Une délicate rencontre entre savoirs autochtones "experts" : enjeux politiques interculturelles dans le domaine de la prévention de la violence à l'égard des femmes kichwa en Amazonie équatorienne

Cette thèse porte sur l'élaboration et la mise en pratique de politiques interculturelles dans le champ de la santé internationale, en se basant sur une ethnographie d'un programme de préven¬tion de la violence de genre dans le canton de Loreto, en Amazonie équatorienne, mis en place par la Croix-Rouge suisse et aujourd'hui géré de concert avec l'Etat équatorien et une organisation kichwa locale. Suivant une approche qui fait varier les échelles d'analyses pour articuler le niveau local, national et international, elle met en évidence les lieux d'intersection et les hiatus entre l'idéal d'interculturalité tel qu'il est conçu «par le haut» et les pratiques qui sont mises en oeuvre au quotidien par des professionnels de la santé et du développement métis équatoriens. Elle révèle ainsi qu'au-delà de l'idéal du respect des « différences culturelles autochtones » et de la symétrie entre les « cultures », les discours et les pratiques de ces professionnels consistent en une entreprise de normalisation et de moralisation des comportements des destinataires kichwa en matière de rapports de genre. Pour affiner ces analyses et dépasser une approche critique de la santé publique, cette thèse explore également les représentations et les pratiques des destinataires - femmes agents de santé et « bénéficiaires » kichwa du programme - en matière de violence et de rapports de genre. Elle montre ainsi que le transfert de normes et de valeurs via la santé publique fait l'objet de mul¬tiples processus d'appropriations, et explore les différentes d'interprétations, de négociations et d'instrumentalisations de la part des destinataires, tant au niveau individuel que collectif. -- Intercultural politics and the prevention of violence against kichwa women in the Ecuadorian Amazon This PhD thesis focuses on the development and application of intercultural policies in the field of international health. It is drawn on an ethnographic fieldwork conducted in canton Loreto, in the Ecuadorian Amazon, about a gender violence prevention program which was set up by the Swiss Red Cross and which is now managed in cooperation with the Ecuadorian State and a local kichwa organization. Following a multiple-scale analysis in order to articulate the local, national and international dynamics, it highlights the intersections and the gaps between, on the one hand, the the institutional prescriptions about the ideal of interculturality and on the other hand, the daily practices of Ecuadorian mestizo health and development profesionals. It reveals that beyond the ideal of respect for «indigenous cultural differences» and of symmetry between «cultures», the discourses and practices of these professionals consist of a normalizing and moralizing enter¬prise concerning the gendered and, more broadly, social behaviors of kichwa «beneficiaries». In order to refine the analysis and to go beyond a critical approach of public health, this thesis also explores the violence and gender relations representations and practices of kichwa women health workers and «beneficiaries», men and women. Thus it shows that the transfer of norms via public health is the subject of multiple processes of appropriation, interpretation, negotiation and instru¬mentalisation both on individual and collective levels by the «beneficiaries».

Signs of a vector's adaptive choice: on the evasion of infectious hosts and parasite-induced mortality

Laboratory and field experiments have demonstrated in many cases that malaria vectors do not feed randomly, but show important preferences either for infected or non-infected hosts. These preferences are likely in part shaped by the costs imposed by the parasites on both their vertebrate and dipteran hosts. However, the effect of changes in vector behaviour on actual parasite transmission remains a debated issue. We used the natural associations between a malaria-like parasite Polychromophilus murinus, the bat fly Nycteribia kolenatii and a vertebrate host the Daubenton's bat Myotis daubentonii to test the vector's feeding preference based on the host's infection status using two different approaches: 1) controlled behavioural assays in the laboratory where bat flies could choose between a pair of hosts; 2) natural bat fly abundance data from wild-caught bats, serving as an approximation of realised feeding preference of the bat flies. Hosts with the fewest infectious stages of the parasite were most attractive to the bat flies that did switch in the behavioural assay. In line with the hypothesis of costs imposed by parasites on their vectors, bat flies carrying parasites had higher mortality. However, in wild populations, bat flies were found feeding more based on the bat's body condition, rather than its infection level. Though the absolute frequency of host switches performed by the bat flies during the assays was low, in the context of potential parasite transmission they were extremely high. The decreased survival of infected bat flies suggests that the preference for less infected hosts is an adaptive trait. Nonetheless, other ecological processes ultimately determine the vector's biting rate and thus transmission. Inherent vector preferences therefore play only a marginal role in parasite transmission in the field. The ecological processes rather than preferences per se need to be identified for successful epidemiological predictions.

Qualitative, quantitative and temporal study of cutting agents for cocaine and heroin over 9 years

Forensic laboratories mainly focus on the qualification and the quantitation of the illicit drug under analysis as both aspects are used for judiciary purposes. Therefore, information related to cutting agents (adulterants and diluents) detected in illicit drugs is limited in the forensic literature. This article discusses the type and frequency of adulterants and diluents detected in more than 6000 cocaine specimens and 3000 heroin specimens, confiscated in western Switzerland from 2006 to 2014. The results show a homogeneous and quite unchanging adulteration for heroin, while for cocaine it could be characterised as heterogeneous and relatively dynamic. Furthermore, the results indicate that dilution affects more cocaine than heroin. Therefore, the results provided by this study tend to reveal differences between the respective structures of production or distribution of cocaine and heroin. This research seeks to promote the systematic analysis of cutting agents by forensic laboratories. Collecting and processing data related to the presence of cutting agents in illicit drug specimens produces relevant information to understand and to compare the structure of illicit drug markets.

Investigation and data adaptive analysis of CARS spectra

In this diploma work advantages of coherent anti-Stokes Raman scattering spectrometry (CARS) and various methods of the quantitative analysis of substance structure with its help are considered. The basic methods and concepts of the adaptive analysis are adduced. On the basis of these methods the algorithm of automatic measurement of a scattering strip size of a target component in CARS spectrum is developed. The algorithm uses known full spectrum of target substance and compares it with a CARS spectrum. The form of a differential spectrum is used as a feedback to control the accuracy of matching. To exclude the influence of a background in CARS spectra the differential spectrum is analysed by means of its second derivative. The algorithm is checked up on the simulated simple spectra and on the spectra of organic compounds received experimentally.

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014.

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma.

Epidemiology and injury patterns of patients consulting following assault by nightclub security agents in a university hospital emergency service and an associated specialised forensic consultation

Introduction: The Violence Medical Unit (VMU), a specialised forensic medical consultation, was created at the Lausanne university Hospital in 2006. All patients consulting at the ED for interpersonal violencerelated injury are referred to the VMU, which provides forensic documentation of the injury and referral to the relevant community based victim-support organisations within 48 hours of the ED visit. This frees the ED medical staff from forensic injury documentation and legal/social referral, tasks for which they lack both time and training. Among community violence, assaults by nightclub security agents against patrons have increased from 6% to 10% between 2007 and 2009. We set out to characterise the demographics, assault mechanisms, subsequent injuries, prior alcohol intake and ED & VMU costs incurred by this group of patients. Methods: We retrospectively included all patients consulting at the VMU due to assault by nightclub security agents from January 2007 to December 2009. Data was obtained from ED & VMU medical, nursing and administrative records. Results: Our sample included 70 patients, of which 64 were referred by the CHUV ED. The victims were typically young (median age 29) males (93%). 77% of assaults occurred on the weekend between 12 PM and 4 AM, and 73% of the victims were under the influence of alcohol. 83% of the patients were punched, kicked and/or head-butted; 9% had been struck with a blunt instrument. 80% of the injuries were in the head and neck area and 19% of the victims sustained fractures. 21% of the victims were prescribed medical leave. Total ED & VMU costs averaged 1048 SFr. Conclusion: Medical staff treating this population of assault victims must be aware of the assault mechanisms and injury patterns, in particular the high probability of fractures, in order to provide adequate diagnosis and care. Associated inebriation mandates liberal use of radiology, as delayed or missed diagnosis may have medical, medicolegal and legal implications. Emergency medical services play an important role in detecting and reporting of such incidents. Centralised management of the forensic documentation facilitates referral to victim support organisations and epidemiological data collection. Magnitudes and trends of the different types of violence can be determined, and this information can be then impact public safety management policies.

Additive effects of rapamycin and aspirin on dendritic cell allostimulatory capacity.

Acting as antigen presenting cells, mature dendritic cells (DCs) initiate both innate and adaptive alloimmune responses. However, immature DCs are weak immunostimulators and mediate tolerogenic effects under certain conditions. Tolerogenic activities of immature DCs can be enhanced by pharmacological agents. Here, we compared pharmacological DC preconditioning with rapamycin and aspirin, applied alone or in combination, on LPS-induced DC maturation and T-cell allostimulatory capacity. Preconditioning with aspirin but not rapamycin tended to reduce the number of mouse bone marrow-derived immature DCs expressing CD40 and major histocompatibility complex class II molecules upon LPS stimulation. Conversely, DC preconditioning with rapamycin, but not aspirin, reduced T-cell alloproliferative responses. A combination of rapamycin and aspirin was more effective than either drug applied alone with respect to inhibition of T-cell alloproliferation. The two agents in combination reduced numbers of CD4(+)IFN-γ(+) Th1 and CD4(+)IL-17(+) Th17 effector cells while maintaining Foxp3(+) regulatory T cells. These results suggest aspirin may moderately enhance rapamycin-mediated inhibition of DC allostimulatory capacity.

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.

Historical Hallmarks of Anticoagulation and Antiplatelet Agents.

Thrombosis is a well known phenomenon among physicians since antiquity. A variety of peculiar agents, such as leeches and bark, were used to prevent it. Hirudin was used during the 19th century. The next eon, heparin, strepokinase, urokinase, TPA, dicumarol, warfarin, aspirin, ticlopidine, Clopidogrel, SSHA and SP54 provoked huge advances in anticoagulation. During 21st century with the use of fondaparinux, dabigatran, rivaroxaban and Ticagrelor antithrombotic prevention and therapeutic interaction entered an era of medical challenges. Although the risk after a thrombotic episode is now highly reduced, blood clots still present damaging or even lethal consequences in human organisms and further research is strongly recommended.

Genomic evidence for adaptive inversion clines in Drosophila melanogaster.

Clines in chromosomal inversion polymorphisms-presumably driven by climatic gradients-are common but there is surprisingly little evidence for selection acting on them. Here we address this long-standing issue in Drosophila melanogaster by using diagnostic single nucleotide polymorphism (SNP) markers to estimate inversion frequencies from 28 whole-genome Pool-seq samples collected from 10 populations along the North American east coast. Inversions In(3L)P, In(3R)Mo, and In(3R)Payne showed clear latitudinal clines, and for In(2L)t, In(2R)NS, and In(3R)Payne the steepness of the clinal slopes changed between summer and fall. Consistent with an effect of seasonality on inversion frequencies, we detected small but stable seasonal fluctuations of In(2R)NS and In(3R)Payne in a temperate Pennsylvanian population over 4 years. In support of spatially varying selection, we observed that the cline in In(3R)Payne has remained stable for >40 years and that the frequencies of In(2L)t and In(3R)Payne are strongly correlated with climatic factors that vary latitudinally, independent of population structure. To test whether these patterns are adaptive, we compared the amount of genetic differentiation of inversions versus neutral SNPs and found that the clines in In(2L)t and In(3R)Payne are maintained nonneutrally and independent of admixture. We also identified numerous clinal inversion-associated SNPs, many of which exhibit parallel differentiation along the Australian cline and reside in genes known to affect fitness-related traits. Together, our results provide strong evidence that inversion clines are maintained by spatially-and perhaps also temporally-varying selection. We interpret our data in light of current hypotheses about how inversions are established and maintained.

Adaptive optimization schemes for mobile VoIP applications Battery life and call quality aspects

In this thesis programmatic, application-layer means for better energy-efficiency in the VoIP application domain are studied. The work presented concentrates on optimizations which are suitable for VoIP-implementations utilizing SIP and IEEE 802.11 technologies. Energy-saving optimizations can have an impact on perceived call quality, and thus energy-saving means are studied together with those factors affecting perceived call quality. In this thesis a general view on a topic is given. Based on theory, adaptive optimization schemes for dynamic controlling of application's operation are proposed. A runtime quality model, capable of being integrated into optimization schemes, is developed for VoIP call quality estimation. Based on proposed optimization schemes, some power consumption measurements are done to find out achievable advantages. Measurement results show that a reduction in power consumption is possible to achieve with the help of adaptive optimization schemes.

New antagonist agents of neuropeptide y receptors

In the CNS, NPY has been implicated in obesity and feeding, endocrine function and metabolism. Potent and selective rNPY antagonists will be able to probe the merits of this approach for the treatment of obesity. We report the synthesis and preliminary evaluation of some hydrazide derivatives as antagonists of rNPY.