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Biomedical subjects

R J Hardy

Publications and source records attributed to R J Hardy.

At least 19 recordsLinked to original sources

Measuring the impact of HIV/AIDS, heart disease and malignant neoplasms on life expectancy in the USA from 1987 to 2000.

OBJECTIVES: Quantifying the impact of a disease on society is an important issue for setting priorities for better allocation of healthcare resources and for evaluating the effectiveness of prevention and control of the disease. STUDY DESIGN: The potential gains in life expectancy due to the elimination of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), heart disease and malignant neoplasms were compared for the US population by age and ethnicity from 1987 to 2000. METHODS: The potential gain in life expectancy after hypothetical elimination of cause-specific deaths is an effective indicator of measuring the impact of a disease on a population. Official age-specific mortality rates, by ethnicity, due to HIV/AIDS, heart disease and malignant neoplasms of the US population from the National Center for Health Statistics were used, and multiple decremental life tables were constructed to find the corresponding potential gains in life expectancy. RESULTS: The potential gains in life expectancy for the US population at birth by complete elimination of HIV/AIDS, heart disease and malignant neoplasms were 0.14, 3.71 and 3.06 years in 1987, respectively. In 1995, the potential gain in life expectancy due to the elimination of HIV/AIDS increased from 0.14 years in 1987 and achieved its highest value (0.41 years), whereas the elimination of heart disease and malignant neoplasms led to potential gains in life expectancy of 3.05 and 3.10 years, respectively. Since 1995, the potential gains in life expectancy at birth by eliminating deaths from HIV/AIDS and heart disease have decreased to 0.13 and 2.67 years, respectively, in 2000. However, the potential gain in life expectancy due to elimination of malignant neoplasms remained relatively stable (3.01 years in 2000). It is well known that HIV/AIDS tends to have a greater impact on people of working age, whereas heart disease and malignant neoplasms have a greater impact on people over 65 years of age. To measure the impact of these diseases on life expectancy in people of working age, a partial multiple decremental life table was constructed and the potential gains in life expectancy were computed by partial or complete elimination of various causes of death during the working years. shows the impact on life expectancy of the US working-age population by eliminating deaths from HIV/AIDS, heart disease and malignant neoplasms by race and sex groups. CONCLUSIONS: Since 1995, there has been a rapid reduction in the burden of HIV/AIDS on the life expectancy for the US population, especially for black males of working age. These results could provide useful information when evaluating public health improvements and allocating resources for future disease control programmes.

Acquired Immunodeficiency Syndrome↗

MUC7 haplotype analysis: results from a longitudinal birth cohort support protective effect of the MUC7*5 allele on respiratory function.

The mucin MUC7 is a glycoprotein that plays a role in bacterial clearance and has candidacidal activity. There are two common allelic forms with 5 or 6 tandem repeats (TR) of a 23 amino acid motif within the highly glycosylated (mucin) domain. The MUC7*5 allele has previously been shown to be less prevalent in patients with asthma, suggesting a protective role in respiratory function. Here we report the characterisation of other frequent genetic variation within and in the vicinity of the gene MUC7. A total of 26 polymorphisms were identified of which 5 are located in transcribed regions. A subset of 8 polymorphisms was selected to represent the major haplotypes, and allelic association was studied in individuals of Northern European ancestry, including known asthmatics. There was low haplotype diversity and strong association between each of the loci, and the MUC7*5 allele-carrying haplotype remained the one most strongly associated with asthma. Five of these polymorphisms have also been tested in the 1946 longitudinal birth cohort, for whom developmental, environmental and respiratory health data are available. We show that the haplotype carrying MUC7*5 is associated with higher FEV1 at 53 years, reduced age-related decline of FEV1, and also reduced incidence of wheeze.

Adolescent↗

Is the association of birth weight with premenopausal breast cancer risk mediated through childhood growth?

Several studies have found positive associations between birth weight and breast cancer risk at premenopausal ages. The mechanisms underlying this association are not known, but it is possible that it may be mediated through childhood growth. We examined data from a British cohort of 2176 women born in 1946 and for whom there were prospective measurements of birth weight and of body size throughout life. In all, 59 breast cancer cases occurred during follow-up, 21 of whom were known to be premenopausal. Women who weighed at least 4 kg at birth were five times (relative risk (RR)=5.03; 95% confidence interval=1.13, 22.5) more likely to develop premenopausal breast cancer than those who weighed less than 3 kg (P-value for linear trend=0.03). This corresponded to an RR of 2.31 (0.95, 5.64) per 1 kg increase in birth weight. Birth weight was also a predictor of postnatal growth, that is, women who were heavy at birth remained taller and heavier throughout their childhood and young adulthood. However, the effect of birth weight on premenopausal breast cancer risk was only reduced slightly after simultaneous adjustment for height and body mass index (BMI) at age 2 years and height and BMI velocities throughout childhood and adolescence (adjusted RR=1.94 (0.74, 5.14) per 1 kg increase in birth weight). The pathways through which birth weight is associated with premenopausal breast cancer risk seem to be largely independent of those underlying the relation of postnatal growth to risk.

Adolescent↗

Childhood growth and breast cancer.

Adult height is known to be positively associated with breast cancer risk. The mechanism underlying this association is complex, since adult height is positively correlated with age at menarche, which in turn is negatively associated with breast cancer risk. The authors used prospective data from a British cohort of 2,547 girls followed from birth in 1946 to the end of 1999 to examine breast cancer risk in relation to childhood growth. As expected, adult height was positively associated with age at menarche and breast cancer. In childhood, cases were taller and leaner, on average, than noncases. Significant predictors of breast cancer risk in models containing all components of growth were height velocity at age 4-7 years (for a one-standard-deviation increase, odds ratio (OR) = 1.54, 95% confidence interval (CI): 1.13, 2.09) and age 11-15 years (OR = 1.29, 95% CI: 0.97, 1.71) and body mass index velocity (weight (kg)/height (m)(2)/year) at age 2-4 years (OR = 0.63, 95% CI: 0.48, 0.83). The effects of these variables were particularly marked in women with early menarche (age <12.5 years). These findings suggest that women who grow faster in childhood and reach an adult height above the average for their menarche category are at particularly increased risk of breast cancer.

Adolescent↗

The life course prospective design: an example of benefits and problems associated with study longevity.

Although the life course prospective study design has many benefits, and information from such studies is in increasing demand for scientific and policy purposes, it has potential inherent design problems associated with its longevity. These are in particular the fixed sample structure and the data collected in early life, which are each determined by the scientific principles of another time and the risk over time of increased sample loss and distortion through loss. The example of a national birth cohort in Britain, studied from birth so far to age 53 years is used to address these questions. Although the response rate is high, avoidable loss, which was low in childhood, increased in adulthood, and was highest in those in adverse socio-economic circumstances and those with low scores on childhood cognitive measures. Recent permanent refusal rate rises may be the result of better tracing and/or a response to increased requests for biological measurement. Nevertheless, the responding sample continues in most respects to be representative of the national population of a similar age. Consistency of response over the study's 20 data collections has been high. The size of the sample responding in adulthood is adequate for the study of the major costly diseases, and for the study of functional ageing and its precursors. This study's continuation has depended not only on scientific value but also policy relevance. Although the problems inherent in the prospective design are unavoidable they are not, in the study described, a barrier to scientific and policy value. That seems also likely in Britain's two later born national birth cohort studies that have continued into adulthood.

Adolescent↗

Measuring the impact of hepatitis A virus in Chinese cities: a life table approach.

The infection of hepatitis A virus is an important public health problem in China. In 1990, a survey on seroprevalence of anti-hepatitis A was conducted in eight large cities of population size between one to four million. The results were used to analyze the impact of hepatitis A. In our study, we used life table techniques to determine the impact that the hepatitis A virus (HAV) has on these eight cities by computing the expected years of life with anti-hepatitis A virus. We compared the results from our approach with those from a previous method. The expected years of life with anti-hepatitis A virus were 53.82, 54.65, 44.26, 53.89, 46.18, 55.77, 55.31 and 49.89 for the eight cities (Xi'an, Huhehaote, Chongqing, Nanjing, Jinan, Ha'erbin, Fuzhou and Nanchang), respectively. The hepatitis A virus had the greatest impact in Ha'erbin in northeastern China; whereas, the impact was lowest in Chongqing in southwestern China. However, based on the previous indicator, Chongqing was ranked the highest among these cities. Through our comparative study of the methods, our approach provides a better measure on the burden of the disease than the previous method. It also identifies subgroups of the population where the disease has its greatest impact on the population.

China↗

Sociodemographic inequalities in the diet of young children in the 1946 British birth cohort.

OBJECTIVE: To evaluate whether there was food and nutrient equality across occupational social classes and geographical region for members of the 1946 British birth cohort at age 4 years. DESIGN: Cross-sectional analysis of selected food groups, energy and nutrients from one-day recall diet records. SETTING: England, Scotland and Wales in 1950. SUBJECTS: Nationally representative sample of 4419 children aged 4 years in 1950 from the MRC National Survey of Health and Development (NSHD) (1946 Birth Cohort). RESULTS: Significant food and nutrient inequalities occurred by region and occupational social class of the father. Disparity in fruit and vegetable consumption primarily led to the nutrient differences, especially with respect to lower vitamin C and carotene intakes in children from Scotland and from a manual social class background. Lower energy intake in Scottish children was attributable to inequality in the consumption of foods providing fat, and also to the retention of the traditional Scottish diet that included porridge and soups. Consumption of some rationed foods -- bacon, orange juice and tea -- was inequitably distributed by father's social class, but others, in particular meat and spreading fats, were consumed more uniformly. In contrast to fruits and vegetables, which showed marked sociodemographic disparities, other non-rationed foods such as bread and potatoes were consumed universally. CONCLUSION: Local cultural norms may have played as strong a part in sociodemographic differences in the diet of children in the early 1950s as did the strict, post-war food rationing that prevailed. In consequence, nutritional equality was not achieved, and the relatively low intake of antioxidant vitamins during early childhood in certain population groups may have compromised health in the long term.

Child Nutritional Physiological Phenomena↗

Leg and trunk length at 43 years in relation to childhood health, diet and family circumstances; evidence from the 1946 national birth cohort.

BACKGROUND: This is a study of the associations of adult leg and trunk length with early life height and weight, diet, socioeconomic circumstances, and health, and parental height, divorce and death. METHOD: The data used were collected in a longitudinal study of the health, development and ageing of a British national birth cohort (N = 2879 in this analysis) studied since birth in 1946. Multiple regression models were used to investigate the relationships. RESULTS: Adult leg and trunk length were each positively associated with parental height, birthweight, and weight at 4 years. Leg length was associated positively with breastfeeding and energy intake at 4 years. Trunk length was associated negatively with serious illness in childhood and possibly also parental divorce, but not with the dietary data. CONCLUSION: Adult leg length is particularly sensitive to environmental factors and diet in early childhood because that is the period of most rapid leg growth. Trunk growth is faster than leg growth after infancy and before puberty, and may be associated with the effects of serious illness and parental separation because of the child's growing sensitivity to stressful circumstances, as well as the result of the biological effects of illness.

Adult↗

Expression of QKI proteins and MAP1B identifies actively myelinating oligodendrocytes in adult rat brain.

We have studied developing oligodendrocytes in tissue sections as they initiate myelination and have found that the transition from premyelinating oligodendrocytes into myelin-bearing cells is accompanied by a dramatic upregulation in expression of the RNA binding QKI proteins. We show that in mature oligodendrocytes in culture, the localization of cytoplasmic QKI isoforms requires an intact cytoskeleton. Together with previous observations, this indicates that cytoplasmic QKI proteins facilitate movement of mRNAs to myelin via the cytoskeleton. In the adult rat brain, we found that a subset of oligodendrocytes displays characteristics of actively myelinating cells seen during development, i.e., connections to myelin sheaths and elevated levels of QKI proteins and also MAP1B. These observations suggest that instead of merely maintaining myelin, oligodendrocytes in the normal adult CNS are capable of responding to demands for new myelin sheaths. This has important implications for the prospect of repair of myelin in demyelinating conditions such as multiple sclerosis.

Age Factors↗

Does cryotherapy affect refractive error? Results from treated versus control eyes in the cryotherapy for retinopathy of prematurity trial.

PURPOSE: To evaluate the effect of cryotherapy on refractive error status between ages 3 months and 10 years in children with birth weights of less than 1251 g in whom severe retinopathy of prematurity (ROP) developed in one or both eyes during the neonatal period. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred ninety-one children in whom severe ROP developed during the neonatal period. INTERVENTION: Cryotherapy for ROP. MAIN OUTCOME MEASURES: Cycloplegic Refraction METHODS: The children underwent repeated follow-up eye examinations, including cycloplegic retinoscopy, between 3 months and 10 years after term due date. Refractive error data from all eyes that were randomized to cryotherapy were compared with data from all eyes that were randomized to serve as controls. Refractive error data were also compared for a subset of children who had both a treated and a control eye that could be refracted. RESULTS: At all ages, the proportion of treated eyes that were unable to be refracted because of retinal detachment, media opacity, or pupillary miosis was approximately half the proportion of the control eyes that were unable to be refracted. When data from all eyes that could be refracted were considered, the distribution of refractive errors between fewer than 8 diopters (D) of myopia and more than 8 D of hyperopia was similar for treated and control eyes at all ages. The proportion of eyes with 8 D or more of myopia was much higher in treated than in control eyes at all ages after 3 months. In the subset of children who had a treated eye and a control eye that could be refracted, distributions of refractive errors in treated versus control eyes were similar at most ages. CONCLUSIONS: In both treated and control eyes, there was an increase in the prevalence of high myopia between 3 and 12 months of age. Between 12 months and 10 years of age, there was little change in distribution of refractive error in treated or control eyes. The higher prevalence of myopia of 8 D or more in treated eyes, as compared with control eyes, may be the result of cryotherapy's preservation of retinal structure in eyes that, in the absence of cryotherapy, would have progressed to retinal detachment.

Astigmatism↗

Reduced lighting does not improve medical outcomes in very low birth weight infants.

OBJECTIVE: To objectively assess the effect of light reduction as an isolated environmental intervention on neonatal morbidity. STUDY DESIGN: Randomized multicenter trial. Neonates < 1251 g birth weight and < 31 weeks gestational age were randomly assigned to receive goggles or to a control group. Goggles that reduced visible light by 97% were placed within 24 hours of birth and remained in use until 31 weeks postmenstrual age or for a minimum of 4 weeks. RESULTS: Four hundred nine infants were enrolled, and outcome data are reported for 359 surviving infants. There were no significant differences between the groups in weight gain, duration of oxygen therapy, mechanical ventilation, or hospital stay either in the unadjusted analyses or in the analyses adjusted for birth weight, gestational age, race, sex, and inborn (born in study hospital) status. There was no difference between the groups in the incidence of intracranial hemorrhage. CONCLUSIONS: This randomized trial of continuous light reduction in the first few weeks of life for very low birth weight infants showed no effect on medical outcomes.

Child Development↗

Neural tube defects among Mexican Americans living on the US-Mexico border: effects of folic acid and dietary folate.

Populations of Mexican descent have high occurrences of neural tube defects (NTDs). A recent study suggested that folic acid supplements may not protect these populations from NTDs. In a case-control study, the authors investigated the role of folic acid and dietary folate intake in NTD risk among Mexican Americans living along the Texas-Mexico border. From January 1995 to February 1999, 148 Mexican-American women with NTD-affected pregnancies and 158 women with normal live births were interviewed in person about use of vitamin supplements and dietary intakes during a 6-month periconceptional period (from 3 months before conception to 3 months after conception). Daily preconceptional consumption of vitamin supplements containing folic acid was 2.5% in control women and 2.0% in case women (odds ratio = 0.77; 95% confidence interval (CI): 0.19, 3.22). With adjustment for maternal age, education, obesity, and previous stillbirth or miscarriage, the risk estimate was essentially null (odds ratio = 1.12; 95% CI: 0.22, 5.78). Combined folic acid intake from diet and supplements showed only a modest risk reduction for intakes of > or = 1.0 mg per day (adjusted odds ratio = 0.73; 95% CI: 0.31, 1.72). The fact that the primary folic acid exposure was in the form of dietary polyglutamates rather than the more easily absorbed supplemental monoglutamates may explain an apparent decreased effect in this population.

Adult↗

Standardized mortality ratio and life expectancy: a comparative study of Chinese mortality.

BACKGROUND: Various models have been proposed for rapid conversion of the standardized mortality ratio (SMR) to life expectancy using data from developed countries. METHODS: We compared two methods for converting the SMR to life expectancy using mortality data from the largest developing country, China. RESULTS: The first model, using the Gompertz function, does not provide a good fit to the life expectancy and SMR of China. The regression lines derived from the second, a log-linear model using parameters estimated from the US white population are not a good fit to Chinese males and older females. However, if the parameters in the log-linear model are estimated using Chinese mortality data, the resultant regression lines fit the data reasonably well. CONCLUSION: The relationship between life expectancy and SMR based on mortality data from developed countries may not be valid for developing countries. Based on our empirical study, separate estimates of the coefficients of the model are required for developing countries.

Adult↗

Severity of neonatal retinopathy of prematurity is predictive of neurodevelopmental functional outcome at age 5.5 years. Behalf of the Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: The purpose of this study was to assess the relation between neonatal retinopathy of prematurity (ROP) in very low birth weight infants and neurodevelopmental function at age 5.5 years. METHODS: Longitudinal follow-up of children occurred in 2 cohorts of the Multicenter Cryotherapy for Retinopathy of Prematurity Study. The extended natural history cohort followed 1199 survivors of <1251 g birth weight from 5 centers. The threshold randomized cohort (ThRz) followed 255 infants <1251 g from 23 centers who developed threshold ROP and who consented to cryotherapy to not more than 1 eye. At 5.5 years both cohorts had ophthalmic and acuity testing and neurodevelopmental functional status determined with the Functional Independence Measure for Children (WeeFIM). RESULTS: Evaluations were completed on 88.7% of the extended natural history cohort; 87% had globally normal functional skills (WeeFIM: >95). As ROP severity increased, rates of severe disability increased from 3.7% among those with no ROP, to 19.7% of those with threshold ROP. Multiple logistic regression analysis demonstrated that better functional status was associated with favorable visual acuity, favorable 2-year neurological score, absence of threshold ROP, having private health insurance, and black race. Evaluations were completed on 87.4% of the ThRz children. In each functional domain, the 134 children with favorable acuity in their better eye had fewer disabilities than did the 82 children with unfavorable acuity: self-care disability 25.4% versus 76.8%, continency disability 4.5% versus 50.0%, motor disability 5.2% versus 42.7%, and communicative-social cognitive disability 22.4% versus 65.9%, respectively. CONCLUSION: Severity of neonatal ROP seems to be a marker for functional disability at age 5. 5 years among very low birth weight survivors. High rates of functional limitations in multiple domains occur in children who had threshold ROP, particularly if they have unfavorable visual acuity.

Child, Preschool↗