cm). Boys in NHANES III were also heavier and had higher body mass index than those in HES II/III. The median estimated ages of onset of pubertal stages in NHANES III were 9.9, 12.2, 13.6, and 15.8 years for genital stages 2-5, respectively, and 11.9, 12.6, 13.6, and 15.7 years for pubic hair stages 2-5, respectively. For some stages, the median estimated age of onset of puberty was earlier among boys in NHANES III than among those in HES III. CONCLUSIONS Differences in mean height at young ages, but not at older ages, suggest that the rate of growth among boys in NHANES III was faster than that of boys in the earlier surveys. This finding, coupled with the finding of earlier ages of onset of some pubertal stages, suggests that boys of this generation may be maturing more rapidly than did boys in the past.

Timing of maturation and predictors of menarche in girls enrolled in a contemporary British cohort

This study describes the timing of puberty in 8- to 13-year-old girls enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) and identifies factors associated with earlier achievement of menarche. Women were enrolled during pregnancy and their offspring were followed prospectively. We analysed self-reported Tanner staging and menstrual status information collected annually from daughters up to age 13. We used survival models to estimate median age of attainment of stage >1 and stage >2 of breast and pubic hair development and of menarche. We also constructed multivariable logistic regression models to identify factors associated with earlier achievement of menarche. About 12% of girls reported Tanner breast stage >1 at age 8; 98% of girls were above stage 1 by age 13. For pubic hair, 5% and 95% of girls had attained a stage >1 by 8 and 13 years, respectively. The estimated median age of entry into stage >1 of breast development was 10.14 years (95% confidence interval [CI], 10.08, 10.19), and for pubic hair development the median age was 10.92 years [95% CI, 10.87, 10.97]. One girl (out of 2953) had attained menarche by age 8; 60% had attained menarche by age 13. The estimated median age at menarche was 12.93 years [95% CI, 12.89, 12.98]. Prenatal predictors of menarche by age 11 (12% of girls) included earlier maternal age at menarche, high maternal pre-pregnancy body mass index, smoking during the third trimester, and non-white race; the single postnatal predictor was the girls body size at 8 years. Age at attainment of breast and pubic hair Tanner stage and age at menarche in the ALSPAC cohort are similar to ages reported in other European studies that were conducted during overlapping time periods. The results also give added support to the strong influence of maternal maturation, pre-adolescent body size and race on the timing of a girls menarche. This cohort will continue to be followed for maturational information until age 17.