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Gene chips and arrays revealed: a primer on their power and their uses.

This article provides an overview and general explanation of the rapidly developing area of gene chips and expression array technology. These are methods targeted at allowing the simultaneous study of thousands of genes or messenger RNAs under various physiological and pathological states. Their technical basis grows from the Human Genome Project. Both methods place DNA strands on glass computer chips (or microscope slides). Expression arrays start with complementary DNA (cDNA) clones derived from the EST data base, whereas Gene Chips synthesize oligonucleotides directly on the chip itself. Both are analyzed using image analysis systems, are capable of reading values from two different individuals at any one site, and can yield quantitative data for thousands of genes or mRNAs per slide. These methods promise to revolutionize molecular biology, cell biology, neuroscience and psychiatry. It is likely that this technology will radically open up our ability to study the actions and structure of the multiple genes involved in the complex genetics of brain disorders.

DNA, Complementary↗

Design and manufacturing of cranioplasty implants by 3-axis cnc milling.

Although various techniques and materials have been used for making cranioplasty implants, personalized cranioplasty implants are high in cost because of expensive materials and production technology, long design and manufacturing time, and intensive labor use. This research was a part of our research project in ASEAN countries to investigate feasible technical solutions of minimizing the implant cost based on available production technologies in the region. The use of 3-axis CNC (Computer Numerical Control) milling techniques for making molds to fabricate PMMA implants was successfully investigated. With the development of a design support program bridging between Computer Aided Design (CAD) and Medical Image Processing (MIP) system, the time for geometrical modeling of implants and molds was reduced to half a day. The machining time to complete a mold was about 5 to 6 hours; and it took maximal 2 hours to fabricate an implant with self-curing PMMA and 3 and half hours for fabricating an implant with heat-curing PMMA. The cost of implants is acceptable for the ASEAN region.

Computer-Aided Design↗

Research methods for illegal drug use in hidden populations: summary report of a European invited expert meeting.

An Invited European Expert Group Meeting was held in Rotterdam that focused on research methods for hidden populations using illicit drugs. Experts from most European Community member states participated and contributed state-of-the-art presentations on various research methodologies. Attention was paid to the more quantitatively oriented research methods, such as surveys using questionnaires, interviews, and routine statistics from treatment and criminal justice as well as to more ethnographically oriented research methodologies. Recommendations were formulated for the near future: research methodology needs to meet all the classical methodological criteria, such as clear definitions, tests on reliability and validity, and clear sampling procedures. Interfacing methods is the key phrase. More quantitatively oriented methods, such as interviewing a random sample from a household survey, seem unsuitable for research on illicit drugs, except perhaps for the use of cannabis. A multifactorial problem, such as illicit drug use and related problems, should be approached in a multidisciplinary way; that is, the integration of different research methodologies. Comparability between individual research projects in different countries requires not only technical adjustments of the data, but also a "framework for communication." Data always need to be interpreted in terms of cultural context. A similar framework should enhance studies with respect to comparison of drug policies and their consequences in different cities or countries.

Epidemiologic Methods↗

Strategies for generation of an siRNA expression library directed against the human genome.

RNA interference (RNAi) is a phenomenon whereby expression of an individual gene is specifically silenced by the introduction of a double-stranded RNA (dsRNA) whose sequence is homologous to that of the gene in question. The generation of a small interfering RNA (siRNA) expression library directed against the entire human genome is a project that requires solutions to many difficult technical problems. We present here some strategies for solving some of these problems, including the development of genetically stable and highly active siRNA expression vectors, a procedure for selection of favorable target sites, and an efficient and inexpensive procedure for constructing an siRNA expression library.

Algorithms↗

Developing a plan for primary health care facilities in Soweto, South Africa. Part II: Applying locational criteria.

This article is the second of a two-part series describing the development of a ten-year plan for primary health care facility development in Soweto. The first article concentrated on the political problems and general methodological approach of the project. This second article describes how the technical problem of planning in the context of scanty information was overcome. The reasoning behind the various assumptions and criteria which were used to assist the planning of the location of facilities is explained, as well as the process by which they were applied. The merits and limitations of this planning approach are discussed, and it is suggested that the approach may be useful to other facility planners, particularly in the developing world.

Catchment Area, Health↗

TRYPNET. New hemoparasite information network.

Although Guyana, Suriname, and French Guiana share borders and climatic and geographic similarities, the countries have maintained little contact, due to language, political, and administrative differences. In 1993, two international organizations involved in the improvement of animal health, the Inter-American Institute for Cooperation on Agriculture (IICA) and CIRAD-EMVT (Centre de Cooperation Internationale en Recherche Agronomique pour le Developpement-Elevage et Medecine Veterinaire des Pays Tropicaux), jointly developed a collaborative project between the veterinary services of the three countries entitled "Hemoparasite Network for the Guianas." This project seeks to pool livestock, laboratory, and technical resources between the three countries in order to generate and exchange information on hemoparasites of livestock. A Hemoparasite Reference Laboratory for the Guianas has been created at the CIRAD-EMVT laboratory in Cayenne, French Guiana. Besides processing ruminant serum samples from the three countries, specialists from this organization conduct training in hemoparasite diagnostic techniques for laboratory personnel from Guyana and Suriname. A large-scale epidemiologic study of hemoparasites of cattle in the three countries is under way, to determine the prevalence, distribution, and clinical and economic significance of hemoparasites in the three countries, particularly Trypanosoma vivax and T. evansi. Preliminary results are presented and discussed. A Hemoparasite Information Network (TRYPNET) has been initiated, including a quarterly hemoparasite newsletter (TRYPNEWS), published in English and Spanish and disseminated to researchers in the Americas, Europe, and Africa. In 1995/96, it is proposed to expand the network's scope to include Venezuela and Brazil.

Abattoirs↗

Pooled DNA genotyping on Affymetrix SNP genotyping arrays.

BACKGROUND: Genotyping technology has advanced such that genome-wide association studies of complex diseases based upon dense marker maps are now technically feasible. However, the cost of such projects remains high. Pooled DNA genotyping offers the possibility of applying the same technologies at a fraction of the cost, and there is some evidence that certain ultra-high throughput platforms also perform with an acceptable accuracy. However, thus far, this conclusion is based upon published data concerning only a small number of SNPs. RESULTS: In the current study we prepared DNA pools from the parents and from the offspring of 30 parent-child trios that have been extensively genotyped by the HapMap project. We analysed the two pools with Affymetrix 10 K Xba 142 2.0 Arrays. The availability of the HapMap data allowed us to validate the performance of 6843 SNPs for which we had both complete individual and pooled genotyping data. Pooled analyses averaged over 5-6 microarrays resulted in highly reproducible results. Moreover, the accuracy of estimating differences in allele frequency between pools using this ultra-high throughput system was comparable with previous reports of pooling based upon lower throughput platforms, with an average error for the predicted allelic frequencies differences between the two pools of 1.37% and with 95% of SNPs showing an error of < 3.2%. CONCLUSION: Genotyping thousands of SNPs with DNA pooling using Affymetrix microarrays produces highly accurate results and can be used for genome-wide association studies.

Alleles↗

The role of early radiological studies after gastric bariatric surgery.

BACKGROUND: The authors investigated early radiological findings after gastric surgery for morbid obesity to evaluate their usefulness in avoiding complications or facilitating treatment. MATERIAL AND METHODS: 413 patients underwent gastric bariatric surgery: 327 had vertical banded gastroplasty (VBG), 55 Roux-en-Y gastric bypass (RYGBP), 22 adjustable silicone gastric banding (ASGB), and 9 biliopancreatic diversion (BPD). A radiological upper gastrointestinal investigation employing water-soluble contrast medium was performed in each patient between the 2nd and 8th postoperative day. Several techniques were employed to assess different radiological findings related to the anatomic modifications after the bariatric surgery. RESULTS: In VBGs, delayed emptying was found in 10 patients (3%), gastric leak in 3 patients (0.9%), vertical suture breakdown in 1 patients (0.3%), and a wide pouch in 4 patients (1.2%). In RYGBP, a leak was detected in 2 patients (3.6%), delayed emptying in 2 (3.6%), and a wide pouch in 5 (9.1%). ASGB required band enlargement for stomal stenosis in 6 patients (27.2%). Temporary delayed emptying from stomal stenosis was also observed in 2 BPDs (22.2%). Overall complications were 35/413 (8.2%). Two cases of gastric leak after VBG were reoperated. Stomal stenosis after ASGB were treated by percutaneous band deflation; other cases were medically treated until complete healing. CONCLUSIONS: Early radiological study after gastric bariatric surgery is advisable, since it detected postoperative complications (gastric perforation, stomal stenosis, etc.) and modified the clinical approach. As the interpretation of these radiographs is often difficult, involving different projections or patient's positions or other technical managements, surgeons and radiologists must interact and be knowledgable.

Biliopancreatic Diversion↗

New concept for the development of a confocal endomicroscope.

It is one of modern medicine's top priorities to reduce the stress for the patient during diagnosis and therapy by designing minimally invasive applications of medical techniques. Microsystems technology has always held the key to minimally invasive solutions in surgery and micro-endoscopy. The new measuring system KOMED is currently developed for the application of in-vivo cellular microscopy. This approach is based on the concept of a miniaturised fibre-optical confocal microscope. The application range of this microsensor system includes the minimally invasive optical biopsy for purposes such as the early detection of tumour cells. In this paper the concept of the KOMED system is described, as well as technical challenges to be solved in the project.

Biopsy↗

Sympathy reconfigured: Some reflections on sympathy, empathy and the discovery of values.

Two words, sympathy and empathy, are commonly used to describe three distinguishable things. These are: i) an elementary, involuntary capacity which puts us in touch with the emotional state of another; ii) the use of 'trial identification' to discover, consciously or unconsciously, the emotional state of another; iii) the affect of compassion. Because these three usages have not been clearly sorted out, and because the word sympathy has been disparaged, empathy has been overused, and a variety of technical terms (including intersubjectivity, recurrent primary identification, projective identification, alpha function etc.), all of which have important specialised applications, have been used confusingly to describe functions at a much higher level of generality. This paper attempts to sort out the three meanings with reference to the history of the two words, and also to show that the use of clear general terms gives us a more intelligible linguistic base from which other matters can be considered: in particular, whether an origin can be discerned for judgements of value other than that of superego internalisation.

Conscience↗

Hopkins Teen Central: Assessment of an internet-based support system for children with cystic fibrosis.

UNLABELLED: Support groups are an important therapeutic intervention for patients with chronic debilitating illnesses. Patients who are difficult to assemble in one physical location may benefit from participating in an electronic support group (ESG). ESGs for adolescents have not been evaluated, although studies have shown a benefit to adult ESGs. Our goals were to create a web-based support service for adolescents with cystic fibrosis (CF) and to qualitatively and quantitatively measure the effects that such a support site could have on patients' relationships with the clinic faculty and staff, access to and interaction with peers with CF, and understanding of CF. METHODS: A highly interactive ESG was developed after discussions with a team of CF specialists and patients. Eighteen of 37 teenagers with CF agreed to use this site. Each patient was asked to assess his or her perceived availability of and comfort with the clinic staff and faculty, perceived support available through peers, knowledge about CF, and perceived usefulness of the Internet as a support tool. RESULTS: Participants logged into the site an average of 4 times each month. Teens who owned home computers accessed the site somewhat more frequently than did teens who were provided with home Internet access for the study. Most activity occurred in those sections of the site that described the participants and that allowed them to socialize. Over one half of the participants e-mailed each other at least once a week, with 77% e-mailing peers at least every other week. There was no significant difference in the participants' scores on a quiz about CF at the beginning and the end of the study; however, there was a significant decrease in perceptions about their knowledge about CF. At the conclusion of the study, participants believed that they had more friends who they could relate to than they did at the beginning of the study. Clinic staff noticed an increase in references to peers among the group who were using the site. In addition, 4 of the teens expressed a desire to get together to meet each other as a result of their interactions on the web site. There was no significant change in perceptions about the perceived availability and comfort with the clinic staff and faculty, support available through peers, knowledge about CF, and the usefulness of the Internet as a support environment. Managing the project was extremely easy, with virtually no technical or procedural issues arising during the study. CONCLUSIONS: Teenagers with a chronic disease will actively participate in an ESG. The social and expressive aspects of their involvement with this support group hold much promise.

Adolescent↗

Health Care Financing Administration--Medicare program; recodification of Medicare regulations. Notice of decision to recodify regulations.

HCFA proposes to reorganize and rewrite existing regulations for the Medicare program (title XVIII of the Social Security Act). The regulations currently located in 42 CFR Part 405 would be reorganized, simplified, and renumbered to make them easier to use, as part of the Department's Operation Common Sense Project. This recodification has been classified as technical. A regualtory analysis is not planned.

Classification↗

[Objectives and organization of the International Conference on Harmonization].

The objective of the International Conference on Harmonization established since 1989 is to allow marketing of new drugs as soon as possible for patient benefit. At the same time harmonization decreases development time by harmonizing the content and the format of the registration file in the three regions: European Union, United States and Japan. ICH is a unique process involving health authorities and industry representatives of the three regions. The Conference which took place in July 1997 was the end of the first step of the process. At the meeting it was decided to pursue this harmonization activity, particularly in initiating a project devoted to the file format (Common Technical Document). The current period will be essentially focused on implementation of the common Guidelines and on their update in relation to scientific progress, the major part of the file now being harmonized in its content.

Drug Industry↗

[Training of sensorial panels consisting of children].

In the development of food products for children, it is advisable to establish the characteristics of the product with groups of children that represent the target population. To ensure the success of the products, the quality and hedonic satisfaction expectatives must be considered. In order to accomplish this premises, a group of children under the Program of Complementary Feeding of the Health Ministry--was selected and trained. The project was developed with a group of 33 children ages 9 to 12 years--from the Republica of Colombia School of Santiago, whose parents agreed and supported the participation of their children in this project. The first step was teaching the technics and methodology of Sensory Evaluation, and increasing their sensitivity. After the 8 programmed sessions, those children who met the minimal requirements for a training group were chosen. The second step was performed during 12 sessions, working with 14 children. The training was aimed at the development of the vocabulary to describe quality and defects, ranking tests, discriminative tests and the use of different scales. Tests to verify reliability, veracity and reproducibility of judgements (p < 0.05) were carried out. The trained group was able to assess different meals of the Program. The obtained results allowed to propose the improvement of some quality criteria of the Program meals.

Child↗

Strategies for development of industrial wastewater reuse in Thailand.

Majority of the industrial activities in Thailand are concentrated around Bangkok Metropolitan Area. The ever increasing industrial activities have led to over exploitation of water resources and discharge of significant pollution load. Therefore, it is important to identify the wastewater reuse potentials and develop strategies for its promotion within the industrial sector. Although technological advances have made it possible to treat effluents for industrial re-use, in practice, the Thai industries do lack in implementation of such technologies. Promotion of cleaner production concepts and advanced new technologies such as membrane technologies could assist the industry for the implementation of wastewater reuse projects in Thailand. This paper discusses various technical, institutional and management related issues to promote industrial wastewater reuse, with few case studies.

Conservation of Natural Resources↗

[How to read a screening mammography (mammotest)].

The purpose of this chapter is to give to the radiologist some practical information in order to be able to read the mammotests, as they are performed in mass screening for breast cancer in France. The examples shown must help to detect as many small cancers as possible, without inflating the false positive rate. Screening mammotests can be read one by one (first reading), or by large series (second or third reading). To improve both the sensitivity and the specificity, reading technique should be strict, with correct fitting (viewboxes, ambiant light). For each case, a technical evaluation is performed (sharpness, contrast, breast projection), followed by the detection phase (asymmetry, abnormal density or calcifications or distorsion). Then, the image is analyzed (eliminating the typical benign conditions), and finally encoded to formalize the result: normal/suspicious for breast cancer. A good working method and a perfect knowledge of normal and pathologic appearances, allow us to reach the recommended rates for detected cancers and positive tests.

Artifacts↗

[A competitive fund of development to improve the quality of university education in Chile. Area of health care].

In 1997, the Chilean Government and the International Bank for Development convened on a strategy to improve Chilean university education. It was based on quality improvement, effectiveness, relevancy and innovation on university education programs. A US$ 245 millions fund was afforded, for a five years competitive grants program, among certain traditional Universities and Technical Education Institutes. The authors reviewed the projects that won the contests during the first three years in the health area, to determine their impact, demands supported, difficulties and assets. These projects obtained 13.6% of the assigned funds (a total of US$ 16.5 millions). Funds were requested mostly to build spaces, obtain equipment, laboratories and computational support. Funds were also requested to carry out methodological changes and teaching improvements. The importance of teaching health sciences in locations outside the Metropolitan area of Santiago, the modification of undergraduate medical curriculum and the development of post graduate networks are emphasized.

Chile↗

Development of a robotic navigation and fracture fixation system.

The use of robotics in surgery is nothing new. However, there are areas of surgery, such as in fracture fixation, where robots have yet to be implemented. This paper considers the choice of robot, gripper and ancillary equipment together with navigation systems necessary for their application. Hitherto robots have seen operation in surgery only in cases where relatively low manipulation forces are required. Nothing yet exists with the capability of handling forces in excess of 200 Newton as would be required in the above scenario. Another encumbrance to robots which are already in medical use is the difficulty in programming. Unfortunately most of these robots are programmed by specialists for a particular application. However, there exists a number of robot programming languages, like Unimation VA-LII (recently superceded by Stäubli V+), which do not require specialist knowledge. The application of industrial robots to the "heavier" side of modern surgery is without doubt technically realisable. The remainder of this research project aims to determine exactly which robots and what ancilliary equipment are needed and then to implement them, first on plastic models and later on cadavers. A second phase is expected to deal with type approval and a final third phase with operations on live patients.

Fracture Fixation↗