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A "worst case" methodology for obtaining a rough but rapid indication of the societal risk from a major accident hazard installation.

This paper describes a methodology developed to provide a rough but rapid indication of the magnitude of the societal risks at and in the vicinity of a major accident hazard installation. It is intended to be used by the UK Health & Safety Executive (HSE) as a first screening tool when examining safety reports submitted under The Control of Major Accident Hazards (COMAH) Regulations 1999. These are the Regulations which implement in the UK the major aspects of Council Directive 96/82/EC, the "Seveso II" Directive. Within the methodology a new weighted risk integral parameter is defined, suitable for comparison with criteria, and its value calculated. The paper includes examples to illustrate the use of the methodology.

Accidents↗

Quantitative computerized image analysis of immunostained lymphocytes. A methodological approach.

A methodological approach by computerized image analysis to quantify immunostained objects in histological sections is described. We have investigated antibodies against CD4, CD8, CD20, CD23 and CD25 in frozen sections of human nasal mucosa; however, the methodology of standardization is of general validity. The study was designed particularly to investigate the following points: 1) light intensity, 2) the grey level for counter staining intensity, 3) the grey level threshold value for positive objects, 4) the minimal acceptable size of a positive object, 5) the influence of the brightness of the light on both the number and the area of objects. Furthermore, random sampling and determination of 6) the area per section, and 7) the number of histological sections to be measured per biopsy. Finally, a study of reproducibility of immunostaining intensity was performed. The influence of the different parameters mentioned above was studied and the values (eg. threshold value) for our particular setting of microscope, image analysis equipment, computer software etc, were defined. The method was then tested for intra- and interindividual variation which was found to be less than 5%. Correlation analysis of the reproducibility gave coefficients of correlation of 0.99, both concerning number of immunopositive objects and immunopositive area. We emphasize the importance of a highly standardized methodology if the numeric data obtained from computer assisted image analysis are to be more accurate than semiquantitative assessments by experienced observers. With a thorough standardization as described in this method it is possible to obtain numeric values, and data with low deviations, which are two obvious and important advantages.

Antigens, CD↗

Using ethnographic methodology in substance abuse treatment outcome research.

The purpose of this article is to argue for a greater inclusion of ethnography as an adjunctive methodology within the context of traditional substance abuse treatment outcome studies. First we describe what is meant by "ethnographic methodology," then discuss the various methodological elements of ethnographic research that are relevant to substance abuse research. A number of suggested applications of ethnographic research pertaining to a substance abuse treatment outcome context are then presented. The article concludes with a discussion about how ethnographic methods can enhance and broaden our understanding of important questions relating to substance abuse treatment processes and outcomes.

Anthropology, Cultural↗

Carbon dioxide in the study of panic disorder: issues of definition, methodology, and outcome.

The carbon dioxide (CO(2)) challenge paradigm has been useful for modeling panic in the laboratory. While showing promise as a technique able to promote a better understanding of the etiology of panic disorder (PD), this goal has been impeded by the lack of standardization of the challenge methodology and by uncertainty concerning the optimal definition and assessment of laboratory panic. The purpose of this paper is to highlight the impact of method variance on laboratory findings and to present recommendations for future challenge research. We begin by reviewing studies that have employed CO(2) as a stimulus for panic provocation focusing on the status of key methodological parameters between the studies and the relationship of these parameters to findings. We then make pragmatic and theoretically-based recommendations concerning approaches to methodological standardization, the establishment of a valid laboratory panic definition and the desirability of using of additional outcome measures. We conclude that although further work is needed to improve the CO(2) challenge laboratory model of panic, this paradigm can play an important role in understanding the psychopathology of PD.

Carbon Dioxide↗

The assessment of emotional distress experienced by people with an intellectual disability: a study of different methodologies.

The assessment of emotional disorders such as anger, depression and stress among people with an intellectual disability has traditionally used one of three methodologies: ratings by a significant other, a clinical interview or self-report. Despite the widespread use of all three methodologies, there is little research into their equivalence. This paper assesses the convergence among these three approaches for 147 people with a mild or moderate intellectual disability across the affective domains of anger, depression and stress. The results showed the overlap among the three methods to be consistently low, although limited convergence was found between self-report and clinical interview. Ratings by work supervisors discriminated least clearly between anger, depression and stress while self-report was the most discriminating between these three overlapping but conceptually distinct states. Suggestions are made for ongoing research into the methodologies of assessing affective states among people with an intellectual disability.

Adolescent↗

Psychopharmacology research for individuals with mental retardation: methodological issues and suggestions.

Psychotropic medications are frequently prescribed for behavior problems and/or psychopathology among individuals with mental retardation (MR). Unfortunately, the methodological integrity of scientific studies that support the use of medications among this population is often lacking. A recent review of the literature revealed that many of the studies that have assessed the efficacy of psychotropic medications for individuals with MR are methodologically flawed. Thus, we have detailed suggestions to improve the quality of future medication studies and avoid the methodological problems that prevent the scientific advancement of psychopharmacological research among individuals with MR.

Clinical Trials as Topic↗

What are the main methodological problems in the estimation of placebo effects?

Researchers disagree whether placebo effects are clinically important. The controversy is partly due to conceptual and methodological problems. The objective of this paper is to analyze the main methodological problems in the estimation of placebo effects. Variations in the meaning of the concept of placebo effect are described, and the main methodological problems are analyzed. The notion of placebo effect has at least two main meanings: effect of placebo intervention, and effect of patient-provider interaction. When the terms are defined pragmatically, effects of placebo can be estimated as the difference between placebo and no-treatment in randomized trials. The effect of patient-provider interaction can similarly be assessed by comparing manipulation of the patient-provider interaction with no manipulation. In both cases bias due to lack of double-blinding is a potential problem.

Confounding Factors, Epidemiologic↗

A methodology for partitioning a vocabulary hierarchy into trees.

Controlled medical vocabularies are useful in application areas such as medical information systems and decision-support systems. However, such vocabularies are large and complex, and working with them can be daunting. It is important to provide a means for orienting vocabulary designers and users to the vocabulary's contents. We describe a methodology for partitioning a vocabulary based on an IS-A hierarchy into small meaningful pieces. The methodology uses our disciplined modeling framework to refine the IS-A hierarchy according to prescribed rules in a process carried out by a user in conjunction with the computer. The partitioning of the hierarchy implies a partitioning of the vocabulary. We demonstrate the methodology with respect to a complex sample of the MED, an existing medical vocabulary.

Models, Theoretical↗

Statistical methodology of phase III cancer clinical trials: advances and future perspectives.

The methodology for conducting cancer clinical trials has undergone enormous changes over the past 25-30 years since the EORTC Data Center was created. The purpose of this paper is to highlight and to provide a historical perspective for the main methodological concepts, both practical and theoretical, which form the basis for the design and analysis of phase III cancer clinical trials within the EORTC Data Center. Some statistical aspects of other associated topics such as quality of life, health economics, meta-analysis and treatment outcome will also be briefly discussed. Finally, some future perspectives and topics for further statistical methodological research will be presented in order to spur statisticians to meet the challenge of efficiently designing and analysing the clinical trials of tomorrow.

Clinical Trials, Phase III as Topic↗

Health related quality of life assessment methodology and reported outcomes in randomised controlled trials of primary brain cancer patients.

Over the last 20 years, the assessment of quality of life (QOL) has become an important endpoint in cancer clinical trials, helping us to understand patient survival and QOL experiences and aiding clinicians in providing the best possible treatment and care, with the least toxicity and ill-effects. In primary brain cancer, these are critical issues. Survival is often limited and treatment difficult to tolerate. In recent years, some authors have questioned the methodological quality of the investigations and the reporting of QOL assessments from randomised controlled trials (RCTs), of cancer patients yet this assessment has never specifically focused on brain cancer. This paper therefore reports a systematic review of the research methodology and QOL assessment reporting in brain cancer patients in RCTs. The search was mainly performed on the following databases: Medline, Cancerlit and the Cochrane Controlled Trials Register. We identified only five RCTs, enrolling a total of 1026 patients. In many of these studies, we had identified methodological limitations which would hinder the interpretation of the results. These included a lack of detailed reporting regarding missing data, use of poorly validated tools, and general limitations regarding the presentation and interpretation of the results. Based on the results of our review, we make recommendations for future investigations to avoid these shortcomings.

Brain Neoplasms↗

Methodologic considerations for research in traditional (alternative) medicine.

The widepsread use, in the United States and other western countries, of alternative medical practices often derived from traditional systems of health has intensified the need to evaluate their safety and effectiveness. These practices tend to generate polarized attitudes of either acceptance or rejections. Opponents reject them because, they claim, good scientific research has not supported their use. Proponents insist that current scientific methodologies are not appropriate to evaluate these practices. This article briefly examines these issue, suggesting that the answer lies between these 2 extreme positions. Various methodologic issues are considered, and suggestions are made to adapt scientific methodology, where appropriate, to respect the particularities of alternative medicine.

Clinical Trials as Topic↗

Some new methodological aspects of the hen's egg test for micronucleus induction (HET-MN).

In a previous publication we introduced the hen's egg test for micronucleus induction (HET-MN) as an extremely simple, inexpensive and rapid animal free genotoxicity assay which is positioned between pure in vitro and in vivo assays, strictly in line with animal protection regulations and ethical aspects. The HET-MN combines the use of the commonly accepted genetic endpoint "formation of micronuclei" with the well characterized and complex model of the chick embryo. The high metabolic competency provided by this model enables metabolic activation, elimination and excretion of xenobiotics including mutagens and promutagens. In this paper we present some new methodological aspects, which are important for improving the experimental protocol. We used cyclophosphamide (CP) and 7,12-dimethyl-benz[a]anthracene (DMBA) as model substances. Dose-response-relationship for both chemicals and cytotoxic effects for CP are described. In addition to the standard proliferation marker PCE/NCE-ratio we found an increased frequency of primitive erythrocytes (E I) and the appearance of proerythroblasts and erythroblasts as further alerting signals for cytotoxic or erythrosuppressive effects. From the total cell population we could further qualify the group of target cells. We found that all definite erythrocytes (E II), observed at day 11 (d11), are relevant target cells, independent from their stage of maturity (polychromatic as well as normochromatic definite erythrocytes). E I cells do not belong to the group of target cells, however. An additional important methodological aspect is the optimal time frame. We found the time period from d8 of incubation (administration of the test substance) up to d11 (time point of blood sampling) as most favorable. In this way an exposure period of up to 72h is covered. Further results indicate that the air cell route provides a higher response to the test substances than the albumen route. The consideration of the described methodological aspects will contribute to the improvement of the experimental protocol of the HET-MN.

9,10-Dimethyl-1,2-benzanthracene↗

A staffing-effectiveness methodology for analyzing human resource and clinical/service screening indicator data.

BACKGROUND: The Hospital of the University of Pennsylvania (Philadelphia), a university-affiliated academic health center, developed and pilot tested a method for analyzing staffing effectiveness. SCREENING INDICATORS: Human resource screening indicators chosen for analysis included direct caregiver indicators (based on nursing and allied health resource data), such as registered nurse (R.N.) turnover rate, and indirect caregiver indicators (based on overall health care organization resource data), such as overall hospital turnover rate. Clinical/service screening indicators consisted of five nursing-sensitive outcome variables. DATA COLLECTION: Patient unit-based data collection at the hospital was institutionally aggregated on a quarterly basis for all human resource and clinical service indicators. Initial methodological development and pilot testing focused on statistical process control chart (SPCC) methodology for longitudinal measurements and the use of spider diagrams for examination of potential relationships within and among all variables, with all variables considered simultaneously in an interrelational analytical process. DISCUSSION: The design, development, and pilot-testing of the staffing-effectiveness methodology led to recommendations for clinical and operational interventions.

Efficiency, Organizational↗

What should be included in meta-analyses? An exploration of methodological issues using the ISPOT meta-analyses.

OBJECTIVE: To explore the impact of methodologic issues on the results of meta-analyses. The following issues were examined: the type of literature search strategy used; inclusion or exclusion of non-peer-reviewed studies; the inclusion or exclusion of non-English language publications; the effect of trial quality; and the inclusion or exclusion of non-placebo-controlled studies. METHODS: The International Study of Perioperative Transfusion (ISPOT) meta-analyses were used to evaluate each of the methodologic issues. The 10 meta-analyses consisted of technologies to reduce the need for perioperative red blood cell transfusion. The number of trials for each of the meta-analyses varied from 2 to 45. Both EMBASE and MEDLINE searches were conducted, including the use of systematic search strategies. RESULTS: MEDLINE identified the vast majority of trials. Alone, MEDLINE would have missed 8 studies compared to 10 for EMBASE. Use of the systematic search strategies greatly reduced the number of articles to be reviewed compared to open searches. Type of publication, country of study origin, inclusion of non-English publications, and trial quality had very little impact on the estimates of effect. The use of placebo versus open-label control affected the magnitude of the odds ratio for two of the meta-analyses. The results of the two meta-analyses were not statistically significant if only placebo-controlled trials were included. CONCLUSIONS: While methodologic issues had very little impact on the ISPOT meta-analyses, further studies are needed in a variety of other clinical settings. Because MEDLINE, coupled with a review of the references in the identified trials, identified the vast majority of trials, one needs to consider the costs and benefits of searching EMBASE and the pursuance of unpublished and unindexed trials.

Databases, Bibliographic↗

Burden in caregivers of cognitively impaired older adults living in the community: methodological issues and determinants.

Considerable burden is reported by informal caregivers of older individuals with cognitive impairment. Significant progress in the understanding of determinants of this burden has been achieved. However, further progress could be attained if we considered important methodological issues that may have limited our understanding of caregiver burden. These issues include subgroups of care recipients and caregivers, measurement issues, research design, and statistical techniques. Fifty-three studies published between 1980 and 1997 (inclusive) that focused on caregiver burden were abstracted to determine the extent to which the methodological issues discussed above were considered. Overall, we found considerable variability among the studies surveyed. Further understanding of the caregiving process and reductions in caregiver burden will depend on the attention to methodological issues and understanding of burden across the whole caregiving career.

Aged↗

The decade 1989-1998 in Spanish psychology: an analysis of research in statistics, methodology, and psychometric theory.

This paper presents an analysis of research published in the decade 1989-1998 by Spanish faculty members in the areas of statistical methods, research methodology, and psychometric theory. Database search and direct correspondence with faculty members in Departments of Methodology across Spain rendered a list of 193 papers published in these broad areas by 82 faculty members. These and other faculty members had actually published 931 papers over the decade of analysis, but 738 of them addressed topics not appropriate for description in this report. Classification and analysis of these 193 papers revealed topics that have attracted the most interest (psychophysics, item response theory, analysis of variance, sequential analysis, and meta-analysis) as well as other topics that have received less attention (scaling, factor analysis, time series, and structural models). A significant number of papers also dealt with various methodological issues (software, algorithms, instrumentation, and techniques). A substantial part of this report is devoted to describing the issues addressed across these 193 papers--most of which are written in the Spanish language and published in Spanish journals--and some representative references are given.

Bibliometrics↗

Methodologies for estimating emissions for the U.S. EPA's NOx SIP call, CER rule, and other complexities.

Emissions inventories play an important role in many air quality decisions, and the importance of obtaining correct emissions data challenges the emissions inventory community to continuously improve its estimation techniques. The Clean Air Act Amendments of 1990 requires states with ozone nonattainment areas (NAAs) to submit periodically a comprehensive, accurate, and actual inventory of ozone precursor emissions until the areas are redesignated to attainment. They require the states with NAAs to report peak ozone season daily and annual estimates of the inventories for the counties that are in nonattainment. The recently proposed U.S. Environmental Protection Agency's (EPA) NO(x) SIP call and the Consolidating Emissions Reporting (CER) rule are more demanding still. The CER rule requires the states to report statewide point source inventories, 3-yr cycle inventories, and NO(x) SIP call inventories by county for all source types, regardless of the attainment status; the estimating periods are peak ozone season daily, 5-month ozone season, and annual estimates. Furthermore, complexities in emissions inventories such as estimating the emissions with different seasonal and multiple controls exist. These complexities and methodologies for estimating emissions for different time periods are not addressed sufficiently either by the EPA's procedure manuals or by the Emissions Inventory Improvement Program guidance documents. This paper presents methodologies for estimating emissions for different time periods and multiple controls. These methodologies will help the EPA, state, and local government agencies to meet the evolving demands of emissions inventories and the reporting requirements of the NO(x) SIP call and the CER rules.

Air Pollutants↗

Integrated methodology for forensic oil spill identification.

A new integrated methodology for forensic oil spill identification is presented. It consists of GC-MS analysis, chromatographic data processing, variable-outlier detection, multivariate data analysis, estimation of uncertainties, and statistical evaluation. The methodology was tested on four groups of diagnostic ratios composed of petroleum biomarkers and ratios within homologous PAH categories. Principal component analysis (PCA) was employed and enabled the simultaneous analysis of many diagnostic ratios. Weathering was taken into account by considering the sampling uncertainties estimated from replicate spill samples. Statistical evaluation ensured an objective matching of oil spill samples with suspected source oils as well as classification into positive match, probable match, and nonmatch. The data analysis is further refined if two or more source oils are classified as probable match by using weighted least squares fitting of the principal components, local PCA models, and additional information relevant to the spill case. The methodology correctly identified the source of two spill samples (i.e., crude oils from Oseberg East and Oseberg Field Centre) and distinguished them from closely related source oils.

Denmark↗