Selective arterialization of a cardiac vein in a model of cardiac microangiopathy and macroangiopathy in sheep

ObjectiveSome patients with significant arteriosclerosis of the heart are not amenable to revascularization of a coronary artery because they have a combination of microangiopathy and significant macroangiopathy. We investigated the benefit of arterialization of a cardiac vein under these circumstances in an acute animal model.MethodsIn the hearts of 8 sheep, microspheres were injected into the left coronary artery; 60 minutes later, a stenosis of the left anterior descending artery was performed. After 45 minutes, retrograde venous revascularization was performed by sewing the left internal thoracic artery to the concomitant vein of the left anterior descending artery in a beating-heart technique. For flow reversal, the vein was ligated proximally to the anastomosis. The efficiency of the bypass graft was evaluated by coronary angiography and flow measurement. Cardiac output, electrocardiography, and mean arterial blood pressure were assessed in each phase of the experiment.ResultsThe ischemic state of the myocardium was confirmed by a significant decrease of cardiac output, stroke volume, and mean arterial blood pressure, and a significant elevation of the ST segment in the electrocardiography. After retrograde venous revascularization was established, cardiac output and stroke volume increased and ST elevations decreased. The grafts showed adequate flow (26.15 ± 2.08 mL/min), and reversed blood flow in the grafted vein was proved by coronary angiography.ConclusionRetrograde venous revascularization is possible and improves cardiac function in a state of acute ischemia caused by a combination of microangiopathy and macroangiopathy

Performance of the SD Bioline rapid diagnostic test as a good alternative to the detection of human African trypanosomiasis in Cameroon

Background: Case detection is essential for the management of human African trypanosomiasis (HAT), which is caused by Trypanosoma brucei gambiense. Prior to parasitological confirmation, routine screening using the card agglutination test for trypanosomiasis (CATT) is essential. Recently, individual rapid diagnostic tests (RDTs) for the serodiagnosis of HAT have been developed. Objective: The purpose of this study was to evaluate the contribution of SD Bioline HAT to the serological screening of human African trypanosomiasis in Cameroonian foci.Methods. Between June 2014 and January 2015, blood samples were collected during surveys in the foci of Campo, Yokadouma, and Fontem. The sensitivity (Se) and specificity (Sp) of SD Bioline HAT were determined using the CATT as the gold standard for the detection of specific antibodies against Trypanosoma brucei gambiense. Results: A total of 88 samples were tested: 59.1% (n=52) in Campo, 31.8% (n=28) in Yokadouma, and 9.1% (n=8) in Fontem. There were 61.4% (n=54) males and 38.4% (n=34) females, and the average age was 35.4 19.0 years. In probed foci, the overall seroprevalence was 11.4% (95% confidence interval: 6.3-19.7) with the CATT method and 18.2% (95% confidence interval: 11.5-27.2%) with the SD Bioline HAT RDT method. The SD Bioline HAT's Se and Sp were 80.0% and 89.7%, respectively. Conclusions: This study demonstrated that the overall performance of the SD Bioline HAT was comparable to that of the CATT, with high specificity in the serological detection of HAT

Comparison of outcomes of minimally invasive mitral valve surgery for posterior, anterior and bileaflet prolapse §

Abstract Objective: We sought to compare the outcomes of minimally invasive mitral valve (MV) surgery for anterior (anterior mitral leaflet, AML), posterior (posterior mitral leaflet, PML) or bileaflet (BL) MV prolapse. Methods: Between August 1999 and December 2007, 1230 patients who presented with isolated AML (n = 156, 12.7%), isolated PML (n = 672, 54.6%) or BL (n = 402, 32.7%) MV prolapse underwent minimally invasive MV surgery. The preoperative mitral regurgitation (MR) grade was 3.3 AE 0.8, left ventricular ejection fraction (LVEF) was 62 AE 12% and mean age was 58.9 AE 13.0 years; 836 patients (68.0%) were male. Mean follow-up time was 2.7 AE 2.1 years, and the follow-up was 100% complete. Results: Overall, the MV repair rate was 94.0% (1156 patients). Seventy-four patients (6.0%) received MV replacement. MV repair for PML prolapse was accomplished in 651 patients (96.9%), for AML in 142 patients (91%) and for BL in 363 patients (90.3%). Repair techniques consisted predominantly of leaflet resection and/or implantation of neochordae, combined with ring annuloplasty. Concomitant procedures were tricuspid valve surgery (n = 56), atrial fibrillation ablation (n = 286) and closure of an atrial septal defect or patent foramen ovale (PFO) (n = 89). The overall duration of cardiopulmonary bypass was 127 AE 40 min and aortic cross-clamp time was 78 AE 33 min. The mean postoperative hospital stay was 11.6 AE 9.7 days for the overall group. Early echocardiographic follow-up revealed excellent valve function in the vast majority of patients, regardless of the repair technique, with a mean MR grade of 0.3 AE 0.5. For the overall group, 5-year survival rate was 87.3% (95% CI: 83.9-90.1) and 5-year freedom from cardiac reoperation rate was 95.6% (95% CI: 94.1-96.7). The log-rank test revealed no significant difference between the three groups regarding long-term survival or freedom from reoperation. Conclusions: Minimally invasive MV repair can be achieved with excellent results. Long-term outcomes and reoperation rates for AML prolapse are not significantly different from PML or BL prolapse.

Tokenizer Choice For LLM Training: Negligible or Crucial?

The recent success of LLMs has been predominantly driven by curating the training dataset composition, scaling of model architectures and dataset sizes and advancements in pretraining objectives, leaving tokenizer influence as a blind spot. Shedding light on this underexplored area, we conduct a comprehensive study on the influence of tokenizer choice on LLM downstream performance by training 24 mono- and multilingual LLMs at a 2.6B parameter scale, ablating different tokenizer algorithms and parameterizations. Our studies highlight that the tokenizer choice can significantly impact the model's downstream performance, training and inference costs. In particular, we find that the common tokenizer evaluation metrics fertility and parity are not always predictive of model downstream performance, rendering these metrics a questionable proxy for the model's downstream performance. Furthermore, we show that multilingual tokenizers trained on the five most frequent European languages require vocabulary size increases of factor three in comparison to English. While English-only tokenizers have been applied to the training of multi-lingual LLMs, we find that this approach results in a severe downstream performance degradation and additional training costs of up to 68%, due to an inefficient tokenization vocabulary

Pour une démocratie socio-environnementale : cadre pour une plate-forme participative « transition écologique »

Contribution publiée in Penser une démocratie alimentaire Volume II – Proposition Lascaux entre ressources naturelles et besoins fondamentaux, F. Collart Dutilleul et T. Bréger (dir), Inida, San José, 2014, pp. 87-111.International audienceL’anthropocène triomphant actuel, avec ses forçages environnementaux et sociaux, est à l’origine de l’accélération des dégradations des milieux de vie sur Terre et de l’accentuation des tensions sociales et géopolitiques. Passer à un anthropocène de gestion équitable, informé et sobre vis-à-vis de toutes les ressources et dans tous les secteurs d’activité (slow anthropocene), impose une analyse préalable sur l’ensemble des activités et des rapports humains. Cette transition dite « écologique », mais en réalité à la fois sociétale et écologique, est tout sauf un ajustement technique de secteurs dits prioritaires et technocratiques. Elle est avant tout culturelle, politique et philosophique au sens propre du terme. Elle est un horizon pour des trajectoires de développement humain, pour des constructions sociales et économiques, censées redéfinir socialement richesse, bien-être, travail etc. La dénomination « transition écologique » est largement véhiculée, mais ses bases conceptuelles ne sont pas entièrement acquises ni même élaborées. Dans ce contexte, les étudiants en première année de Master BioSciences à l’Ecole Normale Supérieure (ENS) de Lyon ont préparé une première étude analytique de ce changement radical et global de société pour mieux comprendre dans quelle société ils souhaitent vivre, en donnant du sens aux activités humaines présentes et à venir. Une trentaine de dossiers sur divers secteurs d’activités et acteurs de la société ont été produits et ont servis de support à cette synthèse. Plus largement, le but est de construire un socle conceptuel et une plate-forme de travail sur lesquels les questions de fond, mais aussi opérationnelles, peuvent être posées et étudiées en permanence. Cette démarche participative est ouverte à la collectivité sur le site http://institutmichelserres.ens-lyon.fr/

Longer and better lives for patients with atrial fibrillation:the 9th AFNET/EHRA consensus conference

Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Methods and results: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. Conclusions: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field