The third dimension in palaeopathology: How can three-dimensional imaging by computed tomography bring an added value to retrospective diagnosis?

Abstract Three-dimensional (3D) imaging is now extensively used for studying ancient human and animal bones. This method has been consensually adopted by palaeoanthropologists, but its interest in palaeopathology has been challenged. The aim of this paper is to illustrate the contribution of 3D reconstructions to retrospective diagnosis in palaeopathology. We selected six palaeopathological cases among our research corpus representing three nosographic categories (trauma, infection and neoplasia) from various periods ranging from the Middle Palaeolithic to the beginning of the Modern Era. For each case, we compared the diagnostic value of plain X-ray, computed tomography (CT) slices, and 3D reconstructions. The latter were performed using TIVMI program, a free software for research use developed by one of us. Reconstructions are obtained by surface extraction that follows a segmentation process. We showed that this 3D method allowed reconstructing/quantifying pathological processes on ancient bones, usefully supplementing conventional radiological analyses and clearly bringing an added value to retrospective diagnosis in palaeopathology

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.

The Qafzeh site (Lower Galilee, Israel) has yielded the largest Levantine hominin collection from Middle Palaeolithic layers which were dated to circa 90-100 kyrs BP or to marine isotope stage 5b-c. Within the hominin sample, Qafzeh 11, circa 12-13 yrs old at death, presents a skull lesion previously attributed to a healed trauma. Three dimensional imaging methods allowed us to better explore this lesion which appeared as being a frontal bone depressed fracture, associated with brain damage. Furthermore the endocranial volume, smaller than expected for dental age, supports the hypothesis of a growth delay due to traumatic brain injury. This trauma did not affect the typical human brain morphology pattern of the right frontal and left occipital petalia. It is highly probable that this young individual suffered from personality and neurological troubles directly related to focal cerebral damage. Interestingly this young individual benefited of a unique funerary practice among the south-western Asian burials dated to Middle Palaeolithic

Eighteenth century Yersinia pestis genomes reveal the long-term persistence of an historical plague focus

© Bos et al. The 14th-18th century pandemic of Yersinia pestis caused devastating disease outbreaks in Europe for almost 400 years. The reasons for plague's persistence and abrupt disappearance in Europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in Europe itself, or successive disease introductions from other locations. Here we present five Y. pestis genomes from one of the last European outbreaks of plague, from 1722 in Marseille, France. The lineage identified has not been found in any extant Y. pestis foci sampled to date, and has its ancestry in strains obtained from victims of the 14th century Black Death. These data suggest the existence of a previously uncharacterized historical plague focus that persisted for at least three centuries. We propose that this disease source may have been responsible for the many resurgences of plague in Europe following the Black Death

Estimation du sexe fœtal à partir de l’ilium

La détermination du sexe est une des problématiques les plus fréquemment rencontrées en anthropologie médico-légale. Chez l’adulte, cette détermination est essentiellement basée sur l’os iliaque et autorise un très fort taux de classification correcte, tandis que chez le fœtus, les études sont beaucoup moins nombreuses et conduisent à des résultats souvent contradictoires.Nous avons recherché sur 83 paires d’ilia fœtaux de la collection ostéologique hongroise de Fazekas et Kosa quels étaient les critères métriques qui décrivaient le mieux le dimorphisme sexuel, en évaluant les différentes méthodes proposées sur l’ilium fœtal et en adaptant certaines de celles proposées chez l’adulte. Nous avons pour cela établi et validé un protocole de prise de clichés photographiques et une méthode de mesure sur image numérisée à partir du logiciel Adobe Photoshop 6‚.Certains des paramètres retenus dans l’étude – principalement ceux qui ont été relevés sur l’échancrure ischiatique – présentant de fortes corrélations avec le sexe, nous avons établi une régression logistique estimant la probabilité d’appartenir à l’un ou l’autre des deux sexes. Le faible pourcentage de discrimination sexuelle obtenu avec cette formule nous a amené à tenir compte de l’âge : nous avons donc structuré notre échantillon en différents groupes d’âge et avons établi une formule permettant de déterminer correctement le sexe dans plus de 85 % des cas (sur l’échantillon qui a servi à l’établir) pour les fœtus dont l’âge est inférieur à 26 semaines d’aménorrhée.Sex estimation is one of the most frequently encountered issues in forensic medicine. While in the case of adults this determination is essentially based on iliac bones and provides a rather reliable classification, there are fewer studies conducted on fetuses and the results are often contradictory.Therefore, we examinated 83 pairs of fetal iliac bones in the Hungarian collection of Fazekas and Kosa and searched for metric criteria that can the best be applied for determining sexual dimorphism. During this research, we tested the different methods proposed for fetal iliac bones and adapted some others used particularly in the case of adults.For this reason, we set up and validated a protocol of taking photographs, as well as a measurement technique developed for numeric pictures with the help of a software program, Adobe Photoshop 6‚.During this study, we selected certain parameters, principally the ones taken on the great sciatic notch, which showed a strong correlation with sex, and we established a logistic regression for estimating the probability of belonging to one sex or the other.The weak percentage of sexual differentiation obtained by this formula led us to take into account age: we organised our sample in different age groups and established a formula that permits correct sex determination in more than 85% of cases (in our sample) for fetuses that are less than 24 gestational weeks old

Inhibition of Chondrosarcoma Growth by mTOR Inhibitor in an In Vivo Syngeneic Rat Model

BACKGROUND: Chondrosarcomas are the second most frequent primary malignant type of bone tumor. No effective systemic treatment has been identified in advanced or adjuvant phases for chondrosarcoma. The aim of the present study was to determine the antitumor effects of doxorubicin and everolimus, an mTOR inhibitor on chondrosarcoma progression. METHODS AND FINDINGS: Doxorubin and/or everolimus were tested in vivo as single agent or in combination in the rat orthotopic Schwarm chondrosarcoma model, in macroscopic phase, as well as with microscopic residual disease. Response to everolimus and/or doxorubicin was evaluated using chondrosarcoma volume evolution (MRI). Histological response was evaluated with % of tumor necrosis, tumor proliferation index, metabolism quantification analysis between the treated and control groups. Statistical analyses were performed using chi square, Fishers exact test. Doxorubicin single agent has no effect of tumor growth as compared to no treatment; conversely, everolimus single agent significantly inhibited tumor progression in macroscopic tumors with no synergistic additive effect with doxorubicin. Everolimus inhibited chondrosarcoma proliferation as evaluated by Ki67 expression did not induce the apoptosis of tumor cells; everolimus reduced Glut1 and 4EBP1 expression. Importantly when given in rats with microscopic residual diseases, in a pseudo neoadjuvant setting, following R1 resection of the implanted tumor, everolimus significantly delayed or prevented tumor recurrence. CONCLUSIONS: MTOR inhibitor everolimus blocks cell proliferation, Glut1 expression and HIF1a expression, and prevents in vivo chondrosarcoma tumor progression in both macroscopic and in adjuvant phase post R1 resection. Taken together, our preclinical data indicate that mTOR inhibitor may be effective as a single agent in treating chondrosarcoma patients. A clinical trial evaluating mTOr inhibitor as neo-adjuvant and adjuvant therapy in chondrosarcoma patients is being constructed