Thérapie assistée par psychédéliques en médecine palliative

La dépression, l’anxiété et la détresse existentielle liées aux maladies terminales ont un impact majeur sur la qualité de vie despatients. Les psychédéliques apparaissent comme des catalyseurs pour l’exploration réflexive, introspective et parfois spirituelle dans le cadre d’une psychothérapie, avec des effets bénéfiques multiples potentiellement rapides et durables. La thérapie assistée par psychédéliques (TAP) combine la préparation, la prise de substances et l’intégration des expériences pour faciliter l’avènement de changements psychospirituels profonds. Malgré les obstacles méthodologiques et administratifs, l’intérêt pour cette approche novatrice continue de croître en raison de son potentiel à offrir des rémissions là où les approches conventionnelles s’avèrent peu efficaces.Depression, anxiety and existential distress associated with terminal illness have a major impact on quality of life among palliative care patients. Psychedelics are emerging as catalysts for reflective, introspective and sometimes spiritual exploration as part of psychotherapy, with potentially rapid and long-lasting multiple beneficial effects. Psychedelic-assisted psychotherapy (PAP) combines preparation, substance intake, and integration of experiences to facilitate profound psychospiritual change. Despite methodological and administrative hurdles, interest in this innovative approach continues to grow because of its potential to offer remission where conventional approaches have shown little benefits

Mechanistic Study and Development of Ni-catalyzedC(sp2)–C(sp2) Bond Forming Methodologies

The work presented in this thesis revolves around the mechanistic and the development of Ni-catalyzed processes. In 2018, our group reported a catalytic method for the synthesis of diversely 2-substituted 1,3-dienes. This work describes the synthesis of conjugated dienes via Ni-catalyzed cross coupling between a vinyl Grignard and enol phosphates. This methodology relies on the use of two complementary biphosphine-nickel complexes – [(dppe)NiCl2] and [(dmpe)NiCl2]. Nickel has been well documented for standing apart from other transition metals in d10 column due to its smaller size, lower reduction potential and lower electronegativity. Its proclivity to access a larger range of oxidation state than palladium, leads to diverse mechanistic scenarios. However, there are few examples of mechanistic studies delving into Ni-catalyzed reactions using C(sp2)–O electrophiles such as aryl ethers, aryl sulfamates, aryl esters and aryl carbonates. Examples dealing with mechanistic investigations of reactions with the vinyl counterparts of the aforementioned functions are even scarcer. The work presented in this Thesis aims at giving a deeper and finer understanding of the studied coupling. Based on supporting stoichiometric organometallic syntheses, structural analyses, reaction monitoring, radical-clock experiments and kinetic investigations, a comparative mechanistic study between the two precatalysts has been conducted. We demonstrate that the two bisphosphine-nickel complexes operate via distinct Ni(0)/Ni(II) catalytic manifolds. Nickel-catalyzed functionalization of alkynes with aryl boronic acids represents a swift gateway to the construction of value-added stereochemically defined highly substituted olefins. The work described in this Thesis deals with the development of a stereo- and regioselective Ni-catalyzed hydroarylation of enynones. Of this project branched out two new reactions. A Ni-catalyzed carbometalative cyclization of enynones with electrophile-tethered aryl boronic acids granting access to indanones scaffolds. A Ni-catalyzed hydroalkoxylation of the C≡C bond of enynones providing a way to highly substituted enol ethers. </p

Tuning Selectivity and Stability in Heteroleptic Lanthanide Adducts by Ligand Design

The terdentate ligands L10-L14 and their heteroleptic [LkLn(hfac) 3 ] complexes (Ln = La, Eu, Gd, Er, Y; H-hfac = 1,1,1,5,5,5-hexafluoropentane-2,4-dione) exhibit multifactorial correlations between the ligand’s structural frameworks, including their level of preorganization and steric congestion, and their affinities and selectivities for catching the trivalent lanthanide containers [Ln(hfac) 3 ]. The polyaromatic ligand scaffolds could be stepwise modulated via lanthanide-template synthetic strategies using intermolecular rhodium-catalyzed insertion reactions. The increasing level of preorganization along the L10→L11→L12 series leads to a duality where larger thermodynamic formation constants with lanthanides in CD2 Cl2 are accompanied by an unexpected decrease of the Ln-N affinities in the solid state, which could be assigned to a limited match between the lanthanide size and the enlarged preorganized cavities. On the contrary, a reduced stability is induced by the connection of additional methyl groups at the 1-position of the benzimidazole moieties in L13 and L1, which is accompanied by an optimization of metal-nitrogen bond lengths. This study contributes to the rational design of highly stable neutral heteroleptic lanthanide -diketonate adducts which resist dissociation in solution; a prerequisite for photophysical applications using these highly luminescent systems at the molecular level.</p

Les occupations néolithiques et de l’âge du Bronze du Domaine de Sousquière (Bouc-Bel-Air, Bouches-du-Rhône). Premiers résultats de l’opération

La fouille préventive du Domaine de Sousquière réalisée en 2018 permet de documenter une succession d’occupations de la fin du Néolithique moyen 1 à l’âge du Bronze ancien 2/3. Ces découvertes viennent s’ajouter aux vestiges mis au jour sur la commune lors d’opérations menées depuis le début des années 1990. 150 aménagements ainsi que plus de 600 artefacts céramiques et lithiques, en place ou colluvionnés, ont été étudiés sur une superficie d’environ 1300 m2. Environ un tiers des vestiges fossoyés peuvent être attribués à six séquences d’occupations de la seconde moitié du Ve millénaire au premier tiers du IIe millénaire av. J.-C., et moins d’une dizaine de structures en creux ont été mises en place à partir des IIIe-Ie s. av. J.-C

Investigation of interactions between fluids and earthquakes based on numerical modelling

The strength and sliding behaviour of faults in the upper crust are largely controlled by friction and effective stress, which is modulated by the fluid pressure. While many studies have investigated the role of friction on the earthquake cycle, relatively little effort has gone into understanding the effects linked to dynamic changes in fluid pressure. Our study aims to explore the complex interactions between long-term tectonic loading, fluid pressure, rapid fault slip and elastic stress transfer that occur during earthquakes on plane faults in two dimensions. Our models incorporate rate- and state-dependent friction and dramatic changes in the fault permeability during sliding. In some models, we have also incorporated shear heating and thermal pressurisation. Our most basic models consider slow fluid pressure generation during the interseismic period. Conversely, during an earthquakes, the permeability increase enables fluid overpressures to rapidly dissipate. This is commonly known as fault valve behaviour. In these modes, earthquakes are nucleated where fluid pressures are locally high. Ruptures are then propagated as slip pulses onto stronger parts of the fault. Our model produces a wide range of sliding velocities from rapid to slow earthquakes, which occur due to high pore pressures prior to rupture. The models also show evidence of aftershocks driven by fluid transfer along the fault plane after the main shock. Overall, we find that relatively modest fluid overpressures tend to reduce coseismic slip, stress drop, maximum sliding velocity, rupture velocity, and the earthquake recurrence time relative to ruptures in a dry crust. We show that fluids can exert an important influence on earthquakes in the crust, mostly due to modulation of the effective stress and variations in permeability and, to a lesser extent, to poroelastic coupling. For models exhibiting 'valve' behaviour, we observe complex ruptures and swarm activity associated with rising fluid pressure. In addition to 'valve' behaviour, faults are sometimes considered to actively pump fluids into or out of fault zones over the earthquake cycle. We have studied one aspect of this pumping through the incorporation of thermal pressurisation arising from shear heating. Our models show that thermal pressurisation has the effect of increasing the stress drop, coseismic slip and sliding velocity relative to pure valve models. Both pump and valve models can explain anomalously weak faults, though they are each associated with distinctly different fluid pressure and strength evolution over the seismic cycle and during rupture. Finally, in addition to studying slip dynamics we have also examined the fluid pressure fields in the Earth's crust following earthquakes. Much research has focused on post-seismic surface deformation that results from earthquake-induced fluid flow, commonly known as 'poroelastic rebound'. These studies have focused exclusively on fluid flow induced by coseismic volumetric changes in the crust. In our investigation we have studied surface deformation linked to breaching of a pressurised fault zone during rupture. Our study shows that regardless of the fault mechanism (i.e., reverse versus normal), fluid drainage induced by rupture tends to cause surface subsidence above the rupture zone after an earthquake. These observations allow us to interpret better the diversity of post-seismic deformation.</p

Sédation palliative en unité hospitalière

Une personne en fin de vie peut présenter des symptômes inconfortables devenant réfractaires à un traitement adéquat. Dans ce cas, l’instauration d’une sédation palliative est indiquée. La majorité des patients hospitalisés et sédatés décèdent en dehors d’une unité spécialisée de soins palliatifs. La sédation palliative doit pouvoir être introduite et adaptée selon les règles de bonnes pratiques. Cet article traite des processus liés à la sédation palliative en unité hospitalière.A person at the end of life may present uncomfortable symptoms becoming refractory to an adequate treatment. In this case, the initiation of palliative sedation is indicated. Most sedated inpatients die outside a specialized palliative care unit. Palliative sedation must be initiated and adapted according to the best clinical practices. This article describes the processes associated with palliative sedation in a hospital unit

Hypertension pulmonaire : comment différencier les causes fréquentes et rares ?

Pulmonary hypertension (PH) is a frequent finding. PH secondary to left heart diseases is the most prevalent form of PH. PH caused by lung diseases and/or hypoxia is the second most frequent cause. The patient should be addressed to an expert center if the PH does not seem to be secondary to a left heart disease or a lung disease, if the PH seems too severe for the underlying cardiac or pulmonary diseases or in the presence of risk factors for PH caused by rare etiologies (group 1, 4 and 5).L’hypertension pulmonaire (HTP) est une manifestation clinique fréquente. L’HTP secondaire aux cardiopathies gauches est la forme la plus prévalente. La deuxième forme la plus fréquente est l’HTP associée à une pneumopathie et/ou à une hypoxie chronique. Le patient devrait être adressé à un centre expert si l’HTP n’est pas facilement attribuable à une cardiopathie gauche ou à une pneumopathie, si l’HTP semble trop sévère pour la cardiopathie ou la pneumopathie sous-jacente ou en cas de présence de facteurs de risque pour une HTP causée par une étiologie rare (groupes 1, 4 et 5)

Évolution et impact de l’approche une seule santé (One Health) en Suisse et dans le monde

Les approches intégrées de la santé comme One Health « une seule santé » sont nécessaires pour aborder les problèmes complexes ne pouvant être résolus par une seule discipline, un seul pays comme le changement climatique, la perte de biodiversité ou la résistance aux antimicrobiens. L’Institut tropical et de santé publique suisse (Swiss TPH), l’un des pionniers internationaux en One Health avec ses partenaires en Afrique, l’Institut de santé globale de l’Université de Genève, qui a aussi adopté One Health, et d’autres activités à Berne et Zurich, font de la Suisse une plaque tournante de recherche et développement sur l’approche One Health dans le monde. Cet article résume l’évolution de cette approche en Suisse et montre à travers d’exemples sa valeur ajoutée.Integrated approaches to health such as One Health are needed to tackle complex problems that cannot be solved by a single discipline or country, such as climate change, biodiversity loss or antimicrobial resistance. The Swiss Tropical and Public Health Institute (Swiss TPH), one of the international pioneers in One Health with its African partners, the Institute of Global Health at the University of Geneva, which has also adopted One Health, and other activities in Berne and Zurich, make Switzerland a hub for One Health research and development worldwide. This article summarizes the development of the One Health approach in Switzerland, and uses examples to demonstrate its added value