A tracking system for conducting epidemiological case-control studies

The automated-respondent tracking system (ARTS) is an event-driven management system developed to monitor data collection during large epidemiological case-control studies. ARTS facilitates the conduct and management of these studies by eliminating the problems and limitations of manually monitoring subjects. This system, developed on an IBM 3032, consists of a series of programs linked by a general update program. Data captured on each subject for every study phase are used to generate lists of subjects requiring further action by the study staff. Additionally, ARTS produces reports reflecting a study's progress. Improved study management and reduced clerical load justify the system's costs. Concepts and programming principles applied to ARTS can be generalized to other epidemiological study designs.     

The cluster method in conducting epidemiological research

The Expanded Programme on Immunization (EPI) whose goal is to reduce morbidity and mortality by providing children with immunizations against diphtheria, pertussis, tetanus, poliomyelitis, measles, and tuberculosis continually faces the problem of documenting immunization coverage rates. Therefore the EPI seeks simple, effective, and inexpensive methods of evaluation which could be implemented in different countries. An example of such a method is a simplified cluster sampling technique of estimation of immunization coverage through the examination of 210 children, selected randomly as 30 groups of 7 children each. In 1978-1984 more than 1000 immunization coverage surveys were performed all over the world, mainly in developing countries. In a modified way this method is also used to collect data on morbidity and mortality of certain EPI target diseases as well as diarrhoeal diseases.     

Molecular tools for speciation and epidemiological studies of Acanthamoeba

Current diagnostic methods for Acanthamoeba identification rely heavily on light microscopic techniques that do not provide sufficient information about the identification of Acanthamoeba at the species level, thus delaying accurate identification of the infective agent. Here we report the use of polymerase chain reaction (PCR)-based restriction enzyme analyses to detect and speciate Acanthamoeba from both clinical and environmental sources by comparing their restriction endonuclease patterns. Significant diversity was observed between and within morphologically defined Acanthamoeba species. The usefulness of PCR-based assays and other available diagnostic methods is discussed. Received: 15 August 2001 / Accepted: 15 October 2001     

Results of conducting an epidemiological survey of diphtheria in 21 territories of the RSFSR

As the result of epidemiological survey of diphtherial infection, carried out in conformity with the unified methodological recommendations in 21 regions of the RSFSR during 1980-1981, the expediency of such experiment was established. Immunity to diphtheria in children aged up to 14 years was high: children with negative Schick tests constituted 96.9-99.1%. No biological changes in Corynebacterium diphtheriae occurred during the term of observation. Toxigenic C. diphtheriae showed a high level of pathogenicity. The epidemiological survey contributed to a more thorough detection of diphtheria patients and carriers releasing toxigenic C. diphtheriae. The quality of clinical bacteriological diagnosis improved. In rare cases angina with the concomitant carriership of toxigenic C. diphtheriae could be diagnosed with the indispensable serological examination of the patients by Jensen's method.     

Radon in Norwegian dwellings and the feasibility of epidemiological studies

Summary The results of a pilot study on radon in Norwegian dwellings are presented together with a discussion on the feasibility of an epidemiological study on the correlation between lung cancer and radon progeny exposure in dwellings. There are large variations in the mean radon concentration in Norwegian municipalities, and the population average indoor radon concentration is high (80–100 Bq m^–3). The large variations and high absolute values, together with excellent lung cancer and smoking habit data, make it feasible to conduct epidemiological studies based on representative exposure data in the Norwegian population.     

Genetical and epidemiological studies of polydactyly in Hungary

Polydactyly is one of the most frequently observed human congenital limb malformations. Sporadic cases of polydactyly have been described, but most show an autosomal dominant pattern of inheritance. The purpose of this study was to investigate the frequency of polydactyly among children born between 1980 and 1997 in Hungary. The predominance of the postaxial type over the preaxial one was less than expected. These malformations affected significantly more boys than girls. The proportion of children with low birth weight affected by polydactyly was higher than expected. Among mothers giving life to offspring with polydactyly, the prevalence was high in the older age group. We analysed the regional distribution in Hungary and the twin frequency in connection with polydactyly. From our results comparing it to the current literature data we made conclusions about the possible causes of the development of polydactyly.     

Ionizing radiation biomarkers for potential use in epidemiological studies

Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100mSv and/or 0.1mSvmin(-1)) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential.     

Biological sample collection and processing for molecular epidemiological studies

Molecular epidemiology uses biomarkers and advanced technology to refine the investigation of the relationship between environmental exposures and diseases in humans. It requires careful handling and storage of precious biological samples with the goals of obtaining a large amount of information from limited samples, and minimizing future research costs by use of banked samples. Many factors, such as tissue type, time of collection, containers used, preservatives and other additives, transport means and length of transit time, affect the quality of the samples and the stability of biomarkers and must be considered at the initial collection stage. An efficient study design includes provisions for further processing of the original samples, such as cryopreservation of isolated cells, purification of DNA and RNA, and preparation of specimens for cytogenetic, immunological and biochemical analyses. Given the multiple uses of the samples in molecular epidemiology studies, appropriate informed consent must be obtained from the study subjects prior to sample collection. Use of barcoding and electronic databases allow more efficient management of large sample banks. Development of standard operating procedures and quality control plans is a safeguard of the samples' quality and of the validity of the analyses results. Finally, specific state, federal and international regulations are in place regarding research with human samples, governing areas including custody, safety of handling, and transport of human samples, as well as communication of study results.Here, we focus on the factors affecting the quality and the potential future use of biological samples and some of the provisions that must be made during collection, processing, and storage of samples, based on our experience in the Superfund Basic Research Program and Children's Environmental Health Center, at the University of California, Berkeley.     

Challenges in applying scientific evidence to width recommendations for riparian management in agricultural Australia

Intact riparian zones maintain aquatic–terrestrial ecosystem function and ultimately, waterway health. Effective riparian management is a major step towards improving the condition of waterways and usually involves the creation of a ‘buffer’ by fencing off the stream and planting vegetation. Determination of buffer widths often reflects logistical constraints (e.g. private land ownership, existing infrastructure) of riparian and adjacent areas, rather than relying on rigorous science. We used published information to support riparian width recommendations for waterways in agricultural Victoria, Australia. We focused on different ecological management objectives (e.g. nutrient reduction or erosion control) and scrutinised the applicability of data across different environmental contexts (e.g. adjacent land use or geomorphology). Not surprisingly, the evidence supported variable ‘effective’ riparian widths, depending on the objective and environmental context. We used this information to develop a framework for determining riparian buffer widths to meet a variety of ecological objectives in south‐east Australia. Widths for reducing nutrient inputs to waterways were most strongly supported with quantitative evidence and varied between 20 and 38 m depending on environmental context. The environmental context was inconsistently reported, making it difficult to recommend appropriate widths, under different land‐use and physiographic scenarios. The evidence to guide width determination generally had high levels of uncertainty. Despite the considerable amount of published riparian research, there was insufficient evidence to demonstrate that implemented widths achieved ecological objectives. We emphasise the need for managers to clearly articulate the objectives of proposed riparian management and carefully consider the environmental context. Monitoring ecological responses associated with different riparian buffer widths is essential to support future management decisions.     

Genetic and epidemiological studies in Dagestan highland isolates

Interpopulation differences in the epidemiology and age of onset of complex diseases, as well as expression of some vital parameters, have been found. The relationship between these interpopulation differences and the genetic processes that have been occurring in the populations throughout their history has been demonstrated. The Daghestan genetic isolates studied are characterized by aggregation of certain complex diseases. In each genetic isolate, almost all affected subjects with homogeneous clinical phenotypes belong to the same large pedigree with a limited number of founders. There is evidence for a large variance of the population risk of schizophrenia (morbid risk) in Daghestan isolates (this parameter varies from 0 to 5%). Examination of 211 cases of schizophrenia earlier diagnosed in Daghestan psychiatric hospitals has shown that only 139 of them meet the DSM-IV criteria for schizophrenia. The remaining 72 subjects have, according to DSM-IV criteria, various schizoaffective and affective disorders; all of these subjects are close relatives of the schizophrenic patients. The age of onset of schizophrenia in the isolates studied varies from 14 to 40 years (20.84 +/- 0.568 years). Offspring of consanguineous marriages exhibit later age at onset and a higher risk of schizophrenia than offspring of exogamous marriages. The results of multivariate genetic analysis indicate that different gene complexes are involved in the pathogeneses of early-onset and late-onset forms of schizophrenia. An association of schizophrenia incidence, its age dependence, and reproductive parameters with polymorphisms of some microsatellite loci have been demonstrated.     

Challenges in analysis and interpretation of microsatellite data for population genetic studies

Advancing technologies have facilitated the ever‐widening application of genetic markers such as microsatellites into new systems and research questions in biology. In light of the data and experience accumulated from several years of using microsatellites, we present here a literature review that synthesizes the limitations of microsatellites in population genetic studies. With a focus on population structure, we review the widely used fixation (F_ST) statistics and Bayesian clustering algorithms and find that the former can be confusing and problematic for microsatellites and that the latter may be confounded by complex population models and lack power in certain cases. Clustering, multivariate analyses, and diversity‐based statistics are increasingly being applied to infer population structure, but in some instances these methods lack formalization with microsatellites. Migration‐specific methods perform well only under narrow constraints. We also examine the use of microsatellites for inferring effective population size, changes in population size, and deeper demographic history, and find that these methods are untested and/or highly context‐dependent. Overall, each method possesses important weaknesses for use with microsatellites, and there are significant constraints on inferences commonly made using microsatellite markers in the areas of population structure, admixture, and effective population size. To ameliorate and better understand these constraints, researchers are encouraged to analyze simulated datasets both prior to and following data collection and analysis, the latter of which is formalized within the approximate Bayesian computation framework. We also examine trends in the literature and show that microsatellites continue to be widely used, especially in non‐human subject areas. This review assists with study design and molecular marker selection, facilitates sound interpretation of microsatellite data while fostering respect for their practical limitations, and identifies lessons that could be applied toward emerging markers and high‐throughput technologies in population genetics.     

Ecological and epidemiological studies of histoplasmosis in the United States of America

Histoplasmosis is a disease that is transmitted from nature to man. The causative agent,Histoplasma capsulatum, grows freely in the soil and the infection is spread by inhalation of the infectious spores. The infection is highly endemic in the central United States. Soil contaminated with fecal droppings of chickens, starlings, blackbirds, and other avian species is a principal source of infection.Paper read at the Eighth International Congresses for Tropical Medicine and Malaria, September 1968, Teheran (Iran).     

DNA methylation analysis from saliva samples for epidemiological studies

Saliva is a non-invasive, easily accessible tissue, which is regularly collected in large epidemiological studies to examine genetic questions. Recently, it is becoming more common to use saliva to assess DNA methylation. However, DNA extracted from saliva is a mixture of both bacterial and human DNA derived from epithelial and immune cells in the mouth. Thus, there are unique challenges to using salivary DNA in methylation studies that can influence data quality. This study assesses: (1) quantification of human DNA after extraction; (2) delineation of human and bacterial DNA; (3) bisulfite conversion (BSC); (4) quantification of BSC DNA; (5) PCR amplification of BSC DNA from saliva and; (6) quantitation of DNA methylation with a targeted assay. The framework proposed will allow saliva samples to be more widely used in targeted epigenetic studies.