bluuebunny/crossref_metadata_2025_split huggingface dataset:
Section introduction
Authors: Nyengaard Jens R. , Evans Stephen M. 
Published: September 2009

Abstract
Information concerning the size of a brain structure and how this changes with normal development and disease provides vital information on the function of the structure. Modern stereology offers a series of methods for estimating size at both the macroscopical level and the microscopical level. This chapter discusses global number-weighted volume estimators (the principle of Cavalieri), local volume estimators of number-weighted mean volume, indirect estimate of number-weighted mean volume, local estimator of volume-weighted mean volume, local estimator of star volume, and estimation of volume and tissue deformation.
The nucleator and the planar and optical rotators applied in rat dorsal root ganglia
Authors: Tandrup Trine 
Published: September 2009

Abstract
The correct parameter for describing size of a neuron perikaryon is a volume or a surface estimate. To obtain unbiased estimates of these three-dimensional parameters careful considerations about sampling of information in three-dimensions are necessary. Stereological principles can obtain such three-dimensional information from two-dimensional section planes using statistical sampling theories. The nucleator, the planar rotator, and the optical rotator are different volume estimators. All three methods can be used in sections of clearly delineated objects associated with a point such as neuron perikarya containing a nucleolus. This chapter discusses stereological principles applied to the rat dorsal root ganglion.
Estimation of number and volume of immunohistochemically stained neurons in complex brain regions
Authors: Dorph-Petersen Karl-Anton , Rosenberg Raben , Nyengaard Jens R. 
Published: September 2009

AbstractOne of the most important methods for studying the central nervous system is by microscopy of histological slides. Advanced histological techniques have put increasing demands upon the tissue processing and, especially in post-mortem studies of the human brain where the investigator has no control of a range of parameters, care has to be taken to make sure that findings are not confounded beyond interpretation. However, no matter how sophisticated the histological techniques, the final sections are still nothing but a sample of the original organ of interest. In order to gain robust information about the brain, attention has to be given to how the sections were sampled. This is the essence of stereology: how to sample the region of interest in such a way that the final sections are directly representative of the original organ. This chapter explains how to manage a worst-case scenario: the use of immunohistochemical techniques in thick vibratome sections from post-mortem human brainstems. The sections show anisotropic shrinkage and a significant impact of lost caps. In addition, the relevant stereological techniques demand that the sections be cut with a random position and rotation without losing track of the exact position in the complex brainstem.
Sexual health interventions are unsuitable for experimental evaluation
Authors: Kippax Susan 
Published: September 2009

Abstract
This chapter argues that most, if not all, sexual health interventions are inherently unsuitable for experimental evaluation. While it is possible to design interventions that can be randomized, in most cases the conditions demanded by experimental evaluation render either the interventions and/or the outcomes trivial. Assessment of interventions can be achieved, but by means other than experimental evaluation.
The limits of generalizability:community-based sexual health interventions among gay men
Authors: Hart Graham , Elford Jonathan 
Published: September 2009

Abstract
This chapter uses two controlled trials of peer-led interventions as case studies to illustrate some of the problems of generalizing or transferring sexual health interventions from one developed country to another. It begins with the rationale for peer-led community interventions and the success of this approach with gay men in the United States. It then describes attempts to transfer such interventions to the United Kingdom, and considers the implications of this experience.
Challenges for future sexual health intervention trials
Authors: Stephenson Judith 
Published: September 2009

Abstract
This chapter begins with a review of discussions in the preceding chapters. It then argues that it is hard to see how policy-makers, service providers, and educators would be better served by not doing trials. However, it is clear that many health promotion trials to date, including those in HIV/STI prevention, have been of poor quality. The ultimate challenge is to ensure that systematic reviews of sexual behaviour intervention trials conducted over the next decade do not conclude that the quality of trials in this area remains poor, or that few interventions have been rigorously evaluated and shown to be effective in improving sexual health.
The endosomal–lysosomal system
Authors: Maxfield Frederick R. , Mukherjee Sushmita 
Published: September 2009

AbstractThis chapter discusses the endosomal-lysosomal system. Many endocytic processes in neurones and glia share similarities with analogous processes in other cells. Thus, much that has been learned from studies in cell types, such as fibroblasts or polarized epithelia, can be used as a starting point for understanding similar processes in the brain. Even endocytic processes that are highly specialized (e.g., synaptic vesicle uptake and recycling) share the use of common elements such as clathrin-coated pits and dynamin for pinching off vesicles and rab and SNARE proteins for regulating vesicle docking and fusion. The geometry and function of neurones does place special requirements on the endocytic system, such as the need to recycle and refill synaptic vesicles very rapidly. Furthermore, the length of some neurons can require vesicles to travel very long distances to reach the somatodendritic region from the axons. The long life of neurons and the special requirements for vesicle transport and recycling may make these cells especially vulnerable to defects in the endosomal/lysosomal systems.
Defects in lysosomal enzyme modification for catalytic activity
Authors: von Figura Kurt , Borissenko Ljudmila V. , Fey Jens , Peng Jianhe , Schmidt Bernhard , Dierks Thomas 
Published: September 2009

Abstract
Two types of modifications are known so far that are required for catalytic activity of lysosomal enzymes. The first type represents the conversion of the catalytically inactive pro-form of cysteinyl- and aspartyl-proteinases into the catalytically active mature form by limited proteolysis. This chapter focuses on the second type of modification, which is represented by the posttranslational generation of a Ca-formylglycine (FGly) residue in the catalytic centre of sulfatases. Deficiency of this modification is the molecular cause of multiple sulfatase deficiency (MSD).
Defects in lysosomal enzyme trafficking
Authors: Hasilik Andrej , Lemansky Peter 
Published: September 2009

AbstractMost known lysosomal enzymes are soluble proteins that are localized in the lysosomal matrix. After biosynthesis, these proteins are targeted to lysosomes by a combination of mechanisms operating to different extents in different tissues. This allows for finely and individually tuning the proportion of lysosomal targeting and secretion. A detailed knowledge is available on the synthesis of mannose-6-phosphate (M6P)-recognition markers on soluble lysosomal enzymes and their M6P-dependent targeting as well as on sorting of M6P receptors and several proteins associated with lysosomal membranes. In humans, defects in the synthesis of M6P residues in lysosomal enzymes present as mucolipidosis (ML) II, in which the phosphorylation is missing completely, and as its milder form, ML III, in which a residual phosphorylation is present. This chapter focuses on the synthesis and sorting of the M6P-bearing soluble lysosomal enzymes.
Defects in lysosomal enzyme protection: galactosialidosis
Authors: d'Azzo Alessandra 
Published: September 2009

AbstractGalactosialidosis (GS) is a neurodegenerative lysosomal storage disorder of glycoprotein metabolism. This disease is unique among storage diseases in that it is caused by a primary defect in a protease, the protective protein/cathepsin A (PPCA). Mutations at the PPCA locus give rise to a prototypical lysosomal disease with heterogeneous clinical manifestations affecting both systemic organs and the nervous system. It is, however, not known to what extent loss of cathepsin A activity contributes to the clinical manifestations in GS patients. The mouse model of GS mimics closely the human severe phenotype and represents a valuable tool for studying the pathogenesis of the disease and developing and implementing therapy. This chapter reviews what has been learned so far about the enzyme and how this knowledge may help to understand the disease.
Spontaneous and engineered mammalian storage disease models
Authors: Hopwood John J. , Crawley Allison C. , Taylor Rosanne M. 
Published: September 2009

AbstractLysosomal storage disorders are inherited disorders of lysosomal organelle dysfunction. The relative rarity of storage diseases, their broad heterogeneous clinical presentation, and varied genetic background, together with ethical restrictions, make studies to understand their pathophysiology or to evaluate the efficacy of therapies difficult in humans. Animals with lysosomal disorders have long been of considerable importance in the development of therapy and in understanding the pathophysiology of these disorders in patients. Authentic animal models complement patients with their availability, genetic homogeneity, and their convenience and flexibility to enable the design of relatively simple experiments.
Inhibition of substrate synthesis: a pharmacological approach for glycosphingolipid storage disease therapy
Authors: Platt Frances M. , Butters Terry D. 
Published: September 2009

AbstractThe neuronopathic lysosomal storage diseases are not currently amenable to therapy due to the difficulties of delivering functional enzyme/protein to the brain. Over two decades ago, an alternative strategy was suggested by Radin based on small-molecule enzyme inhibitors for treating a subset of these disorders, the glycosphingolipidoses. Recently, the efficacy of this approach has been demonstrated in animal disease models and in the clinic. This chapter discusses these studies. It begins with a brief background on glycosphingolipids (GSLs) and GSL storage diseases, as it provides insights into the potentials and the limitations of drug-based strategies for treating this family of predominantly neurodegenerative disorders.
Gene therapy
Authors: Sands Mark S. 
Published: September 2009

AbstractThe delivery of genetic material and subsequent expression of a therapeutic protein in a whole animal or patient has proven technically difficult. The transfer of genetic material into cultured cells has been accomplished by microinjection-, chemical- (dextran, calcium phosphate, and cationic lipids), receptor ligand-, and viral-mediated approaches. Most of these approaches are either impractical or far too inefficient for in vivo applications. Viral vectors represent one of the most promising methods of gene transfer. Most of the progress with gene therapy approaches in whole animal models of human disease has been made using viral gene transfer vectors. This chapter discusses gene therapy for CNS manifestations of lysosomal storage diseases, focusing on studies utilizing viral-mediated approaches.
Bias and confounding in spatial epidemiology
Authors: Elliott P. , Wakefield J. C. 
Published: September 2009

AbstractThis chapter addresses some of the issues affecting the interpretation of spatial epidemiological studies. It separates the two concepts of bias and confounding. In general, bias and confounding are major problems affecting all observational studies, and are not special to spatial studies. However, there are several forms of bias that are specific to spatial studies. These include selection effects, denominator bias, exposure inaccuracy bias and the errors-in-variables problem, spatial dependency, significance tests, and ecological bias. The chapter also discusses socio-economic confounding as this is a major potential source of bias in spatial epidemiology.
Bayesian approaches to disease mapping
Authors: Wakefield J. C. , Best N. G. , Waller L. 
Published: September 2009

AbstractThis chapter examines the underlying assumptions of Bayesian methods for disease mapping and discusses mathematical details. The chapter proceeds as follows. Section 7.2 describes a three-state hierarchical model within which disease mapping data may be viewed. Section 7.3 considers implementation and simulation-based techniques. Section 7.4 provides two illustrative examples of the use of Bayesian disease mapping models. Section 7.5 considers some extensions and alternative approaches to the models presented. Section 7.6 provides a concluding discussion.
Clustering, cluster detection, and spatial variation in risk
Authors: Wakefield J. C. , Kelsall J. E. , Morris S. E. 
Published: September 2009

AbstractThis chapter discusses issues relating to, and reviews methods proposed for, cluster detection and clustering. The chapter proceeds as follows. Section 8.2 reviews of methods proposed for assessing the level of clustering in a set of data, and for cluster detection. Section 8.3 provides illustrative examples of the methods discussed in the previous section. Section 8.4 provides a concluding discussion.
Assessment of disease risk in relation to a pre-specified source
Authors: Morris S. E. , Wakefield J. C. 
Published: September 2009

AbstractThis chapter reviews specific problems of the assessment of disease risk in relation to a pre-specified source. The chapter proceeds as follows. Section 9.2 provides a context for point-source studies and describes a general statistical framework. Section 9.3 describes a number of conventional epidemiological techniques while Section 9.4 describes semi-parametric statistical approaches to modelling. Section 9.5 reviews regression methods. Section 9.6 illustrates a number of methods using data on the incidence of stomach cancer in the proximity of a municipal incinerator. Section 9.7 provides a concluding discussion.
Exposure assessment
Authors: Briggs D. J. 
Published: September 2009

AbstractThis chapter reviews different exposure assessment methods. It argues that there is no single or optimal method for defining and assessing exposures. Much depends on the scientific circumstances of the study: the pollutant and sources under investigation, the scale of the analysis, the study design, the specific aetiological hypothesis which motivates it, and the purposes of the study. Fitness of purpose must then be the key criterion in selecting the method for exposure assessment.
Dispersion modelling
Authors: Colvile R. , Briggs D. J. 
Published: September 2009

Abstract
This chapter is concerned with the processes and mechanisms by which human populations are exposed to environmental contaminants, focusing on the process of dispersion by turbulent diffusion. It discusses the problems and limitations of the approach, including the availability of data. It addresses the use of dispersion modelling in exposure assessment for epidemiological studies. It shows that dispersion modelling provides a potentially powerful tool for exposure assessment.
Combining models of health and exposure data: the SAVIAH study
Authors: Best N. G. , Ickstadt K. , Wolpert R. L. , Briggs D. J. 
Published: September 2009

AbstractThis chapter describes a regression-based approach to air pollution mapping, developed as part of the European Union-funded SAVIAH (Small-Area Variations In Air Quality and Health) project. The approach involves the use of monitored NO2 concentrations as a marker of traffic-related pollution, integrated with data about road networks, traffic volume, and topography within a geographical information system environment, and feeding a regression model to predict air pollution across the study area.
Water quality and health
Authors: Kanarek M. 
Published: September 2009

AbstractThis chapter focuses on the association between drinking water quality and health. It considers pollutants that have been linked to cancer mortality and incidence, including asbestos, arsenic, chlorination by-products, nitrates, and radium. It discusses the problems that plague researchers in conducting studies of drinking water and health. It argues that drinking water epidemiology studies on both infectious and non-infectious agents are an essential component of public health research. However, mainstream epidemiology has not paid enough attention to this potential source of disease, mainly due to the difficulty of drinking water studies, especially in terms of exposure assessment.
US trends
Authors: Luepker R. V. 
Published: September 2009

Abstract
This chapter discusses trends in coronary heart disease (CHD) in the United States, including mortality trends, morbidity trends, and factors associated with temporal CHD trends. CHD mortality adjusted for age continues to decline in the United States. However, crude mortality, unadjusted for age, has changed more modestly, with CHD being postponed, and manifesting at progressively older ages. The incidence of acute myocardial infarction (AMI) — defined to include both first hospitalized event and out-of-hospital death as first CHD manifestation — is declining modestly, mainly due to a decline in out-of-hospital mortality. Recurrent or second AMI is declining at a rate greater that incident AMI, particularly in the 1990s, as is case fatality for hospitalized AMI. There is also evidence that the severity of hospitalized AMI is declining.
Coronary heart disease in Central and Eastern Europe and the former Soviet Union
Authors: Bobak M. , Marmot M. 
Published: September 2009

AbstractThis chapter discusses trends in coronary heart disease (CHD) in Central and Eastern Europe (CEE) and the former Soviet Union (FSU). The chapter has three parts. First, it describes the levels and trends of mortality from CHD in CEE/FSU. Second, it reviews the possible explanations for the high rates and for the trends. Finally, it considers a few aspects of CHD in CEE/FSU that provide important findings or hypotheses relevant for the rest of the world, such as socio-economic inequalities, impact of societal transformation, and binge drinking.
Developing countries
Authors: Reddy K. S. 
Published: September 2009

AbstractThis chapter discusses trends in coronary heart disease (CHD) and cardiovascular disease (CVD) in developing countries. According to the Global Burden of Disease Study, developing countries contributed 3.5 million of the 6.2 million global deaths attributable to CHD in 1990. he projections envisage that these countries will account for 7.8 million of the 11.1 million deaths related to CHD in 2020. Nearly half of these deaths will occur below the age of seventy years, in contrast to less than a quarter of CHD deaths in the rich industrial countries. Proportional mortality rates of deaths attributable to CVD have also risen in these countries, from 24.5% in 1990 to 28.5% in 1998.
Trends in all-cause and cardiovascular mortality: a comparison between Belgium, the Netherlands, and Denmark, 1950–99
Authors: Joossens J. V. , Kesteloot H. 
Published: September 2009

AbstractThis chapter compares mortality trends and possible explanatory factors in three developed affluent countries: Belgium, the Netherlands, and Denmark. These countries have similar socio-economic systems, and each has a social healthcare system covering the whole population, but they have important differences in employment. All-cause mortality is used as the ‘gold standard’ against which to validate cardiovascular mortality. To explore which factors might explain the observed changes in mortality in the three countries, levels and time-related changes in mortality rates in both sexes are compared with changes in lifestyle and in socio-economic factors, primarily unemployment.
Dietary patterns and coronary heart disease risk
Authors: Erlinger T. P. , Appel L. J. 
Published: September 2009

AbstractThis chapter describes and compares selected dietary patterns, each of which has been associated with reduced coronary heart disease (CHD) risk. The dietary patterns include those consumed by free-living persons (i.e., a traditional Mediterranean diet consumed in Crete, vegetarian diets, diets consumed in rural China, and a traditional Okinawan diet) and diets tested in clinical trials (i.e., Lyon Diet Heart Study, Indo-Mediterranean Diet Heart Study, and the DASH clinical trial). Several distinct dietary patterns are associated with lower CHD rates and with improved CHD risk factors. A common feature of these diets is an emphasis on plant-based foods. Accordingly, fibre intake is high while saturated fat intake is low, less than 10% kcal in all instances. When total fat intake is high, that is, over 30% kcal, the predominant fat is monounsaturated fats. N-3 polyunsaturated fats are frequently consumed in small quantities and in a variety of forms. Carbohydrate intake is typically high; the predominant forms appear to be complex carbohydrates, likely from whole grain products with minimal processing.
Alcohol and coronary heart disease
Authors: Bobak M. , Marmot M. 
Published: September 2009

AbstractThis chapter reviews the evidence on the consumption of alcohol and the risk of coronary heart disease (CHD) and with compares it mortality in general. The chapter has four general sections. The first section studies of ‘average’ volume of drinking and CHD. It reviews the results of the studies, the potential biases in studies of alcohol, the biological mechanisms for the cardioprotective effects of alcohol, the possibility that the effect of alcohol is modified by background cardiovascular risk, and the public health implications of the results. The second section examines the role of drinking patterns, namely the effect of binge and heavy drinking on CHD. It then reviews the evidence linking different types of alcoholic beverages with CHD risk. Finally, the effects of alcohol on all-cause mortality are summarized.
Obesity
Authors: Dyer A. R. , Stamler J. , Greenland P. 
Published: September 2009

AbstractThis chapter reviews studies on the link between obesity and coronary heart disease (CHD). These include results from the Chicago Heart Association Detection Project in Industry Study and the Western Electric Study. Studies confirm that overweight is one of the major CHD/CVD risk factors. Concerted efforts are needed for its prevention and treatment.
Women and cardiovascular heart disease
Authors: Kuller L. H. 
Published: September 2009

AbstractThis chapter assesses the substantially lower incidence and mortality due to coronary heart disease (CHD) for women as compared to men. It considers three major current hypotheses to explain these differences: (i) the lower risk among women is due to hormonal differences or tissue-specific hormone receptors; (ii) differences in the distribution of body fat and subsequent metabolic changes, including insulin resistance and distribution of lipoprotein particles, account for the differences in coronary atherosclerosis and clinical CHD among men and women; and (iii) variations in immune response and inflammation are important determinants of differences in CHD between men and women.