Development and standardization of solid phase assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). A report on the second phase of an international cooperative study on the standardization of ANCA assays

Anti-neutrophil cytoplasmic antibodies (ANCA) are diagnostic markers for systemic vasculitis. They are classically I detected by an indirect immunofluorescence test using normal donor neutrophils as substrate. This assay lacks antigenic specificity and is not quantitative. The 'EC/BCR Project for ANCA Assay Standardization' is an international collaboration study with the aim to develop and standardize solid phase assays for ANCA detection. In this part of the study the isolation and characterization of proteinase-3 and myeloperoxidase, the two main target molecules for ANCA, and the development and standardization of ELISAs with these antigens are described. Six laboratories successfully isolated purified proteinase-3 preparations that could be used. Three of these preparations, together with one myeloperoxidase preparation, were subsequently used for ANCA testing by ELISA. The ELISA technique was standardized in two rounds of testing in the 14 participating laboratories. The coefficient of variation of these new assays decreased from values of approx. 50% in the first round to approx. 20% in the second round. We conclude that purified proteinase-3 and myeloperoxidase can be used in standardized ELISAs for ANCA detection. Whether such procedures offer advantages over the IIF test will be determined in a prospective clinical study.

Highlights from the 13th St Gallen International Breast Cancer Conference 2013. Access to innovation for patients with breast cancer: how to speed it up?

The recognition that early breast cancer is a spectrum of diseases each requiring a specific systemic therapy guided the 13th St Gallen International Breast Cancer Consensus Conference [1]. The meeting assembled 3600 participants from nearly 90 countries worldwide. Educational content has been centred on the primary and multidisciplinary treatment approach of early breast cancer. The meeting culminated on the final day, with the St Gallen Breast Cancer Treatment Consensus, established by 40-50 of the world's most experienced opinion leaders in the field of breast cancer treatment. The major issue that arose during the consensus conference was the increasing gap between what is theoretically feasible in patient risk stratification, in treatment, and in daily practice management. We need to find new paths to access innovations to clinical research and daily practice. To ensure that continued innovation meets the needs of patients, the therapeutic alliance between patients and academic-led research should to be extended to include relevant pharmaceutical companies and drug regulators with a unique effort to bring innovation into clinical practice. We need to bring together major players from the world of breast cancer research to map out a coordinated strategy on an international scale, to address the disease fragmentation, to share financial resources, and to integrate scientific data. The final goal will be to improve access to an affordable, best standard of care for all patients in each country.

Prenegotiation public commitment in domestic and international bargaining

We use a formal bargaining model to examine why, in many domestic and international bargaining situations, one or both negotiators make public statements in front of their constituents committing themselves to obtaining certain benefits in the negotiations. We find that making public commitments provides bargaining leverage, when backing down from such commitments carries domestic political costs. However, when the two negotiators face fairly similar costs for violating a public commitment, a prisoner's dilemma is created in which both sides make high public demands which cannot be satisfied, and both negotiators would be better off if they could commit to not making public demands. However, making a public demand is a dominant strategy for each negotiator, and this leads to a suboptimal outcome. Escaping this prisoner's dilemma provides a rationale for secret negotiations. Testable hypotheses are derived from the nature of the commitments and agreements made in equilibrium.

Standardizing clinical trials workflow representation in UML for international site comparison.

BACKGROUND: With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. METHODS: Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. RESULTS: Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. CONCLUSIONS: This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows.

Developments among International Scientific and Health Bodies on Dual-Use Issue

Presentation at the Controlling Dangerous Pathogens Project Regional Workshop on Dual-Use Research, Teresopolis, Brazil

Furnishing a Globalized World: Local Distinctiveness in the International Furniture Industry

Advances in technology, communication, and transportation over the past thirty years have led to tighter linkages and enhanced collaboration across traditional borders between nations, institutions, and cultures. This thesis uses the furniture industry as a lens to examine the impacts of globalization on individual countries and companies as they interact on an international scale. Using global value chain analysis and international trade data, I break down the furniture production process and explore how countries have specialized in particular stages of production to differentiate themselves from competitors and maximize the benefits of global involvement. Through interviews with company representatives and evaluation of branding strategies such as advertisements, webpages, and partnerships, I investigate across four country cases how furniture companies construct strong brands in an effort to stand out as unique to consumers with access to products made around the globe. Branding often serves to highlight distinctiveness and associate companies with national identities, thus revealing that in today’s globalized and interconnected society, local differences and diversity are more significant than ever.

International guidelines for management of metastatic breast cancer: Can metastatic breast cancer be cured?

A distinctive subset of metastatic breast cancer (MBC) is oligometastatic disease, which is characterized by single or few detectable metastatic lesions. The existing treatment guidelines for patients with localized MBC include surgery, radiotherapy, and regional chemotherapy. The European School of Oncology-Metastatic Breast Cancer Task Force addressed the management of these patients in its first consensus recommendations published in 2007. The Task Force endorsed the possibility of a more aggressive and multidisciplinary approach for patients with oligometastatic disease, stressing also the need for clinical trials in this patient population. At the sixth European Breast Cancer Conference, held in Berlin in March 2008, the second public session on MBC guidelines addressed the controversial issue of whether MBC can be cured. In this commentary, we summarize the discussion and related recommendations regarding the available therapeutic options that are possibly associated with cure in these patients. In particular, data on local (surgery and radiotherapy) and chemotherapy options are discussed. Large retrospective series show an association between surgical removal of the primary tumor or of lung metastases and improved long-term outcome in patients with oligometastatic disease. In the absence of data from prospective randomized studies, removal of the primary tumor or isolated metastatic lesions may be an attractive therapeutic strategy in this subset of patients, offering rapid disease control and potential for survival benefit. Some improvement in outcome may also be achieved with optimization of systemic therapies, possibly in combination with optimal local treatment. © 2010. Published by Oxford University Press.

Genetic deficiency of the fourth component of complement :clinical, immunological and genetical studies in a further family. IXth International Complement Workshop

info:eu-repo/semantics/published

Research in statistical education — planning of an international survey

As announced in the November 2000 issue of MathStats&OR [1], one of the projects supported by the Maths, Stats & OR Network funds is an international survey of research into pedagogic issues in statistics and OR. I am taking the lead on this and report here on the progress that has been made during the first year. A paper giving some background to the project and describing initial thinking on how it might be implemented was presented at the 53rd session of the International Statistical Institute in Seoul, Korea, in August 2001 in a session on The future of statistics education research [2]. It sounded easy. I considered that I was something of an expert on surveys having lectured on the topic for many years and having helped students and others who were doing surveys, particularly with the design of their questionnaires. Surely all I had to do was to draft a few questions, send them electronically to colleagues in statistical education who would be only to happy to respond, and summarise their responses? I should have learnt from my experience of advising all those students who thought that doing a survey was easy and to whom I had to explain that their ideas were too ambitious. There are several inter-related stages in survey research and it is important to think about these before rushing into the collection of data. In the case of the survey in question, this planning stage revealed several challenges. Surveys are usually done for a purpose so even before planning how to do them, it is advisable to think about the final product and the dissemination of results. This is the route I followed.

Preface [Special Issue: International Symposium on Combinatorial Optimisation (CO2000)]

Preface [Special Issue containing a selection of papers presented at the International Symposium on Combinatorial Optimisation (CO2000) held at the University of Greenwich, London, from 12-14 July 2000.

International perspectives on energy policy and the role of nuclear power

In this book, expert energy economists assess the energy policy of thirty-one countries and the role of nuclear power. For many years the shock of Chernobyl took nuclear power off the agenda in most countries. Intense public relations activities by the industry, increasing evidence of climate change and failures to effectively reduce greenhouse gas emissions, have brought nuclear power issues back to the forefront of policy discussion in the nuclear renaissance countries. But some countries are just not prepared to go in that direction and, indeed, are still divesting themselves of their nuclear legacy, the nuclear phase-out countries. And how are nuclear issues being approached in the industrializing countries? An in-depth country-by-country analysis is presented within this framework. Out of such an analysis emerge thematic discussions on, among others, strategy in energy policy; nuclear plant safety, the impacts of nuclear accidents; the adequacy of nuclear power expertise. [Source: publisher's product description].