Moon-sur-Elle – Le Bourg

Cette affaire concerne la perte d’un « Thunderbolt » P-47 piloté par le second lieutenant William McGowan lors d’une opération de chasse au-dessus de Moon-sur-Elle dans le département de la Manche, en opération de soutien au débarquement de la plage de Normandie le 6 juin 1944. Le lieutenant d’aviation, Paul E. Stryker, qui accompagnait le SLT McGowan, a rapporté que l’avion du SLT McGowan avait été touché par un tir anti-aérien à environ 152,4 m d’altitude, avait percuté le sol après être pa..

Retinoic acid controls the homeostasis of pre-cDC–derived splenic and intestinal dendritic cells

Dendritic cells (DCs) comprise distinct populations with specialized immune-regulatory functions. However, the environmental factors that determine the differentiation of these subsets remain poorly defined. Here, we report that retinoic acid (RA), a vitamin A derivative, controls the homeostasis of pre-DC (precursor of DC)–derived splenic CD11b(+)CD8α(−)Esam(high) DCs and the developmentally related CD11b(+)CD103(+) subset within the gut. Whereas mice deprived of RA signaling significantly lost both of these populations, neither pre-DC–derived CD11b(−)CD8α(+) and CD11b(−)CD103(+) nor monocyte-derived CD11b(+)CD8α(−)Esam(low) or CD11b(+)CD103(−) DC populations were deficient. In fate-tracking experiments, transfer of pre-DCs into RA-supplemented hosts resulted in near complete conversion of these cells into the CD11b(+)CD8α(−) subset, whereas transfer into vitamin A–deficient (VAD) hosts caused diversion to the CD11b(−)CD8α(+) lineage. As vitamin A is an essential nutrient, we evaluated retinoid levels in mice and humans after radiation-induced mucosal injury and found this conditioning led to an acute VAD state. Consequently, radiation led to a selective loss of both RA-dependent DC subsets and impaired class II–restricted auto and antitumor immunity that could be rescued by supplemental RA. These findings establish a critical role for RA in regulating the homeostasis of pre-DC–derived DC subsets and have implications for the management of patients with immune deficiencies resulting from malnutrition and irradiation

The Evaluation and Refinement of Nonmetric Sex and Ancestry Assessment Methods in Modern Japanese and Thai Individuals

Effective biological profiles in forensic anthropology and bioarchaeology depend on the development, validation, and refinement of population-specific methods. However, most methods were developed in North America on individuals of African and European descent, and it is unlikely that such methods can generate accurate biological profiles for Asian individuals. Moreover, Native Americans have served as biological proxies for Asians due to their distantly shared genetic history, resulting in largely untested assumptions that Native Americans and Asians are homogenous and share nonmetric sexually dimorphic skeletal features and a unique suite of cranial traits that can be used in ancestry assessment. This study explores nonmetric sexual dimorphism and cranial nonmetric variability in 1,397 modern Japanese and Thai individuals 17 to 96 years of age. The first objective tests and refines the methods based on 15 traits used to predict sex from the cranium, pelvis, clavicle, and humerus that were developed on non-Asian populations. The second objective establishes 37 cranial and mandibular trait frequencies to determine if the Japanese and Thai differ from each other and from Native Americans in trait expressions. Further, the affects of sex, age, population, inter-trait correlations, intraobserver error, and secular change on the traits are assessed. The results indicate that population-specific sex assessment methods perform better in classifying the Japanese and Thai compared to those developed on non-Asian populations, producing correct classification rates of 66-98%. Additionally, the majority of cranial and mandibular traits used in ancestry assessment significantly differ in frequency between the Japanese and Thai, resulting in correct classification rates of 60-90%. Further, the Japanese and Thai are different from Native Americans in the expression of nonmetric traits. However, sex, age, population, intraobserver error, and secular change affect many nonmetric traits, thereby complicating their use in sex and ancestry assessment. This study demonstrates that the Japanese, Thai, and Native Americans are not skeletally homogenous, as they exhibit differences in sexual dimorphism and in the expression of cranial trait frequencies due to unique population histories. Moreover, the findings of this research underscore the importance of developing population-specific biological profile methods for diverse Asian populations, such as those provided here

Population-Inclusive Assigned-Sex-at-Birth Estimation from Skull Computed Tomography Scans

Methods for estimating assigned, binary sex at birth from skeletonized remains have primarily been developed for specific population groups in the U.S. (e.g., African American, European American, Hispanic) and, thus, inherently rely on ancestry estimation as a foundational component for constructing the biological profile. However, ongoing discussions in forensic anthropology highlight pressing issues with ancestry estimation practices. Therefore, this research provides population-inclusive assigned-sex estimation models for cases where ancestry is not estimated or is truly unknown. The study sample (n = 431) includes 3D volume-rendered skull computed tomography scans from the novel New Mexico Decedent Image Database of African, Asian, European, Latin, and Native Americans. Five standard nonmetric traits were scored, and eighteen standard measurements were obtained. Binary logistic regressions and discriminant function analyses were employed to produce models and classification accuracies, and intraobserver reliability was assessed. The population-inclusive nonmetric and metric models produced cross-validated classification accuracies of 81.0–87.0% and 86.7–87.0%, respectively, which did not differ significantly from the accuracy of most population-specific models. Moreover, combined nonmetric and metric models increased accuracy to 88.8–91.6%. This study indicates that population-inclusive assigned-sex estimation models can be used instead of population-specific models in cases where ancestry is intentionally not estimated, given current concerns with ancestry estimation

Assumed differences; Unquestioned typologies: The oversimplification of race and ancestry in forensic anthropology

Forensic anthropologists traditionally estimate “race” or “ancestry” as part of the biological profile. While practitioners may have changed the terms used to describe regionally patterned human skeletal variation, the degree to which they have altered their typological approaches remains unclear. This study analyzed 119 peer-reviewed forensic anthropology articles published in four relevant journals (1966–2020) by matching combination(s) of the key words “race,” “ancestry,” “ethnicity,” and/or “population affinity.” Results indicated that while “ancestry” has supplanted “race,” this change has not brought concurrent modifications in approach, nor deeper scrutiny of underlying concepts. “Race” and “ancestry” were infrequently defined in 13% and 12% of sampled articles, respectively, and a plethora of social, geographic, and pseudoscientific terms persisted. Forensic anthropologists increasingly engaged with questions addressing the forces patterning human biological variation: 65% of studies postdating 1999 discussed population histories/structures and microevolution; 38% between 1966–1999. Fewer studies contextualized or critiqued approaches to analyzing population variation (32% of studies postdating 1999; 4% from 1966–1999), and virtually no studies considered the possibility that skeletal variation reflected embodied social inequity (5% of studies postdating 1999; 0% from 1966–1999). This lack of interrogation and clarity contributes to the faulty notion that all forensic anthropologists share similar definitions and leads to an oversimplification of complex biocultural processes. While the lack of definitions and biocultural engagement may be partly due to editorial and peer-review pressures, it is likely that many forensic anthropologists have not interrogated their own perspectives. This article holds that it is essential for us to do so.Journal Articl

The effects of orthopedic pathological conditions and systemic diseases on the prevalence of hip osteoarthritis in Modern African- and European-Americans

Osteoarthritis (OA) is a leading cause of disability among aging adults. In the U.S., many individuals living with total hip replacements attribute OA as the cause. However, the majority of anthropological OA research excludes pathological individuals (i.e., individuals with systemic disease, traumatic injuries, or orthopedic devices). Thus, little is known about how implants and pathological conditions impact OA beyond a general acceptance that they likely increase OA risk. This study adds to the skeletal research surrounding OA by directly investigating its relationship with age, disease, and implants. The proximal femora of 186 African- and European-American individuals (21–95 years old) from the Edmonds Orthopedic Pathology Collection (National Museum of Health and Medicine; Armed Forces Institute of Pathology) were analyzed. The individuals were grouped into three cohorts: disease; non-disease; and previous injury/implant. Jurmain’s (1990) ordinal scoring method was used to categorize OA changes as: none/slight; moderate; severe; and ankylosis. Intra-rater reliability for the scoring of OA was perfect, while inter-rater reliability was moderate. Results from Chi-square tests, exploratory data analysis, and ordinal logistic regression showed that there was a statistically significant relationship (p <0.001) between degree of OA, age, recorded disease (e.g., cancer), and evidence of previous injury (i.e., healed fractures, fracture fixation devices). In contrast with the expectation that different populations exhibit different patterns of OA, no significant sex or ancestry effects were observed. These results help researchers better understand the etiology and contemporary risk factors of OA as well as identifying an additional subset of the population who may be at greater risk for developing OA – i.e., individuals with fractures, implants, and systemic disease, especially those in older age cohorts (60+ years).Journal Articl

Responding to the American Academy of Forensic Sciences vision, mission, and values statements: Comments, revisions, and proposed actions

We wish to begin a dialogue within the forensic science community surrounding the American Academy of Forensic Sciences (AAFS) vision, mission, and values statements, recently updated by the AAFS Board of Directors (BoD), Academy staff, and Springboard International. Summaries of the statements are available on the AAFS website, and more detailed information was emailed to members as an AAFS News Alert on March 31, 2021 from the AAFS president Carl McClary. We believe that the statements, as currently written, do not provide meaningful guidance about the Academy’s vision and mission, nor do they adequately describe the values of the forensic scientists the Academy serves. Our authorship includes Anthropology Section student affiliates, trainee affiliates, and fellows, with AAFS membership ranging from years to decades. We are active participants in this organization, and we are committed to serving and improving it. It is our hope that the current AAFS leadership, in keeping with President McClary’s theme of “A Responsive Academy,” considers our critique in the productive spirit in which it is intended, potentially responding by making positive changes to these statements that will enable them to better serve as guiding principles for our practitioner community. We address aspects of the vision, mission, and values statements in turn. The text of these statements is presented in italicized quotes below[1].Journal ArticleArticle #: 10019

RAS Mutations Are Independently Associated with Decreased Overall Survival and Event-Free Survival in Patients with AML Receiving Induction Chemotherapy

Background: Activating mutations of NRAS and KRAS genes are common in newly diagnosed acute myeloid leukemia (AML), occurring in 11-16% and 4-5% of patients, respectively. RAS mutations are frequently acquired at time of progression from MDS to AML and are associated with poor survival. Next generation sequencing (NGS) at diagnosis and during complete remission has shown that RAS mutations have high clearance rates with induction chemotherapy. In the CALGB 8525 study, RAS-mutant younger patients (age <60 years) randomized to treatment with high-dose cytarabine consolidation had a lower 10-year cumulative incidence of relapse when compared to RAS WT patients. We performed a single center retrospective study to determine the outcomes of NRAS and KRAS mutated AML in patients receiving induction chemotherapy. Methods: We retrospectively reviewed the charts of patients with newly diagnosed AML treated at Memorial Sloan Kettering Cancer Center between January 1, 2014 to May 15, 2019. Patients with pathologic confirmation of AML and treatment with induction chemotherapy were included. Age < 18 years old, treatment with a pediatric induction regimen, a diagnosis of biphenotypic AML, unknown RAS mutation status at diagnosis, or treatment an outside institution were criteria for exclusion. All patients underwent NGS from a diagnostic bone marrow aspirate (BMA) with MiSeq or MSK-IMPACT platforms. Mutations present with a variant allele frequency (VAF) ≥ 1% were retained. Response was evaluated per ELN 2017 criteria. Immunophenotypic MRD was identified in BMA by multiparameter flow cytometry. Any level of residual disease was considered MRD+. Baseline characteristics were evaluated by Fisher's exact test and Wilcoxon rank sum tests. Kaplan-Meier estimates were used to summarize OS and EFS. Multivariable cox regression, including time-dependent variables was performed on univariate factors with p<0.05. Results: 202 patients, including 162 WT and 40 RAS mutant met inclusion criteria for further analysis. Mutations in NRAS and KRAS occurred in 14%, and 8% of patients, respectively with 6 patients having co-occurring NRAS and KRAS mutations. At baseline, the RAS mutant AML cohort had a significantly greater proportion of patients with AML-MRC and a trend toward fewer patients receiving allogeneic stem cell transplant. (Table 1.) Cytogenetic abnormalities were similar among RAS and WT patients. Sequencing at diagnosis revealed an increased frequency of FLT3 TKD, RUNX1, TET2, WT1, and ETV6 mutations and a decreased frequency of FLT3-ITD and TP53 mutations in the RAS mutant cohort. Response rates and MRD negative remission rates to induction chemotherapy were similar between RAS and WT AML patients (Table 2). With a median follow up of 25 months among survivors, RAS mutant AML was associated with a significant decrease in median EFS (4.9 vs. 11.4 months, p< 0.01) and a near significant decrease in median OS (12 vs. 30.1 months, p=0.057) (Figure 1 and 2). After controlling for variables with p<0.05 on univariate analysis including age, prior myeloid malignancy, AML classification, ELN risk, transplantation, and re-induction, RAS mutation was independently associated with an increased risk of death (HR 1.85, p=0.016) and decreased EFS (HR 2.19, p< 0.01) on multivariate analyses (Tables 3 and 4). Among 77 patients with paired sequencing at diagnosis and at time of CR or CRi, all RAS mutations (n=17) were cleared (Figure 3). Additionally, other RAS pathway mutations had high clearance rates including PTPN11 (n=8, 100%), NF1 (n=3, 100%, and CBL (n= 4, 80%) (Figure 3). RAS mutation clearance also occurred in 3 out of 8 patients (38%) not achieving CR or CRi after induction. RAS mutation clearance persisted in 6 out of 10 responding patients at time of relapse. Conclusions: In summary, the presence of RAS mutations in patients with AML receiving induction chemotherapy was associated with decreased overall and event free survival. RAS mutant AML was enriched among patients with AML-MRC and prior myeloid neoplasms, which was also associated with decreased survival. Lastly, treatment with chemotherapy led to a high rate of RAS mutation clearance in responders that persisted at the time of disease relapse. The poor prognosis of RAS mutant AML despite RAS mutation clearance suggests that other therapies are needed in combination with chemotherapy to improve outcomes in this high-risk population. Disclosures Cai: Imago Biosciences, Inc.: Consultancy. Viny:Hematology News: Membership on an entity's Board of Directors or advisory committees; Mission Bio: Other: Sponsored travel. Goldberg:American Society of Clinical Oncology: Research Funding; Abbvie: Research Funding; ADC Therapeutics: Research Funding; American Society of Hematology: Research Funding; DAVA Oncology: Honoraria; Pfizer: Research Funding; Arog Pharmaceuticals: Research Funding; Abbvie: Consultancy; Daiichi-Sankyo: Consultancy, Research Funding; Celgene: Consultancy. Tallman:BioLineRx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Biosight: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Consultancy; Cellerant: Research Funding; ADC Therapeutics: Research Funding; Orsenix: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KAHR: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees. Stein:Astellas Pharma US, Inc: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Membership on an entity's Board of Directors or advisory committees; Bioline: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees