Search

Background & Aims: In clinical practice, the diagnosis of alcohol-associated hepatitis (AH) is mostly based on non-invasive criteria, which were defined at a consensus conference by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). These criteria were recently modified by adding C-reactive protein (CRP) and termed NIAAAm-CRP criteria, which showed superior diagnostic accuracy for presence of alcohol-associated steatohepatitis (ASH) on liver histology. The aim of our study was to validate the diagnostic accuracy of both original NIAAA criteria and NIAAAm-CRP criteria for presence of ASH on liver histology in an independent cohort. Methods: Data from a large multinational cohort of 445 patients with alcohol-associated liver disease (ALD) that served to establish a novel grading and staging system of alcohol-associated liver disease were analyzed retrospectively. Diagnosis of ASH was based on presence of hepatocyte ballooning plus lobular neutrophil infiltration and established in virtual consensus meetings of multiple expert liver pathologists. Results: Complete data including CRP values were available in 346 patients. Overall diagnostic accuracy for prediction of ASH was 73% for NIAAA criteria and 77% for NIAAAm-CRP criteria. In a subgroup with suspected severe AH (MELD >20, n = 123), overall diagnostic accuracy for prediction of ASH was 69% for NIAAA criteria and 74% for NIAAAm-CRP criteria. Conclusion: Our findings confirm recent data on suboptimal diagnostic accuracy of original NIAAA criteria and validate slightly better but still suboptimal performance of NIAAAm-CRP criteria for presence of ASH. Impact and Implications: Alcohol-associated steatohepatitis (ASH) is diagnosed on liver histology but liver biopsy is not always feasible. Non-invasive diagnosis based on clinical findings has been proposed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria and recently improved using NIAAAm-CRP criteria. Our findings validate slightly better but still suboptimal performance of NIAAAm-CRP criteria for the presence of histological ASH. Clinical trials of novel drugs should focus on histologically proven ASH.

RÉSUMÉLe projet HOMONIM phase 3 est mené par MétéoFrance et le Shom sous la maîtrise d’ouvrage de la Direction Générale de la Prévention des Risques (DGPR). Il vise à améliorer les capacités opérationnelles de modélisation des niveaux marins et des vagues à la côte pour aider la gestion du risque de submersion marine. Les principaux travaux de R&D en cours et à venir dans le projet HOMONIM3 sont abordés dans cet article : configuration de façade Manche – Atlantique du nouveau modèle de niveau marin TOLOSASW, calibration de la prévision d’ensemble (PE) de surcotes, mise en place d’une PE des vagues en côtier, modélisation couplée vagues/niveaux/courants à très haute résolution, pour le littoral Nord-Aquitain, et la modélisation non hydrostatique. Ces résultats sont susceptibles de servir aux modèles de prévision des inondations à proximité des estuaires ou des fleuves près de leur embouchure, en leur fournissant, sur leur frontière maritime, une condition limite plus réaliste, et cohérente avec les prévisions utilisées pour le dispositif de la Vigilance Vagues-Submersion (VVS), ainsi qu’une information, pour un jour donné, sur la prévisibilité des modèles ou sur l’existence de scénarios océaniques alternatifs.

Objectives: As there is no ranking designed for schools of Public Health, the aim of this project was to create one.Methods: To design the Public Health Academic Ranking (PHAR), we used the InCites Benchmarking and Analytics™ software and the Web Of Science™ Core Collection database. We collected bibliometric data on 26 schools of Public Health from each continent, between August and September 2022. We included 11 research indicators/scores, covering four criteria (productivity, quality, accessibility for readers, international collaboration), for the period 2017–2021. For the Swiss School of Public Health (SSPH+), a network gathering faculties across different universities, a specific methodology was used, with member-specific research queries.Results: The five top schools of the PHAR were: London School of Hygiene and Tropical Medicine, Public Health Foundation of India, Harvard T.H. Chan School of Public Health, SSPH+, Johns Hopkins Bloomberg School of Public Health.Conclusion: The PHAR allows worldwide bibliometric ordering of schools of Public Health. As this is a pilot project, the results must be taken with caution. This article aims to critically discuss its methodology and future improvements.

Background & Aims: The diagnosis of primary liver cancers (PLCs) can be challenging, especially on biopsies and for combined hepatocellular-cholangiocarcinoma (cHCC-CCA). We automatically classified PLCs on routine-stained biopsies using a weakly supervised learning method. Method: We selected 166 PLC biopsies divided into training, internal and external validation sets: 90, 29 and 47 samples, respectively. Two liver pathologists reviewed each whole-slide hematein eosin saffron (HES)-stained image (WSI). After annotating the tumour/non-tumour areas, tiles of 256x256 pixels were extracted from the WSIs and used to train a ResNet18 neural network. The tumour/non-tumour annotations served as labels during training, and the network's last convolutional layer was used to extract new tumour tile features. Without knowledge of the precise labels of the malignancies, we then applied an unsupervised clustering algorithm. Results: Pathological review classified the training and validation sets into hepatocellular carcinoma (HCC, 33/90, 11/29 and 26/47), intrahepatic cholangiocarcinoma (iCCA, 28/90, 9/29 and 15/47), and cHCC-CCA (29/90, 9/29 and 6/47). In the two-cluster model, Clusters 0 and 1 contained mainly HCC and iCCA histological features. The diagnostic agreement between the pathological diagnosis and the two-cluster model predictions (major contingent) in the internal and external validation sets was 100% (11/11) and 96% (25/26) for HCC and 78% (7/9) and 87% (13/15) for iCCA, respectively. For cHCC-CCA, we observed a highly variable proportion of tiles from each cluster (cluster 0: 5-97%; cluster 1: 2-94%). Conclusion: Our method applied to PLC HES biopsy could identify specific morphological features of HCC and iCCA. Although no specific features of cHCC-CCA were recognized, assessing the proportion of HCC and iCCA tiles within a slide could facilitate the identification of cHCC-CCA. Impact and implications: The diagnosis of primary liver cancers can be challenging, especially on biopsies and for combined hepatocellular-cholangiocarcinoma (cHCC-CCA). We automatically classified primary liver cancers on routine-stained biopsies using a weakly supervised learning method. Our model identified specific features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Despite no specific features of cHCC-CCA being recognized, the identification of hepatocellular carcinoma and intrahepatic cholangiocarcinoma tiles within a slide could facilitate the diagnosis of primary liver cancers, and particularly cHCC-CCA.

Abstract The gut microbiota and the endocannabinoidome (eCBome) play important roles in regulating energy homeostasis, and both are closely linked to dietary habits. However, the complex and compositional nature of these variables has limited our understanding of their interrelationship. This study aims to decipher the interrelation between dietary intake and the gut microbiome–eCBome axis using two different approaches for measuring dietary intake: one based on whole food and the other on macronutrient intakes. We reveal that food patterns, rather than macronutrient intakes, were associated with the gut microbiome–eCBome axis in a sample of healthy men and women (n = 195). N-acyl-ethanolamines (NAEs) and gut microbial families were correlated with intakes of vegetables, refined grains, olive oil and meats independently of adiposity and energy intakes. Specifically, higher intakes in vegetables and olive oil were associated with increased relative abundance of Clostridiaceae, Veillonellaceae and Peptostreptococaceae, decreased relative abundance of Acidominococaceae, higher circulating levels of NAEs, and higher HDL and LDL cholesterol levels. Our findings highlight the relative importance of food patterns in determining the gut microbiome–eCBome axis. They emphasize the importance of recognizing the contribution of dietary habits in these systems to develop personalized dietary interventions for preventing and treating metabolic disorders through this axis.

Marine sediments play a crucial role in the global carbon cycle by acting as the ultimate sink of both terrestrial and marine organic carbon. To understand the spatiotemporal variability in the content, sources, and dynamics of organic carbon in marine sediments, a curated and harmonized database of organic carbon and associated parameters is needed, which has prompted the development of the Modern Ocean Sediment Archive and Inventory of Carbon (MOSAIC) database (http://mosaic.ethz.ch/, last access: 26 July 2023; https://doi.org/10.5281/zenodo.8322094, Paradis, 2023; https://doi.org/10.5168/mosaic019.1, Van der Voort et al., 2019​​​​​​​). MOSAIC version 2.0 has expanded the spatiotemporal coverage of the original database by >400 % and now holds data from more than 21 000 individual sediment cores from different continental margins on a global scale. Additional variables have also been incorporated into MOSAIC v.2.0 that are crucial to interpret the quantity, origin, and age of organic carbon in marine sediments globally. Sedimentological parameters (e.g. grain size fractions and mineral surface area) help understand the effect of hydrodynamic sorting and mineral protection on the distribution of organic carbon, while molecular biomarker signatures (e.g. lignin phenols, fatty acids, and alkanes) can help constrain the specific origin of organic matter. MOSAIC v.2.0 also stores data on specific sediment and molecular fractions, which provide further insight into the processes that affect the degradation and ageing of organic carbon in marine sediments. Data included within MOSAIC are continuously expanding, and version control will allow users to benefit from updated versions while ensuring reproducibility of their findings.

Microbial-mediated nitrate removal from groundwater is widely recognized as the predominant mechanism for nitrate attenuation in contaminated aquifers and is largely dependent on the presence of a carbon-bearing electron donor. The repeated exposure of a natural microbial community to an electron donor can result in the sustained ability of the community to remove nitrate; this phenomenon has been clearly demonstrated at the laboratory scale. However, in situ demonstrations of this ability are lacking. For this study, ethanol (electron donor) was repeatedly injected into a groundwater well (treatment) for six consecutive weeks to establish the sustained ability of a microbial community to remove nitrate. A second well (control) located upgradient was not injected with ethanol during this time. The treatment well demonstrated strong evidence of sustained ability as evident by ethanol, nitrate, and subsequent sulfate removal up to 21, 64, and 68%, respectively, as compared to the conservative tracer (bromide) upon consecutive exposures. Both wells were then monitored for six additional weeks under natural (no injection) conditions. During the final week, ethanol was injected into both treatment and control wells. The treatment well demonstrated sustained ability as evident by ethanol and nitrate removal up to 20 and 21%, respectively, as compared to bromide, whereas the control did not show strong evidence of nitrate removal (5% removal). Surprisingly, the treatment well did not indicate a sustained and selective enrichment of a microbial community. These results suggested that the predominant mechanism(s) of sustained ability likely exist at the enzymatic- and/or genetic-levels. The results of this study demonstrated the in situ ability of a microbial community to remove nitrate can be sustained in the prolonged absence of an electron donor.

Despite growing research on individual differences in child bilinguals, few studies have focused on the development of syntax, included both languages, and studied newly arrived school-age migrant children. Accordingly, this study investigated the syntactic development of heritage language (HL) Syrian Arabic and L2 English by Syrian refugee children (N = 119) recently arrived in Canada using a sentence repetition task. Regression analyses showed that a partially overlapping set of child-level (input and cognitive skills) and language-level (syntactic structure) factors accounted for performance in each language. HL performance was particularly sensitive to language, cognitive, and input variables indexing cumulative HL exposure. L2 performance, however, was sensitive to cognitive and environmental variables indexing current and cumulative L2 use. Finally, despite stronger performance in Arabic than in English, results revealed interdependence between the two languages, indicating that participants with stronger syntactic abilities in their HL tended to have stronger syntactic abilities in their emerging L2.

Microbial-mediated nitrate removal from groundwater is widely recognized as the predominant mechanism for nitrate attenuation in contaminated aquifers and is largely dependent on the presence of a carbon-bearing electron donor. The repeated exposure of a natural microbial community to an electron donor can result in the sustained ability of the community to remove nitrate; this phenomenon has been clearly demonstrated at the laboratory scale. However, in situ demonstrations of this ability are lacking. For this study, ethanol (electron donor) was repeatedly injected into a groundwater well (treatment) for six consecutive weeks to establish the sustained ability of a microbial community to remove nitrate. A second well (control) located upgradient was not injected with ethanol during this time. The treatment well demonstrated strong evidence of sustained ability as evident by ethanol, nitrate, and subsequent sulfate removal up to 21, 64, and 68%, respectively, as compared to the conservative tracer (bromide) upon consecutive exposures. Both wells were then monitored for six additional weeks under natural (no injection) conditions. During the final week, ethanol was injected into both treatment and control wells. The treatment well demonstrated sustained ability as evident by ethanol and nitrate removal up to 20 and 21%, respectively, as compared to bromide, whereas the control did not show strong evidence of nitrate removal (5% removal). Surprisingly, the treatment well did not indicate a sustained and selective enrichment of a microbial community. These results suggested that the predominant mechanism(s) of sustained ability likely exist at the enzymatic- and/or genetic-levels. The results of this study demonstrated the in situ ability of a microbial community to remove nitrate can be sustained in the prolonged absence of an electron donor.

Abstract Unlike for advanced liver fibrosis, the practical rules for the early non-invasive diagnosis of cirrhosis in NAFLD remain not well defined. Here, we report the derivation and validation of a stepwise diagnostic algorithm in 1568 patients with NAFLD and liver biopsy coming from four independent cohorts. The study algorithm, using first the elastography-based tests Agile3+ and Agile4 and then the specialized blood tests FibroMeterV3G and CirrhoMeterV3G, provides stratification in four groups, the last of which is enriched in cirrhosis (71% prevalence in the validation set). A risk prediction chart is also derived to allow estimation of the individual probability of cirrhosis. The predicted risk shows excellent calibration in the validation set, and mean difference with perfect prediction is only −2.9%. These tools improve the personalized non-invasive diagnosis of cirrhosis in NAFLD.

Abstract Background The implementation of virtual devices can facilitate the role of therapists (e.g., patient motivation, intensity of practice) to improve the effectiveness of treatment for children with cerebral palsy. Among existing therapeutic devices, none has been specifically designed to promote the application of principles underlying evidence-based motor skill learning interventions. Consequently, evidence is lacking regarding the effectiveness of virtual-based sessions in motor function rehabilitation with respect to promoting the transfer of motor improvements into daily life activities. We tested the effectiveness of implementing a recently developed virtual device (REAtouch®), specifically designed to enable the application of therapeutic motor skill learning principles, during a Hand Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) intervention. Methods Forty children with unilateral cerebral palsy (5–18 years; MACS I-III; GMFCS I-II) were randomly assigned to a control group or a “REAtouch®” experimental group for a 90-h HABIT-ILE day-camp intervention (two weeks). Children in the REAtouch® group spent nearly half of their one-on-one therapeutic time using the REAtouch®. Participants underwent three testing sessions: the week before (T1), after intervention (T2), and at three months follow-up (T3). The primary outcome was the Assisting Hand Assessment (T3–T1; blinded). Secondary outcomes measured uni-bimanual hand function, stereognosis, gait endurance, daily life abilities, and functional goals. Accelerometers and a manual report of daily activities served to document therapeutic dosage and treatment characteristics. We used one-way RMANOVA to compare the efficacies of the two interventions, and non-inferiority analyses to contrast changes in the “REAtouch®” group versus the “HABIT-ILE” control group. Results We found significant improvements in both groups for most of the outcome measures (p

Abstract Background Early data on COVID-19 (based primarily on PCR testing) indicated a low burden in Sub-Saharan Africa. To better understand this, this study aimed to estimate the incidence rate and identify predictors of SARS-CoV-2 seroconversion in the two largest cities of Burkina Faso. This study is part of the EmulCOVID-19 project (ANRS-COV13). Methods Our study utilized the WHO Unity protocol for cohort sero-epidemiological studies of COVID-19 in general population. We conducted random sampling stratified by age group and sex. Individuals aged 10 years and older in the cities of Ouagadougou and Bobo-Dioulasso, Burkina Faso were included and surveyed at 4 time points, each 21 days apart, from March 3 to May 15, 2021. WANTAI SARS-CoV-2 Ab ELISA serological tests were used to detect total antibodies (IgM, IgG) in serum. Predictors were investigated using Cox proportional hazards regression. Results We analyzed the data from 1399 participants (1051 in Ouagadougou, 348 in Bobo-Dioulasso) who were SARS-CoV-2 seronegative at baseline and had at least one follow-up visit. The incidence rate of SARS-CoV-2 seroconversion was 14.3 cases [95%CI 13.3–15.4] per 100 person-weeks. The incidence rate was almost three times higher in Ouagadougou than in Bobo-Dioulasso (Incidence rate ratio: IRR = 2.7 [2.2–3.2], p

Abstract Two tumor (Classical/Basal) and stroma (Inactive/active) subtypes of Pancreatic adenocarcinoma (PDAC) with prognostic and theragnostic implications have been described. These molecular subtypes were defined by RNAseq, a costly technique sensitive to sample quality and cellularity, not used in routine practice. To allow rapid PDAC molecular subtyping and study PDAC heterogeneity, we develop PACpAInt, a multi-step deep learning model. PACpAInt is trained on a multicentric cohort (n = 202) and validated on 4 independent cohorts including biopsies (surgical cohorts n = 148; 97; 126 / biopsy cohort n = 25), all with transcriptomic data (n = 598) to predict tumor tissue, tumor cells from stroma, and their transcriptomic molecular subtypes, either at the whole slide or tile level (112 µm squares). PACpAInt correctly predicts tumor subtypes at the whole slide level on surgical and biopsies specimens and independently predicts survival. PACpAInt highlights the presence of a minor aggressive Basal contingent that negatively impacts survival in 39% of RNA-defined classical cases. Tile-level analysis ( > 6 millions) redefines PDAC microheterogeneity showing codependencies in the distribution of tumor and stroma subtypes, and demonstrates that, in addition to the Classical and Basal tumors, there are Hybrid tumors that combine the latter subtypes, and Intermediate tumors that may represent a transition state during PDAC evolution.

ObjectiveTo quantify and communicate risk equivalencies for alcohol-and tobacco-attributable mortality by comparing per standard drinks consumed to per number of cigarettes smoked in Canada.MethodsAlcohol-and tobacco-attributable premature deaths (≤75 years of age) and years of life lost (YLL) were estimated using a lifetime risk modeling approach. Alcohol-attributable death statistics were obtained from the 2023 Canadian Guidance on Alcohol and Health data source. Tobacco-attributable death statistics were derived from the Mortality Population Risk Tool (MPoRT) model.ResultsThe risk of alcohol use on premature death and YLL increased non-linearly with the number of drinks consumed, while the risk for tobacco use on these two measures increased linearly with the number of cigarettes smoked. Males who consumed 5 drinks/day—a standard drink contains 13.45 grams of alcohol in Canada—had an equivalent risk as smoking 4.9 cigarettes/day (when modeling for premature death) and 5.1 cigarettes/day (when modeling for YLL). Females who consumed 5 drinks/day experienced an equivalent risk as smoking 4.2 cigarettes/day for premature deaths and YLL. At all levels of alcohol consumption females and males who consumed

Background & Aims: Hepatocellular adenomas (HCAs) are rare, benign, liver tumours classified at the clinicopathological, genetic, and proteomic levels. The β-catenin-activated (b-HCA) subtypes harbour several mutation types in the β-catenin gene (CTNNB1) associated with different risks of malignant transformation or bleeding. Glutamine synthetase is a surrogate marker of β-catenin pathway activation associated with the risk of malignant transformation. Recently, we revealed an overexpression of glutamine synthetase in the rims of exon 3 S45-mutated b-HCA and exon 7/8-mutated b-HCA compared with the rest of the tumour. A difference in vascularisation was found in this rim shown by diffuse CD34 staining only at the tumour centre. Here, we aimed to characterise this tumour heterogeneity to better understand its physiopathological involvement. Methods: Using mass spectrometry imaging, genetic, and proteomic analyses combined with laser capture microdissection, we compared the tumour centre with the tumour rim and with adjacent non-tumoural tissue. Results: The tumour rim harboured the same mutation as the tumour centre, meaning both parts belong to the same tumour. Mass spectrometry imaging showed different spectral profiles between the rim and the tumour centre. Proteomic profiling revealed the significant differential expression of 40 proteins at the rim compared with the tumour centre. The majority of these proteins were associated with metabolism, with an expression profile comparable with a normal perivenous hepatocyte expression profile. Conclusions: The difference in phenotype between the tumour centres and tumour rims of exon 3 S45-mutated b-HCA and exon 7/8-mutated b-HCA does not depend on CTNNB1 mutational status. In a context of sinusoidal arterial pathology, tumour heterogeneity at the rim harbours perivenous characteristics and could be caused by a functional peripheral venous drainage. Impact and implications: Tumour heterogeneity was revealed in β-catenin-mutated hepatocellular adenomas (b-HCAs) via the differential expression of glutamine synthase at tumour rims. The combination of several spatial approaches (mass spectrometry imaging, genetic, and proteomic analyses) after laser capture microdissection allowed identification of a potential role for peripheral venous drainage underlying this difference. Through this study, we were able to illustrate that beyond a mutational context, many factors can downstream regulate gene expression and contribute to different clinicopathological phenotypes. We believe that the combinations of spatial analyses that we used could be inspiring for all researchers wanting to access heterogeneity information of liver tumours.

Synaptic plasticity, the process whereby neuronal connections are either strengthened or weakened in response to stereotyped forms of stimulation, is widely believed to represent the molecular mechanism that underlies learning and memory. The holoenzyme calcium/calmodulin-dependent protein kinase II (CaMKII) plays a well-established and critical role in the induction of a variety of forms of synaptic plasticity such as long-term potentiation (LTP), long-term depression (LTD) and depotentiation. Previously, we identified the GTPase Rem2 as a potent, endogenous inhibitor of CaMKII. Here, we report that knock out of Rem2 enhances LTP at the Schaffer collateral to CA1 synapse in hippocampus, consistent with an inhibitory action of Rem2 on CaMKII in vivo. Further, re-expression of WT Rem2 rescues the enhanced LTP observed in slices obtained from Rem2 conditional knock out (cKO) mice, while expression of a mutant Rem2 construct that is unable to inhibit CaMKII in vitro fails to rescue increased LTP. In addition, we demonstrate that CaMKII and Rem2 interact in dendritic spines using a 2pFLIM-FRET approach. Taken together, our data lead us to propose that Rem2 serves as a brake on synaptic potentiation via inhibition of CaMKII activity. Further, the enhanced LTP phenotype we observe in Rem2 cKO slices reveals a previously unknown role for Rem2 in the negative regulation of CaMKII function.

Suicide is a complex, multidimensional event, and a significant challenge for prevention globally. Artificial intelligence (AI) and machine learning (ML) have emerged to harness large-scale datasets to enhance risk detection. In order to trust and act upon the predictions made with ML, more intuitive user interfaces must be validated. Thus, Interpretable AI is one of the crucial directions which could allow policy and decision makers to make reasonable and data-driven decisions that can ultimately lead to better mental health services planning and suicide prevention. This research aimed to develop sex-specific ML models for predicting the population risk of suicide and to interpret the models. Data were from the Quebec Integrated Chronic Disease Surveillance System (QICDSS), covering up to 98% of the population in the province of Quebec and containing data for over 20,000 suicides between 2002 and 2019. We employed a case-control study design. Individuals were considered cases if they were aged 15+ and had died from suicide between January 1st, 2002, and December 31st, 2019 (n = 18339). Controls were a random sample of 1% of the Quebec population aged 15+ of each year, who were alive on December 31st of each year, from 2002 to 2019 (n = 1,307,370). We included 103 features, including individual, programmatic, systemic, and community factors, measured up to five years prior to the suicide events. We trained and then validated the sex-specific predictive risk model using supervised ML algorithms, including Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGBoost) and Multilayer perceptron (MLP). We computed operating characteristics, including sensitivity, specificity, and Positive Predictive Value (PPV). We then generated receiver operating characteristic (ROC) curves to predict suicides and calibration measures. For interpretability, Shapley Additive Explanations (SHAP) was used with the global explanation to determine how much the input features contribute to the models' output and the largest absolute coefficients. The best sensitivity was 0.38 with logistic regression for males and 0.47 with MLP for females; the XGBoost Classifier with 0.25 for males and 0.19 for females had the best precision (PPV). This study demonstrated the useful potential of explainable AI models as tools for decision-making and population-level suicide prevention actions. The ML models included individual, programmatic, systemic, and community levels variables available routinely to decision makers and planners in a public managed care system. Caution shall be exercised in the interpretation of variables associated in a predictive model since they are not causal, and other designs are required to establish the value of individual treatments. The next steps are to produce an intuitive user interface for decision makers, planners and other stakeholders like clinicians or representatives of families and people with live experience of suicidal behaviors or death by suicide. For example, how variations in the quality of local area primary care programs for depression or substance use disorders or increased in regional mental health and addiction budgets would lower suicide rates.

BackgroundCharting is an essential component of professional nursing practice and is arguably a key element of patient safety in surgery: without proper, objective, and timely documentation, both benign and tragical errors can occur. From surgery on wrong patients to wrong limbs, to the omission of antibiotics administration, many harms can happen in the operating room. Documentation has thus served as a safeguard for patient safety, professional responsibility, and professional accountability. In this context, we were puzzled by the practices we observed with respect to charting compliance with the surgical safety checklist (SSC) during a study of surgical teams in a large, urban teaching hospital in Canada (pseudonym 'C&C').MethodsThis article leverages institutional ethnography and a subset of data from a larger study to describe and explain the social organisation of the system that monitored surgical safety compliance at C&C from the standpoint of operating room nurses. This data included fieldnotes from observations of 51 surgical cases, on-the-spot interviews with nurses, formal interviews with individuals who were involved in the design and implementation of the SSC, and open-ended questions from two rounds of survey of OR teams.FindingsWe found that the compliance form and not the SSC itself formed the basis for reporting. To meet hospital accuracy in charting goals and legislated compliance documentation reporting requirements nurses 'pre-charted' compliance with the surgical checklist. The adoption of this workaround technically violated nursing charting principles and put them in ethically untenable positions.ConclusionsDocumenting compliance of the SSC constituted a moral hazard, constrained nurses' autonomy and moral agency, and obscured poor checklist adherence. The findings highlight how local and extra local texts, technologies and relations create ethical issues, raise questions about the effectiveness of resulting data for decision-making and contribute to ongoing conversations about nursing workarounds.

Antimicrobial resistance can be effectively limited by improving the judicious use of antimicrobials in food production. However, its effect on the spread of AMR genes in animal populations is not well described. In the province of Québec, Canada, a new legislation implemented in 2019 has led to an unprecedented reduction in the use of critical antimicrobials in dairy production. We aimed to investigate the potential link between ESBL/AmpC E. coli isolated before and after legislation and to determine the presence of plasmids carrying genes responsible for critical AMR. We collected fecal samples from calves, cows, and manure pit from 87 Québec dairy farms approximately 2 years before and 2 years after the legislation came into effect. The whole genomes of 183 presumptive ESBL/AmpC E. coli isolated after cefotaxime enrichment were sequenced. Their phylogenetic characteristics (MLST, serogroup, cgMLST) and the presence of virulence and resistance genes and replicons were examined. A maximum likelihood phylogenetic tree was constructed based on single nucleotide polymorphism (SNPs). We identified 10 clonal lineages (same cgMLST) and 7 clones (SNPs ≤ 52). Isolates belonging to these clones could be found on different farms before and after the legislation, strongly suggesting a clonal spread of AMR genes in the population during this 4-year period. All isolates were multidrug resistant (MDR), with clone 2 being notable for the presence of macrolide, fluoroquinolone, and third-generation cephalosporin resistance genes. We also identified clinically relevant ExPEC (ST10) and APEC-like lineages (ST117, ST58, ST88) associated with the presence of ExPEC and APEC virulence genes, respectively. Our data also suggests the presence of one epidemic plasmid belonging to the IncY incompatibility group and carrying qnrs1 and blaCTX–M–15. We demonstrated that AMR genes spread through farms and can persist over a 4-year period in the dairy cattle population through both plasmids and E. coli clones, despite the restriction of critical antimicrobial use. MDR ExPEC and APEC-like STs are present in the normal microbiota of cattle (more frequently in calves). These data increase our knowledge on gene dissemination dynamics and highlight the fact that biosecurity measures should be enhanced in this industry to limit such dissemination.

Erythropoietic protoporphyria (EPP) is a rare metabolic disease of the heme biosynthetic pathway where an enzymatic dysfunction results in protoporphyrin IX (PPIX) accumulation in erythroid cells. The porphyrins are photo-reactive and are responsible for severe photosensitivity in patients, thus drastically decreasing their quality of life. The liver eliminates PPIX and as such, the main and rare complication of EPP is progressive cholestatic liver disease, which can lead to liver failure. The management of this complication is challenging, as it often requires a combination of approaches to promote PPIX elimination and suppress the patient's erythropoiesis. Here we described a 3-year follow-up of an EPP patient, with three episodes of liver involvement, aggravated by the coexistence of a factor VII deficiency. It covers all the different types of intervention available for the management of liver disease, right through to successful allogeneic hematopoietic stem cell transplantation.

PurposeUveal melanoma is the most common eye cancer in adults. Approximately 50% of patients with uveal melanoma develop metastatic uveal melanoma (mUM) in the liver, even after successful treatment of the primary lesions. mUM is refractory to current chemo- and immune-therapies, and most mUM patients die within a year. Uveal melanoma is characterized by gain-of-function mutations in GNAQ/GNA11, encoding Gαq proteins. We have recently shown that the Gαq-oncogenic signaling circuitry involves a noncanonical pathway distinct from the classical activation of PLCβ and MEK-ERK. GNAQ promotes the activation of YAP1, a key oncogenic driver, through focal adhesion kinase (FAK), thereby identifying FAK as a druggable signaling hub downstream from GNAQ. However, targeted therapies often activate compensatory resistance mechanisms leading to cancer relapse and treatment failure.Experimental designWe performed a kinome-wide CRISPR-Cas9 sgRNA screen to identify synthetic lethal gene interactions that can be exploited therapeutically. Candidate adaptive resistance mechanisms were investigated by cotargeting strategies in uveal melanoma and mUM in vitro and in vivo experimental systems.ResultssgRNAs targeting the PKC and MEK-ERK signaling pathways were significantly depleted after FAK inhibition, with ERK activation representing a predominant resistance mechanism. Pharmacologic inhibition of MEK and FAK showed remarkable synergistic growth-inhibitory effects in uveal melanoma cells and exerted cytotoxic effects, leading to tumor collapse in uveal melanoma xenograft and liver mUM models in vivo.ConclusionsCoupling the unique genetic landscape of uveal melanoma with the power of unbiased genetic screens, our studies reveal that FAK and MEK-ERK cotargeting may provide a new network-based precision therapeutic strategy for mUM treatment.See related commentary by Harbour, p. 2967.

Abstract Background Mapping patient and work flow and cost analysis studies can help determine the most efficient and cost effective way of providing health services while still maintaining the best standards of care. This study used both time and motion methodology and hospital data to assess the contribution of staff time and facility usage to the overall cost of cancer care during patient visits to a comprehensive cancer centre in Quebec, using metastatic colorectal cancer as a model. Methods A workflow diagram was created mapping direct and indirect steps involved during a patient’s physician or treatment (FOLFOX/bevacizumab or XELOX/bevacizumab) visit. Staff were timed as they performed each task and this data together with compensation amounts were used to calculate personnel costs. Mean work times and 95% confidence intervals (CI) were calculated. Operation and maintenance (O&M) costs for the Centre were calculated using information from hospital databases. All costs were presented in constant Canadian dollars for the 2010–2011 fiscal year period. Results For physician visits, direct and indirect personnel costs were $9.25 (95%CI:$7.00-$11.51) and O&M costs were $60.21, for a total of $69.46 (95%CI:$67.21-$71.72). For treatment visits, personnel and O&M costs were $71.91 (95%CI:$45.53-$98.29) and $62.00 respectively for a total of $133.91 (95%CI:$107.53-$160.29). When calculated for treatment alone, the total cost was $136.06 (95%CI:$109.16-$162.95) for FOLFOX/bevacizumab and $119.94 (95%CI:$96.89-$142.99) for XELOX/bevacizumab. The highest cumulative personnel costs were for the pharmacists and nurses ($38.87 and $34.82 respectively). Regarding patient flow, total time in between steps was 77.6 and 49.5 minutes for a physician or treatment visit respectively. Conclusions This study from a health care provider’s perspective, demonstrated that in the context of increasingly expensive therapies, costs associated with staff time and facility usage do not contribute greatly to the overall cost of treating cancer at this cancer centre. It also illustrated the need for improvements in patient and work flow to reduce wait times in the clinic.

This exploratory study aimed to identify the ways psychologists working in schools supported students' mental health during school closures related to the COVID-19 pandemic. An online survey was developed to determine (a) how psychologists working in schools across the United States, Canada, Germany, and Australia supported students' mental health during COVID-19, (b) how their services changed during COVID-19, and (c) potential differences between countries concerning difficulties supporting students' mental health during this time. The survey was based on previous research and was subsequently piloted. Using convenience and snowball sampling, 938 participants (U.S. n = 665; Canada n = 48; Germany n = 140; Australia n = 85) completed the online survey. Overall, school psychology services across these four countries pivoted from psychoeducational assessments to virtual counseling, consultation, and the development/posting of online support directly to children or parents to use with their children. There was some variation between countries; during the pandemic, significantly more psychologists in Germany and Australia provided telehealth/telecounseling than those in the United States and Canada, and psychologists in Germany provided significantly more hardcopy material to support children than psychologists in other countries. There is a need to ensure psychologists have the appropriate technological skills to support school communities during periods of school closure, including, but not limited to, virtual counseling and the administration of psychoeducational assessments.

Abstract Background The longitudinal relation between parenting practices and styles with children’s body mass index z-scores (zBMI) is poorly understood. Previous studies suggest the relationship may be complex, but small samples and short follow-ups diminish the strength of the evidence. The objectives of this study were to investigate whether the relationship is bidirectional, time-varying, and lagged using data from a large, representative birth cohort of Quebec children. Methods Data were from the Québec Longitudinal Study of Child Development (QLSCD), a prospective birth cohort (n = 1,602). The mothers’ interactions with their children (at ages 6, 8, 10, and 12 years) were utilized in factor analysis to identify three latent parenting practices (disciplinarian, lenient, and responsive). The parenting practices were analyzed with K-means clustering to identify the parenting styles. The temporal and bidirectional relationships were assessed in a cross-lagged path analysis using a structural equation modelling framework. Mixed models controlling for age, sex, income, mother’s education, and whether the participant was first-born were estimated. Missing data were handled with full information maximum likelihood. Results From the linear mixed models, greater lenient and responsive parenting practices were associated with higher zBMI (B = 0.03, p