Protocol for assessing maternal, environmental and epigenetic risk factors for dental caries in children

Background Expenditure on dental and oral health services in Australia is $3.4 billion AUD annually. This is the sixth highest health cost and accounts for 7 % of total national health expenditure. Approximately 49 % of Australian children aged 6 years have caries experience in their deciduous teeth and this is rising. The aetiology of dental caries involves a complex interplay of individual, behavioural, social, economic, political and environmental conditions, and there is increasing interest in genetic predisposition and epigenetic modification. Methods The Oral Health Sub-study; a cross sectional study of a birth cohort began in November 2012 by examining mothers and their children who were six years old by the time of initiation of the study, which is ongoing. Data from detailed questionnaires of families from birth onwards and data on mothers’ knowledge, attitudes and practices towards oral health collected at the time of clinical examination are used. Subjects’ height, weight and mid-waist circumference are taken and Body Mass Index (BMI) computed, using an electronic Bio-Impedance balance. Dental caries experience is scored using the International Caries Detection and Assessment System (ICDAS). Saliva is collected for physiological measures. Salivary Deoxyribose Nucleic Acid (DNA) is extracted for genetic studies including epigenetics using the SeqCap Epi Enrichment Kit. Targets of interest are being confirmed by pyrosequencing to identify potential epigenetic markers of caries risk. Discussion This study will examine a wide range of potential determinants for childhood dental caries and evaluate inter-relationships amongst them. The findings will provide an evidence base to plan and implement improved preventive strategies.

Biological and environmental determinants

This chapter describes biological and environmental determinants of the health of Australians, providing a background to the development of successful public health activity. You will recall from the introduction to Section 2 that health determinants are the biomedical, genetic, behavioural, socioeconomic and environmental factors that impact on health and wellbeing. These determinants can be influenced by interventions and by resources and systems (Australian Institute of Health and Welfare (AIHW) AIHW 2012a). Many factors combine to affect the health of individuals and communities. People’s circumstances and the environment determine whether a population is healthy or not. Factors such as where people live, the state of their environment, genetics, their education level and income, and their relationships with friends and family are all likely to impact on their health. The determinants of population health reflect the context of people’s lives; however, people have limited control over many of these determinants (WHO 2007).

Microbiological, environmental and proteolytic aspects in chronic rhinosinusitis with nasal polyposis

Chronic rhinosinusitis is one of the most common chronic respiratory tract diseases affecting up to 15% of the adult population in the Western world. It may be perpetuated by factors predisposing to sinus ostial obstruction together with inflammatory changes in the sinus mucosa. Chronic rhinosinusitis is associated with asthma, and it may represent the same disease process. Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma share also the characteristic inflammatory features and histopathologic feature of airway remodelling. Remodelling is considered as a key event in the pathogenesis of asthma. It is controlled by a delicate balance between the matrix metalloproteinases (MMPs) and their regulators. The purpose of the present study was to evaluate the microbiological findings, inflammatory features and MMP and tissue inhibitor of metalloproteinases-1 (TIMP-1) expression in CRSwNP. The results were related to the patient history, exposure to moisture and clinical outcome in order to find out possible explanations for the etiology and chronicity of CRSwNP. Bacterial culture results were similar in patients and in controls and do not explain the chronic course of CRSwNP. The presence of fungi seems to be more common in CRSwNP than chronic rhinosinusitis in general, and they should be actively searched for using microbiological as well as histological methods. Typical outdoor fungal species were found in nasal lavage samples taken from controls in the autumn but not in the winter, reflecting environmental exposure. Exposure to moisture was reported by 46% of the CRSwNP patients, which is in accordance to the Finnish general population. Exposed patients did not differ significantly from non-exposed subjects with regards to microbiological findings, tissue eosinophilia and clinical outcome. Significantly elevated levels of collagenase-2 (MMP-8) and interleukin (IL)-8 but not tumour necrosis factor-α were found in CRSwNP patients. In particular, the activation of mesenchymal-type MMP-8 but not polymorphonuclear-type MMP-8 was associated with elevated IL-8 levels. IL-8 and MMP-8 may form an inductive cytokine-proteinase cascade in CRSwNP pathogenesis and provide a target for novel therapies and a diagnostic tool for monitoring CRSwNP treatment. The proteolytic spectrum is different in eosinophilic and non-eosinophilic CRSwNP with the up-regulation of MMP-8 and MMP-9 in non-eosinophilic CRSwNP, suggesting different pathophysiology in these subgroups. The lack of MMP up-regulation was associated with a poor prognostic factor and worse clinical outcome, representing a possible synergic anti-inflammatory function of MMP-8 and MMP-9 in CRSwNP. This study provides new information about possible immunologic mechanisms in the pathogenesis of CRSwNP. The recently discovered anti-inflammatory/ defensive properties of MMP-8 and MMP-9 in animal models are reported for the first time in a clinical setting in human inflammatory diseases.

Molecular Genetic Studies of Melanocortin Receptors in Morbid Obesity

The prevalence of obesity is increasing at an alarming rate in all age groups worldwide. Obesity is a serious health problem due to increased risk of morbidity and mortality. Although environmental factors play a major role in the development of obesity, the identification of rare monogenic defects in human genes have confirmed that obesity has a strong genetic component. Mutations have been identified in genes encoding proteins of the leptin-melanocortin signaling system, which has an important role in the regulation of appetite and energy balance. The present study aimed at identifying mutations and genetic variations in the melanocortin receptors 2-5 and other genes active on the same signaling pathway accounting for severe early-onset obesity in children and morbid obesity in adults. The main achievement of this thesis was the identification of melanocortin-4 receptor (MC4R) mutations in Finnish patients. Six pathogenic MC4R mutations (308delT, P299H, two S127L and two -439delGC mutations) were identified, corresponding to a prevalence of 3% in severe early-onset obesity. No obesity causing MC4R mutations were found among patients with adult-onset morbid obesity. The MC4R 308delT deletion is predicted to result in a grossly truncated nonfunctional receptor of only 107 amino acids. The C-terminal residues, which are important in MC4R cell surface targeting, are totally absent from the mutant 308delT receptor. In vitro functional studies supported a pathogenic role for the S127L mutation since agonist induced signaling of the receptor was impaired. Cell membrane localization of the S127L receptor did not differ from that of the wild-type receptor, confirming that impaired function of the S127L receptor was due to reduced signaling properties. The P299H mutation leads to intracellular retention of the receptor. The -439delGC deletion is situated at a potential nescient helix-loop-helix 2 (NHLH2) -binding site in the MC4R promoter. It was demonstrated that the transcription factor NHLH2 binds to the consensus sequence at the -439delGC site in vitro, possibly resulting in altered promoter activity. Several genetic variants were identified in the melanocortin-3 receptor (MC3R) and pro-opiomelanocortin (POMC) genes. These polymorphisms do not explain morbid obesity, but the results indicate that some of these genetic variations may be modifying factors in obesity, resulting in subtle changes in obesity-related traits. A risk haplotype for obesity was identified in the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) gene through a candidate gene single nucleotide polymorphism (SNP) genotyping approach. An ENPP1 haplotype, composed of SNPs rs1800949 and rs943003, was shown to be significantly associated with morbid obesity in adults. Accordingly, the MC3R, POMC and ENPP1 genes represent examples of susceptibility genes in which genetic variants predispose to obesity. In conclusion, pathogenic mutations in the MC4R gene were shown to account for 3% of cases with severe early-onset obesity in Finland. This is in line with results from other populations demonstrating that mutations in the MC4R gene underlie 1-6% of morbid obesity worldwide. MC4R deficiency thus represents the most common monogenic defect causing human obesity reported so far. The severity of the MC4-receptor defect appears to be associated with time of onset and the degree of obesity. Classification of MC4R mutations may provide a useful tool when predicting the outcome of the disease. In addition, several other genetic variants conferring susceptibility to obesity were detected in the MC3R, MC4R, POMC and ENPP1 genes.

Water quality: Indicators, human impact and environmental health

This book provides an overview of state of the art assessments of water quality; with an understanding how water quality is affected, and improving water quality for irrigation, drinking and recreation activities.

Agricultural expansion and climate change in the Taita Hills, Kenya: an assessment of potential environmental impacts

The indigenous cloud forests in the Taita Hills have suffered substantial degradation for several centuries due to agricultural expansion. Currently, only 1% of the original forested area remains preserved in this region. Furthermore, climate change imposes an imminent threat for local economy and environmental sustainability. In such circumstances, elaborating tools to conciliate socioeconomic growth and natural resources conservation is an enormous challenge. This dissertation tackles essential aspects for understanding the ongoing agricultural activities in the Taita Hills and their potential environmental consequences in the future. Initially, alternative methods were designed to improve our understanding of the ongoing agricultural activities. Namely, methods for agricultural survey planning and to estimate evapotranspiration were evaluated, taking into account a number of limitations regarding data and resources availability. Next, this dissertation evaluates how upcoming agricultural expansion, together with climate change, will affect the natural resources in the Taita Hills up to the year 2030. The driving forces of agricultural expansion in the region were identified as aiming to delineate future landscape scenarios and evaluate potential impacts from the soil and water conservation point of view. In order to investigate these issues and answer the research questions, this dissertation combined state of the art modelling tools with renowned statistical methods. The results indicate that, if current trends persist, agricultural areas will occupy roughly 60% of the study area by 2030. Although the simulated land use changes will certainly increase soil erosion figures, new croplands are likely to come up predominantly in the lowlands, which comprise areas with lower soil erosion potential. By 2030, rainfall erosivity is likely to increase during April and November due to climate change. Finally, this thesis addressed the potential impacts of agricultural expansion and climate changes on Irrigation Water Requirements (IWR), which is considered another major issue in the context of the relations between land use and climate. Although the simulations indicate that climate change will likely increase annual volumes of rainfall during the following decades, IWR will continue to increase due to agricultural expansion. By 2030, new cropland areas may cause an increase of approximately 40% in the annual volume of water necessary for irrigation.

Origins of the sex differences in handedness and mental rotation ability : genetic, environmental and hormonal effects

In humans, well-replicated and robust sex differences in cognitive functions exist for handedness and mental rotation ability. A common characteristic in human cognitive functions is the lateralization of language functions. Handedness is a common measure of laterality and is related to language lateralization. The prevalence of left-handedness is higher in males than in females, the male to female ratio being about 1.2. Among cognitive abilities, the largest sex difference is evident in the Vandenberg and Kuse Mental Rotation Test (MRT), which requires the ability to rotate objects in mental space. On average, males achieve scores one standard deviation higher than females in the MRT. The present thesis investigated the origins of the sex differences in laterality and spatial ability as represented by handedness and mental rotation ability, respectively. Two population-based Finnish twin cohorts were utilized in this study. Handedness was studied in 25 810 twins and 4068 singletons born before 1958 from the Older Finnish Twin Cohort, and in 4736 twins born in 1983-87 from the FinnTwin12. MRT was studied in a sub-sample of 804 young adult participants from the FinnTwin12 sample. The main findings of this study were: 1) the prevalence of left-handedness was higher among males than among females in both singletons and in twins; 2) males had significantly higher scores than females in MRT; 3) about one quarter of the variance in handedness and about half of the variance in MRT was explained by genetic effects, whereas the remainder of the variance in these traits was explained by environmental effects unique to each individual. The magnitude of the genetic effects was similar in both sexes; 4) left-handedness was significantly less common in female co-twins of a male than in female co-twins of a female, and female co-twins of a male scored significantly higher than did female co-twins of a female in the Mental Rotation Test. This dissertation discusses whether these differences between females from opposite- and same-sex twin pairs are due to the prenatal transfer of testosterone from the male fetus in females with male co-twins or whether they arise from postnatal socialization effects.

Governance theory as a framework for empirical research : a case study on local environmental policy-making in Helsinki, Finland

Governance has been one of the most popular buzzwords in recent political science. As with any term shared by numerous fields of research, as well as everyday language, governance is encumbered by a jungle of definitions and applications. This work elaborates on the concept of network governance. Network governance refers to complex policy-making situations, where a variety of public and private actors collaborate in order to produce and define policy. Governance is processes of autonomous, self-organizing networks of organizations exchanging information and deliberating. Network governance is a theoretical concept that corresponds to an empirical phenomenon. Often, this phenomenon is used to descirbe a historical development: governance is often used to describe changes in political processes of Western societies since the 1980s. In this work, empirical governance networks are used as an organizing framework, and the concepts of autonomy, self-organization and network structure are developed as tools for empirical analysis of any complex decision-making process. This work develops this framework and explores the governance networks in the case of environmental policy-making in the City of Helsinki, Finland. The crafting of a local ecological sustainability programme required support and knowledge from all sectors of administration, a number of entrepreneurs and companies and the inhabitants of Helsinki. The policy process relied explicitly on networking, with public and private actors collaborating to design policy instruments. Communication between individual organizations led to the development of network structures and patterns. This research analyses these patterns and their effects on policy choice, by applying the methods of social network analysis. A variety of social network analysis methods are used to uncover different features of the networked process. Links between individual network positions, network subgroup structures and macro-level network patterns are compared to the types of organizations involved and final policy instruments chosen. By using governance concepts to depict a policy process, the work aims to assess whether they contribute to models of policy-making. The conclusion is that the governance literature sheds light on events that would otherwise go unnoticed, or whose conceptualization would remain atheoretical. The framework of network governance should be in the toolkit of the policy analyst.

Determinants and Consequences of Information Sharing with Key Suppliers

As companies become more efficient with respect to their internal processes, they begin to shift the focus beyond their corporate boundaries. Thus, the recent years have witnessed an increased interest by practitioners and researchers in interorganizational collaboration, which promises better firm performance through more effective supply chain management. It is no coincidence that this interest comes in parallel with the recent advancements in Information and Communication Technologies, which offer many new collaboration possibilities for companies. However, collaboration, or any other type of supply chain integration effort, relies heavily on information sharing. Hence, this study focuses on information sharing, in particular on the factors that determine it and on its value. The empirical evidence from Finnish and Swedish companies suggests that uncertainty (both demand and environmental) and dependency in terms of switching costs and asset specific investments are significant determinants of information sharing. Results also indicate that information sharing improves company performance regarding resource usage, output, and flexibility. However, companies share information more intensely at the operational rather than the strategic level. The use of supply chain practices and technologies is substantial but varies across the two countries. This study sheds light on a common trend in supply chains today. Whereas the results confirm the value of information sharing, the contingent factors help to explain why the intensity of information shared across companies differ. In the future, competitive pressures and uncertainty are likely to intensify. Therefore, companies may want to continue with their integration efforts by focusing on the determinants discussed in this study. However, at the same time, the possibility of opportunistic behavior by the exchange partner cannot be disregarded.

Corporate Environmental Responsibility in Demand Networks (summary section only)

Research on corporate responsibility has traditionally focused on the responsibilities of companies within their corporate boundaries only. Yet this view is challenged today as more and more companies face the situation in which the environmental and social performance of their suppliers, distributors, industry or other associated partners impacts on their sales performance and brand equity. Simultaneously, policy-makers have taken up the discussion on corporate responsibility from the perspective of globalisation, in particular of global supply chains. The category of selecting and evaluating suppliers has also entered the field of environmental reporting. Companies thus need to tackle their responsibility in collaboration with different partners. The aim of the thesis is to further the understanding of collaboration and corporate environmental responsibility beyond corporate boundaries. Drawing on the fields of supply chain management and industrial ecology, the thesis sets out to investigate inter-firm collaboration on three different levels, between the company and its stakeholders, in the supply chain, and in the demand network of a company. The thesis is comprised of four papers: Paper A discusses the use of different research approaches in logistics and supply chain management. Paper B introduces the study on collaboration and corporate environmental responsibility from a focal company perspective, looking at the collaboration of companies with their stakeholders, and the salience of these stakeholders. Paper C widens this perspective to an analysis on the supply chain level. The focus here is not only beyond corporate boundaries, but also beyond direct supplier and customer interfaces in the supply chain. Paper D then extends the analysis to the demand network level, taking into account the input-output, competitive and regulatory environments, in which a company operates. The results of the study broaden the view of corporate responsibility. By applying this broader view, different types of inter-firm collaboration can be highlighted. Results also show how environmental demand is extended in the supply chain regardless of the industry background of the company.

Strategic Priorities, Company Performance and Attitudes Towards Management Accounting Techniques: an Empirical Study

The study investigates whether there is an association between different combinations of emphasis on generic strategies (product differentiation and cost efficiency) and perceived usefulness of management accounting techniques. Previous research has found that cost leadership is associated with traditional accounting techniques and product differentiation with a variety of modern management accounting approaches. The present study focuses on the possible existence of a strategy that mixes these generic strategies. The empirical results suggest that (a) there is no difference in the attitudes towards the usefulness of traditional management accounting techniques between companies that adhere either to a single strategy or a mixed strategy; (b) there is no difference in the attitudes towards modern and traditional techniques between companies that adhere to a single strategy, whether this is product differentiation or cost efficiency, and c) companies that favour a mixed strategy seem to have a more positive attitude towards modern techniques than companies adhering to a single strategy