Appropriateness of therapy for active Crohn's disease: results of a multidisciplinary international expert panel (EPACT II)

Introduction: The development of novel therapies and the increasing number of trials testing management strategies for luminal Crohn's disease (CD) have not filled all the gaps in our knowledge. Thus, in clinical practice, many decisions for CD patients need to be taken without high quality evidence. For this reason, a multidisciplinary European expert panel followed the RAND method to develop explicit criteria for the management of individual patients with active, steroid-dependent (ST-D) and steroid-refractory (ST-R) CD. Methods: Twelve international experts convened in Geneva, Switzerland in December 2007, to rate explicit clinical scenarios, corresponding to real daily practice, on a 9-point scale according to the literature evidence and their own expertise. Median ratings were stratified into three categories: appropriate (7-9), uncertain (4-6) and inappropriate (1-3). Results: Overall, panelists rated 296 indications pertaining to mild-to-moderate, severe, ST-D, and ST-R CD. In anti-TNF naïve patients, budesonide and prednisone were found appropriate for mildmoderate CD, and infliximab (IFX) when those had previously failed or had not been tolerated. In patients with prior success with IFX, this drug with or without co-administration of a thiopurine analog was favored. Other anti-TNFs were appropriate in case of intolerance or resistance to IFX. High doses steroids, IFX or adalimumab were appropriate in severe active CD. Among 105 indications for ST-D or ST-R disease, the panel considered appropriate the thiopurine analogs, methotrexate, IFX, adalimumab and surgery for limited resection, depending on the outcome of prior therapies. Anti-TNFs were generally considered appropriate in ST-R. Conclusion: Steroids, including budesonide for mild-to-moderate CD, remain first-line therapies in active luminal CD. Anti-TNFs, in particular IFX with respect to the amount of available evidence, remain second-line for most indications. Thiopurine analogs are preferred to anti-TNFs when steroids are not appropriate, except when anti-TNFs were previously successful. These recommendations are available online (www.epact.ch). A prospective evaluation of these criteria in a large database in Switzerland in underway to validate these criteria.

Preliminary report of the first season work of the International Pluridisciplinary Archaeological Expedition to Bactria 2007

A prior long-term and complex evaluation of the already available data on the geophysical prospecting during the first season work carried out at 2006, at the archaeological site of Tchinguiz Tepe of Termez, took place to decide the strategy to follow during the campaign of 2007. This previous evaluation of the information, on one hand, leaded to the decision to increase the geophysical prospecting at Tchinguiz Tepe, on the other hand, to decide the exact location of areas where the archaeological interventions.would carry out. The main objective at the beginning of this new season was to crosscheck the reliabilityof the measurements and, at the same time, to establish the unknown up to the present archaeologicaland chronological sequence of Tchinguiz Tepe. Meanwhile, the geophysical prospecting also wasextended to the outskirts of the city were the localisation of an unknown up to now Buddhist Monasterywas possible.

Preliminary report of the first season work of the International Pluridisciplinary Archaeological Expedition to Bactria 2006

The International Pluridisciplinary Archaeological Expedition in Bactria (IPAEB) was created in 2006.The name underlines the international character of the team (which includes Uzbeks, Spanish, French, British and Greek members), the presence of specialists from various fields apart from archaeology and the fame of Bactria1.

Preliminary report of the first season work of the International Pluridisciplinary Archaeological Expedition to Bactria 2008

This year the development of our project can be divided into two main clearly different parts, on one hand the laboratory work, where the sampled ceramic individuals has been prepared and analyzed and the elaboration of the data obtained during the excavation of 2007 has been finished and, on the other hand, the field work developed at the archaeological site during this specific year (2008).In the mark of the analytical work a significant number of ceramic individuals (144) from the different stratigraphical units from various areas of the excavation of Termez and Tchinguiz Tepe sampled duringthe new and previous field works has been archaeometrically characterized. This specific material includedindividuals dated into the Hellenistic and Sassanian period, which has been confirmed by C14dating upon organic samples.At the same time, in the mark of the field work of 2008 the archaeological record, already started tobe under study during the excavation of 2007, has been completed and two new archaeological recordshave been registered on of which is located in the area of Tchinguiz Tepe. For the archeological studythe information of the previous geophysical prospecting has been indisputably taken into considerationand the same methodology has been applied to crosscheck the latter archaeological results.

Preliminary Report of the work of the International Pluridisciplinary Archaeological Expedition to Bactria (2009)

Institute of Archaeology & Institute of Fine Arts. Academy of Science of the Republic of Uzbekistan- Universitat de Barcelona- Ministerio de Cultura (Gobierno de España)- Ministerio de Ciencia e Innovación (Gobierno de España)

Correlation of the IJK Roadmeter to the International Roughness Index, MLR-91-5, 1992

The Iowa Department of Transportation has been determining a present serviceability index (PSI) on the primary highway system since 1968. A CHLOE profilometer has been used as the standard for calibrating the Roadmeters that do the system survey. The current Roadmeter, an IJK Iowa DOT developed unit, is not considered an acceptable Roadmeter for determining the FHWA required International Roughness Index (IRI). Iowa purchased a commercial version of the South Dakota type profile (SD Unit) to obtain IRI. This study was undertaken to correlate the IRI to the IJK Roadmeter and retire the Roadmeter. One hundred forty-seven pavement management sections (IPMS) were tested in June and July 1991 with both units. Correlation coefficients and standard error of estimates were: r' Std. Error PCC pavements 0.81 0.15 Composite pavements 0.71 0.18 ACC pavements 0.77 0.17 The correlation equations developed from this work will allow use of the IRI to predict the IJK Roadmeter response with sufficient accuracy. Trend analysis should also not be affected.

Analytical progresses of the International Olympic Committee and World Anti-Doping Agency Olympic laboratories.

The Summer Olympic Games constitute the biggest concentration of human sports and activities in a particular place and time since 776 BCE, when the written history of the Olympic Games in Olympia began. Summer and Winter Olympic anti-doping laboratories, accredited by the International Olympic Committee in the past and the World Anti-Doping Agency in the present times, acquire worldwide interest to apply all new analytical advancements in the fight against doping in sports, hoping that this major human event will not become dirty by association with this negative phenomenon. This article summarizes the new analytical progresses, technologies and knowledge used by the Olympic laboratories, which for the vast majority of them are, eventually, incorporated into routine anti-doping analysis.

Recent advances in biocuration: meeting report from the fifth International Biocuration Conference.

The 5th International Biocuration Conference brought together over 300 scientists to exchange on their work, as well as discuss issues relevant to the International Society for Biocuration's (ISB) mission. Recurring themes this year included the creation and promotion of gold standards, the need for more ontologies, and more formal interactions with journals. The conference is an essential part of the ISB's goal to support exchanges among members of the biocuration community. Next year's conference will be held in Cambridge, UK, from 7 to 10 April 2013. In the meanwhile, the ISB website provides information about the society's activities (http://biocurator.org), as well as related events of interest.

Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.

BACKGROUND: Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. PURPOSE: To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. METHODS: From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. RESULTS: The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. LIMITATIONS: Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. CONCLUSIONS: BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.

ISBN (international standard book number) -an international perspective

Esitelmä Suomen ISBN-keskus 30 vuotta -juhlassa Helsingin yliopistossa 7.11.2002