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The advent of lung cancer screening and detection of smaller nodules amplifies the need to clarify the oncological quality of sublobar resections. Furthermore, studies comparing sublobar resections to lobectomies offer conflicting conclusions. We hypothesize that this is driven, in part, by inconsistency in reporting; that is, variable interpretation of what constitutes an operative segment. Without an established standard, 2 very different operations may be reported as segmental resections, leaving the data on sublobar approaches subject to interpretative variability.A retrospective audit was performed on all segmental resections from May 2016 to December 2019 at Brigham and Women's Hospital. Pathology and operative reports were reviewed, with particular attention to the dissection of the component artery, vein, and bronchus. Resections with dissection and division of at least 1 major vascular structure (the segmental artery or vein), as well as the segmental bronchus, met operative criteria for anatomic segmentectomy. Surgical quality metrics were compared between the 2 groups.There were 271 segmental resections: 219 (80.8%) were anatomic segmentectomies and 52 (19.2%) were nonanatomic segmentectomies. For the entire cohort, nonanatomic segmentectomies had smaller margins (1.0 vs 1.5 cm; P = .02), fewer lymph nodes (2.0 vs 6.0; P .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P .001). Similarly, there were smaller margins (1.5 vs 1.8 cm; P = .03), fewer lymph nodes (2.0 vs 6.0; P .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P .001) in nonanatomic segmentectomies for non-small cell lung cancer.Nearly 20% of reported segmentectomies may not meet criteria for true segmental resection. Therefore, prior studies may need further scrutiny to clarify outcomes and results. Establishing a professional standard may help mitigate ambiguity in published data on this subject.

Gastric and esophageal adenocarcinomas represent a biologically heterogeneous disease. The identification, in early eighties, of human epidermal growth factor receptor 2 (HER2) overexpression, being present in 12 to 20% of the cases, marked a major milestone in the efforts of unraveling the molecular complexity of this disease. This led to the development of anti-HER2-therapies, trastuzumab being the first to demonstrate, in combination with cisplatin and 5FU/capecitabine chemotherapy, an improvement in response rate and survival in the first-line setting of patients with metastatic, HER2-positive gastroesophageal adenocarcinomas. Afterwards, during a decade, several studies have tried new strategies either to block HER2 pathway differently or to combine different anti-HER2, without efficacy. Everything changed with studies demonstrating additive effect between anti-HER2 and immune checkpoint inhibitors and leading to phase III clinical trials combining anti-HER2 and anti-PD-L1/PD1 therapies. Pembrolizumab, a PD-1 inhibitor, was recently granted by FDA an accelerated approval, in patients with HER2-positive gastro-oesophageal adenocarcinomas, in combination with trastuzumab and platinum-based chemotherapy following meaningful improvement in overall response rate over standard treatment. Progression-free and overall-survival results are still awaited to change our first-line standard treatment. Furthermore, new HER2 inhibitors have been developed, blocking HER2-mediated pathway signaling via different mechanisms from pan-HER inhibition to anti-HER2 antibody drug conjugates with promising results in pretreated patients. Trastuzumab-deruxtecan has in particular showed interesting results in pretreated patients. We present here a review of the recent data and perspectives in HER2-positive metastatic gastroesophageal adenocarcinomas.

Introduction: Depression is often under-detected in long-term care (LTC) patients with major neurocognitive disorders (MNCD) and is associated with important morbidity, mortality, and costs. Observer-rated outcome measures (ObsROMs) could help resolve this problematic; however, evidence on their accuracy is scattered in the literature. This systematic review aimed at summarizing this evidence. Methods: A literature search was conducted in 7 databases using keywords, MeSHs, and bibliographic searches. We included studies published before January 2022 and reporting on the accuracy of a depression ObsROM used in LTC patients with MNCD. Data extraction, analysis, synthesis, and study methodological quality assessments were done by two authors, and discrepancies were resolved by consensus. Results: Among 9,660 articles retrieved, 8 studies reporting on 11 depression measures were included. Scales were classified as patient-reported outcome measures used as Obs­ROMs or true ObsROMs. Among the first category, the Cornell Scale for Depression in Dementia (CSDD) and the Montgomery-Asberg Depression Rating Scale (MADRS) performed best (area under the curve [AUC]: 0.73–0.87), although both presented with low positive predictive values and high negative predictive values. Among the second category, the Nursing Homes Short Depression Inventory (NH-SDI) performed best, with an AUC of 0.93 and ≥85% sensitivity, specificity, and predictive values. Conclusion: The CSDD and MADRS may be useful to rule out depression in LTC patients with MNCD, whereas the NH-SDI may be useful to rule in and out depression within this same population. Before recommending their use, adequately powered studies to further examine their accuracy in different contexts are necessary.

Flash point temperatures of HNBR–PC and HNBR–PC–LiTFSI gel polymer electrolytes with different nitrile content are reported. Molecular interactions were found to impact gel flammability.

Background Self-administered instruments are used to measure components of work environments that cannot be measured directly. The Healthy Work Environment Assessment Tool (HWEAT) of the American Association of Critical-Care Nurses is a promising instrument. However, it is available only in English and Japanese, precluding its use in other populations and cross-national comparisons. Objectives To describe the Canadian French translation and cross-cultural adaptation of the HWEAT (F-HWEAT) and to explore its factor structure and psychometric properties. Methods Cross-cultural adaptation of the HWEAT and collection of evidence of validity via an electronic cross-sectional survey. Results A total of 564 intensive care unit nurses participated in the validation study. Confirmatory factor analysis supported the presence of a single overarching factor measured by the F-HWEAT. The Cronbach α for the instrument was 0.89 (95% CI, 0.88-0.91). The mean and median interitem correlations were both 0.32, and item-partial total correlations ranged from 0.33 to 0.64. The overall F-HWEAT score indicated that nurses believed their work environment needed improvements. Moderate positive correlations were found between the overall F-HWEAT score and nurses’ perceptions of care quality (r = 0.45 [95% CI, 0.38-0.51]) and safety (r = 0.48 [95% CI, 0.40-0.55]). Conclusion The results support the use of the F-HWEAT in French-speaking populations. Using the F-HWEAT will help elucidate areas needing improvement and expand global dialogues about healthy critical care work environments. With this information, nurse leaders and researchers can develop and implement modern strategies to improve the work conditions of intensive care unit nurses.

International audience; BackgroundNeuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis.MethodsALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated.ResultsOverall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3–7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7–13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (

The Surveillance, Epidemiology and End Results (SEER) and the National Cancer Database (NCDB) are databases for cancer analysis that may be subject to error in data reporting. This study examined the rates and impact of discordant data for non-small cell lung cancer.NCDB and SEER were queried for non-small cell lung cancer pathologic tumor, node, metastasis data (NCDB) or "derived" data (SEER). Discordancy between descriptors with stage and impact of outlier data were analyzed.Incomplete staging was noted in 71.5% of the NCDB and 10.3% of SEER patients. A total of 174 829 patients from the NCDB and 117 114 from SEER were analyzed. The NCDB had 97 cases with ≥20 positive lymph nodes recorded vs 27 in SEER (P.001). Mean and median sampled lymph nodes were skewed with inclusion of these data points (P .001). The NCDB misclassified 0.99% tumors5 cm as stage I vs 0.04% in SEER (P.001). The NCDB misstaged positive lymph nodes as pathologic N0 (0.59%) or stage 0 or stage I (0.65%). The NCDB misclassified pathologic N1 as lower than stage II (0.91%) or N2 as lower than stage III (0.36%). The NCDB misclassified stage I with documentation of pathologic N1 or N3 disease (0.24%) or stage II with evidence of N2 or N3 disease (0.50%). The NCDB misclassified pathologic M1 as pathologic stageIV in 0.9% of cases and misclassified 19.8% of stage IV as pathologic M0. SEER collaborative staging had no discordance (P.001).The NCDB and SEER are 2 powerful cancer databases. However, the cumulative discordancy rate was 4.9% for the NCDB and 0.008% for SEER, with more misstaging and outliers in the NCDB.

Cet article étudie un segment de l’histoire longue de l’exclusion religieuse des comédiens et des comédiennes, de l’épisode des cendres dispersées d’Adrienne Lecouvreur sur les bords de Seine (1730) à l’enterrement houleux de Françoise Raucourt (1815). Dans une capitale passionnée par le théâtre, celles et ceux qui en font leur métier doivent procéder à différentes stratégies de contournement pour échapper à l’excommunication. La Révolution ne supprime aucunement la menace de cette exclusion, et sous l’Empire puis la Restauration les heurts avec l’Église ciblent particulièrement les femmes de spectacle. Néanmoins, le retentissement de ces conflits est désormais public et possède une forte portée politique. This article examines a segment of the long history of religious exclusion of actors and actresses, from the episode of Adrienne Lecouvreur’s ashes scattered on the banks of the Seine (1730) to the stormy burial of Françoise Raucourt (1815). In a capital city passionate about theater, those who made it their profession had to use various evasive strategies to avoid excommunication. The Revolution in no way removed the threat of this exclusion, and under the Empire and then the Restoration the clashes with the Church targeted the women of the theatre in particular. Nevertheless, the repercussion of these conflicts was now public and had a strong political impact.

Entre les XVIe et XIXe siècles, la France nous offre des marginalités un miroir à bien des facettes. Que l’approche soit économique, religieuse, politique ou culturelle, nous sommes ramenés au rapport difficile à l’altérité que construit un modèle univoque de pouvoir, une monarchie absolue ou des empires qui marient le trône et l’autel, autour d’un roi ou d’un empereur de guerre. À travers les contributions réunies dans ce recueil, l’on souhaite réfléchir à la manière dont ces mises au ban ont construit la figure de l’autre, de l’étranger, au sein même de son propre pays d’origine ou d’accueil, ou ont défini en creux des droits civils et civiques, indissolublement liés à une communauté de destins, de pensée, d’intérêts. Aucune des marginalités, des souffrances imposées ne va cependant sans résistances, sans luttes opiniâtres et prolongées pour la reconnaissance, pour les libertés, individuelles et collectives, pour l’égalité des droits, ce que l’actualité ne dément jamais. Between the 16th and 19th centuries, France offered us a multifaceted mirror of marginality. Whether the approach is economic, religious, political or cultural, we are brought back to the difficult relationship with otherness constructed by a univocal model of power, an absolute monarchy or empires that married the throne and the altar, around a king or a war emperor. The aim of the contributions in this collection is to reflect on the way in which these banishments have constructed the figure of the other, the foreigner, within his own country of origin or host country, or have defined civil and civic rights that are indissolubly linked to a community of destinies, thoughts and interests. However, none of the marginalisation and suffering imposed is without resistance, without stubborn and protracted struggles for recognition, for individual and collective freedoms, for equal rights, as current events never deny.

O ensaio, desde o ponto de vista da Filosofia da Diferença e de teóricos da educação e do currículo, problematiza a prática de uma docência-epidérmica de uma professora-artista num Centro de Artes de uma universidade pública. Desenvolvendo o pensamento acerca de um currículo-epidérmico enquanto território nômade e superfície de atravessamento, defende a possibilidade de a docência-epidérmica fazer rasgos nas grades curriculares e inventar traçados inesperados e singulares. Tematiza o currículo enquanto território que articula camadas estriadas e lisas e convida a uma travessia-epidérmica cujo movimento acontece num espaço intermezzo. Uma travessia que pedagogicamente privilegia os acontecimentos e a criação de conceitos, que se faz pela desterritorialização e a reterritorialização, pondo o conhecimento em movimento, interpelando estados e tocando os corpos. Nessa travessia importam os atravessamentos, a experiência que inventa outros modos de existência.

International audience; Treating large bone defects or fragile patients may require enhancing the bone regeneration rate to overcome a weak contribution from the body. This work investigates the osteogenic potential of nutrient fisetin, a flavonoid found in fruits and vegetables, as a doping agent inside the structure of a SiO 2 − CaO bioactive glass−poly(caprolactone) (BG−PCL) hybrid scaffold. Embedded in the full mass of the BG− PCL hybrid during one-pot synthesis, we demonstrate fisetin to be delivered sustainably; the release follows a first-order kinetics with active fisetin concentration being delivered for more than 1 month (36 days). The biological effect of BG−PCL−fisetin-doped scaffolds (BG−PCL−Fis) has been highlighted by in vitro and in vivo studies. A positive impact is demonstrated on the adhesion and the differentiation of rat primary osteoblasts, without an adverse cytotoxic effect. Implantation in critical-size mouse calvaria defects shows bone remodeling characteristics and remarkable enhancement of bone regeneration for fisetin-doped scaffolds, with the regenerated bone volume being twofold that of nondoped scaffolds and fourfold that of a commercial trabecular bovine bone substitute. Such highly bioactive materials could stand as competitive alternative strategies involving biomaterials loaded with growth factors, the use of the latter being the subject of growing concerns.

Benzoquinones can undergo reversible reductions and are attractive candidates for use as active materials in green carbon-based batteries. Related compounds of potential utility include 4,4'-diphenoquinones, which have extended quinonoid structures with two carbonyl groups in different rings. Diphenoquinones are a poorly explored class of compounds, but a wide variety can be synthesized, isolated, crystallized, and fully characterized. Experimental and computational approaches have established that typical 4,4'-diphenoquinones have nearly planar cores in which two cyclohexadienone rings are joined by an unusually long interannular C═C bond. Derivatives unsubstituted at the 3,3',5,5'-positions react readily by hydration, dimerization, and other processes. Association of diphenoquinones in the solid state normally produces chains or sheets held together by multiple C-H···O interactions, giving structures that differ markedly from those of the corresponding 4,4'-dihydroxybiphenyls. Electrochemical studies in solution and in the solid state show that diphenoquinones are reduced rapidly and reversibly at potentials higher than those of analogous benzoquinones. Together, these results help bring diphenoquinones into the mainstream of modern chemistry and provide a foundation for developing redox-active derivatives for use in carbon-based electrochemical devices.

Background Patient decision aids should help people make evidence-informed decisions aligned with their values. There is limited guidance about how to achieve such alignment. Purpose To describe the range of values clarification methods available to patient decision aid developers, synthesize evidence regarding their relative merits, and foster collection of evidence by offering researchers a proposed set of outcomes to report when evaluating the effects of values clarification methods. Data Sources MEDLINE, EMBASE, PubMed, Web of Science, the Cochrane Library, and CINAHL. Study Selection We included articles that described randomized trials of 1 or more explicit values clarification methods. From 30,648 records screened, we identified 33 articles describing trials of 43 values clarification methods. Data Extraction Two independent reviewers extracted details about each values clarification method and its evaluation. Data Synthesis Compared to control conditions or to implicit values clarification methods, explicit values clarification methods decreased the frequency of values-incongruent choices (risk difference, –0.04; 95% confidence interval [CI], –0.06 to –0.02; P < 0.001) and decisional conflict (standardized mean difference, –0.20; 95% CI, –0.29 to –0.11; P < 0.001). Multicriteria decision analysis led to more values-congruent decisions than other values clarification methods (χ2 = 9.25, P = 0.01). There were no differences between different values clarification methods regarding decisional conflict (χ2 = 6.08, P = 0.05). Limitations Some meta-analyses had high heterogeneity. We grouped values clarification methods into broad categories. Conclusions Current evidence suggests patient decision aids should include an explicit values clarification method. Developers may wish to specifically consider multicriteria decision analysis. Future evaluations of values clarification methods should report their effects on decisional conflict, decisions made, values congruence, and decisional regret.

Fire plays a major role in the structuring and functioning of boreal ecosystems. As peatlands are important components of boreal forests, the impact of fire upon these wetter ecosystems is increasingly studied, but with the focus on treed peatlands and Sphagnum-dominated bogs so far. Important fires occurring more frequently in the past decade in southern Northwest Territories (Canada) provide the opportunity to assess early post-fire vegetation regeneration in open rich fens (one, two, and five years post-fire) and to better understand early recovery succession. We aimed to (i) evaluate whether and how open rich fens are affected by fire, and (ii) describe short-term vegetation regeneration for both bryophytes and vascular species. A shift was observed between pioneer bryophytes and brown mosses between the second and fifth year post-fire. Vascular plants, especially slow-growing species and the ones reproducing mainly by seeds, recovered partially. The first bryophyte species recovering were pioneer species adapted to colonize burned environments such as Marchantia polymorpha L. or Ceratodon purpureus (Hedw.) Brid. For vascular plant species, the ones previously present and able to regrow rapidly from unburned plant structures (base of tussocks, rhizomes, roots) were represented by species like Betula glandulosa Michx. or Carex aquatilis Wahlenb. The wetter conditions and lower fuel availability of fen depressional biotopes were important factors controlling the resistance and regeneration of species associated with them.

Summary Introduction Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. Materials and methods Working groups from the Groupe d’Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the “formal consensus” method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. Results Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of “induced oral lichenoid lesions” were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. Conclusion This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

Canada is a leading producer, and exporter of peat used for horticultural purposes. Nevertheless, in that context, peat extraction requires the removal of vegetation and the drainage of Sphagnum-dominated peatlands causing disturbances of hydrological regimes and the disappearance of biodiversity as well as most ecosystems services. Moreover, when peat extraction is over, the formerly extracted peatlands become a source of greenhouse gases due to the oxidation of residual peat. Without human intervention, horticultural post-extracted peatlands will almost never return to their original pre-disturbance state. In order to solve this ecological problem, the Peatland Ecology Research Group (PERG) developed in the late 1990s an active ecological restoration method better known as the Moss Layer Transfer Technique (MLTT). Thus, the MLTT allows not only to restore the specific hydrology, but also to restore the Sphagnum carpet as well as typical peatland vegetation communities. Given the effectiveness of the MLTT to restore Sphagnum-dominated peatlands in a short period of time, it is now necessary to clarify and define the notion of a successful peatland restoration work. To achieve this, the present research project uses a fundamental tool of the science of ecological restoration embodied by the reference ecosystem. Consequently, the use of a reference set perform by natural peatlands makes it possible, through the intermediary of the vegetation communities, to appreciate the similarity or the ecological distance of the restored peatlands according to the time up since the restoration. This research work thus underlines the capacity of the MLTT to restore functional peatlands ecosystems on the basis of certain foundations taught by ecological restoration in the context of global climate change and erosion of biodiversity.

Partial edentulism, one or more teeth missing, is one of the most common dental problems that can be found in the population. It has multiple resolution possibilities depending on the individual characteristics of the patient. One of these options is the removable partial denture (RPD), which allows for solving complex clinic problems in a faster way and with a considerably lower operational cost compared to other treatment modalities. However, important discontentment has been reported among patients who have opted for this treatment. One of the discomforting factors for users of removable partial prostheses is the presence of visible retainers in the anterior area. In some cases, it could be possible to eliminate the retainers in the anterior sector, providing retention by mechanical friction and the choice of a removal axis.

Introduction: Nursing home (NH) staff mention knowledge deficits regarding the management of behavioural and psychological symptoms of dementia (BPSDs) in residents with neurocognitive disorders (NCDs). Staff training therefore appears to be necessary, however existing evidence on best training practices and their outcomes remain scattered. This systematic review aimed to: 1) identify the best clinical practices and theoretical bases of staff training interventions on BPSD management in NHs, and 2) summarize the effects of these interventions on resident and staff outcomes. Methods: A mixed methods systematic review was conducted. Two nurse researchers independently searched nine electronic databases to identify studies on the efficacy of staff training interventions aiming BPSD management in NHs, on a variety of resident and staff outcomes. The search was conducted for articles published between 1996 and 2022, using selected keywords, MeSH terms, and predefined eligibility criteria. The methodological quality of the retrieved studies was assessed using JBI checklists. Results: Overall, 39 studies in 47 articles were included. Ten categories of trainings were identified, of which three demonstrated the most promising results on both residents and staff: 1) structured protocols and models, 2) person-centred bathing, and 3) communication techniques. The methodological quality of the retrieved studies was generally weak. Issues with intervention feasibility and reproducibility were also noted. Discussion/Conclusion: Training interventions incorporating structured protocols and models, person-centered bathing and communication techniques are associated with better staff and resident outcomes. However, there is a strong need for high-quality research to strengthen existing evidence, ensure feasibility and reproducibility.

IntroductionMany dietary guidelines promote the substitution of animal proteins with plant-based proteins for health benefits but also to help transitioning toward more sustainable dietary patterns. The aim of this study was to examine the food and nutrient characteristics as well as the overall quality and costs of dietary patterns consistent with lower intakes of animal-based protein foods and with higher intakes of plant-based protein foods among French Canadian adults.MethodsDietary intake data, evaluated with 24 h recalls, from 1,147 French-speaking adults of the PRÉDicteurs Individuels, Sociaux et Environnementaux (PREDISE) study conducted between 2015 and 2017 in Québec were used. Usual dietary intakes and diet costs were estimated with the National Cancer Institute’s multivariate method. Consumption of animal- and plant-based protein foods was classified into quarters (Q) and differences in food and nutrient intakes, Healthy Eating Food Index (HEFI)-2019 scores and diet costs across quarters were assessed using linear regression models adjusted for age and sex.ResultsParticipants with lower intakes of animal-based protein foods (Q1 vs. Q4) had a higher HEFI-2019 total score (+4.0 pts, 95% CI, 0.9 to 7.1) and lower daily diet costs (-1.9 $CAD, 95% CI, –2.6 to -1.2). Participants with higher intakes of plant-based protein foods (Q4 vs. Q1) had a higher HEFI-2019 total score (+14.6 pts, 95% CI, 12.4 to 16.9) but no difference in daily diet costs (0.0$CAD, 95% CI, -0.7 to 0.7).DiscussionIn a perspective of diet sustainability, results from this study among French-speaking Canadian adults suggest that a shift toward a dietary pattern focused primarily on lower amounts of animal-based protein foods may be associated with a better diet quality at lower costs. On the other hand, transitioning to a dietary pattern focused primarily on higher amounts of plant-based protein foods may further improve the diet quality at no additional cost.

Tregs fail to migrate to the tumor in Ccr2-/- mice but accumulate in the dLN

The CCL2 chemokine receptor CCR2 drives cancer by mediating the recruitment of monocytes and myeloid-derived suppressor cells to the tumor microenvironment. In this study, we extend the significance of CCR2 in this setting by identifying a new role for it in mediating recruitment of CD4+ T regulatory cells (Treg). Following tumor initiation, an expanded population of CCR2+ Tregs required CCR2 expression to traffic between draining lymph nodes (dLN) and the tumor. This Treg subset was enriched in the fraction of tumor antigen–specific cells in the dLN, where they displayed an activated immunosuppressive phenotype. Notably, in mouse models, low-dose cyclophosphamide treatment preferentially depleted CCR2+ Treg, enhancing priming of tumor-specific CD8+ T cells. In the MMTV-PyMT transgenic mouse model of breast cancer and in oral squamous cell carcinoma patients, tumor development was associated with decreased blood frequency and inversely increased tumor frequency of CCR2+ Tregs. Our results define a novel subset of CCR2+ Treg involved in tumoral immune escape, and they offer evidence that this Treg subset may be preferentially eradicated by low-dose cyclophosphamide treatment. Cancer Res; 76(22); 6483–94. ©2016 AACR.

CCL2-AF647 staning allows specific characterization of CCR2 receptor expression on Tregs

Supplemental Figure 1: Transfection of 22rv1 with FLuc-IRES-mCherry and 22rv1_PSCA with Fluc-IRES-GFP and FACS sorting created FLuc expressing PSCA positive and negative cell lines. Supplemental Figure 2: H&E Staining of 22rv1 and 22rv1_PSCA intratibial xenografts shows mixed osteolytic (blue dashed arrows) and osteoblastic (solid red arrows) type tumor formation. Supplemental Figure 3: Comparison of optical imaging, 18F-Fluoride Bone Scan, and A11 immunoPET in mice bearing 22rv1 intratibial xenograft 6 weeks post-xenograftimplantation. Supplemental Figure 4: Comparison of optical imaging, 18F-Fluoride Bone Scan, and A11 immunoPET in a mouse bearing a 22rv1_PSCA intratibial xenograft at 2 and 6 weeks postxenograft- implantation. Supplemental Figure 5: Quantification of tumor necrosis using ImageJ based color Segmentation. Supplemental Figure 6: H&E staining of LAPC-9 tumors treated with either MDV-3100 or vehicle control. Supplemental Table 1: 44 hour biodistribution of mice bearing 22rv1 and 22rv1_PSCA intratibial xenografts. Histologic analysis of control and MDV-3100 treated tumors.

The dynamic of Tregs is reduced in the dLN of Ccr2-/- mice compared to WT mice

Non-cycling Treg accumulate in the dLN of Ccr2-/- mice compare to WT mice

Includes mat and methods and legends relative to supplementary figures

Co-production of conservation projects is favored by incorporating local ecological knowledge into project design and implementation. Using a mixed method approach, we asked how the territorial practices and knowledge of cowboys and livestock farmers inform their attitudes to this proposed project. We predicted that cowboy territorial practices would be reduced in diversity compared to the past, and that this may be associated with a reduction in coping or adaptation capacity in the face of environmental challenges. We further predicted that due to growing environmental and social pressures reducing traditional livelihood opportunities for this group, they are likely to see the guanaco reintroduction project in a conflictual and negative light. We additionally predicted that they would perceive local carnivorous species in a conflictual and negative way. We found that territorial practices among the sample had indeed decreased in diversity. The sample coped with changing socio-ecological conditions by taking up other jobs. However, we also found that they had majority favorable views on the guanaco reintroduction project. Yet their knowledge of current guanaco behavior led them to believe that the project would fail. However, they also observed that pumas and condors changed their behaviors. We suggest that there are opportunities to co-produce knowledge about the possibility of flexible and adaptive guanaco behavior, which may lead to restoration and create more sustainable future scenarios, by engaging with the territorial practices and local ecological knowledge of cowboys and livestock farmers.

National audience; Objectifs : Implémenter un pipeline pour le traitement des images IRM 7T pour l’imagerie QSM , défini avec Common Workflow Language (CWL) qui garantit sa pérennité et sa portabilité. En outre, on montre la faisabilité de ce type de traitement réalisé dans l’environnement Cloud des infrastructures Européennes de recherche.Matériels et Méthodes : (i) Données : la base de données SENIOR [1] acquises à NeuroSpinab, France (Siemens Magnetom 7T, antenne 1Tx/32Rx Nova Medical). La MGRE (10 échos) a été reconstruite en utilisant la combinaison d’antenne virtuelle (VCC) [2]. (ii) Cloud: Une machine virtuelle (14 cœurs, 32 Go de RAM) a été déployée et configurée automatiquement dans le Cloud de.NBIc. (iii) Traitement des données: Le pipeline a été implémenté dans le contexte du projet QSM4SENIORd en utilisant CWL qui définit les étapes dont il est composé, ainsi que ses entrées et sorties, et les scripts Python qui effectuent le traitement correspondant. La méthode consiste initialement à pré-filtrer les données de phase de la MGRE. Pour isoler les variations du champ interne cérébral (∆B_in), l'algorithme des gradients conjugués de l'équation normale ∆W_∆^2 ∆B_in=∆W_∆^2 ∆B est appliqué [3]. Un masque permettant d'exclure les voxels aberrants est également calculé. Les données prétraitées sont utilisées comme entrées pour l’algorithme MEDI.Résultats: La figure 1 montre un exemple du QSM calculé dans le Cloud en utilisant le pipeline implémenté en CWL qui est exécuté dans un environnement virtuel contenant tous les modules Python nécessaires.Conclusion : Nous présentons les résultats préliminaires d'un calcul automatique de QSM cérébral sur le Cloud sans besoin de puissantes machines de calcul en interne. Ceci démontre la capacité de traitement à distance des données de recherche. Grâce a l’implémentation en CWL, une automatisation et portabilité du workflow est plausible, en offrant la possibilité de programmer l'analyse de l'ensemble de la cohorte en important les données DICOM dans les serveurs et d'exporter ensuite les résultats. Références : [1] Haeger, A., et al. (2020). Alzheimer's research & therapy, vol. 12(1), article 77. [2] Blaimer, M., et al. (2016). Magnet Reson Med, 75(3), 1086-1099 [3] de Rochefort, L., et al. (2009). Proc Intl Soc Magnet Reson Med, 17(c), 1134.

Implémentation d'un pipeline pour le traitement des images IRM 7T pour l’imagerie QSM , défini avec Common Workflow Language (CWL) qui garantit sa pérennité et sa portabilité. En outre, on montre la faisabilité de ce type de traitement réalisé dans l’environnement Cloud des infrastructures Européennes de recherche.

Implémentation d'un pipeline pour le traitement des images IRM 7T pour l’imagerie QSM, défini avec Common Workflow Language (CWL) qui garantit sa pérennité et sa portabilité. En outre, on montre la faisabilité de ce type de traitement réalisé dans l’environnement Cloud des infrastructures Européennes de recherche.&nbsp

Autism is characterized by atypical social communication and stereotyped behaviors. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are detected in 1–2% of patients with autism and intellectual disability, but the mechanisms underpinning the symptoms remain largely unknown. Here, we characterized the behavior of Shank3Δ11/Δ11 mice from 3 to 12 months of age. We observed decreased locomotor activity, increased stereotyped self-grooming and modification of socio-sexual interaction compared to wild-type littermates. We then used RNAseq on four brain regions of the same animals to identify differentially expressed genes (DEGs). DEGs were identified mainly in the striatum and were associated with synaptic transmission (e.g., Grm2, Dlgap1), G-protein-signaling pathways (e.g., Gnal, Prkcg1, and Camk2g), as well as excitation/inhibition balance (e.g., Gad2). Downregulated and upregulated genes were enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 (D1-MSN) and the dopamine 2 receptor (D2-MSN), respectively. Several DEGs (Cnr1, Gnal, Gad2, and Drd4) were reported as striosome markers. By studying the distribution of the glutamate decarboxylase GAD65, encoded by Gad2, we showed that the striosome compartment of Shank3Δ11/Δ11 mice was enlarged and displayed much higher expression of GAD65 compared to wild-type mice. Altogether, these results indicate altered gene expression in the striatum of Shank3-deficient mice and strongly suggest, for the first time, that the excessive self-grooming of these mice is related to an imbalance in the striatal striosome and matrix compartments.

We develop stable and printable precursor inks from binary metal halides; the inkjet-printed textile-based CuBrI thin-film transistors at a low temperature of 60 °C demonstrated the potential for printing complementary circuits in wearable electronic textiles.

A partir do acervo de experiências artísticas e educativas do Grupo Patafísica, o ensaio apresenta um percurso por este arquivo fotográfico, cujas gestualidades foram capturadas pelos mediadores integrantes do grupo. Para compreender pontos de inflexão entre o campo da arte e a produção de pensamento, interessa perceber lampejos criativos que emergem do rastro dessas experiências amalgamadas nesses registros por meio da experiência estética. O exercício de olhar agora para essas imagens opera uma atualização que compreende as insurgências narrativas como potenciais tarefas da infância, aqui apresentadas menos como campo social e mais como produção de pensamento. Para isso, a articulação teórica com Gilles Deleuze, Georges Didi-Huberman e François Lyotard busca as sobrevivências e as resistências destes arquivos.

OBJECTIVE: Optimizing a self-persuasion intervention app for adolescent HPV vaccination requires investigating its hypothesized mechanisms. Guided by the experimental medicine approach, we tested whether (a) self-persuasion intervention components (verbalize vaccination reasons, choose HPV topics) changed putative mechanisms (memory, autonomous motivation) and (b) measures of the putative mechanisms were associated with HPV vaccination. METHODS: These are secondary analyses from a randomized 2 (cognitive processing: verbalize reasons vs. listen) × 2 (choice: choose HPV topics vs. assigned) factorial trial (Tiro et al., 2016). Undecided parents (N = 161) with an unvaccinated child (11–17 years old) used the self-persuasion app, recalled reasons for vaccination (memory measure), and completed an autonomous motivation measure. Adolescent vaccination status was extracted from electronic medical records 12 months post-intervention. RESULTS: The verbalize component resulted in greater recall accuracy of vaccination reasons (p < .001); however, the choose topics component did not increase autonomous motivation scores (p = .74). For associations with HPV vaccination, recall accuracy was not associated (ps > .51), but autonomous motivation scores significantly predicted vaccination (ps < .03), except when controlling for baseline motivation (p = .22). CONCLUSION: The intervention app engages parents in reasons for vaccination; however, memory may not be a viable mechanism of vaccination. Although the intervention did not affect autonomous motivation, associations with vaccination status suggest it is a viable intervention target for HPV vaccination but alternative strategies to change it are needed. Future testing of a refined app should examine implementation strategies to optimize delivery in clinical or community settings.

Background Bioactive lipids produced by human cells or by the gut microbiota might play an important role in health and disease. Dietary intakes are key determinants of the gut microbiota, its production of short-chain (SCFAs) and branched-chain fatty acids (BCFAs), and of the host endocannabinoidome signalling, which are all involved in metabolic diseases. This hypothesis-driven longitudinal fixed sequence nutritional study, realized in healthy participants, was designed to determine if a lead-in diet affects the host response to a short-term dietary intervention. Participants received a Mediterranean diet (MedDiet) for 3 days, a 13-day lead-in controlled diet reflecting the average Canadian dietary intake (CanDiet), and once again a MedDiet for 3 consecutive days. Fecal and blood samples were collected at the end of each dietary phase to evaluate alterations in gut microbiota composition and plasma levels of endocannabinoidome mediators, SCFAs, and BCFAs. Results We observed an immediate and reversible modulation of plasma endocannabinoidome mediators, BCFAs, and some SCFAs in response to both diets. BCFAs were more strongly reduced by the MedDiet when the latter was preceded by the lead-in CanDiet. The gut microbiota response was also immediate, but not all changes due to the CanDiet were reversible following a short dietary MedDiet intervention. Higher initial microbiome diversity was associated with reduced microbiota modulation after short-term dietary interventions. We also observed that BCFAs and 2-monoacylglycerols had many, but distinct, correlations with gut microbiota composition. Several taxa modulated by dietary intervention were previously associated to metabolic disorders, warranting the need to control for recent diet in observational association studies. Conclusions Our results indicate that lipid mediators involved in the communication between the gut microbiota and host metabolism exhibit a rapid response to dietary changes, which is also the case for some, but not all, microbiome taxa. The lead-in diet influenced the gut microbiome and BCFA, but not the endocannabinoidome, response to the MedDiet. A higher initial microbiome diversity favored the stability of the gut microbiota in response to dietary changes. This study highlights the importance of considering the previous diet in studies relating the gut microbiome with lipid signals involved in host metabolism.

A travers ce chapitre, les auteurs présentent différentes méthodes permettant d’utiliser le signal provenant d’acquisitions IRM en écho de gradient pour extraire simultanément différentes métriques d’intérêt. Ces mesures qui ont pour dénominateur commun la capacité d’exprimer à l’échelle macroscopique un paramètre caractérisant un tissu à l’échelle microscopique, constituent la matière première des biomarqueurs en imagerie.

A presente escrita busca ensaiar a docência como encontro a partir do arquivo de uma faculdade universitária. No próprio exercício de ensaiar, a escrita é operada por afecções de experiências docentes, pandêmicas e pré-pandêmicas, bem como por atravessamentos provocados por algumas imagens-pistas encontradas nesse arquivo. Intercorrido pela força intensiva do encontro com essas imagens-testemunho, o ensaio tende a discorrer por um movimento de abertura ao que pede passagem em tal arquivo docente. Assim, cada imagem produz vagas que, durante a passagem e não ponto de chegada, intenta uma vibração, um ritonelo que devém arranjos para inventar uma docência como encontro.Nesse sentido, para ensaiar a docência como encontro, a escrita navega pelos pensamentos de Gilles Deleuze e Félix Guattari e Spinoza. E

Topology optimization has been identified as a powerful tool to improve aircraft structures for many years. Yet, innovative layouts have not been successfully implemented in commercial aircraft for several reasons. One reason identified by our research group is the lack of design constraints during topology optimization, such as buckling stability, which yields complex solutions that are not easily manufacturable. Second, the complexity of the resulting layouts makes integration with other systems highly challenging. With respect to these challenges, we propose a new heuristic layout optimization process: complexity-driven layout exploration for aircraft structures (CD-LEAS). The new process addresses the challenges of complexity and nonlinear constraints, such as buckling, in aircraft structure layout optimization. The novelty of CD-LEAS comes from the integration of a relative complexity metric as a driver to navigate the design space efficiently. Two case studies of commonly used stiffened panels are carried out to showcase the performance of the process. The results show that using complexity to navigate an explicit design space allows our process to quickly output a family of simple, light, stiff and buckling-resistant layouts.

Additional file 1: Figure S1. Metataxonomic sequencing library size. Total sequence counts of the microbiota samples regrouped by study visits.

Additional file 5: Figure S5. Clustering of bioactive lipid profiles. Principal component analysis (PCA) on bioactive lipid profiles. A) Loading plot representing the contribution of lipids from each category to the variability between individuals at different visits. Ellipses show the effect of B) diet and C) individuals on samples. The ellipses represent the 95% confidence interval of the mean of points as computed with the FactoMineR package for the effect of B) diet, C) participants and D) the five clusters of samples distinguished from hierarchical clustering of the PCA. E) Hierarchical clustering on principal components (HCPC) of lipid profile of individuals at different visits. Variables contributing to the difference between the clusters are displayed on the dendrogram. A colored bar is printed below the dendrogram represents the visit to which the sample belongs. F) Heatmap of the lipid concentration for each sample divided by cluster and molecule category. For better visualization, the concentration values were centered around the mean for each metabolite.