[The first steps towards advanced practice for radiation therapists]. / Les prémices de la pratique avancée pour le manipulateur en radiothérapie.

The implementation of advanced practice in RT requires evidence regarding the clinical practices of radiation therapists (RTT) in the field. In this context, the goal of this article is to report the roles assigned to RTT in order to meet the demands of patients, RT services, and/or healthcare professionals. As part of the French Society of Oncologic Radiotherapy's congress, the Radiotherapy Committee of the French Association of radiographers presented a scientific program encompassing three main themes: patient follow-up by a RTT, the expertise of an RTT in Image Guided Radiation Therapy (IGRT), Adaptive Radiotherapy (ART), and the involvement of a RTT in research. This article presents an overview of five oral presentations that highlight concrete examples of roles assigned to RTTs in these specific domains. The follow-up of patients has been assigned to RTT. Research and development have been recognized as activities in which RTT play a significant role. The establishment of RTT specializing in IGRT has been reported to facilitate decision-making and is essential in ensuring professional expertise. Lastly, there is a need to enhance RTT skills in adaptive RT to support the implementation of this technique. These roles described as advanced practice meet needs and require a specific organisational framework and appropriate education and training (master type). Activities such as post-RT follow-up, validation of positioning imaging, delineation, writing research protocols, and involvement in the development of technological innovations were identified as essential tasks that can be assigned to RTT.

Factors Influencing Carbon Stocks and Accumulation Rates in Eelgrass Meadows Across New England, USA.

Increasing the protection of coastal vegetated ecosystems has been suggested as one strategy to compensate for increasing carbon dioxide (CO2) in the atmosphere as the capacity of these habitats to sequester and store carbon exceeds that of terrestrial habitats. Seagrasses are a group of foundation species that grow in shallow coastal and estuarine systems and have an exceptional ability to sequester and store large quantities of carbon in biomass and, particularly, in sediments. However, carbon stocks (Corg stocks) and carbon accumulation rates (Corg accumulation) in seagrass meadows are highly variable both spatially and temporally, making it difficult to extrapolate this strategy to areas where information is lacking. In this study, Corg stocks and Corg accumulation were determined at 11 eelgrass meadows across New England, representing a range of eutrophication and exposure conditions. In addition, the environmental factors and structural characteristics of meadows related to variation in Corg stocks were identified. The objectives were accomplished by assessing stable isotopes of δ13C and δ15N as well as %C and %N in plant tissues and sediments, measuring grain size and 210Pb of sediment cores, and through assessing site exposure. Variability in Corg stocks in seagrass meadows is well predicted using commonly measured environmental variables such as grain size distribution. This study allows incorporation of data and insights for the northwest Atlantic, where few studies on carbon sequestration by seagrasses have been conducted.

Same father, same face: Deep learning reveals selection for signaling kinship in a wild primate.

Many animals rely on facial traits to recognize their kin; however, whether these traits have been selected specifically for this function remains unknown. Using deep learning for face recognition, we present the first evidence that interindividual facial resemblance has been selected to signal paternal kinship. Mandrills (Mandrillus sphinx) live in matrilineal societies, in which females spend their entire lives not only with maternal half-sisters (MHS) but also with paternal half-sisters (PHS). We show that PHS have more differentiated social relationships compared to nonkin, suggesting the existence of kin recognition mechanisms. We further demonstrate that facial resemblance increases with genetic relatedness. However, PHS resemble each other visually more than MHS do, despite both kin categories sharing similar degrees of genetic relatedness. This paternally derived facial resemblance among PHS indicates selection to facilitate kin recognition. This study also highlights the potential of artificial intelligence to study phenotypic evolution.

A longitudinal molecular study of the ecology of malaria infections in free-ranging mandrills.

Unravelling the determinants of host variation in susceptibility and exposure to parasite infections, infection dynamics and the consequences of parasitism on host health is of paramount interest to understand the evolution of complex host-parasite interactions. In this study, we evaluated the determinants, temporal changes and physiological correlates of Plasmodium infections in a large natural population of mandrills (Mandrillus sphinx). Over six consecutive years, we obtained detailed parasitological and physiological data from 100 male and female mandrills of all ages. The probability of infection by Plasmodium gonderi and P. mandrilli was elevated (ca. 40%) but most infections were chronical and dynamic, with several cases of parasite switching and clearance. Positive co-infections also occurred between both parasites. Individual age and sex influenced the probability of infections with some differences between parasites: while P. mandrilli appeared to infect its hosts rather randomly, P. gonderi particularly infected middle-aged mandrills. Males were also more susceptible to P. gonderi than females and were more likely to be infected by this parasite at the beginning of an infection by the simian immunodeficiency virus. P. gonderi, and to a lesser extent P. mandrilli, influenced mandrills' physiology: skin temperatures and neutrophil/lymphocyte ratio were both impacted, generally depending on individual age and sex. These results highlight the ecological complexity of Plasmodium infections in nonhuman primates and the efforts that need to be done to decipher the epidemiology of such parasites.

CtIP fusion to Cas9 enhances transgene integration by homology-dependent repair.

In genome editing with CRISPR-Cas9, transgene integration often remains challenging. Here, we present an approach for increasing the efficiency of transgene integration by homology-dependent repair (HDR). CtIP, a key protein in early steps of homologous recombination, is fused to Cas9 and stimulates transgene integration by HDR at the human AAVS1 safe harbor locus. A minimal N-terminal fragment of CtIP, designated HE for HDR enhancer, is sufficient to stimulate HDR and this depends on CDK phosphorylation sites and the multimerization domain essential for CtIP activity in homologous recombination. HDR stimulation by Cas9-HE, however, depends on the guide RNA used, a limitation that may be overcome by testing multiple guides to the locus of interest. The Cas9-HE fusion is simple to use and allows obtaining twofold or more efficient transgene integration than that with Cas9 in several experimental systems, including human cell lines, iPS cells, and rat zygotes.

Seasonal glucocorticoid production correlates with a suite of small-magnitude environmental, demographic, and physiological effects in mandrills.

OBJECTIVES: The activation of the hypothalamic-pituitary-adrenal axis is a neuroendocrine response to external and internal changes that animals face on a predictable or unpredictable basis. Across species, variation in glucocorticoid production has been related to such changes. In this study, we investigated the predictable, seasonal sources of variation in the levels of fecal glucocorticoid metabolites (fGCM) in a large natural population of mandrills (Mandrillus sphinx) in Southern Gabon. MATERIALS AND METHODS: Using five years of regular behavioral monitoring and hormone analyses performed on 1,233 fecal samples collected on 99 individuals of both sexes and all ages and General Linear Mixed Models, we studied the three main seasonal predictors of fGCM concentrations: (i) weather conditions, (ii) number of adult males, and (iii) female reproductive status. These three predictors all vary seasonally in mandrills. RESULTS: We first showed an increase in fGCM concentrations during the short dry season while controlling for other factors. Pregnant females, which include the large majority of adult females at this time of the year, mainly drove this increase, although a combination of other small-magnitude, season-related effects linked to climatic events and demographic changes also partly explained this seasonal trend. Indeed, fGCM concentrations increased with both low temperatures (and low rainfall) and high numbers of adult males present in the group. These seasonal changes, while correlated, held true throughout the studied years and when restricting our analyses to a given season. Finally, we found that older mandrills showed on average higher fGCM concentrations than younger ones and that medium-ranked females exhibited the highest levels of fGCMs. DISCUSSION: The observed patterns suggest that plasticity in mandrills' metabolism in the form of glucocorticoid production allows them to adjust to predictable changes in climatic, demographic and physiological conditions by mobilizing and redirecting energetic resources toward appropriate, calibrated seasonal responses.

Social shaping of voices does not impair phenotype matching of kinship in mandrills.

Kin selection theory provides a strong theoretical framework to explain the evolution of altruism and cooperative behaviour among genetically related individuals. However, the proximate mechanisms underlying kin discrimination, a necessary process to express kin-related behaviour, remain poorly known. In particular, no study has yet unambiguously disentangled mechanisms based on learned familiarity from true phenotype matching in kin discrimination based on vocal signals. Here we show that in addition to genetic background, social accommodation also shapes individual voices in an Old World monkey (Mandrillus sphinx), even though primate vocalizations were thought to be innate and little flexible. Nonetheless, social shaping of voice parameters does not impair kin discrimination through phenotype-matching of unknown relatives, revealing unexpected discriminatory versatility despite signal complexity. Accurate signal production and perception, therefore, provide a basis for kin identification and kin-biased behaviour in an Old World primate.

[Mesothelioma and familial Mediterranean fever: A relationship?]. / Mésothéliome et fièvre méditerranéenne familiale : quelle relation ?

INTRODUCTION: The majority of pleural and peritoneal mesotheliomas are linked to asbestos exposure but, in around 20% of cases, no history of such exposure is found. Periodic disease is associated with recurrent serositis, which could favor the development of mesothelioma. CASE REPORT: We report a case of pleural mesothelioma in a 50-year-old Lebanese woman, with no detectable exposure to asbestos but suffering from periodic disease (familial Mediterranean fever) with recurrent episodes of serositis. DISCUSSION: Many cases of peritoneal mesothelioma in patients with FMF are reported in the literature. This is the second reported case of pleural mesothelioma associated with periodic disease. Because of the low incidence of both diseases, further publications are required to support the hypothesis of a causal link. It is important, therefore, that all cases of an association of periodic disease and mesothelioma are reported.

Mediastinal recurrence from ovarian cystadenocarcinoma presenting as pleuro-pericardial cyst.

A 56 year-old woman (treated for ovarian cystadenocarcinoma 9-yrs before) presented a slowly increasing dyspnea. CT-scan revealed a mediastinal cyst with typical radiological pattern compatible with benign pleuro-pericardial cyst. The cyst was removed via right thoracoscopy. Surprisingly, the pathology were indicative of cystic mediastinal recurrence from ovarian adenocarcinoma.

Genetic structure in a dynamic baboon hybrid zone corroborates behavioural observations in a hybrid population.

Behaviour and genetic structure are intimately related: mating patterns and patterns of movement between groups or populations influence the movement of genetic variation across the landscape and from one generation to the next. In hybrid zones, the behaviour of the hybridizing taxa can also impact the incidence and outcome of hybridization events. Hybridization between yellow baboons and anubis baboons has been well documented in the Amboseli basin of Kenya, where more anubis-like individuals tend to experience maturational and reproductive advantages. However, it is unknown whether these advantages are reflected in the genetic structure of populations surrounding this area. Here, we used microsatellite genotype data to evaluate the structure and composition of baboon populations in southern Kenya. Our results indicate that, unlike for mitochondrial DNA, microsatellite-based measures of genetic structure concord with phenotypically based taxonomic distinctions and that the currently active hybrid zone is relatively narrow. Isolation with migration analysis revealed asymmetric gene flow in this region from anubis populations into yellow populations, in support of the anubis-biased phenotypic advantages observed in Amboseli. Populations that are primarily yellow but that receive anubis gene flow exhibit higher levels of genetic diversity than yellow populations far from the introgression front. Our results support previous work that indicates a long history of hybridization and introgression among East African baboons. Specifically, it suggests that anubis baboons are in the process of gradual range expansion into the range of yellow baboons, a pattern potentially explained by behavioural and life history advantages that correlate with anubis ancestry.

Honest olfactory ornamentation in a female-dominant primate.

Sexual selection theory predicts that potential mates or competitors signal their quality to conspecifics. Whereas evidence of honest visual or vocal signals in males abounds, evidence of honest signalling via scent or by females is scarce. We previously showed that scent marks in male lemurs seasonally encode information about individual heterozygosity - a reliable predictor of immunocompetence and survivorship. As female lemurs dominate males, compete over resources, and produce sexually differentiated scent marks that likely evolved via direct selection, here we tested whether females also advertise genetic quality via olfactory cues. During the breeding season specifically, individual heterozygosity correlated negatively with the diversity of fatty acids (FAs) expressed in labial secretions and positively with the diversity of heavy FA esters. As odour-gene relationships predictive of health and survivorship emerged during a period critical to mate choice and female competition, we posit that genital scent marks function as honest olfactory ornaments in females.

Opposites attract: MHC-associated mate choice in a polygynous primate.

We investigated reproduction in a semi-free-ranging population of a polygynous primate, the mandrill, in relation to genetic relatedness and male genetic characteristics, using neutral microsatellite and major histocompatibility complex (MHC) genotyping. We compared genetic dissimilarity to the mother and genetic characteristics of the sire with all other potential sires present at the conception of each offspring (193 offspring for microsatellite genetics, 180 for MHC). The probability that a given male sired increased as pedigree relatedness with the mother decreased, and overall genetic dissimilarity and MHC dissimilarity with the mother increased. Reproductive success also increased with male microsatellite heterozygosity and MHC diversity. These effects were apparent despite the strong influence of dominance rank on male reproductive success. The closed nature of our study population is comparable to human populations for which MHC-associated mate choice has been reported, suggesting that such mate choice may be especially important in relatively isolated populations with little migration to introduce genetic variation.

Genetic evidence reveals temporal change in hybridization patterns in a wild baboon population.

The process and consequences of hybridization are of interest to evolutionary biologists because of the importance of hybridization in understanding reproductive isolation, speciation, and the influence of introgression on population genetic structure. Recent studies of hybridization have been enhanced by the advent of sensitive, genetic marker-based techniques for inferring the degree of admixture occurring within individuals. Here we present a genetic marker-based analysis of hybridization in a large-bodied, long-lived mammal over multiple generations. We analysed patterns of hybridization between yellow baboons (Papio cynocephalus) and anubis baboons (Papio anubis) in a well-studied natural population in Amboseli National Park, Kenya, using genetic samples from 450 individuals born over the last 36 years. We assigned genetic hybrid scores based on genotypes at 14 microsatellite loci using the clustering algorithm implemented in STRUCTURE 2.0, and assessed the robustness of these scores by comparison to pedigree information and through simulation. The genetic hybrid scores showed generally good agreement with previous morphological assessments of hybridity, but suggest that genetic methods may be more sensitive for identification of low levels of hybridity. The results of our analysis indicate that the proportion of hybrids in the Amboseli population has grown over time, but that the average proportion of anubis ancestry within hybrids is gradually decreasing. We argue that these patterns are probably a result of both selective and nonselective processes, including differences in the timing of life-history events for hybrid males relative to yellow baboon males, and stochasticity in long-distance dispersal from the source anubis population into Amboseli.

Age at maturity in wild baboons: genetic, environmental and demographic influences.

The timing of early life-history events, such as sexual maturation and first reproduction, can greatly influence variation in individual fitness. In this study, we analysed possible sources of variation underlying different measures of age at social and physical maturation in wild baboons in the Amboseli basin, Kenya. The Amboseli baboons are a natural population primarily comprised of yellow baboons (Papio cynocephalus) that occasionally hybridize with anubis baboons (Papio anubis) from outside the basin. We found that males and females differed in the extent to which various factors influenced their maturation. Surprisingly, we found that male maturation was most strongly related to the proportion of anubis ancestry revealed by their microsatellite genotypes: hybrid males matured earlier than yellow males. In contrast, although hybrid females reached menarche slightly earlier than yellow females, maternal rank and the presence of maternal relatives had the largest effects on female maturation, followed by more modest effects of group size and rainfall. Our results indicate that a complex combination of demographic, genetic, environmental, and maternal effects contribute to variation in the timing of these life-history milestones.

Paternal effects on offspring fitness in a multimale primate society.

When females mate with multiple males, paternal care is generally expected to be negligible, because it may be difficult or impossible for males to discriminate their own offspring from those of other males, and because engaging in paternal care may reduce male mating opportunities. Consequently, males in multimale societies are not predicted to provide direct benefits to their offspring. We have recently demonstrated, however, that males in a typical multimale primate society (yellow baboons, Papio cynocephalus) discriminate their own offspring from those of other males and provide care to them in the form of repeated support during agonistic encounters. This observation raises the question of whether fathers enhance offspring fitness in this species. Here we use 30 years of data on age at maturity for 118 yellow baboons with known fathers. We show that the father's presence in the offspring's social group during the offspring's immature period accelerated the timing of physiological maturation in daughters. Sons also experienced accelerated maturation if their father was present during their immature period, but only if the father was high ranking at the time of their birth. Because age at reproductive maturity has a large impact on lifetime reproductive success, our results indicate a direct effect of paternal presence on offspring fitness. This relationship in turn suggests that the multiple roles that males play in multimale animal societies have not been sufficiently examined or appreciated and that paternal effects may be more pervasive than previously appreciated.

Inbreeding depression in non-human primates: a historical review of methods used and empirical data.

Offspring born to related parents may show reduced fitness due to inbreeding depression. Although evidence of inbreeding depression has accumulated for a variety of taxa during the past two decades, such analyses remain rare for primate species, probably because of their long generation time. However, inbreeding can have important fitness costs and is likely to shape life-history traits in all living species. As a consequence, selection should have favored inbreeding avoidance via sex-biased dispersal, extra-group paternity, or kin discrimination. In this paper, we review empirical studies on the effects of inbreeding on fitness traits or fitness correlates in primate species. In addition, we report the methods that have been used to detect inbreeding in primate populations, and their development with the improvement of laboratory techniques. We focus particularly on the advantages and disadvantages using microsatellite loci to detect inbreeding. Although the genetic data that are typically available (partial pedigrees, use of microsatellite heterozygosity as an estimate of genomewide inbreeding) tend to impose constraints on analyses, we encourage primatologists to explore the potential effects of inbreeding if they have access to even partial pedigrees or genetic information. Such studies are important because of both the value of basic research in inbreeding depression in the wild and the conservation issues associated with inbreeding, particularly in threatened species, which include more than half of the currently living primate species.

Life history correlates of inbreeding depression in mandrills (Mandrillus sphinx).

Inbreeding depression reflects the negative consequences of increased homozygosity at genes that affect fitness. We investigate inbreeding depression in a semi-free-ranging colony of mandrills (Mandrillus sphinx), using high-quality pedigree data, comprising five maternal generations and 20 years of morphological and demographic data. We examine the relationship between inbreeding coefficients and four fitness correlates: two growth parameters (mass and height for age) and longevity in both sexes, and age at first conception in females. Inbreeding was correlated with both growth parameters, but only in females, with inbred females being smaller than noninbred females. Inbreeding was also correlated significantly with age at first conception, with inbred females giving birth earlier in life than noninbred females. We suggest that sex-biased maternal investment may explain this sex-differential response to inbreeding, although the lack of a significant association between inbreeding and growth in males may also be due to the provisioned nature of the colony. The surprising relationship between age at first conception and inbreeding may be related to smaller adult size in inbred females, or to their being less able to escape from male sexual coercion.

Genetic diversity and reproductive success in mandrills (Mandrillus sphinx).

Recent studies of wild animal populations have shown that estimators of neutral genetic diversity, such as mean heterozygosity, are often correlated with various fitness traits, such as survival, disease susceptibility, or reproductive success. We used two estimators of genetic diversity to explore the relationship between heterozygosity and reproductive success in male and female mandrills (Mandrillus sphinx) living in a semifree ranging setting in Gabon. Because social rank is known to influence reproductive success in both sexes, we also examined the correlation between genetic diversity and social rank in females, and acquisition of alpha status in males, as well as length of alpha male tenure. We found that heterozygous individuals showed greater reproductive success, with both females and males producing more offspring. However, heterozygosity influenced reproductive success only in dominant males, not in subordinates. Neither the acquisition of alpha status in males, nor social rank in females, was significantly correlated with heterozygosity, although more heterozygous alpha males showed longer tenure than homozygous ones. We also tested whether the benefits of greater genetic diversity were due mainly to a genome-wide effect of inbreeding depression or to heterosis at one or a few loci. Multilocus effects best explained the correlation between heterozygosity and reproductive success and tenure, indicating the occurrence of inbreeding depression in this mandrill colony.

Perioperative analysis of biopsies issued from mediastinoscopy.

BACKGROUND: The objective of this study was to evaluate frozen sections of samples obtained at mediastinoscopy for their clinical usefulness. METHODS: This study retrospectively reviewed the records of all patients who underwent mediastinoscopy with perioperative frozen sections in a 1-year period. RESULTS: A total of 123 consecutive patients underwent the procedure. There were no false-positive results. Of the 71 malignant proliferations, 67 were diagnosed from frozen sections. The technique never failed to establish the absence of mediastinal nodal involvement in patients with suspected or proven lung tumors and enlarged nodes (n = 18) who underwent immediate thoracotomy. Frozen sections allowed recognition (n = 36) or strong suspicion (n = 4) of N2 disease in patients subsequently treated by induction chemotherapy. The technique never failed to establish the nonresectability of lung cancer in patients for whom this condition was suspected perioperatively (clinical stage IIIb; n = 10). CONCLUSIONS: Mediastinoscopy with frozen sections remains an extremely useful tool for the management of paratracheal or subcarinal mediastinal disease.

Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer.

BACKGROUND: In advanced metastatic colorectal adenocarcinoma, the addition of a neo-adjuvant systemic treatment to surgery might translate into a survival advantage, although this is yet to be confirmed by ongoing randomized trials. The objective of this study was to assess the effects of preoperative systemic chemotherapy on the morphology of non-tumoral liver. PATIENTS AND METHODS: A large series of surgically resected liver metastases (n=153) was selected. Light microscopy, electron microscopy, and immunohistochemistry using antibodies against endothelial cells (CD31) and hepatic stellate cells (alpha-SM actin, CRBP-1) were performed to identify sinusoidal wall integrity. RESULTS: We found that 44 (51%) of the 87 post-chemotherapic liver resection specimens had sinusoidal dilatation and hemorrhage, related to rupture of the sinusoidal barrier. In contrast, the 66 livers treated by surgery alone remained normal. In 21 out of the 44 post-chemotherapy patients (48%), perisinusoidal and veno-occlusive fibrosis also developed. Sinusoidal injury persisted several months after end of chemotherapy, and fibrosis may progress. Development of lesions was strongly correlated to the use of oxaliplatin; 34 out of 43 patients (78%) treated with this drug showed striking sinusoidal alterations. CONCLUSIONS: Systemic neo-adjuvant chemotherapy in metastatic colorectal cancer frequently causes morphological lesions involving hepatic microvasculature. Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplatin.