Centre Alexandre Koyré

The Anthropocene, in which humankind has become a geological force, is a major scientific proposal; but it also means that the conceptions of the natural and social worlds on which sociology, political science, history, law, economics and philosophy rest are called into question.
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\nThe Anthropocene and the Global Environmental Crisis captures some of the radical new thinking prompted by the arrival of the Anthropocene and opens up the social sciences and humanities to the profound meaning of the new geological epoch, the ‘Age of Humans’. Drawing on the expertise of world-recognised scholars and thought-provoking intellectuals, the book explores the challenges and difficult questions posed by the convergence of geological and human history to the foundational ideas of modern social science.
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\nIf in the Anthropocene humans have become a force of nature, changing the functioning of the Earth system as volcanism and glacial cycles do, then it means the end of the idea of nature as no more than the inert backdrop to the drama of human affairs. It means the end of the ‘social-only’ understanding of human history and agency. These pillars of modernity are now destabilised. The scale and pace of the shifts occurring on Earth are beyond human experience and expose the anachronisms of ‘Holocene thinking’. The book explores what kinds of narratives are emerging around the scientific idea of the new geological epoch, and what it means for the ‘politics of unsustainability’.

BACKGROUND AND PURPOSE: Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. METHODS: Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype. RESULTS: Common variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5×10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (PIS=1.62×10(-7)) and ABO (PIS=2.6×10(-4)), as well as at HDAC9 (PLAS=2.32×10(-12)), 9p21 (PLAS=3.70×10(-6)), RAI1-PEMT-RASD1 (PLAS=2.69×10(-5)), EDNRA (PLAS=7.29×10(-4)), and CYP17A1-CNNM2-NT5C2 (PLAS=4.9×10(-4)). CONCLUSIONS: Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.

This essay traces the parallel, but unrelated, evolution of two sets of reactions to traditional idealist history of science in a world-historical context. While the scholars who fostered the postcolonial approach, in dealing with modern science in the non-West, espoused an idealist vision, they nevertheless stressed its political and ideological underpinnings and engaged with the question of its putative Western roots. The postidealist history of science developed its own vision with respect to the question of the global spread of modern science, paying little heed to postcolonial debates. It then proposes a historiographical approach developed in large part by historians of South Asian politics, economics, and science that, without compromising the preoccupations of each of the two groups, could help construct a mutually comprehensible and connected framework for the understanding of the global workings of the sciences.

Blood flow produces mechanical frictional forces, parallel to the blood flow exerted on the endothelial wall of the vessel, the so-called wall shear stress (WSS). WSS sensing is associated with several vascular pathologies, but it is first a physiological phenomenon. Endothelial cell sensitivity to WSS is involved in several developmental and physiological vascular processes such as angiogenesis and vascular morphogenesis, vascular remodeling, and vascular tone. Local conditions of blood flow determine the characteristics of WSS, i.e., intensity, direction, pulsatility, sensed by the endothelial cells that, through their effect of the vascular network, impact WSS. All these processes generate a local-global retroactive loop that determines the ability of the vascular system to ensure the perfusion of the tissues. In order to account for the physiological role of WSS, the so-called shear stress set point theory has been proposed, according to which WSS sensing acts locally on vessel remodeling so that WSS is maintained close to a set point value, with local and distant effects of vascular blood flow. The aim of this article is (1) to review the existing literature on WSS sensing involvement on the behavior of endothelial cells and its short-term (vasoreactivity) and long-term (vascular morphogenesis and remodeling) effects on vascular functioning in physiological condition; (2) to present the various hypotheses about WSS sensors and analyze the conceptual background of these representations, in particular the concept of tensional prestress or biotensegrity; and (3) to analyze the relevance, explanatory value, and limitations of the WSS set point theory, that should be viewed as dynamical, and not algorithmic, processes, acting in a self-organized way. We conclude that this dynamic set point theory and the biotensegrity concept provide a relevant explanatory framework to analyze the physiological mechanisms of WSS sensing and their possible shift toward pathological situations.

Objectives: To identify predictive factors for irreversible transmural intestinal necrosis (ITIN) in acute mesenteric ischemia (AMI) and establish a risk score for ITIN. Methods: This single-center prospective cohort study was performed between 2009 and 2015 in patients with AMI. The primary outcome was the occurrence of ITIN, confirmed by specimen analysis in patients who underwent surgery. Patients who recovered from AMI with no need for intestinal resection were considered not to have ITIN. Clinical, biological and radiological data were compared in a Cox regression model. Results: A total of 67 patients were included. The origin of AMI was arterial, venous, or non-occlusive in 61%, 37%, 2% of cases, respectively. Intestinal resection and ITIN concerned 42% and 34% of patients, respectively. Factors associated with ITIN in multivariate analysis were: organ failure (hazard ratio (HR): 3.1 (95% confidence interval (CI): 1.1–8.5);P=0.03), serum lactate levels >2 mmol/l (HR: 4.1 (95% CI: 1.4–11.5);P=0.01), and bowel loop dilation on computerized tomography scan (HR: 2.6 (95% CI: 1.2–5.7);P=0.02). ITIN rate increased from 3% to 38%, 89%, and 100% in patients with 0, 1, 2, and 3 factors, respectively. Area under the receiver operating characteristics curve for the diagnosis of ITIN was 0.936 (95% CI: 0.866–0.997) depending on the number of predictive factors. Conclusions: We identified three predictive factors for irreversible intestinal ischemic injury requiring resection in the setting of AMI. Close monitoring of these factors could help avoid unnecessary laparotomy, prevent resection, as well as complications due to unresected necrosis, and possibly lower the overall mortality.

Transformative adaptation will be increasingly important to effectively address the impacts of climate change and other global drivers on social-ecological systems. Enabling transformative adaptation requires new ways to evaluate and adaptively manage trade-offs between maintaining desirable aspects of current social-ecological systems and adapting to major biophysical changes to those systems. We outline such an approach, based on three elements developed by the Transformative Adaptation Research Alliance (TARA): (1) the benefits of adaptation services; that sub-set of ecosystem services that help people adapt to environmental change; (2) The values-rules-knowledge perspective (vrk) for identifying those aspects of societal decision-making contexts that enable or constrain adaptation and (3) the adaptation pathways approach for implementing adaptation, that builds on and integrates adaptation services and the vrk perspective. Together, these elements provide a future-oriented approach to evaluation and use of ecosystem services, a dynamic, grounded understanding of governance and decision-making and a logical, sequential approach that connects decisions over time. The TARA approach represents a means for achieving changes in institutions and governance needed to support transformative adaptation.

Depuis vingt ans, le problème climatique s’est hissé au sommet de l’agenda mondial, et un processus multilatéral s’est mis en place pour y répondre. Or, les concentrations de gaz à effet de serre dans l’atmosphère, responsables des dérèglements climatiques, ont atteint un niveau record en 2013. Comment apprécier le bilan de ces négociations ? Revenant sur le traitement politique du changement climatique, du protocole de Kyoto à aujourd’hui, les auteurs proposent une analyse de ces enjeux et d’une gouvernance qui suscite autant d’attentes qu’elle crée de désillusions. Est-il possible de changer de paradigme, alors que le monde connaît des accélérations majeures et se voit confronté à de multiples crises ? Dans quel cadre repenser le défi climatique pour y faire face et l’inscrire dans le champ des futurs ? Une référence sur le changement climatique et les questions stratégiques qu’il pose : rapports entre science et politique et rôle des experts, évolution de la géopolitique du climat, transition énergétique en Europe, aux États-Unis et dans les grands pays émergents, articulations entre problème climatique et globalisation, entre adaptation et développement.

Although brain neuroinflammation may play an instrumental role in the pathophysiology of Alzheimer's disease, its actual impact on disease progression remains controversial, being reported as either detrimental or protective. This work aimed at investigating the temporal relationship between microglial activation and clinical progression of Alzheimer's disease. First, in a large cohort of patients with Alzheimer's disease we analysed the predictive value of microglial activation assessed by 18F-DPA-714 PET imaging on functional, cognitive and MRI biomarkers outcomes after a 2-year follow-up. Second, we analysed the longitudinal progression of 18F-DPA-714 binding in patients with Alzheimer's disease by comparison with controls, and assessed its influence on clinical progression. At baseline, all participants underwent a clinical assessment, brain MRI, 11C-PiB, 18F-DPA-714 PET imaging and TSPO genotyping. Participants were followed-up annually for 2 years. At the end of the study, subjects were asked to repeat a second 18F-DPA-714-PET imaging. Initial 18F-DPA-714 binding was higher in prodromal (n = 33) and in demented patients with Alzheimer's disease (n = 19) compared to controls (n = 17). After classifying patients into slow and fast decliners according to functional (Clinical Dementia Rating change) or cognitive (Mini-Mental State Examination score decline) outcomes, we found a higher initial 18F-DPA-714 binding in slow than fast decliners. Negative correlations were observed between initial 18F-DPA-714 binding and the Clinical Dementia Rating Sum of Boxes score increase, the MMSE score loss and the progression of hippocampal atrophy. This suggests that higher initial 18F-DPA-714 binding is associated with better clinical prognosis. Twenty-four patients with Alzheimer's disease and 15 control subjects performed a second DPA-PET. We observed an increase of 18F-DPA-714 in patients with Alzheimer's disease as compared with controls (mean 13.2% per year versus 4.2%) both at the prodromal (15.8%) and at the demented stages (8.3%). The positive correlations between change in 18F-DPA-714 binding over time and the three clinical outcome measures (Clinical Dementia Rating, Mini-Mental State Examination, hippocampal atrophy) suggested a detrimental effect on clinical Alzheimer's disease progression of increased neuroinflammation after the initial PET examination, without correlation with PiB-PET uptake at baseline. High initial 18F-DPA-714 binding was correlated with a low subsequent increase of microglial activation and favourable clinical evolution, whereas the opposite profile was observed when initial 18F-DPA-714 binding was low, independently of disease severity at baseline. Taken together, our results support a pathophysiological model involving two distinct profiles of microglial activation signatures with different dynamics, which differentially impact on disease progression and may vary depending on patients rather than disease stages.

When do states acquire nuclear weapons? To address this question, a strategic theory of nuclear proliferation must take into account the security goals of all of the key actors: the potential proliferator, its adversaries, and, when present, its allies. To acquire nuclear weapons, a state must possess both the willingness and the opportunity to proliferate. Willingness requires the presence of a grave security threat against which no ally offers reliable protection. Opportunity requires that the state pursuing nuclear weapons possess high relative power vis-à-vis its adversaries or enjoy the protection of a powerful ally. Whereas a relatively weak state without a powerful ally lacks the opportunity to develop a nuclear capability, one with such an ally lacks the willingness to do so. Therefore, only powerful states or relatively weak states with allies that do not guarantee fulfillment of at least some of their key security goals will acquire the bomb. These claims are supported by the overall pattern of nuclear proliferation as well as detailed analyses of the Soviet, Iraqi, Pakistani, South Korean, and West German nuclear development cases.

OBJECTIVE: Elevated levels of plasma trimethylamine N-oxide (TMAO), the product of gut microbiome and hepatic-mediated metabolism of dietary choline and L-carnitine, have recently been identified as a novel risk factor for the development of atherosclerosis in mice and humans. The goal of this study was to identify the genetic factors associated with plasma TMAO levels. APPROACH AND RESULTS: We used comparative genome-wide association study approaches to discover loci for plasma TMAO levels in mice and humans. A genome-wide association study in the hybrid mouse diversity panel identified a locus for TMAO levels on chromosome 3 (P=2.37 × 10(-6)) that colocalized with a highly significant (P=1.07 × 10(-20)) cis-expression quantitative trait locus for solute carrier family 30 member 7. This zinc transporter could thus represent 1 positional candidate gene responsible for the association signal at this locus in mice. A genome-wide association study for plasma TMAO levels in 1973 humans identified 2 loci with suggestive evidence of association (P=3.0 × 10(-7)) on chromosomes 1q23.3 and 2p12. However, genotyping of the lead variants at these loci in 1892 additional subjects failed to replicate their association with plasma TMAO levels. CONCLUSIONS: The results of these limited observational studies indicate that, at least in humans, genes play a marginal role in determining TMAO levels and that any genetic effects are relatively weak and complex. Variation in diet or the repertoire of gut microbiota may be more important determinants of plasma TMAO levels in mice and humans, which should be investigated in future studies.

Using data from OECD economies, we show that inflation targeters suffered smaller output losses during disinflations when compared to nontargeters. We also study why some countries choose to inflation target while others do not and find that higher average inflation and smaller debt levels render the adoption of the regime more likely. Applying Heckman's procedure to control for selection bias does not alter the link between inflation targeting and less costly disinflations.

In this article, we review how two eminent Viennese system thinkers, Paul A Weiss and Ludwig von Bertalanffy, began to develop their own perspectives toward a system theory of life in the 1920s. Their work is especially rooted in experimental biology as performed at the Biologische Versuchsanstalt, as well as in philosophy, and they converge in basic concepts. We underline the conceptual connections of their thinking, among them the organism as an organized system, hierarchical organization, and primary activity. With their system thinking, both biologists shared a strong desire to overcome what they viewed as a "mechanistic" approach in biology. Their interpretations are relevant to the renaissance of system thinking in biology--"systems biology." Unless otherwise noted, all translations are our own.

Romano Antonella. La Contre-Réforme Mathématique. Constitution et diffusion d’une culture mathématique jésuite à la Renaissance (1540-1640) Rome : Ecole française de Rome, 1999. 728 p. (Bibliothèque des Écoles françaises d'Athènes et de Rome, 306)

Laurence Talairach-Vielmas explores Victorian representations of femininity in narratives that depart from mainstream realism, from fairy tales by George MacDonald, Lewis Carroll, Christina Rossetti, Juliana Horatia Ewing, and Jean Ingelow, to sensation novels by Wilkie Collins, Mary Elizabeth Braddon, Rhoda Broughton, and Charles Dickens. Feminine representation, Talairach-Vielmas argues, is actually presented in a hyper-realistic way in such anti-realistic genres as children's literature and sensation fiction. In fact, it is precisely the clash between fantasy and reality that enables the narratives to interrogate the real and re-create a new type of realism that exposes the normative constraints imposed to contain the female body. In her exploration of the female body and its representations, Talairach-Vielmas examines how Victorian fantasies and sensation novels deconstruct and reconstruct femininity; she focuses in particular on the links between the female characters and consumerism, and shows how these serve to illuminate the tensions underlying the representation of the Victorian ideal.

INTRODUCTION: Glaucoma is a sight-threatening retinal neuropathy associated with elevated intraocular pressure (IOP) due to degeneration and fibrosis of the trabecular meshwork (TM). Glaucoma medications aim to reduce IOP without targeting the specific TM pathology, Bone-marrow mesenchymal stem cells (MSCs) are used today in various clinical studies. Here, we investigated the potential of MSCs therapy in an glaucoma-like ocular hypertension (OHT) model and decipher in vitro the effects of MSCs on primary human trabecular meshwork cells. METHODS: Ocular hypertension model was performed by cauterization of 3 episcleral veins (EVC) of Long-Evans male rat eyes. MSCs were isolated from rat bone marrow, amplified in vitro and tagged with quantum dot nanocrystals. Animals were distributed as 1) MSCs group receiving 5.10(5)cells/6μl Minimum Essential Medium and 2) MEM group receiving 6μl MEM (n = 10 each). Injections were performed into the anterior chamber of 20 days-hypertensive eyes and IOP was monitored twice a week for 4 weeks. At the end of experiment, cell distribution in the anterior segment was examined in confocal microscopy on flat mounted corneas. Moreover, we tested in vitro effects of MSCs conditioned medium (MSC-CM) on primary human trabecular meshwork cells (hTM cells) using Akt activation, myosin phosphorylation and TGF-β2-dependent profibrotic phenotype in hTM cells. RESULTS: We demonstrated a rapid and long-lasting in vivo effect of MSCs transplantation that significantly reduced IOP in hypertensive eyes induced by EVC. MSCs were located to the ciliary processes and the TM. Enumeration of RGCs on whole flat-mounted retina highlighted a protective effect of MSCs on RGCs death. In vitro, MSC-CM promotes: (i) hTM cells survival by activating the antiapoptotic pathway, Akt, (ii) hTM cells relaxation as analyzed by the decrease in myosin phosphorylation and (iii) inhibition of TGF-β2-dependent profibrotic phenotype acquisition in hTM cells. CONCLUSIONS: MSCs injection in the ocular anterior chamber in a rat model of OHT provides neuroprotective effect in the glaucoma pathophysiology via TM protection. These results demonstrate that MSCs constitute promising tool for treating ocular hypertension and retinal cell degeneration.

<titre>R&#233;sum&#233;</titre>Renon&#231;ant &#224; la philosophie religieuse de l&#8217;histoire comme au dualisme de l&#8217;&#226;me et du corps, l&#8217;anthropologie europ&#233;enne des secondes Lumi&#232;res consacre l&#8217;alliance des sciences physiques et des arts du gouvernement. Le diagnostic social sacrifie &#224; la l&#233;galit&#233; formelle de la nature. L&#8217;homme est red&#233;fini comme un &#171;&#160;produit naturel&#160;&#187;, au &#171;&#160;physique&#160;&#187; comme au &#171;&#160;moral&#160;&#187;. L&#8217;urgence de son &#233;tude est incessamment rappel&#233;e. On esp&#232;re en fait h&#226;ter l&#8217;&#233;mancipation de l&#8217;humanit&#233; en approfondissant l&#8217;analyse de son rapport au monde et la marche n&#233;cessaire de sa Civilisation. Le paradigme &#171;&#160;naturaliste&#160;&#187;, fond&#233; sur la comparaison, le classement et l&#8217;approche nomoth&#233;tique des faits sociaux, acquiert vers 1800 une autorit&#233; sans pr&#233;c&#233;dent. Les anthropologues deviennent experts pour tout ce qui regarde l&#8217;investigation &#171;&#160;statistique&#160;&#187; de la condition humaine sous les diff&#233;rents climats. Il s&#8217;agit alors de comprendre les d&#233;terminismes g&#233;n&#233;raux de l&#8217;&#233;volution du genre humain, de mettre &#224; jour les ressorts cach&#233;s de sa f&#233;licit&#233;. La v&#233;rit&#233;, la moralit&#233; des actes et la conduite des affaires publiques s&#8217;y trouvent, dit-on, pareillement int&#233;ress&#233;es. La redistribution des recherches dans la d&#233;cennie 1795-1805 donne ainsi un nouvel &#233;lan &#224; la r&#233;flexion classique sur la nature humaine, sous sa triple d&#233;termination temporelle, spatiale et sociale&#160;: l&#8217;origine, la race, le progr&#232;s. Cet article propose une synth&#232;se des traits dominants de la pens&#233;e naturaliste, de ses ambitions r&#233;formatrices comme de ses contradictions fonci&#232;res.

Launched in 2019, the French Citizens' Convention for Climate (CCC) tasked 150 randomly chosen citizens with proposing fair and effective measures to fight climate change. This was to be fulfilled through an "innovative co-construction procedure", involving some unspecified external input alongside that from the citizens. Did inputs from the steering bodies undermine the citizens' accountability for the output? Did co-construction help the output resonate with the general public, as is expected from a citizens' assembly? To answer these questions, we build on our unique experience in observing the CCC proceedings and documenting them with qualitative and quantitative data. We find that the steering bodies' input, albeit significant, did not impair the citizens' agency, creativity, and freedom of choice. While succeeding in creating consensus among the citizens who were involved, this co-constructive approach, however, failed to generate significant support among the broader public. These results call for a strengthening of the commitment structure that determines how follow-up on the proposals from a citizens' assembly should be conducted.

ABSTRACT We develop a model in which customer capital depends on key talents' contribution and pure brand recognition. Customer capital guarantees stable demand but is fragile to financial constraints risk if retained mainly by talents, who tend to quit financially constrained firms, damaging customer capital. Using a proprietary, granular brand‐perception survey, we construct a firm‐level measure of the inalienability of customer capital (ICC) that captures the degree to which customer capital depends on talents. Firms with higher ICC have higher average returns, higher talent turnover, and more precautionary financial policies. The ICC‐sorted long‐short portfolio's spread comoves with financial constraints factor.

This introduction presents an overview of key concepts discussed in subsequent chapters of this book. The book explains the rethinking of the social sciences and humanities prompted by the arrival of the 'Age of Humans', an ironic moniker since modernity has supposedly been the age of humanism. It draws together scholars who have a prescient insight into the significance of the new epoch. Some critique the idea of the Anthropocene from various social science perspectives, while others argue that the Anthropocene demands a re-examination of those very social sciences. Politics in the Anthropocene is about the collision of the system Earth with the system world, traditionally conceived as the political and social organisation of the former, which served as a background for the latter. The advent of the Anthropocene challenges some established boundaries between nature and culture, between climate and politics, between natural sciences and the social sciences and humanities.

OBJECTIVE: Genome-wide association studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks. APPROACHES AND RESULTS: Using pathways (gene sets) from Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets (9889 cases/11 089 controls), nominally significant gene sets were tested for replication in a meta-analysis of 9 additional studies (15 502 cases/55 730 controls) from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication P<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix (ECM) integrity, innate immunity, axon guidance, and signaling by PDRF (platelet-derived growth factor), NOTCH, and the transforming growth factor-β/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (eg, semaphoring-regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared with random networks (P<0.001). Network centrality analysis (degree and betweenness) further identified genes (eg, NCAM1, FYN, FURIN, etc) likely to play critical roles in the maintenance and functioning of several of the replicated pathways. CONCLUSIONS: These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD.