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Abstract: Acid mine drainage (AMD) is an environmental problem produced when sulphides come in contact with an oxidant (± bacteria) and water, producing acid generation and metals leaching. One solution [...]

Most fuel cycle simulation tools are based either on fixed recipes or assembly calculations for reactor modeling. Due to the high number of calculations and extensive computational power requirements, full-core computations are often seen as not viable for this purpose. However, this leads to additional hypotheses and modeling biases, thus limiting the realism of the resulting fuel cycle. For several applications, the current modeling method is sufficient, but precise calculations of discharged fuel composition may require further refinements. CLASS (Core Library for Advanced Simulation Scenarios) is a dynamic fuel cycle simulation code developed since 2012 with reactor models based on neural networks to produce nuclear data and physical quantities. Past work has shown a first coupling between CLASS and DONJON5 to quantify neural networks approach biases. This work assesses the applicability of 3D full-core diffusion calculations using the DONJON5 code coupled with nuclear scenario simulations involving a realistic PWR core at equilibrium cycle conditions. DONJON5 interpolates burnup dependent diffusion coefficients and cross sections generated beforehand by DRAGON5, a deterministic lattice calculation tool. Whereas previous studies considered only homogeneous reactors (i.e. homogeneous assembly in terms of composition and enrichment as well as homogeneous core), the present contribution focuses on the integration of full-core calculations in CLASS for fuel cycles involving a MOX/UO2 PWR core (i.e. 1/3 MOx–2/3 UOx). The DONJON5 model considered in this work describes a core with critical boron concentration at each time step partially loaded with MOx heterogeneous assemblies composed of three enrichments. In fuel cycle calculations, the main issue is to adapt, in the fabrication stage, the fresh fuel composition for the reactor with regards to the isotopic composition of the available stocks. This work presents a fuel loading model based on power peaking factors minimization that respects irradiation cycle length, 235U enrichment as well as Pu concentration and fissile quality, hence, ensuring a more uniform power distribution in the core.

Abstract Background The impact of an aging population on the psychiatric emergency service (PES) has not been fully ascertained. Cognitive dysfunctions aside, many DSM-IV disorders may have a lower prevalence in the elderly, who appear to be underrepresented in the PES. We therefore attempted to more precisely assess their patterns of PES use and their clinical and demographic characteristics. Methods Close to 30,000 visits to a general hospital PES (Montreal, Quebec, Canada) were acquired between 1990 and 2004 and pooled with over 17,000 visits acquired using the same methodology at three other services in Quebec between 2002 and 2004. Results The median age of PES patients increased over time. However, the proportion of yearly visits attributable to the elderly (compared to those under 65) showed no consistent increase during the observation period. The pattern of return visits (two to three, four to ten, eleven or more) did not differ from that of patients under 65, although the latter made a greater number of total return visits per patient. The elderly were more often women (62%), widowed (28%), came to the PES accompanied (42%) and reported « illness » as an important stressor (29%). About 39% were referred for depression or anxiety. They were less violent (10%) upon their arrival. Affective disorders predominated in the diagnostic profile, they were less co-morbid and more likely admitted than patients under 65. Conclusion Although no proportional increase in PES use over time was found the elderly do possess distinct characteristics potentially useful in PES resource planning so as to better serve this increasingly important segment of the general population.

Abstract Background Several recent studies have reported a significant increase in medical emergency department (ED) use for reasons of mental health. The diagnostic profile of these patients however differs from that usually described for patients visiting the psychiatric emergency service (PES). Few studies have specifically focused upon long-term PES utilization rates. Those that do typically present data from the early 80s, suggesting that deinstitutionalization may be an important contributing factor to the increases found. The aim of this study was to assess PES use using a more recent time frame and, the effects of non-specific factors, such as population growth, on this use. Methods Visits per year at several different types of PESs were obtained; (a) for an 11-year period at a general hospital PES while the surrounding population remained stable, (b) at that same PES while the catchment area population doubled over a period of a few years, (c) for an 11-year period at two PESs without catchment areas while the surrounding population increased and (d-) for a 12-year period at a PES in a mental health facility while the surrounding population increased. Moderately conservative criteria were used to define either a trend or, a significant increase in utilization rates. Results Each site had an inherent, 7 to 15% yearly variability in the number of PES visits. Over time however, only those where the surrounding population increased (either by an increase in the catchment area size or a regional increase in the population census) showed a trend or, a significant increase in utilization rates. These increases however were modest and of the order of 12 to 19%. Conclusion Long observation periods are required in order to detect stable changes in PES utilization rates over time. As such, population growth may be but one of several factors underlying these increases. Organizational changes in mental health care delivery in the vicinity of the services that showed an increase could also have contributed. These latter would simply have redistributed (to the PES) the pre existing pool of mental health care patients, resulting in an increase that is more apparent than real.

Abstract Background The psychiatric emergency service (PES) is a major hub in the mental health care delivery system. The aim of this study was to more precisely define what psychiatrists consider to be a psychiatric emergency and to examine the underlying basis of this assessment. Methods Over twenty-two thousand PES visits were assessed prospectively for pertinence and urgency by psychiatrists in four functionally and structurally different services in the province of Quebec, Canada. This study took place between July 15 1996 and August 31, 2004. Results Overall, 57% of visits were judged pertinent and urgent (P/U), 30% pertinent but not urgent (P/NU) and 13% neither pertinent nor urgent (NP/NU). Between 50 and 60% of P/U tagged visits were diagnosed with an affective or a psychotic disorder, often with a suicidal content. They also more frequently resulted in a short-term observation in the PES or a hospitalization. Variables suggesting the presence of a behaviorally disturbed state (aggressive behaviors, involuntary or police referrals) were equally likely to be found in P/U or NP/NU visits. Legal confinement following the consultation was almost exclusively seen in visits judged P/U. The percent of visits tagged P/U at the four individual sites varied substantially above and below the 57% value for the combined data. Interestingly, no major inter-site differences in diagnostic profiles for the three pertinence and urgency anchor points were found that might account for this variability. Finally, visits from high frequency users were less likely to be judged P/U than visits from patients attending less frequently. Conclusion Primary consideration for a P/U tag was a visit characterized by a behaviorally disturbed state and/or, suicidal ideation (or attempts) within the context of either an underlying psychotic or affective disorder, especially if poor judgment was an issue. Some specific diagnoses appeared to qualify the above core clinical considerations, increasing or decreasing the probability of a P/U tag. Finally, non-clinical site-specific factors related to the individual services themselves, such as the number of readily available specialized resources, also appeared to qualify this assessment. These data may prove useful for the future development of this service.

Human airway and corneal epithelial cells, which are critically altered during chronic infections mediated by Pseudomonas aeruginosa, specifically express the inflammasome sensor NLRP1. Here, together with a companion study, we report that the NLRP1 inflammasome detects exotoxin A (EXOA), a ribotoxin released by P. aeruginosa type 2 secretion system (T2SS), during chronic infection. Mechanistically, EXOA-driven eukaryotic elongation factor 2 (EEF2) ribosylation and covalent inactivation promote ribotoxic stress and subsequent NLRP1 inflammasome activation, a process shared with other EEF2-inactivating toxins, diphtheria toxin and cholix toxin. Biochemically, irreversible EEF2 inactivation triggers ribosome stress-associated kinases ZAKα- and P38-dependent NLRP1 phosphorylation and subsequent proteasome-driven functional degradation. Finally, cystic fibrosis cells from patients exhibit exacerbated P38 activity and hypersensitivity to EXOA-induced ribotoxic stress-dependent NLRP1 inflammasome activation, a process inhibited by the use of ZAKα inhibitors. Altogether, our results show the importance of P. aeruginosa virulence factor EXOA at promoting NLRP1-dependent epithelial damage and identify ZAKα as a critical sensor of virulence-inactivated EEF2., (© 2023 Pinilla et al.)

Dynamic contacts are formed between endoplasmic reticulum (ER) and mitochondria that enable the exchange of calcium and phospholipids. Disturbed contacts between ER and mitochondria impair mitochondrial dynamics and are a molecular hallmark of Parkinson's disease, which is also characterized by impaired complex I activity and dopaminergic neuron degeneration. Here, we analyzed the role of cysteine-rich with EGF-like domain (Creld), a poorly characterized risk gene for Parkinson's disease, in the regulation of mitochondrial dynamics and function. We found that loss of Creld leads to mitochondrial hyperfusion and reduced ROS signaling in Drosophila melanogaster , Xenopus tropicalis , and human cells. Creld fly mutants show differences in ER-mitochondria contacts and reduced respiratory complex I activity. The resulting low-hydrogen peroxide levels are linked to disturbed neuronal activity and lead to impaired locomotion, but not neurodegeneration, in Creld mutants. We conclude that Creld regulates ER-mitochondria communication and thereby hydrogen peroxide formation, which is required for normal neuron function.

Background: Behavioral mitigation strategies to slow the spread of COVID-19 have resulted in sweeping lifestyle changes, with short- and long-term psychological, well-being, and quality of life implications. The Attitudes About COVID-19 and Health (ATTACH) study focuses on understanding attitudes and beliefs while considering the impact on mental and physical health and the influence of broader demographic and geographic factors on attitudes, beliefs, and mental health burden., Objective: In this assessment of our first wave of data collection, we provide baseline cohort description of the ATTACH study participants in the United Kingdom, the United States, and Mexico. Additionally, we assess responses to daily poll questions related to COVID-19 and conduct a cross-sectional analysis of baseline assessments collected in the UK between June 26 and October 31, 2020., Methods: The ATTACH study uses smartphone app technology and online survey data collection. Participants completed poll questions related to COVID-19 2 times daily and a monthly survey assessing mental health, social isolation, physical health, and quality of life. Poll question responses were graphed using 95% Clopper-Pearson (exact) tests with 95% CIs. Pearson correlations, hierarchical linear regression analyses, and generalized linear models assessed relationships, predictors of self-reported outcomes, and group differences, respectively., Results: By October 31, 2020, 1405, 80, and 90 participants had consented to participate in the UK, United States, and Mexico, respectively. Descriptive data for the UK daily poll questions indicated that participants generally followed social distancing measures, but worry and negative impacts on families increased as the pandemic progressed. Although participants generally reported feeling that the reasons for current measures had been made clear, there was low trust that the government was doing everything in its power to meet public needs. In the UK, 1282 participants also completed a monthly survey (94.99% [1326/1396] White, 72.22% [1014/1404] female, and 20.12% [277/1377] key or essential workers); 18.88% (242/1282) of UK participants reported a preexisting mental health disorder, 31.36% (402/1282) reported a preexisting chronic medical illness, and 35.11% (493/1404) were aged over 65; 57.72% (740/1282) of participants reported being more sedentary since the pandemic began, and 41.89% (537/1282) reported reduced access to medical care. Those with poorer mental health outcomes lived in more deprived neighborhoods, in larger households (Ps<.05), had more preexisting mental health disorders and medical conditions, and were younger than 65 years (all Ps<.001)., Conclusions: Communities who have been exposed to additional harm during the COVID-19 pandemic were experiencing worse mental outcomes. Factors including having a medical condition, or living in a deprived neighborhood or larger household were associated with heightened risk. Future longitudinal studies should investigate the link between COVID-19 exposure, mental health, and sociodemographic and residential characteristics., (©Anna M Hood, Hanne Stotesbury, Jennifer Murphy, Melanie Kölbel, April Slee, Charlie Springall, Matthew Paradis, Nadia Saraí Corral-Frías, Azalea Reyes-Aguilar, Alfredo B Cuellar Barboza, Amy E Noser, Stacey Gomes, Monica Mitchell, Sharon M Watkins, Melinda Butsch Kovacic, Fenella J Kirkham, Lori E Crosby. Originally published in JMIR Mental Health (https://mental.jmir.org), 07.10.2021.)

Background: Human Papillomavirus (HPV) is the most common sexually transmitted infection in Canada and around the world. Vaccination is an effective prevention strategy, but uptake is low, especially among newcomers to Canada. We sought to understand newcomers' knowledge, attitudes, and beliefs (KAB) on HPV and HPV vaccination and their role in HPV vaccine acceptance., Methods: Newcomers were defined as individuals born outside Canada, (i.e., individuals born in a different country, the majority of whom are immigrants or refugees, but also includes students and undocumented migrants). Eligible participants were newcomers, aged 16 or older and who could read or write in English, French or Arabic. Surveys were administered in two community health centres in Ottawa, Canada that primarily engage with newcomer populations. Follow-up interviews were conducted either at the community health centre or over the phone, depending on participants' preferences., Results: Fifty participants completed the survey, the majority of whom were women (74%) and spoke Arabic as their first language (54%). Seven participants completed supplemental interviews to complement their survey responses. The majority (70%) of participants had not previously heard of HPV. Less than half (46%) knew that the vaccine is effective in preventing certain types of cancer; nearly 40% incorrectly believed the vaccine could cure HPV. Qualitative interviews supported the survey findings., Conclusions: Despite a lack of HPV knowledge due to cultural and language barriers, there is still a strong desire among newcomers to receive the vaccine, especially when accompanied by a physician recommendation. Cultural and language-appropriate resources are needed to help newcomers make informed vaccination decisions and promote HPV vaccine uptake.

Significant maturation of swimming in zebrafish ( Danio rerio ) occurs within the first few days of life when fish transition from coiling movements to burst swimming and then to beat-and-glide swimming. This maturation occurs against a backdrop of numerous developmental changes - neurogenesis, a transition from predominantly electrical to chemical-based neurotransmission, and refinement of intrinsic properties. There is evidence that spinal locomotor circuits undergo fundamental changes as the zebrafish transitions from burst to beat-and-glide swimming. Our electrophysiological recordings confirm that the operation of spinal locomotor circuits becomes increasingly reliant on glycinergic neurotransmission for rhythmogenesis governing the rhythm of tail beats. This transition occurred at the same time that we observed a change in rhythmicity of synaptic inhibition to spinal motoneurons (MNs). When we examined whether the transition from weakly to strongly glycinergic dependent rhythmogenesis occurred at a uniform pace across the length of the spinal cord, we found that this transition occurred earlier at caudal segments than at rostral segments of the spinal cord. Furthermore, while this rhythmogenic transition occurred when fish transition from burst swimming to beat-and-glide swimming, these two transitions were not interdependent. These results suggest that there is a developmental transition in the operation of spinal locomotor circuits that is gradually set in place in the spinal cord in a caudo-rostral temporal sequence., (Copyright © 2020 Roussel et al.)

Background: The Canadian CT Head Rule (CCHR), the Canadian Transient Ischemic Attack (TIA) Score, and the Subarachnoid Hemorrhage (SAH) Rule have all previously demonstrated the potential to significantly standardize care and improve the management of patients in emergency departments (EDs). On the basis of user feedback, we believe that the addition of these rules to the Ottawa Rules App has the potential to increase the app's usability and user acceptability., Objective: This study aimed to evaluate the perceived usefulness, acceptability, and uptake of the enhanced Ottawa Rules App (which now includes CCHR, TIA, and SAH Rules) among ED clinicians (medical students, residents, nurses, and physicians)., Methods: The enhanced Ottawa Rules App was publicly released for free on iOS and Android operating systems in November 2018. This study was conducted across 2 tertiary EDs in Ottawa, Canada. Posters, direct enrollment, snowball sampling, and emails were used for study recruitment. A 24-question Web-based survey was administered to participants via email, and this was used to determine user acceptability of the app and Technology Readiness Index (TRI) scores. In-app user analytics were collected to track user behavior, such as the number of app sessions, length of app sessions, frequency of rule use, and the date app was first opened., Results: A total of 77 ED clinicians completed the study, including 34 nurses, 12 residents, 14 physicians, and 17 medical students completing ED rotations. The median TRI score for this group was 3.38, indicating a higher than average propensity to embrace and adopt new technologies to accomplish goals in their work or daily lives. The majority of respondents agreed or strongly agreed that the app helped participants accurately carry out the clinical rules (56/77, 73%) and that they would recommend this app to their colleagues (64/77, 83%). Feedback from study participants suggested further expansion of the app-more clinical decision rules (CDRs) and different versions of the app tailored to the clinician role. Analysis and comparison of Google Analytics data and in-app data revealed similar usage behavior among study-enrolled users and all app users globally., Conclusions: This study provides evidence that using the Ottawa Rules App (version 3.0.2) to improve and guide patient care would be feasible and widely accepted. The ability to verify self-reported user data (via a Web-based survey) against server analytics data is a notable strength of this study. Participants' continued app use and request for the addition of more CDRs warrant the further development of this app and call for additional studies to evaluate its feasibility and usability in different settings as well as assessment of clinical impact., (©Amanda My Linh Quan, Ian Stiell, Jeffrey J Perry, Michelle Paradis, Erica Brown, Jordan Gignac, Lindsay Wilson, Kumanan Wilson. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 29.01.2020.)

In humans, hereditary sensory neuropathies (HSN), also known as hereditary sensory and autonomic neuropathies (HSAN), constitute a clinically and genetically heterogeneous group of disorders characterized by progressive sensory loss, often accompanied by chronic skin ulcerations and nail dystrophic changes. To date, although around 20 genes have already been discovered, they do not explain the genetic causes of all patients. In dogs, similar neuropathies are also diagnosed, several breeds being predisposed to specific forms of the disease. Indeed, the breed specificity of most canine genetic diseases is due to the small numbers of founders and high levels of inbreeding. Recent knowledge and tools developed to study the canine genome efficiently allows deciphering the genetic bases of such diseases. To date, a dozen breeds are recognized to develop specific HSN. For the Border collie and hunting dog breeds, the genes involved have recently been discovered. Other affected breeds thus constitute potential genetic models, with new genes to be found in dogs that can be considered as candidate genes for human HSAN/HSN. Here, we review the different forms of human and canine HSAN/HSN and we present a novel form in Fox terrier cases, highlighting the advantages of the dog model for such rare human diseases.

Objectives: Newcomers experience unique challenges with respect to vaccination. These challenges are compounded by the need to navigate complex vaccination catch-up schedules upon arrival in their new home countries. Our group has pioneered the development of CANImmunize, a free, bilingual, pan-Canadian digital application designed to empower individuals to manage their vaccination records. To inform how a vaccine tracking app such as CANImmunize might be tailored to meet the unique needs of newcomers, this study sought to determine commonly spoken languages, technology use, and current methods of vaccine tracking among recent newcomers to Canada., Methods: Government-assisted refugees attending a health clinic in Ottawa, Canada were invited to complete a 17-question needs assessment survey. The survey captured data on household demographics, spoken languages, country of origin, technology use and methods used to track vaccination history., Results: 50 newcomers completed the needs assessment survey. Arabic was the predominant language spoken by surveyed individuals. Although 92% of participants owned a smartphone, the majority did not actively use digital health applications. 18 (36%) participants reported being vaccinated before arriving in Canada. 27 (54%) participants were parents, 23 of whom reported that their children were vaccinated prior to arrival in Canada. 38 (76%) participants indicated that they would use a vaccine tracking app such as CANImmunize if it were translated into their primary language of communication., Conclusions: The results of our study indicate that mobile technology may be a useful tool to help newcomer families stay on track with provincial and territorial immunization schedules.

Background: The Ottawa Ankle Rules, Ottawa Knee Rule, and Canadian C-Spine Rule-together known as The Ottawa Rules-are a set of internationally validated clinical decision rules developed to decrease unnecessary diagnostic imaging in the emergency department. In this study, we sought to develop and evaluate the use of a mobile app version of The Ottawa Rules., Objective: The primary objective of this study was to determine acceptability of The Ottawa Rules app among emergency department clinicians. The secondary objective was to evaluate the effect of publicity efforts on uptake of The Ottawa Rules app., Methods: The Ottawa Rules app was developed and publicly released for free on iOS and Android operating systems in April 2016. Local and national news and academic media coverage coincided with app release. This study was conducted at a large tertiary trauma care center in Ottawa, Canada. The study was advertised through posters and electronically by email. Emergency department clinicians were approached in person to enroll via in-app consent for a 1-month study during which time they were encouraged to use the app when evaluating patients with suspected knee, foot, or neck injuries. A 23-question survey was administered at the end of the study period via email to determine self-reported frequency, perceived ease of use of the app, and participant Technology Readiness Index scores., Results: A total of 108 emergency department clinicians completed the study including 42 nurses, 33 residents, 20 attending physicians, and 13 medical students completing emergency department rotations. The median Technology Readiness Index for this group was 3.56, indicating a moderate degree of openness for technological adoption. The majority of survey respondents indicated favorable receptivity to the app including finding it helpful to applying the rules (73/108, 67.6%), that they would recommend the app to colleagues (81/108, 75.0%), and that they would continue using the app (73/108, 67.6%). Feedback from study participants highlighted a desire for access to more clinical decision rules and a higher degree of interactivity of the app. Between April 21, 2016, and June 1, 2017, The Ottawa Rules app was downloaded approximately 4000 times across 89 countries., Conclusions: We have found The Ottawa Rules app to be an effective means to disseminate the Ottawa Ankle Rules, Ottawa Knee Rule, and Canadian C-Spine Rule among all levels of emergency department clinicians. We have been successful in monitoring uptake and access of the rules in the app as a result of our publicity efforts. Mobile technology can be leveraged to improve the accessibility of clinical decision tools to health professionals., (©Michelle Paradis, Ian Stiell, Katherine M Atkinson, Julien Guerinet, Yulric Sequeira, Laura Salter, Alan J Forster, Malia SQ Murphy, Kumanan Wilson. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 11.06.2018.)

Sphingolipidoses are inherited diseases belonging to the class of lysosomal storage diseases (LSDs), which are characterized by the accumulation of indigestible material in the lysosome caused by specific defects in the lysosomal degradation machinery. While some LSDs can be efficiently treated by enzyme replacement therapy (ERT), this is not possible if the nervous system is affected due to the presence of the blood-brain barrier. Sphingolipidoses in particular often present as severe, untreatable forms of LSDs with massive sphingolipid and membrane accumulation in lysosomes, neurodegeneration and very short life expectancy. The digestion of intralumenal membranes within lysosomes is facilitated by lysosomal sphingolipid activator proteins (saposins), which are cleaved from a prosaposin precursor. Prosaposin mutations cause some of the severest forms of sphingolipidoses, and are associated with perinatal lethality in mice, hampering studies on disease progression. We identify the Drosophila prosaposin orthologue Saposin-related (Sap-r) as a key regulator of lysosomal lipid homeostasis in the fly. Its mutation leads to a typical spingolipidosis phenotype with an enlarged endolysosomal compartment and sphingolipid accumulation as shown by mass spectrometry and thin layer chromatography. S ap-r mutants show reduced viability with ∼50% survival to adulthood, allowing us to study progressive neurodegeneration and analyze their lipid profile in young and aged flies. Additionally, we observe a defect in sterol homeostasis with local sterol depletion at the plasma membrane. Furthermore, we find that autophagy is increased, resulting in the accumulation of mitochondria in lysosomes, concomitant with increased oxidative stress. Together, we establish Drosophila Sap-r mutants as a lysosomal storage disease model suitable for studying the age-dependent progression of lysosomal dysfunction associated with lipid accumulation and the resulting pathological signaling events., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Competing Interests: Declaration of Conflicting Interests:The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.