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Empirical data and moral theory. A plea for integrated empirical ethics.

Ethicists differ considerably in their reasons for using empirical data. This paper presents a brief overview of four traditional approaches to the use of empirical data: "the prescriptive applied ethicists," "the theorists," "the critical applied ethicists," and "the particularists." The main aim of this paper is to introduce a fifth approach of more recent date (i.e. "integrated empirical ethics") and to offer some methodological directives for research in integrated empirical ethics. All five approaches are presented in a table for heuristic purposes. The table consists of eight columns: "view on distinction descriptive-prescriptive sciences," "location of moral authority," "central goal(s)," "types of normativity," "use of empirical data," "method," "interaction empirical data and moral theory," and "cooperation with descriptive sciences." Ethicists can use the table in order to identify their own approach. Reflection on these issues prior to starting research in empirical ethics should lead to harmonization of the different scientific disciplines and effective planning of the final research design. Integrated empirical ethics (IEE) refers to studies in which ethicists and descriptive scientists cooperate together continuously and intensively. Both disciplines try to integrate moral theory and empirical data in order to reach a normative conclusion with respect to a specific social practice. IEE is not wholly prescriptive or wholly descriptive since IEE assumes an interdepence between facts and values and between the empirical and the normative. The paper ends with three suggestions for consideration on some of the future challenges of integrated empirical ethics.

Empirical Research↗

Healthcare informatics research: from data to evidence-based management.

Healthcare informatics research is a scientific endeavor that applies information science, computer technology, and statistical modeling techniques to develop decision support systems for improving both health service organizations' performance and patient care outcomes. The analytical strategies include (1) the formulation of a data warehouse for exploration, (2) data mining, (3) the application of confirmatory statistical analysis, (4) simulation via an interface with computer and information system technologies, and (5) translational research. Healthcare informatics research will help to direct evidence-based strategic management.

Decision Support Systems, Clinical↗

Health-related quality of life outcomes measures.

OBJECTIVE: To review critically the features of measures of generic health-related quality of life (HRQOL) for disability outcomes research. DATA SOURCES: A search of electronic databases, summary reviews, books, and government documents was performed. Comment and experiences from participants of a conference on outcomes research were also incorporated. STUDY SELECTION: English language literature from scientists from a broad range of disciplines and research settings, including medicine, nursing, social science, and public health, and health services research and practice. DATA EXTRACTION: A critical review of measures that have been or might be used to measure disability outcomes. DATA SYNTHESIS: Commonly used generic measures of HRQOL can be applied to disability outcomes research with some caveats. Three common tools are the Medical Outcomes Study Short-Form Health Survey (SF-36), Sickness Impact Profile (SIP), and Quality of Well-Being (QWB) scale. The SF-36 and SIP have been used with some success in research with people with disability. The QWB scale has been used less frequently. CONCLUSION: Most studies using generic HRQOL tools are of groups with specific impairments rather than heterogeneous groups of people with disability. None of the tools appears to measure HRQOL without some potential biases (eg, inappropriate wording) for people with disability, but more specific testing of these problems is needed. Also needed are studies to determine whether these tools can measure meaningful longitudinal changes.

Persons with Disabilities↗

Treatment of itching associated with intrahepatic cholestasis of pregnancy.

OBJECTIVE: To review the drug therapy for the treatment of itching associated with intrahepatic cholestasis of pregnancy (ICP). DATA SOURCES: A comprehensive literature search was conducted in MEDLINE (1966-July 2002) using the following MeSH terms: pregnancy, itching, intrahepatic cholestasis, cholestyramine, ursodeoxycholic acid, and phenobarbital. Current Contents (1966-July 2002), International Pharmaceutical Abstracts (1970-June 2002), and Cochrane Database were also searched using those terms. Web of Science search was used to search references found in articles. DATA SYNTHESIS: Eight clinical trials and several observational studies were identified evaluating the safety and efficacy of ursodeoxycholic acid (UDCA) in the treatment of ICP. Although these studies were small and inconsistent, improvement in maternal and fetal morbidity was demonstrated. Observational studies suggest that cholestyramine may be associated with improved maternal morbidity without a documented improvement in fetal outcome. Two observational studies evaluated the efficacy of phenobarbital for ICP treatment. Phenobarbital use was not associated with improved maternal or fetal morbidity/mortality. CONCLUSIONS: Data from large, well-designed, randomized, controlled trials of treatment of ICP are lacking. Data that are available support the use of UDCA as a first-line agent and cholestyramine as a second-line agent for treatment of ICP. There is little evidence to recommend phenobarbital in the treatment of itching associated with that condition.

Adult↗

Were today's professors good students? Case study of the Zagreb University School of Medicine.

AIM: To determine whether the medical school grades of today's professors at the Zagreb University School of Medicine could serve as the predictors of their subsequent academic success. METHODS: We performed a retrospective descriptive study of medical school grades of professors and/or assistant professors at the Zagreb University School of Medicine from 1990 to 2003. The professors were divided into four groups according to the course they taught: Basic Science, Clinical Non-Surgery, Clinical Surgery, and Public Health. In total, data for 297 professors were analyzed. RESULTS: Today's professors were above-average students. The analysis of grades of professors teaching different disciplines revealed that Basic Science professors were the best students, followed by Non-Surgery and Surgery professors, whereas Public Health professors were the worst. Grades that professors earned in Public Health courses were the highest, followed by grades in Non-Surgical and Surgical courses. The grades in Basic Science courses were the lowest. CONCLUSION: Professors at the Zagreb University School of Medicine were above-average students and their grades seem to be important predictors of future success in academic career. Among today's professors, Basic Science professors were the best students.

Croatia↗

Basic science in a predoctoral family practice curriculum.

A course in applied basic science was designed with topic material organized according to anatomic body regions. Details of the diagnostic method were explained early in the course, and clinical procedures for data gathering and problem analyzing were followed while the significance of basic science knowledge in dealing with clinical situations was described. A collection of 35mm slides constituted the focal point of the course. The authors conducted the course together and an atmosphere of intellectual honesty was developed through open discussion between faculty and students. Student curiosity was respected and rewarded. Summaries of the discussions were prepared retrospectively by the faculty instructors for review gy the students. This experience proved that family physicians can demonstrate effectively the relevance of basic science to clinical medicine.

Curriculum↗

The Brazilian investment in science and technology.

An analysis of Brazilian federal expenditures in science and technology is presented is this study. The 1990-1999 data were compiled from records provided by two federal agencies (MCT and CNPq) responsible for managing most of the national budget related to these activities. The results indicate that the federal investments in Brazilian science and technology stagnated during the last decade (US$ 2.32 billion in 1990, US$ 2.39 billion in 1996, and US$ 2.36 billion in 1999). In contrast, a great increase in private investments in research was acknowledged both by industry and by the government during the same period, from US$ 2.12 to US$ 4.64 billion. However, this investment did not result in an increase in invention patents granted to residents (492 in 1990 and only 232 in 1997) or in a reduction of patent costs. Despite this unfavorable scenario, the number of graduate programs in the country has increased two-fold in the last decade and the contribution of Brazilians to the database of the Institute for Scientific Information has increased 4.7-fold from 1990 (2,725 scientific publications) to 2000 (12,686 scientific publications). Unstable federal resources for science, together with the poor returns of private resources in terms of developing new technologies, may jeopardize the future of Brazilian technological development.

Brazil↗

Clinical and demographic characteristics of psychiatric inpatients admitted via emergency and non-emergency routes at a university hospital in Pakistan.

OBJECTIVE: To examine the differences in the demographic and clinical characteristics of patients admitted through emergency versus non-emergency routes and see if these two groups of patients were significantly different from each other with respect to criteria mentioned in the title. METHODS: Retrospective data was analysed in all 2576 patient records were reviewed and these patients were divided in two groups with respect to their mode of admission (emergency vs non emergency). These groups were then compared with respect to sex, age, length of stay, discharge status and diagnostic categories. Statistical package for social sciences version 8.0 (SPSS 8.0) was used to analyze the data. SETTING: The study was conducted at the Aga Khan University Hospital, is a private tertiary care hospital with a 13 bed psychiatric facility. RESULTS: When these two groups were compared, significant differences were found, with ER patients having a shorter length of stay and youngest mean age, proportion of females admitted via ER was greater than those in non-ER group. There were significantly more women in each group who were married. The percentage of patients who left against medical advice was greater in the ER group. In both the groups mood disorders including Bipolar disorder and major depressive disorders was the most prevalent category with psychotic disorders to follow. The percentage of patients in both these categories was greater in the non-ER group where as percentage of patients with conversion disorder was higher in the ER group. CONCLUSION: Significant differences were found in the patient characteristics admitted via ER versus Non ER. Shorter length of stay in ER group might indicate an acute episode resolving quickly. Studies need to be done prospectively to determine the difference in the two groups thus ascertaining the level of care needed for each group. Lastly, the high proportion of patients coming through the ER also indicates that there exists a need for primary care involvement in mental health care thus reducing the need for emergency room usage. Clinical and Demographic Characteristics of inpatients admitted via emergency and non-emergency routes at a university hospital in Pakistan.

Adult↗

This view of science: Stephen Jay Gould as historian of science and scientific historian, popular scientist and scientific popularizer.

Science historian Ronald Numbers once remarked that the two most influential historians of science of the 20th century were Thomas Kuhn and Stephen Jay Gould. All historians are deeply familiar with Kuhn's work and influence, and most know of the remarkable impact Gould has had on evolutionary theory through both his professional and popular works. But little attention has been paid to the depth, scope, and importance of Gould's rôle as historian and philosopher of science, and his use of popular science exposition to reinforce old knowledge and generate new. This paper presents the results of an extensive quantitative content analysis of Gould's 22 books, 101 book reviews, 479 scientific papers, and 300 Natural History essays, in terms of their subject matter (Evolutionary Theory, History and Philosophy of Science, Natural History, Paleontology/Geology, Social Science/Commentary), and thematic dichotomies (Theory-Data, Time's Arrow-Time's Cycle, Adaptationism- Nonadaptationalism, Punctuationism-Gradualism, Contingency-Necessity). Special emphasis is placed on the interaction between the subjects and themata, how Gould has used the history of science to reinforce his evolutionary theory (and vice versa), and how his philosophy of science has influenced both his evolutionary theory and his historiography. That philosophy can best be summed up in a quotation from Charles Darwin, frequently cited by Gould: 'All observation must be for or against some view if it is to be of any service'. Gould followed Darwin's advice throughout his career, including his extensive writings on the history and philosophy of science.

Biological Evolution↗

Systematic review of the problems and issues of accessing specialist palliative care by patients, carers and health and social care professionals.

OBJECTIVES: To determine the problems and issues of accessing specialist palliative care by patients, informal carers and health and social care professionals involved in their care in primary and secondary care settings. DATA SOURCES: Eleven electronic databases (medical, health-related and social science) were searched from the beginning of 1997 to October 2003. Palliative Medicine (January 1997-October 2003) was also hand-searched. STUDY SELECTION: Systematic search for studies, reports and policy papers written in English. DATA EXTRACTION: Included papers were data-extracted and the quality of each included study was assessed using 10 questions on a 40-point scale. RESULTS: The search resulted in 9921 hits. Two hundred and seven papers were directly concerned with symptoms or issues of access, referral or barriers and obstacles to receiving palliative care. Only 40 (19%) papers met the inclusion criteria. Several barriers to access and referral to palliative care were identified including lack of knowledge and education amongst health and social care professionals, and a lack of standardized referral criteria. Some groups of people failed to receive timely referrals e.g., those from minority ethnic communities, older people and patients with nonmalignant conditions as well as people that are socially excluded e.g., homeless people. CONCLUSIONS: There is a need to improve education and knowledge about specialist palliative care and hospice care amongst health and social care professionals, patients and carers. Standardized referral criteria need to be developed. Further work is also needed to assess the needs of those not currently accessing palliative care services.

Aged↗

Background and framework for ILSI's collaborative evaluation program on alternative models for carcinogenicity assessment. International Life Sciences Institute.

The willingness of the agencies involved in the regulation of pharmaceuticals to accept data from newly proposed models for carcinogenicity testing (eg, transgenic animals, neonatal rodent models, initiation-promotion models) has stimulated international interest in gaining experience and a greater understanding of the strengths and limitations of the specific models. Over a 4-year period, the International Life Sciences Institute (ILSI) Health and Environmental Science Institute (HESI) has coordinated a large-scale collaborative research program to help to better characterize the responsiveness of several models proposed for use in carcinogenicity assessment. The overall objective of this partnership among industry, government, and academic scientists was to evaluate the ability of these new models to provide useful information for human cancer risk assessment. This research program reflected a commitment of nearly US$35 million by over 50 industrial, govemment, and academic laboratories from the United States, Europe, and Japan. Evaluation of the models required the development of standardized protocols to allow reproducibility and comparability of data obtained across multiple laboratories. Test compounds were selected on the basis of mechanistically meaningful carcinogenic activity or noncarcinogenicity in the rodent bioassay as well as humans. Criteria were established for dose selection, pathology review, quality control, and for evaluation of study outcome. The database from these studies represents an important contribution to the future application of new models for human cancer risk assessment. Beyond the data, the collaborative process by which the models were evaluated may also represent a prototype for assessing new methods in the future.

Academies and Institutes↗

Cancer risk assessment for 1,3-butadiene: data integration opportunities.

The US Environmental Protection Agency recently released its new guidelines for carcinogen risk assessment together with supplemental guidance for assessing susceptibility from early-life exposure to carcinogens. In particular, these guidelines encourage the use of mechanistic data in support of dose-response characterization at doses below those at which an increase in tumor frequency over background levels might be detected. In this context of the utility of mechanistic data for human cancer risk assessment, the International Life Sciences Institute (ILSI) has developed a human relevance framework (HRF) that can be used to assess the plausibility of a mode of action (MoA) described for animal models operating in humans. The MoA is described as a sequence of key events and processes that result in an adverse outcome. A key event is a measurable precursor step that is in itself a necessary element of the MoA or is a bioindicator for such an element. A number of cellular and molecular perturbations have been identified as key events whereby DNA-reactive chemicals can produce tumors. These include DNA adducts in target tissues, gene mutations and/or chromosomal alterations in target tissues and enhanced cell proliferation in target tissues. This type of data integration approach to quantitative cancer risk assessment can be applied to 1,3-butadiene, for example, using data on biomarkers in exposed Czech workers [1]. For this study, an extensive range of biomarkers of exposure and response was assessed, including: polymorphisms in metabolizing enzymes; urinary concentrations of several metabolites of 1,3-butadiene; hemoglobin adducts; HPRT mutations in T-lymphocytes; chromosomal aberrations by FISH and conventional staining procedures; sister chromatid exchanges. Exposure levels were monitored in a comprehensive fashion. For risk assessment purposes, these data need to be considered in the context of how they inform the MoA for leukemia, the tumor type reported to be increased in synthetic rubber workers exposed to 1,3-butadiene. Also, for the HRF it is necessary to establish key events for a MoA in rodents for the induction of tumors by 1,3-butadiene. There is clearly a species difference in sensitivity to tumor induction, with mice being much more sensitive than rats; key events need to explain this difference. For butadiene, the MoA is DNA-reactivity and subsequent mutagenicity and so following the EPA's cancer guidelines, a linear extrapolation is used from the point of departure (POD), unless additional data support a non-linear extrapolation. For the present case, the human bioindicator data are not informative as far as dose-response characterization is concerned. Mouse chromosome aberration data for in vivo exposures might be used for establishing a POD, with linear extrapolation from this POD. The available cytogenetic data from rodent studies appear to be sufficiently extensive and consistent for this to be a viable approach. This approach of using MoA and key events to establish the human relevance can lead to the development of specific informative bioindicators of response that can be used as surrogates to predict the shape of the tumor dose response curve at low doses. Truly informative predictors of tumor responses should be able to provide estimates of human tumor frequencies at low, environmental exposures to 1,3-butadiene.

Animals↗

Where's the evidence that active learning works?

Calls for reforms in the ways we teach science at all levels, and in all disciplines, are wide spread. The effectiveness of the changes being called for, employment of student-centered, active learning pedagogy, is now well supported by evidence. The relevant data have come from a number of different disciplines that include the learning sciences, cognitive psychology, and educational psychology. There is a growing body of research within specific scientific teaching communities that supports and validates the new approaches to teaching that have been adopted. These data are reviewed, and their applicability to physiology education is discussed. Some of the inherent limitations of research about teaching and learning are also discussed.

Cognitive Science↗

The predictivity of the toxicity of pharmaceuticals in humans from animal data--an interim assessment.

This project was undertaken by the International Life Sciences Institute's Health and Environmental Sciences Institute (ILSI-HESI) to develop an improved understanding of the extent to which various types of human toxicities (HTs) manifested during clinical trials could be predicted from standard toxicology studies. A multi-company database of 131 pharmaceutical agents to-date was based on compounds with one or more demonstrated HTs identified during clinical development. These interim results support a true positive prediction rate of animal models for human toxicity of 69%, and also that study results from non-rodent (dog, primate) species have good potential to identify HTs from many therapeutic classes. The continuing assessment of a larger database may have impact on the identification of new toxicology methodologies, and may lead to optimization of non-clinical study designs and improved assessments.

Animals↗

PROPHET, a national computing resource for life science research.

PROPHET is a national computing resource tailored to meet the data management and analysis needs of life scientists working in a wide variety of disciplines, ranging from pharmacology to molecular biology. The PROPHET system offers a fully integrated graphics-oriented environment designed to aid research scientists in the manipulation and analysis of scientific spreadsheets of data, graphs, molecular structures, biological simulation models, and protein and nucleic acid sequences, and it includes access to a range of molecular structure and sequence databases. This paper briefly describes the PROPHET system, some of its current capabilities, and plans for a new fully distributed version of the system now under development.

Amino Acid Sequence↗

PROPHET--a national computing resource for life science research.

PROPHET is a national computing resource tailored to meet the data management and analysis needs of life scientists working in a wide variety of disciplines, ranging from pharmacology to molecular biology. The PROPHET system offers a fully integrated graphics-oriented environment designed for the manipulation and analysis of tabular data, graphs, molecular structures, biological simulation models, and protein and nucleic acid sequences, and it includes access to molecular structure and sequence databases.

Computer Communication Networks↗