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It is clear that the endocrine system presents a number of target sites for the induction of adverse effects by environmental agents (Fig. 1). There are numerous examples demonstrating that reproductive and developmental processes may be exquisitely sensitive to exposure and there are clear effects induced by presumed endocrine-disrupting chemicals in a variety of species. The concerns raised by studies of wildlife and humans place added significance on a better understanding of the myriad of effects attributed to endocrine disruptors. But there remains a large void between the study of relatively high exposure levels used in laboratory settings versus the relatively low levels found in the general environment. It is also equally clear that the term "endocrine disruption' has been applied to situations where the biological basis is far from conclusive. This may be a moot point in situations where populations are experiencing adverse effects on reproduction, but as scientists we must be vigilant of the appropriate use of descriptive terminology, particularly in cases where public awareness and concern are as great as this. Not only is there a need for better test procedures (both in vivo and in vitro) to characterize the potential of environmental agents to disrupt endocrine function in laboratory species, but there is also a need for a more comprehensive understanding of the normal physiological processes associated with reproduction and development in those wildlife species studied. At the same time, obtaining better information on the transport, fate and bioavailability of chemicals released into the environment remains an important but imposing task. The goals of risk characterization are to carefully delineate cause-and-effect relationships, define the dose-response relationships, and determine whether environmental exposures exceed acceptable levels. A concerted research effort is needed to fill the voids in our knowledge and reduce the large uncertainties that exist today. Only then can regulatory actions take place within the confines of legislative mandates, remediation strategies and considerations of international use and transport. Towards this end, the US Environmental Protection Agency (EPA) sponsored two workshops in 1995 (Ankley et al. 1996, Kavlock et al. 1996) at which groups of international scientists began the process of identifying research needs. Similar efforts also took place in several European countries at about the same time (Danish Environmental Protection Agency 1995, Medical Research Council 1995, Umweltbundesamt 1995). More recently, a Working Group on Endocrine Disruptors has been established within the Committee on the Environment and Natural Resources of the US Government's National Science and Technology Council. The objectives of this Working Group are to (1) formulate a framework for identifying research needs related to the health and ecological effects of endocrine-disrupting chemicals; (2) conduct an inventory of on-going federal research programs; and (3) identify research gaps and facilitate a co-ordinated research plan to address them. These efforts were largely completed in the Fall of 1996 and the information will be made available via the Internet (http;@www.cpa.gov/endocrine). The group also plans to work more broadly with other governments and private industry and public interest groups conducting research on this tissue to co-ordinate research and disseminate scientific information. Persons wishing to know more about this effort should contact the authors. The issue of endocrine disruption has raised the consciousness of many researchers, both within and outside the toxicology community, and has attracted considerable public and political interest. We now have the beginnings of international co-operation to identify the most important scientific uncertainties and to dedicate resources to address the critical gaps. (ABSTRACT TRUNCATED)
Medical research facilities, indeed all the nation's constructed facilities, must be designed, operated, and maintained in a manner that supports the health, safety, and productivity of the occupants. The National Construction Goals, established by the National Science and Technology Council, envision substantial improvements in occupant health and worker productivity. The existing research and best practices case studies support this conclusion, but too frequently building industry professionals lack the knowledge to design, construct, operate, and maintain facilities at these optimum levels. There is a need for more research and more collaborative efforts between medical and facilities engineering researchers and practitioners in order to attain the National Construction Goals. Such collaborative efforts will simultaneously support attainment of the National Health Goals. This article is the summary report of the Healthy Buildings Committee for the Leadership Conference: Biomedical Facilities and the Environment sponsored by the National Institutes of Health, the National Association of Physicians for the Environment, and the Association of Higher Education Facilities Officers on 1--2 November 1999 in Bethesda, Maryland, USA.
BACKGROUND: The epidemiology of tuberculosis in Taiwan has been influenced by the introduction of multiple Mycobacterium tuberculosis lineages and by the ageing of the population. We conducted a population-based study to investigate M tuberculosis transmission in Kaohsiung, a city in southern Taiwan. METHODS: In this study, we performed whole-genome sequencing (WGS) of M tuberculosis isolates from all culture-positive cases of tuberculosis notified in Kaohsiung between Jan 1, 2019 and Dec 31, 2023. We obtained routine epidemiological data for each case collected through the national tuberculosis control programme. We characterised the lineage composition of the isolate collection and evaluated genomic clustering of isolates, defined as a difference of 12 or fewer single-nucleotide polymorphisms. Univariable and multivariable logistic regression analyses were performed to estimate the odds of a case belonging to a genomic cluster based on host factors (age, sex, sputum smear status, and residential region) and pathogen factors (drug resistance status and strain lineage). Spatial aggregation of large genomic clusters (including greater than or equal to ten isolates) was assessed using a non-parametric statistical clustering method. We used a Bayesian transmission tree inference method to explore the patterns of age-dependent transmission. FINDINGS: During the study period, 5667 tuberculosis cases were notified in Kaohsiung, 4916 (86·7%) of which were culture-positive. Of these 4916 cases, whole-genome sequencing was successfully performed for 4168 (84·8%) isolates. 1219 (29·2%) of 4168 individuals were female and 2947 (70·7%) were male; the median age was 69·7 years (IQR 57·4-80·7). The dominant lineages were lineage 1 (1749 [42·0%] of 4168 isolates), lineage 2 (1510 [36·2%]), and lineage 4 (905 [21·7%]). 1069 (25·6%) of 4168 were genomically linked and formed 287 clusters. Lineage 2 isolates had higher odds (aOR 2·15 [95% CI 1·80-2·52]) than lineage 1 isolates of genomic clustering across all regions, whereas lineage 4 isolates had a significantly higher risk (2·75 [1·16-6·89]) of genomic clustering than lineage 1 only in the rural northeast region, inhabited primarily by indigenous populations. Spatial clustering analysis corroborated these lineage-region interactions. Although younger adults (<35 years) had the highest individual-level odds (5·64 [4·16-7·68]) of clustering in the logistic regression analysis compared with those aged 80 years or older, the transmission inference indicated that individuals aged 55-74 years were responsible for a greater proportion of inferred transmission events, contributing 50·8% of all transmission events. INTERPRETATION: This sequencing study revealed that older adults (aged ≥65 years) might have played a substantial and under-recognised role in the transmission of tuberculosis in Taiwan. The lineage-specific clustering and spatial patterns suggested that both pathogen characteristics and host demographics shaped tuberculosis transmission dynamics. These findings support the use of integrated genomic surveillance to guide precision tuberculosis control and motivate further research on age-specific transmission pathways and targeted interventions to advance tuberculosis elimination efforts. FUNDING: Taiwan National Health Research Institutes and Taiwan National Science and Technology Council.
The potential health and ecological effects of endocrine disrupting chemicals has become a high visibility environmental issue. The 1990s have witnessed a growing concern, both on the part of the scientific community and the public, that environmental chemicals may be causing widespread effects in humans and in a variety of fish and wildlife species. This growing concern led the Committee on the Environment and Natural Resources (CENR) of the National Science and Technology Council to identify the endocrine disruptor issue as a major research initiative in early 1995 and subsequently establish an ad hoc Working Group on Endocrine Disruptors. The objectives of the working group are to 1) develop a planning framework for federal research related to human and ecological health effects of endocrine disrupting chemicals; 2) conduct an inventory of ongoing federal research programs; and 3) identify research gaps and develop a coordinated interagency plan to address priority research needs. This communication summarizes the activities of the federal government in defining a common framework for planning an endocrine disruptor research program and in assessing the status of the current effort. After developing the research framework and compiling an inventory of active research projects supported by the federal government in fiscal year 1996, the CENR working group evaluated the current federal effort by comparing the ongoing activities with the research needs identified in the framework. The analysis showed that the federal government supports considerable research on human health effects, ecological effects, and exposure assessment, with a predominance of activity occurring under human health effects. The analysis also indicates that studies on reproductive development and carcinogenesis are more prevalent than studies on neurotoxicity and immunotoxicity, that mammals (mostly laboratory animals) are the main species under study, and that chlorinated dibenzodioxins and polychlorinated biphenyls are the most commonly studied chemical classes. Comparison of the inventory with the research needs should allow identification of underrepresented research areas in need of attention.
Recent advances in molecular pathology and molecular genetics have created new concerns about the use of human biologic materials in research. Since researchers now have the ability to extract and amplify DNA from minuscule archived samples, virtually any human tissue sample can potentially become the template for a test that provides information that may relate to the inherited genes of an individual. Researchers using human biologic materials should follow the 3 basic principles that have been defined for all ethical human subjects research: respect for persons, beneficence, and justice. Institutional Review Boards are responsible for providing review of the risks and benefits of research proposals to safeguard the rights and welfare of human subjects. Currently, there is considerable debate concerning the role of informed consent procedures and the Institutional Review Board oversight process in situations when researchers use human biologic materials that have been anonymized or coded. In 1999, the National Bioethics Advisory Commission is expected to make recommendations to President Clinton and the National Science and Technology Council that are expected to clarify the balance between respect for personal autonomy and the societal need to pursue biomedical research to improve the health and welfare of all individuals.
BACKGROUND: There is evidence that pyridoxine deficiency may alter the immune response. It is not known whether a deficiency of this vitamin is evident in subjects with primary Sjögren's syndrome (SS). OBJECTIVE: We studied whether subjects with primary SS showed a biochemical deficiency of pyridoxine, and if it is associated with abnormal production of interleukin-2 from lymphocytes stimulated in vitro with phytohemagglutinin (PHA). DESIGN: Two studies were conducted, (i) biochemical and nutritional assessments were performed in a cross-over study in subjects with primary SS, who were supplemented with 25 mg/day of pyridoxine or placebo for 3 months. After 1 month washout, they were supplemented for 3 months with placebo, (ii) patients with SS and matched controls received pyridoxine or placebo for 45 days, and a blood sample was obtained to study IL-2 production and expression in T-lymphocytes stimulated with PHA. RESULTS: Subjects with primary SS showed limited dietary intake of pyridoxine and biochemical deficiency of this vitamin assessed through the activation coefficient of the erythrocyte aspartate aminotransferase. The biochemical deficiency did not affect production nor mRNA expression of IL-2 from T-lymphocytes stimulated in vitro with PHA compared with the control group. Supplementation of subjects with primary SS with 25 mg/day with pyridoxine for 45 days did not produce any significant change as compared to those patients supplemented with placebo. CONCLUSIONS: Subjects with primary SS showed biochemical deficiency of pyridoxine, possibly due to limited intake of this vitamin which was corrected by supplementation with pyridoxine. However, IL-2 production and mRNA expression from stimulated lymphocytes were unaffected by supplementation, probably because the deficiency was not severe enough to affect the immune system. SPONSORSHIP: This work was supported by the National Council of Science and Technology (CONACYT), Mexico, grant no. 212226-5-0902PM.
Graduate programs provide the highest level of formal education and thus are crucial for the development of any country. However, official Brazilian data clearly show a dramatic decrease in the number and values of scholarships available to graduate programs in Brazil over the last few years, despite the importance and growth of such programs. Between 1995 and 2004, investment by the Coordenadoria de Aperfeiçoamento de Pessoal do Ensino Superior (CAPES, subordinate to the Ministry of Education and Culture) in funding scholarships, corrected for inflation in the period, actually decreased by 51%. In addition, during the period between 1994 and 2004, there was a loss of about 60% in the purchasing power of the graduate scholarships provided by CAPES and the National Council for Science and Technology (CNPq). To reverse this trend, we propose the development of sectorial funding for Brazilian graduate programs to guarantee the availability and continuity of financial support for this strategic activity.
OBJECTIVE: To describe and analyze the general characteristics and methodology of indexed publications by the health staff of the Mexican Social Security Institute in 1997. MATERIAL AND METHODS: Original articles were evaluated. The primary sources included Index Medicus, Current Contents and the Mexican National Council of Science and Technology (CONACYT) index. The following information was gathered for each article: affiliation and chief activity of the first author; impact factor of the journal; research type; field of study; topic of study, and methodological conduction. This latter point included congruence between design and objective, reproducibility of methods, applicability of the analysis, and pertinence of the conclusions. RESULTS: A total of 300 original articles was published of which 212 (71%) were available for the present study: full-time investigators (FTI) generated 109 articles and investigators with clinical activities (CAI) wrote 103 articles. The median impact factor of the journals in which FTI published was 1.337 (0.341 to 37.297) and for CAI publications, 0.707 (0.400 to 4.237). Biomedical research predominated in the first group (41%) and clinical investigation in the second (66%). Statistically significant differences were identified for the methodological conduction between groups of investigators. CONCLUSIONS: Descriptive studies and publications in journals without impact factor predominated. The FTI group had the highest bibliographic production of original articles in indexed journals with an impact factor.
Science is a complex human activity that is modeled by a myriad of factors beyond the researcher's control, especially in the medical sciences, where human and economic resources, as well as bioethical and regulatory factors play an important role. Bioethical and regulatory factors are similar between the US, Canada and Mexico, however these countries differ markedly in their economic and human resources: In Canada and the US there are government institutions (CIHR and NIH, respectively) to specifically provide funding to health research, while in Mexico the principal source of funding for all sciences is the National Council for Science and Technology (CONACYT). The NIH budget for clinical research alone during 2002 was over 7 US billion dollars; the CIHR funding for health research projects was approximately 300 US million dollars, while the support from CONACYT for research and infrastructure in health was aproximately 70 US million dollars. In the year 2000, the US had 8.17 researchers in all areas per 1,000 habitants--of the economically active population (EAP)--, Canada had 5.78 and Mexico 0.55 researchers. These factors impact greatly the scientific productivity: While Canada and the US contributed in 1991-1998 with 31.4% of the world's scientific productivity--measured as the number of articles published--, Latin America contributed with only 2.4% of the world's productivity. This paper also discusses other factors that model science, scientific inquiry, and scientific activity such as, the role of the industry, the media and scientific journals. How these factors influence the Medical Sciences in North America is exemplified herein.
Recent developments in the fields of chemistry, molecular biology, computer science, and communications promise to transform the way that many things will be done in the near future in diverse fields of scientific R&D. Fortunately for less developed countries (LDCs) some of the technologies involved are user friendly and safe, avoiding the need for radioactive precursors, large machines, or expensive reagents. For instance, tissue culture, polymerase chain reaction (PCR), dideoxi-sequencing, and recombinant DNA techniques have already invaded clinical laboratories, agricultural field stations, and natural history museums, even in some developing nations. Somatic cell culture for plant biotechnology and immunologic techniques for diagnosis have had wide applications for over a decade in all countries in the Central American Isthmus. More recently, recombinant DNA techniques, including PCR, have been introduced for diagnostic purposes and research at the two largest universities in Costa Rica and at other public institutions and are also used in Guatemala and Panama. Honduras and Nicaragua are only now acquiring these technologies for diagnostic purposes. Biotechnological applications in industry seem to be lagging behind, and presently no good links exist between research laboratories and industry for advanced applications. The application of biotechnologies in environmental problems is slowly underway, with molecular studies of natural wildlife populations and primary forest trees. A major effort is needed to create safe and effective ways of dealing with environmental degradation, wastes, and byproducts of tropical agriculture and industry. The creation of the National Biodiversity Institute (INBio) in Costa Rica to elaborate an inventory of flora and fauna and to prospect for useful substances provides a unique opportunity for biotechnological applications. In addition, government policies to promote biotechnological development are supported by CONICIT (National Research Council), the Ministry of Science and Technology, the newly established Costa Rican Academy of Science, and the national universities. Other countries in the region are beginning to take similar action. At the Cell and Molecular Biology Center (CIBCM) our strategy is to obtain the key components and infrastructure to handle nucleic acids and manage genetic information in databanks. Training has been an important priority during the last decade, with over 20 Central American students receiving graduate degrees in virology, molecular biology, genetics, and immunology, with support from German and Swedish governmental institutions. Diagnosis of viral diseases in cultivated plants and animals was done initially at CIBCM for research and later on a contractual basis for both the public and private agricultural sectors. DNA hybridization and PCR techniques are now replacing or being used concurrently with immunologic techniques.(ABSTRACT TRUNCATED AT 400 WORDS)
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Highly polymorphic segments of the human genome containing variable numbers of tandem repeats (VNTRs) have been widely used to establish DNA profiles of individuals for use in forensics. Methods of estimating the probability of occurrence of matching DNA profiles between two randomly selected individuals have been subject to extensive debate regarding the possibility of significant substructure occurring within the major races. We have sampled two Caucasian subpopulations, Finns and Italians, at four commonly used VNTR loci to determine the extent to which the subgroups differ from each other and from a mixed Caucasian database. The data were also analyzed for the occurrence of linkage disequilibrium among the loci. The allele frequency distributions of some loci were found to differ significantly among the subpopulations in a manner consistent with population substructure. Major differences were also found in the probability of occurrence of matching DNA profiles between two individuals chosen at random from the same subpopulation. With respect to the Finnish and Italian subpopulations, the conventional product rule for estimating the probability of a multilocus VNTR match using a mixed Caucasian database consistently yields estimates that are artificially small. Systematic errors of this type were not found using the interim ceiling principle recently advocated in the National Research Council's report [National Research Council (1992) DNA Technology in Forensic Science (Natl. Acad. Sci., Washington)]. The interim ceiling principle is based on currently available racial or ethnic databases and sets an arbitrary lower limit on each VNTR allele frequency. In the future the ceiling frequencies are expected to be established from more adequate data acquired for relevant VNTR loci from multiple subpopulations.
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From a national perspective, the central prerequisite of the proper application of medical technology is the timely determination of efficacy, cost, safety, and societal impact. This applies to both the introduction of the new methods and the retirement of older methods that may have outlived their usefulness. Within that framework, the rapid diffusion of innovative methods of great value must be balanced against the cost of premature enthusiasm for techniques with little or no incremental diagnostic or therapeutic gain. A nongovernmental Council on Health Care Technology Assessment of the Institute of Medicine-National Academy of Sciences was established by the Congress in 1986. The Council was charged to serve as an information clearing-house, a center to promote research and education, and a stimulus to establish better methods of assessment and more prompt identification of potentially important technologies. It represents virtually all of the constituencies concerned with adequate evaluation of new and existing methods. The Council confronts the critical problems of timing, bias, the quality of primary data collection, new methods of secondary data analysis, the nature of the "laboratory" in which technology assessment is best accomplished, the "exploitative" character of technology assessment research, appropriate diffusion, and ethnical issues. The appropriate use of technology in modern health care depends on the resolution of these issues.