Swiss School of Archaeology in Greece
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Free-running 5D whole-heart MRI for isotropic cardiac function measurements at 3T without contrast agents.
No full textTo optimize and characterize an interrupted 5D free-running framework at 3 T for detailed cardiac function assessment without the use of breath holding or contrast agents.
A free-running 3D radial gradient echo sequence was periodically interrupted with a preparation and a recovery module to optimize native blood-to-myocardium contrast at 3 T. Lipid signal was suppressed using a numerically optimized water-excitation RF pulse to reduce lipid streaking artifacts and to improve overall image quality. Optimal acquisition parameters were established for a 5-min scan time using extended phase graph simulations. A compressed sensing-based reconstruction incorporating cardiac and respiratory inter-bin deformation fields was employed to generate 5D images of the whole heart. The sharpness and contrast between the left ventricular blood pool and myocardium, along with the functional measurements of the left ventricle from the 5D datasets, were compared to routine 2D cine imaging in 16 healthy volunteers and three patients referred for clinically indicated CMR.
The proposed method resulted in lower contrast vs. and sharpness vs. , but enabled similar left-ventricle ejection fraction assessment , limits of , intraclass correlation with high reproducibility compared to 2D cine.
The proposed contrast-free, interrupted free-running 5D imaging provides left ventricular functional assessments comparable to 2D cine at 3 T, while offering an improved patient experience through shorter scan times and free breathing
No meta-analytical effect of economic inequality on well-being or mental health
No full textExposure to economic inequality is widely thought to erode subjective well-being and mental health, which carries important societal implications. However, existing studies face reproducibility issues, and theory suggests that inequality only affects individuals in disadvantaged contexts. Here we present a meta-analysis of 168 studies using multilevel data (11,389,871 participants from 38,335 geographical units) identified across 10 bibliographical databases (2000–2022). Contrary to popular narratives, random-effects models showed that individuals in more unequal areas do not report lower subjective well-being (standardized odds ratio (OR_+0.05) = 0.979, 95% confidence interval = 0.951–1.008). Moreover, although inequality initially seemed to undermine mental health, the publication-bias-corrected association was null (OR_+0.05 = 1.019; 0.990–1.049). Meta-analytical effects were smaller than the smallest effect of interest, and specification curve analyses confirmed these results across ≈95% of 768 alternative models. When assessing study quality and certainty of evidence using ROBINS-E and GRADE criteria, ROBINS-E rated 80% of studies at high risk of bias, and GRADE assigned greater certainty to the null effects than to the negative effects. Meta-regressions revealed that the adverse association between inequality and mental health was confined to low-income samples. Moreover, machine-learning analyses indicated that the association with well-being was negative in high-inflation contexts but positive in low-inflation contexts. These moderation effects were replicated using Gallup World Poll data (up to 2 million participants). These findings challenge the view that economic inequality universally harms psychological health and can inform public health policy
De l’autopsie au jugement : Conclusion médico-légale vs Interprétation juridique
No full textEn cas de mort suspecte, une autopsie médico-légale doit être ordonnée par un ministère public. Cependant, une telle mort peut uniquement être suspectée s'il existe des indices visuels de l’intervention d’une tierce personne. Pour un médecin qui constate le décès, il est difficile de déterminer, juste en faisant un simple examen du cadavre, s'il s'agit d'une mort naturelle, d'un accident, d'un suicide ou d'un homicide. C’est souvent uniquement après l’autopsie que l’on peut répondre à la question d’une éventuelle intervention d’une tierce personne. Cependant, l’interprétation du médecin légiste doit encore être soumise à l’examen de la justice pour être évaluée.
Ainsi, ce travail a pour but de comprendre les liens et les influences que pourraient avoir les constatations médico-légales faites par le médecin légiste sur les verdicts des tribunaux durant la période de 2008 à 2018 dans les cantons romands de Suisse (Genève, Vaud, Fribourg, Valais, Neuchâtel et le Jura).
Dans un premier temps, nous avons sélectionné tous les cas d’homicides volontaires qui ont été traités par le CURML (Centre universitaire romand de médecine légale) entre 2008 et 2018 pour en faire une analyse statistique et établir des tendances.
Dans un second temps, nous nous sommes procurés les verdicts dans les différents tribunaux où les cas d’homicides volontaires que nous avions sélectionnés avaient été jugés, afin de mettre en corrélation les données du CURML avec ces verdicts.
Enfin, l'étude met en évidence le lien complexe entre les conclusions médico-légales, la qualification juridique de meurtre ou assassinat et la sévérité de la peine prononcée. En effet, nos résultats suggèrent un lien entre certaines constatations médico-légales telles que la capacité d’agir, la présence de lésions de défense et la peine. Cependant, ces différents liens sont extrêmement difficiles à établir principalement à cause de la multiplicité des facteurs qui ne relèvent pas de l’apport du médecin-légiste dans l’affaire et qui sont utilisés par le juge pour fixer une peine
Discovering Society, Inventing Sociology. Sieyès and the Revolutionary Origins of the Science of Society
No full textProton pump inhibitor exposure, trabecular bone score, and BMD: a registry-based cohort study.
No full textProton pump inhibitors (PPI) are widely prescribed medications. Proton pump inhibitors exposure may be associated with lower trabecular bone score (TBS), but has not shown a consistent effect on BMD. We hypothesized that abdominal obesity, which is associated with both gastroesophageal disease and PPI use, could confound the relationship between PPI use and TBS. We assessed the effect of PPI use on TBS (primary measurement) and BMD (secondary measurements) before and after adjustment for sagittal abdominal diameter (SAD), a DXA-derived measure of abdominal soft-tissue thickness. The study population comprised 60 930 individuals (90.3% women, mean age 65.7 yr) that included 11 340 (18.6%) with PPI use in the preceding 12 mo. PPI exposure was categorized from medication persistence ratio (MPR) as non-use (referent), minimal (MPR 0.01-0.25), mild (MPR 0.26-0.5), moderate (MPR 0.51-0.75), and high use (MPR 0.76-1). When logistic regression models were minimally adjusted for age, sex, and scanner, increasing PPI use versus non-use was associated with progressively increasing odds ratios (ORs) for TBS in the lowest tertile (minimal 1.11 [95% CI 1.02-1.22], mild 1.18 [1.04-1.34], moderate 1.34 [1.17-1.53], high 1.41 [1.31-1.52]) but inversely with osteoporotic BMD (minimal 0.97 [0.89-1.06], mild 0.85 [0.75-0.97], moderate 0.82 [0.72-0.94]), and high 0.76 [0.70-0.82]). Sagittal abdominal diameter was greater in PPI users than non-users. After further adjustment for SAD, PPI use was not associated with lower TBS or BMD. Similar patterns were seen in men and women, and for longer durations of PPI use. Among 4742 with a second DXA (mean interval 3.4 yr), PPI use was not associated with more rapid TBS or BMD loss compared to non-users. In conclusion, PPI use is associated with greater SAD, an indicator of abdominal obesity. SAD and other clinical variables have a confounding effect on TBS and BMD measurements. When fully adjusted, PPI exposure did not significantly decrease TBS or BMD.© The Author(s) 2025. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research
Des chiffres ‘pour tarir […] les sources du crime’ : la construction des statistiques pénitentiaires (Suisse, 1889-1910)
No full textGemistocytic tumor cells programmed for glial scarring characterize T cell confinement in IDH-mutant astrocytoma.
No full textIsocitrate dehydrogenase 1/2 mutant (IDHmt) astrocytoma is considered a T cell-deprived tumor, yet little is known regarding the phenotypes underlying T cell exclusion. Using bulk, single nucleus and spatial RNA and protein profiling, we demonstrate that a distinct spatial organization underlies T cell confinement to the perivascular space (T cell cuff) in IDHmt astrocytoma. T cell cuffs are uniquely characterized by a high abundance of gemistocytic tumor cells (GTC) in the surrounding stroma. Integrative analysis shows that GTC-high tumors are enriched for lymphocytes and tumor associated macrophages (TAM) and express immune cell migration and activation programs. Specifically, GTCs constitute a distinct sub-cluster of the astrocyte-like tumor cell state that co-localizes with immune reactive TAMs. Neighboring GTCs and TAMs express receptor-ligand pairs characteristic of reactive astrogliosis and glial scarring, such as SPP1/CD44 and IL-1β/IL1R1. Collectively, we reveal that T cell confinement in IDHmt astrocytomas associates with GTC-TAM networks that mimic glial scarring mechanisms
Gute Rechtsetzung - Ein Kommentar unter besonderer Berücksichtigung des Lobbyings privater Akteure
No full textIdentification and characterization of new regulators in endolysosomal TLR biogenesis and signalling
No full textSensing of nucleic acids by endolysosomal Toll-like receptors (TLRs) is essential for triggering host defense responses. Upon ligand engagement, TLR7-9 recruits adaptor proteins to activate NF-κB, MAPK, and IRF pathways, leading to the production of pro-inflammatory cytokines and type I interferon (IFN). Dysregulation of TLR7/9 signaling, leading to IRF5 overactivation, has been implicated in inflammatory and autoimmune diseases such as systemic lupus erythematosus (SLE). Despite the established importance of TLR signaling for immune responses and SLE, the detailed regulatory network controlling TLR7/9-induced responses remains incompletely understood. Therefore, this thesis aims to better define the molecular mechanisms regulating the TLR7/9-IRF5 signaling pathway. We previously identified the TASL protein as the fourth innate immune adaptor interacting with SLC15A4 at the endolysosomes, required for TLR7/9-induced IRF5 activation. While the SLC15A4-TASL complex plays a crucial role in this pathway, several unresolved questions regarding its regulation and biological relevance remain and were addressed in the first part of this thesis. Here, we demonstrate that the main function of SLC15A4 is to act as a scaffold to recruit TASL, whilst its transporter function is dispensable to anchor it to endolysosomes. We further show that SLC15A4 binds TASL when it adopts a cytosol-open conformation. Importantly, this interaction can be chemically targeted. We identified the compound C5/Feeblin, which binds and stabilizes SLC15A4 in an outward-facing conformation incompatible with TASL binding. As a result, TASL is degraded, leading to specific impairment of IRF5 activation and downstream cytokine production. The potential SLC15A4-TASL inhibition is particularly relevant, as we also demonstrate that the complex is essential across immune cell types for TLR7/9 responses in vitro and in vivo, as well as for antiviral immunity and the pathogenesis of SLE. Additionally, we provide insights into how phosphorylation and interaction with co-chaperones modulate TASL stability and activity. In the second part of the thesis, we explore additional regulatory mechanisms of TLR7/9 signaling independent from the SLC15A4-TASL complex. We identify CCDC134 as a novel regulator of TLR biogenesis and responses. Located in the ER, CCDC134 binds and stabilizes the TLR chaperone Gp96, ensuring its proper folding and trafficking. Deletion of CCDC134 leads to Gp96 hyperglycosylation and subsequent ER-associated protein degradation (ERAD)-mediated clearance, impairing the folding, trafficking and signaling of both plasma membrane and endolysosomal TLRs. Together, these findings uncover important regulators of TLR biogenesis and signaling, providing a deeper molecular understanding of innate immune responses and offering valuable insights for the development of targeted therapies in SLE and other disorders