Christopher J Knüsel
email: christopher.knusel@u-bordeaux.fr

Sébastien Adrien Thibeault

Sébastien Villotte

Veronique Laborde

Aurélie Fort

A Cranial Injury from the Earliest Gravettian at the Cro-Magnon Rock Shelter (Vézère Valley, Dordogne, southwest France)

Keywords: Penetrating trauma, Upper Paleolithic, Survival, Mortuary treatment

come   L'archive ouverte pluridisciplinaire

Introduction

Paleopathological assessments of Pleistocene humans include descriptions, diagnoses and interpretations of traumatic lesions that permit assessment of injury risk; post-traumatic survival; manner and, occasionally, cause of death; instances of interpersonal violence; and evidence of social support and care (e.g., Trinkaus and Zimmermann 1982;[START_REF] Belcastro | Funerary practices of the Iberomaurusian population of Taforalt (Tafoughalt, Morocco,11-12,000BP): the case of Grave XII[END_REF][START_REF] Trinkaus | Neandertals, early modern humans, and rodeo riders[END_REF][START_REF] Trinkaus | The death and burial of Sunghir 1[END_REF][START_REF] Estabrook | Trauma in the Krapina Neandertals: violence in the Middle Palaeolithic?[END_REF]Sala et al., 2015Sala et al., , 2016;;Mirazon Lahr et al., 2016;[START_REF] Trinkaus | External auditory exostoses and hearing loss in the Shanidar 1 Neandertal[END_REF]; see inventory in Wu et al., 2011). Moreover, on a population level these studies contribute to diachronic comparisons (Beier et al., 2018a, b). Certain attributions of suspected lesions have precipitated disagreements about their traumatic origin based on distinguishing post-mortem breakages (those occurring a considerable time after death when the bone had lost much of its collagen and elasticity) from peri-mortem lesions (those sustained around the time of death when bone had retained enough collagen and thus elasticity to resist fracture) [START_REF] Kranioti | State of the art forensic techniques reveal evidence of interpersonal violence ca. 30,000 years ago[END_REF](Kranioti et al., , 2020;;[START_REF] Soficaru | Peri-mortem versus post-mortem damage: The recent case of Cioclovina 1[END_REF]. The neurocranial lesion of the earlier Upper Paleolithic Cro-Magnon 2 cranium is of particular interest in this context because of its early date and owing to its lengthy study history reflecting not only on the capacity to distinguish such lesions, but also what type and how evidence is reported and interpreted. Initially documented by [START_REF] Lartet | Une sépulture des troglodytes du Périgord (crânes des Eyzies): A troglodyte burial in the Périgord (the skulls of Les Eyzies)[END_REF] and [START_REF] Pruner-Bey | An account of the human bones found in the cave of Cro-Magnon, in Dordogne[END_REF], the Cro-Magnon 2 lesion represents one of the earliest suspected cases of cranial trauma noted in a Pleistocene human, and it remains one of the relatively few known from the earlier Upper Paleolithic.

Cro-Magnon 2 and its archaeological context

The analysis presented here is based on study of the original Cro-Magnon 2 cranium (catalogue number 4254) in the Muséum national d'Histoire naturelle (MNHN), Paris.

Paleopathological evidence is provided from the literature, primarily for the roughly contemporaneous earlier Upper Paleolithic (Early and Middle Upper Paleolithic; E/MUP) remains from Europe, but reference is made as well to other Pleistocene cases of trauma.

The Cro-Magnon rock-shelter, located along the banks of the Vézère river, Les Eyzies-de-Tayac-Sireuil, southwestern France, gained immediate fame with the discovery of human remains associated with extinct fauna and prehistoric artefacts in March 1868 (Lartet and Christy, 1868). Since that time, these remains have achieved iconic status for the study of the earliest Upper Paleolithic modern humans in Europe. Because the remains themselves lack sufficient collagen for dating purposes, the most recent date between 28, 220 BP to 27, 140 BP with 95% confidence is based on an absolute dating of humanly modified (i.e. pierced) Littorina littorea shell from the same location (Henry- [START_REF] Henry-Gambier | Les fossiles de Cro-Magnon (Les Eyzies-de-Tayac, Dordogne): nouvelles données sur leur position chronologique et leur attribution culturelle[END_REF], and relative dating of similar ornaments from the Gravettian sequence from the Abri Pataud rock shelter located 300m downstream from the Cro-Magnon rock-shelter (Henry- [START_REF] Henry-Gambier | An Early Gravettian cultural attribution for the human fossils from the Cro-Magnon rock shelter (Les Eyzies-de-Tayac, Dordogne)[END_REF]. This date places them in the Mid-Upper Paleolithic (MUP), or more precisely within an early phase of the Gravettian technocomplex (33-31,000 cal BP) (Henry- [START_REF] Henry-Gambier | An Early Gravettian cultural attribution for the human fossils from the Cro-Magnon rock shelter (Les Eyzies-de-Tayac, Dordogne)[END_REF].

Having been commingled in the 19th century, the recently partly separated (i.e. "individuated") and re-associated human remains from the Cro-Magnon rock-shelter [START_REF] Thibeault | Disentangling Cro-Magnon: a multiproxy approach to reassociate lower limb skeletal remains and to determine the biological profiles of the adult individuals[END_REF][START_REF] Partiot | The Cro-Magnon babies: morphology and mortuary implications of the Cro-Magnon immature remains[END_REF][START_REF] Villotte | Disentangling Cro-Magnon: the adult upper limb skeleton[END_REF][START_REF] Trinkaus | Disentangling Cro-Magnon: the dental and alveolar remains[END_REF] provide the opportunity to re-evaluate pathological skeletal lesions and their distribution in the remains attributed to the Cro-Magnon sample. This presentation addresses the defect on the frontal of the cranium that is today known as Cro-Magnon 2.

Earlier descriptions of the defect

From early on after the discovery of the Cro-Magnon 2 remains researchers noted the perforation on the frontal of the cranium. Moreover, the descriptions of the state of preservation of the remains at the time match the appearance today. There are three descriptions of the defect, all from the Reliquae Aquitaniae.

Édouard Lartet (1865Lartet ( -1875: 70) : 70) recorded the following: "Among these bones were found, on the left of the old man [i.e. Cro-Magnon 1], the skeleton of a woman […], whose skull presents in front a deep wound, made by a cutting instrument, but which did not kill her at once, as the bone has been partly repaired within; indeed our physicians think that she survived several weeks." Lartet considered that the defect to be an ante-mortem (i.e. healing) injury based on medical opinion at the time.

In his description of a cranium identified as Number 3, Pruner-Bey (1865-1875: 79) observed: " […] in this female skull I have to notice [sic] an injury from violence. In the region of the right frontal eminence is a penetrating wound, which, inflicted during life, has cicatrized on its edges, as is plainly seen. This wound, traversing obliquely the right frontal eminence, has a narrow lozenge-shape; and one of the lance-heads of chipped flint found in the Cave perfectly fits it. Moreover, on the left side of the skull the two anterior thirds of the temporal region are wanting, and the remaining edges of the parietal and frontal have such an appearance as leaves us in doubt whether the present condition of this part of the skull is due to injury during life or to subsequent damage." Pruner-Bey ascribed the defect to a penetrating wound in life, observed evidence of healing, and, moreover, distinguished, albeit not definitively, the appearance of the defect from the breakages occurring on the opposite, left side of the vault.

Finally, Broca (1865 -1875: 100) wrote: "The right half of the frontal bone is penetrated, above the outer half of the orbit, by an oblique hole 33 millimetres (1.299 inch) long, 12 (0.472 inch) wide in the middle, and narrowing to sharp angles at the end, therefore in all probability made by a blow with a small stone axe. It was certainly made during life, and probably produced death, but not immediately; for we perceive on the inner face of the frontal, around the hole, a vascularity of the bone and a deposit of finely porous bony matter, which must have required from fifteen to twenty days for its production. The little fragment of bone, probably driven into the brain, has not been found; and there is no splintering of the table of the skull, the aperture in which has nearly as sharp an edge as that outside. Hence the blow must have been given with very great force. […] the woman's wound was evidently given [i.e. inflicted] by a murderer." Broca considered the defect to have been an in vivo injury from a violent blow that may have been fatal, but not immediately so. Moreover and importantly, Broca described porous bone from increased vascularity surrounding the defect endocranially that indicates an in vivo porous bone response, and he surmised the loss of a detached and embedded piece of bone subsequently. Furthermore, he describes the margins of the defect as sharp ectocranially and endocranially. Therefore, the margins were not rounded like those of a healed lesion and thus had a peri-mortem appearance.

In the 19th century, and shortly after the discovery of these remains, all three researchers considered that the wound to be perimortem-that is, occurring around the time of death-and also that it showed evidence of healing (and was thus also antemortem), the latter of which would indicate survival for a period of time after receiving the injury. The traumatic hypothesis has subsequently been repeated many times (e.g. Courville, 1967, Holt andFormicola, 2008: 80) and, seems only to have been called into question once more recently, but in a decisive, and opposing manner.

In 1967, Dastugue re-visited the Cro-Magnon 2 remains. He argued that the frontal defect was produced post-mortem by an excavation implement ("le choc d'un outil tel qu'un pic ou une pioche") ("a blow from a tool like a pick or pickaxe") (1967: 490). He ascribes many of the osseous anomalies in the Cro-Magnon remains, including those more recently ascribed to pathological lesions, as being due to breakage/damage produced during excavation or due to diagenetic processes. Although quoting an earlier description by [START_REF] Vallois | Nouvelles recherches sur les hommes fossiles de l'abri de Cro-Magnon[END_REF] who described the borders of the defect as being "nets et perpendiculaires" ("sharp and perpendicular"), [START_REF] Dastugue | Pathologie des hommes fossiles de l'abri de Cro-Magnon[END_REF] noted that, despite the porous bone formation and sharp margins that the appearance was not that of an in vivo injury and, moreover, that an apparent absence of radiating fractures (although see below) disqualifies this aperture as having been caused by cranial trauma. Dastugue wrote (1967: 490): "Il est véritablement taillé à l'emportepièce et ne comporte aucune fracture esquilleuse de la table interne… Les fractures du crâne dues à ce mécanisme créent en général des lésions de la table interne plus étendues que celles de la table externe et comportant de multiples irradiations esquilleuses. Par contre, sur un crâne sec, le choc d'un outil tel que pic ou pioche peut fort bien détacher un morceau d'os sur toute l'épaisseur de la paroi en laissant un orifice à bords abrupts. Ajoutons qu'on ne voit pas très bien, s'il y avait eu ostéite, pourquoi celle-ci serait limitée à la table interne et n'intéresserait ni le diploë, ni la corticale superficielle." ("It is truly a cut-out piece and does not include any fracture of the internal table… Fractures of the cranium due to this mechanism generally create lesions of the internal table that are more extensive than those of the external table and comprising multiple radiating fractures. On the other hand, on a dry cranium, the impact of a tool such as a pick or pickaxe may very well detach a piece of bone over the entire thickness of the cranial wall, leaving an orifice with abrupt edges. Let us add that we do not see very well, if there had been "osteitis", why this would be limited to the internal table and would not affect either the diploë or the superficial cortex."). He intimates that, although he observed the reactive bone on the endocranial surface, he did not ascribe any diagnostic importance to what he seems to have considered an in vivo process but insufficient evidence for a peri-mortem injury because there was no corresponding reactive bone on the ectocranial surface of the cranial vault, in addition to the absence of radiating fractures. These contradictory statements motivated this reconsideration.

Material and methods

Paleopathological assessment of Cro-Magnon 2 (which is marked with a "4" on the frontal of the specimen, inventory number 4254) is based on visual observation of the original cranium in the Muséum National d'Histoire naturelle (MNHN), Paris, in addition to microtomodensitometric (μCT) scan acquired at the AST-RX platform at the MNHN. This scan was obtained with the microfocus tube of the μCT scanner "v|tome|xL 240" (GE Sensing and Inspection Technologies Phoenix X ray). Using NRecon v2.0 (Bruker microCT), the final volume was reconstructed in 16-bit format with a isotropic voxel size of 110 μm.

Surface rendering and 3D analyses of this cranium was performed with Avizo v.9 (Visualization Sciences Group Inc.), undertaken at UMR 5199 Bordeaux and in the MNHN.

The right side of the cranium is incomplete, where a large portion of the right occipital and posterior part of the right parietal are missing (Figure 1). Moreover, a portion of the tabula externa has exfoliated from the extant part of the right parietal due to diagenetic effects. The cranial base, with the exception of the left petrous temporal, is missing. The left mastoid process is present as is the petrous temporal on that side. Using 44 numbered zones of a recording method modified from [START_REF] Hussain | A comprehensive analysis of cranio-facial trauma[END_REF] for medico-legal study of trauma (cf. Knüsel et al., 2021), the cranium is 61% complete, with 27 out of 44 zones being at least 75% complete and present.

Morphological description

The cranium is distorted with notable torsion present in the vault. Due to previous reconstruction of the right zygomatic arch, the face appears to be asymmetrical as well. There is, however, also evidence of in vivo congenital asymmetry in the supra-orbital area, the right superciliary arch being more robust than the left.

Because only the right mastoid process is preserved, an etiology of this vault asymmetry cannot be ascribed unreservedly to torsion of the cranial vault related to muscular torticollis (cf. [START_REF] Skinner | Cranial asymmetry and muscular torticollis in prehistoric Northwest Coast Natives from British Columbia (Canada)[END_REF][START_REF] Douglas | Wryneck in the ancient Hawaiians[END_REF][START_REF] Knüsel | More Circe than Cassandra: the Princess of Vix in ritualised social context[END_REF], although this dysmorphic option would be a reasonable differential diagnostic choice in a more complete cranium based on modern orthopedic definitions of the condition (cf. Salter, 1999: 171-172;Dandy, 1993: 353-354;Graham, 2007: 130-140). The attachment area of the left portion of M. semispinalis capitis is well marked, ending at the preserved cruciform eminence internally, which is visible due to breakage of the vault. The digastric fossa is also well-marked medially from the mastoid process on the left side but cannot be compared with its homologue on the right side due to incompleteness.

The cranial vault is well-marked endocranially by middle meningeal grooves. There is a series of four non-perforating depressions in a horse-shoe shape internally on the right frontal, just anterior to the coronal suture. These have rounded margins that suggest a longstanding in vivo origin. Another similar structure can be seen on the endocranial surface of the right parietal about 11mm from the sagittal suture. These are Pacchionion depressions or arachnoid granulations, which are associated with aging in adults [START_REF] Gregg | Unusual osteolytic defects in ancient South Dakota skulls[END_REF][START_REF] Ikushima | MRI of arachnoid granulations within the dural sinuses using a FLAIR pulse sequence[END_REF]Ikushima et al., : 1047, table 2), table 2). The presence of Pacchionion depressions would support an age-at-death assessment similar to that of the older female infra-cranial Beta individual based on auricular surface metamorphosis and pelvic morphology [START_REF] Gambier | Révision du sexe et de l'âge au décès des fossiles de Cro-Magnon (Dordogne, France) à partir de l'os coxal[END_REF][START_REF] Thibeault | Disentangling Cro-Magnon: a multiproxy approach to reassociate lower limb skeletal remains and to determine the biological profiles of the adult individuals[END_REF]. However, the right M 1 and M 2 are only modestly worn, the least worn of the Cro-Magnon dental remains, and indicate an age-at-death for Cro-Magnon 2 in the late third or fourth decade of life in the context of the Early to Mid-Upper Paleoolithic [START_REF] Trinkaus | Disentangling Cro-Magnon: the dental and alveolar remains[END_REF].

Although tempted to do so, [START_REF] Thibeault | Disentangling Cro-Magnon: a multiproxy approach to reassociate lower limb skeletal remains and to determine the biological profiles of the adult individuals[END_REF] caution against sex assessment based on the indeterminate results of a linear discriminant function analysis for sex assessment undertaken by [START_REF] Guyomarc'h | New data on the paleobiology of the Gravettian individual L2A from Cussac cave (Dordogne, France) through a virtual approach[END_REF]. A female attribution is in keeping with [START_REF] Henry-Gambier | Comportement des populations d'Europe au Gravettien: pratiques funéraires et interprétations[END_REF] assessment of the right os coxae, CM 4316, from the Cro-Magnon assemblage as being from a female of more than 50 and possibly 60 years of age at death [START_REF] Gambier | Révision du sexe et de l'âge au décès des fossiles de Cro-Magnon (Dordogne, France) à partir de l'os coxal[END_REF]. A female assessment of the cranium is in keeping with the vertical appearance and lack of supra-orbital rugosity of the frontal of the specimen, female characteristics. In sum, the Cro-Magnon 2 cranium, although of indeterminate sex, is that of an adult at least in the third to fourth decade of life and possibly much older, as much as 50 to 60 years of age death if associated with the right os coxae present in the assemblage, retaining evidence of cranial dysmorphy, a type of congenital condition. If it can be associated with the infra-cranial remains of individual Beta [START_REF] Thibeault | Disentangling Cro-Magnon: a multiproxy approach to reassociate lower limb skeletal remains and to determine the biological profiles of the adult individuals[END_REF], then Cro-Magnon 2 was possibly female.

The frontal defect

There is a lozenge-shaped perforation in the region of the right frontal bone just superior to the anterior extension of the superior temporal line, where the perforation terminates, and in the region of the right frontal boss, which it penetrates (Figure 2). This perforation measures 40mm in length and is 11mm at its widest, central part. The inferior margin of the defect is straighter, while the superior part is more irregular with a more elliptical outline. The external margins of this defect are sharp with an acute angle throughout its circumference but especially so on its right inferior aspect, while the internal margins of the defect have a decorticated appearance (Figure 3). A sloping depression is visible around the entire circumference of this defect, endocranially. There is a raised part of the ectocranial surface, splitting the diploë between the ectocranial and endocranial surfaces, about 22mm from the inferior part of the defect at the temporal line, giving this area an angled, rectilinear or square appearance (Figures 2 and3).

At the parasagittal margin of the defect, ectocranially, there is an area that is of lighter color with an irregular margin (Figure 4). This external feature corresponds with a similarly lighter color area internally with a rectangular margin (Figure 3). The irregular appearance of this area contrasts markedly with that of the defect margin, which is smooth, especially visible laterally in Figure 2, just superior to the circled area. This appears to be a post-mortem artifact perhaps from sample removal from the internal endocranial margin of the defect at some point in the more recent past.

Linear fissures with curved outlines appear in the vicinity of the defect (Figure 4). One extends from the posterior part of the defect to another larger fissure running irregularly in the transverse plane paracoronally that has been filled with reparative conservation material.

A second linear fissure runs from the right anterior part of the defect to the right supra-orbital margin. It, too, has been filled with reparative conservation material. A third, more subtle fissure runs from the lateral margin of the defect along the temporal fossa and is interrupted by a larger break inferiorly. This fissure and the one entering the orbit are more clearly indicated on the virtual surface rendering of the cranium (Figure 5). All three fissures originate from the defect. The use of reparative conservation material means that the surfaces of these fissures are obscured, hindering important insights into the state of the bone when these fissures occurredthat is, whether in a fresh or dried state. As a consequence, a μCTscan was employed to visualize the fracture margins, where the margin of the fracture meets the cranial vault cortical bone, and fracture surfaces of these fissures (for definitions of these terms, see Johnson, 1985: 177, fig. 5.5;Lyman, 1994: 323, fig. 8.6;Knüsel 2005: 52, fig. 1).

A linear, non-penetrating depression affects the ectocranial surface superior to the more elliptical margin of the defect (Figure 4), which is also faintly visible on the μCT-scan (Figure 5) but not on the endocranial surface (Figure 6). The appearance of this depression, which does not penetrate the vault, and thus does not affect the endocranial surface, is different from those of the fissures which penetrate the full thickness of the vault. On this basis this depressed area appears to be a post-mortem phenomenon and joins a series of other abrasions on the ectocranial surface of the vault. Study of these suspected post-mortem taphonomic abrasions are beyond the scope of this treatment, which concentrates more specifically on the larger frontal defect.

Lastly, there is porous fiber bone formation endocranially covering much of the right portion of the anterior cranial fossa superior to the right orbit but that does not extend to the internal frontal crest, the morphology of which is unaffected and normal (Figures 2 and6).

Timing of the defect: peri-or post-mortem?

In recent years, a series of papers have been published with renewed intent to distinguish the timing of bone breakages using a variety of terms to describe characteristics providing increased differential diagnostic clarity [START_REF] Berryman | Applying forensic technologies to interpreting cranial fracture[END_REF][START_REF] Berryman | Recognizing gunshot and blunt cranial trauma through fracture interpretation[END_REF][START_REF] Knüsel | The physical evidence of warfare-subtle stigmata?[END_REF][START_REF] Fleming-Farrell | Virtual assessment of perimortem and postmortem blunt force cranial trauma[END_REF][START_REF] Jordana | Diagnosis of skull fractures according to postmortem interval: an experimental approach in a porcine model[END_REF]O'Driscoll and Thompson, 2014;[START_REF] Forsom | Getting to the point: An experimental approach to improving the identification of penetrating projectile trauma to bone caused by medieval arrows[END_REF][START_REF] Kranioti | Forensic investigation of cranial injuries due to blunt force trauma: current best practice[END_REF]Ribeiro et al., 2020, among others) (Table 1). Among the features assessed in suspected cases of peri-mortem cranial fractures, and that repeatedly feature in trait lists, are the following: the shape of the fracture outline, the presence of radiating fractures, the presence of a bevel, sharp undulating fracture margins/edges, acute or obtuse fracture angles, flaking and crushing (comminution) of fracture margins, smooth texture of fracture surfaces, and presence of hinging of marginal bone fragments (Table 1).

Based on a virtual study of known peri-mortem fractures, [START_REF] Fleming-Farrell | Virtual assessment of perimortem and postmortem blunt force cranial trauma[END_REF] found that the fracture margin (or edge) and fracture angle were diagnostically inconclusive, but a smooth texture of the fracture surface was a good and predominant indicator of peri-mortem fractures, as was hinging (partial or incomplete fracture) and a fracture outline that was regular (i.e. helicoidal or spiral) were good predominant indicators. Fleming-Farrell et al.

(2013) note that although the fracture edge (i.e. margin) is a good indicator when observing dry bone specimens, its lack of clarity on tomodensitometric images (CT-images) reduces the diagnostic contribution of such images. The fracture margin remains a good indicator for identifying trauma in archaeological skeletal remains. However, in their study of blunt force cranial trauma, [START_REF] Ribeiro | Distinction between perimortem and postmortem fractures in human cranial bone[END_REF] found that undulating margins, flake defects and crushed margins (cf. marginal bone fragments) are the traits that show the highest correlation with blunt force peri-mortem cranial trauma.

The ectocranial surface of the cranial vault is the location most directly affected by a traumatic lesion, producing depressed fractures in blunt-force trauma and linear fractures in sharp-force trauma. Sharp-force trauma may also have characteristics of blunt-force trauma due to the weight of the striking implement/weapon. Perforation of the ectocranial surfacepenetrating traumacan occur in either type if the force is great enough and more easily if that force is concentrated in a restricted area, with both leaving adhering comminuted fragments (flakes or spalls), referred to as "scales" and "peels" by [START_REF] Ribeiro | Distinction between perimortem and postmortem fractures in human cranial bone[END_REF], which are adhering fragments of bone along the fracture margins. Even though these ectocranial features are indicative of cranial trauma, the most diagnostic features of perimortem cranial injuries affect the endocranial surface of the cranial vault, and these effects are more often catastrophic because of their potential to damage the underlying meninges and associated blood vessels, the sharp edges of detached fragments cutting these structures leading to internal hemorrhaging (i.e. bleeding) and the formation of a hematoma, an accumulation of blood which exerts pressure on the brain.

The key distinguishing features of peri-mortem lesions, then, are the following: sharp angulation of the fracture margin with respect to the cortical surface of the bone (forming either acute or obtuse fracture angles with respect to the cortical bone surface), the shape of the fracture outline (i.e. the shape of the fracture pattern being helicoidal/spiral/curving/undulating and not transverse as in post-mortem breakage), the smooth texture of the fracture surface and not irregular with bony projections (spicules) as in post-mortem breakages, and the presence of radiating fractures with bone spalls or flaking and "peeling" (cortical delamination) (cf. [START_REF] Ribeiro | Distinction between perimortem and postmortem fractures in human cranial bone[END_REF] due to deformation of the vault (Table 1). The most diagnostic characteristic is the presence of a bevel around the perforation at the point of impact internally. The bevel forms by inward bending of the cranial vault and displacement of cranial bone internally with crushing around the margins of the ectocranial bone defect (cf. [START_REF] Berryman | Recognizing gunshot and blunt cranial trauma through fracture interpretation[END_REF]Arbour, 2008: 152-153).

Results

The differential diagnosis addresses whether or not the defect is the result of a peri-mortem injury (and is thus a traumatic lesion) or, alternatively, is attributable to post-mortem breakage. This differential diagnosis concentrates on linking the ectocranial appearance of the Cro-Magnon 2 cranial defect to the more diagnostically informative endocranial changes.

Radiating fractures

Radiating fractures are a diagnostic feature of cranial trauma due to the deformation of the entire cranial vault induced by an impact and the anisotropic response (resistance to deformation with its entire surface), with fractures often emanating from the ends ("termini", singular "terminus") of a perforating lesion (Knüsel 2005: 54, figs. 7 and 8). The meandering curving, rather than right-angled, fissures appear to be the result of radiating fractures associated with the defect (Table 1). These fractures radiate from the point of impact as noted by [START_REF] Kroman | Fracture propagation in the human cranium: a re-testing of popular theories[END_REF] and [START_REF] Berryman | Recognizing gunshot and blunt cranial trauma through fracture interpretation[END_REF]. One of these radiating fractures in the cranial vault of Cro-Magnon 2 extends from the posterior part of the defect and is interrupted by a larger taphonomically induced break running irregularly in the transverse plane paracoronally, which had been filled with reparative conservation material (Figure 4).

A second, terminal radiating fracture from the inferior border of the defect runs from the right anterior part of the defect to the right supra-orbital margin. It, too, has been filled with reparative conservation material (Figure 4). A third such fracture in the right sphenoid runs inferiorly from the defect into and along the temporal fossa (Figures 4 and5).

Confirmation of the timing of the formation of the curvilinear fissures would come from inspection of their fracture surfaces, but due to these breaks being filled with reparative conservation adhesive, they could not be assessed directly, but could be with the surface rendering of 2D slices created from the 3D model. Because virtual images cannot completely replace dry bone observations they are best employed as a supplement to observation of specimens, but they are still informative [START_REF] Fleming-Farrell | Virtual assessment of perimortem and postmortem blunt force cranial trauma[END_REF]. The reparative preparations cannot be altered, being part of the curated museum specimen, so separation of them is not possible. Based on the presence of undulating/curving fracture outlines accompanied by fracture surfaces lacking in spicules and smooth in appearance, these fissures appear to be peri-mortem radiating fractures. These characteristics can especially be observed on the inferior part of the defect (Figures 2 and4) (and see below) and on virtual surface rendering (Figure 5). Thus, despite the presence of post-mortem breaks and surface abrasions, contra Dastugue, there do appear to be peri-mortem radiating fractures present around the defect.

Fracture margins and surface

The straighter, sharp fracture margin of the defect, inferiorly, identifies the entry wound of the injury, while the more irregular, ovoid margin with small marginal defects, superiorly, reflects removal of the implement [START_REF] Boylston | Evidence for weapon-related trauma in British archaeological samples[END_REF]Kimmerle and Baraybar, 2008: 278, figs. 6.12a, b), like the one seen in Figures 2 and4 of the ectocranial surface of Cro-Magnon 2, while the internal bevel seen in Figures 3 and6 of the endocranial surface occurs due to tension and in-bending created by cranial vault deformation on impact with an object. In Figure 4, the perforation has the sharp margins of a peri-mortem traumatic lesion and, as noted above, radiating fractures emanate from the defect. The exposed fracture surfaces, and especially the inferior, lateral margin, are smooth and undulating, like those associated with a peri-mortem fracture (Table 1). The fragmentation of the tabula interna produces a beveled margin around the defect that is due to tensile deformation of the inner table and the comminution (crushing) that accompanies blunt force trauma [START_REF] Berryman | Recognizing gunshot and blunt cranial trauma through fracture interpretation[END_REF][START_REF] Knüsel | The physical evidence of warfare-subtle stigmata?[END_REF]. The presence of bone flakes, sharp fracture margin morphology and internal bevel of the tabula interna suggest that this fracture occurred when the bone retained elastic properties that deformed upon exposure to applied stress.

Endocranial porous bone formation

The porous fiber bone formation seen endocranially in Cro-Magnon 2 resembles porous bone formation in images and descriptions provided by the Surgeon General of the United States Joseph K. Barnes in the Medical and Surgical History of the War of the Rebellion, which contains published medical reports on American Civil War (1861-1865) casualties who had suffered cranial injuries due to battle-related trauma or as a result of altercations between mobilized soldiers in non-battle-related circumstances. These men survived for a period of time afterwards, but ultimately died of complications related to their injuries. Surgeon G. L.

Pancoast, United States Volunteers, described the appearance of these injuries as "necrosed and cribiform" (i.e. porous with small holes) and went on to note soft tissue effects, writing: "The dura mater and parts of the cerebral substance in the vicinity were congested and filled with coagulated blood." (quoted in Barnes (1870: 297)). In photographs in [START_REF] Barnes | The Medical and Surgical History of the War of the Rebellion[END_REF] figs. 1 and 2 in plates between pages 142 and 143), the same type of porous bone reactions can be observed in these casualties of cranial injuries.

Internal hemorrhaging follows both blunt and sharp force cranial trauma. As [START_REF] Caldicott | Not just another 'head lac' … low velocity penetrating intra-cranial injuries: a case report and review of the literature[END_REF]Caldicott et al. ( : 1047) ) note in their more recent work on penetrating cranial trauma due to penetrative stabbing: "The major initial consequence of intracranial stabbing is intracranial hemorrhage and localized brain injury; the degree of impairment dependent upon the point of injury and track of weapon." Due to the morphological configuration of the cranium and its blood supply, penetrating injuries remain localized to the point of impact. The porous fiber bone formation in Cro-Magnon 2 occurs only in the vicinity of the defect and does not involve the whole of the endocranial surface, or even the whole of the frontal portion of it. It is thus restricted in its distribution to the area of the defect. Its localized distribution argues against a more generalized intra-cranial phenomenon. Its restricted presence around the defect suggests a localized vascular reaction, such as an intra-cranial hematoma restricted to the right half of the anterior cranial fossa in Cro-Magnon 2. This deposit does not resemble adhering sediment on visual inspection as well as in computer tomographic visualization of the defect (Figure 7).

The timing of the injury and the type of implement responsible

While porous bone formation indicates intracranial hemorrhaging, there is no obvious rounding of the margins of the lesion of Cro-Magnon 2 because death intervened before entry into this somewhat later phase of healing-thus the margins of the defect remained in the "sharp" condition. This later-occurring healing process is intimated by Barnes (1870: 57-58) in the entry for Private Charles H.:

"The case of Private Charles H., 37 years of age, found in comatose state having received a head injury, a depressed fracture, of the inferior portion of the right parietal on 27th September 1863. The punctured wound was treated by elevation and removal of the broken fragments and trephination performed that left an aperture of 4 x 2 inches (50.8 x 101.6 mm) in the vault, which was covered by flaps of integument and sutured. After this treatment, the patient regained consciousness almost immediately and was recovering until October 20th of the same year when he became "stupid and sullen and taking no notice of anything" (p. 57), comatose with signs of compression injury of the brain, and died on the 27th of October. At autopsy, 20 hours after death, he was found to have developed an abscess of the right hemisphere of the brain. At that point "the edges of the aperture were found to be rounded off and in the process of repair" (Barnes 1870: 58). This rounding of the aperture occurred a month after the initial injury.

The absence of rounding of the margins of the defect indicates that Cro-Magnon 2 likely died within at least a month of having sustained the penetrating injury. The presence of porous bone formation endocranially indicates that this fracture occurred in the immediate antemortem interval (i.e. before death) due to the incomplete resolution of this lesion, leaving it in a porous rather than a more remodeled state. In injuries with a known medical history fibrous bone formation was evident within between 2 weeks to a few months of death from osteoblastic activity and commonly occurred during the second and third weeks post-injury in many cases. Osteoblastic activity results in "fiber-bone periostitis" (Sledzik and Kelly, quoted in Sauer, 1998: 322). By the sixth week post-injury all of [START_REF] Barbian | Healing following cranial trauma[END_REF] sample based on Barnes' accounts and preserved specimens showed bony reaction.

Barnes depicts examples of this initial healing response in the Medical and Surgical History of the War of the Rebellion (1870: 143 and 145). Being casualties of the American Civil War of the 1860s, these individuals pre-date the use of antibiotics, which means that the bony response of Upper Paleolithic Cro-Magnon 2 is comparable to that from this later-period sample due to the absence of anti-biotic treatments that accelerate healing, and this would also have exposed Cro-Magnon 2 to the same infectious sequelae after contamination of the wound with microbes (see below). The presence of these changes in Cro-Magnon 2 indicate that the injury occurred within weeks and healing was incomplete at the time of death.

Fragmentation of the tabula interna results in multiple pieces of detached bone, the sharp edges of which cut the delicate arteries and veins that line the endocranium. Bone fragments may become embedded in the brain, as in the case of private Michael B., who died after being hit in the head by a fellow soldier with a musket butt following the Battle of Gettysburg (Pennsylvania, USA) in 1863 (Barnes 1870: 44, fig. 15) "At the autopsy, made fourteen hours after death, the left side of the calvarium was removed, and a number of long fragments were found imbedded in the middle lobe of the left hemisphere, the brain tissue being broken up as far as the left lateral ventricle." The force of fractures that exceed the elastic bone response permit especially objects with a narrow edge or point to penetrate the cranial vault and underlying brain, especially when delivered at high velocity, as with projectile points, whether of metal [START_REF] Forsom | Getting to the point: An experimental approach to improving the identification of penetrating projectile trauma to bone caused by medieval arrows[END_REF] or stone (O'Driscoll and Thompson, 2014).

Slower velocity impacts (like that from a musket butt), those with less force than projectile injuries, like those from hand-held pointed weapon-tools (cf. Meyer et al., 2015, fig. 2) also produce fractures of the vault due to tensile forces exerted on the inner table from compressive force exerted on the ectocranial surface and that resemble the lesion described above.

Comment on Dastugue's differential diagnosis

There are thus several observations made as a result of this analysis that contradict Dastugue's arguments, and these are summarized here. The first is that there is an internal bevel (Figures 3 and6) and there are, indeed, radiating fractures emanating from the defect that had been filled with adhesive (Figures 2 and4). Moreover, the smooth fracture surface of the defect can be seen in Figure 2 and in the μCT -image (Figure 5) acquired from visualization of the defect (Figure 7). Dastugue's propensity to ascribe lesions to taphonomic changes without reference to replicative research or published literature suggests that this is perhaps a default reaction to potential taphonomic effects on archaeological remains. His view is at odds with the earlier diagnostic opinions of this defect, and the one offered in this treatment.

Additional support for the traumatic hypothesis comes in Barnes' (1870) accounts of head wounds and their sequelae. The cause of death was often meningitis (epidural abscess), probably from post-traumatic bacterial infection producing swelling beneath the three layered (dura mater, arachnoid, and pia mater) membranous covering of the brain that lines the endocranial surface of the cranial vault. In these accounts the cortical surface of the tabula externa is described as having been contused, with often only superficial scalp wounds. At autopsy, even the least invasive of injuries seem to have been sufficient to provide access for bacteria leading to bacterial infection. In some individuals, even for wounds leading to death, "no osseous lesion could be detected" (Barnes: 112) externally, but exfoliated bone of the tabula interna was found at autopsy, as in the case of Private William Smith of Company G of the 4th New York Heavy Artillery, who suffered a contusion of the left parietal from a conchoidal (i.e. pointed and hollow cylindrical shape, rather than round) penetrating musket ball (Minié ball). Barnes (1870: 112, see also figs. I and II of the photographic plate accompanying page 142) notes: "On removing of the skull cap it was found that a plate of bone, about one inch long and three quarters of an inch broad [25.4 x 19.05mm], had been separated by exfoliation from the inner table, and was adherent to the dura mater immediately beneath the position of the original scalp wound. The brain was removed with the membranes entire, but a moderate quantity of blood and serum being found beneath the dura….". Injuries were predominantly internal, an abscess beneath the dura mater, and not external, and these often proved fatal. Death, preceded by delirium and a comatose state, sometimes with convulsions, resulted a month or a few weeks after the initial injury. A similar result and sequelae could be expected to have been in the case of Cro-Magnon 2.

Thus, the absence of reactive bone externally is not a contra-indication for cranial trauma.

It is likely that if small comminuted fragments, as suspected by Broca (above) survived, they were not recognized as such and recovered in the 19th century. What persists in the Cro-Magnon 2 cranial remains is the porous fiber bone that was adhering to the dural membrane lining the tabula interna of the cranial vault (Figure 7).

Paleopathogical interpretation

The cranial perforation in Cro-Magnon 2 appears to be a blunt force penetrating injury (penetrating trauma) in zones 15 and 16 using the recording method of [START_REF] Hussain | A comprehensive analysis of cranio-facial trauma[END_REF]. This location is above the hat-brim line, which indicates that Cro-Magnon 2 had more likely received this wound during an assault resulting from interpersonal aggression, rather than as a result of accidental trauma (cf. [START_REF] Kremer | Discrimination of falls and blows in blunt head trauma: systematic study of the hat brim line rule in relation to skull fractures[END_REF][START_REF] Kremer | Discrimination of falls and blows in blunt head trauma: assessment of predictability through combined criteria[END_REF][START_REF] Guyomarc'h | Discrimination of falls and blows in blunt head trauma: a multi-criteria approach[END_REF][START_REF] Kranioti | Forensic investigation of cranial injuries due to blunt force trauma: current best practice[END_REF]. The defect has the appearance of penetrating blunt force trauma with an object having a blunt edge, not sharp like those of metal tools and weapons, rather like a stone axe or spear-point perhaps. In other words, it is more like a chop-mark, rather than an incision, the latter of which would be expected with a sharp metal cutting edge.

The length of the lesion differs from that suspected to have been produced by a stone adze, which has a more restricted impact area (cf. [START_REF] Moreno-Ibáñez | Was it an axe or an adze? A cranial trauma case study from the Late Neolithic -Chalcolithic site of Cova Foradada (Calafell, Spain)[END_REF]Wahl and König 1987), so perhaps a stone axe could be suspected. This assessment accords with those of medical examiners from the 19th century cited above, who suspected the defect had been produced by a flint (i.e. stone) spearhead or axe.

Porous bone formation around the defect suggests survival of this injury for a period of time of at least two weeks (cf. [START_REF] Barbian | Healing following cranial trauma[END_REF] but not long enough to produce rounding of the margins of the wound, which suggest survival for a more lengthy period of time, perhaps more than a month. The newly deposited endocranial bone is stained reddish orange (as are the grooves of the meningeal arteries) due to the presence of red ochre (hematite) with these remains and the more porous nature of the reparative porous bone (Figure 3). [START_REF] Barbian | Healing following cranial trauma[END_REF] note that this type of lesion represents an initial or early response to bone trauma which is likely due to an inflammatory response. The circumstances or manner of death would thus be from the after-effects of this injury or from other soft tissue injuries leaving no visible sequelae. Thus, it cannot be considered definitively the cause of death, although this injury may eventually have been a lethal one from post-traumatic infection. The manner of death, then, seems to have been the result of interpersonal violence and the mode of death by blunt force penetrating trauma.

Discussion

The Pleistocene Context

The traumatic lesion in Cro-Magnon 2 joins other traumatic lesions among Early/Mid Upper Paleolithic individuals in documenting the levels of risk and survival of trauma among these populations. Given the subcutaneous nature of the neurocranial vault and hence the susceptibility of the pericranium to traumatic insults, small ectocranial lesions are well documented in this sample, as they are in other Late Pleistocene samples. Minor E/MUP lesions are known from Cioclovina 1, Dolní Věstonice 3, 13, 15 and 16, Mladeč 5 and Pavlov 1 [START_REF] Soficaru | The human cranium from the Peştera Cioclovina Uscată, Romania: context, age, taphonomy, morphology and paleopathology[END_REF][START_REF] Vlček | Die Mammutjäger von Dolní Vĕstonice[END_REF][START_REF] Trinkaus | Skeletal and dental paleopathology[END_REF][START_REF] Teschler-Nicola | Pathological alterations and traumas in the human skeletal remains from Mladeč[END_REF]. Similar ones are well documented for Late Upper Paleolithic humans [START_REF] Brennan | Health and Disease in the Middle and Upper Paleolithic of Southwestern France: a Bioarcheological Study[END_REF], Middle Paleolithic Neandertals (e.g., [START_REF] Trinkaus | The Shanidar Neandertals[END_REF][START_REF] Estabrook | Trauma in the Krapina Neandertals: violence in the Middle Palaeolithic?[END_REF][START_REF] Wu | Neurocranial trauma on the late archaic human remains from Xujiayao, northern China[END_REF], and Middle Pleistocene humans (e.g. Weidenreich 1936;[START_REF] Pérez | Paleopathological evidence of the cranial remains from the Sima de los Huesos Middle Pleistocene site (Sierra de Atapuerca, Spain). Description and preliminary inferences[END_REF] [see inventory and references in Wu et al. (2011)].

More serious neurocranial lesions are less common. The only other E/MUP neurocranial injury is the mid-frontal depressed fracture of Dolní Vestonice 11/12, one which nonetheless healed long before death [START_REF] Trinkaus | Skeletal and dental paleopathology[END_REF]. To these can be added the likely fatal cervical incision of Sunghir 1, with a penetrating injury to the body of the first thoracic vertebra [START_REF] Trinkaus | The death and burial of Sunghir 1[END_REF].

There are several other cases of potentially life-threatening cranial trauma among Pleistocene humans, including frontal depressed fractures of Qafzeh 11 and Maba 1, the parietal lesions of Cova Negra 1, Nanjing 1 and Krapina 34.7, the frontal injury of Saint-Césaire 1, and the facial fracture of Shanidar 1 (de [START_REF] De Lumley | Anténéandertaliens et Néandertaliens du bassin méditerranéen occidental européen[END_REF][START_REF] Trinkaus | The Shanidar Neandertals[END_REF]Zollikofer et al., 2002;[START_REF] Mann | A Neandertal parietal fragment from Krapina (Croatia) with a serious cranial trauma[END_REF][START_REF] Shang | An ectocranial lesion on the Middle Pleistocene human cranium from Hulu Cave, Nanjing, China[END_REF]Wu et al., 2011;[START_REF] Coqueugniot | Earliest cranio-encephalic trauma from the Levantine Middle Palaeolithic: 3D reappraisal of the Qafzeh 11 Skull, consequences of pediatric brain damage on individual life condition and social care[END_REF].

This case joins the peri-mortem projectile injury on the left antero-lateral aspect of the first thoracic vertebra of Sunghir 1 [START_REF] Trinkaus | The death and burial of Sunghir 1[END_REF] and, more recently, from the Upper Paleolithic Cioclovina (Romania) calvaria, a male, dated to ca. 33 cal ka BP, with a linear fracture on the posterior cranium accompanied by radiating fractures and a larger right parietal injury, with concentric fractures, seem to have been sustained as a result of interpersonal violence involving one or more assailants, in addition to two healed blunt force injuries on the frontal. Although the origin and timing (peri-mortem versus post-mortem) of the depressed fracture on the right parietal has been more recently disputed [START_REF] Soficaru | Peri-mortem versus post-mortem damage: The recent case of Cioclovina 1[END_REF] and rebutted by Kranioti and colleagues (2020), the two smaller antemortem (i.e. healed) depressed fractures on the frontal, identified as HF1 and HF2 in figure 4 in [START_REF] Kranioti | State of the art forensic techniques reveal evidence of interpersonal violence ca. 30,000 years ago[END_REF] that were identified in previous studies, have not been disputed, nor has the linear occipital fracture. The location above the hat-brim line of these lesions suggests a more likely origin in interpersonal violence, so whatever the status of the larger defect on the right parietal, this individual is a recidivist for cranial trauma (having more than a single injury) (cf. [START_REF] Judd | Ancient Injury Recidivism: An Example from the Kerma Period of Ancient Nubia[END_REF].

Of these traumatic lesions, only those of Sunghir 1 and Saint-Césaire 1 can be directly attributed to penetrating cranial trauma and to them can be added the rib incision of Shanidar 3 [START_REF] Trinkaus | The Shanidar Neandertals[END_REF][START_REF] Churchill | Shanidar 3 Neandertal rib puncture wound and Paleolithic weaponry[END_REF]. The others can be variously attributed to forms of blunt force trauma, whether intentional or accidental, interpersonal or otherwise. Moreover, all of these lesions (except that of Sunghir 1) are evident because they were non-fatal or not immediately fatal, which indicates possible social support during the post-traumatic survival interval. The frontal lesion of Cro-Magnon 2 therefore joins a suite of similar traumatic injuries in the Pleistocene, only some of which can be conclusively attributed to interpersonal violence.

The Mortuary Context

Given the location of the injury in the frontal bone sustained by Cro-Magnon 2above the hat-brim lineit was more likely the result of interpersonal aggression rather than an accident. The absence of similar injuries in the other individuals from the Abri de Cro-Magnon indicate that, on present evidence, this does not appear to have been received during a mass killing, but rather as an isolated event. The association of an individual dying as a result of violent injury with others deposited nearby in the same context is not without precedent during the Upper Paleolithic, but the absence of mass graves of this antiquity indicates that the scale of violence did not involve the greater numbers as indicated, for example, by the mass graves of the European Early Neolithic (cf. [START_REF] Meyer | Mass graves of the LBK patterns and peculiarities, in Early Farmers: The View from Archaeology and Science[END_REF], or the evidence for repeated, though largely non-lethal, violent confrontation, as at the Çatalhöyük Neolithic mega-site in Turkey (Knüsel et al., 2021), or the repeated and fatal penetrating projectile trauma found at Late Pleistocene Jebel Sahaba (Sudan) [START_REF] Crevecoeur | New insights on interpersonal violence in the Late Pleistocene based on the Nile Valley cemetery of Jebel Sahaba[END_REF].

Cro-Magnon 2 also survived for a period of time after the incident but without the time (and extent of remedial treatment) necessary to achieve complete healing prior to death. The circumstances of death, then, appear to have been unusual, and the ubiquitous presence of red ochre on the Cro-Magnon human remains suggest potential implications for curing and apotropaic functions. The other E/MUP fatal injury, that of Sunghir 1, also led to burial with abundant ochre (Bader, 1998;[START_REF] Trinkaus | Diversity and differential disposal of the dead at Sunghir[END_REF], although ochre was common in Upper Paleolithic burials [START_REF] Henry-Gambier | Comportement des populations d'Europe au Gravettien: pratiques funéraires et interprétations[END_REF][START_REF] Trinkaus | The People of Sunghir: Burials, Bodies and Behavior in the Earlier Upper Paleolithic[END_REF], often being considered a symbolic attribute [START_REF] Bar-Yosef | The Upper Paleolithic revolution[END_REF] due to its bright red color. Its attested medicinal propertiesowing to the iron salts it containsalso means that it may have served as an astringent and antiseptic in remedial treatments such as a treatment for burns, as well as a deodorant among Aboriginal Australians [START_REF] Velo | Ochre as medicine: a suggestion for the interpretation of the archaeological record[END_REF][START_REF] Wreschner | Red ochre and human evolution: a case for discussion[END_REF][START_REF] Wreschner | More on Paleolithic ochre[END_REF]. In this regard Cro-Magnon 2 adds to a group of individuals of "special status", unusual people, a growing number with congenital conditions [START_REF] Formicola | From the Sunghir children to the Romito dwarf: aspects of the Upper Paleolithic funerary landscape[END_REF][START_REF] Trinkaus | An abundance of developmental anomalies and abnormalities in Pleistocene people[END_REF]) and those who, like Sunghir 1, died in unusual circumstances in the Upper Paleolithic.

Cro-Magnon 2 was described as being found next to the remains of Cro-Magnon 1 (Lartet and Christy 1865-1875; see Lartet 2018 and above), a pairing that is reminiscent of the position of the double burial of a male and female at Grotte des Enfants [START_REF] Formicola | Tall guys and fat ladies: Grimaldi's Upper Paleolithic burials and figurines in an historical perspective[END_REF]. Although the lack of detailed recording of the mortuary context of Cro-Magnon 1 and 2 cannot indicate if these were simultaneous or successive depositions, these remains add to the growing number of individuals intentionally deposited in the same feature as multiple (simultaneous) or collective (successive) interments, such as those from Dolní Věstonice [START_REF] Svoboda | Dolní Věstomice -Pavlov. Explaining Paleolithic Settlement in Central Europe[END_REF], Barma Grande [START_REF] Formicola | The triplex burial of Barma Grande (Grimaldi, Italy)[END_REF][START_REF] Henry-Gambier | Comportement des populations d'Europe au Gravettien: pratiques funéraires et interprétations[END_REF], the paired infants from Krems-Wachtberg [START_REF] Einwögerer | Upper Palaeolitihic infant burials[END_REF], and the two children at Sunghir (Bader 1998), or deposited near to one another, such as those from Baousso da Torre (Henry- [START_REF] Henry-Gambier | Comportement des populations d'Europe au Gravettien: pratiques funéraires et interprétations[END_REF]. The disposition of the remains of these individuals adds increasing evidence attesting to the influence of selective criteria, perhaps related to kin relations or due to socioritual cosmological concepts.

Conclusion

The right frontal cranial defect of Cro-Magnon 2 indicates a low velocity but forceful impact producing a blunt-force penetrating traumatic neurocranial injury when the bone retained its elastic (i.e. in vivo) properties. Because there is evidence of intra-cranial reactive bone, the appearance of this lesion is also indicative of an antemortem injury. Intra-cranial porous bone formation indicates intra-cranial hemorrhaging and the location of a hematoma, and this is consistent with initial survival of the injury but is also a likely indication of the manner of death after a period of time from secondary effects, such as shock, blood loss, and infection, in the pre-antibiotic era. Post-traumatic seizures and delirium are common with brain injuries [START_REF] Barnes | The Medical and Surgical History of the War of the Rebellion[END_REF], and these may be suspected to have been the case for Cro-Magnon 2 after sustaining this injury. The circumstances in which Cro-Magnon 2 perished may have contributed to the funerary treatment of this individual, with ochre applied to the corpse and/or in the grave, as well as burial with others, including the congenitally pathological Cro-Magnon 1 individual (cf. Tillaud 1981Tillaud /2, 1985[START_REF] Tillaud | Pathographie du sujet No. 1 de Cro-Magnon[END_REF][START_REF] Charlier | Did Cro-Magnon 1 have neurofibromatosis type 1?[END_REF], similarly deemed to have been special/unusual and thus attributed special ritual treatment (cf. [START_REF] Ucko | Ethnography and archaeological interpretation of funerary remains[END_REF]. Wu, X.J., Schepartz, L.A., Lui, W., Trinkaus, E. (2011)

Table caption:

Table 1: Distinctive features of cranial peri-mortem fractures versus post-mortem breakages and as assessed in the Cro-Magnon 2 cranium

  Figure captions:

Figure 1 :

 1 Figure 1: Anatomical views of the Cro-Magnon 2 cranium: a, left lateral view; b, right lateral

Figure 2 :

 2 Figure 2: Ectocranial view of the lozenge-shaped defect on the right frontal bone of Cro-

Figure 3 :

 3 Figure 3: An endocranial view of the frontal defect of Cro-Magnon 2. Porous bone formation

Figure 4 :

 4 Figure 4: An ectocranial view of the frontal defect of Cro-Magnon 2. Ectocranial linear

Figure 5 :

 5 Figure 5: Virtual view of the linear fissures with curved fracture outlines that appear in the

Figure 6 :

 6 Figure 6: An endocranial view of the frontal fossa of Cro-Magnon 2 with the defect, around

Figure 7 :

 7 Figure 7: Upper register: 3D visualization of the defect with the porous fiber bone on the

Figure 1

 1 Figure 1 Cro-Magnon 2 cranium

  et al. (2013);Knüsel et al.,

Table 1

 1 Cro-Magnon 2 Click here to access/download;Table;Table 1 Cro-Magnon 2.docx


Elise Beck

Christiane Weber

Michel Granet

APPLICATION OF THE FUZZY LOGIC TO THE STUDY OF THE EXPOSURE TO DANGEROUS INDUSTRIES The case of the urban area of Mulhouse (Haut-Rhin, France)

Keywords: Industrial risk, exposure to dangerous industries, GIS, fuzzy sets theory, urban area, Mulhouse

The present study is part of a larger research which aims at addressing the conjunction of the seismic and industrial risks. It is applied to the urban area of Mulhouse, a medium sized French city. In this paper, the focus is done on the evaluation of the exposure to a dangerous industry. We chose to evaluate it by using the fuzzy sets theory (to a lesser extent the fuzzy logic). This method is still not widely spread in the field of the industrial risks, although it seems to provide many advantages. The different steps of an application of the fuzzy logic to the evaluation of the exposure to dangerous industries will be presented, as well as some concrete results for the urban area of Mulhouse. The whole study is carried out within a geographic information system (GIS).

INTRODUCTION

Cities and urban areas are dangerous sites, as they accumulate high densities of population as well as many human industrial activities. Some of them can represent a threat for the population. This has been clearly illustrated by the Toulouse's (France) recent accident, in September 2001, when the explosion of chemical products caused the death of 30 persons. Despite the Seveso European and national legislations, many people live close to dangerous industries like oil tanks, chemical or nuclear plants. That is why it is important to consider these populations and hence to acquire a better knowledge on industrial risks to enhance risk mitigation. The evaluation of the exposure to an industrial danger can be done using different methods. The fuzzy sets theory, which has been used in various domains since the 1950's, shows interesting advantages to this problematic. In this paper, after having presented the case study and the general purpose, we shall describe the general principles of the fuzzy sets theory and of the fuzzy logic, as well as their advantages to the study of risks. We shall end by presenting preliminary results for the urban area of Mulhouse (France).

GENERAL CONTEXT Case Study

The present study is part of a larger research which takes place in the urban area of Mulhouse, a city located in the north-eastern part of France, close to the Swiss and German borders (map 1). This city can be considered as a "multirisk" area, as it is exposed to several natural and technological risks: floods, mud flows, earthquakes, dangerous industries (chemical plants…), networks of hazardous materials transport and a dam. Among all these different threats, the research focuses on the seismic and the industrial risks.

Mulhouse is located in the Upper Rhine Graben, where the general stress field (oriented North-West/South-East) is due to the collision of the European and African Plates, which leads to the reactivation of inherited faulting systems. The seismicity is low to moderate, however, some catastrophic events like the Basel's earthquake (1356, with macroseimic intensity Io=IX-X), could occur. This earthquake is considered as the strongest seismic event in Western Europe for the last thousand years, and its consequences were dramatic in the context of the fourteenth century.

Several dangerous industrial sites are located in the urban area of Mulhouse (map 2): two chemical plants (one being specialized in the transport of chemical materials), an important site with oil tanks and a freight station. The latter is considered as a dangerous one because of the large amount of hazardous materials which are stored there or travel through the station. According to the French legislation, all these sites are characterized by a PPI (for "Plan Particulier d'Intervention"). This emergency plan defines a zoning for each dangerous industry. This zoning corresponds to the area concerned by the consequences of an accident, according to the worst scenario determined by the "studies of dangers". Map 2 shows the location of the four dangerous sites and their corresponding PPI zoning. We can notice that one of the two PPI zonings of the freight station totally includes the city of Mulhouse. Moreover, two places show a higher level of danger as the corresponding PPI zonings are superimposed (around the freight station and around the TYM industry). The present French legislation does not take into account neither this concentration of industrial risks nor the conjunction of two risks (seismic and industrial). An important issue is to know the consequences of such multiplication of risks to prevent some major disaster.

Map 1: Location of the urban area of Mulhouse.

Finally, Mulhouse concentrates 200 000 inhabitants (1999 census), which illustrates the vulnerability of the region. Moreover, many industrial activities take place in this area, as for example an important car factory which employs about 12 000 persons. The vulnerability of the urban area city is also due to the organization of the road and railways networks (map 2), which totally hem the city. This results in urbanization problems and could also lead to serious difficulties in the management of a major crisis like a strong earthquake. We can easily imagine that the emergency services would hardly succeed in moving in the city.

General purpose

We have seen that the urban area of Mulhouse is exposed to several different risks that somewhere accumulate. The general research aims at assessing the conjunction between them. In other words, its objective is to evaluate the impact of a strong earthquake on the urban system of Mulhouse, and particularly on the dangerous industries [START_REF] Beck | Risque sismique et risques technologiques. Application à l'agglomération de Mulhouse[END_REF], using a geographic information system (GIS). What could happen if an earthquake similar to the Basel's one occurred in a near future? In order to answer this question, we first of all need to evaluate the seismic and industrial risks. As a matter of fact, a good mitigation of risks starts with a good knowledge of the phenomena. Then, if we consider that the risk is the result of the combination between hazard and vulnerability, it is necessary to characterize the vulnerable elements and to estimate the industrial and seismic hazards. In the case of dangerous industries, we would rather use the term "accident" than "hazard".

The study is carried out within a geographic information system (GIS). This tool has proved to be very efficient in the field of risks [START_REF] Glatron | La représentation et la gestion des risques urbains par les systèmes d'information géographique[END_REF]. For example, it allows to arrange, analyse and represent spatial data. In that way, it provides the possibility of modelling phenomena like risks by combining layers of hazard and vulnerability.

Map 2: Location of the dangerous industries in the urban area of Mulhouse.

Different methods can be used to evaluate the exposure to dangerous industries. The final choice of the method depends on the scale of study (national, regional, local) and on the data that are available or that can be acquired in a reasonable time. Rather than evaluating the consequences of an explosion, a fire or a pollution, which requires many data that are frequently inaccessible, we decided to represent the exposure of the population and the buildings to these threats. This exposure is to some extent symbolized by the PPI zoning, which is obtained from several studies of dangers. However, the largest zoning defined for this emergency plan corresponds to a zoning of constant diameter around the dangerous site, and this representation is not satisfying. Without neglecting the information provided by the PPI zoning, we preferred to moderate its delimitations and particularly the rigidity of its limits: how should we interpret the fact that a building is located on the edge of the zoning? And what about two houses located on both sides of this limit: does that mean that the house located out of the PPI is not exposed to the industrial danger? It seemed necessary to integrate this uncertainty in our study. The fuzzy sets theory allows to take into account this uncertainty, this is why it is applied to the evaluation of the accumulated exposure to dangerous industries. The area of exposure to dangerous industries can thus be compared to a "fuzzy geographical space", as defined by Rolland-May [START_REF] Rolland-May | La théorie des ensembles flous et son intérêt en géographie[END_REF], since its limits are fuzzy. Thus, the fuzzy sets theory can be applied to our study.

The originality of this approach does not come from the fact that we apply the fuzzy sets theory to environmental or geographic problems, since many other authors used this method [START_REF] Ercanoglu | Use of fuzzy relations to produce landslide susceptibility maps of a landslide prone area (West Black Sea Region, Turkey)[END_REF][START_REF] Hedge | Modelling Land Cover Change: a fuzzy approach[END_REF][START_REF] Rolland-May | La théorie des ensembles flous et son intérêt en géographie[END_REF][START_REF] Tannier | From the observations to the construction of an urban dynamics simulation model: an inductive approach[END_REF]. However, it rather lies in the choice of this approach for the evaluation of the exposure to dangerous industries, much more often considered using probabilistic models [START_REF] Glatron | A geographical method to assess technological hazards. The example of the storage and the distribution of the fuel oils in the urban region of Ile-de-France[END_REF][START_REF] Tixier | Review of 62 risk analysis methodologies of industrial plants[END_REF].

METHODOLOGY General Principles of the Fuzzy Sets Theory and the Fuzzy Logic -Advantages to the Study of Risks

The fuzzy sets theory is an extension of the sets theory defined by Cantor [START_REF] Cantor | Gesammelte Abhandlungen mathematischen und philosophischen Inhalts[END_REF]. According to him, an element belongs or does not belong to a given set. The intermediate situation does not exist, which can become constraining when, for example, the spatial limits of the given unit are not well defined or not precise. In opposition, the theory of the fuzzy sets, stated by Zadeh in the 1960's [START_REF] Zadeh | Fuzzy sets[END_REF], makes it possible to define degrees of membership to a fuzzy set, with degrees varying between 0 and 1 (fig. 1). The sets theory defined by Cantor can be considered to some extent as a particular case of the fuzzy sets theory, where all the membership degrees are either 0 or 1.

The fuzzy sets theory is a general theoretical frame for the use of mathematical, statistical or logical fuzzy operations. In our case, we chose the fuzzy logic and the fuzzy mathematics.

The application of the fuzzy sets theory and the fuzzy logic to a given field can be declined in four steps [START_REF] Zimmermann | Fuzzy set theory and its application[END_REF]. First of all, the input and output variables (i.e. the variables which will be integrated in the analysis) must be chosen. In our case, each variable corresponds to a data layer which will be integrated in the GIS. Then, a membership function is applied to each input variable. The membership function allows to associate with each element of a given set a real number in the interval [1;0]. This real number corresponds to the membership degree of the element to the set. The membership function can take very various shapes (linear, triangular, bell-shaped, etc.). This first step requires to consider the literature, experiments and the experience and knowledge of experts. The step of the fuzzification is illustrated by figure 2 with the example of a variable called "distance to a dangerous industry". We can notice on figure 2 the use of linguistic variables ("low, mean, high").

Figure 2: Example of membership function of the variable "distance to a dangerous industry". The distance "700 m" belongs to the fuzzy set "low distance" with a membership degree of 0.34 and to the fuzzy set "medium distance" with a degree of 0.66 (from Griot [START_REF] Griot | Evaluation de la vulnérabilité en vue de la préparation aux interventions de la Sécurité Civile[END_REF]).

Once all the variables are "fuzzyfied", the aggregation operators (or fuzzy operators) have to be chosen. They stand for logical combinations (or numerical combinations, depending on which approach we choose) between the input variables and correspond to numerical or Boolean operations between the membership degrees. The output variable is actually the result of the combination between the input variables. Many different fuzzy aggregators are available, but the five most used are: the "fuzzy AND", the "fuzzy OR" (fuzzy logic), the fuzzy sum, the fuzzy product and the gamma operator (fuzzy mathematics) [START_REF] An | Application of fuzzy set theory to integrated mineral exploration[END_REF]. For example, if we applied the "fuzzy OR" to our problematic, we would obtain the following rule: if the distance to an industry where a fire could occur is small, OR if the distance to an industry where an explosion could occur is small, then the total exposure to a dangerous industry is high. The choice of the operators depends on the problematic and the objective that has to be reached. For example, the "fuzzy OR" leads to results that are controlled by the maximum value of the different membership degrees. As advised by Bonham-Carter [START_REF] Bonham-Carter | Geographic Information Systems for Geoscientists, modelling with GIS[END_REF], it is preferable to combine different operators in a model.

The third step is simply the application of the aggregation operators, i.e. the simulations. Several simulations are usually necessary in order to calibrate the model.

The final step consists in coming back to the context, in other words, in proceeding to a "defuzzification", which corresponds to the transformation of the membership degrees (issued from the combination of the input variables) to output variables.

Of course, among the different methods used to evaluate hazards in general, we could retain another one than the fuzzy sets theory. Each method has advantages and drawbacks: the fuzzy sets theory and the fuzzy logic also have.

The fuzzy logic is a flexible method, since it is used in various domains [START_REF] Bouchon-Meunier | Logique floue, principes, aide à la décision[END_REF], including in the field of risks (susceptibility to landslides [START_REF] Ercanoglu | Use of fuzzy relations to produce landslide susceptibility maps of a landslide prone area (West Black Sea Region, Turkey)[END_REF]; consequences of an earthquake on buildings [START_REF] Fischer | An integrated model for earthquake risk assessment of buildings[END_REF]). Concerning the variables, the fuzzy sets theory has the advantage to be used either for qualitative or quantitative variables, and to analyse them on comparable ranges of values. Moreover, as indicated by its name, it allows to integrate variables with high uncertainties (in particular uncertainties of location). In addition, it allows to use multi-source, multi-scale and heterogeneous data [START_REF] Binaghi | Slope instability zonation: a comparison between certainty factor and fuzzy Dempster-Shafer approaches[END_REF].

The second advantage lies in its capacity to represent a smooth transition from a state to another [START_REF] Bonvicini | Risk analysis of hazardous materials transportation: evaluating uncertainty by means of fuzzy logic[END_REF], which is a major asset in the study of risks. For example, if one considers a PPI zoning, its definition is geometrical, since, at the present time, it corresponds to a circle (or an ellipse) of a certain diameter. When a building is crossed by the limit of the zoning, it is, by definition, inside the PPI, but also apart from this one. What is really its statute? One can thus rather think of smooth transitions between the state of being in a zoning or not.

The third advantage is that the model developed using the fuzzy sets theory is enhanced by the a priori knowledge of the expert [START_REF] Hedge | Modelling Land Cover Change: a fuzzy approach[END_REF]. Indeed, the expert acts in the selection of the membership functions and in the choice of the aggregation operators. A good knowledge of the system is therefore needed. However, this part of subjectivity can also represent a disadvantage, since two experts may not have the same opinions and will not make the same choices. This is why it is essential to gather several experts in order to select the membership functions and the aggregation operators with more objectivity [START_REF] Griot | Evaluation de la vulnérabilité en vue de la préparation aux interventions de la Sécurité Civile[END_REF]. In some cases, a priori knowledge and expertise can be advantageous. Indeed, it can influence the result of the modelling, depending on its final objective, by adding more weight to such or such variable. It should be noticed that certain methods allow to determine the membership degrees more objectively [START_REF] Binaghi | Slope instability zonation: a comparison between certainty factor and fuzzy Dempster-Shafer approaches[END_REF][START_REF] Ercanoglu | Use of fuzzy relations to produce landslide susceptibility maps of a landslide prone area (West Black Sea Region, Turkey)[END_REF].

In conclusion, the fuzzy sets theory and the fuzzy logic can certainly be applied to the field of urban risks, and more particularly to the case of dangerous industries. As previously said, carrying out such a method requires to select input variables and aggregation operators. These choices which will be discussed now.

Variables

We consider that the exposure to dangerous industries E is a function of three variables: the expected effects e, the spatial potential p and the type of accumulation a, as indicated by the following formula (1):

) , , ( a p e f E [START_REF] An | Application of fuzzy set theory to integrated mineral exploration[END_REF] The expected effects of an industrial accident e can be: an explosion, a fire, a leak of toxic products. We think relevant to symbolize that an industry can generate effects of different nature, and that the danger represented by a site on which a fire and an explosion can occur is higher than that the threat of a site only concerned by the fire. This is why three variables are assigned to the expected effects (fig. 3): explosion, fire and leak of toxic products.

The spatial potential p (2) due to an industry is introduced. It can be understood as a gradient of intensity decreasing from the centre of the industry, in opposition to the PPI zoning, which is uniform. This is especially true if we consider that the effects (fire, explosion, leak of polluting and/or harmful products) are not the same close to the source and at the edge of the PPI zoning. In addition, the more numerous the industries are, the higher is the exposure: "the potential pi produced in a point i by a mass M in a point j is proportional to this mass and inversely proportional to its distance dij" (translated from Hiegel, [START_REF] Hiegel | Des risques urbains méconnus: les risques technologiques mineurs. Exemple des stationsservice à Strasbourg[END_REF]).

ij j i d M p   (2)
with pi the potential in i, Mj the mass at the point j, dij the distance between i and j,  a constant. The mass can be represented as a weight applied to an industry.

The variable resulting from the combination between the three types of effects is called "accumulated expected effects". It symbolizes the accumulation of different effects potentially generated by only one or by two industries, or the accumulation of similar effects generated by two different sites. The type of accumulation a depends on the combination between the effects (fig. 4): it can be simple (only one variable "effect"), minor (two effects produced by two different factories) or major (two different effects generated by the same factory (with probable "domino" effects)). This accumulation effect will be introduced into the model during the choice of the membership degrees. Other variables could have been integrated, like the 3D-shape of the buildings, which would introduce barrier effects, or the proximity of a centre of emergency, which would decrease the exposure. However, our model will not take into account these aspects for the moment.

Fuzzification

Once the variables are chosen, the membership degrees have to be defined. But first of all, we will describe the method that was used to obtain the spatial limits of the accumulated effects. One way could be to generate a map for each expected effect, and then to combine the three variables using the fuzzy sets theory, but we found much more efficient to proceed in another way. We applied the methodology developed by Propeck-Zimmermann [START_REF] Propeck-Zimmermann | Cartographie des risques technologiques majeurs : nouvelles perspectives avec les SIG[END_REF]. First of all, we only considered the PPI zonings (as they are presently delimited) and not the scenarios zonings (this should be done in a further step). This method consists in superimposing the different PPI zonings and counting the number of PPI which accumulate on a single point (map 3). If many PPI zonings are superimposed, the exposure is higher.

Map 3: Super-imposition of PPI zonings, indicating a higher danger in some areas.

We added an information by characterizing the expected effect for each PPI. Eight combinations of the expected effects can be observed for the region of Mulhouse ("site A, B and C" indicate if the effects are expected for one, two or three different industries):

- The following map illustrates the eight cases observed.

Map 4: Map of the accumulated expected effects in the urban area of Mulhouse.

Before integrating the potential, we chose to first represent the influence of distance on the exposure to dangerous industries, without taking into account the weight of industries (map 5).

Map 5: Distance to dangerous industries in the urban area of Mulhouse.

We finally retained the membership degrees for each class of the two variables a and p, as described in table 1. Calibration operations will be necessary to validate these choices. Table 1: Membership degrees for each fuzzy class of each variable. The membership function assigned to the variable of distance is continuous: the maximum distance of 5 000 m has a membership degree of 0, the distance of 10 m (and less) has a membership degree of 1.

Aggregation Operators

The choice of the operators, which depends on the objective of the research [START_REF] Zimmermann | Fuzzy set theory and its application[END_REF], will be done after several simulations, in order to calibrate the model. The choice of the operator will depend on how the different variables should be combined. It seemed significant to represent the increase of the exposure due to the combination of the two variables. Thus, the "fuzzy OR" (3) might not be an appropriate operator, as it only retains the maximum of the two memberships degrees that are combined.

)) ( )... ( )... ( ), ( max(

2 1 x x x x n i n com binatio      
where combination and i(x) represent respectively the membership degree resulting from the combination between the different variables and the membership degree of the element x to the fuzzy class i.

The fuzzy algebraic sum (4) has an increasing effect and allows to represent these cumulative effects. However, this operator is also known as it leads to an over-estimation.

       n i i n combinatio x x 1 ) ( 1 1 ) (   (4)
where combination and i(x) represent respectively the membership degree resulting from the combination between the different variables and the membership degree of the element x to the fuzzy class i.

We could also use the gamma operator [START_REF] Bonvicini | Risk analysis of hazardous materials transportation: evaluating uncertainty by means of fuzzy logic[END_REF]. It is a good compromise between the increasing effects of the fuzzy sum and the balancing effects of the fuzzy product [START_REF] Bonham-Carter | Geographic Information Systems for Geoscientists, modelling with GIS[END_REF]. It could also be used to represent a cumulative effect of the two variables.

 

                          n i i n i i n combinatio x x x 1 1 1 ) ( 1 1 ) ( ) ( (5)
where combination and i(x) represent respectively the membership degree resulting from the combination between the different variables and the membership degree of the element x to the fuzzy class i, and 0   1.

PRELIMINARY RESULTS

The exposure to a dangerous industry is the result of the combination between the variable of the accumulated expected effects and the variable of distance (the combination with the variable of spatial potential will be done later). Two simulations were done, the first one using the fuzzy sum (map 6), the second one using the gamma operator (with = 0.9, which seems to be the most appropriate [START_REF] Lobry | Analyse de suscetibilité à l'érosion en zone méditerranéenne[END_REF]) (map 7). The two maps show a higher exposure around the freight station and the TYM and EPM factories, what is due to the superimposition of the PPI zonings as well as the short distance to dangerous sites. The results obtained from the combination of the two variables with the fuzzy sum may be over-estimated, however, this map takes better into account the inverse gradient of exposure due to the distance outside of the PPI zonings. As a matter of fact, the weight of the variable of accumulated effects seems to be overvalued and a membership degree of 0 is assigned to any cell located out of the PPI zonings.

These preliminary results tend to show that the fuzzy sum may be more adapted to our study. Further investigations need to be done, in order to integrate the weight of the factories (and the influence of two near factories) by the way of the spatial potential.

Map 6: map of exposure to dangerous industries in Mulhouse obtained with the fuzzy sum. A membership degree of 1 represents a high exposure.

CONCLUSION AND FURTHER DEVELOPMENTS

In this paper, we have presented a study realized in the framework of a global research, which aims at evaluating the consequences of an earthquake on an urban area, and particularly on the dangerous industries. The paper has introduced a methodology of evaluation of the exposure to dangerous industries. It has been applied on the urban area of Mulhouse, which is characterized by four dangerous sites (three "Seveso" sites and a freight station). We chose to use the fuzzy sets theory, as it provides very interesting advantages to the study of risks in general. Two variables have been considered: the accumulated expected effects and the spatial potential of dangerous industries. These variables have been retained in order to illustrate that the exposure is higher when several industries are close together. We have also used the potential in order to point out that the effects of an industry are greater at a short distance than very far from it. The variables have been combined with two aggregation operators, the fuzzy sum and the gamma operator. The first simulations show that two sites are more exposed to dangerous sites (close to the freight station and near the TYM and EPM factories). The integration of the distance (or the spatial potential) into the model allows to define gradients of exposure inversely proportional to the distance to dangerous industries. The fuzzy sum seems to be more adapted to our study than the gamma operator.

The further step will consist in combining the layer of exposure to dangerous industries with the layer of the vulnerable elements, in order to obtain a map of the industrial risk. Then, we will combine the map of industrial risk with the map of seismic risk, in order to identify the areas of combined and accumulated risks, i.e. the areas of greatest danger. These maps could be worth it for the authorities who are in charge of the management of risks.

Map 7: map of exposure to dangerous industries in Mulhouse obtained with the gamma operator. A membership degree of 1 represents a high exposure.

Figure 1 :

 1 Figure 1: Membership function of a given variable x: the sets theory (according to Cantor) (left) vs the fuzzy sets theory (according to Zadeh) (right).

Figure 3 :

 3 Figure 3: Combination of the different variables, resulting in the evaluation of the exposure to dangerous industries. The accumulation effect can be simple, minor or major, as defined by figure 4.

Figure 4 :

 4 Figure 4: Different types of accumulation depending on the number of sources (one or two industries) and on the type of expected effects (different or similar).

Case 1 :

 1 leak of toxic products (site A); -Case 2: leak of toxic products (site A) + leak of toxic products (site A) (two different toxic products); -Case 3: leak of toxic products (site A) + leak of toxic products (site A) + leak of toxic products (site B); -Case 4: explosion (site A) + leak of toxic products (site A) + leak of toxic products (site A); -Case 5: explosion (site A) + leak of toxic products (site A) + leak of toxic products (site A) + leak of toxic products (site B); -Case 6: boil over (site A); -Case 7: boil over (site B) + leak of toxic products (site B); -Case 8: boil over (site B) + leak of toxic products (site B) + leak of toxic products (site C).

2 Case 3 : 3 Case 4 : 4 Case 5 : 5 Case 6 : 8 Case 8 :

 2334455688 Case 1: leak of toxic products (site A) 0.1 Case 2: leak of toxic products (site A) + leak of toxic products (site A) 0.leak of toxic products (site A) + leak of toxic products (site A) + leak of toxic products (site B) 0.explosion (site A) + leak of toxic products (site A) + leak of toxic products (site A) 0.explosion (site A) + leak of toxic products (site A) + leak of toxic products (site A) + leak of toxic products (site B) 0.boil over (site A) 0.6 Case 7: boil over (site B) + leak of toxic products (site B) 0.boil over (site B) + leak of toxic products (site B) + leak of toxic products (site C

AUTHORS INFORMATION

Elise BECK elise.beck@lorraine.u-strasbg.


Clémentine Louet

Méline Saubin

Axelle Andrieux

Antoine Persoons

Mathilde Gorse

Jérémy Pétrowski

Stéphane De Mita

Bénédicte Fabre

Sébastien Duplessis

Pascal Frey

Fabien Halkett

Association of two co-occurring mutations at the AvrMlp7 avirulence locus in poplar rust during the breakdown of RMlp7 resistance gene

Keywords: Melampsora larici-populina, molecular evolution, gene-for-gene interaction, pathogen, fungi

The deployment of plant varieties carrying resistance (R) genes exerts strong selection pressures towards pathogen populations. Several studies reported the rapid evolution of avirulence (Avr) genes to escape R-mediated plant immunity and identified a variety of mechanisms leading to virulence.

The poplar rust fungus Melampsora larici-populina is the most damaging pathogen of poplars. A major adaptive event occurred in 1994 with the breakdown of RMlp7 resistance gene in poplar.

Population genomics studies identified a locus in the genome of M. larici-populina, which likely corresponds to the AvrMlp7 candidate avirulence gene. We used a population genetics approach combined with dedicated qPCR assays on a comprehensive set of 281 isolates, covering 27 years (encompassing the resistance breakdown event), to validate the candidate locus and to assess its polymorphism. We found two mechanisms, a point mutation and a deletion, that allowed the pathogen to escape RMlp7-mediated resistance. Six diploid genotypes were thus characterized at the candidate locus (three avirulent and three virulent). In addition, a temporal analysis revealed that the two virulence alleles pre-existed (harboured as avirulent heterozygous genotypes) since the early samplings and were found in association (as virulent genotypes) at the time of the resistance breakdown. Our study documented that, in a diploid pathogen, combining virulence determinisms is adaptive.