R&D cooperation between Spanish firms and scientific partners: what is the role of tertiary education?

This paper explores the factors that determine firm’s R&D cooperation with different partners, paying special attention on the role of tertiary education (degree and PhDs level) in facilitating the connection between the firms and the to scientific bodies (technology centres, public research centres and universities). Here, we attempt to answer two questions. First, are innovative firms that carry out internal and external R&D activities more likely to cooperate on R&D projects with other partners? Second, do Spanish innovative firms with a high participation of researchers with degrees or PhDs tend to cooperate more with scientific partners? To answer both questions we apply a three-dimensional approach on a firm level Panel Data with a sample of 4.998 manufacturing and services Spanish firms. First, we run a complementary test between external R&D acquisition and skilled research workers and find that firms which carry out external R&D activities obtain a greater return on R&D cooperation when they have skilled workers in R&D, especially in high-tech manufactures and KIS services. Second, we carry out a 2-step tobit model to estimate, in the first stage, the determinants that explain whether Spanish innovative firms cooperate or not; and in the second stage the factors that affect the choice of partners. And third, we apply an ordered probit model to test the marginal effects of explanatory variables on the different partners. Here we contrast some of the most interesting empirical hypotheses of previous studies, and which emphasize the role of employees with degrees and PhDs in facilitating cooperative R&D between firms and scientific partners. JEL classification: O31, O33, O38. Key words: Determinants R&D cooperation, industry-university flows, PhD research workers.

Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval.

Methadone is administered as a chiral mixture of (R,S)-methadone. The opioid effect is mainly mediated by (R)-methadone, whereas (S)-methadone blocks the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel more potently, which can cause drug-induced long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias. To investigate whether substitution of (R,S)-methadone by (R)-methadone could reduce the corrected QT (QTc) interval, (R,S)-methadone was replaced by (R)-methadone (half-dose) in 39 opioid-dependent patients receiving maintenance treatment for 14 days. (R)-methadone was then replaced by the initial dose of (R,S)-methadone for 14 days (n = 29). Trough (R)-methadone and (S)-methadone plasma levels and electrocardiogram measurements were taken. The Fridericia-corrected QT (QTcF) interval decreased when (R,S)-methadone was replaced by a half-dose of (R)-methadone; the median (interquartile range [IQR]) values were 423 (398-440) milliseconds (ms) and 412 (395-431) ms (P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of -3.9 ms (95% confidence interval [CI], -7.7 to -0.2) per week (P = .04). The QTcF value increased when (R)-methadone was replaced by the initial dose of (R,S)-methadone for 14 days; median (IQR) values were 424 (398-436) ms and 424 (412-443) ms (P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3-8.1) per week (P = .006). Substitution of (R,S)-methadone by (R)-methadone reduces the QTc interval value. A safer cardiac profile of (R)-methadone is in agreement with previous in vitro and pharmacogenetic studies. If the present results are confirmed by larger studies, (R)-methadone should be prescribed instead of (R,S)-methadone to reduce the risk of cardiac toxic effects and sudden death.

r-Sm14 - pRSETA efficacy in experimental animals

Previous studies carried out with Sm14 in experimental vaccination against Schistosoma mansoni or Fasciola hepatica infections were performed with recombinant Sm14 (rSm14) produced in Escherichia coli by the pGEMEX system (Promega). The rSm14 was expressed as a 40 kDa fusion protein with the major bacteriophage T7 capsid protein. Vaccination experiments with this rSm14 in animal models resulted in consistent high protective activity against S. mansoni cercariae challenge and enabled rSm14 to be included among the vaccine antigens endorsed by the World Health Organization for phase I/II clinical trials. Since the preparation of pGEMEX based rSm14 is time consuming and results in low yield for large scale production, we have tested other E. coli expression systems which would be more suitable for scale up and downstream processing. We expressed two different 6XHis-tagged Sm14 fusion proteins in a T7 promoter based plasmids. The 6XHis-tag fusions allowed rapid purification of the recombinant proteins through a Ni+2-charged resin. The resulted recombinant 18 and 16 kDa proteins were recognized by anti-Sm14 antibodies and also by antiserum against adult S. mansoni soluble secreted/excreted proteins in Western-Blot. Both proteins were also protective against S. mansoni cercariae infection to the same extent as the rSm14 expressed by the pGEMEX system.

Rhodnius amazonicus Almeida, Santos & Sposina, 1973, Bona Species, Close to R. pictipes Stål, 1872 (Heteroptera, Reduviidae, Triatominae)

The discovery of two atypical specimens of Rhodnius pictipes Stål, 1872 in French Guiana and the examination of the female holotype of R. amazonicus Almeida, Santos & Sposina, 1973, the only specimen of this species so far known, lead us to propose the rehabilitation of R. amazonicus synonymized with R. pictipes. The male is described for the first time and the female redescribed. Both external characters and genitalia distinguish R. amazonicus from R. pictipes. R. amazonicus shows affinities not only with pictipes but also with R. stali Lent, Jurberg & Galvão, 1993 and R. paraensis Sherlock, Guitton & Miles, 1977. A key is provided for these four species forming, in all likelihood, a natural group, i.e. the "pictipes group".

Suivi prospectif à une année des prothèses de genou F.I.R.S.T. Evolution avec analyse ambulatoire de la marche

Le but de mon travail de master est de pr��senter les r��sultats à une année postopératoire d'une étude prospective sur une nouvelle prothèse totale du genou : la F.I.R.S.T. Evolution. Cette prothèse s'intéresse à des patients plus jeunes, avec une importante laxité des ligaments collatéraux. L'étude finale suivra à cinq ans une cohorte de cinquante patients environ. Actuellement, nous suivons 17 patients opér��s avec cette prothèse (dont 9 femmes et 8 hommes, 9 genoux droits et 8 genoux gauches) avec un âge moyen de 69,10 ans (de 42 à 83 ans). Pour l'obtention des r��sultats, les patients ont remplis des questionnaires spécifiques couramment utilisés (Eq5D, WOMAC, KSS, échelle analogique de la douleur EVA/VAS, UCLA activity-rating level), ont bénéficié de contr��les radiologiques r��guliers et d'une analyse r��gulière de la marche, à trois vitesses différentes. Cette analyse est objective et se base sur un système de capteurs miniaturisés. Les r��sultats cliniques obtenus à une année démontrent une amélioration globale de la fonction du genou et de la qualité de vie per��ue par le patient (Eq5D, WOMAC, EVA/VAS, KSS, UCLA). Les données à une année de l'analyse de marche montrent une amélioration significative dans tous les paramètres du cycle de marche et aux différentes vitesses. En comparant nos r��sultats avec ceux pr��cédemment obtenus, nous pouvons être satisfaits car ils se sont amélior��s depuis la dernière échéance à 6 mois. De plus, nos r��sultats à une année suivent ceux obtenus dans d'autres études utilisant les mêmes questionnaires et une analyse objective de la marche. On s'attend à ce que ces données se stabilisent voire continuent de s'améliorer dans les années à venir.

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population.

Sunk costs, extensive R&D subsidies and permanent inducement effects

We study whether there is scope for using subsidies to smooth out barriers to R&D performance and expand the share of R&D firms in Spain. We consider a dynamic model with sunk entry costs in which firms’ optimal participation strategy is defined in terms of two subsidy thresholds that characterise entry and continuation. We compute the subsidy thresholds from the estimates of a dynamic panel data type-2 tobit model for an unbalanced panel of about 2,000 Spanish manufacturing firms. The results suggest that “extensive” subsidies are a feasible and efficient tool for expanding the share of R&D firms.

Local Distance-Based Generalized Linear Models using the dbstats package for R

This paper introduces local distance-based generalized linear models. These models extend (weighted) distance-based linear models firstly with the generalized linear model concept, then by localizing. Distances between individuals are the only predictor information needed to fit these models. Therefore they are applicable to mixed (qualitative and quantitative) explanatory variables or when the regressor is of functional type. Models can be fitted and analysed with the R package dbstats, which implements several distancebased prediction methods.

The MIGCLIM R package - seamless integration of dispersal constraints into projections of species distribution models

The MIGCLIM R package is a function library for the open source R software that enables the implementation of species-specific dispersal constraints into projections of species distribution models under environmental change and/or landscape fragmentation scenarios. The model is based on a cellular automaton and the basic modeling unit is a cell that is inhabited or not. Model parameters include dispersal distance and kernel, long distance dispersal, barriers to dispersal, propagule production potential and habitat invasibility. The MIGCLIM R package has been designed to be highly flexible in the parameter values it accepts, and to offer good compatibility with existing species distribution modeling software. Possible applications include the projection of future species distributions under environmental change conditions and modeling the spread of invasive species.

Genome-wide association analysis identifies 20 loci that influence adult height.

Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.

Variants in MTNR1B influence fasting glucose levels.

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

Implamantació de SAP R/3 en un entorn logístic

Aquest treball és un projecte d'implementació dels mòduls de logística i moviment de materials de l'ERP SAP R/3 en un centre de distribució de peces de recanvi d'una marca d'automòbils.