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OMERACT 7 psoriatic arthritis workshop: synopsis.

Outcome Measures in Rheumatology (OMERACT) conferences have developed a process by which outcome measures to be included in clinical trials are identified by consensus. During OMERACT 7, held in Asilomar, CA, USA, in May 2004, a workshop on outcome measures in psoriatic arthritis was held. Information derived through a previous Delphi exercise and nominal group process was shared with the participants, as were the results from a study using completed clinical trials with biological therapies. On the basis of the evidence presented and discussions in breakout groups at the OMERACT conference, a set of domains to be included in clinical trials in psoriatic arthritis was developed and a research agenda for further studies in psoriatic arthritis proposed.

Arthritis, Psoriatic↗

Clinical trial experience by simulation: a workshop report.

A new computer program for experimental design simulation was used in a three-day postgraduate workshop on clinical trials. Participants were given information on a fictitious new drug and asked to design a trial to evaluate it. On the first day they reviewed the data and designed a protocol, and results for these specifications were generated on the computer. The second day was spent analysing results, and on the last day the findings of the different studies were presented at a symposium. Flexibility of the program ensured a high degree of realism in all trials and emphasised the influence of design on results and conclusions.

Adolescent↗

How could pathologists improve the initial diagnosis of colitis? Evidence from an international workshop.

BACKGROUND: The taking of multiple colorectal biopsies is in widespread use although there is little research into their benefit for the pathological diagnosis of inflammatory bowel disease. There is also still debate about appropriate morphological criteria for interpreting these biopsies. AIMS: To determine the effect of single versus multiple biopsies on the accuracy of diagnosis and to study the accuracy and reproducibility of the different criteria used in the diagnosis of multiple biopsies by expert and non-expert pathologists. METHOD: Thirteen expert and 12 non-expert international diagnostic histopathologists attended a workshop. Sixty cases with full follow up were viewed, blinded, in two rounds. Diagnoses were made on rectal biopsies and then full colonoscopic series. RESULTS: Experts correctly identified 24% of Crohn's disease cases (non-experts, 12%) from the rectal biopsies. This improved to 64% (non-experts, 60%) with the full series. The accuracy of the diagnosis of ulcerative colitis also improved slightly with the full series from 64% to 74% overall. Experts had a similar (moderate) level of agreement and accuracy to non-experts. For Crohn's disease, the likelihood ratios (LR) for the most important individual features were 12.4 for granulomas and 3.3 for focal or patchy inflammation. Features favouring ulcerative colitis were diffuse crypt architectural irregularity (LR, 3.4), general crypt epithelial polymorphs (LR, 3.7), and reduced crypt numbers (LR, 2.9). CONCLUSIONS: A full colonoscopic series gave more accurate diagnosis than a rectal biopsy. Accurate pathologists used the same evidence based criteria for multiple biopsies as for single biopsies.

Biopsy↗

An inexpensive method of quality assessment in anastomosis workshops.

A method of comparing the quality of intestinal anastomoses performed in craft workshops is described. The equipment is readily available in any hospital, inexpensive and requires no technical construction. The apparatus accurately measures the intraluminal pressure at the first sign of anastomotic leak and a method of deriving the wall tension is explained. Calculation of wall tension at the point of failure allows comparison of anastomoses of different size. An instructor can therefore monitor the improvement of an individual trainee or rank a class according to the quality of their anastomoses.

Anastomosis, Surgical↗

Report on the second international workshop on the CCN family of genes.

For the second time, researchers from leading laboratories in the CCN field gathered in Saint-Malo, France, to participate in the Second International Workshop on the CCN family of genes. In addition to the regular research communications, meeting highlights included the inauguration of the first CCN newsletter (http://ccnnewsletter.free.fr) and the recognition of the International CCN Society (http://www.ccnsociety.jussieu.fr) as an important medium for the exchange of scientific knowledge and resources in the CCN field. Once more, the high quality of scientific communications and individual interactions set the stage for an extremely fruitful meeting.

Animals↗

International Union of Physiological Sciences teaching workshop, April 7-10, 2005, Pali Mountain, California.

Fifty-six physiologists from fourteen countries participated in the sixth International Union of Physiological Sciences Teaching Workshop. The four-day program included a poster session, a debate on integrative versus disciplinary curricula, and interactive lectures on evidence-based education, inquiry laboratories, and student preparation for physiology courses. Participants worked in small groups on one of four topics: developing free web-based laboratory resources, information technology, curriculum planning and design, and other issues in classroom teaching.

California↗

Experience with a physiology workshop for high school and college teachers.

Science education in the United States at all academic levels is widely perceived to need direct assistance from professional scientists. The current dearth of quality applicants from this country to medical and graduate schools suggests that our existing undergraduate and high school science curriculum is failing to provide the necessary stimulus for gifted students to seek careers in the health sciences. Recognizing the need to become more directly helpful to high school and college science teachers, members of the faculty of the Department of Physiology and Biophysics at the University of Kentucky College of Medicine held a 5.5-day Physiology Summer Workshop during June, 1989. Participants included 25 college teachers from Kentucky and 5 other states plus 22 Kentucky high school teachers. The presence of the two levels of educators provided communication about curricular concerns that would be best addressed by mutual action and/or interaction. Each day's activities included morning lectures on selected aspects of organ system and cellular physiology, a series on integrative physiology, and afternoon laboratory sessions. The laboratory setting allowed the instructor to expand on principles covered in lecture as well as provided the opportunity for in-depth discussion. A selection of evening sessions was presented on 1) grants available for research projects, 2) obtaining funds for laboratory equipment, and 3) graduate education in physiology.

Capital Financing↗

A method of improving student learning in physiology: the small group workshop.

This teaching innovation replaces standard physiology laboratories with small group workshop tasks dealing with selected physiology problems and data. Working with a series of question sheets, the students focus on establishing a knowledge base and solving problems relating to physiology. Initial experiences show an improvement in student motivation and attitude and improved feedback to students. The major benefits of this approach include 1) enhancement of written and oral communication skills, 2) listening and interacting with group members, 3) correct use of reference materials to find answers, and 4) self-reliance and improved interest in related subject material.

Education, Pharmacy↗

From bench to bedside and back--report on the European Helicobacter pylori Study Group Xth International Workshop on Gastroduodenal Pathology and Helicobacter pylori.

The Xth International Workshop on Gastroduodenal Pathology and Helicobacter pylori was held in Lisbon, Portugal, from September 12 to 14, 1997. State-of-the-art reviews and research findings were presented to over 2000 participants. This review focuses on important new developments and serves as a rapid communication of clinically relevant material.

Drug Therapy, Combination↗

Implementing practice guidelines: a workshop on guidelines dissemination and implementation with a focus on asthma and COPD.

The present supplement summarizes the proceedings of the symposium "Implementing practice guidelines: A workshop on guidelines dissemination and implementation with a focus on asthma and COPD", which took place in Quebec City, Quebec, from April 14 to 16, 2005. This international symposium was a joint initiative of the Laval University Office of Continuing Medical Education (Bureau de la Formation Médicale Continue), the Canadian Thoracic Society and the Canadian Network for Asthma Care, and was supported by many other organizations and by industrial partners. The objectives of this meeting were to examine the optimal implementation of practice guidelines, review current initiatives for the implementation of asthma and chronic obstructive pulmonary disease (COPD) guidelines in Canada and in the rest of the world, and develop an optimal strategy for future guideline implementation. An impressive group of scientists, physicians and other health care providers, as well as policy makers and representatives of patients' associations, the pharmaceutical industry, research and health networks, and communications specialists, conveyed their perspectives on how to achieve these goals. This important event provided a unique opportunity for all participants to discuss key issues in improving the care of patients with asthma and COPD. These two diseases are responsible for an enormous human and socioeconomic burden around the world. Many reports have indicated that current evidence-based guidelines are underused by physicians and others, and that there are many barriers to an effective translation of recommendations into day-to-day care. There is therefore a need to develop more effective ways to communicate key information to both caregivers and patients, and to promote appropriate health behaviours. This symposium contributed to the initiation of what could become the "Canadian Asthma and COPD Campaign", aimed at improving care and, hence, the quality of life of those suffering from these diseases. It is hoped that this event will be followed by other meetings that focus on how to improve the transfer of key recommendations from evidence-based guidelines into current care, and how to stimulate research to accomplish this.

Asthma↗

Genetics and cytogenetics of multiple myeloma: a workshop report.

Much has been learned regarding the biology and clinical implications of genetic abnormalities in multiple myeloma. Because of recent advances in the field, an International Workshop was held in Paris in february of 2003. This summary describes the consensus recommendations arising from that meeting with special emphasis on novel genetic observations. For instance, it is increasingly clear that translocations involving the immunoglobin heavy-chain locus are important for the pathogenesis of one-half of patients. As a corollary, it also clear that the remaining patients, lacking IgH translocations, have hyperdiploidy as the hallmark of their disease. Several important genetic markers are associated with a shortened survival such as chromosome 13 monosomy, hypodiploidy, and others. The events leading the transformation of the monoclonal gammopathy of undetermined significance (MGUS) to myeloma are still unclear. One of the few differential genetic lesions between myeloma and MGUS is the presence of ras mutations in the latter. Gene expression platforms are capable of detecting many of the genetic aberrations found in the clonal cells of myeloma. Areas in need of further study were identified. The study of the genetic aberrations will likely form the platform for targeted therapy for the disease.

Aneuploidy↗

A blueprint for a Human Epigenome Project: the AACR Human Epigenome Workshop.

Epigenetic processes control the packaging and function of the human genome and contribute to normal and pathologic states, including cancer. The time is ripe to undertake an international effort to identify all the chemical changes and relationships between chromatin constituents that provide function to the genetic code. A timely workshop of leading experts, convened by the American Association for Cancer Research (AACR), confirmed that the technology is at hand to begin defining human epigenomes at high resolution.

DNA Methylation↗

State of the translational science: summary of Baltimore workshop on gene re-expression as a therapeutic target in cancer January 2003.

A workshop was held in Baltimore, Maryland in January 2003 to discuss translational aspects of cancer therapies targeted at impacting aberrant gene transcription due to epigenetic changes. The mission of the meeting was the development of strategies for scientifically sound, clinically feasible applications targeting epigenetics in cancer therapy. Sessions included preclinical discussions of DNA methylation, the histone code, chromatin remodeling, and transcriptional control. Data on the histone deacetylase and DNA methyltransferase inhibitors under preclinical and clinical investigation were presented and discussed. The optimal correlative laboratory studies for monitoring clinical trials with these agents remain controversial. DNA methyltransferase and histone deacetylase inhibitors will be combined with each other to maximally re-express genes silenced through promoter methylation. Other classes of agents that may be rationally combined with these classes of drugs include retinoids, steroid hormones, and cytotoxic drugs.

Acetylation↗

Diagnosis and treatment of growth hormone deficiency in children and adolescents: towards a consensus. Ten years after the Availability of Recombinant Human Growth Hormone Workshop held in Pisa, Italy, 27-28 March 1998.

This article summarizes the content of an international workshop on the diagnosis and treatment of growth hormone deficiency (GHD) in children and adolescents that was held in Pisa, Italy, in March 1998. The issues discussed are divided into those addressing the definition and diagnosis, and the treatment of GHD in children and adolescents, and those concerning the transition of patients with GHD from adolescence to adulthood. Recommendations are presented for improving the diagnosis and management of children and adolescents with GHD and issues are highlighted that require further studies to be undertaken before recommendations can be made.

Adolescent↗

Epitope specificity of 30 monoclonal antibodies against cytokeratin antigens: the ISOBM TD5-1 Workshop.

The epitope specificities of 30 monoclonal antibodies (MAbs) against the most common human cytokeratins. i.e., Nos. 8, 18, and 19, in epithelial cells were investigated in the ISOBM TD-5 Workshop. Seven research groups from universities or companies participated independently in the evaluation of the antibody specificities. The complex assembly of cytokeratins in vivo, with obligatory heterologous dimeric combinations of different cytokeratins from each of the two major groups, comprising together more than 20 different individual cytokeratins, made analysis of the antibody reactivity patterns with isolated single cytokeratins necessary. The concordance of the evaluations was striking and independent of the technologies used. As antigens purified individual cytokeratins, chemically degraded purified cytokeratins, recombinant intact and truncated cytokeratins, as well as specific synthesized shorter peptides were used. In order to elucidate the epitope specificity, reactivity patterns in ELISA assays and immunoblots with partial enzymatic degradation of the antigens were performed. Competitive cross-inhibition experiments between antibodies using antigens and antibodies in all possible combinations were performed with radioimmunometric assays, BIAcore, and ELISA technology. All 30 antibodies could convincingly be classified with regard to target cytokeratin. One MAb (192) had to be deleted due to dual specificities in both isotype and epitope specificity against its target. Six antibodies bound selectively to cytokeratin 8, 14 to cytokeratin 18, and 10 to cytokeratin 19, as demonstrated by using native, recombinant, and synthesized antigens. The immunodominant part of the molecule for all three types of cytokeratins was located in the region of amino acid (aa) 270-400. Out of the six MAbs reactive with cytokeratin 8, four MAbs, i.e., 178, 199, 202, and 206, were reactive with a sequence in the interval aa 340-365, and MAb 191 reacted with a closely related epitope. The remaining antibody, 192, presented dual specificities. At least two closely related major immunogenic epitopes could be identified in cytokeratin 8. In cytokeratin 18 four distinct epitopes could be documented, again with the dominating sequence region 270-429 as target for 10 (181, 184, 186, 188, 189, 190, 193, 196, 198, and 200) out of 14 antibodies. Since MAb 193 is known to react with the M3 epitope, aa 322-342 in cytokeratin 18, this entire group is reactive in the region close to the charge shift, in the middle of the rod 2B region, as shown by competitive binding. The remaining four anticytokeratin 18 antibodies (180, 185, 203, and 205) displayed unique, noncompetitive binding to this filament. Cytokeratin 19, reactive with altogether ten antibodies, displayed two major epitopes, all of them also within the large immunodominant region. MAbs 179, 195, 197, and 204 were reactive with the peptides aa 311-335 also known as the KS 19.1 epitope, and MAbs 182, 183, 187, 194, and 201 bound to peptide aa 346-367, known as the BM 19.21 epitope. One antibody, 231, was selectively reactive with aa 356-370 in cytokeratin 19. A complex pattern of binding specificities comprising at least ten different, noncompetitive epitopes, mainly situated in the rod portion, 2A and 2B, situated close to the charge shift in the rod of all three cytokeratins was documented. Out of the 29 classifiable antibodies, altogether 22 were reactive in this very short region, i.e., from aa 311 to 370 in all cytokeratin filaments. The remaining seven antibodies displayed unique binding properties. The implications of the findings are of significance both for immunohistochemistry and for assaying circulating heterodimeric, partially degraded complexes in patients' blood for tumor marker evaluation.

Amino Acid Sequence↗

Immunohistochemical profiles of 30 monoclonal antibodies against cytokeratins 8, 18 and 19. Second report of the TD5 workshop.

In the first report of the TD5 workshop (TD5-1), the epitope specificities of 30 different monoclonal antibodies against cytokeratins 8, 18 and 19 were determined. This second report presents the immunohistochemical profiles of these antibodies using human appendix and normal skin for evaluation. Each antibody was tested by one or two different laboratories recruited from the Dutch Working Group on Immunohistochemistry and Cytochemistry. Eight different laboratories participated. The histological specimens were pretreated by the participants in three different ways for immunohistochemistry: microwave antigen retrieval in citrate buffer, enzymatic digestion to restore epitope exposure, no specific treatment (untreated paraffin-embedded samples), and tested blindly without knowledge of cytokeratin or epitope specificity of the antibodies at three different concentrations of 50, 10 and 1 microg/ml. Most of the tested antibodies (29/30) were useful in at least one pretreatment method, with microwave antigen retrieval being the most sensitive approach. For some antibodies, very high backgrounds were observed. Furthermore, it can be concluded that 11 MAbs performed well using all three staining protocols, including untreated paraffin-embedded sections. Interestingly, all the antibodies with documented selected specificity towards cytokeratin 8 (i.e. 178, 191, 199, 202 and 206) are reactive with an immunodominant region corresponding to amino acids 340-365 on cytokeratin 8, which evidently is well-suited as target for immunohistochemical interactions. Similarly, three antibodies with the same capacity to react with untreated samples had specificity against cytokeratin 19 (i.e. 179, 197 and 204) in the corresponding region in this filament, i.e. amino acids 311-335, or the KS 19.1 epitope. None of the six antibodies against the other major cytokeratin 19 epitope (BM 19.21) were found useful for immunohistochemistry on untreated samples. The overall conclusions from the present investigation are that all cytokeratin-8-specific antibodies with defined epitope specificities were very useful. Only one of the major two epitopes on cytokeratin 19 seems to be available for efficient immunohistochemistry. Cytokeratin 18 exposes some epitopes outside the immunodominant region reactive with the antibodies 190, 203 and 205 which can be used for untreated samples. The implications of these findings are of significance both for diagnostic histopathology and for the biology of tumor marker epitope expression in tissues.

Animals↗

Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin. San Diego, Calif., November 17-23, 1996.

Sixteen research groups participated in the ISOBM TD-4 Workshop in which the reactivity and specificity of 56 monoclonal antibodies against the MUC1 mucin was investigated using a diverse panel of target antigens and MUC1 mucin-related synthetic peptides and glycopeptides. The majority of antibodies (34/56) defined epitopes located within the 20-amino acid tandem repeat sequence of the MUC1 mucin protein core. Of the remaining 22 antibodies, there was evidence for the involvement of carbohydrate residues in the epitopes for 16 antibodies. There was no obvious relationship between the type of immunogen and the specificity of each antibody. Synthetic peptides and glycopeptides were analyzed for their reactivity with each antibody either by assay of direct binding (e.g. by ELISA or BiaCore) or by determining the capacity of synthetic ligands to inhibit antibody binding interactions. There was good concordance between the research groups in identifying antibodies reactive with peptide epitopes within the MUC1 protein core. Epitope mapping tests were performed using the Pepscan analysis for antibody reactivity against overlapping synthetic peptides, and results were largely consistent between research groups. The dominant feature of epitopes within the MUC1 protein core was the presence, in full or part, of the hydrophilic sequence of PDTRAPAP. Carbohydrate epitopes were less easily characterized and the most useful reagents in this respect were defined oligosaccharides, rather than purified mucin preparations enriched in particular carbohydrate moieties. It was evident that carbohydrate residues were involved in many epitopes, by regulating epitope accessibility or masking determinants, or by stabilizing preferred conformations of peptide epitopes within the MUC1 protein core. Overall, the studies, highlight concordance between groups rather than exposing inconsistencies which gives added confidence to the results of analyses of the specificity of antimucin monoclonal antibodies.

Amino Acid Sequence↗

Analysis of the carbohydrate specificity of ISOBM TD-4 Workshop anti-MUC1 antibodies.

The panel of ISOBM TD-4 Workshop antibodies was tested against a range of carbohydrate antigens consisting of (a) ovarian cyst mucins expressing A, B, H, Le(a), Le(x), Le(b), Le(y) and precursor (nonfucosylated) specificities, (b) ovine submaxillary mucin (OSM, expressing sialyl Tn) and desialylated OSM (expressing Tn) and (c) synthetic glycoconjugates (Le(a)-PAA and Le(x)-PAA). The assay used was an ELISA method using rabbit anti-mouse Ig as the second reagent. Thirty-five of the 51 antibodies were unreactive with this group of antigens and presumably react with MUC1 peptide or a carbohydrate specificity not represented. Two MAbs (127 and 128) detected Le(x) antigen and one MAb (157) reacted with A blood group. MAb 151 (and possibly 152) detected sialyl Tn epitopes. Three antibodies (139, 149 and 168) reacted with nonfucosylated structures (possibly LNT or LNneoT). A number of MAbs (137, 145, 162, 163 and 164) reacted widely with the panel of antigens; whether these are nonspecific reactions due to 'sticky' antibodies or caused by the presence of MUC1 peptide in the antigen preparations is uncertain.

Animals↗