11 research outputs found
SEEMP: A Networked Marketplace for Employment Services
No full textThe purpose of this chapter is to introduce the SEEMP marketplace of employment mediators, detailing the business objectives and main features of the SEEMP integrated technology platform. The purpose of SEEMP is to enable the meeting of Job Offers from employers and CVs of job seekers by developing an e-marketplace, improving the business activity of brokers in an employment market currently characterised by: Multiplicity of the players on the market and diversity of the distribution networks: Job Seekers and CVs are distributed across many online databases, brokers and intermediaries. In order to be sufficiently visible, a candidate or an enterprise has to contact several intermediaries, for example temporary work agencies, employment websites, with a redundancy of information and multiplication of the effort needed to correctly classify, qualify and maintain their data. Lack of common standard for Job Offer and CV: The lack of standardized descriptions and search criteria shared by the intermediaries prevents them to exchange information easily and effectively. Insufficient information sharing among the players on the labour market: Inspite of various existing information systems for e-employment, data sharing between entities of intermediary networks remains insufficient. The same holdsfor the cooperation aspects among players in the market, which need cooperative information systems technology. This paper is organized as follows. In Sect. 2, we state the overall objectives of the SEEMP project and state the market vision of the project. In Sect. 3, we present the methodologies adopted in SEEMP in terms of minimal shared commitment that drives the SEEMP policies, and we describe the adopted best practices which help to clarify the agreement levels established for SEEMP and the SEEMP architecture used to implement the interoperability framework. In Sect. 4, we provide a demonstrative use case of the elements described in the paper; this use case is rather simple but proves difficult to solve at a European scale. Finally, in Sect. 5 we introduce some elements of discussion such as a comparison between SEEMP with EURES and other job boards and employment search engines, and set the stage for evaluating the SEEMP benefits for its intended actors; finally we give the concluding remarks
Macrosteatotic hepatocyte defatting: optimization through reaction-flow modeling
No full textSince there is a shortage of transplantable livers, the donor pool needs to be increased. One method to accomplish this is to recondition extended criteria donor grafts, a large portion of which are moderate to severe macrosteatotic livers. Transplantation of these livers often leads to primary nonfunction caused by an increased susceptibility to the effects of ischemia reperfusion injury (I/R) that result from the harvesting, transportation, and transplantation of the liver. Our lab has developed a novel procedure to recondition these livers through an ex vivo perfusion that will reduce the hepatic triglyceride content before the onset of the effects of I/R injury. To be feasibly performed in a clinical setting, the defatting must be completed in a matter of hours. While attempts to identify the ideal defatting cocktail in static culture only resulted in defatting livers after days of treatment, the rate of defatting increases to more a clinically relevant timeframe in a flow environment. My project focuses on understanding the differences between a static and flow environment and using this information to develop the ideal parameters for defatting. I hypothesize that using flow and appropriate defatting agents, steatotic hepatocytes can be defatted in a clinically relevant time of hours, without harming viability or function, to a level that reduces or eliminates increased sensitivity to I/R injury. In order to prove the hypothesis I will use the following 3 specific aims: 1. Develop a metabolic flux analysis model to explore defatting metabolic pathways. 2. Develop a computational fluid dynamics and kinetic model of a vitro flow reactor to optimize key transport parameters. 3. Validate the optimal conditions of flow has on the viability and function in hepatocyte cell lines.Ph.D.Includes bibliographical referencesby Gabriel Yarmus
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
No full textWe conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis
The effect of position on cardiopulmonary outcomes in preterm infants during bottle feeding
No full textBackground. Feeding in preterm infants is a complex motor activity requiring physiologic stability, behavioral readiness and the sensorimotor synchronization of multiple muscle groups; to effectively coordinate sucking, swallowing and breathing. The elevated sidelying position is suggested as a potential therapeutic intervention strategy to support bottle feeding in preterm infants. Purpose. The primary purpose of this study was to investigate the effect of position on cardiopulmonary parameters in preterm infants during oral feeding. In addition, nonlinear methods of analysis of respiratory waveforms (Approximate Entrophy) were used to examine respiratory variability during oral feeding. Methods. Twelve healthy preterm infants were studied using a within-subject cross over design to compare semiupright and the elevated sidelying position during bottle feeding. Outcomes measures were cardiopulmonary physiology (heart rate, respiratory rate, oxygen saturation and respiratory pattern variability), behavioral state and feeding efficiency (volume intake and length of feeding). Results. The principle findings related to cardiopulmonary physiology revealed no significant difference in heart rate, respiratory rate, percent hemoglobin oxygen saturation or respiratory variability between the semiupright and elevated sidelying position, during oral feeding in healthy preterm infants. Feeding outcomes did not differ significantly between the semiupright and elevated sidelying position. Nonlinear measures of respiratory waveforms proved useful in assessing variability in respiratory patterns in healthy preterm during bottle feeding. Conclusions. Either the semiupright position or the elevated sidelying may be beneficial for healthy preterm infants transitioning to oral feeding. Analysis of respiratory waveforms may prove useful clinically for assessing variability in infant breathing patterns.Ph.D.Includes bibliographical referencesby Caryn Bradle
In vitro screening system for macrosteatosis reversal in liver cells
No full textOrthotopic liver transplantation is the only therapeutic option for end-stage liver disease, but it is limited by the scarcity of suitable grafts. Macrosteatotic livers exhibit elevated triglyceride (TG) levels in the form of large lipid droplets (LDs), elevated reactive oxygen species (ROS) and reduced adenosine triphosphate (ATP) levels in the liver’s hepatocytes. These abnormalities increase sensitivity of hepatocytes to ischemia and reperfusion (I/R) stress during transplantation and to increased hepatocyte death and graft failure following transplantation. Macrosteatosis reversal several weeks prior to live-donor liver transplantation reduces graft I/R sensitivity and enables successful transplantation. However, to apply this concept to livers from deceased donors, the defatting process must be accelerated using ex-vivo perfusion with defatting agents. To explore macrosteatosis defatting phenomena and to identify potent defatting agents prior to whole liver studies, an in-vitro system simulating macrosteatosis was developed. Primary rat hepatocyte cultures incubated for several days with elevated free fatty acid (FFA) levels exhibited characteristics of clinical macrosteatosis based on LD morphology, elevated TG levels and elevated sensitivity to hypoxia and reoxygenation (H/R) induced stress, simulating I/R. This novel system was used to explore the ability of selected defatting cocktails to reverse macrosteatosis and reduce H/R sensitivity as measured by hepatocyte viability and function. We found that pretreatment of macrosteatotic cultures with an L-carnitine supplemented defatting cocktail under hyperoxic conditions for 48h prior to H/R induction led to a ~82% reduction in the number of macrosteatotic LDs and to a ~57% reduction in intrahepatic TG by promoting bete-oxidation of FFAs. Furthermore, this treatment reduced ROS stress by ~32%, elevated the ATP levels to that of lean controls and fully abolished H/R associated hepatic death. Treated cultures maintained ~83% viability and exhibited superior functionality compared to untreated macrosteatotic cultures as assessed by urea secretion and bile canalicular transport 48h post H/R stress. The developed system is suitable for exploring additional defatting cocktails that may reverse macrosteatosis and elevated H/R sensitivity. The developed in-vitro defatting routine can now be scaled-up for whole organ perfusion systems to recover macrosteatotic livers in order to mitigate the persistent shortage of suitable livers for transplantation.Ph. D.Includes bibliographical referencesby Nir Israel Nati
SEEMP: Meaningful Service-based Collaboration Among Labour Market Actors
No full textSEEMP is an European Project that promotes increased partnership between labour market actors and the development of closer relations between private and public employment services, making optimal use of the various actors’ specific characteristics, thus providing job-seekers and employers with better services”. The need for such a flexible collaboration gives rise to the issue of interoperability in both data exchange and share of services. SEEMP proposes a solution that relies on the concepts of services and semantics in order to provide a meaningful service-based collaboration among labour market actors
Stratified medicine for mental disorders
No full textThere is recognition that biomedical research into the causes of mental disorders and their treatment needs to adopt new approaches to research. Novel biomedical techniques have advanced our understanding of how the brain develops and is shaped by behaviour and environment. This has led to the advent of stratified medicine, which translates advances in basic research by targeting aetiological mechanisms underlying mental disorder. The resulting increase in diagnostic precision and targeted treatments may provide a window of opportunity to address the large public health burden, and individual suffering associated with mental disorders. While mental health and mental disorders have significant representation in the "health, demographic change and wellbeing" challenge identified in Horizon 2020, the framework programme for research and innovation of the European Commission (2014-2020), and in national funding agencies, clear advice on a potential strategy for mental health research investment is needed. The development of such a strategy is supported by the EC-funded "Roadmap for Mental Health Research" (ROAMER) which will provide recommendations for a European mental health research strategy integrating the areas of biomedicine, psychology, public health well being, research integration and structuring, and stakeholder participation. Leading experts on biomedical research on mental disorders have provided an assessment of the state of the art in core psychopathological domains, including arousal and stress regulation, affect, cognition social processes, comorbidity and pharmacotherapy. They have identified major advances and promising methods and pointed out gaps to be addressed in order to achieve the promise of a stratified medicine for mental disorders
Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index
No full textThe phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ~4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity. © 2014 Hoggart et al
Papel del factor de transcripción Kruppel-like factor 2 en la disfunción endotelial hepática asociada a la hipertensión portal y al daño por isquemia y reperfusión
No full textEl endotelio disfuncional presenta, entre otras caracteristicas, alteración en los mecanismos de vasodilatación, complicaciones trombóticas, disminución de la resistencia al estrés oxidativo, aumento de la expresión de moléculas de adhesión y de la secreción de moléculas proinflamatorias. El factor de transcripción endotelial KLF2 juega un importante papel en la regulación del fenotipo protector endotelial y su expresión depende de las fuerza hemodinámicas generadas por el flujo sanguíneo y de la administración exógena de estatinas.
La hipertensión portal y el daño hepático por I/R son dos condiciones patológicas asociadas a disfunción endotelial. Los trastornos estructurales característicos de la cirrosis hepática, la mayor causa prevalente de hipertensión portal en nuestro entorno, se acompañan de variaciones en las fuerzas hemodinámicas que pueden modificar la expresión de KLF2 y su programa transcripcional vasoprotector. Asímismo, durante la isquemia asociada a la preservación de injertos hepáticos para transplante, la interrupción de las fuerzas hemodinámicas generadas por el flujo sanguíneo podría resultar en la reducción de los programas endoteliales vasoprotectores, que se debería en parte a la pérdida de expresión de KLF2.
Los trabajos de investigación de la presente tesis doctoral amplian el conocimiento de los mecanismos moleculares responsables de la disfunción endotelial hepática, demostrando:
1. Que KLF2 está muy expresado en los hígados cirróticos y que su expresión se induce en las fases tempranas de la progresión de la enfermedad, representando un mecanismo compensador para mejorar los desórdenes vasculares característicos de los hígados cirróticos.
2. Que los hígados preservados en condiciones de transplante muestran un descenso tiempo-dependiente de KLF2, acompañado de daño hepático y aumentada resistencia vascular.
Además, demostran que la modulación farmacologica de la expresión de KLF2 puede ser beneficiosa tanto en el tratamiento de la hipertensión portal como en la preservación de los injertos hepáticos para transplante
Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1
No full textAbdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression
