Glutathione transferase Ti and M1 genotype polymorphism in the normal population of Shanghai

Glutathione transferases are known to be important enzymes in the metabolism of xenobiotics. In humans genetic polymorphisms have been reported for the hGSTM1 and hGSTT1 genes leading to individual differences in susceptibility towards toxic effects, such as cancer. This study describes the distribution of the two polymorphisms of hGSTT1 and hGSTM1 in the normal Chinese population of Shanghai. Out of 219 healthy individuals having been genotyped for GSTTI and GSTMI, 108 (49%) were identified to be homozygously deficient for the GSTT1 gene and 107 (49%) for the GSTM1 gene.

European aspects of standard setting in occupational hygiene and medicine

Occupational standards concerning the allowable concentrations of chemical compounds in the ambient air of workplaces have been established in several countries at national levels. With the integration of the European Union, a need exists for establishing harmonized Occupational Exposure Limits. For analytical developments, it is apparent that methods for speciation or fractionation of carcinogenic metal compounds will be of increasing practical importance for standard setting. Criteria of applicability under field conditions, cost-effectiveness, and robustness are practical driving forces for new developments. When the European Union issued a list of 62 chemical substances with Occupational Exposure Limits in 2000, 25 substances received a 'skin' notation. The latter indicates that toxicologically significant amounts may be taken up via the skin. Similar notations exist on national levels. For such substances, monitoring concentrations in ambient air will not be sufficient; biological monitoring strategies will gain further importance in the medical surveillance of workers who are exposed to such compounds. Proceedings in establishing legal frameworks for a biological monitoring of chemical exposures within Europe are paralleled by scientific advances in this field. A new aspect is the possibility of a differential adduct monitoring, using blood proteins of different half-life or lifespan. This technique allows differentiation between long-term mean exposure to reactive chemicals and short-term episodes, for example, by accidental overexposure. For further analytical developments, the following issues have been addressed as being particularly important: New dose monitoring strategies, sensitive and reliable methods for detection of DNA adducts, cytogenetic parameters in biological monitoring, methods to monitor exposure to sensitizing chemicals, and parameters for individual susceptibilities to chemical toxicants.

Markers of genetic susceptibility in human environmental hygiene and toxicology : the role of selected CYP, NAT and GST genes

Inherited genetic traits co-determine the susceptibility of an individual to a toxic chemical. Special emphasis has been put on individual responses to environmental and industrial carcinogens, but other chronic diseases are of increasing interest. Polymorphisms of relevant xenobiotic metabolising enzymes may be used as toxicological susceptibility markers. A growing number of genes encoding enzymes involved in biotransformation of toxicants and in cellular defence against toxicant-induced damage to the cells has been identified and cloned, leading to increased knowledge of allelic variants of genes and genetic defects that may result in a differential susceptibility toward environmental toxicants. "Low penetrating" polymorphisms in metabolism genes tend to be much more common in the population than allelic variants of "high penetrating" cancer genes, and are therefore of considerable importance from a public health point of view. Positive associations between cancer and CYP1A1 alleles, in particular the *2C I462V allele, were found for tissues following the aerodigestive tract. Again, in most cases, the effect of the variant CYP1A1 allele becomes apparent or clearer in connection with the GSTM1 null allele. The CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squameous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has also pointed to interactive effects. Of particular interest for the industrial and environmental field is the isozyme CYP2E1. Several genotypes of this isozyme have been characterised which seem to be associated with different levels of expression of enzyme activity. The acetylator status for NAT2 can be determined by genotyping or by phenotyping. In the pathogenesis of human bladder cancer due to occupational exposure to "classical" aromatic amines (benzidine, 4-aminodiphenyl, 1-naphthylamine) acetylation by NAT2 is regarded as a detoxication step. Interestingly, the underlying European findings of a higher susceptibility of slow acetylators towards aromatic amines are in contrast to findings in Chinese workers occupationally exposed to aromatic amines which points to different mechanisms of susceptibility between European and Chinese populations. Regarding human bladder cancer, the hypothesis has been put forward that genetic polymorphism of GSTM1 might be linked with the occurrence of this tumour type. This supports the hypothesis that exposure to PAH might causally be involved in urothelial cancers. The human polymorphic GST catalysing conjugation of halomethanes, dihalomethanes, ethylene oxide and a number of other industrial compounds could be characterised as a class theta enzyme (GSTT1) by means of molecular biology. "Conjugator" and "non-conjugator" phenotypes are coincident with the presence and absence of the GSTT1 gene. There are wide variations in the frequencies of GSTT1 deletion (GSTT1 *0/0) among different ethnicities. Human phenotyping is facilitated by the GST activity towards methyl bromide or ethylene oxide in erythrocytes which is representative of the metabolic GSTT1 competence of the entire organism. Inter-individual variations in xenobiotic metabolism capacities may be due to polymorphisms of the genes coding for the enzymes themselves or of the genes coding for the receptors or transcription factors which regulate the expression of the enzymes. Also, polymorphisms in several regions of genes may cause altered ligand affinity, transactivation activity or expression levels of the receptor subsequently influencing the expression of the downstream target genes. Studies of individual susceptibility to toxicants and gene-environment interaction are now emerging as an important component of molecular epidemiology.

Morphometric modelling of ageing in the human pubic symphysis : sexual dimorphism in an Australian population

Despite the prominent use of the pubic symphysis for age estimation in forensic anthropology, little has been documented regarding the quantitative morphological and micro-architectural changes of this surface. Specifically, utilising post-mortem computed tomography data from a large, contemporary Australian adult population, this study aimed to evaluate sexual dimorphism in the morphology and bone composition of the symphyseal surface; and temporal characterisation of the pubic symphysis in individuals of advancing age. The sample consisted of multi-slice computed tomography (MSCT) scans of the pubic symphysis(slice thickness: 0.5 mm, overlap: 0.1 mm) of 200 individuals of Caucasian ancestry aged 15–70 years, obtained in 2011. Surface rendering reconstruction of the symphyseal surface was conducted in OsiriX1 (v.4.1) and quantitative analyses in Rapidform XOSTM and OsteomeasureTM. Morphometric variables including inter-pubic distance, surface area, circumference, maximum height and width of the symphyseal surface and micro-architectural assessment of cortical and trabecular bone compositions were quantified using novel automated engineering software capabilities. The major results of this study are correlated with the macroscopic ossification and degeneration pattern of the symphyseal surface, demonstrating significant age-related changes in the morphometric and bone tissue variables between 15 and 70 years. Regardless of sex, the overall dimensions of the symphyseal surface increased with age, coupled with a decrease in bone mass in the trabecular and cortical bone compartments. Significant differences between the ventral, dorsal and medial cortical surfaces were observed, which may be correlated to bone formation activity dependent on muscle activity and ligamentous attachments. Our study demonstrates significant sexual dimorphism at this site, with males exhibiting greater surface dimensions than females. These baseline results provide a detailed insight into the changes in the structure of the pubic symphysis with ageing and sexually dimorphic features associated with the cortical and trabecular bone profiles.

Household food insecurity is associated with less physical activity among children and adults in the U.S. population

Background Household food insecurity and physical activity are each important public-health concerns in the United States, but the relation between them was not investigated thoroughly. Objective We wanted to examine the association between food insecurity and physical activity in the U.S. population. Methods Physical activity measured by accelerometry (PAM) and physical activity measured by questionnaire (PAQ) data from the NHANES 2003–2006 were used. Individuals aged <6 y or >65 y, pregnant, with physical limitations, or with family income >350% of the poverty line were excluded. Food insecurity was measured by the USDA Household Food Security Survey Module. Adjusted ORs were calculated from logistic regression to identify the association between food insecurity and adherence to the physical-activity guidelines. Adjusted coefficients were obtained from linear regression to identify the association between food insecurity with sedentary/physical-activity minutes. Results In children, food insecurity was not associated with adherence to physical-activity guidelines measured via PAM or PAQ and with sedentary minutes (P > 0.05). Food-insecure children did less moderate to vigorous physical activity than food-secure children (adjusted coefficient = −5.24, P = 0.02). In adults, food insecurity was significantly associated with adherence to physical-activity guidelines (adjusted OR = 0.72, P = 0.03 for PAM; and OR = 0.84, P < 0.01 for PAQ) but was not associated with sedentary minutes (P > 0.05). Conclusion Food-insecure children did less moderate to vigorous physical activity, and food-insecure adults were less likely to adhere to the physical-activity guidelines than those without food insecurity.

Weight-related differences in glucose metabolism and free fatty acid production in two South African population groups

OBJECTIVE The effects of free fatty acids (FFA), leptin, tumour necrosis factor (TNF) alpha and body fat distribution on in vivo oxidation of a glucose load were studied in two South African ethnic groups. DESIGN AND MEASUREMENTS Anthropometric and various metabolic indices were measured at fasting and during a 7h oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis and subcutaneous and visceral fat mass was assessed using a five- and two-level CT-scan respectively. Glucose oxidation was evaluated by measuring the ratio of (13)CO(2) to (12)CO(2) in breath following ingestion of 1-(13)C-labelled glucose. SUBJECTS Ten lean black women (LBW), ten obese black women (OBW), nine lean white women (LWW) and nine obese white women (OWW) were investigated after an overnight fast. RESULTS Visceral fat levels were significantly higher (P < 0.01) in obese white than black women, despite similar body mass indexes (BMIs). There were no ethnic differences in glucose oxidation however; in the lean subjects of both ethnic groups the area under the curve (AUC) was higher than in obese subjects (P < 0.05 for both) and was found to correlate negatively with weight (r = -0.69, P < 0.01) after correcting for age. Basal TNF alpha concentrations were similar in all groups. Percentage suppression of FFAs at 30 min of the OCTT was 24 +/- 12% in OWW and - 38 +/- 23% (P < 0.05) in OBW, ie the 30 min FFA level was higher than the fasting level in the latter group. AUC for FFAs during the late postprandial period (120 - 420 min) was significantly higher in OWW than OBW (P < 0.01) and LWW (P < 0.01) and correlated positively with visceral fat mass independent of age (r = 0.78, P < 0.05) in the OWW only. Leptin levels were higher (P < 0.01) both at fasting and during the course of the OCTT in obese women from both ethnic groups compared to the lean women. CONCLUSIONS Glucose oxidation is reduced in obese subjects of both ethnic groups; inter- and intra-ethnic differences were observed in visceral fat mass and FFA production and it is possible that such differences may play a role in the differing prevalences of obesity-related disorders that have been reported in these two populations.

Get a life? The impact of the European working time directive : the case of UK senior doctors

This paper seeks to identify the effect of the implementation of the European Working Time Directive (EWTD) on the working hours of UK doctors. The Labour Force Survey is used to compare the working hours of doctors with a variety of control groups before and after the implementation of the directive. The controls include those unconstrained by the directive and doctor counterparts working in Europe. We use differences-in-differences and matching methods to estimate the impact of this natural experiment, distinguishing between the anticipation and enactment of the EWTD. We find that the legislation reduced the hours of senior doctors by around 8 hours in total including the component attributable to anticipation effects and allowing for (exogenously set) rising wages.

The healthy immigrant effect: Patterns and evidence from four countries

The existence of a healthy immigrant effect—where immigrants are on average healthier than the native born—is a widely cited phenomenon across a multitude of literatures including epidemiology and the social sciences. There are many competing explanations. The goals of this paper are twofold: first, to provide further evidence on the presence of the healthy immigrant effect across source and destination country using a set of consistently defined measures of health; and second, to evaluate the role of selectivity as a potential explanation for the existence of the phenomenon. Utilizing data from four major immigrant recipient countries, USA, Canada, UK, and Australia allows us to compare the health of migrants from each with the respective native born who choose not to migrate. This represents a much more appropriate counterfactual than the native born of the immigrant recipient country and yields new insights into the importance of observable selection effects. The analysis finds strong support for the healthy immigrant effect across all four destination countries and that selectivity plays an important role in the observed better health of migrants vis a vis those who stay behind in their country of origin.

Convergence in European corporate governance : the audit committee concept

This paper analyses recent corporate governance codes issued by 20 countries for evidence of convergence in corporate governance systems in Europe. The analysis shows that there has been a degree of convergence towards an Anglo-Saxon model of corporate governance as the audit committee concept is widely accepted in countries with both unitary and two-tier governance systems. Further, the latest audit committee recommendations in countries that have issued several governance codes show a strengthening of the recommendations for an audit committee over time in line with the Anglo-Saxon audit committee concept and convergence with the debate in the US and UK on issues such as the independence and financial expertise of members. However, consistent with the literature on the convergence of European corporate governance systems, at an operational level there is limited consistency in the recommended structure and role of audit committees.

Maternal psychological distress mediates the relationship between asthma and physician visits in a population-based sample of adolescents

Objective This study examined whether maternal psychological distress mediates the relationship between presence of adolescent asthma and number of physician visits, and whether the association between maternal psychological distress and physician visits is moderated by adolescent general health. Methods Data were obtained from the Mater University Study of Pregnancy and included 4025 adolescents. Path analysis was used to examine mediating and moderating effects. Results Maternal psychological distress was found to partially mediate the relationship between adolescent asthma and number of physician visits, accounting for 25% of the effect of adolescent asthma on physician visits (p = .046). There was no evidence to suggest that adolescent general health moderated the association between maternal psychological distress and physician visits (p = .093). Conclusions The findings suggest that maternal psychological distress is associated with increased physician visits, regardless of adolescents' general health. Lowering maternal psychological distress may serve to reduce health care utilization and costs among adolescents with asthma.

2nd ESMO consensus conference on lung cancer : early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, earlystage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

The establishment of an ISO compliant cancer biobank for Jordan and its neighboring countries through knowledge transfer and training

Research studies aimed at advancing cancer prevention, diagnosis, and treatment depend on a number of key resources, including a ready supply of high-quality annotated biospecimens from diverse ethnic populations that can be used to test new drugs, assess the validity of prognostic biomarkers, and develop tailor-made therapies. In November 2011, KHCCBIO was established at the King Hussein Cancer Center (KHCC) with the support of Seventh Framework Programme (FP7) funding from the European Union (khccbio.khcc.jo). KHCCBIO was developed for the purpose of achieving an ISO accredited cancer biobank through the collection, processing, and preservation of high-quality, clinically annotated biospecimens from consenting cancer patients, making it the first cancer biobank of its kind in Jordan. The establishment of a state-of-the-art, standardized biospecimen repository of matched normal and lung tumor tissue, in addition to blood components such as serum, plasma, and white blood cells, was achieved through the support and experience of its European partners, Trinity College Dublin, Biostor Ireland, and accelopment AG. To date, KHCCBIO along with its partners, have worked closely in establishing an ISO Quality Management System (QMS) under which the biobank will operate. A Quality Policy Manual, Validation, and Training plan have been developed in addition to the development of standard operating procedures (SOPs) for consenting policies on ethical issues, data privacy, confidentiality, and biobanking bylaws. SOPs have also been drafted according to best international practices and implemented for the donation, procurement, processing, testing, preservation, storage, and distribution of tissues and blood samples from lung cancer patients, which will form the basis for the procurement of other cancer types. KHCCBIO will be the first ISO accredited cancer biobank from a diverse ethnic Middle Eastern and North African population. It will provide a unique and valuable resource of high-quality human biospecimens and anonymized clinicopathological data to the cancer research communities world-wide.

Resilience of water supply systems in meeting the challenges posed by climate change and population growth

This research project provides a scientifically robust approach for assessing the resilience of water supply systems, which are critical infrastructure, to impacts of climate change and population growth. An approach for the identification of trigger points that allows timely and appropriate management actions to be taken to avoid catastrophic system failure is an important outcome of this project. In the current absence of a formal method to evaluate the resilience of a water supply system, the approach developed in this study was based on the characterisation of resilience of a water supply system to a range of surrogate measures. Accordingly, a set of indicators are proposed to evaluate system behaviour and logistic regression analysis was used to assess system behaviour under predicted rainfall, storage and demand conditions.

Incidence trends of keratinocytic skin cancers and melanoma in Israel 2006-2011

BACKGROUND The incidence of skin cancer, both melanoma and keratinocyte cancers (KC) is rising throughout the world, specifically squamous cell carcinomas(SCC) and basal cell carcinoma(BCC), being the most common of all cancers. OBJECTIVE To determine trends in incidence of Melanoma, BCC and SCC among 1.7 million members of Maccabi Healthcare Services from 2006 to 2011. METHODS Data on newly diagnosed Melanoma, SCC and BCC cases was collected from the MHS Cancer Registry and based on histology reports from the centralized pathology lab. Age-specific and overall age-adjusted European standardized rates were computed. Trends were estimated by calculating Average Annual Percentage Change(AAPC). RESULTS During the six year study period, a total of 16,079 subjects were diagnosed with at least one BCC, 4,767 with SCC and 1,264 with invasive melanoma. Age-standardized incidence rates were 188, 58 and 17 per 100,000 person years for BCC, SCC and melanoma, respectively. All lesions were more common among males and primarily affected the elderly. BCC rates were stable throughout the study period(AAPC -0.7%, 95%CI -4.5% to 3.2%) while SCC incidence increased significantly(AAPC 15.5%, 95%CI: 2.6% to 30.0%). In contrast, melanoma rates continuously decreased with a significant AAPC of -3.0%, 95%CI (-4.5 to -0.1). CONCLUSIONS Previously unreported, the incidence of KC in Israel is high. The disparities in incidence trends between SCC, BCC and melanoma allude to their different etiologies. These findings underscore the importance of continuous monitoring, education and prevention programs in a growing high risk population.

Mainstreaming biophilic urbanism in Australian cities : a response to climate change, resource shortages and population pressures

This thesis explored how biophilic urbanism, or the integration of natural features into increasingly dense urban environments, has become mainstream in cities around the world. Fourteen factors uncovered through a case study investigation provide insight for decision makers and change agents in Australia to use biophilic urbanism to address impacts of population growth, climate change and resource shortages. The thesis uses an inductive research approach to explore how barriers to the integration of multi-functional vegetated and water design elements into the built environment, such that these become and standard inclusions in urban design and development processes.