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Abstract In the Earth, the flow of crystal-bearing magma is thought to be non-Newtonian and shear thinning, but the physical origin for this is poorly understood. We use hydro-granular theory to show that the decoupled migration of crystals toward conduit cores during magma ascent is a tenable microphysical mechanism for plug flow, emergent in an otherwise purely Newtonian crystal-bearing magma. We use a numerical conduit model to define the flow development length beyond which crystal migration dominates and strain localises near conduit margins. Applied to magma ascent scenarios, we show that this crystal-migration strain localisation only develops in high crystallinity magmas or magmas ascending in very narrow cracks/conduits. In all other scenarios, crystals do not contribute to non-Newtonian behaviour and such magmas are usually strictly Newtonian. The ascent of very crystal-rich dome magma could be associated with strain localisation and crystal depletion at the conduit margins, lubricating ascent through the crust.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

Abstract The potential of immune checkpoint inhibitors (ICI) may be limited in situations where immune cell fitness is impaired. Here, we show that the efficacy of cancer immunotherapies is compromised by the accumulation of senescent cells in mice and in the context of therapy-induced senescence (TIS). Resistance to immunotherapy is associated with a decrease in the accumulation and activation of CD8 T cells within tumors. Elimination of senescent cells restores immune homeostasis within the tumor micro-environment (TME) and increases mice survival in response to immunotherapy. Using single-cell transcriptomic analysis, we observe that the injection of ABT263 (Navitoclax) reverses the exacerbated immunosuppressive profile of myeloid cells in the TME. Elimination of these myeloid cells also restores CD8 T cell proliferation in vitro and abrogates immunotherapy resistance in vivo. Overall, our study suggests that the use of senolytic drugs before ICI may constitute a pharmacological approach to improve the effectiveness of cancer immunotherapies.

Research framework: Adoption has existed for many years as an institution that promotes family ties, taking forms that vary based on place, culture and time. However, the ways in which the social actors involved use adoption reveal specific conceptions of the child, the family, affiliations and family relationships. Objectives: This issue aims to identify the evolution of certain social and legislative adoption practices and to discuss the family and identity realities associated with adoption, in order to provide an analysis of how it has changed over time.Methodology: The articles in this issue highlight the many aspects of adoption: not only does it affect a number of different actors (adopters, adoptees and parents of origin), but it also raises concerns and questions of a social, legal and family nature.Results: Adoption is a subject of study at the intersection of several disciplines, including law, anthropology, sociology, psychology and social work. The various cases discussed in this issue also illustrate the importance of reflecting on the implications of adoption for individuals, families and society as a whole.Conclusions: The cases cited in these articles illustrate the need to approach adoption from a dynamic perspective that takes into account the evolution, contexts and changes involved in all the issues associated with it.Contribution: This issue is intended to stimulate reflection, both now and in the future.

Cadre de recherche : L’adoption, comme institution créatrice de liens filiatifs, existe depuis de nombreuses années et prend différentes formes selon les lieux, les cultures et l’époque. Toutefois, l’utilisation que les acteurs sociaux en font témoigne d’une certaine conception de l’enfant, de la famille, des affiliations et des relations familiales.Objectifs : Le présent numéro souhaite identifier l’évolution de certaines pratiques sociales et législatives en matière d’adoption, discuter des réalités familiales et identitaires associées à cette institution et comprendre comment elle s’est transformée.Méthodologie : Les différentes contributions des autrices et auteurs mettent en lumière la multiplicité des enjeux que touchent l’adoption : non seulement celle-ci concerne différents acteurs (adoptants, adoptés et parents d’origine), mais elle soulève également des préoccupations et des réflexions de nature sociale, juridique et familiale.Résultats : L’adoption constitue donc un objet d’étude qui se situe au carrefour de plusieurs disciplines telles que le droit, l’anthropologie, la sociologie, la psychologie et le travail social. Les différents cas de figure rapportés et discutés dans le présent numéro illustrent également la pertinence de réfléchir aux implications que pose l’adoption pour les individus, mais aussi pour les familles et pour la société dans son ensemble.Conclusions : Ces exemples révèlent la nécessité d’aborder les problématiques associées à l’adoption dans une perspective dynamique qui tienne compte de l’évolution, des contextes et des changements relatifs à son utilisation.Contribution : Le présent numéro se veut une contribution à ces réflexions actuelles et à venir.

ABSTRACT The detection of Clostridioides difficile infections (CDI) relies on testing the stool of patients by toxin antigen detection or PCR methods. Although PCR and antigenic methods have significantly reduced the time to results, delays in stool collection can significantly add to the turnaround time. The use of rectal swabs to detect C. difficile could considerably reduce the time to diagnosis of CDI. We developed a new rapid PCR assay for the detection of C. difficile and evaluated this PCR assay on both stool and rectal swab specimens. We recruited a total of 623 patients suspected of C. difficile infection. Stool samples and rectal swabs were collected from each patient and tested by our PCR assay. Stool samples were also tested by the cell cytotoxicity neutralization assay (CCNA) as a reference. The PCR assay detected C. difficile in 60 stool specimens and 61 rectal swabs for the 64 patients whose stool samples were positive for C. difficile by CCNA. The PCR assay detected an additional 35 and 36 stool and rectal swab specimens positive for C. difficile, respectively, for sensitivity with stools and rectal swabs of 93.8% and 95.3%, specificity of 93.7% and 93.6%, positive predictive values of 63.2% and 62.9%, and negative predictive values of 99.2% and 99.4%. Detection of C. difficile using PCR on stools or rectal swabs yielded reliable and similar results. The use of PCR tests on rectal swabs could reduce turnaround time for CDI detection, thus improving CDI management and control of C. difficile transmission.IMPORTANCEClostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, resulting in high morbidity, mortality, and economic burden. In clinical laboratories, CDI testing is currently performed on stool samples collected from patients with diarrhea. However, the diagnosis of CDI can be delayed by the time required to collect stool samples. Barriers to sample collection could be overcome by using a rectal swab instead of a stool sample. Our study showed that CDI can be identified rapidly and reliably by a new PCR assay developed in our laboratory on both stool and rectal swab specimens. The use of PCR tests on rectal swabs could reduce the time for the detection of CDI and improve the management of this infection. It should also provide a useful alternative for infection-control practitioners to better control the spread of C. difficile.

Summary: Immunotherapy remains underexploited in acute myeloid leukemia (AML) compared to other hematological malignancies. Currently, gemtuzumab ozogamicin is the only therapeutic antibody approved for this disease. Here, to identify potential targets for immunotherapeutic intervention, we analyze the surface proteome of 100 genetically diverse primary human AML specimens for the identification of cell surface proteins and conduct single-cell transcriptome analyses on a subset of these specimens to assess antigen expression at the sub-population level. Through this comprehensive effort, we successfully identify numerous antigens and markers preferentially expressed by primitive AML cells. Many identified antigens are targeted by therapeutic antibodies currently under clinical evaluation for various cancer types, highlighting the potential therapeutic value of the approach. Importantly, this initiative uncovers AML heterogeneity at the surfaceome level, identifies several antigens and potential primitive cell markers characterizing AML subgroups, and positions immunotherapy as a promising approach to target AML subgroup specificities.

Background Allogeneic hematopoietic stem cell transplantation (HSCT) remains the standard of care for chemotherapy-refractory leukemia patients, but cure rates are still dismal. To prevent leukemia relapse following HSCT, we aim to improve the early graft-versus-leukemia effect mediated by natural killer (NK) cells. Our approach is based on the adoptive transfer of Therapeutic Inducers of Natural Killer cell Killing (ThINKK). ThINKK are expanded and differentiated from HSC, and exhibit blood plasmacytoid dendritic cell (pDC) features. We previously demonstrated that ThINKK stimulate NK cells and control acute lymphoblastic leukemia (ALL) development in a preclinical mouse model of HSCT for ALL. Here, we assessed the cellular identity of ThINKK and investigated their potential to activate allogeneic T cells. We finally evaluated the effect of immunosuppressive drugs on ThINKK-NK cell interaction.Methods ThINKK cellular identity was explored using single-cell RNA sequencing and flow cytometry. Their T-cell activating potential was investigated by coculture of allogeneic T cells and antigen-presenting cells in the presence or the absence of ThINKK. A preclinical human-to-mouse xenograft model was used to evaluate the impact of ThINKK injections on graft-versus-host disease (GvHD). Finally, the effect of immunosuppressive drugs on ThINKK-induced NK cell cytotoxicity against ALL cells was tested.Results The large majority of ThINKK shared the key characteristics of canonical blood pDC, including potent type-I interferon (IFN) production following Toll-like receptor stimulation. A minor subset expressed some, although not all, markers of other dendritic cell populations. Importantly, while ThINKK were not killed by allogeneic T or NK cells, they did not increase T cell proliferation induced by antigen-presenting cells nor worsened GvHD in vivo. Finally, tacrolimus, sirolimus or mycophenolate did not decrease ThINKK-induced NK cell activation and cytotoxicity.Conclusion Our results indicate that ThINKK are type I IFN producing cells with low T cell activation capacity. Therefore, ThINKK adoptive immunotherapy is not expected to increase the risk of GvHD after allogeneic HSCT. Furthermore, our data predict that the use of tacrolimus, sirolimus or mycophenolate as anti-GvHD prophylaxis regimen will not decrease ThINKK therapeutic efficacy. Collectively, these preclinical data support the testing of ThINKK immunotherapy in a phase I clinical trial.

At the core of New Public Management (NPM) reforms sits the concept of accountability of publicly funded organizations. In Canada, it is suggested that provinces have increased the number of accountability procedures imposed on universities and that those measures would have had an impact on professors' academic workload. This study discusses the evolution of academic workload and evaluation of professors' activities over the last decade, as well as the current distribution of academic workload among the university staff. It relies on the Canadian faculty's perspectives collected through the 2007 Changing Academic Profession (CAP) study (n = 1151) and the 2017 Academic Profession in the Knowledge Society (APIKS) study (n = 2968). Findings suggest that academic workload increased significantly in the 10 years that academic activities are significantly more evaluated, although by academics themselves in a smaller proportion, and that the administrative burden lies more heavily on female and senior faculty members. Descriptive statistics and a MANOVA comparing the scores of five variables in 2007 and 2017 suggest that academic workload increased significantly in 10 years, academic activities are significantly more evaluated, although less by academics themselves, female academics report dedicating more time to administrative tasks and being more frequently evaluated, and senior administrative staff and external reviewers are perceived as being more involved in the evaluation of academic activities in 2017 than in 2007. Our interpretation is that accountability measures could increase professors' administrative burden and grant more authority to non-academic staff.

The teaching profession has been studied and discussed from a problem-oriented point of view and cultivated by a problem-oriented scientific tradition. Years of research have enabled a better understanding of difficult teaching conditions and teachers' ill-being; an ideological and scientific shift, however, appears necessary to enrich and broaden our present knowledge. One particular question arises: which determinants optimize teachers' professional well-being? In response, our study seeks to identify indicators that allow teachers to create, maintain or restore a state of professional well-being. Our research objective thus aims to describe teachers' indicators regarding the "optimal functioning" that characterizes professional well-being (Seligman, 2011). The research protocol targets physical education teachers insofar as they are now recognized as leaders and models for promoting healthy lifestyles in schools and communities (MEQ, 2001). The methodology involved 5 focus groups composed of 37 teachers from 7 regions of Quebec. As the findings indicate, this approach allowed us to paint an integrative portrait of teachers' indicators relative to professional well-being. Two categories have proved effective in terms of professional well-being: the first is Self and includes 4 variables: meaning, positive emotions, engagement and vitality; the second is Others and includes 3 sub-categories: students, colleagues and school administration. The sub-categories comprise 6 variables divided as follows: positive relationships, learning, collaboration, transfer (specifically for the two first sub-categories), followed by vision and valorization for the third sub-category.

Objective To compare health outcomes and costs given in the emergency department (ED) and walk-in clinics for ambulatory children presenting with acute respiratory diseases.Design A retrospective cohort study.Setting This study was conducted from April 2016 to March 2017 in one ED and one walk-in clinic. The ED is a paediatric tertiary care centre, and the clinic has access to lab tests and X-rays.Participants Inclusion criteria were children: (1) aged from 2 to 17 years old and (2) discharged home with a diagnosis of upper respiratory tract infection (URTI), pneumonia or acute asthma.Main outcome measures The primary outcome measure was the proportion of patients returning to any ED or clinic within 3 and 7 days of the index visit. The secondary outcome measures were the mean cost of care estimated using time-driven activity-based costing and the incidence of antibiotic prescription for URTI patients.Results We included 532 children seen in the ED and 201 seen in the walk-in clinic. The incidence of return visits at 3 and 7 days was 20.7% and 27.3% in the ED vs 6.5% and 11.4% in the clinic (adjusted relative risk at 3 days (aRR) (95% CI) 3.17 (1.77 to 5.66) and aRR at 7 days 2.24 (1.46 to 3.44)). The mean cost (95% CI) of care (CAD) at the index visit was $C96.68 (92.62 to 100.74) in the ED vs $C48.82 (45.47 to 52.16) in the clinic (mean difference (95% CI): 46.15 (41.29 to 51.02)). Antibiotic prescription for URTI was less common in the ED than in the clinic (1.5% vs 16.4%; aRR 0.10 (95% CI 0.03 to 0.32)).Conclusions The incidence of return visits and cost of care were significantly higher in the ED, while antibiotic use for URTI was more frequent in the walk-in clinic. These data may help determine which setting offers the highest value to ambulatory children with acute respiratory conditions.

IntroductionRhythmic transcranial magnetic stimulation (rhTMS) has been shown to enhance auditory working memory manipulation, specifically by boosting theta oscillatory power in the dorsal auditory pathway during task performance. It remains unclear whether these enhancements (i) persist beyond the period of stimulation, (ii) if they can accelerate learning and (iii) if they would accumulate over several days of stimulation. In the present study, we investigated the lasting behavioral and electrophysiological effects of applying rhTMS over the left intraparietal sulcus (IPS) throughout the course of seven sessions of cognitive training on an auditory working memory task.MethodsA limited sample of 14 neurologically healthy participants took part in the training protocol with an auditory working memory task while being stimulated with either theta (5 Hz) rhTMS or sham TMS. Electroencephalography (EEG) was recorded before, throughout five training sessions and after the end of training to assess to effects of rhTMS on behavioral performance and on oscillatory entrainment of the dorsal auditory network.ResultsWe show that this combined approach enhances theta oscillatory activity within the fronto-parietal network and causes improvements in auditoryworking memory performance. We show that compared to individuals who received sham stimulation, cognitive training can be accelerated when combined with optimized rhTMS, and that task performance benefits can outlast the training period by ∼ 3 days. Furthermore, we show that there is increased theta oscillatory power within the recruited dorsal auditory network during training, and that sustained EEG changes can be observed ∼ 3 days following stimulation.DiscussionThe present study, while underpowered for definitive statistical analyses, serves to improve our understanding of the causal dynamic interactions supporting auditory working memory. Our results constitute an important proof of concept for the potential translational impact of non-invasive brain stimulation protocols and provide preliminary data for developing optimized rhTMS and training protocols that could be implemented in clinical populations.

Polyphosphates (polyP) are chains of inorganic phosphates that can reach over 1,000 residues in length. In Escherichia coli, polyP is produced by the polyP kinase (PPK) and is thought to play a protective role during the response to cellular stress. However, the molecular pathways impacted by PPK activity and polyP accumulation remain poorly characterized. In this work, we used label-free mass spectrometry to study the response of bacteria that cannot produce polyP (Δppk) during starvation to identify novel pathways regulated by PPK. In response to starvation, we found 92 proteins significantly differentially expressed between wild-type and Δppk mutant cells. Wild-type cells were enriched for proteins related to amino acid biosynthesis and transport, while Δppk mutants were enriched for proteins related to translation and ribosome biogenesis, suggesting that without PPK, cells remain inappropriately primed for growth even in the absence of the required building blocks. From our data set, we were particularly interested in Arn and EptA proteins, which were down-regulated in Δppk mutants compared to wild-type controls, because they play a role in lipid A modifications linked to polymyxin resistance. Using western blotting, we confirm differential expression of these and related proteins in K-12 strains and a uropathogenic isolate, and provide evidence that this mis-regulation in Δppk cells stems from a failure to induce the BasRS two-component system during starvation. We also show that Δppk mutants unable to up-regulate Arn and EptA expression lack the respective L-Ara4N and pEtN modifications on lipid A. In line with this observation, loss of ppk restores polymyxin sensitivity in resistant strains carrying a constitutively active basR allele. Overall, we show a new role for PPK in lipid A modification during starvation and provide a rationale for targeting PPK to sensitize bacteria towards polymyxin treatment. We further anticipate that our proteomics work will provide an important resource for researchers interested in the diverse pathways impacted by PPK.

Abstract Background Older adults with frailty are at an increased risk of adverse outcomes after surgery. Exercise before surgery (exercise prehabilitation) may reduce adverse events and improve recovery after surgery. However, adherence with exercise therapy is often low, especially in older populations. The purpose of this study was to qualitatively assess the barriers and facilitators to participating in exercise prehabilitation from the perspective of older people with frailty participating in the intervention arm of a randomized trial. Methods This was a research ethics approved, nested descriptive qualitative study within a randomized controlled trial of home-based exercise prehabilitation vs. standard care with older patients (≥ 60 years) having elective cancer surgery, and who were living with frailty (Clinical Frailty Scale ≥ 4). The intervention was a home-based prehabilitation program for at least 3 weeks before surgery that involved aerobic activity, strength and stretching, and nutritional advice. After completing the prehabilitation program, participants were asked to partake in a semi-structured interview informed by the Theoretical Domains Framework (TDF). Qualitative analysis was guided by the TDF. Results Fifteen qualitative interviews were completed. Facilitators included: 1) the program being manageable and suitable to older adults with frailty, 2) adequate resources to support engagement, 3) support from others, 4) a sense of control, intrinsic value, noticing progress and improving health outcomes and 5) the program was enjoyable and facilitated by previous experience. Barriers included: 1) pre-existing conditions, fatigue and baseline fitness, 2) weather, and 3) guilt and frustration when unable to exercise. A need for individualization and variety was offered as a suggestion by participants and was therefore described as both a barrier and facilitator. Conclusions Home-based exercise prehabilitation is feasible and acceptable to older people with frailty preparing for cancer surgery. Participants identified that a home-based program was manageable, easy to follow with helpful resources, included valuable support from the research team, and they reported self-perceived health benefits and a sense of control over their health. Future studies and implementation should consider increased personalization based on health and fitness, psychosocial support and modifications to aerobic exercises in response to adverse weather conditions.

Echinococcus spp. is an emerging zoonotic parasite of high concern. In Canada, an increase in the number of human and animal cases diagnosed has been reported, but information regarding the parasite's distribution in wildlife reservoir remains limited. A cross-sectional study was conducted to estimate the prevalence of wild canids infected with Echinococcus spp. and Echinococcus multilocularis in areas surrounding populated zones in Québec (Canada); to investigate the presence of areas at higher risk of infection; to evaluate potential risk factors of the infection; and as a secondary objective, to compare coproscopy and RT-PCR diagnostic tests for Taenia spp. and Echinococcus identification. From October 2020 to March 2021, fecal samples were collected from 423 coyotes (Canis latrans) and 284 red foxes (Vulpes vulpes) trapped in 12 administrative regions. Real-time PCR for molecular detection of genus Echinococcus spp. and species-specific Echinococcus multilocularis were performed. A total of 38 positive cases of Echinococcus spp., of which 25 were identified as E. multilocularis, were detected. Two high-risk areas of infection were identified. The prevalence of Echinococcus spp. was 22.7% (95% CI 11.5-37.8%) in the Montérégie centered high-risk area, 26.5% (95% CI 12.9-44.4%) in the Bas-St-Laurent high-risk area, and 3.0% (95%CI 1.8-4.7%) outside those areas. For E. multilocularis, a prevalence of 20.5% (95% CI 9.8-35.3%) was estimated in the high-risk area centered in Montérégie compared to 2.4% (95% CI 1.4-3.9%) outside. Logistic regression did not show any association of infection status with species, sex, or geolocation of capture (p > 0.05). This study shows the circulation of Echinococcus in a wildlife cycle in 9/12 administrative regions of Québec.

Here, we introduce the Early Relational Health (ERH) Learning Community's bold, large-scale, collaborative, data-driven and practice-informed research agenda focused on furthering our mechanistic understanding of ERH and identifying feasible and effective practices for making ERH promotion a routine and integrated component of pediatric primary care. The ERH Learning Community, formed by a team of parent/caregiver leaders, pediatric care clinicians, researchers, and early childhood development specialists, is a workgroup of Nurture Connection—a hub geared toward promoting ERH, i.e., the positive and nurturing relationship between young children and their parent(s)/caregiver(s), in families and communities nationwide. In response to the current child mental health crisis and the American Academy of Pediatrics (AAP) policy statement promoting ERH, the ERH Learning Community held an in-person meeting at the AAP national headquarters in December 2022 where members collaboratively designed an integrated research agenda to advance ERH. This agenda weaves together community partners, clinicians, and academics, melding the principles of participatory engagement and human-centered design, such as early engagement, co-design, iterative feedback, and cultural humility. Here, we present gaps in the ERH literature that prompted this initiative and the co-design activity that led to this novel and iterative community-focused research agenda, with parents/caregivers at the core, and in close collaboration with pediatric clinicians for real-world promotion of ERH in the pediatric primary care setting.

Abstract Introduction Life‐prolonging therapies (LPTs) are rapidly evolving for the treatment of advanced prostate cancer, although factors associated with real‐world uptake are not well characterized. Methods In this cohort of prostate‐cancer decedents, we analyzed factors associated with LPT access. Population‐level databases from Ontario, Canada identified patients 65 years or older with prostate cancer receiving androgen deprivation therapy and who died of prostate cancer between 2013 and 2017. Univariate and multivariable analyses assessed the association between baseline characteristics and receipt of LPT in the 2 years prior to death. Results Of 3575 patients who died of prostate cancer, 40.4% (n = 1443) received LPT, which comprised abiraterone (66.3%), docetaxel (50.3%), enzalutamide (17.2%), radium‐223 (10.0%), and/or cabazitaxel (3.5%). Use of LPT increased by year of death (2013: 22.7%, 2014: 31.8%, 2015: 41.8%, 2016: 49.1%, and 2017: 57.9%, p

This systematic review and meta-analysis examined the effectiveness of parent-infant interventions for parents of preterm infants on parental sensitivity compared to standard care or active comparators. This review follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration ID: CRD42016047083). Database searches were performed from inception to 2020 to identify eligible randomized controlled trials. Two review authors independently selected studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias assessment tool and quality of evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) guidelines. A total of 19 studies (n = 2,111 participants) were included and 14 were suitable to be pooled in our primary outcome meta-analysis. Results show no significant effect of parent-infant interventions over standard care or basic educational programs, on parental sensitivity. Results may not necessarily be due to the ineffectiveness of the interventions but rather due to implementation failure or high risk of bias of included studies.

People with antisocial personality disorder (ASPD-nonPPD) are described as insensitive to others and as relentlessly pursuing their goals. A severe form of antisociality is observed in psychopathic personality disorder (ASPD-PPD). In the spectrum of emotional reactivity, people with ASPD-nonPPD present more emotional dysregulation, whereas people with ASPD-PPD exhibit a reduced or nonexistent emotional response. To personally engage people with ASPD-nonPPD and ASPD-PPD, we used emotionally charged autobiographical stimuli, specifically their self-defining memories (SDMs). As these participants exhibit high control over voluntary responses, we measured neurophysiological indicators (heart rate variability (HRV) and electrodermal activity (EDA)). In the resting task and the SDM task, people with ASPD-PPD had significantly higher HRV, suggesting higher emotion regulation abilities. Conversely, the EDA of people with ASPD-nonPPD and ASPD-PPD reflects less activation during the SDM task than when resting. We suggest that people with ASPD-PPD are more adaptive to stimuli that provide less emotional activation. Furthermore, the correlation analysis results suggested that the higher people with ASPD-PPD score on Factor 1 of the Psychopathy Checklist-Revised (PCL-R), the less emotional activation they exhibit. This low activation (EDA) associated with good emotion regulation abilities (HRV) is thought to be the signature of psychopathy.

Introduction : Au Québec, le développement de la pratique de l’ergothérapie en déficience intellectuelle est en pleine émergence au regard du nombre d’ergothérapeutes engagés dans l’offre de services destinée à cette clientèle. Néanmoins, les écrits et les outils liés à l’ergothérapie au Québec dans ce domaine restent limités pour soutenir les ergothérapeutes dans l’accomplissement de leur plein potentiel professionnel. Objectif : Cette étude vise à brosser le portrait de la pratique de l’ergothérapie auprès des personnes ayant une déficience intellectuelle au Québec. Méthode : L’enquête utilisant un questionnaire en ligne, diffusé aux ergothérapeutes par le biais de leur association professionnelle, comprenait des questions liées aux motifs de référence en ergothérapie, aux stratégies d’évaluation et aux méthodes d’intervention utilisées, ainsi qu’aux défis rencontrés dans la pratique. Résultats : Un total de 53 ergothérapeutes a rempli le questionnaire. Les participants travaillent dans divers contextes de pratique et répondent à une variété de demandes de consultation, principalement en lien avec le soutien à l’autonomie. Les ergothérapeutes utilisent plusieurs outils d’évaluation, mais notent un défi concernant la standardisation et l’utilisation des valeurs normatives. Les ergothérapeutes agissent majoritairement à titre de consultants et constatent un accès limité à des formations pour soutenir leur développement professionnel. Conclusion : Bien que les rôles de l’ergothérapeute soient multiples, il semble qu’une faible implication de ces professionnels soit observée dans plusieurs sphères de vie des personnes ayant une déficience intellectuelle. Divers champs d’exercices de l’ergothérapie resteraient à développer au Québec, notamment dans le soutien aux transitions de vie, auprès des personnes présentant des incapacités significatives, et dans l’inclusion socioprofessionnelle. ----- Introduction: In Quebec, the occupational therapy practice in intellectual disability is in full development with regard to the number of occupational therapists involved in services intended for people with an intellectual disability. Nevertheless, scientific literature and professional tools related to occupational therapy specific to this context remains limited to support occupational therapist in achieving their full potential. Aim: This study aims to explore the occupational therapy practice amongst people with an intellectual disability in Quebec. Method: This survey using an online questionnaire, distributed to occupational therapists through their professional association, included closed and open-ended questions related to reasons for referral in occupational therapy services, currently used assessment strategies and intervention methods, as well as challenges encountered by occupational therapists. Results: A total of 53 occupational therapists completed the survey. Participants work in many practice settings and respond to a variety of consultation requests, primarily related to support of autonomy in daily activities. Occupational therapists use several assessment tools, but identify a challenge regarding the standardization and the use of normative values. Occupational therapists mostly act as consultants and report limited access to training supporting their professional development. Conclusion: Although the roles of occupational therapist are multiple, a limited involvement of these professionals is noted in several life domains of people with an intellectual disability. Various fields of expertise still need to be developed in Quebec, notably in the support during life transitions, in interventions with people with significant disabilities, and in socioprofessional inclusion.

Symptomatic vertebrobasilar atherosclerotic disease is rarely encountered but represents a high-risk factor for recurrent transient ischemic attack or stroke. Posterior strokes are usually associated with embolism or hemodynamic impairment. Extensive disease involving the V3 and V4 segments of the vertebral artery (VA) remains infrequent, and optimal management is limited owing to the infrequency of this disease. We illustrate the case of a 65-year-old man who presented with recurrent transient episodes of dizziness with acute onset of instability, nausea, and left visual blurring. Magnetic resonance imaging findings of the head were normal, and computed tomography angiography revealed severe atherosclerotic disease of both VAs, with proximal occlusion of the right VA and multiple tight stenoses of the left VA at the V1 and V4 segments. Duplex ultrasound found markedly reduced anterograde flow in the VAs and basilar arteries and nonsignificant stenosis of the internal carotid arteries. Optimal medical treatment led to a decrease of transient symptoms. However, the patient developed a cerebellar infarction in the left posteroinferior cerebellar artery territory with left VA V4 segment occlusion. Surgical revascularization of the right VA was decided by the multidisciplinary team. Through an anterolateral approach of the right VA V3 segment, revascularization was performed using a common carotid artery-to-right VA bypass using a reversed saphenous vein graft. The patient fully recovered and was free of symptoms during the next 14 months of follow-up. In the case of extensive VA occlusive disease, surgical reconstruction of the distal VA using a bypass from the common carotid artery represents an option to improve hemodynamics and/or eliminate an embolic source of posterior stroke on a case-by-case basis.

Abstract Cycles of stress build-up and release are inherent to tectonically active planets. Such stress oscillations impart strain and damage, prompting mechanically loaded rocks and materials to fail. Here, we investigate, under uniaxial conditions, damage accumulation and weakening caused by time-dependent creep (at 60, 65, and 70% of the rocks’ expected failure stress) and repeating stress oscillations (of ± 2.5, 5.0 or 7.5% of the creep load), simulating earthquakes at a shaking frequency of ~ 1.3 Hz in volcanic rocks. The results show that stress oscillations impart more damage than constant loads, occasionally prompting sample failure. The magnitudes of the creep stresses and stress oscillations correlate with the mechanical responses of our porphyritic andesites, implicating progressive microcracking as the cause of permanent inelastic strain. Microstructural investigation reveals longer fractures and higher fracture density in the post-experimental rock. We deconvolve the inelastic strain signal caused by creep deformation to quantify the amount of damage imparted by each individual oscillation event, showing that the magnitude of strain is generally largest with the first few oscillations; in instances where pre-existing damage and/or the oscillations’ amplitude favour the coalescence of micro-cracks towards system scale failure, the strain signal recorded shows a sharp increase as the number of oscillations increases, regardless of the creep condition. We conclude that repetitive stress oscillations during earthquakes can amplify the amount of damage in otherwise mechanically loaded materials, thus accentuating their weakening, a process that may affect natural or engineered structures. We specifically discuss volcanic scenarios without wholesale failure, where stress oscillations may generate damage, which could, for example, alter pore fluid pathways, modify stress distribution and affect future vulnerability to rupture and associated hazards.

Antigen-specific T cell expansion ex vivo followed by adoptive transfer enables targeting of a multitude of microbial and cancer antigens. However, clinical-scale T cell expansion from rare precursors requires repeated stimulation, which may lead to T cell dysfunction and limited therapeutic potential. We used a clinically compliant protocol to expand Epstein-Barr virus (EBV) and Wilms tumor 1 (WT1) antigen-specific CD8+ T cells, and leveraged T cell exhaustion-associated inhibitory receptor blockade to improve T cell expansion. Several inhibitory receptors were expressed early by ex vivo-expanded antigen-specific CD8+ T cells, including PD-1 and TIM3, with co-expression matching evidence of T cell dysfunction as the cultures progressed. Introduction of anti-PD-L1 and anti-TIM3 blockade in combination (but not individually) to the culture led to markedly improved antigen-specific T cell expansion without inducing T cell dysfunction. Single-cell RNA sequencing (RNA-seq) and T cell receptor (TCR) repertoire profiling revealed that double blockade does not impart specific transcriptional programs in T cells or alterations in TCR repertoires. However, combined blockade may affect gene expression in a minority of clonotypes in a donor-specific fashion. We conclude that antigen-specific CD8+ T cell manufacturing can be improved by using TIM3 and PD-L1/PD-1 axis blockade in combination. This approach is readily applicable to several adoptive immunotherapy strategies.

In August 2021, a legionellosis outbreak involving 7 persons occurred within a 500-meter radius in the Montérégie region of Québec, Canada. Near real-time modeling of wind direction along with epidemiologic and environmental investigations identified the possible source. Modeling wind direction could help identify likely Legionella pneumophila sources during legionellosis outbreaks.

Measurement(s) Lobster sex • Lobster size • Lobster moult stage • °Brix value of hemolymph • Lobster shell hardness Technology Type(s) Eye • Vernier Caliper • Microscopic assessemnt of pleopods • Refractometer • Physical assessment of lobster carapace Factor Type(s) Year • Month • Lobster fishing area (LFA) • Location • Sampling event • Water depth Sample Characteristic - Organism Homarus americanus Sample Characteristic - Environment marine water body Sample Characteristic - Location Northwest Atlantic Ocean coastal waters of Canada

The permeability of magma in volcanic conduits controls the fluid flow and pore pressure development that regulates gas emissions and the style of volcanic eruptions. The architecture of the permeable porous structure is subject to changes as magma deforms and outgasses during ascent. Here, we present a high-resolution study of the permeability distribution across two conduit shear zones (marginal and central) developed in the dacitic spine that extruded towards the closing stages of the 1991–1995 eruption at Unzen volcano, Japan. The marginal shear zone is approximately 3.2 m wide and exhibits a 2 m wide, moderate shear zone with porosity and permeability similar to the conduit core, transitioning into a ∼ 1 m wide, highly sheared region with relatively low porosity and permeability, as well as an outer 20 cm wide cataclastic fault zone. The low-porosity, highly sheared rock further exhibits an anisotropic permeability network, with slightly higher permeability along the shear plane (parallel to the conduit margin), and is locally overprinted by oblique dilational Riedel fractures. The central shear zone is defined by a 3 m long by ∼ 9 cm wide fracture ending bluntly and bordered by a 15–40 cm wide damage zone with permeability enhanced by ∼ 3 orders of magnitude; directional permeability and resultant anisotropy could not be measured from this exposure. We interpret the permeability and porosity of the marginal shear zone to reflect the evolution of compactional (i.e. ductile) shear during ascent up to the point of rupture, which was estimated by Umakoshi et al. (2008) at ∼ 500 m depth. At this point the compactional shear zone would have been locally overprinted by brittle rupture, promoting the development of a shear fault and dilational Riedel fractures during repeating phases of increased magma ascent rate, enhancing anisotropic permeability that channels fluid flow into and along the conduit margin. In contrast, we interpret the central shear zone as a shallow, late-stage dilational structure, which partially tore the core of the spine, leaving a slight permanent displacement. We explore constraints from monitored seismicity and stick-slip behaviour to evaluate the rheological controls, which accompanied the shift from compactional toward dilational shear as magma approached the surface, and discuss their importance in controlling the permeability development of magma evolving from overall ductile to increasingly brittle behaviour during ascent and eruption.

Summary: Skin plays central roles in systemic physiology, and it undergoes significant functional changes during aging. Members of the peroxisome proliferator-activated receptor-gamma coactivator (PGC-1) family (PGC-1s) are key regulators of the biology of numerous tissues, yet we know very little about their impact on skin functions. Global gene expression profiling and gene silencing in keratinocytes uncovered that PGC-1s control the expression of metabolic genes as well as that of terminal differentiation programs. Glutamine emerged as a key substrate promoting mitochondrial respiration, keratinocyte proliferation, and the expression of PGC-1s and terminal differentiation programs. Importantly, gene silencing of PGC-1s reduced the thickness of a reconstructed living human epidermal equivalent. Exposure of keratinocytes to a salicylic acid derivative potentiated the expression of PGC-1s and terminal differentiation genes and increased mitochondrial respiration. Overall, our results show that the PGC-1s are essential effectors of epidermal physiology, revealing an axis that could be targeted in skin conditions and aging.

Background: For females undergoing cystectomy and urinary diversion, decreases in sexual and urinary functions can have a significant impact on quality of life. Pelvic organ–preserving (POP) radical cystectomy (RC) has been proposed as an approach to improve postoperative functional outcomes. Objective: To evaluate postoperative functional outcomes of a robotic approach for female POP RC with intracorporeal urinary diversion. Design, setting, and participants: This was a multicenter retrospective study evaluating sexual, urinary, and oncological outcomes for sexually active females undergoing POP robot-assisted RC for ≤T2 bladder cancer. Exclusion criteria included multifocal, trigonal, or locally advanced tumors. Surgical procedure: We describe a step-by-step technique for POP robot-assisted RC with intracorporeal urinary diversion. Measurements: The primary outcome of the study was evaluation of sexual and urinary functions following surgery. Oncological outcomes were evaluated as a secondary endpoint. Results and limitations: Our study included 23 females who underwent POP robot-assisted RC between 2008 and 2020 with intracorporeal neobladder (87%) or ileal conduit (13%) reconstruction. The median follow-up was 20 mo. A postoperative sexual function questionnaire was completed by 15 patients (65%). Of those, 13 (87%) resumed sexual activity at a median of 6 mo after surgery. Of the patients with a neobladder, 14 (70%) achieved daytime continence and 16 (80%) achieved nighttime continence. Cancer-specific and overall survival were both 91%. The results are limited by their retrospective nature. Conclusions: POP robot-assisted RC with orthotopic neobladder allows a majority of female patients to return to sexual activity after surgery. This approach should be considered for selected sexually active women. Patient summary: We evaluated 23 women with bladder cancer who underwent surgical removal of the bladder with preservation of their reproductive organs. Following this surgery, a majority of patients resumed sexual activity. For selected patients, this technique can be performed without compromising cancer control.

(1) Background: While goat milk formula (GMF) is an alternative to cow milk formula (CMF), infants’ preferences for one over the other have not been formally assessed. Specifically, our aim in this study was to determine whether infants experience fewer feeding behavior problems with whole milk-based GMF than with conventional whey-based CMF. (2) Methods: This was a multicenter, double-blind, randomized controlled trial with two-arm parallel assignment conducted in six pediatricians’ offices in or near Paris, France, between June 2018 and 31 December 2021. Overall, 64 healthy infants (≤4 months old), predominantly formula-fed, were randomly assigned to either the whole milk-based GMF (n = 33) or whey-based CMF (n = 31) arm. Parents completed the Baby Eating Behavior Questionnaire (BEBQ) and the modified QUALIN questionnaire to evaluate infant feeding behavior and quality of life (psychomotor and socioemotional development), respectively, at inclusion (1 to 5 days before milk delivery) and the final visit (day 28 ± 3 after milk delivery). Informed consent was obtained for all recruited patients, and an ethical committee approved the study. (3) Results: Changes in BEBQ Enjoyment of Food and Slowness in Eating subscale scores from inclusion to final visit did not differ between arms. However, there were significant improvements in subscale scores for Food Responsiveness (GMF: 0.15 ± 1; CMF: −0.48 ± 0.81; p = 0.010) and General Appetite (GMF: 0.26 ± 1.2; CMF: −0.48 ± 0.88; p = 0.012), and modified QUALIN (GMF: 4.6 ± 9.4; CMF: −0.40 ± 7.6; p = 0.03) scores in favor of the GMF group. (4) Conclusions: In this double-blind, randomized controlled trial, GMF-fed infants exhibited a greater general appetite than CMF-fed infants, possibly due to differences in the composition of these formulas (i.e., protein and lipid profiles). In addition, GMF-fed infants enjoyed a better quality of life. There was no difference in food enjoyment between groups. These findings suggest that whole-milk-based GMF could be an attractive alternative to whey-based CMF. Clinical trial registration: NCT03488758 (clinicaltrials.gov).

IntroductionEarly in the COVID-19 pandemic, reagent availability was not uniform, and infrastructure had to be urgently adapted to undertake COVID-19 surveillance.MethodsBefore the validation of centralized testing, two enzyme-linked immunosorbent assays (ELISA) were established independently at two decentralized sites using different reagents and instrumentation. We compared the results of these assays to assess the longitudinal humoral response of SARS-CoV-2-positive (i.e., PCR-confirmed), non-hospitalized individuals with mild to moderate symptoms, who had contracted SARSCoV-2 prior to the appearance of variants of concern in Québec, Canada.ResultsThe two assays exhibited a high degree of concordance to identify seropositive individuals, thus validating the robustness of the methods. The results also confirmed that serum immunoglobulins persist ≥ 6 months post-infection among non-hospitalized adults and that the antibodies elicited by infection cross-reacted with the antigens from P.1 (Gamma) and B.1.617.2 (Delta) variants of concern.DiscussionTogether, these results demonstrate that immune surveillance assays can be rapidly and reliably established when centralized testing is not available or not yet validated, allowing for robust immune surveillance.

Summary: Neutralizing antibodies (NAbs) hold great promise for clinical interventions against SARS-CoV-2 variants of concern (VOCs). Understanding NAb epitope-dependent antiviral mechanisms is crucial for developing vaccines and therapeutics against VOCs. Here we characterized two potent NAbs, EH3 and EH8, isolated from an unvaccinated pediatric patient with exceptional plasma neutralization activity. EH3 and EH8 cross-neutralize the early VOCs and mediate strong Fc-dependent effector activity in vitro. Structural analyses of EH3 and EH8 in complex with the receptor-binding domain (RBD) revealed the molecular determinants of the epitope-driven protection and VOC evasion. While EH3 represents the prevalent IGHV3-53 NAb whose epitope substantially overlaps with the ACE2 binding site, EH8 recognizes a narrow epitope exposed in both RBD-up and RBD-down conformations. When tested in vivo, a single-dose prophylactic administration of EH3 fully protected stringent K18-hACE2 mice from lethal challenge with Delta VOC. Our study demonstrates that protective NAbs responses converge in pediatric and adult SARS-CoV-2 patients.

Abstract SARS-CoV-2 variants of concern (VOCs) have emerged worldwide, with implications on the spread of the pandemic. Characterizing the cross-reactivity of antibodies against these VOCs is necessary to understand the humoral response of non-hospitalized individuals previously infected with SARS-CoV-2, a population that remains understudied. Thirty-two SARS-CoV-2-positive (PCR-confirmed) and non-hospitalized Canadian adults were enrolled 14–21 days post-diagnosis in 2020, before the emergence of the B.1.351 (also known as Beta), B.1.617.2 (Delta) and P.1 (Gamma) VOCs. Sera were collected 4 and 16 weeks post-diagnosis. Antibody levels and pseudo-neutralization of the ectodomain of SARS-CoV-2 spike protein/human ACE-2 receptor interaction were analyzed with native, B.1.351, B.1.617.2 and P.1 variant spike proteins. Despite a lower response observed for the variant spike proteins, we report evidence of a sustained humoral response against native, B.1.351, B.1.617.2 and P.1 variant spike proteins among non-hospitalized Canadian adults. Furthermore, this response inhibited the interaction between the spike proteins from the different VOCs and ACE-2 receptor for ≥ 16 weeks post-diagnosis, except for individuals aged 18–49 years who showed no inhibition of the interaction between B.1.617.1 or B.1.617.2 spike and ACE-2. Interestingly, the affinity (KD) measured between the spike proteins (native, B.1.351, B.1.617.2 and P.1) and antibodies elicited in sera of infected and vaccinated (BNT162b2 and ChAdOx1 nCoV-19) individuals was invariant. Relative to sera from vaccine-naïve (and previously infected) individuals, sera from vaccinated individuals had higher antibody levels (as measured with label-free SPR) and more efficiently inhibited the spike–ACE-2 interactions, even among individuals aged 18–49 years, showing the effectiveness of vaccination.

Abstract Background Genetic studies have been tremendously successful in identifying genomic regions associated with a wide variety of phenotypes, although the success of these studies in identifying causal genes, their variants, and their functional impacts has been more limited. Methods We identified 145 genes from IBD-associated genomic loci having endogenous expression within the intestinal epithelial cell compartment. We evaluated the impact of lentiviral transfer of the open reading frame (ORF) of these IBD genes into the HT-29 intestinal epithelial cell line via transcriptomic analyses. By comparing the genes in which expression was modulated by each ORF, as well as the functions enriched within these gene lists, we identified ORFs with shared impacts and their putative disease-relevant biological functions. Results Analysis of the transcriptomic data for cell lines expressing the ORFs for known causal genes such as HNF4a, IFIH1, and SMAD3 identified functions consistent with what is already known for these genes. These analyses also identified two major clusters of genes: Cluster 1 contained the known IBD causal genes IFIH1, SBNO2, NFKB1, and NOD2, as well as genes from other IBD loci (ZFP36L1, IRF1, GIGYF1, OTUD3, AIRE and PITX1), whereas Cluster 2 contained the known causal gene KSR1 and implicated DUSP16 from another IBD locus. Our analyses highlight how multiple IBD gene candidates can impact on epithelial structure and function, including the protection of the mucosa from intestinal microbiota, and demonstrate that DUSP16 acts a regulator of MAPK activity and contributes to mucosal defense, in part via its regulation of the polymeric immunoglobulin receptor, involved in the protection of the intestinal mucosa from enteric microbiota. Conclusions This functional screen, based on expressing IBD genes within an appropriate cellular context, in this instance intestinal epithelial cells, resulted in changes to the cell’s transcriptome that are relevant to their endogenous biological function(s). This not only helped in identifying likely causal genes within genetic loci but also provided insight into their biological functions. Furthermore, this work has highlighted the central role of intestinal epithelial cells in IBD pathophysiology, providing a scientific rationale for a drug development strategy that targets epithelial functions in addition to the current therapies targeting immune functions.

The mechanisms for replicating and segregating DNA are highly conserved across eukaryotes. A comparative genomic analysis of a free-living protist finds a surprising lack of protein complexes involved in these processes, suggesting that the organism uses alternative mechanisms to process DNA.

Previous research has shown that high frequency lexical items, such as AWL words and formulaic expressions, may differentiate between texts written by expert and novice writers (Chen & Baker, 2010; Hancioglu, 2009), and that lexical features related to breadth, depth, and accessibility differentiate among texts from L2 writers of different proficiency levels (Crossley & McNamara, 2009, 2012; Crossley, Weston, McLain Sullivan, & McNamara, 2011). The current study compared the essays written by EAP students in response to either a cause or an effect writing prompt. As part of their EAP writing class, the students (N = 94) had two weeks to read six source texts and take notes to prepare for an integrative-writing exam. Students' essays were assessed by three raters using a holistic rubric, and five lexical features of their essays were analyzed: percentage of AWL word use, content word frequency, word familiarity, imagability, and lexical diversity. The results indicated that responses to the effect prompt were rated significantly lower than cause essays, contained more frequent and familiar words, and had a lower percentage of AWL words. However, there was no significant correlation between essay ratings and lexical features. Potential explanations for the findings and pedagogical implications are discussed.