Mortalité maternelle et périnatalité au premier millénaire à Lisieux (Calvados, France)

La fouille exhaustive d’un vaste ensemble funéraire suburbain à Lisieux (Calvados) a montré l’implantation successive de deux cimetières chronologiquement distincts et probablement sans lien entre eux. Le plus vaste a perduré pendant plus d’un siècle, du début du ive s. aux premières années du ve s. ; le second, de superficie nettement plus réduite, s’est installé sur le même site dans la seconde moitié du vie s. jusqu’au début du ixe s. Dans quatre sépultures, l’association étroite d’un squelette féminin et d’un enfant décédé en période périnatale (fœtus en place dans le bassin adulte, nouveau-né déposé au contact direct du corps maternel) suggère la probabilité de décès d’origine obstétricale. La typologie de ces tombes et leur localisation à l’intérieur de l’espace sépulcral ne les distinguaient en rien de la majorité des autres inhumations. La position respective des squelettes sur le terrain et l’examen macroscopique, microscopique et radiologique des pièces osseuses en laboratoire ont permis de reconstituer le déroulement chronologique probable de chaque événement (décès intervenus en cours de grossesse, lors de l’accouchement ou durant le post-partum), de mettre en évidence certains indices constituant des facteurs de risque pour la mère ou l’enfant, puis d’argumenter, au cas par cas, les causes obstétricales, directes ou indirectes, ayant pu conduire à cette issue fatale.The complete excavation of a large suburban necropolis in Lisieux (Calvados, France) has brought to light two chronologically distinct, apparently unconnected cemeteries. The first was in use for just over one century, from the beginning of the 4th century A.D. to the early 5th century A.D. The second cemetery, covering a smaller area on the same site, lasted from the second half of the 6th century A.D. to the beginning of the 9th century A.D. In four burials, a female adult and an immature skeleton are in direct association (foetus inside the pelvis or newborn lain on the female body) suggesting the probability of maternal deaths. The typology of these graves and their organisation within the burial ground do not distinguish them from most of the other burials. Observation of the positions of both skeletons during excavation, and macroscopic, microscopic and radiological examination of the bones in the laboratory has enabled the reconstitution of each obstetrical event (death occurring before, during or after delivery), the indication of certain maternal or foetal risks, and an argumentation, case by case, for the obstetrical causes which could have led directly or indirectly to these maternal deaths

Fronto-Temporal Disconnection Within the Presence Hallucination Network in Psychotic Patients With Passivity Experiences.

Psychosis, characterized by hallucinations and delusions, is a common feature of psychiatric disease, especially schizophrenia. One prominent theory posits that psychosis is driven by abnormal sensorimotor predictions leading to the misattribution of self-related events. This misattribution has been linked to passivity experiences (PE), such as loss of agency and, more recently, to presence hallucinations (PH), defined as the conscious experience of the presence of an alien agent while no person is actually present. PH has been observed in schizophrenia, Parkinson's disease, and neurological patients with brain lesions and, recently, the brain mechanisms of PH (PH-network) have been determined comprising bilateral posterior middle temporal gyrus (pMTG), inferior frontal gyrus (IFG), and ventral premotor cortex (vPMC). Given that the experience of an alien agent is a common feature of PE, we here analyzed the functional connectivity within the PH-network in psychotic patients with (N = 39) vs without PE (N = 26). We observed reduced fronto-temporal functional connectivity in patients with PE compared to patients without PE between the right pMTG and the right and left IFG of the PH-network. Moreover, when seeding from these altered regions, we observed specific alterations with brain regions commonly linked to auditory-verbal hallucinations (such as Heschl's gyrus). The present connectivity findings within the PH-network extend the disconnection hypothesis for hallucinations to the specific case of PH and associates the PH-network with key brain regions for frequent psychotic symptoms such as auditory-verbal hallucinations, showing that PH are relevant to the study of the brain mechanisms of psychosis and PE

Catalytic reductive N-alkylation of amines using carboxylic acids

We report a catalytic reductive alkylation reaction of primary or secondary amines with carboxylic acids. The two-phase process involves silane mediated direct amidation followed by catalytic reduction

Dental calculus and isotopes provide direct evidence of fish and plant consumption in Mesolithic Mediterranean

In this contribution we dismantle the perceived role of marine resources and plant foods in the subsistence economy of Holocene foragers of the Central Mediterranean using a combination of dental calculus and stable isotope analyses. The discovery of fish scales and flesh fragments, starch granules and other plant and animal micro-debris in the dental calculus of a Mesolithic forager dated to the end of the 8th millenium BC and buried in the Vlakno Cave on Dugi Otok Island in the Croatian Archipelago demonstrates that marine resources were regularly consumed by the individual together with a variety of plant foods. Since previous stable isotope data in the Eastern Adriatic and the Mediterranean region emphasises that terrestrial-based resources contributed mainly to Mesolithic diets in the Mediterranean Basin, our results provide an alternative view of the dietary habits of Mesolithic foragers in the Mediterranean region based on a combination of novel methodologies and data

Photocatalytic Nanolithography of Self-Assembled Monolayers and Proteins

Self-assembled monolayers of alkylthiolates on gold and alkylsilanes on silicon dioxide have been patterned photocatalytically on sub-100 nm length-scales using both apertured near-field and apertureless methods. Apertured lithography was carried out by means of an argon ion laser (364 nm) coupled to cantilever-type near-field probes with a thin film of titania deposited over the aperture. Apertureless lithography was carried out with a helium–cadmium laser (325 nm) to excite titanium-coated, contact-mode atomic force microscope (AFM) probes. This latter approach is readily implementable on any commercial AFM system. Photodegradation occurred in both cases through the localized photocatalytic degradation of the monolayer. For alkanethiols, degradation of one thiol exposed the bare substrate, enabling refunctionalization of the bare gold by a second, contrasting thiol. For alkylsilanes, degradation of the adsorbate molecule provided a facile means for protein patterning. Lines were written in a protein-resistant film formed by the adsorption of oligo(ethylene glycol)-functionalized trichlorosilanes on glass, leading to the formation of sub-100 nm adhesive, aldehyde-functionalized regions. These were derivatized with aminobutylnitrilotriacetic acid, and complexed with Ni2+, enabling the binding of histidine-labeled green fluorescent protein, which yielded bright fluorescence from 70-nm-wide lines that could be imaged clearly in a confocal microscope

Neonate Human Remains: A Window of Opportunity to the Molecular Study of Ancient Syphilis

Ancient DNA (aDNA) analysis can be a useful tool in bacterial disease diagnosis in human remains. However, while the recovery of Mycobacterium spp. has been widely successful, several authors report unsuccessful results regarding ancient treponemal DNA, casting doubts on the usefulness of this technique for the diagnosis of ancient syphilis. Here, we present results from an analysis of four newborn specimens recovered from the crypt of “La Ermita de la Soledad” (XVI–XVII centuries), located in the province of Huelva in the southwest of Spain. We extracted and analyzed aDNA in three independent laboratories, following specific procedures generally practiced in the aDNA field, including cloning of the amplified DNA fragments and sequencing of several clones. This is the most ancient case, reported to date, from which detection of DNA from T. pallidum subspecies pallidum has been successful in more than one individual, and we put forward a hypothesis to explain this result, taking into account the course of the disease in neonate individuals

Syphilis at the Crossroad of Phylogenetics and Paleopathology

The origin of syphilis is still controversial. Different research avenues explore its fascinating history. Here we employed a new integrative approach, where paleopathology and molecular analyses are combined. As an exercise to test the validity of this approach we examined different hypotheses on the origin of syphilis and other human diseases caused by treponemes (treponematoses). Initially, we constructed a worldwide map containing all accessible reports on palaeopathological evidences of treponematoses before Columbus's return to Europe. Then, we selected the oldest ones to calibrate the time of the most recent common ancestor of Treponema pallidum subsp. pallidum, T. pallidum subsp. endemicum and T. pallidum subsp. pertenue in phylogenetic analyses with 21 genetic regions of different T. pallidum strains previously reported. Finally, we estimated the treponemes' evolutionary rate to test three scenarios: A) if treponematoses accompanied human evolution since Homo erectus; B) if venereal syphilis arose very recently from less virulent strains caught in the New World about 500 years ago, and C) if it emerged in the Americas between 16,500 and 5,000 years ago. Two of the resulting evolutionary rates were unlikely and do not explain the existent osseous evidence. Thus, treponematoses, as we know them today, did not emerge with H. erectus, nor did venereal syphilis appear only five centuries ago. However, considering 16,500 years before present (yBP) as the time of the first colonization of the Americas, and approximately 5,000 yBP as the oldest probable evidence of venereal syphilis in the world, we could not entirely reject hypothesis C. We confirm that syphilis seems to have emerged in this time span, since the resulting evolutionary rate is compatible with those observed in other bacteria. In contrast, if the claims of precolumbian venereal syphilis outside the Americas are taken into account, the place of origin remains unsolved. Finally, the endeavor of joining paleopathology and phylogenetics proved to be a fruitful and promising approach for the study of infectious diseases

GWAS for quantitative resistance phenotypes in Mycobacterium tuberculosis reveals resistance genes and regulatory regions

YesDrug resistance diagnostics that rely on the detection of resistance-related mutations could expedite patient care and TB eradication. We perform minimum inhibitory concentration testing for 12 anti-TB drugs together with Illumina whole-genome sequencing on 1452 clinical Mycobacterium tuberculosis (MTB) isolates. We evaluate genome-wide associations between mutations in MTB genes or non-coding regions and resistance, followed by validation in an independent data set of 792 patient isolates. We confirm associations at 13 non-canonical loci, with two involving non-coding regions. Promoter mutations are measured to have smaller average effects on resistance than gene body mutations. We estimate the heritability of the resistance phenotype to 11 anti-TB drugs and identify a lower than expected contribution from known resistance genes. This study highlights the complexity of the genomic mechanisms associated with the MTB resistance phenotype, including the relatively large number of potentially causal loci, and emphasizes the contribution of the non-coding portion of the genome.Biomedical research grant from the American Lung Association (PI MF, RG-270912-N), a K01 award from the BD2K initiative (PI MF, ES026835), and an NIAID U19 CETR grant (P.I. M.M., AI109755), the Belgian Science Policy (Belspo) (L.R., C.J.M.)

Language Proficiency and Migration: An Argument Against Testing

This paper aims at questioning the rationale for language testing in immigration policies. Although we consider knowledge of the host country’s language(s) useful and desirable for both the migrant and the host society, we argue that mandatory language testing cannot be justified. Our purpose is to offer justifications for rejecting language as a legitimate tool for controlling state borders and to regulate (access to) citizenship of a liberal democracy