Artículos de revistas sobre el tema "Frédéric Boyer"

Il existe un lien privilégié entre Les Écritures et l’écriture, entre le christianisme, la littérature et la poésie. En régime chrétien, La Nouvelle traduction de la Bible (Bayard 2001) est le dernier chantier d’envergure innovateur d’un point de vue biblique et littéraire. Comment ce travail a-t-il contribué à féconder les œuvres d’une génération d’écrivains comme Valère Novarina et Frédéric Boyer ? Une nouvelle vitalité du christianisme peut-elle advenir du côté de la littérature contemporaine ?

Abstract Background: Resistance to PD1/L1 immune checkpoint inhibitors (ICIs) in advanced NSCLC patients is observed in about 80% of individuals with no robust predictive biomarker yet. The PIONeeR trial (NCT03493581) aims to predict such resistances through a comprehensive multiparametric biomarkers analysis. Methodology: Among the >300 advanced NSCLC patients (pts) recruited in PIONeeR, we focused on the first 137 ≥2nd line ECOG PS0-1 pts treated with single-agent nivolumab, pembrolizumab or atezolizumab. Tumor tissue was collected at baseline and pts were re-biopsied at 6 weeks, and blood-sampled every cycle throughout the 24 weeks post C1D1. Response to PD1/L1 ICIs was assessed by RECIST 1.1 every 6 weeks. Immune contexture was characterized in tumor & blood of each pt through FACS for circulating immune cell subtypes quantification and endothelial activation, blood soluble factors dosage, dual- & multiplex IHC/digital pathology to quantify immune cells infiltrating the tumor, WES for TMB & ICI plasma dosage, leading to 331 measured biomarkers in addition to routine clinical parameters. Multivariable (MV) logistic regression was used to examine the association of each biomarker (controlled by sex, age, smoking status, histological type & PDL1+ Tumor Cells) with the risk of Early Progression (EP), i.e. within 3.5 months of treatment. Multivariable Cox regression analysis was conducted for association with PFS and OS. Results: Overall, the 137 pts were mainly male (64%), smokers (92%) and <70yrs (68%). Tumors were mainly non-squamous (79%) with >1% PDL1+ TC in 36% of the cases, and 21% of pts were still on treatment at data cut-off. Archived samples were available for 80% of pts at inclusion and re-biopsy was available in 52.9% of these cases. The median follow up was 19.8 months, 22.5% of pts did not progress at data cut-off while 62% presented EP. Tumor Cytotoxic T-cells density, especially PD1+ were lower in EP (MV OR=0.45, p=0.022); conversely, higher proportions of circulating cytotoxic T-cells and activated T-cells (HLA-DR+) were observed in EP (MV OR=3.8, p<0.001). Among other biomarkers, Tregs (MV OR=0.44, p=0.018), NK cell subsets (MV OR≤0.44, p<0.05), albumin (MV OR=0.4, p<0.01) and PDL1 TC % (MV OR=0.27, p<0.01) were decreased whereas alkaline phosphatase was increased (OR=3, p=0.018). >65% inter-pt variability was observed in plasma exposures for all ICIs, with 8-10% of pts displaying trough levels below the target engagement threshold. Data will be presented through unsupervised clustering algorithms & multi-modal supervised learning methods. Changes after 6 weeks of treatment will be analyzed to further investigate drugs mechanisms of action. Conclusion: The PIONeeR trial provides with the 1st comprehensive biomarkers’ analysis to establish predictive models of resistance in advanced NSCLC pts treated with PD1/L1 ICIs and highlights how tumor and circulating biomarkers are complementary. Citation Format: Laurent Greillier, Florence Monville, Vanina Leca, Frédéric Vely, Stephane Garcia, Joseph Ciccolini, Florence Sabatier, Gilbert Ferrani, Nawel Boudai, Lamia Ghezali, Marcellin Landri, Clémence Marin, Mourad Hamimed, Laurent Arnaud, Melanie Karlsen, Kevin Atsou, Sivan Bokobza, Pauline Fleury, Arnaud Boyer, Clarisse Audigier-Valette, Stéphanie Martinez, Hervé Pegliasco, Patrice Ray, Lionel Falchero, Antoine Serre, Nicolas Cloarec, Louisiane Lebas, Stephane Hominal, Patricia Barre, Sarah Zahi, Ahmed Frikha, Pierre Bory, Maryannick Le Ray, Lilian Laborde, Virginie Martin, Richard Malkoun, Marie Roumieux, Julien Mazieres, Maurice Perol, Eric Vivier, Sebastien Benzekry, Jacques Fieschi, Fabrice Barlesi. Comprehensive biomarkers analysis to explain resistances to PD1-L1 ICIs: The precision immuno-oncology for advanced non-small cell lung cancer (PIONeeR) trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB120.

IntroductionThe common origin of the adjective “corporeal” and the noun “corpse” in the Latin root corpus points to the value of mortuary practices for investigating how the human body is objectified. In post-mortem rituals, the body—formerly the manipulator of objects—becomes itself the object that is manipulated. Thus, these funerary rituals provide a type of double reflexivity, where the object and subject of manipulation can be used to reciprocally illuminate one another. To this extent, any consideration of corporeality can only benefit from a discussion of how the body is objectified through mortuary practices. This paper offers just such a discussion with respect to a selection of two contrasting mortuary practices, in the context of the prehistoric past and the Classical Era respectively. At the most general level, we are motivated by the same intellectual impulse that has stimulated expositions on corporeality, materiality, and incarnation in areas like phenomenology (Merleau-Ponty 77–234), Marxism (Adorno 112–119), gender studies (Grosz vii–xvi), history (Laqueur 193–244), and theology (Henry 33–53). That is to say, our goal is to show that the body, far from being a transparent frame through which we encounter the world, is in fact a locus where historical, social, cultural, and psychological forces intersect. On this view, “the body vanishes as a biological entity and becomes an infinitely malleable and highly unstable culturally constructed product” (Shilling 78). However, for all that the cited paradigms offer culturally situated appreciations of corporeality; our particular intellectual framework will be provided by cognitive science. Two reasons impel us towards this methodological choice.In the first instance, the study of ritual has, after several decades of stagnation, been rewarded—even revolutionised—by the application of insights from the new sciences of the mind (Whitehouse 1–12; McCauley and Lawson 1–37). Thus, there are good reasons to think that ritual treatments of the body will refract historical and social forces through empirically attested tendencies in human cognition. In the present connection, this means that knowledge of these tendencies will reward any attempt to theorise the objectification of the body in mortuary rituals.In the second instance, because beliefs concerning the afterlife can never be definitively judged to be true or false, they give free expression to tendencies in cognition that are otherwise constrained by the need to reflect external realities accurately. To this extent, they grant direct access to the intuitive ideas and biases that shape how we think about the world. Already, this idea has been exploited to good effect in areas like the cognitive anthropology of religion, which explores how counterfactual beings like ghosts, spirits, and gods conform to (and deviate from) pre-reflective cognitive patterns (Atran 83–112; Barrett and Keil 219–224; Barrett and Reed 252–255; Boyer 876–886). Necessarily, this implies that targeting post-mortem treatments of the body will offer unmediated access to some of the conceptual schemes that inform thinking about human corporeality.At a more detailed level, the specific methodology we propose to use will be provided by conceptual blending theory—a framework developed by Gilles Fauconnier, Mark Turner, and others to describe how structures from different areas of experience are creatively blended to form a new conceptual frame. In this system, a generic space provides the ground for coordinating two or more input spaces into a blended space that synthesises them into a single output. Here this would entail using natural or technological processes to structure mortuary practices in a way that satisfies various psychological needs.Take, for instance, W.B. Yeats’s famous claim that “Too long a sacrifice / Can make a stone of the heart” (“Easter 1916” in Yeats 57-8). Here, the poet exploits a generic space—that of everyday objects and the effort involved in manipulating them—to coordinate an organic input from that taxonomy (the heart) with an inorganic input (a stone) to create the blended idea that too energetic a pursuit of an abstract ideal turns a person into an unfeeling object (the heart-as-stone). Although this particular example corresponds to a familiar rhetorical figure (the metaphor), the value of conceptual blending theory is that it cuts across distinctions of genre, media, language, and discourse level to provide a versatile framework for expressing how one area of human experience is related to another.As indicated, we will exploit this versatility to investigate two ways of objectifying the body through the examination of two contrasting mortuary practices—cremation and inhumation—against different cultural horizons. The first of these is the conceptualisation of the body as an object of a technical process, where the post-mortem cremation of the corpse is analogically correlated with the metallurgical refining of ore into base metal. Our area of focus here will be Bronze Age cremation practices. The second conceptual scheme we will investigate focuses on treatments of the body as a vegetable object; here, the relevant analogy likens the inhumation of the corpse to the planting of a seed in the soil from which future growth will come. This discussion will centre on the Classical Era. Burning: The Body as Manufactured ObjectThe Early and Middle Bronze Age in Western Europe (2500-1200 BCE) represented a period of change in funerary practices relative to the preceding Neolithic, exemplified by a move away from the use of Megalithic monuments, a proliferation of grave goods, and an increase in the use of cremation (Barrett 38-9; Cooney and Grogan 105-121; Brück, Material Metaphors 308; Waddell, Bronze Age 141-149). Moreover, the Western European Bronze Age is characterised by a shift away from communal burial towards single interment (Barrett 32; Bradley 158-168). Equally, the Bronze Age in Western Europe provides us with evidence of an increased use of cist and pit cremation burials concentrated in low-lying areas (Woodman 254; Waddell, Prehistoric 16; Cooney and Grogan 105-121; Bettencourt 103). This greater preference for lower-lying location appears to reflect a distinctive change in comparison to the distribution patterns of the Neolithic burials; these are often located on prominent, visible aspects of a landscape (Cooney and Grogan 53-61). These new Bronze Age burial practices appear to reflect a distancing in relation to the territories of the “old ancestors” typified by Megalithic monuments (Bettencourt 101-103). Crucially, the Bronze Age archaeological record provides us with evidence that indicates that cremation was becoming the dominant form of deposition of human remains throughout Central and Western Europe (Sørensen and Rebay 59-60).The activities associated with Bronze Age cremations such as the burning of the body and the fragmentation of the remains have often been considered as corporeal equivalents (or expressions) of the activities involved in metal (bronze) production (Brück, Death 84-86; Sørensen and Rebay 60–1; Rebay-Salisbury, Cremations 66-67). There are unequivocal similarities between the practices of cremation and contemporary bronze production technologies—particularly as both processes involve the transformation of material through the application of fire at temperatures between 700 ºC to 1000 ºC (Musgrove 272-276; Walker et al. 132; de Becdelievre et al. 222-223).We assert that the technologies that define the European Bronze Age—those involved in alloying copper and tin to produce bronze—offered a new conceptual frame that enabled the body to be objectified in new ways. The fundamental idea explored here is that the displacement of inhumation by cremation in the European Bronze Age was motivated by a cognitive shift, where new smelting technologies provided novel conceptual metaphors for thinking about age-old problems concerning human mortality and post-mortem survival. The increased use of cremation in the European Bronze Age contrasts with the archaeological record of the Near Eastern—where, despite the earlier emergence of metallurgy (3300–3000 BCE), we do not see a notable proliferation in the use of cremation in this region. Thus, mortuary practices (i.e. cremation) provide us with an insight into how Western European Bronze Age cultures mediated the body through changes in technological objects and processes.In the terminology of conceptual blending, the generic space in question centres on the technical manipulation of the material world. The first input space is associated with the anxiety attending mortality—specifically, the cessation of personal identity and the extinction of interpersonal relationships. The second input space represents the technical knowledge associated with bronze production; in particular, the extraction of ore from source material and its mixing with other metals to form an alloy. The blended space coordinates these inputs to objectify the human body as an object that is ritually transformed into a new but more durable substance via the cremation process. In this contention we use the archaeological record to draw a conceptual parallel between the emergence of bronze production technology—centring on transition of naturally occurring material to a new subsistence (bronze)—and the transitional nature of the cremation process.In this theoretical framework, treating the body as a mixture of substances that can be reduced to its constituents and transformed through technologies of cremation enabled Western European Bronze Age society to intervene in the natural process of putrefaction and transform the organic matter into something more permanent. This transformative aspect of the cremation is seen in the evidence we have for secondary burial practices involving the curation and circulation of cremated bones of deceased members of a group (Brück, Death 87-93). This evidence allows us to assert that cremated human remains and objects were considered products of the same transformation into a more permanent state via burning, fragmentation, dispersal, and curation. Sofaer (62-69) states that the living body is regarded as a person, but as soon as the transition to death is made, the body becomes an object; this is an “ontological shift in the perception of the body that assumes a sudden change in its qualities” (62).Moreover, some authors have proposed that the exchange of fragmented human remains was central to mortuary practices and was central in establishing and maintaining social relations (Brück, Death 76-88). It is suggested that in the Early Bronze Age the perceptions of the human body mirrored the perceptions of objects associated with the arrival of the new bronze technology (Brück, Death 88-92). This idea is more pronounced if we consider the emergence of bronze technology as the beginning of a period of capital intensification of natural resources. Through this connection, the Bronze Age can be regarded as the point at which a particular natural resource—in this case, copper—went through myriad intensive manufacturing stages, which are still present today (intensive extraction, production/manufacturing, and distribution). Unlike stone tool production, bronze production had the addition of fire as the explicit method of transformation (Brück, Death 88-92). Thus, such views maintain that the transition achieved by cremation—i.e. reducing the human remains to objects or tokens that could be exchanged and curated relatively soon after the death of the individual—is equivalent to the framework of commodification connected with bronze production.A sample of cremated remains from Castlehyde in County Cork, Ireland, provides us with an example of a Bronze Age cremation burial in a Western European context (McCarthy). This is chosen because it is a typical example of a Bronze Age cremation burial in the context of Western Europe; also, one of the authors (MG) has first-hand experience in the analysis of its associated remains. The Castlehyde cremation burial consisted of a rectangular, stone-lined cist (McCarthy). The cist contained cremated, calcined human remains, with the fragments generally ranging from a greyish white to white in colour; this indicates that the bones were subject to a temperature range of 700-900ºC. The organic content of bone was destroyed during the cremation process, leaving only the inorganic matrix (brittle bone which is, often, described as metallic in consistency—e.g. Gejvall 470-475). There is evidence that remains may have been circulated in a manner akin to valuable metal objects. First of all, the absence of long bones indicates that there may have been a practice of removing salient remains as curatable records of ancestral ties. Secondly, remains show traces of metal staining from objects that are no longer extant, which suggests that graves were subject to secondary burial practices involving the removal of metal objects and/or human bone. To this extent, we can discern that human remains were being processed, curated, and circulated in a similar manner to metal objects.Thus, there are remarkable similarities between the treatment of the human body in cremation and bronze metal production technologies in the European Bronze Age. On the one hand, the parallel between smelting and cremation allowed death to be understood as a process of transformation in which the individual was removed from processes of organic decay. On the other hand, the circulation of the transformed remains conferred a type of post-mortem survival on the deceased. In this way, cremation practices may have enabled Bronze Age society to symbolically overcome the existential anxiety concerning the loss of personhood and the breaking of human relationships through death. In relation to the former point, the resurgence of cremation in nineteenth century Europe provides us with an example of how the disposal of a human body can be contextualised in relation to socio-technological advancements. The (re)emergence of cremation in this period reflects the post-Enlightenment shift from an understanding of the world through religious beliefs to the use of rational, scientific approaches to examine the natural world, including the human body (and death). The controlled use of fire in the cremation process, as well as the architecture of crematories, reflected the industrial context of the period (Rebay-Salisbury, Inhumation 16).With respect to the circulation of cremated remains, Smith suggests that Early Medieval Christian relics of individual bones or bone fragments reflect a reconceptualised continuation of pre-Christian practices (beginning in Christian areas of the Roman Empire). In this context, it is claimed, firstly, that the curation of bone relics and the use of mobile bone relics of important, saintly individuals provided an embodied connection between the sacred sphere and the earthly world; and secondly, that the use of individual bones or fragments of bone made the Christian message something portable, which could be used to reinforce individual or collective adherence to Christianity (Smith 143-167). Using the example of the Christian bone relics, we can thus propose that the curation and circulation of Bronze Age cremated material may have served a role similar to tools for focusing religiously oriented cognition. Burying: The Body as a Vegetable ObjectGiven that the designation “the Classical Era” nominates the entirety of the Graeco-Roman world (including the Near East and North Africa) from about 800 BCE to 600 CE, there were obviously no mortuary practices common to all cultures. Nevertheless, in both classical Greece and Rome, we have examples of periods when either cremation or inhumation was the principal funerary custom (Rebay-Salisbury, Inhumation 19-21).For instance, the ancient Homeric texts inform us that the ancient Greeks believed that “the spirit of the departed was sentient and still in the world of the living as long as the flesh was in existence […] and would rather have the body devoured by purifying fire than by dogs or worms” (Mylonas 484). However, the primary sources and archaeological record indicate that cremation practices declined in Athens circa 400 BCE (Rebay-Salisbury, Inhumation 20). With respect to the Roman Empire, scholarly opinion argues that inhumation was the dominant funerary rite in the eastern part of the Empire (Rebay-Salisbury, Inhumation 17-21; Morris 52). Complementing this, the archaeological and historical record indicates that inhumation became the primary rite throughout the Roman Empire in the first century CE. Inhumation was considered to be an essential rite in the context of an emerging belief that a peaceful afterlife was reflected by a peaceful burial in which bodily integrity was maintained (Rebay-Salisbury, Inhumation 19-21; Morris 52; Toynbee 41). The question that this poses is how these beliefs were framed in the broader discourses of Classical culture.In this regard, our claim is that the growth in inhumation was driven (at least in part) by the spread of a conceptual scheme, implicit in Greek fertility myths that objectify the body as a seed. The conceptual logic here is that the post-mortem continuation of personal identity is (symbolically) achieved by objectifying the body as a vegetable object that will re-grow from its own physical remains. Although the dominant metaphor here is vegetable, there is no doubt that the motivating concern of this mythological fabulation is human mortality. As Jon Davies notes, “the myths of Hades, Persephone and Demeter, of Orpheus and Eurydice, of Adonis and Aphrodite, of Selene and Endymion, of Herakles and Dionysus, are myths of death and rebirth, of journeys into and out of the underworld, of transactions and transformations between gods and humans” (128). Thus, such myths reveal important patterns in how the post-mortem fate of the body was conceptualised.In the terminology of mental mapping, the generic space relevant to inhumation contains knowledge pertaining to folk biology—specifically, pre-theoretical ideas concerning regeneration, survival, and mortality. The first input space attaches to human mortality; it departs from the anxiety associated with the seeming cessation of personal identity and dissolution of kin relationships subsequent to death. The second input space is the subset of knowledge concerning vegetable life, and how the immersion of seeds in the soil produces a new generation of plants with the passage of time. The blended space combines the two input spaces by way of the funerary script, which involves depositing the body in the soil with a view to securing its eventual rebirth by analogy with the sprouting of a planted seed.As indicated, the most important illustration of this conceptual pattern can be found in the fertility myths of ancient Greece. The Homeric Hymns, in particular, provide a number of narratives that trace out correspondences between vegetation cycles, human mortality, and inhumation, which inform ritual practice (Frazer 223–404; Carney 355–65; Sowa 121–44). The Homeric Hymn to Demeter, for instance, charts how Persephone is abducted by Hades, god of the dead, and taken to his underground kingdom. While searching for her missing daughter, Demeter, goddess of fertility, neglects the earth, causing widespread devastation. Matters are resolved when Zeus intervenes to restore Persephone to Demeter. However, having ingested part of Hades’s kingdom (a pomegranate seed), Persephone is obliged to spend half the year below ground with her captor and the other half above ground with her mother.The objectification of Persephone as both a seed and a corpse in this narrative is clearly signalled by her seasonal inhumation in Hades’ chthonic realm, which is at once both the soil and the grave. And, just as the planting of seeds in autumn ensures rebirth in spring, Persephone’s seasonal passage from the Kingdom of the Dead nominates the individual human life as just one season in an endless cycle of death and rebirth. A further signifying element is added by the ingestion of the pomegranate seed. This is evocative of her being inseminated by Hades; thus, the coordination of vegetation cycles with life and death is correlated with secondary transition—that from childhood to adulthood (Kerényi 119–183).In the examples given, we can see how the Homeric Hymn objectifies both the mortal and sexual destiny of the body in terms of thresholds derived from the vegetable world. Moreover, this mapping is not merely an intellectual exercise. Its emotional and social appeal is visible in the fact that the Eleusinian mysteries—which offered the ritual homologue to the Homeric Hymn to Demeter—persisted from the Mycenaean period to 396 CE, one of the longest recorded durations for any ritual (Ferguson 254–9; Cosmopoulos 1–24). In sum, then, classical myth provided a precedent for treating the body as a vegetable object—most often, a seed—that would, in turn, have driven the move towards inhumation as an important mortuary practice. The result is to create a ritual form that makes key aspects of human experience intelligible by connecting them with cyclical processes like the seasons of the year, the harvesting of crops, and the intergenerational oscillation between the roles of parent and child. Indeed, this pattern remains visible in the germination metaphors and burial practices of contemporary religions such as Christianity, which draw heavily on the symbolism associated with mystery cults like that at Eleusis (Nock 177–213).ConclusionWe acknowledge that our examples offer a limited reflection of the ethnographic and archaeological data, and that they need to be expanded to a much greater degree if they are to be more than merely suggestive. Nevertheless, suggestiveness has its value, too, and we submit that the speculations explored here may well offer a useful starting point for a larger survey. In particular, they showcase how a recurring existential anxiety concerning death—involving the fear of loss of personal identity and kinship relations—is addressed by different ways of objectifying the body. Given that the body is not reducible to the objects with which it is identified, these objectifications can never be entirely successful in negotiating the boundary between life and death. In the words of Jon Davies, “there is simply no let-up in the efforts by human beings to transcend this boundary, no matter how poignantly each failure seemed to reinforce it” (128). For this reason, we can expect that the record will be replete with conceptual and cognitive schemes that mediate the experience of death.At a more general level, it should also be clear that our understanding of human corporeality is rewarded by the study of mortuary practices. No less than having a body is coextensive with being human, so too is dying, with the consequence that investigating the intersection of both areas is likely to reveal insights into issues of universal cultural concern. For this reason, we advocate the study of mortuary practices as an evolving record of how various cultures understand human corporeality by way of external objects.ReferencesAdorno, Theodor W. Metaphysics: Concept and Problems. Trans. Rolf Tiedemann. Stanford: Stanford UP, 2002.Atran, Scott. In Gods We Trust: The Evolutionary Landscape of Religion. Oxford: Oxford UP, 2002.Barrett, John C. “The Living, the Dead and the Ancestors: Neolithic and Bronze Age Mortuary Practices.” The Archaeology of Context in the Neolithic and Bronze Age: Recent Trends. Eds. John. C. Barrett and Ian. A. Kinnes. 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