糖尿病流行病学研究策略及分子遗传学研究进展

流行病学是现代医学的一门重要的基础学科,也是一门应用广泛的应用学科。流行病学作为方法学在复杂疾病研究中有不可替代的作用。糖尿病具有复杂疾病属性,应该以系统的多层次的流行病学方法为研究策略。本文从流行病学与临床医学、遗传学及分子生物学交叉所形成的分支学科--临床流行病学、遗传流行病学及分子流行病学三个方面对糖尿病的研究进展作一综述,并从分子遗传学角度列举了部分糖尿病的候选基因。提出糖尿病的研究应该从宏观流行病学(如社会环境等因素的影响)和微观流行病学(如分子遗传等)结合系统地进行研究。     

Discussion on the problems of general epidemiology

The key problems of general epidemiology: the subject, method, causality in the epidemic process, the main categories and laws, the systematization of infectious pathology and epidemiological terminology are under discussion. It is at this stage when students should form valid notions, well grounded on scientific facts and practical experience, concerning the epidemiology of noninfectious diseases with due regard to the existing differences in the interpretation of the causes of the epidemic process in noninfectious diseases and to the characteristic distribution of noninfectious diseases among the population under the influence of environmental factors without any participation of parasitic systems. The review of the notion apparatus of the theoretical epidemiology and putting it in order in accordance with general biological concepts are proposed in connection with the necessity of differentiation between the epidemic process proper (in cases of anthroponosis) and the epidemic manifestations of epizoonotic and epiphytotic processes (in cases of zoonoses and sapronoses).     

Arsenic in the aetiology of cancer

Arsenic, one of the most significant hazards in the environment affecting millions of people around the world, is associated with several diseases including cancers of skin, lung, urinary bladder, kidney and liver. Groundwater contamination by arsenic is the main route of exposure. Inhalation of airborne arsenic or arsenic-contaminated dust is a common health problem in many ore mines. This review deals with the questions raised in the epidemiological studies such as the dose-response relationship, putative confounders and synergistic effects, and methods evaluating arsenic exposure. Furthermore, it describes the metabolic pathways of arsenic, and its biological modes of action. The role of arsenic in the development of cancer is elucidated in the context of combined epidemiological and biological studies. However, further analyses by means of molecular epidemiology are needed to improve the understanding of cancer aetiology induced by arsenic.     

Experience in organizing primary specialization in epidemiology

Experience in the organization of the primary stage of specialization in epidemiology is described. In the process of this specialization the students study the subject and the methods of an epidemiologist's work, practice their skills in epidemiological analysis, acquire experience and skills necessary for work with scientific literature and in research. Grounds for the necessity of summarizing the working experience of different chairs in the form of methodological recommendations to be universally used through the country are given.     

糖尿病流行病学研究策略及分子遗传学研究进展

流行病学是现代医学的一门重要的基础学科,也是一门应用广泛的应用学科。流行病学作为方法学在复杂疾病研究中有不可替代的作用。糖尿病具有复杂疾病属性,应该以系统的多层次的流行病学方法为研究策略。本文从流行病学与临床医学、遗传学及分子生物学交叉所形成的分支学科一临床流行病学、遗传流行病学及分子流行病学三个方面对糖尿病的研究进展作一综述,并从分子遗传学角度列举了部分糖尿病的候选基因。提出糖尿病的研究应该从宏观流行病学（如社会环境等因素的影响）和微观流行病学（如分子遗传等）结合系统地进行研究。     

Role of epidemiological science and practice in protecting the health of the population of the country

The historical stages of the development of epidemiology as a science with a specific object of study, is summarized. One of the greatest theoretical generalizations is the doctrine on the natural focality of diseases. New principles of theoretical epidemiology, new theories and concepts are analyzed. The role of infectious pathology as one of the main criteria of the population health is emphasized as well as a wide spread of infectious (parasitic) diseases. The specific feature of the present stage of epidemiological situation is the dominating and constantly increasing role of viruses in the etiology of infectious diseases. The effectiveness of vaccinal prophylaxis to control vaccine-preventable infections is substantiated. The role of epidemiological science in revealing the epidemiological regularities of emerging and re-emerging infections is emphasized.     

Light,endocrine systems and cancer--a meeting report

The International Symposium "Light, Endocrine Systems and Cancer" was held on May 2-3 at Cologne University, Germany. The symposium was organized by Professor Claus Piekarski and Dr. Thomas C. Erren, Institute and Polyclinic for Occupational and Social Medicine. The main goal of the symposium was to evaluate the epidemiological and experimental data on the effect of the exposure to light-at-night on cancer risk and to indicate the main directions of future research in the field. The symposium covered also the mechanisms and epidemiology of skin cancer which, however, are not included in the present summary.     

Spatial epidemiology: an emerging (or re-emerging) discipline

Spatial epidemiology is the study of spatial variation in disease risk or incidence. Several ecological processes can result in strong spatial patterns of such risk or incidence: for example, pathogen dispersal might be highly localized, vectors or reservoirs for pathogens might be spatially restricted, or susceptible hosts might be clumped. Here, we briefly describe approaches to spatial epidemiology that are spatially implicit, such as metapopulation models of disease transmission, and then focus on research in spatial epidemiology that is spatially explicit, such as the creation of risk maps for particular geographical areas. Although the spatial dynamics of infectious diseases are the subject of intensive study, the impacts of landscape structure on epidemiological processes have so far been neglected. The few studies that demonstrate how landscape composition (types of elements) and configuration (spatial positions of those elements) influence disease risk or incidence suggest that a true integration of landscape ecology with epidemiology will be fruitful.     

Once again on the professional language of epidemiologists

Grounds for the adoption of a unified, commonly accessible, professional terminology by specialists are presented. The emphasis is made on the unification and uniformity of using the terms "epidemiological" and "epidemic". A small dictionary explaining the true or false sense of terms in epidemiology is proposed.     

Relating Phylogenetic Trees to Transmission Trees of Infectious Disease Outbreaks

Transmission events are the fundamental building blocks of the dynamics of any infectious disease. Much about the epidemiology of a disease can be learned when these individual transmission events are known or can be estimated. Such estimations are difficult and generally feasible only when detailed epidemiological data are available. The genealogy estimated from genetic sequences of sampled pathogens is another rich source of information on transmission history. Optimal inference of transmission events calls for the combination of genetic data and epidemiological data into one joint analysis. A key difficulty is that the transmission tree, which describes the transmission events between infected hosts, differs from the phylogenetic tree, which describes the ancestral relationships between pathogens sampled from these hosts. The trees differ both in timing of the internal nodes and in topology. These differences become more pronounced when a higher fraction of infected hosts is sampled. We show how the phylogenetic tree of sampled pathogens is related to the transmission tree of an outbreak of an infectious disease, by the within-host dynamics of pathogens. We provide a statistical framework to infer key epidemiological and mutational parameters by simultaneously estimating the phylogenetic tree and the transmission tree. We test the approach using simulations and illustrate its use on an outbreak of foot-and-mouth disease. The approach unifies existing methods in the emerging field of phylodynamics with transmission tree reconstruction methods that are used in infectious disease epidemiology.     

Achieving disbelief: thought styles,microbial variation,and American and British epidemiology, 1900–1940

The role of bacterial variation in the waxing and waning of epidemics was a subject of lively debate in late nineteenth and early twentieth-century bacteriology and epidemiology. The notion that changes in bacterial virulence were responsible for the rise and fall of epidemic diseases was an often-voiced, but little investigated hypothesis made by late nineteenth-century epidemiologists. It was one of the first hypotheses to be tested by scientists who attempted to study epidemiological questions using laboratory methods. This paper examines how two groups of experimental epidemiologists, the British group led by W. W. C. Topley and Major Greenwood, and an American group directed by Leslie T. Webster at the Rockefeller Institute, studied the role of variations in bacterial virulence in the course of laboratory epidemics of mouse typhoid. Relying on Ludwik Fleck’s concept of thought styles and thought collectives, the paper analyzes the fundamental conceptual differences between these two groups of researchers and analyzes the kinds of innovations they introduced as they attempted to integrate bacteriological and epidemiological approaches. The paper shows that the stylistic differences between the two groups can be understood better in the context of the institutional histories and disciplinary relations of epidemiology and bacteriology in the two countries.     

Prostate cancer pathology, screening, and epidemiology

Recent advances in the understanding of prostate cancer pathology, screening methods, and epidemiology were discussed at the 11th International Prostate Cancer Update. Regarding pathology, Dr. Gary Miller enumerated several factors that lead to the perception of prostate cancer as "unpredictable." These include the disease's multifocal nature, variable progression rates, and the uncertainty regarding the point at which carcinomas metastasize. Screening methods have been the subject of research by the Laval University Prostate Cancer Screening Program since 1988. Dr. Fernand Labrie presented the results of this 10-year study. Dr. Daisaku Hirano presented data from his studies of prostate cancer epidemiology in Japan as compared to the United States. The role of environmental factors, particularly diet, in prostate cancer pathogenesis and development is supported by the increase of the disease in Japan, concurrent with the "westernization" of diet there. Finally, useful information was presented on new computer- and Internet-based diagnostic and research tools.     

Network theory and SARS: predicting outbreak diversity

Many infectious diseases spread through populations via the networks formed by physical contacts among individuals. The patterns of these contacts tend to be highly heterogeneous. Traditional "compartmental" modeling in epidemiology, however, assumes that population groups are fully mixed, that is, every individual has an equal chance of spreading the disease to every other. Applications of compartmental models to Severe Acute Respiratory Syndrome (SARS) resulted in estimates of the fundamental quantity called the basic reproductive number R0--the number of new cases of SARS resulting from a single initial case--above one, implying that, without public health intervention, most outbreaks should spark large-scale epidemics. Here we compare these predictions to the early epidemiology of SARS. We apply the methods of contact network epidemiology to illustrate that for a single value of R0, any two outbreaks, even in the same setting, may have very different epidemiological outcomes. We offer quantitative insight into the heterogeneity of SARS outbreaks worldwide, and illustrate the utility of this approach for assessing public health strategies.     

Evaluation of the reproductive and developmental risks of caffeine

A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the "pregnancy signal," which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine is an abortafacient for the wide range of human caffeine exposures. Almost all the congenital malformation epidemiology studies were negative. Animal pharmacokinetic studies indicate that the teratogenic plasma level of caffeine has to reach or exceed 60 μg/ml, which is not attainable from ingesting large amounts of caffeine in foods and beverages. No epidemiological study described the "caffeine teratogenic syndrome." Six of the 17 recent epidemiology studies dealing with the risk of caffeine and fetal weight reduction were negative. Seven of the positive studies had growth reductions that were clinically insignificant and none of the studies cited the animal literature. Analysis of caffeine's reproductive toxicity considers reproducibility and plausibility of clinical, epidemiological, and animal data. Moderate or even high amounts of beverages and foods containing caffeine do not increase the risks of congenital malformations, miscarriage or growth retardation. Pharmacokinetic studies markedly improve the ability to perform the risk analyses.     

The identification, typing and fingerprinting of Salmonella: laboratory aspects and epidemiological applications

Since the 1930s, traditional methods of strain identification based on serotyping and phage typing have been the foundation of salmonella epidemiology. Although the incidence of diseases such as typhoid and paratyphoid has decreased in recent years, food-poisoning caused by non-typhoidal salmonella strains has now reached epidemic proportions in many countries, despite improvements in sanitation and hygiene. Precise strain identification is an essential prerequisite for epidemiological investigations aimed at combating the spread of these strains and eradicating the sources of infection. Modern methods of genotypic typing, particularly those based on physical characterization of the plasmid content of the organism have already proved invaluable for the identification and differentiation of strains in many outbreaks. These plasmid typing methods are now increasingly used with serotyping and phage typing for many epidemiological investigations. Other methods of genotypic typing, particularly those based on recognition of small differences in chromosome structure, are not yet practical for the examination of large numbers of strains. Nevertheless, improvements in small-scale methods for chromosomal DNA extraction coupled with the increasing use of non-isotopic labels for identification of restriction fragment length polymorphisms may provide a new dimension to Salmonella epidemiology.     

Analysis of continuous covariables in epidemiological studies: Dose‐response modelling and confounder adjustment

The analysis of continuous covariables with regression models commonly used in epidemiology are reviewed and compared. While some methods have been in use for decades, other more recent methods are not yet common or have not yet been formally described. It is shown that recently developed methods such as fractional polynomials and others are very useful to obtain dose‐response curves or for confounder adjustment. Different methods have their specific merits making it difficult to give general recommendations. The application of some of the methods is demonstrated with real data examples from epidemiological studies. Some suggestions for practical strategies in analysing continuous covariables are given.     

Epidemiological reflections of the contribution of anthropology to public health policy and practice

Academic disciplines like anthropology and epidemiology provide a niche for researchers to speak the same language, and to interrogate the assumptions that they use to investigate problems. How anthropological and epidemiological methods communicate and relate to each other affects the way public health policy is created but the philosophical underpinnings of each discipline makes this difficult. Anthropology is reflective, subjective and investigates complexity and the individual; epidemiology, in contrast, is objective and studies populations. Within epidemiological methods there is the utilitarian concept of potentially sacrificing the interests of the individual for the benefits of maximizing population welfare, whereas in anthropology the individual is always included. Other strengths of anthropology in the creation of public health policy include: its attention to complexity, questioning the familiar; helping with language and translation; reconfiguring boundaries to create novel frameworks; and being reflective. Public health requires research that is multi-, inter- and trans-disciplinary. To do this, there is a need for each discipline to respect the 'dignity of difference' between disciplines in order to help create appropriate and effective public health policy.     

Persons, Places, and times: the meanings of repetition in an STD clinic

In this article we work the tensions between the way clinical medicine and public health necessarily construct the problem of "repetition" in the context of a sexually transmitted disease (STD) clinic and the ways patients narrate their illness experiences. This tension-between clinical and epidemiological exigencies and the messiness of lived experience-is a recurring theme of work conducted at the intersections of epidemiology, anthropology, and clinical medicine. Clinically, repeated infections are a threat to the individual body and to "normal" biological processes like reproduction. From a public health perspective, "repeaters" are imagined to be part of a "core group" that keeps infections in circulation, endangering the social body. Yet patients' accounts are anchored in particular social histories, and their experiences rely on different time scales than those implicated in either of these types of readings. Extended analyses are provided of two such accounts: one in which repetition can be "read" as part of a performance of recovery, and one in which repetition is bound up in the effort to avoid becoming the involuntary subject of institutionally administered intervention. We argue the need to open up the category of repeaters to include the social and draw on work by Cheryl Mattingly to suggest that one way to do this in the context of the STD clinic might be to adopt forms of therapeutic practice that make use of interpretive, in addition to technical, skills.