Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Modernising Nursing Careers : Setting the Direction (PDF 278 KB)

This report sets the direction for modernising nursing careers.

Multi-stage oligopoly models with nested logit demand structures: A simplifying approach

Solving multi-stage oligopoly models by backward induction can easily become a com- plex task when rms are multi-product and demands are derived from a nested logit frame- work. This paper shows that under the assumption that within-segment rm shares are equal across segments, the analytical expression for equilibrium pro ts can be substantially simpli ed. The size of the error arising when this condition does not hold perfectly is also computed. Through numerical examples, it is shown that the error is rather small in general. Therefore, using this assumption allows to gain analytical tractability in a class of models that has been used to approach relevant policy questions, such as for example rm entry in an industry or the relation between competition and location. The simplifying approach proposed in this paper is aimed at helping improving these type of models for reaching more accurate recommendations.

Nursing Needs Assessment Tool User Guide 2006 (PDF 207 KB)

The user guide describes how to undertake an assessment using the nursing needs assessment tool.

Evaluation of different POCT devices for glucose measurement in a clinical neonatal setting.

Hypoglycaemia is a major cause of neonatal morbidity and may induce long-term developmental sequelae. Clinical signs of hypoglycaemia in neonatal infants are unspecific or even absent, and therefore, precise and accurate methods for the assessment of glycaemia are needed. Glycaemia measurement in newborns has some particularities like a very low limit of normal glucose concentration compared to adults and a large range of normal haematocrit values. Many bedside point-of-care testing (POCT) systems are available, but literature about their accuracy in newborn infants is scarce and not very convincing. In this retrospective study, we identified over a 1-year study period 1,324 paired glycaemia results, one obtained at bedside with one of three different POCT systems (Elite? XL, Ascensia? Contour? and ABL 735) and the other in the central laboratory of the hospital with the hexokinase reference method. All three POCT systems tended to overestimate glycaemia values, and none of them fulfilled the ISO 15197 accuracy criteria. The Elite XL appeared to be more appropriate than Contour to detect hypoglycaemia, however with a low specificity. Contour additionally showed an important inaccuracy with increasing haematocrit. The bench analyzer ABL 735 was the most accurate of the three tested POCT systems. Both of the tested handheld glucometers have important drawbacks in their use as screening tools for hypoglycaemia in newborn infants. ABL 735 could be a valuable alternative, but the blood volume needed is more than 15 times higher than for handheld glucometers. Before daily use in the newborn population, careful clinical evaluation of each new POCT system for glucose measurement is of utmost importance.

Profitability, uncertainty and multi-product firm product proliferation: The Spanish car industry

This article studies how product introduction decisions relate to profitability and uncertainty in the context of multi-product firms and product differentiation. These two features, common to many modern industries, have not received much attention in the literature as compared to the classical problem of firm entry, even if the determinants of firm and product entry are quite different. The theoretical predictions about the sign of the impact of uncertainty on product entry are not conclusive. Therefore, an econometric model relating firms’ product introduction decisions with profitability and profit uncertainty is proposed. Firm’s estimated profits are obtained from a structural model of product demand and supply, and uncertainty is proxied by profits’ variance. The empirical analysis is carried out using data on the Spanish car industry for the period 1990-2000. The results show a positive relationship between product introduction and profitability, and a negative one with respect to profit variability. Interestingly, the degree of uncertainty appears to be a driving force of entry stronger than profitability, suggesting that the product proliferation process in the Spanish car market may have been mainly a consequence of lower uncertainty rather than the result of having a more profitable market. Keywords: Product introduction, entry, uncertainty, multiproduct firms, automobile JEL codes: L11, L13

Construcción de un modelo Multi- Regional Input-Output (MRIO) medioambiental para Cataluña y el resto de España: Estudio del balance en CO2 incorporado en el comercio

El objetivo de este estudio es analizar el impacto, en emisiones de CO2, de la demanda final de Cataluña en relación a los vínculos comerciales interregionales con el resto de España y el resto del mundo. Este proceso implica el análisis del balance en CO2 incorporado para Cataluña, lo que permitirá evaluar la responsabilidad de la economía catalana respecto a estas emisiones. Para este propósito se construye, para esta determinada desagregación regional, un modelo Multi-Regional Input-Output (MRIO) extendido al medioambiente con sectores verticalmente integrados. La incorporación de la técnica de la integración vertical nos permite un enfoque alternativo para el Balance Neto y un análisis más detallado de los vínculos interregionales entre los diversos sectores productivos, centrado en la responsabilidad última de la demanda final de cada sector en cada región. Hasta el momento, los estudios previos sobre los impactos medioambientales incorporados al comercio español se han centrado principalmente en el ámbito nacional. No obstante, por un lado el comercio interregional con el resto de España en términos monetarios representa cerca de la mitad del comercio exterior catalán. Por otro lado, los distintos metabolismos energéticos de ambas economías tienen como consecuencia una importante diferencia en la intensidad de emisión en la producción de bienes y servicios. Esta situación genera para Cataluña un déficit en el Balance Neto estimado con el resto de España, aún teniendo un importante superávit monetario. De esto se desprende la importancia de integrar el nivel interregional en los estudios de los impactos medioambientales incorporados en el comercio y, en consecuencia, en la planificación y formalización de políticas económicas y ambientales a nivel nacional.

Conditioned polarized Caco-2 cell monolayers allow to discriminate for the ability of gut-derived microorganisms to modulate permeability and antigen-induced basophil degranulation.

BACKGROUND: Food allergy is a common allergic disorder--especially in early childhood. The avoidance of the allergenic food is the only available method to prevent further reactions in sensitized patients. A better understanding of the immunologic mechanisms involved in this reaction would help to develop therapeutic approaches applicable to the prevention of food allergy. OBJECTIVE: To establish a multi-cell in vitro model of sensitized intestinal epithelium that mimics the intestinal epithelial barrier to study the capacity of probiotic microorganisms to modulate permeability, translocation and immunoreactivity of ovalbumin (OVA) used as a model antigen. METHODS: Polarized Caco-2 cell monolayers were conditioned by basolateral basophils and used to examine apical to basolateral transport of OVA by ELISA. Activation of basophils with translocated OVA was measured by beta-hexosaminidase release assay. This experimental setting was used to assess how microorganisms added apically affected these parameters. Basolateral secretion of cytokine/chemokines by polarized Caco-2 cell monolayers was analysed by ELISA. RESULTS: Basophils loaded with OVA-specific IgE responded to OVA in a dose-dependent manner. OVA transported across polarized Caco-2 cell monolayers was found to trigger basolateral basophil activation. Microorganisms including lactobacilli and Escherichia coli increased transepithelial electrical resistance while promoting OVA passage capable to trigger basophil activation. Non-inflammatory levels of IL-8 and thymic stromal lymphopoietin were produced basolaterally by Caco-2 cells exposed to microorganisms. CONCLUSION: The complex model designed in here is adequate to learn about the consequence of the interaction between microorganisms and epithelial cells vis-a-vis the barrier function and antigen translocation, two parameters essential to mucosal homeostasis. It can further serve as a direct tool to search for microorganisms with anti-allergic and anti-inflammatory properties.

The prevention of transmission of blood-borne diseases in the health-care setting

  The risk of transmission of blood-borne pathogens in the health-care setting has become a matter of increasing concern in Ireland in recent years. Health-care workers undertaking exposure-prone procedures are at risk of contracting blood-borne diseases from the patients they are treating and there is also a small risk that patients who are undergoing such procedures may become infected by the health-care workers who are treating them. An Advisory Group on the Transmission of Infectious Diseases in the Health-Care Setting was established in 1995 to advise the Minister for Health on the prevention of the transmission of such diseases. The Advisory Group published its report in 1997. It was realised at that time that this matter would need to be kept under review and a Standing Advisory Committee was established. Guidelines on this subject were published by the Advisory Committee in June1999. In the current document, these guidelines have been substantially revised in the light of recent information and technical developments and are now considered to be a Code of Practice in the area of prevention of the transmission of blood-borne pathogens in the health-care setting.    

Protective immunity of single and multi-antigen DNA vaccines against schistosomiasis

We evaluated the usefulness of the combination of three plasmids encoding tegumental (pECL and pSM14) and muscular (pIRV5) antigens of the Schistosoma mansoni on improving the protective immunity over the use of a single antigen as DNA vaccines. Female BALB/c mice were inoculated twice with 25 µg DNA plasmid within two weeks interval. The challenge was performed with 80 cercarias of a regional isolate of S. mansoni (SLM) one week after the last immunization. Six weeks after challenge, all mice were perfused for worm load determination. The following groups were analyzed: saline; empty vector; monovalent formulations of pECL; pSM14 and pIRV5 and also double combinations of pECL/pIRV5 and pIRV5/pSM14 and a triple combination of pECL/pIRV5/pSM14. The protection was expressed as a percentage of worm loads in each group compared with the saline group. The results obtained were 41% (p < 0.05); 52% (p < 0.05); 51% (p < 0.05); 48% (p < 0.05); 55% (p < 0.05); 45% (p < 0.05); 65% (p < 0.05) for each group respectively.

Optimització d'una aplicacio bioinformàtica d'alineament de seqüències executada en processadors multi-core i many-core (GPUs)

Las aplicaciones de alineamiento de secuencias son una herramienta importante para la comunidad científica. Estas aplicaciones bioinformáticas son usadas en muchos campos distintos como pueden ser la medicina, la biología, la farmacología, la genética, etc. A día de hoy los algoritmos de alineamiento de secuencias tienen una complejidad elevada y cada día tienen que manejar un volumen de datos más grande. Por esta razón se deben buscar alternativas para que estas aplicaciones sean capaces de manejar el aumento de tamaño que los bancos de secuencias están sufriendo día a día. En este proyecto se estudian y se investigan mejoras en este tipo de aplicaciones como puede ser el uso de sistemas paralelos que pueden mejorar el rendimiento notablemente.