A qualitative study on integrated management systems in a non-leading country in certifications

The aim of this study is to analyse the integration of management systems (MSs) in a country with low certifications number and growth rate and propose a research agenda towards improving the competitiveness of organisations that implement multiple MSs. The main research questions focus on the implementation process itself and the effect of low level of national certification to the integration process. To serve this research purpose, an exploratory research is designed in Greece (a country with relatively low certification counts and rates to the ISO 9001 and ISO 14001 management standards). A case study approach is employed to enable deeper and comprehensive reasoning. A cross-case analysis is presented to explore patterns, similarities and differences among organisations. Findings show that four out of five organisations analysed are integrating its MSs at different levels, the integration methodology applied is similar for all organisations but audits are the most dissimilar aspect. This study is one of the first that addresses MSs' integration in Greece exploring contingency factors

La integración de sistemas de gestión basados en estándares internacionales: resultados de un estudio empírico realizado en la CAPV

Este artículo se ha realizado en el marco de los Proyectos de Investigación titulados “Los sistemas integrados de gestión (SIG) en las empresas españolas” (SEC2006-06682/ECON) financiado por el Ministerio de Educación y Ciencia dentro de la convocatoria de ayuda a proyectos de I+D y “Análisis de la implantación de los Sistemas de Gestión Medioambiental en las empresas de la CAPV: generación de propuestas innovadoras para su integración organizativa”, financiado por la UPV-EHU en su convocatoria general de Proyectos de Investigación de 2006.El éxito en la difusión de los estándares de gestión ha llevado a las organizaciones a tratar de avanzar en su integración. Paralelamente, en el ámbito académico se han comenzado a publicar las primeras investigaciones que analizan dichos aspectos. En este sentido, la literatura existente sobre la integración de sistemas de gestión se basa, principalmente, en estudios teóricos en los que se describe qué es un sistema integrado de gestión, la metodología de integración, los niveles de integración de la empresa y sus ventajas y desventajas, como principales aspectos a tener en cuenta en el proceso. Ene ste artículo se resumen los primeros resultados descriptivos de un trabajo de campo cuantitativo finalizado recientemente en las empresas de la Comunidad Autónoma del País Vasco, con el objetivo de obtener algún tipo de evidencia empírica sobre cuál es el grado de integración de los diferentes estándares de sistemas de gestión en las empresas vascas, así como de recoger la opinión de las empresas que ya han implantado algún estándar internacional de sistemas de gestión sobre la dirección que ha de tomar el proceso de creación de estos estándares.Cámara de Gipuzko

MicroRNA-19b downregulates insulin 1 through targeting transcription factor NeuroD1

AbstractMiR-17-92 cluster miRNAs are disclosed to contribute to the development of multiple organs and tumorigenesis, but their roles in pancreas development remains unclear. In this study, we found that miR-19b, a member of miR-17-92, was highly expressed in the pancreatic progenitor cells, and miR-19b could target the 3′ UTR of NeuroD1 mRNA to decrease its protein and mRNA levels. Functional analysis showed that miR-19b exerted little effect on the proliferation of pancreatic progenitors, whereas it inhibited the expression of insulin 1, but not insulin 2 in MIN6 cells. These results suggest that miR-19b can downregulate insulin 1 expression through targeting transcription factor NeuroD1, and thus regulate the differentiation and function of β-cells

A phase II study of sequential 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel in advanced breast cancer (Protocol PV BC 97/01)

Sequential administration of the association of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel could be better tolerated than the association of an anthracycline and paclitaxel while having a similar antitumour effect. 69 patients with advanced breast cancer previously untreated with anthracyclines or paclitaxel entered a phase II multicentre study in which FEC was followed by paclitaxel. Both regimens were administered 4 times every 21 days. The median follow-up is 20 months and 38/69 patients have died. Grade III–IV toxicity was acceptable. Leukopenia occurred in 26% of patients, thrombocytopenia in 2% and anaemia in 4%. One patient had reversible heart failure during FEC therapy. Peripheral neuropathy and arthralgia-myalgia occurred in 9% and 4% of patients, respectively and one patient had respiratory hypersensitivity during paclitaxel treatment. 9 patients did not complete therapy because of: treatment refusal (n= 1), cardiac toxicity (n= 1), early death during FEC chemotherapy (n= 1), major protocol violations (n= 4), hypersensitivity reaction (n= 1) and early death during paclitaxel chemotherapy (n= 1). The overall response rate was 65% (95% CI = 53–76), and 7% of patients had stable disease. Therapy was defined as having failed in 28% of patients because they were not evaluable (13%) or had progressive disease (15%). The median time to progression and survival are 13.2 and 23.5 months, respectively. Sequential FEC-paclitaxel is a suitable strategy for patients with metastatic breast cancer who have not been previously treated with anthracyclines and/or taxanes. In fact, it avoids major haematologic toxicity and has a good antitumour effect. © 2001 Cancer Research Campaign http://www.bjcancer.co

QTL linkage analysis of connected populations using ancestral marker and pedigree information

The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the current mapping populations from locus-specific identity by descent (IBD) matrices that capture ancestral marker and pedigree information. Moreover, we demonstrate how the parental IBD data can be incorporated into a QTL linkage analysis framework by using two approaches: a Threshold IBD model (TIBD) and a Latent Ancestral Allele Model (LAAM). The TIBD and LAAM models are empirically tested via numerical simulation based on the structure of a commercial maize breeding program. The simulations included a pilot dataset with closely linked QTL on a single linkage group and 100 replicated datasets with five linkage groups harboring four unlinked QTL. The simulation results show that including parental IBD data (similarly for TIBD and LAAM) significantly improves the power and particularly accuracy of QTL mapping, e.g., position, effect size and individuals’ genotype probability without significantly increasing computational demand

Natural Strain Variation and Antibody Neutralization of Dengue Serotype 3 Viruses

Dengue viruses (DENVs) are emerging, mosquito-borne flaviviruses which cause dengue fever and dengue hemorrhagic fever. The DENV complex consists of 4 serotypes designated DENV1-DENV4. Following natural infection with DENV, individuals develop serotype specific, neutralizing antibody responses. Monoclonal antibodies (MAbs) have been used to map neutralizing epitopes on dengue and other flaviviruses. Most serotype-specific, neutralizing MAbs bind to the lateral ridge of domain III of E protein (EDIII). It has been widely assumed that the EDIII lateral ridge epitope is conserved within each DENV serotype and a good target for vaccines. Using phylogenetic methods, we compared the amino acid sequence of 175 E proteins representing the different genotypes of DENV3 and identified a panel of surface exposed amino acids, including residues in EDIII, that are highly variant across the four DENV3 genotypes. The variable amino acids include six residues at the lateral ridge of EDIII. We used a panel of DENV3 mouse MAbs to assess the functional significance of naturally occurring amino acid variation. From the panel of antibodies, we identified three neutralizing MAbs that bound to EDIII of DENV3. Recombinant proteins and naturally occurring variant viruses were used to map the binding sites of the three MAbs. The three MAbs bound to overlapping but distinct epitopes on EDIII. Our empirical studies clearly demonstrate that the antibody binding and neutralization capacity of two MAbs was strongly influenced by naturally occurring mutations in DENV3. Our data demonstrate that the lateral ridge “type specific” epitope is not conserved between strains of DENV3. This variability should be considered when designing and evaluating DENV vaccines, especially those targeting EDIII

A hierarchical Bayesian model for understanding the spatiotemporal dynamics of the intestinal epithelium

Our work addresses two key challenges, one biological and one methodological. First, we aim to understand how proliferation and cell migration rates in the intestinal epithelium are related under healthy, damaged (Ara-C treated) and recovering conditions, and how these relations can be used to identify mechanisms of repair and regeneration. We analyse new data, presented in more detail in a companion paper, in which BrdU/IdU cell-labelling experiments were performed under these respective conditions. Second, in considering how to more rigorously process these data and interpret them using mathematical models, we use a probabilistic, hierarchical approach. This provides a best-practice approach for systematically modelling and understanding the uncertainties that can otherwise undermine the generation of reliable conclusions-uncertainties in experimental measurement and treatment, difficult-to-compare mathematical models of underlying mechanisms, and unknown or unobserved parameters. Both spatially discrete and continuous mechanistic models are considered and related via hierarchical conditional probability assumptions. We perform model checks on both in-sample and out-of-sample datasets and use them to show how to test possible model improvements and assess the robustness of our conclusions. We conclude, for the present set of experiments, that a primarily proliferation-driven model suffices to predict labelled cell dynamics over most time-scales