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Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia.

Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging.

SummaryThis article is about the planar configurations of the toy called Rubik’s Snake (or Rubik’s Twist), where all Snake pieces have a triangular face lying in the same plane. Any such configuration with ncorners can be obtained from the straight Snake with exactly ntwists of the physical toy (in such a way that the Snake does not self-intersect during the construction). We also discuss a number of other interesting properties; in particular, we classify all convex subsets of the plane that can be precisely covered by such a planar configuration. The proofs only require high school mathematics.

Uveal melanoma is the most common intraocular tumor in adults. Our group has previously developed a human uveal melanoma animal model; however, adverse effects caused by the immunosuppressive agent, cyclosporine A, prevented animals from surviving more than 12 weeks. In this study, we tested multiple cyclosporine A doses over an extended disease course up to 20 weeks, providing complete clinical imaging of intraocular tumors, histopathological analysis and liquid biopsy biomarker analysis. Twenty albino rabbits were divided into four groups with different daily cyclosporine A schedules (0–10 mg/kg) and inoculated with human uveal melanoma cell lines, 92.1 or MP41, into the suprachoroidal space. Rabbits were monitored with fundoscopy, ultrasound and optical coherence tomography. Intraocular tumors (macroscopic or microscopic) were detected in all study animals. Tumor size and growth were correlated to cyclosporine A dose, with tumors regressing when cyclosporine A was arrested. All tumors expressed HMB-45 and MelanA; however, tumor size, pigmentation and cell morphology differed in 92.1 vs. MP41 tumors. Finally, across all groups, circulating tumor DNA from plasma and aqueous humor was detected earlier than tumor detection by imaging and correlated to tumor growth. In conclusion, using three clinically relevant imaging modalities (fundoscopy, ultrasonography and optical coherence tomography) and liquid biopsy, we were successfully able to monitor tumor progression in our rabbit xenograft model of human uveal melanoma.

•There are issues with the criteria for post-hematopoietic stem cell transplantation (HSCT) bronchiolitis obliterans syndrome (BOS) leading to delayed diagnosis.•Several solutions that can be implemented to improve the criteria.•A multidisciplinary group has proposed new criteria for post-HSCT BOS in children.

Lobstering industry workers are known to have poor overall health and low safety records, but there is still a gap in information concerning Canadian lobster fishers. This study aimed to report occupational health and safety characteristics of an Atlantic Canada community of lobster fishers and to assess differences between captains and deckhands. Twenty-eight participants (10 captains, 18 deckhands) were questioned and self-reported on lifestyle, general health status, work-related musculoskeletal disorders and traumatic injuries. The data collected reveal both groups’ high prevalence of cardiometabolic and musculoskeletal health issues. Captains reported more occupational exposition and health issues, and showed poorer lifestyle habits than deckhands. Fishers reported potential solutions to reduce occupational risks, presented as three types: lifestyle, working behaviours and leadership. This study evaluated a community of Canadian lobster fishers regarding their occupational health and safety. Potential avenues for mitigating occupational risk specific to this community will nurture future implementation.

Our systematic review aimed to investigate the prevalence of post-traumatic stress symptoms (PTSS) and post-traumatic stress disorder (PTSD) among parents within 12 months of their child’s burn injury. A literature search was conducted in PubMed, Embase, Web of Science, Psychinfo, and CINAHL on January 6, 2023, for quantitative studies reporting the prevalence of PTSD and/or PTSS in parents within 12 months following their child’s burn injury. The risk of bias was assessed using the Mixed Methods Appraisal Tool version 2018. A narrative synthesis of prevalence was presented. We identified 15 articles that met our inclusion criteria. The prevalence of PTSS within 12 months following the burn injury ranged from 6% to 49%. Prevalence estimates of PTSD within the 12 months following a burn injury were limited, ranging from 4.4% to 22%. Our findings highlight the significant impact of burn injuries on parental mental health, with a considerable proportion of parents experiencing PTSS within 12 months following their child’s burn injury. Prevalence estimates for PTSD were limited and warrant further investigation. Our review also underscores the need for standardization of PTSS/PTSD terminology. Timely and targeted psychological support is needed for parents in the aftermath of their child’s burn injury.

The RAS–MAPK pathway regulates cell proliferation, differentiation and survival, and its dysregulation is associated with cancer development. The pathway minimally comprises the small GTPase RAS and the kinases RAF, MEK and ERK. Activation of RAF by RAS is notoriously intricate and remains only partially understood. There are three RAF isoforms in mammals (ARAF, BRAF and CRAF) and two related pseudokinases (KSR1 and KSR2). RAS-mediated activation of RAF depends on an allosteric mechanism driven by the dimerization of its kinase domain. Recent work on human RAFs showed that MEK binding to KSR1 promotes KSR1–BRAF heterodimerization, which leads to the phosphorylation of free MEK molecules by BRAF. Similar findings were made with the single DrosophilaRAF homolog. Here we show that the fly scaffold proteins CNK and HYP stabilize the KSR–MEK interaction, which in turn enhances RAF–KSR heterodimerization and RAF activation. The cryogenic electron microscopy structure of the minimal KSR–MEK–CNK–HYP complex reveals a ring-like arrangement of the CNK–HYP complex allowing CNK to simultaneously engage KSR and MEK, thus stabilizing the binary interaction. Together, these results illuminate how CNK contributes to RAF activation by stimulating the allosteric function of KSR and highlight the diversity of mechanisms impacting RAF dimerization as well as the regulatory potential of the KSR–MEK interaction.

Unattachment to a regular primary care professional can affect children’s and adolescents’ well-being, considering their unique health needs. Having no alternative, many turn to emergency departments for non-urgent conditions. To help unattached patients access healthcare services while on waitlists, Quebec’s government implemented single access points in each administrative region across the province. Our study aimed to describe the paediatric population using single access points and identify associations between their characteristics and need for a medical appointment. Clinical-administrative data of 1,323 paediatric access point users in the Montérégie region from November 2022 to March 2023 were utilized to conduct bivariate and multivariable regression analyses. Our study showed that young age, assessment trajectory, and specific reasons for calling were more likely to necessitate a medical appointment. While access points improve accessibility to doctors, questions remain regarding the relevance of medical consultations, inequities, and possible security issues resulting from the overall process.

Exacerbation frequency strongly influences treatment choices in patients with severe asthma.

Decision-making about antireflux procedures (ARPs) to treat gastroesophageal reflux disease in children with neurologic impairment and gastrostomy tubes is challenging and likely influenced by physicians’ experience and perspectives. This study will explore physician attitudes about ARPs and determine if there are relationships to clinical practice and personal characteristics.This is a national observational cross-sectional study that used an electronic questionnaire addressing reported practice, attitudes regarding the ARPs, and responses to clinical vignettes. Participants were physicians in Canadian tertiary-care pediatric settings. Descriptive statistics were used to analyze physician attitudes. Multivariable logistic regression modeling was used to determine associations between physician and practice characteristics and likelihood to consider ARP.Eighty three respondents represented 12 institutions, with a majority from general or complex care pediatrics. There was a wide disparity between likelihood to consider ARP in each clinical scenario. Likelihood to consider ARP ranged from to 19% to 78% depending on the scenario. Two scenarios were equally split in whether the respondent would offer an ARP. None of the demographic characteristics were significantly associated with likelihood to consider ARP. Often, gastrojejunostomy tubes alone were considered (56% to 68%).There is considerable variability in physician attitudes toward and recommendations regarding ARPs to treat gastroesophageal reflux disease. We did not find a significant association with clinical experience or location of practice. More research is needed to define indications and outcomes for ARPs. This is a scenario where shared decision-making, bringing together physician and family knowledge and expertise, is likely the best course of action.

The article highlights Esther Gonthier's influential career in Canadian opera, where she has dedicated over 40 years to the crucial but often unseen role of vocal coach. Topics include Gonthier's extensive experience working with prominent conductors and soloists, her significant contributions to opera through collaboration and recordings, and her early musical training and development that led to her exceptional skills as a collaborative pianist.

Gait speed is a robust health biomarker in older adults, correlating with the risk of physical and cognitive impairments, including dementia. Myelination plays a crucial role in neurotransmission and consequently affects various functions, yet the connection between myelination and motor functions such as gait speed is not well understood. Understanding this link could offer insights into diagnosing and treating neurodegenerative diseases that impair mobility. This study analyzed 437 longitudinal observations from 138 cognitively unimpaired adults, aged 22 to 94 years, to investigate the relationship between myelin content and changes in gait speed over an average of 6.42 years. Myelin content was quantified using a novel multicomponent magnetic resonance relaxometry method, and both usual and rapid gait speeds (UGS, RGS) were measured following standard protocols. Adjusting for covariates, we found a significant fixed effect of myelin content on UGS and RGS. Longitudinally, lower myelin content was linked to a greater decline in UGS, particularly in brain regions associated with motor planning. These results suggest that changes in UGS may serve as a reliable marker of neurodegeneration, particularly in cognitively unimpaired adults. Interestingly, the relationship between myelin content and changes in RGS was only observed in a limited number of brain regions, although the reason for such local susceptibility remains unknown. These findings enhance our understanding of the critical role of myelination in gait performance in unimpaired adults and provide evidence of the interconnection between myelin content and motor function impairment.

Alport syndrome has been linked to three different genes, that is, COL4A3, COL4A4and COL4A5. It is characterized by progressive and non-specific glomerulosclerosis with irregular thickening of the glomerular basement membrane (GBM). At times, the histopathologic picture is dominated by lesions that are consistent with focal and segmental glomerulosclerosis or IgA nephropathy. Here, we report the cases of two related individuals (mother and son) who were diagnosed with COL4A5-related Alport syndrome due to a missense variant (p.Gly1170Ser) in a G-X-Y repeat and found to present the same highly unusual histopathological abnormalities on their kidney biopsies. One of the abnormalities shared, which does not appear to have been reported, was reduced COL4A5 immunolabeling that was limited to Bowman’s capsule even though the ultrastructure of the GBM was distorted. The other abnormality was superimposed segmental IgA deposition in both individuals, accompanied by mesangial changes in the mother. We feel that these findings provide novel insight into the mechanisms of disease manifestation in Alport syndrome. They suggest, in particular, that collagen expression and/or assemblies in Bowman’s capsule is more vulnerable to missense mutations in COL4A5than elsewhere in the kidney. Our findings also suggest that certain coinherited gene polymorphisms act as unexpectedly important phenotypic determinants in COL4A-related disorders.

Children born before 28 weeks’ gestation are at increased risk of chronic kidney disease (CKD). Urine biomarkers may shed light on mechanistic pathways and improve the ability to forecast CKD. We evaluated whether urinary biomarkers in neonates of low gestational age (GA) are associated with a reduced estimated glomerular filtration rate (eGFR) over time.

Over the last three decades, numerous studies have concluded that African American, Hispanic, Native American, Alaska Native, Native Hawaiian, and working-class White communities are disproportionately exposed to environmental harms and risks. More recent studies have concluded that although the adverse effects of climate change are being felt throughout the United States, they are not evenly distributed. This Article explores how several states have initiated climate justice litigation to address this issue. Specifically, it examines how Rhode Island, Minnesota, and the District of Columbia have filed state-law claims against fossil fuel companies, asking state courts to consider liability, compensation, and remedies for harms related to climate change. It concludes that tribes, acting as sovereigns, may also want to consider climate justice litigation. [ABSTRACT FROM AUTHOR]

The article offers information on conductor Jacques Lacombe, highlighting his career and accomplishments in the world of opera. Topics include Lacombe's early education in Quebec and Vienna, his roles at Opéra de Montréal and the Orchestre symphonique de Montréal, and his international guest conducting engagements with prestigious organizations.

Some children are born with a genetic disorder that causes high cholesterol, which leads to heart disease. Children with high cholesterol can be treated with evolocumab, a medication that lowers blood cholesterol. Because cholesterol is important for development and adequate function of the brain, there is a concern that lowering cholesterol in children may affect mental ability. In this study, we tested whether treating children with evolocumab for 80 weeks affected mental ability in performing several tasks. A battery of tests that measure executive function (Groton Maze Learning Test), visual learning (One Card Learning Test), visual attention (Identification Test), and psychomotor function (Detection Test) showed no decrease in performance across visits during 80 weeks of evolocumab treatment.Performance on all tasks was similar for the children who received placebo for the first 24 weeks then received evolocumab for an additional 80 weeks (placebo/evolocumab) and those who received evolocumab for 24 weeks then received evolocumab for an additional 80 weeks (evolocumab/evolocumab).Graphical AbstractHeFH, heterozygous familial hypercholesterolaemia; LDL-C, low density lipoprotein cholesterol; LLT, lipid-lowering therapy; OLE, open-label extension; PCSK9, proprotein convertase subtilisin/kinase 9; RCT, randomized controlled trial; SC, subcutaneous.

BackgroundThere is increasing recognition of the prevalence and risk factors for mental health symptoms and disorders among adult elite athletes, with less research involving elite youth athletes. This scoping review aimed to characterise the mental health and well-being of elite youth athletes who travel internationally and compete for their sport.MethodFour databases were searched in March 2023. Inclusion criteria were studies with elite youth athlete populations (mean age 12–17 years) reporting mental health and well-being outcomes. Data from included studies were charted by outcome, and risk/protective factors identified.ResultsSearches retrieved 3088 records, of which 33 studies met inclusion criteria, encapsulating data from 5826 athletes (2538 males, 3288 females). The most frequently studied issue was disordered eating (k=16), followed by anxiety (k=7), depression (k=5) and mixed anxiety/depression (k=2). Caseness estimates (a symptom level where mental health treatment is typically indicated) for disordered eating were wide ranging (0%–14% for males; 11%–41% for females), whereas only two studies estimated caseness for depression (7% in a mixed-sex sample; 14% for males, 40% for females) and one for anxiety (8% for males, 28% for females). Common risk factors for mental ill-health included sex, athlete status (compared with non-athletes) and social/relationship factors (with coaches/parents/peers). Contradictory evidence was observed for elite/competition level, which was associated with higher and lower rates of disordered eating.ConclusionFurther representative research into the mental health and well-being of elite youth athletes is needed to enhance understanding and guide prevention and intervention measures.

ObjectiveTo describe the evidence pertaining to associations between growth, maturation and injury in elite youth athletes.DesignScoping review.Data sourcesElectronic databases (SPORTDiscus, Embase, PubMed, MEDLINE and Web of Science) searched on 30 May 2023.Eligibility criteriaOriginal studies published since 2000 using quantitative or qualitative designs investigating associations between growth, maturation and injury in elite youth athletes.ResultsFrom an initial 518 titles, 36 full-text articles were evaluated, of which 30 were eligible for final inclusion. Most studies were quantitative and employed prospective designs. Significant heterogeneity was evident across samples and in the operationalisation and measurement of growth, maturation and injury. Injury incidence and burden generally increased with maturity status, although growth-related injuries peaked during the adolescent growth spurt. More rapid growth in stature and of the lower limbs was associated with greater injury incidence and burden. While maturity timing did not show a clear or consistent association with injury, it may contribute to risk and burden due to variations in maturity status.ConclusionEvidence suggests that the processes of growth and maturation contribute to injury risk and burden in elite youth athletes, although the nature of the association varies with injury type. More research investigating the main and interactive effects on growth and maturation on injury is warranted, especially in female athletes and across a greater diversity of sports.

ObjectiveThe objective of this study is to characterise the key factors that influence positive engagement and desirable developmental outcomes in sport among elite youth athletes by summarising the methods, groups and pertinent topical areas examined in the extant published research.DesignScoping review.Data sourcesWe searched the databases SPORTDiscus, APA PsycINFO, Web of Science and Sports Medicine & Education Index for peer-reviewed, published in English articles that considered the factors influencing positive developmental outcomes for athletes under 18 years competing at a national and/or international level.ResultsThe search returned 549 articles, of which 43 met the inclusion criteria. 16 studies used a qualitative approach, 14 collected quantitative data, 2 adopted mixed methods and 11 were reviews. Seven articles involved athletes competing in absolute skill contexts (ie, against the best athletes of any age) while the majority involved athletes competing in relative skill contexts (ie, against the best in a specific age or developmental group). The studies described the characteristics of the athletes, as well as their training, relationships with others, social and physical environments, and/or their overall developmental pathways.ConclusionExisting research on positive engagement in elite youth sport aligned with and mapped onto established models of positive development in youth sport more generally. Our findings further support that, while certain youth athletes may demonstrate extraordinary performance capabilities, they are still children who benefit from positive engagement prompted and reinforced by developmentally appropriate and supportive activities, relationships and environments.

With the pronounced ongoing growth of global youth sports, opportunities for and participation of youth athletes on the world sports stage, including the Olympic Games, are expected to escalate. Yet, adolescence is a vulnerable period of development and inherently dynamic, with non-linear and asynchronous progression of physical, physiological, psychological and social attributes. These non-concurrent changes within and between individuals are accompanied by irregular and unpredictable threats and impediments. Likewise, the evident age-based criteria and conventional path for those youth athletes deemed eligible candidates for the Olympic Games are not well or consistently defined. Furthermore, the unstructured and largely varying policies and practices across the sporting International Federations specific to youth participation underscore the need to establish a contemporary universal paradigm that would enable elite youth athletes to navigate an individualised healthy pathway to personal, athletic and sport success. First, we reviewed and summarised key challenges facing elite youth athletes and the relevant evidence fundamental to facilitating and supporting central aspects of health and well-being, while empowering safe, sustainable and positive engagement during athletic and personal advancement and competition. Second, we developed and present a modern elite youth athlete model that emphasises a child-centred, practical framework with corresponding guidelines and recommendations to protect health and well-being while safely and favourably managing international sport competition. Our proposed evidence-informed paradigm will enable and support individualised pathways for healthy, well-rounded and sustainable positive engagement while achieving sport success for youth contending or aiming to compete at world-class international sporting events.

BackgroundAutoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking.Research questionDescribe the characteristics and clinical outcomes of patients diagnosed with aPAP, and to identify risk factors associated with opportunistic infections.MethodsWe conducted a retrospective cohort including all patients diagnosed with aPAP between 2008 and 2018 in France and Belgium. Data were collected using a standardised questionnaire including demographics, comorbidities, imaging features, outcomes and microbiological data.ResultsWe included 104 patients, 2/3 were men and median age at diagnosis was 45 years. With a median follow-up of 3.4 years (IQR 1.7–6.6 years), 60 patients (58%), developed at least one infection, including 23 (22%) with opportunistic infections. Nocardiaspp was the main pathogen identified (n=10). Thirty-five (34%) patients were hospitalised due to infection. In univariate analysis, male gender was associated with opportunistic infections (p=0.04, OR=3.88; 95% CI (1.02 to 22.06)). Anti-granulocyte macrophage colony-stimulating factor antibody titre at diagnosis was significantly higher among patients who developed nocardiosis (1058 (316–1591) vs 580 (200–1190), p=0.01). Nine patients had died (9%), but only one death was related to infection.InterpretationPatients with aPAP often presented with opportunistic infections, especially nocardiosis, which highlights the importance of systematic search for slow-growing bacteria in bronchoalveolar lavage or whole lung lavage.

Major depressive disorder (MDD) is the leading cause of disability worldwide. Of individuals with MDD, 30% to 50% are unresponsive to common antidepressants, highlighting untapped causal biological mechanisms. Dysfunction in the microbiota-gut-brain axis has been implicated in MDD pathogenesis. Exposure to chronic stress disrupts blood-brain barrier integrity; still, little is known about intestinal barrier function in these conditions, particularly for the small intestine, where absorption of most foods and drugs takes place.

This article digs into the numeric uncertainty for supraharmonic assessment methods and proposes a robust reference for calibration. A detailed resource survey of candidate methods, digital Special International Committee on Radio Interference (D-CISPR) and light-quasi-peak (QP), shows that computing resources should not be the primary concern, considering both necessitates an acceptable level of resources and requires the same mid-range field-programmable gate array (FPGA). Furthermore, a new criterion for selecting and optimizing numerical methods is proposed: the variability caused by time-shifting operations. D-CISPR, a proposed D-CISPR variation, the light-QP, and the proposed numerical-heterodyne methods were studied with the CISPR 16 impulse train test and three examples of real-world signals. Results demonstrate that the variability concerning time shift is less than 1% for the D-CISPR-based methods but up to 50% for the light-QP method.

The primary objective of our multicenter prospective study was to describe the incidence of late-onset non-infectious pulmonary complications (LONIPCs) in children undergoing hematopoietic cell transplantation (HCT) using sensitive criteria for pulmonary function test (PFT) abnormalities including the non-specific pattern of airflow obstruction. Secondary objectives were to assess the factors associated with LONIPC occurrence and the sensitivity of the 2014 NIH-Consensus Criteria of bronchiolitis obliterans syndrome (BOS). PFT and clinical assessment were performed prior to HCT and at 6, 12, 24, and 36 months post-HCT. LONIPC diagnosis was validated by an Adjudication Committee. The study comprised 292 children from 12 centers. Thirty-two individuals (11%, 95% CI: 8–15%) experienced 35 LONIPCs: 25 BOS, 4 interstitial lung diseases, 4 organizing pneumonia and 2 pulmonary veno-occlusive diseases. PFT abnormalities were obstructive defects (FEV1/FVC z-score < −1.645; n= 12), restrictive defects (TLC < 80% predicted, FEV1and FVC z-scores < −1.645; n= 7) and non-specific pattern (FEV1and FVC z-score< −1.645, FEV1/FVC z-score > −1.645, and TLC > 80% predicted; n= 8). HCT for malignant disease was the only factor associated with LONIPC (P= 0.04). The 2014 NIH-Consensus Criteria would only diagnose 8/25 participants (32%) as having BOS. In conclusion, 11% of children experienced a LONIPC in a prospective design. Clinical Trials.gov identifier (NCT number): NCT02032381.

ABSTRACTLive cell imaging is a standard technique in experimental biology that enables the observation of isolated cells and tissue slices in real time and the testing of cellular responses to changes in buffer composition. However, most live cell imaging devices require the use of dedicated microscopes and/or specialised stage adaptors, and come at a reasonably high cost. We employed 3D printing technology to create a low-cost imaging chamber with side ports to exchange fluids, to be used on upright microscopes. The chamber increased the functionality of a standard upright epifluorescent microscope to allow dynamic, real-time calcium imaging of cultured hypothalamic astrocytes from mice, and to test the effects of ATP stimulation upon calcium signalling. It was also used on slices obtained from the mouse brain using a brain matrix slicer. The advantages of this chamber include a very simple design that can be used with upright epifluorescence microscopes, does not require any special stage adaptor, and includes ports to permit fluid exchange during imaging. This chamber is ideal for educational settings with undergraduate laboratories that do not have access to dedicated inverted fluorescent microscopes for tissue culture experiments.

Background: Gallstone disease will affect 15% of the adult population with concomitant common bile duct stone (CBDS) occurring in up to 30%. Endoscopic retrograde cholangiopancreatography (ERCP) is the mainstay of management for removal of CBDS, as cholecystectomy for the prevention of recurrent biliary event (RBE). RBE occurs in up to 47% if cholecystectomy is not done. The goal of this study was to evaluate the timing of occurrence of RBE after common bile duct clearance with ERCP and associated outcomes. Methods: The records of all patients who underwent ERCP for gallstone disease followed by cholecystectomy, in a single center from 2010 to 2022, were reviewed. All RBE were identified. Actuarial incidence of RBE was built. Patients with and without RBE were compared. Results: The study population is composed of 529 patients. Mean age was 58.0 (18–95). There were 221 RBE in 151 patients (28.5%), 39/151 (25.8%) having more than one episode. The most frequent RBE was acute cholecystitis (n = 104) followed by recurrent CBDS (n = 95). Median time for first RBE was 34 days. Actuarial incidence of RBE started from 2.5% at 7 days to reach 53.3% at 1 year. Incidence-rate of RBE was 2.9 per 100 person-months. Patients with RBE had significant longer hospitalisation time (11.7 vs 6.4 days; P&lt; 0.0001), longer operative time (66 vs 48 min; P&lt; 0.0001), longer postoperative stay (2.9 vs 0.9 days; P&lt; 0.0001), higher open surgery rate (7.9% vs 1.3%; P&lt; 0.0001), and more complicated pathology (23.8% vs 5.8%; P&lt; 0.0001) and cholecystitis (64.2% vs 25.9%; P&lt; 0.0001) as final diagnoses. Conclusions: RBE occurred in 28.5% of the subjects at a median time of 34 days, with an incidence of 2.5% as early as 1 week. Cholecystectomy should be done preferably within 7 days after common bile duct clearance in order to prevent RBE and adverse outcomes.

Introduction: This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries. Methods: This retrospective and prospective observational study enrolled patients initiated on evolocumab during August 2017 to July 2019 at 49 sites across Canada, Mexico, Colombia, Saudi Arabia and Kuwait. Medical records data were extracted within 6 months prior to (baseline) and every 3 months for 12 months post evolocumab initiation and reported as available. Results: A total of 578 patients were enrolled (40.1% female, median age 60 [interquartile range (IQR) 51–68] years); 83.7% had atherosclerotic cardiovascular disease and/or familial hypercholesterolemia. Median low-density lipoprotein cholesterol (LDL-C) at baseline was 3.4 (IQR 2.7–4.2) mmol/L (131.5 [IQR 104.4–162.4] mg/dL), with 75.6% of patients receiving a statin (59.2% high intensity). Compared to baseline, the median lowest LDL-C was reduced by 70.2% and remained stable over 12 months of treatment. Guideline-recommended LDL-C thresholds &lt; 1.8, &lt; 1.4 and &lt; 1.0 mmol/L (&lt; 70, &lt; 55 and &lt; 40 mg/dL) were achieved by 75.3%, 63.6% and 47.4% of patients. LDL-C outcomes were consistent across high- and very high-risk patients. Background lipid-lowering therapy remained relatively stable. No serious treatment-emergent adverse events were reported, and persistence to evolocumab was 90.2% at 12 months. Conclusion: These findings provide real-world evidence that evolocumab use is in accordance with its international guideline-recommended place in dyslipidemia therapy, as well as confirmation of its effectiveness and safety in a heterogeneous population. Evolocumab can address a healthcare gap in the management of dyslipidemia by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk. Graphical Abstract:

The article focuses on soprano Jonelle Sills's flourishing career within the Canadian opera scene, illustrating her journey from training in Ontario to her recent performances across Toronto, Edmonton, and Vancouver in Canada. It highlights her unexpected debut as Mimi at the Canadian Opera Co. and discusses the shifting landscape for Canadian singers, emphasizing their increasing opportunities within the country and the evolving practices of opera companies.

AbstractThis study examined the group and individual part score profiles of individuals with mild intellectual disability (ID) who participated in a clinical validity study supporting the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) and a comparison group without ID derived from the WISC-V norming sample. Descriptive analyses revealed that both groups exhibited flat profiles of part scores (i.e., the five WISC-V factor indexes), with mean global composites and part scores in the Very Low range for the ID group and in the Average range for the comparison group. However, few participants in either group exhibited profiles similar to their respective group profile, and many in both groups exhibited substantial profile scatter. Examination of global composites and part scores obtained by individuals with ID revealed that the WISC-V’s global composites consistently identified those with ID using score thresholds of 70 to 75, but many individuals with ID obtained part scores much higher than this criterion. No meaningful differences were found between Black and White participants with ID. Implications focus on the risks associated with using part score elevation or profile scatter to defer identification of ID when all other criteria for the condition have been met.Impact StatementBecause the cognitive profile of those with intellectual disability (ID) is generally low and flat, indicating a deficit in overall intellectual functioning with little variation among part scores, many presume that individuals with this disorder will exhibit the same pattern. Although most individuals with ID exhibit a low IQ consistent with the disorder, many exhibit much higher part scores, and significant part score scatter is common in individuals with ID. Failure to identify individuals with ID due to part score elevation or to significant profile scatter will likely have unintended negative consequences.

Background Enhanced Recovery After Surgery (ERAS) programs have become a mainstay of modern surgical care, and efforts to decrease postoperative opioid consumption have been increasingly employed. A previous study from our institution demonstrated that ERAS protocols decreased opioid use in the first 48 hours after surgery by 61%. In the present study, a lidocaine infusion was added for postoperative pain control. The aim was to analyze the differences in opioid requirements with and without this infusion in the first 48 hours after laparoscopic colectomy in ERAS patients.Methods Retrospective review of patients was conducted at an academically affiliated tertiary care hospital. The population included patients undergoing elective laparoscopic colon surgery enrolled in the ERAS program with the implementation of a lidocaine drip from June 2019 to October 2019, and compared to a previous patient cohort of ERAS patients evaluated without the lidocaine drip from September 2015 to May 2018.Results The primary endpoint was postoperative opioid use in the first 48 hours based on IV morphine milligram equivalents (MME). Secondary measures included type of surgery, age, BMI, prior abdominal surgery, and prior opioid use. Median MMEs were 6.0 in the lidocaine infusion group and 12.5 in the group without lidocaine, representing a 52% reduction (p < 0.001).Discussion This study demonstrates a significant reduction in post-op opioid use in ERAS patients who receive a lidocaine infusion after laparoscopic colectomy. Further studies should focus on measures to limit the treatment side effects in order to maximize the opioid-sparing benefits of this intervention.

ABSTRACT:Objective:Intracerebral abscess is a life-threatening condition for which there are no current, widely accepted neurosurgical management guidelines. The purpose of this study was to investigate Canadian practice patterns for the medical and surgical management of primary, recurrent, and multiple intracerebral abscesses.Methods:A self-administered, cross-sectional, electronic survey was distributed to active staff and resident members of the Canadian Neurosurgical Society and Canadian Neurosurgery Research Collaborative. Responses between subgroups were analyzed using the Chi-square test.Results:In total, 101 respondents (57.7%) completed the survey. The majority (60.0%) were staff neurosurgeons working in an academic, adult care setting (80%). We identified a consensus that abscesses >2.5 cm in diameter should be considered for surgical intervention. The majority of respondents were in favor of excising an intracerebral abscess over performing aspiration if located superficially in non-eloquent cortex (60.4%), located in the posterior fossa (65.4%), or causing mass effect leading to herniation (75.3%). The majority of respondents were in favor of reoperation for recurrent abscesses if measuring greater than 2.5 cm, associated with progressive neurological deterioration, the index operation was an aspiration and did not include resection of the abscess capsule, and if the recurrence occurred despite prior surgery combined with maximal antibiotic therapy. There was no consensus on the use of topical intraoperative antibiotics.Conclusion:This survey demonstrated heterogeneity in the medical and surgical management of primary, recurrent, and multiple brain abscesses among Canadian neurosurgery attending staff and residents.1

ABSTRACT:Background:Non-penetrating head and neck trauma is associated with extracranial traumatic vertebral artery injury (eTVAI) in approximately 1–2% of cases. Most patients are initially asymptomatic but have an increased risk for delayed stroke and mortality. Limited evidence is available to guide the management of asymptomatic eTVAI. As such, we sought to investigate national practice patterns regarding screening, treatment, and follow-up domains.Methods:A cross-sectional, electronic survey was distributed to members of the Canadian Neurosurgical Society and Canadian Spine Society. We presented two cases of asymptomatic eTVAI, stratified by injury mechanism, fracture type, and angiographic findings. Screening questions were answered prior to presentation of angiographic findings. Survey responses were analyzed using descriptive statistics.Results:One hundred-eight of 232 (46%) participants, representing 20 academic institutions, completed the survey. Case 1: 78% of respondents would screen for eTVAI with computed topography angiography (CTA) (97%), immediately (88%). The majority of respondents (97%) would treat with aspirin (89%) for 3–6 months (46%). Respondents would follow up clinically (89%) or radiographically (75%), every 1–3 months. Case 2: 73% of respondents would screen with CTA (96%), immediately (88%). Most respondents (94%) would treat with aspirin (50%) for 3–6 months (35%). Thirty-six percent of respondents would utilize endovascular therapy. Respondents would follow up clinically (97%) or radiographically (89%), every 1–3 months.Conclusion:This survey of Canadian practice patterns highlights consistency in the approach to screening, treatment, and follow-up of asymptomatic eTVAI. These findings are relevant to neurosurgeons, spinal surgeons, stroke neurologists, and neuro-interventionalists.

En l’espace d’une cinquantaine d’année, la réglementation a fait de la personne compétente en radioprotection (PCR) l’acteur principal de la radioprotection dans les différents établissements mettant en œuvre des rayonnements ionisants pour assurer la protection des travailleurs – mais aussi depuis peu celle du public – notamment lors de l’utilisation de sources non scellées. La réglementation définit le rôle et les missions de la PCR, précise son articulation avec les autres acteurs et fixe les modalités de sa formation. Les fonctions de la PCR ont par ailleurs sensiblement évolué avec la création des conseillers en radioprotection (CRP). L’objectif de cet article est d’analyser et de comprendre l’évolution historique de la fonction de PCR, exercée actuellement par plus de 10 000 personnes en France, pour mieux en dégager les enjeux de demain.

Structural high vacuum die casting has been growing significantly over the past decades. It is typically done with special (primary type) alloys, special melt treatment practices, high vacuum, a carefully engineered die casting process applying many best practices in our industry. Structural die castings are growing in size and complexity and die casting machines are getting bigger and bigger - and those castings are becoming a significant challenge with current technologies. It was now found that Rheocasting - a process of preparing a semi-solid slurry (with 30-45% solid fraction) that is injected slower and in a laminar way into the cavity, can take structural die casting to completely new heights, enable the casting of parts that would otherwise be impossible to cast and at the same time reduce or eliminate some of the current problems of structural die casting. With Rheocasting, lower purity (secondary) aluminum alloys can be used and excellent properties can be achieved as cast and heat treated (T5, T6/7). Rheocasting has had a breakthrough in the telecom and other industries, but it has now been optimized to become an essential tool in the toolbox of making structural castings. This paper shows the developments that lead to the successful series production of a large (about 4’ long) hinge pillar for an Electric Vehicle (EV). It explains the challenges and how they were overcome, and some of the possibilities of the process regarding alloys, heat treatments and achievable properties. It also shows how Rheocasting can help die casters produce more complex (thin and thick walled) and very large castings with the highest integrity. It can replace structural low-pressure permanent mold (LPPM) castings and reduce wall thickness, improve tolerances and make them more economical. Rheocasting can enable die casters to enter this new market of structural castings including Gigacastings, produce parts previously thought impossible to cast (and on much smaller machines than thought), and expand the growing structural die casting market even faster and further.

Selenized yeast is commonly used as a highly bioavailable source of selenium in dietary supplements and feed additives and is used in research settings in various disciplines due to the large number of selenium-containing metabolites formed during growth. With the selenomethionine being the major form of selenium present in selenized yeasts, its accurate quantitation is essential, however, values are frequently underestimated due to the costly and time-consuming hydrolysis-based sample preparation required to release the selenoamino acid from proteins for analysis. The National Research Council Canada has developed an 82-Se-enriched selenized yeast Certified Reference Material, SEEY-1 (DOI: 10.4224/crm.2023.seey-1) intended to be used as a matrix-matched spike material for isotope dilution analysis of selenized yeasts. The total selenium and selenomethionine contents of SEEY-1 were determined to be 322.1 ± 4.8 mg/kg (k= 2) and 635.6 ± 16.8 mg/kg (k= 2), respectively. Here we present results on the preparation of the 82-Se-enriched yeast, the certification process, and provide an example of the use of SEEY-1 as a matrix-matched spike for the analysis of selenomethionine in a sample of selenized yeast. We demonstrate here that SEEY-1 is able to compensate for the partial digestion of yeast proteins and provide reliable analytical data on Se amino acid content in under an hour instead of the 16 hours required for conventional complete acid hydrolysis.

The benefits of masting (volatile, quasi-synchronous seed production at lagged intervals) include satiation of seed predators, but these benefits come with a cost to mutualist pollen and seed dispersers. If the evolution of masting represents a balance between these benefits and costs, we expect mast avoidance in species that are heavily reliant on mutualist dispersers. These effects play out in the context of variable climate and site fertility among species that vary widely in nutrient demand. Meta-analyses of published data have focused on variation at the population scale, thus omitting periodicity within trees and synchronicity between trees. From raw data on 12 million tree-years worldwide, we quantified three components of masting that have not previously been analysed together: (i) volatility, defined as the frequency-weighted year-to-year variation; (ii) periodicity, representing the lag between high-seed years; and (iii) synchronicity, indicating the tree-to-tree correlation. Results show that mast avoidance (low volatility and low synchronicity) by species dependent on mutualist dispersers explains more variation than any other effect. Nutrient-demanding species have low volatility, and species that are most common on nutrient-rich and warm/wet sites exhibit short periods. The prevalence of masting in cold/dry sites coincides with climatic conditions where dependence on vertebrate dispersers is less common than in the wet tropics. Mutualist dispersers neutralize the benefits of masting for predator satiation, further balancing the effects of climate, site fertility and nutrient demands.

Frailty and malnutrition in patients with heart failure are barriers to durable left ventricular assist device (D-LVAD) support and heart transplantation. Moreover, cachexia in patients with advanced heart failure carries a high mortality risk. There are no guidelines for these patients other than increased caloric intake and rehabilitation. Patients suffering from cardiac cachexia and heart failure may benefit from temporary, percutaneous assist device support to improve the underlying heart disease and reverse the catabolic state. We retrospectively reviewed patients from January 2017 to January 2022. All patients who received Impella support (5.0 or 5.5, Abiomed) before D-LVAD implantation were screened. Those who met the criteria for cardiac cachexia were included. Patient demographics, nutritional and biochemical markers, and survival data were collected. A total of 14 patients were included. The majority of patients were male (85.7%) with ischemic cardiomyopathy (64.3%). Caloric intake, physical strength, and ambulation improved. Prealbumin levels improved from a median of 13.7–18.0 mg/dl (p< 0.006) while on Impella 5.0 or 5.5 support. All patients survived to discharge and the 6 month follow-up. In conclusion, use of the Impella device improves cardiogenic shock symptoms and, consequently, may improve cachexia status prior to D-LVAD implantation.

Lower uterine segment (LUS) thickness measurement using transabdominal ultrasound (TA‐US), transvaginal ultrasound (TV‐US), or the combination of both methods can detect scar defect in women with prior cesarean. We aimed to compare the sensitivity of three approaches. Women with prior cesarean underwent LUS thickness measurement at 34–38 weeks' gestation. Among those who underwent repeat cesarean before labor, we compared the accuracy of TA‐US, TV‐US, and the thinner of the two measurements (the “combined measurement”) for uterine scar dehiscence using the area under the curve (AUC) of receiver operating curves with their 95% confidence intervals (CI). We calculated the sensitivity and specificity of the three approaches using a cut‐off of 2.3 mm based on prior literature. We included 747 participants. The mean LUS thickness was greater with TA‐US (3.8 ± 1.6 mm) compared with TV‐US (3.5 ± 1.9 mm) or the combined measurement (3.2 ± 1.5 mm; P< .001). The AUC was 78% (95% CI: 69%–87%), 85% (95% CI: 79%–91%), and 88% (95% CI: 82%–93%), respectively (all with P< .001). The AUC difference between TA‐US and the combined measurement was not significant (P= .057). A LUS below 2.3 mm would have predicted 9 (45%) of the 20 cases of uterine scar dehiscence using TA‐US, 17 (85%) using TV‐US, and 18 (90%) using the combined measurement (P< .01). The choice of ultrasound approach influences the measurement of the LUS thickness. The combination of the TA‐US and TV‐US seems to be superior for the detection of uterine dehiscence.

The combination of optical time transfer and optical clocks opens up the possibility of large-scale free-space networks that connect both ground-based optical clocks and future space-based optical clocks. Such networks promise better tests of general relativity1–3, dark-matter searches4and gravitational-wave detection5. The ability to connect optical clocks to a distant satellite could enable space-based very long baseline interferometry6,7, advanced satellite navigation8, clock-based geodesy2,9,10and thousandfold improvements in intercontinental time dissemination11,12. Thus far, only optical clocks have pushed towards quantum-limited performance13. By contrast, optical time transfer has not operated at the analogous quantum limit set by the number of received photons. Here we demonstrate time transfer with near quantum-limited acquisition and timing at 10,000 times lower received power than previous approaches14–24. Over 300 km between mountaintops in Hawaii with launched powers as low as 40 µW, distant sites are synchronized to 320 attoseconds. This nearly quantum-limited operation is critical for long-distance free-space links in which photons are few and amplification costly: at 4.0 mW transmit power, this approach can support 102 dB link loss, more than sufficient for future time transfer to geosynchronous orbits.

AbstractBACKGROUNDDyspnea is an extremely prevalent and debilitating symptom in chronic obstructive pulmonary disease (COPD), affecting up to 74% of patients despite optimal medical therapy. Sublingual fentanyl citrate (SLF) has a fast onset of action and a short half-life, both interesting characteristics to treat acute breakthrough dyspnea without inducing metabolite accumulation. The Montreal Chest Institute (MCI) COPD specialty clinic has been using low-dose SLF for patients with advanced COPD experiencing significant episodic dyspnea despite high intensity inhaled therapy. We present here a retrospective chart review, the largest to date, to report on a “real life” experience.METHODSAll included patients had a formal diagnosis of COPD and were seen in the MCI COPD specialty clinic between January 1, 2015 and January 1, 2021. All patients prescribed SLF, irrespective of the duration of use, were enrolled in this chart review. Extent of symptom relief, categorized into either major, intermediateor no improvements, and adverse effects were inferred from in-person or telephone follow-up appointment clinical notes. An exacerbation was defined as a self-reported acute increase in symptoms leading to oral corticosteroid use or hospitalization. Rates of exacerbation and hospitalization in the 12 months before SLF initiation and during SLF use were compared.RESULTSIn total, 17 COPD patients were given SLF during the study period. The mean FEV1was 0.51 L (21% predicted). All participants reported MRC5/5 dyspnea and were prescribed regular low-dose oral morphine for daily breathlessness prior to SLF initiation. Most patients used SLF for more than 6 months, and 76.5% of the study group found intermediateor majorimprovement in breathlessness episodes. There was no significant change in the rates of exacerbation and admission for acute respiratory failure while on SLF.CONCLUSIONIn this review, we report real-life, long-term data on severe COPD patients using self-controlled as-needed SLF, showing patient acceptability, an improvement in dyspnea, and limited side effects. Hence, this represents an important step toward the first effective alternative rescue medication for the relief of breakthrough dyspnea since short-acting inhalers. Further study using a randomized trial design is required to confirm the efficacy of this therapy.

Background.Parents of a child considered to have special needs are at greater risk of stress and exhaustion. Although many occupational therapy interventions can help these children, they often require significant time and energy from families. Purpose.To document the perspectives of parents and occupational therapists regarding ways to offer services that help build families’ capacities without overloading them. Method.A qualitative descriptive design guided online community forums with 41 parents and occupational therapists in Quebec, Canada. Findings.Nine key principles to build the capacities of families without overburdening them were identified. These include being sensitive to possible negative impacts of services, avoiding overwhelming the family with information or recommendations, taking the needed time, highlighting the positive, and offering flexible conditions for services. Implications.Our findings help identify how capacity-building rehabilitation services can be offered to families to optimize positive outcomes and minimize harms.

Peripheral allogeneic hematopoietic stem cell transplant recipients are the most vulnerable patients to community-acquired respiratory viruses such as respiratory syncytial virus, influenza virus, or others. These patients are likely to develop severe acute viral infections; community-acquired respiratory viruses have also been identified as triggers of bronchiolitis obliterans (BO). BO is a manifestation of pulmonary graft-versus-host disease, most often leading to irreversible ventilatory impairment. To date, there are no data on whether Severe acute respiratory syndrome ​coronavirus 2 (SARS-CoV-2) could be a trigger for BO. Here, we report the first report of a case of bronchiolitis obliterans syndrome following SARS-CoV-2 infection occurring 10 months after allogeneic hematopoietic stem cell transplant with a flare of underlying extra thoracic graft-versus-host disease. This observation provides a new perspective and should be of particular interest to clinicians, suggesting the need for close monitoring of pulmonary function test (PFTs) after SARS-CoV-2 infection. The mechanisms leading to bronchiolitis obliterans syndrome after SARS-CoV-2 infection require further investigation.