Absence of p53 gene mutations in a tumor panel representative of pilocytic astrocytoma diversity using a p53 functional assay.

Although p53-gene mutations occur with significant frequency in diffuse low-grade and high-grade astrocytomas, and are postulated to play an important role in tumorigenesis in these cases, the role of the p53 gene in pilocytic astrocytomas remains unclear. Published data using DNA-based assays for p53-gene analysis in these tumors have shown contradictory results in mutation frequency (0-14%). It is not known whether these heterogeneous results stem from the biological diversity of this tumor group or from technical problems. To re-evaluate p53-gene status in pilocytic tumors, we analyzed 18 tumors chosen to represent the clinical and biological heterogeneity of this tumor type with respect to anatomical location, patient age, gender, ethnic origin (Caucasian or Japanese) and the concomitant occurrence of neurofibromatosis type 1 (NF1). All primary tumors were histologically diagnosed as pilocytic astrocytoma (WHO grade I), except for one anaplastic pilocytic astrocytoma (WHO grade III) which developed in an NF1 patient and recurred as glioblastoma multiforme (WHO grade IV). p53 mutations were detected using an assay in yeast which tests the transcriptional activity of p53 proteins synthesized from tumor mRNA-derived p53-cDNA templates. None of 18 tumors, including 3 NF1-related tumors, showed p53-gene mutations between and including exons 4 and 11. We conclude that p53-gene mutations are extremely rare findings in pilocytic astrocytomas, and are absent even in those exceptional cases in which malignant progression of such tumors has occurred.

Appropriate maintenance treatment for Crohn's disease: results of a multidisciplinary international expert panel - EPACT II

Introduction: Biological. therapy has dramatically changed management of Crohn's disease (CD). New data have confirmed the benefit and relative long-term safety of anti-TNF alpha inhibition as part of a regular scheduled administration programme. The EPACT appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD thus required updating. Methods: A multidisciplinary international expert panel (EPACT II, Geneva, Switzerland) discussed and anonymously rated detailed, explicit clinical indications based on evidence in the literature and personal expertise. Median ratings (on a 9-point scale) were stratified into three assessment categories: appropriate (7-9), uncertain (4-6 and/or disagreement) and inappropriate (1-3). Experts ranked appropriate medication according to their own clinical practice, without any consideration of cost. Results: Three hundred and ninety-two specific indications for maintenance treatment of CD were rated (200 for MIR and 192 for SIR). Azathioprine, methotrexate and/or anti-TNF alpha antibodies were considered appropriate in 42 indications, corresponding to 68% of all appropriate interventions (97% of MIR and 39% of SIR). The remaining appropriate interventions consisted of mesalazine and a "wait-and-see" strategy. Factors that influenced the panel's voting were patient characteristics and outcome of previous treatment. Results favour use of anti-TNF alpha agents after failure of any immunosuppressive therapy, while earlier primary use remains controversial. Conclusion: Detailed explicit appropriateness criteria (EPACT) have been updated for maintenance treatment of CD. New expert recommendations for use of the classic immunosuppressors as well as anti-TNF alpha agents are now freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Precast Concrete Panel Thickness for Epoxy-Coated Prestressing Strands, Volume 2, HR-353, 1994

This final report for Phase 1 of the research on epoxy-coated, prestressing strands in precast prestressed concrete (PC) panels has been published in two volumes. Volume 1--Technical Report contains the problem description, literature review, and survey results; descriptions of the test specimens, experimental tests, and analytical models; discussions of the analytical and experimental results; summary, conclusions, and recommendations; list of references; and acknowledgments. Volume 2--Supplemental Report contains additional information in the form of appendix material for Volume 1 on the questionnaires, strand forces, geometry of the specimens, concrete crack patterns that formed in the strand transfer length and strand development length specimens, concrete strains in the strand transfer length specimens, and load-point deflections and strand-slip measurements for the strand development length specimens. Appendix A contains the questionnaires that were sent to the design agencies and precast concrete producers. A summary of the results to the questions on the surveys are given as the number of respondents who provided the same answers and as paraphrased comments from the respondents. Appendix B contains graphs of strand force versus time, strand force versus temperature, and strand force versus strand cutting sequence for the concrete castings. Appendix C contains figures that show the location of each specimen in the prestress bed, the geometrical configurations for the strand transfer length (T-type) specimens and strand development length (D-type) specimens, and the concrete cracks that developed in some of the T-type specimens when they were prestressed. Appendix D contains figures that show the concrete cracks that developed in the D-type specimens during the strand development length tests. For each of these tests, the sequence of the failure for the specimen is specified. Appendix E contains graphs of concrete strain versus distance from the end of the T-type specimens that were instrumented with internal embedment strain gages. Appendix F contains graphs of load versus load-point deflection and load versus strand-slip for the strand development length tests of the D-type specimens.

Systems Genetics of Metabolism: The Use of the BXD Murine Reference Panel for Multiscalar Integration of Traits.

Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to study single gene function. Here, we systematically acquired metabolic phenotypes by using the EUMODIC EMPReSS protocols across a large panel of isogenic but diverse strains of mice (BXD type) to study the genetic control of metabolism. We generated and analyzed 140 classical phenotypes and deposited these in an open-access web service for systems genetics (www.genenetwork.org). Heritability, influence of sex, and genetic modifiers of traits were examined singly and jointly by using quantitative-trait locus (QTL) and expression QTL-mapping methods. Traits and networks were linked to loci encompassing both known variants and novel candidate genes, including alkaline phosphatase (ALPL), here linked to hypophosphatasia. The assembled and curated phenotypes provide key resources and exemplars that can be used to dissect complex metabolic traits and disorders.

Désaccoutumance au tabac: recommandations d'un panel d'experts = Tabakentwohnung: Empfehlungen einer Expertengruppe

[Table des matières] 1.1. Membres du panel d'experts. 1.2. Représentants des instances mandantes. 2. Recommandations. 2.1. Premier objectif : faire progresser les fumeurs dans leur désaccoutumance (population des fumeurs, population de soignants). 2.2. Deuxième objectif : modifier la norme. 2.3. Troisième objectif : remboursement des prestations médicales. 2.4. Quatrième objectif : recherche sur le tabagisme. 3. Bibliographie. 1.1. Mitglieder der Expertengruppe. 1.2. Vertreterinnen und Vertreter der Auftraggeber. 2. Empfehlungen. 2.1. Ziel 1: die Rauchenden in die Entwicklung zu Nichtrauchenden weiterbringen (Die Rauchenden, das medizinische Personal). 2.2. Ziel 2 : Wandel der Verhaltensnormen. 2.3. Ziel 3 : Rückzahlung der medizinischen Leistungen. 2.4. Ziel 4 : Erforschung über dem Tabakkonsum. 3. Bibliographie.

The Determinants of Exit in Argentina: Core and Peripheral Regions

This paper analyses the regional determinants of exit in Argentina. We find evidence of a dynamic revolving door by which past entrants increase current exits, particularly in the peripheral regions. In the central regions, current and past incumbents cause an analogous displacement effect. Also, exit shows a U-shaped relationship with respect to the informal economy, although the positive effect is weaker in the central regions. These findings point to the existence of a core-periphery structure in the spatial distribution of exits. Key words: firm exit, count data models, Argentina JEL: R12; R30; C33

Fusion of protoplasts with irradiated microprotoplasts as a tool for radiation hybrid panel in citrus

The objective of this work was to combine asymmetric somatic hybridization (donor-recipient fusion or gamma fusion) to microprotoplast-mediated chromosome transfer, as a tool to be used for chromosome mapping in Citrus. Swinglea glutinosa microprotoplasts were irradiated either with 50, 70, 100 or 200 gamma rays and fused to cv. Ruby Red grapefruit or Murcott tangor protoplasts. Cell colonies were successfully formed and AFLP analyses confirmed presence of S. glutinosa in both 'Murcott' tangor and 'Ruby Red' grapefruit genomes.

Cyanogenesis and the onset of tapping panel dryness in rubber tree

The objective of this work was to study the influence of cyanogenesis on the onset of irreversible tapping panel dryness (TPD) and the physiological and histological aspects of secondary phloem in the trunk (tapping panel) of rubber trees (Hevea spp.). Two cyanogenic compounds, linamarin and KCN, were applied separately on the trunk bark of healthy mature trees belonging to two Brazilian clones (Fx 4098 and Fx 3899). Changes in histology, latex pressure potential (ΨP) and cyanogenic potential (HCNp) were followed in the trunk inner barks. In addition, the HCNp levels were determined in TPD-affected plants of both clones. The applications of linamarin or KCN in healthy plants decreased latex ΨP, and formed tylosoids associated with in situ coagulation of latex. The clone Fx 4098 had the higher HCNp and showed the quicker and stronger responses to the cyanogenic compounds. Plants with TPD syntoms had a higher HCNp than the untreated healthy ones. Since histological changes are also structural markers of early TPD, it can be inferred that excessive release of cyanide can induce it in sensitive rubber clones

Early detection of lung cancer: a statement from an expert panel of the Swiss university hospitals on lung cancer screening.

The discussion about setting up a program for lung cancer screening was launched with the publication of the results of the National Lung Screening Trial, which suggested reduced mortality in high-risk subjects undergoing CT screening. However, important questions about the benefit-harm balance and the details of a screening program and its cost-effectiveness remain unanswered. A panel of specialists in chest radiology, respiratory medicine, epidemiology, and thoracic surgery representing all Swiss university hospitals prepared this joint statement following several meetings. The panel argues that premature and uncontrolled introduction of a lung cancer screening program may cause substantial harm that may remain undetected without rigorous quality control. This position paper focuses on the requirements of running such a program with the objective of harmonizing efforts across the involved specialties and institutions and defining quality standards. The underlying statement includes information on current evidence for a reduction in mortality with lung cancer screening and the potential epidemiologic implications of such a program in Switzerland. Furthermore, requirements for lung cancer screening centers are defined, and recommendations for both the CT technique and the algorithm for lung nodule assessment are provided. In addition, related issues such as patient management, registry, and funding are addressed. Based on the current state of the knowledge, the panel concludes that lung cancer screening in Switzerland should be undertaken exclusively within a national observational study in order to provide answers to several critical questions before considering broad population-based screening for lung cancer.

A civil society response on the report of the UN High-Level Panel on system-wide coherence

Abordamos el Informe del Grupo de Alto Nivel sobre la Coherencia en todo el Sistema de las Naciones Unidas («Informe del Grupo») y el proceso de reforma de las Naciones Unidas del que forma parte como grupos de la sociedad civil que tienen una larga experiencia por lo que se refiere a propugnar reformas del sistema de las Naciones Unidas.

Immunopathogenesis of Asthma and Atopic Diseases – The specific Role of a selected Panel of Genes in human T helper Cell Differentiation

T helper cell (Th) functions are crucial for proper immune defence against various intra- and extracellular pathogens. According to the specific immune responses, Th cells can be classified into subtypes, Th1 and Th2 cells being the most frequently characterized classes. Th1 and Th2 cells interact with other immune cells by regulating their functions with specific cytokine production. IFN, IL-2 and TNF- are the cytokines predominantly produced by Th1 cells whereas Th2 cells produce Th2-type cytokines, such as IL-4, IL-5 and IL-13. Upon TCR activation and in the presence of polarizing cytokines, Th cells differentiate into effector subtypes from a common precursor cell. IFN and IL-12 are the predominant Th1 polarizing cytokines whereas IL-4 directs Th2 polarization. The cytokines mediate their effects through specific receptor signalling. The differentiation process is complex, involving various signalling molecules and routes, as well as functions of the specific transcription factors. The functions of the Th1/Th2 cells are tightly regulated; however, knowledge on human Th cell differentiation is, as yet, fairly poor. The susceptibility for many immune-mediated disorders often originates from disturbed Th cell responses. Thus, research is needed for defining the molecular mechanisms involved in the differentiation and balanced functions of the Th cells. Importantly, the new information obtained will be crucial for a better understanding of the pathogenesis of immune-mediated disorders, such as asthma or autoimmune diseases. In the first subproject of this thesis, the role of genetic polymorphisms in the human STAT6, GATA3 and STAT4 genes were investigated for asthma or atopy susceptibility in Finnish asthma families by association analysis. These genes code for key transcription factors regulating Th cell differentiation. The study resulted in the identification of a GATA3 haplotype that associated with asthma and related traits (high serum IgE level). In the second subproject, an optimized method for human primary T cell transfection and enrichment was established. The method can be utilized for functional studies for the selected genes of interest. The method was also utilized in the third subproject, which aimed at the identification of novel genes involved in early human Th cell polarization (0-48h) using genome-wide oligonucleotide arrays. As a result, numerous genes and ESTs with known or unknown functions were identified in the study. Using an shRNA knockdown approach, a panel of novel IL-4/STAT6 regulated genes were identified in the functional studies of the genes. Moreover, one of the genes, NDFIP2, with a previously uncharacterized role in the human Th differentiation, was observed to promote IFN production of the differentiated Th1 cells. Taken together, the results obtained have revealed potential new relevant candidate genes serving as a basis for further studies characterizing the detailed networks involved in the human Th cell differentiation as well as in the genetic susceptibility of Th-mediated immune disorders.

Market entry order and competitive advantage of the firm

A firm that wishes to launch a new product to the market is faced with a difficult task of deciding what the best moment for the launch is. Timing may also be critical when a firm plans to adopt new processes or intends to head for new markets. The critical question the firm needs to tackle is whether it will try to reach the so-called first-mover advantage by acting earlier than its rivals. The first-mover position may reward the entrant with various opportunities to gain competitive advantage over later movers. However, there are also great risks involved in the early market entry, and sometimes the very first entrant fails even before the followers enter the market. The follower, on the other hand, may be able to free-ride on the earlier entrants' investments and gain from the languished uncertainties that characterize the new markets. According to the current understanding the occurrence of entry order advantages depends not only on the mechanism and attributes in the firm's environment that provide the initial opportunities but also on the firm's ability to capitalize on these advantage opportunities. This study contributes to this discussion by analyzing the linkages between the asset base of the firm, characteristics of the operating environment and the firm's entry timing orientation. To shed light on the relationship between the entry timing strategy and competitive advantage, this study utilizes the concept of entry timing orientation. The rationale for choosing this type of approach arises from the inability of previously employed research tools to reach the underlying factors that result in entry timing advantage. The work consists of an introductory theoretical discussion on entry timing advantages and of four research publication. The empirical findings support the understanding that entry timing advantage is related to the characteristics of the firm's operating environment but may also be related to firm-specific factors. This in turn suggests that some of the traditional ways of detecting and measuring first-mover advantage - which to some extent ignore these dimensions - may be outdated.