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Biomedical subjects

L Parker

Publications and source records attributed to L Parker.

At least 37 records · Page 2Linked to original sources

Do circumstances in early life contribute to tooth retention in middle age?

The relative contributions of factors operating in fetal life, childhood, and adulthood to risk of disease in middle age have become an important research issue, though oral health has rarely been considered. This study investigated the relative impacts of risk factors operating at different stages throughout life on the number of teeth retained at ages 49-51 yrs based on data from the Newcastle Thousand Families cohort. Very little variation in tooth retention in middle age was explained by factors operating at earlier stages in life. The previously noted relationship between childhood socio-economic status and oral health in adulthood appears, with respect to tooth retention, to diminish with increasing age as adult socio-economic position and lifestyle factors have an increasing effect. Promotion of a healthier adult lifestyle and continued improvements in oral hygiene would appear to be the public health interventions most likely to increase tooth retention in middle age.

Adolescent↗

Childhood solid tumours in relation to population mixing around the time of birth.

In a retrospective cohort study of 673 787 live births in the Northern Region of England, 1975-1994, we investigated whether a higher level of population mixing around birth was a risk factor for solid tumours, by diagnostic group (Hodgkin's disease, brain and spinal tumours, neuroblastoma, other solid tumours), diagnosed during 1975-2001 under age 15 years. Logistic regression was used to relate risk to population mixing, based on (i) all movers and (ii) incomers from outside the region. Both ward and county district level analyses were performed. There was a decreased risk of brain and spinal tumours with increasing population mixing based on incomers from outside the region (OR for trend across three categories=0.79, 95% CI: 0.66-0.95, P=0.01 in the ward level analysis). Although this may be because of chance, it is consistent with a role of exposure to infection and immunological response in the aetiology of these tumours. For other tumour groups, there was no consistent evidence of an association between risk and population mixing.

Adolescent↗

Childhood leukaemia and non-Hodgkin's lymphoma in relation to proximity to railways.

We investigated whether living close to railway lines is a risk factor for childhood leukaemia and non-Hodgkin's lymphoma in electoral wards in England and Wales, 1966-1987. The national rail network, 1966-1987, was digitised and the numbers of cases in each ward were related to two measures of environmental exposure to railways: a proximity and a density function, contributions to these functions being weighted by the frequency of use and time in use of each stretch of railway. Poisson regression was used to derive rate ratios in relation to these measures of exposure to railways, both unadjusted and adjusted for population mixing. We found no association between risk of leukaemia and railway proximity (unadjusted rate ratio for trend from the lowest to the median value=1.006, 95% CI: 0.998 - 1.013, P=0.14) and a very small association with railway density, of marginal statistical significance (rate ratio for trend=1.001, 95% CI: 1.000 - 1.003, P=0.05). This effect depended on two deprived, urban wards with high railway density and high population mixing and became nonsignificant (P=0.09) after allowing for population mixing. The very weak association between railway density and risk of childhood leukaemia is likely to be a consequence of the association between population mixing and proximity to railways in very deprived, urban wards.

Child↗

A lifecourse study of risk for hyperinsulinaemia, dyslipidaemia and obesity (the central metabolic syndrome) at age 49-51 years.

AIMS: Suboptimal maternal nutrition and catch-up growth in early childhood predispose to insulin resistance and other components of metabolic syndrome in later life. A central metabolic syndrome (CMS) has been identified comprising obesity, dyslipidaemia and insulin resistance. This study was designed to investigate determinants of risk for CMS. METHODS: Persons born in Newcastle in May and June 1947 (n = 358) were followed to 1996-1998. A lifecourse approach was used to estimate the proportion of variance in a summary measure of CMS at age 49-51 years accounted for by factors operating at different stages of life. RESULTS: After adjustment for other early life variables, childhood catch-up growth in men accounted for significant variation in the CMS score independent of adult lifestyle. In adulthood, exercise level in men and smoking in both genders were independently associated with CMS. Over two-thirds of explained variation in the CMS score in women, and almost half in men, was accounted for exclusively by factors measured in adulthood. CONCLUSIONS: While risk for CMS in men is compounded by early life disadvantage, promotion of a healthier adult lifestyle and a reduction in the number of people taking up smoking would appear to be the public health interventions most likely to reduce the prevalence of CMS in middle age.

Body Mass Index↗

Comparison of Health and Safety Executive and Cumbrian birth cohort studies of risk of leukaemia/non-Hodgkin's lymphoma in relation to paternal preconceptional irradiation.

In 1993, a case-control study by the Health and Safety Executive (HSE) assessed the risk of leukaemia and non-Hodgkin's lymphoma (LNHL) among children of fathers employed at the Sellafield nuclear installation in relation to paternal preconceptional irradiation (PPI). It concluded that the statistical association between risk of LNHL and PPI was confined to children born in the village of Seascale, where the dose-response was extremely high and very significant. In contrast, in 2002, a Cumbrian birth cohort study, investigating largely the same cases, concluded that this statistical association was not significantly different among children born inside and outside Seascale and estimated the dose-response inside Seascale to be much lower. This review makes a detailed comparison of the two studies, considering their design, data and analyses. The differences between their findings are due to: (i) differences in the distribution of offspring-years which are differential with respect to dose category and Seascale birth status, (ii) a non-Seascale high-dose case included in the Cumbrian but not the HSE study, (iii) differences between analyses using categorical and continuous PPI dose and (iv) the presence of Seascale controls with PPI over 200 mSv in the Cumbrian but not the HSE study.

Adolescent↗

Adverse pregnancy outcomes around incinerators and crematoriums in Cumbria, north west England, 1956-93.

STUDY OBJECTIVE: To investigate the risk of stillbirth, neonatal death, and lethal congenital anomaly among babies of mothers living close to incinerators and crematoriums in Cumbria, north west England, 1956-93. DESIGN: Retrospective cohort study. Logistic regression was used to investigate the risk of each outcome in relation to proximity at birth to incinerators and crematoriums, adjusting for social class, year of birth, birth order, and multiple births. Continuous odds ratios for trend with proximity to sites were estimated. SETTING: All 3234 stillbirths, 2663 neonatal deaths, and 1569 lethal congenital anomalies among the 244 758 births to mothers living in Cumbria, 1956-1993. MAIN RESULTS: After adjustment for social class, year of birth, birth order, and multiple births, there was an increased risk of lethal congenital anomaly, in particular spina bifida (odds ratio 1.17, 95% CI: 1.07 to 1.28) and heart defects (odds ratio 1.12, 95% CI: 1.03 to 1.22) around incinerators and an increased risk of stillbirth (odds ratio 1.04, 95% CI: 1.01 to 1.07) and anencephalus (odds ratio 1.05, 95% CI: 1.00 to 1.10) around crematoriums. CONCLUSIONS: The authors cannot infer a causal effect from the statistical associations reported in this study. However, as there are few published studies with which to compare our results, the risk of spina bifida, heart defects, stillbirth, and anencephalus in relation to proximity to incinerators and crematoriums should be investigated further, in particular because of the increased use of incineration as a method of waste disposal.

Congenital Abnormalities↗

Childhood solid tumours in relation to infections in the community in Cumbria during pregnancy and around the time of birth.

In a retrospective cohort study of all 99 976 live births in Cumbria, 1975-1992, we investigated whether higher levels of community infections during the mother's pregnancy and in early life were risk factors for solid tumours (brain/spinal and other tumours), diagnosed 1975-1993 under age 15 years. Logistic regression was used to relate risk to incidence of community infections in three prenatal and two postnatal quarters. There was an increased risk of brain/spinal tumours among children exposed around or soon after birth to higher levels of community infections, in particular measles (OR for trend=2.1, 95%CI : 1.3-3.6, P=0.008) and influenza (OR for exposure=3.3, 95%CI : 1.5-7.4, P=0.005). There was some evidence of an association between exposure to infections around and soon after birth and risk of other tumours, but this may have been a chance finding. The findings are consistent with other recent epidemiological studies suggesting brain tumours may be associated with perinatal exposure to infections.

Adolescent↗

Paternal preconceptional irradiation, population mixing and solid tumors in the children of radiation workers (England).

OBJECTIVE: To investigate whether there was an increased incidence of solid tumors among offspring of male radiation workers at the Sellafield nuclear installation in Cumbria, northwest England and whether paternal preconceptional irradiation was associated with the risk of solid tumors. METHODS: A cohort study of 266,710 live births in Cumbria, 1950-1991, followed up to age 25 years on the end of 1991. RESULTS: Children of radiation workers had a non-significantly increased risk of solid tumors (RR= 1.5, 95% CI: 0.9-2.4, p = 0.09), determined largely by an increased risk of cancers excluding leukemias, lymphomas, brain, spinal and gender-specific tumors (RR= 1.9, 95% CI: 1.0-3.3, p = 0.05), which was partly explained by differing patterns of parental migration (adjusted RR= 1.7, 95% Cl: 0.8-3.2, p = 0.50). Within children of radiation workers there was no evidence of an increased risk with increasing paternal preconception dose of external radiation (hazard ratio per 100 mSv for all solid tumors=0.6, 95% CI: 0.1-1.8, p = 0.52). CONCLUSIONS: Any observed excess of solid tumors in children of radiation workers may be partly explained by population mixing. Fathers' occupational exposure to radiation before conception was not found to be risk factor for solid tumors in their children.

Adolescent↗

Dose-response effect of walking exercise on weight loss. How much is enough?

OBJECTIVE: Exercise is the cornerstone of behavioral weight loss programs. The total volume of exercise needed to both promote weight loss and elicit health benefits has not been sufficiently investigated. The aim of this study was to examine the effects of two different volumes of walking 'metabolic fitness' exercise prescriptions, in combination with a low-fat, ad libitum diet (LFAL) on weight loss and additional modifiable health-related variables (HRV) in an ethnically diverse sample of overweight premenopausal women. DESIGN: Clinical 12 week weight loss intervention study with a 5.0-5.8 MJ diet daily with (a). participants walking 30 min, 5 days per week (DEX1), (b). participants walking 60 min, five times per week (DEX2) or (c). a diet only control group (DO). SUBJECTS: A mixed racial sample (predominantly Hispanic) of 56 subjects (mean BMI=34.26+/-6.61, mean age= 39.45+/-7.34) completed the 12 week program. MEASUREMENTS: Various body weight, body composition and fat distribution variables, dietary intake and additional HRV such as blood lipids, blood pressure and an estimate of cardiorespiratory fitness at baseline and after 3 months. RESULTS: All groups showed similar and significant (P<0.001) declines in body weight, percentage body fat, BMI, WHR, fat mass, fat-free mass and diastolic blood pressure following the program. In addition, total cholesterol, triacylglycerol and the TC:HDL ratio displayed a significant time effect (P<0.05). Significant interactions (P<0.05) were found for waist circumference, sagittal diameter, estimated VO(2max) and LDL-C, with both exercise groups showing similar and significantly greater (P<0.05) improvements than DO. Significant interactions (P<0.05) were also observed for several dietary variables. CONCLUSION: Our study showed no dose-response effect of walking exercise on weight loss over diet alone. Both lower and higher volume metabolic fitness prescriptions resulted in similar and significant beneficial changes in several HRV. This data suggests that 30 min of walking on most days of the week may be as beneficial as 60 min (in combination with diet) in promoting numerous additional healthful outcomes over diet alone following a 12 week weight loss program.

Adipose Tissue↗

Implications of childhood obesity for adult health: findings from thousand families cohort study.

OBJECTIVE: To determine whether being overweight in childhood increases adult obesity and risk of disease. DESIGN: Prospective cohort study. SETTING: City of Newcastle upon Tyne. PARTICIPANTS: 932 members of thousand families 1947 birth cohort, of whom 412 attended for clinical examination age 50. MAIN OUTCOME MEASURES: Blood pressure; carotid artery intima-media thickness; fibrinogen concentration; total, low density lipoprotein, and high density lipoprotein cholesterol concentrations; triglyceride concentration; fasting insulin and 2 hour glucose concentrations; body mass index; and percentage body fat. RESULTS: Body mass index at age 9 years was significantly correlated with body mass index age 50 (r=0.24, P<0.001) but not with percentage body fat age 50 (r=0.10, P=0.07). After adult body mass index had been adjusted for, body mass index at age 9 showed a significant inverse association with measures of lipid and glucose metabolism in both sexes and with blood pressure in women. However, after adjustment for adult percentage fat instead of body mass index, only the inverse associations with triglycerides (regression coefficient= -0.21, P<0.01) and total cholesterol (-0.17, P<0.05) in women remained significant. CONCLUSIONS: Little tracking from childhood overweight to adulthood obesity was found when using a measure of fatness that was independent of build. Only children who were obese at 13 showed an increased risk of obesity as adults. No excess adult health risk from childhood or teenage overweight was found. Being thin in childhood offered no protection against adult fatness, and the thinnest children tended to have the highest adult risk at every level of adult obesity.

Adipose Tissue↗

Childhood cancer registrations in the developing world: still more boys than girls.

It has been shown previously that in many developing countries the reported incidence of childhood cancer for boys is substantially higher than for girls and that this difference is related to economic development of the country under study. The aim of the present study was to investigate the relationship between the sex ratio of children registered with malignant diseases and national economic development. Sex ratios for childhood cancer registration were obtained for populations within 53 countries from the second volume of the International Incidence of Childhood Cancer (range boys:girls 1.09-2.05). Demographic, economic and health data for the corresponding countries were obtained from published statistics and used to determine the extent to which sex ratios were associated with national economic status. The ratio of boys:girls registered with childhood cancer increased with decreasing gross domestic product and with increasing infant mortality, suggesting that boys are increasingly more likely than girls to be registered with increasing economic disadvantage. Combining these results with childhood cancer registration data from northern England suggests that little of the predominance of boys reaching a specialist centre can be explained by differences between boys and girls in early deaths from the disease. The previously observed differences in the childhood cancer registration sex ratio in developing countries still exist. Hence, international differences in the incidence of childhood cancer should be interpreted cautiously as they may not necessarily reflect only differences in the underlying occurrence of disease

Adolescent↗

Specificity of natural and artificial substrates for human Cdc25A.

Cdc25A is a dual-specific protein phosphatase involved in the regulation of the kinase activity of Cdk-cyclin complexes in the eukaryotic cell cycle. To understand the mechanism of this important regulator, we have generated highly purified biochemical reagents to determine the kinetic constants for human Cdc25A with respect to a set of peptidic, artificial, and natural substrates. Cdc25A and its catalytic domain (dN25A) demonstrate very similar kinetics toward the artificial substrates p-nitrophenyl phosphate (k(cat)/K(m) = 15-25 M(-1) s(-1)) and 3-O-methylfluorescein phosphate (k(cat)/K(m) = 1.1-1.3 x 10(4) M(-1) s(-1)). Phospho-peptide substrates exhibit extremely low second-order rate constants and a flat specificity profile toward Cdc25A and dN25A (k(cat)/K(m) = 1 to 10 M(-1) s(-1)). In contrast to peptidic substrates, Cdc25A and dN25A are highly active phosphatases toward the natural substrate, T14- and Y15-bis-phosphorylated Cdk2/CycA complex (Cdk2-pTpY/CycA) with k(cat)/K(m) values of 1.0-1.1 x 10(6) M(-1) s(-1). In the context of the Cdk2-pTpY/CycA complex, phospho-threonine is preferred over phospho-tyrosine by more than 10-fold. The highly homologous catalytic domain of Cdc25c is essentially inactive toward Cdk2-pTpY/CycA. Taken together these data indicate that a significant degree of the specificity of Cdc25 toward its Cdk substrate resides within the catalytic domain itself and yet is in a region(s) that is outside the phosphate binding site of the enzyme.

Amino Acid Sequence↗

A new look at the accelerating universe.

We show that the cosmological model having zero cosmological constant, but containing the vacuum energy of a simple quantized free scalar field of low mass (VCDM model), agrees with the cosmic microwave background radiation (CMBR) and supernova (SNe-Ia) data at least as well as the classical cosmological model with a small nonzero cosmological constant. We also show that in the VCDM model the ratio of vacuum pressure to vacuum energy density is less than -1. We display the VCDM results for a set of parameters that give a very good fit to the CMBR power spectrum, and show that the same parameters also give a good fit to the SNe-Ia data.

Journal Article↗

Neuroblastoma: changing incidence and survival in young people aged 0-24 years. A report from the North of England Young Persons' Malignant Disease Registry.

BACKGROUND AND PROCEDURE: Population based data for neuroblastoma in children and young adults under 25 years at diagnosis were ascertained from the Northern Region Young Persons' Malignant Disease Registry for the period 1968-1995. Age-standardised incidence rates were calculated (ASR) and changes in incidence and survival were investigated. Over the study period 144 patients were registered, of these 136 were children under 15 years at diagnosis (median age: 2.2 years, ASR: 8.6 cases per million children per year), and 8 were 15-24 years (ASR 0.6). RESULTS AND CONCLUSIONS: Incidence of childhood neuroblastoma in the North of England increased significantly over time; ASRs were 5.8 for 1968-1981 and 9.5 for 1982-1995 (rate ratio: 1.6, 95%; CI 1.2-2.3). The increase in incidence was seen in both infants and older children, and in both low stage and advanced disease. Overall 5 year survival was 15% for 1968-1981 and 40% for 1982-1995 (P < 0.0001). Significant improvements in survival were documented across different stage and age-groups, including those over 1 with stage 4 disease (0% versus 18%, P < 0.0001). Further research is needed to investigate the reasons for the increasing incidence of neuroblastoma.

Adolescent↗

The origins of height fear: an evaluation of neoconditioning explanations.

The present research sought to establish a reliable and valid instrument for assessing the relevance of neoconditioning factors (e.g. latent inhibition, UCS inflation/revaluation, prior fear levels, prior expectancies of harm, fear and pain levels experienced during supposed learning events), in the development of human fear. Fifty-four undergraduate height-fearful students completed the new origins instrument (OQ-II), while 54 matched controls completed a modified version (OQM-II) that examined their prior experiences with heights. In general, few differences between groups were found. Height-fearful and control subjects did not differ on trait anxiety, the frequency of negative encounters with heights, the age at which these events had occurred, prior fear levels, prior expectancies of harm, or reports of UCS inflation/revaluation procedures. However, in a finding directly opposite to that expected from a conditioning account, the mean fear and pain scores reported by subjects who had experienced direct conditioning events were significantly higher in the non-fearful group than in the height-fearful group. These findings are discussed in terms of associative and non-associative models of fear.

Adolescent↗