Analytical Strategies for Doping Control Purposes: Needs, Challenges, and Perspectives.

The fight against doping in sports has been governed since 1999 by the World Anti-Doping Agency (WADA), an independent institution behind the implementation of the World Anti-Doping Code (Code). The intent of the Code is to protect clean athletes through the harmonization of anti-doping programs at the international level with special attention to detection, deterrence and prevention of doping.1 A new version of the Code came into force on January 1st 2015, introducing, among other improvements, longer periods of sanctioning for athletes (up to four years) and measures to strengthen the role of anti-doping investigations and intelligence. To ensure optimal harmonization, five International Standards covering different technical aspects of the Code are also currently in force: the List of Prohibited Substances and Methods (List), Testing and Investigations, Laboratories, Therapeutic Use Exemptions (TUE) and Protection of Privacy and Personal Information. Adherence to these standards is mandatory for all anti-doping stakeholders to be compliant with the Code. Among these documents, the eighth version of International Standard for Laboratories (ISL), which also came into effect on January 1st 2015, includes regulations for WADA and ISO/IEC 17025 accreditations and their application for urine and blood sample analysis by anti-doping laboratories.2 Specific requirements are also described in several Technical Documents or Guidelines in which various topics are highlighted such as the identification criteria for gas chromatography (GC) and liquid chromatography (LC) coupled to mass spectrometry (MS) techniques (IDCR), measurements and reporting of endogenous androgenic anabolic agents (EAAS) and analytical requirements for the Athlete Biological Passport (ABP).

Co-evolutionary dynamics between public good producers and cheats in the bacterium Pseudomonas aeruginosa.

The production of beneficial public goods is common in the microbial world, and so is cheating - the exploitation of public goods by nonproducing mutants. Here, we examine co-evolutionary dynamics between cooperators and cheats and ask whether cooperators can evolve strategies to reduce the burden of exploitation, and whether cheats in turn can improve their exploitation abilities. We evolved cooperators of the bacterium Pseudomonas aeruginosa, producing the shareable iron-scavenging siderophore pyoverdine, together with cheats, defective in pyoverdine production but proficient in uptake. We found that cooperators managed to co-exist with cheats in 56% of all replicates over approximately 150 generations of experimental evolution. Growth and competition assays revealed that co-existence was fostered by a combination of general adaptions to the media and specific adaptions to the co-evolving opponent. Phenotypic screening and whole-genome resequencing of evolved clones confirmed this pattern, and suggest that cooperators became less exploitable by cheats because they significantly reduced their pyoverdine investment. Cheats, meanwhile, improved exploitation efficiency through mutations blocking the costly pyoverdine-signalling pathway. Moreover, cooperators and cheats evolved reduced motility, a pattern that likely represents adaptation to laboratory conditions, but at the same time also affects social interactions by reducing strain mixing and pyoverdine sharing. Overall, we observed parallel evolution, where co-existence of cooperators and cheats was enabled by a combination of adaptations to the abiotic and social environment and their interactions.

Pilas de combustible soportadas sobre el anodo de una sola camara basadas en electrolitos de ceria dopada con Gd

La utilización de electrolitos soportados en el ánodo es una estrategia muy útil para mejorar las propiedades eléctricas de las pilas de combustible de óxido sólido, debido a que permiten disminuir considerablemente el espesor de los electrolitos. Para este trabajo, se han preparado exitosamente pilas de combustible de óxido sólido con electrolitos de ceria dopada con Gd, Ce1-xGdxO2-y (CGO) soportados sobre un ánodo formado por un cermet de Ni/CGO. Dichas pilas se han instalado y caracterizado en un reactor de una sola cámara donde se ha hecho circular una mezcla de propano y aire. Para ello, se han preparado mezclas de polvos de NiO y de ceria dopada con gadolinia, con diferentes composiciones y tamaño de partículas, para obtener los ánodos con porosidades apropiadas y así utilizarlos como soporte del electrolito en las pilas. Los polvos de los electrolitos de CGO se han preparado por la técnica sol-gel y se han depositado por"dip coating" con diferentes espesores (15-30 ¿m) utilizando una tinta preparada a partir de partículas nanométricas dispersadas en una resina comercial. Los cátodos de La1-xSrxCoO3-S (LSCO) se han preparado también por la técnica sol-gel y se han depositado sobre la capa fina del electrolito. Finalmente, las propiedades eléctricas se han determinado en un reactor de una sola cámara dónde el propano se ha mezclado con aire sintético por encima del límite superior de inflamabilidad. En estas condiciones experimentales se han obtenido altas densidades de potencia estables, controlando las velocidades de flujo total de gas transportador y la presión parcial de propano.

Pilas de combustible de una sola camara, basadas en electrolitos de ceria dopada con gadolinia y operadas con metano y propano

La principal ventaja de las pilas de combustible de óxido sólido (SOFCs) de una sola cámara, frente a las bicamerales convencionales, es que permiten simplificar el diseño del dispositivo y operar con mezclas de hidrocarburos (metano, propano...) y aire, sin necesidad de separar ambos gases, por medio del uso de electrodos selectivos a la oxidación del combustible y reducción del oxidante. En el presente trabajo, se han fabricado monopilas soportadas sobre electrolitos de ceria dopada con gadolinia (GDC), de 200 ¿m de espesor, usando Ni-GDC como ánodo y LSC(La0.5Sr0.5CoO3-¿)-GDC-Ag2O como cátodo. Las propiedades eléctricas de la celda se determinaron en un reactor de una sola cámara, usando mezclas de metano + aire y propano + aire. Se investigó la influencia de la temperatura, de las presiones parciales del combustible y oxígeno, y de la velocidad de flujo total sobre el rendimiento de las pilas preparadas. Así, la densidad de potencia se incrementó fuertemente con el aumento de la temperatura, la velocidad de flujo total y la composición de hidrocarburo. Una vez se optimizaron los parámetros operacionales, la celda presentó unas densidades de potencia máximas de 70 y 320 mW/ cm2, operando con propano a 600ºC y con metano a 795ºC, respectivamente.

Nanocarriers for DNA Vaccines: Co-Delivery of TLR-9 and NLR-2 Ligands Leads to Synergistic Enhancement of Proinflammatory Cytokine Release

Adjuvants enhance immunogenicity of vaccines through either targeted antigen delivery or stimulation of immune receptors. Three cationic nanoparticle formulations were evaluated for their potential as carriers for a DNA vaccine, and muramyl dipeptide (MDP) as immunostimulatory agent, to induce and increase immunogenicity of Mycobacterium tuberculosis antigen encoding plasmid DNA (pDNA). The formulations included (1) trimethyl chitosan (TMC) nanoparticles, (2) a squalene-in-water nanoemulsion, and (3) a mineral oil-in-water nanoemulsion. The adjuvant effect of the pDNA-nanocomplexes was evaluated by serum antibody analysis in immunized mice. All three carriers display a strong adjuvant effect, however, only TMC nanoparticles were capable to bias immune responses towards Th1. pDNA naturally contains immunostimulatory unmethylated CpG motifs that are recognized by Toll-like receptor 9 (TLR-9). In mechanistic in vitro studies, activation of TLR-9 and the ability to enhance immunogenicity by simultaneously targeting TLR-9 and NOD-like receptor 2 (NLR-2) was determined by proinflammatory cytokine release in RAW264.7 macrophages. pDNA in combination with MDP was shown to significantly increase proinflammatory cytokine release in a synergistic manner, dependent on NLR-2 activation. In summary, novel pDNA-Ag85A loaded nanoparticle formulations, which induce antigen specific immune responses in mice were developed, taking advantage of the synergistic combinations of TLR and NLR agonists to increase the adjuvanticity of the carriers used.

Co-opetition: Coexistence of cooperation and competition in public sector – A case study in one city’s public companies

Business actions do not take place in isolation. Complementary competencies and capabilities are the most important resources in the exponential knowledge growth. These resources are partially accessed via business partners. A company needs partners and the capability to cooperate, but also the awareness of the competitive tension, when operating in the market with multiple actors. The co-opetition research studies the occurrence and the forms of simultaneous cooperation and competition between companies or their units. Public sector’s governmental and municipal organs have been transformed into companies over the past years. Despite of their non-profit nature, public sector and public companies are adopting business doctrines from private sector towards efficient business operations. This case study aims to show, how co-opetition concept can be observed within public sector companies and in their operations with others, how public companies cooperate but also compete with others and why this happens. This thesis also explicates advantages and disadvantages of the co-opetition phenomenon.

Simulated Patient as Co-facilitators: Benefits and Challenges of the Interprofessional Team OSCE (Submission #9350).

Hypothesis: The quality of care for chronic patients depends on the collaborative skills of the healthcare providers.1,2 The literature lacks reports of the use of simulation to teach collaborative skills in non-acute care settings. We posit that simulation offers benefits for supporting the development of collaborative practice in non-acute settings. We explored the benefits and challenges of using an Interprofessional Team - Objective Structured Clinical Examination (IT-OSCE) as a formative assessment tool. IT-OSCE is an intervention which involves an interprofessional team of trainees interacting with a simulated patient (SP) enabling them to practice collaborative skills in non-acute care settings.5 A simulated patient are people trained to portray patients in a simulated scenario for educational purposes.6,7 Since interprofessional education (IPE) ultimately aims to provide collaborative patient-centered care.8,9 We sought to promote patient-centeredness in the learning process. Methods: The IT-OSCE was conducted with four trios of students from different professions. The debriefing was co-facilitated by the SP with a faculty. The participants were final-year students in nursing, physiotherapy and medicine. Our research question focused on the introduction of co-facilitated (SP and faculty) debriefing after an IT-OSCE: 1) What are the benefits and challenges of involving the SP during the debriefing? and 2) To evaluate the IT-OSCE, an exploratory case study was used to provide fine grained data 10, 11. Three focus groups were conducted - two with students (n=6; n=5), one with SPs (n=3) and one with faculty (n=4). Audiotapes were transcribed for thematic analysis performed by three researchers, who found a consensus on the final set of themes. Results: The thematic analysis showed little differentiation between SPs, student and faculty perspectives. The analysis of transcripts revealed more particularly, that the SP's co-facilitation during the debriefing of an IT-OSCE proved to be feasible. It was appreciated by all the participants and appeared to value and to promote patient-centeredness in the learning process. The main challenge consisted in SPs feedback, more particularly in how they could report accurate observations to a students' group rather than individual students. Conclusion: In conclusion, SP methodology using an IT-OSCE seems to be a useful and promising way to train collaborative skills, aligning IPE, simulation-based team training in a non-acute care setting and patient-centeredness. We acknowledge the limitations of the study, especially the small sample and consider the exploration of SP-based IPE in non-acute care settings as strength. Future studies could consider the preparation of SPs and faculty as co-facilitators. References: 1. Borrill CS, Carletta J, Carter AJ, et al. The effectiveness of health care teams in the National Health Service. Aston centre for Health Service Organisational Research. 2001. 2. Reeves S, Lewin S, Espin S, Zwarenstein M. Interprofessional teamwork for health and social care. Oxford: Wiley-Blackwell; 2010. 3. Issenberg S, McGaghie WC, Petrusa ER, Gordon DL, Scalese RJ. Features and uses of high-fidelity medical simulations that lead to effective learning - a BEME systematic review. Medical Teacher. 2005;27(1):10-28. 4. McGaghie W, Petrusa ER, Gordon DL, Scalese RJ. A critical review of simulation-based medical education research: 2003-2009. Medical Education. 2010;44(1):50-63. 5. Simmons B, Egan-Lee E, Wagner SJ, Esdaile M, Baker L, Reeves S. Assessment of interprofessional learning: the design of an interprofessional objective structured clinical examination (iOSCE) approach. Journal of Interprofessional Care. 2011;25(1):73-74. 6. Nestel D, Layat Burn C, Pritchard SA, Glastonbury R, Tabak D. The use of simulated patients in medical education: Guide Supplement 42.1 - Viewpoint. Medical teacher. 2011;33(12):1027-1029. Disclosures: None (C) 2014 by Lippincott Williams & Wilkins, Inc.

"Tu seras Psychologue, ma fille". La transmission intergénérationnelle du choix professionnel : Une co-construction entre parents et enfants.

The aim of the study is to understand how the family influences the choice of becoming a psychologist and how an occupational choice is repeated in the family, via intergenerational transmission. We interviewed seven female students in a Master of Science in Psychology : first, they filled in a genosociogramm including data about occupations of their ancestors on about four generations ; then, they took part into a semi-structured qualitative enquiry. Our results have shown that a little bit less than half of the subjects have a parent who have social or care jobs, but more than half if we add the grand-parents. In a conscious level, subjects tend to deny any kind of family influence, in the majority ; afterwards, they discover influences they didn't notice. Secondly, the content analysis reveals five categories of family influence : the educational path (doubts, choices), the choice of psychology via the development of self-efficacy (interest, personality and soft skills), the exploration of occupations and activities during childhood and adulthood (leisure activities, professional world, suggestions, advice, education), the transmission of values (immaterial and material) and the family relationships during childhood and teenage years (relationship issues and difficulties, confidences and secrets, relationships and role in the brotherhood and/or sisterhood). The importance for the career counselor to investigate the relational context of his/her consultant is discussed, as much as the need for him to think about his own motivations to help others, linked with his family background.

Sosiaalisten ongelmien retoriikkaa : tapaus doping

Summary: Rhetoric in discussing social problems: The case of doping

Fast and sensitive supercritical fluid chromatography - tandem mass spectrometry multi-class screening method for the determination of doping agents in urine.

This study shows the possibility offered by modern ultra-high performance supercritical fluid chromatography combined with tandem mass spectrometry in doping control analysis. A high throughput screening method was developed for 100 substances belonging to the challenging classes of anabolic agents, hormones and metabolic modulators, synthetic cannabinoids and glucocorticoids, which should be detected at low concentrations in urine. To selectively extract these doping agents from urine, a supported liquid extraction procedure was implemented in a 48-well plate format. At the tested concentration levels ranging from 0.5 to 5 ng/mL, the recoveries were better than 70% for 48-68% of the compounds and higher than 50% for 83-87% of the tested substances. Due to the numerous interferences related to isomers of steroids and ions produced by the loss of water in the electrospray source, the choice of SFC separation conditions was very challenging. After careful optimization, a Diol stationary phase was employed. The total analysis time for the screening assay was only 8 min, and interferences as well as susceptibility to matrix effect (ME) were minimized. With the developed method, about 70% of the compounds had relative ME within the range ±20%, at a concentration of 1 and 5 ng/mL. Finally, limits of detection achieved with the above-described strategy including 5-fold preconcentration were below 0.1 ng/mL for the majority of the tested compounds. Therefore, LODs were systematically better than the minimum required performance levels established by the World anti-doping agency, except for very few metabolites.

Randomized, crossover, double-blind, placebo-controlled trial to assess the lipid lowering effect of co-formulated TDF/FTC

Abstract INTRODUCTION: Previous studies have described improvements on lipid parameters when switching from other antiretroviral drugs to tenofovir (TDF) and impairments in lipid profile when discontinuing TDF. [1-3] It is unknown, however, if TDF has an intrinsic lipid-lowering effect or such findings are due to the addition or removal of other offending agents or other reasons. MATERIALS AND METHODS: RESULTS: 46 subjects with a median age of 43 (40-48) years were enrolled in the study: 70% were male, 56% received DRV/r and 44% LPV/r. One subject withdrew the study voluntarily at week 4 and another one interrupted due to diarrhoea at week 24. Treatment with TDF/FTC decreased total, LDL and HDL-cholesterol from 235.9 to 204.9 (p<0.001), 154.7 to 127.6 (p<0.001) and 50.3 to 44.5 mg/dL (p<0.001), respectively. In comparison, total, LDL and HDL-cholesterol levels remained stable during placebo exposure. Week 12 total cholesterol (p<0.001), LDL-cholesterol (p<0.001) and HDL-cholesterol (p=0.011) levels were significantly lower in TDF/FTC versus placebo. Treatment with TDF/FTC reduced the fraction of subjects with abnormal fasting total-cholesterol (≥200 mg/dL) from 86.7% to 56.8% (p=0.001) and LDL-cholesterol (≥130 mg/dL) from 87.8% to 43.9% (p<0.001), which was not observed with placebo. There were no virological failures, and CD4 and triglyceride levels remained stable regardless of exposure. CONCLUSION: Coformulated TDF/FTC has an intrinsic lipid-lowering effect, likely attributable to TDF.

SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites

The Class IIa histone deacetylases (HDAC)4 and HDAC5 play a role in neuronal survival and behavioral adaptation in the CNS. Phosphorylation at 2/3 N-terminal sites promote their nuclear export. We investigated whether non-canonical signaling routes to Class IIa HDAC export exist because of their association with the co-repressor Silencing Mediator Of Retinoic And Thyroid Hormone Receptors (SMRT). We found that, while HDAC5 and HDAC4 mutants lacking their N-terminal phosphorylation sites (HDAC4(MUT), HDAC5(MUT)) are constitutively nuclear, co-expression with SMRT renders them exportable by signals that trigger SMRT export, such as synaptic activity, HDAC inhibition, and Brain Derived Neurotrophic Factor (BDNF) signaling. We found that SMRT's repression domain 3 (RD3) is critical for co-shuttling of HDAC5(MUT), consistent with the role for this domain in Class IIa HDAC association. In the context of BDNF signaling, we found that HDAC5(WT), which was more cytoplasmic than HDAC5(MUT), accumulated in the nucleus after BDNF treatment. However, co-expression of SMRT blocked BDNF-induced HDAC5(WT) import in a RD3-dependent manner. In effect, SMRT-mediated HDAC5(WT) export was opposing the BDNF-induced HDAC5 nuclear accumulation observed in SMRT's absence. Thus, SMRT's presence may render Class IIa HDACs exportable by a wider range of signals than those which simply

Reações de Etanol com CO/H2 na Presença do Sistema Catalítico Ru(acac)3/I-

The hydrocarbonylation reaction of ethanol with a CO/H2 mixture assisted by Ru(acac)3/iodide was investigated. Bronsted and Lewis acids and iodides salt were used as homogeneous promoters. The etherification reaction was the main reaction under typical acidic conditions of the catalytic system. When a hydrocarbon solvent (toluene) was added to the initial reaction, the alcohol conversion and the carbonylation products were increased. The catalytic activity of the Bronsted acids (conv. EtOH = 71-92%) was higher than that of the Lewis acids promoters (conv. EtOH = 65-85%). The salt present the lower catalytic activity among the promoters used. The long time reaction carried out with ethanol showed an increase of the product selectivity of the homologation and carbonylation reactions while the etherification reaction selectivity decreased. The recycled ether led to 60-65% ethanol conversion to C5 and C6 products. The main catalytic species are H+[Ru(CO)3I3]-, [HRu3(CO)11]- and [HRu(CO)4]-. The first one is active in the carbonylation and homologation reactions of alcohols while the two others take part only in the homologation reaction.