ALARA principles in practice: reduced frame and pulse rates for middle meningeal artery embolization.

Objective: As the prevalence of neuroendovascular interventions increases, it is critical to mitigate unnecessary radiation for patients, providers, and health care staff. Our group previously demonstrated reduced radiation dose and exposure during diagnostic angiography by reducing the default pulse and frame rates. We applied the same technique for basic neuroendovascular interventions. Methods: We performed a retrospective review of prospectively acquired data after implementing a quality improvement protocol in which pulse rate and frame rate were reduced from 15 p/s to 7.5 p/s and 7.5 f/s to 4.0 f/s respectively. We studied consecutive, unilateral middle meningeal artery embolizations treated with particles. Total radiation dose, radiation per angiographic run, total radiation exposure, and exposure per run were calculated. Multivariable log-linear regression was performed to account for patient body mass index (BMI), number of angiographic runs, and number of vessels catheterized. Results: A total of 20 consecutive, unilateral middle meningeal artery embolizations were retrospectively analyzed. The radiation reduction protocol was associated with a 39.2% decrease in the total radiation dose and a 37.1% decrease in radiation dose per run. The protocol was associated with a 41.6% decrease in the total radiation exposure and a 39.5% decrease in exposure per run. Conclusions: Radiation reduction protocols can be readily applied to neuroendovascular interventions without increasing overall fluoroscopy time and reduce radiation dose and exposure by 39.2% and 41.6% respectively. We strongly encourage all interventionalists to be cognizant of pulse rate and frame rate when performing routine interventions.

Loss of the long form of Plod2 phenocopies contractures of Bruck syndrome - osteogenesis imperfecta.

Bruck syndrome is an autosomal recessive form of osteogenesis imperfecta (OI) caused by biallelic variants in PLOD2 or FKBP10 and is characterized by joint contractures, bone fragility, short stature, and scoliosis. PLOD2 encodes LH2, which hydroxylates type I collagen telopeptide lysines, a critical step for collagen crosslinking. The Plod2 global knockout mouse model is limited by early embryonic lethality, thus the role of PLOD2 in skeletogenesis is not well understood. We generated a novel Plod2 mouse line modeling a variant identified in two unrelated individuals with Bruck syndrome: PLOD2 c.1559dupC, predicting a frameshift and loss of the long isoform LH2b. In the mouse, the duplication led to loss of LH2b mRNA as well as significantly reduced total LH2 protein. This model, Plod2fs/fs, survived up to E18.5 although in non-Mendelian genotype frequencies. The homozygous frameshift model recapitulated the joint contractures seen in Bruck syndrome and had indications of absent type I collagen telopeptide lysine hydroxylation in bone. Genetically labeling tendons with Scleraxis-GFP in Plod2fs/fs mice revealed the loss of extensor tendons in the forelimb by E18.5 and developmental studies showed extensor tendons developed through E14.5 but were absent starting at E16.5. Second harmonic generation showed abnormal tendon type I collagen fiber organization, suggesting structurally abnormal tendons. Characterization of the skeleton by µCT and Raman spectroscopy showed normal bone mineralization levels. This work highlights the importance of properly crosslinked type I collagen in tendon and bone, providing a promising new mouse model to further our understanding of Bruck syndrome.

Bruck syndrome is a rare disease where individuals have brittle bone as well as contracted or stiff joints. Mutations in two genes are associated with Bruck syndrome and, in this work, we focus on PLOD2. Mice without Plod2 die at an early embryonic stage, before they have a chance to fully develop. In this work, we created a mouse with a PLOD2 mutation seen in people with Bruck syndrome. Some of these new Bruck syndrome model mice survived to a later gestational age, but all died at birth. The Bruck syndrome mice were small and had contracted joints. We found they were missing tendons in their arms and had structurally abnormal tendons in their knees. Bone mineralization was normal, but there were indications that the modifications needed for normal type I collagen structure were absent. Overall, this is an advantageous new mouse model of Bruck syndrome that can be used to study this rare disease and highlights the importance of Plod2 in tendon.

Tumor-derived GLI1 promotes remodeling of the immune tumor microenvironment in melanoma.

BACKGROUND: Melanoma progression is based on a close interaction between cancer cells and immune cells in the tumor microenvironment (TME). Thus, a better understanding of the mechanisms controlling TME dynamics and composition will help improve the management of this dismal disease. Work from our and other groups has reported the requirement of an active Hedgehog-GLI (HH-GLI) signaling for melanoma growth and stemness. However, the role of the downstream GLI1 transcription factor in melanoma TME remains largely unexplored. METHODS: The immune-modulatory activity of GLI1 was evaluated in a syngeneic B16F10 melanoma mouse model assessing immune populations by flow cytometry. Murine polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were differentiated from bone marrow cells and their immunosuppressive ability was assessed by inhibition of T cells. Conditioned media (CM) from GLI1-overexpressing mouse melanoma cells was used to culture PMN-MDSCs, and the effects of CM were evaluated by Transwell invasion assay and T cell inhibition. Cytokine array analysis, qPCR and chromatin immunoprecipitation were performed to explore the regulation of CX3CL1 expression by GLI1. Human monocyte-derived dendritic cells (moDCs) were cultured in CM from GLI1-silenced patient-derived melanoma cells to assess their activation and recruitment. Blocking antibodies anti-CX3CL1, anti-CCL7 and anti-CXCL8 were used for in vitro functional assays. RESULTS: Melanoma cell-intrinsic activation of GLI1 promotes changes in the infiltration of immune cells, leading to accumulation of immunosuppressive PMN-MDSCs and regulatory T cells, and to decreased infiltration of dendric cells (DCs), CD8 + and CD4 + T cells in the TME. In addition, we show that ectopic expression of GLI1 in melanoma cells enables PMN-MDSC expansion and recruitment, and increases their ability to inhibit T cells. The chemokine CX3CL1, a direct transcriptional target of GLI1, contributes to PMN-MDSC expansion and recruitment. Finally, silencing of GLI1 in patient-derived melanoma cells promotes the activation of human monocyte-derived dendritic cells (moDCs), increasing cytoskeleton remodeling and invasion ability. This phenotype is partially prevented by blocking the chemokine CCL7, but not CXCL8. CONCLUSION: Our findings highlight the relevance of tumor-derived GLI1 in promoting an immune-suppressive TME, which allows melanoma cells to evade the immune system, and pave the way for the design of new combination treatments targeting GLI1.

Biofilm mitigation in hybrid chemical-biological upcycling of waste polymers.

Introduction: Accumulation of plastic waste in the environment is a serious global issue. To deal with this, there is a need for improved and more efficient methods for plastic waste recycling. One approach is to depolymerize plastic using pyrolysis or chemical deconstruction followed by microbial-upcycling of the monomers into more valuable products. Microbial consortia may be able to increase stability in response to process perturbations and adapt to diverse carbon sources, but may be more likely to form biofilms that foul process equipment, increasing the challenge of harvesting the cell biomass. Methods: To better understand the relationship between bioprocess conditions, biofilm formation, and ecology within the bioreactor, in this study a previously-enriched microbial consortium (LS1_Calumet) was grown on (1) ammonium hydroxide-depolymerized polyethylene terephthalate (PET) monomers and (2) the pyrolysis products of polyethylene (PE) and polypropylene (PP). Bioreactor temperature, pH, agitation speed, and aeration were varied to determine the conditions that led to the highest production of planktonic biomass and minimal formation of biofilm. The community makeup and diversity in the planktonic and biofilm states were evaluated using 16S rRNA gene amplicon sequencing. Results: Results showed that there was very little microbial growth on the liquid product from pyrolysis under all fermentation conditions. When grown on the chemically-deconstructed PET the highest cell density (0.69 g/L) with minimal biofilm formation was produced at 30°C, pH 7, 100 rpm agitation, and 10 sL/hr airflow. Results from 16S rRNAsequencing showed that the planktonic phase had higher observed diversity than the biofilm, and that Rhodococcus, Paracoccus, and Chelatococcus were the most abundant genera for all process conditions. Biofilm formation by Rhodococcus sp. And Paracoccus sp. Isolates was typically lower than the full microbial community and varied based on the carbon source. Discussion: Ultimately, the results indicate that biofilm formation within the bioreactor can be significantly reduced by optimizing process conditions and using pure cultures or a less diverse community, while maintaining high biomass productivity. The results of this study provide insight into methods for upcycling plastic waste and how process conditions can be used to control the formation of biofilm in bioreactors.

Characterizing placental pericytes: Hypoxia and proangiogenic signalling.

INTRODUCTION: Pericytes wrap microvessels and interact with endothelial cells to regulate vascular growth. Though pericyte dropout has been reported in pathological human placentae and mouse models of placental pathology, there has been limited investigation of the role and function of placental pericytes in vascular health and pathology. This study aimed to investigate the angiogenic potential of human placental pericytes relative to other villous cell populations. METHODS: Primary human placental pericytes, human umbilical vein endothelial cells (HUVEC), and BeWo cells ( ± 20 µM forskolin) were cultured in 1 % O2 or ambient air, followed by analysis of secreted angiogenic factors (ELISA). Additionally, the placental pericytes and HUVECs were co-cultured in a 3D sprouting assay to assess the capacity of pericytes to contribute to vascular sprouts. RESULTS: 1 % O2 affected secretion of angiogenic factors in placental pericytes, HUVECs, and syncytialized BeWo cells. Specifically, in placental pericytes, angiopoietin-1 (ANG1) and soluble fms-like tyrosine kinase-1 (sFLT1) were decreased, while vascular endothelial growth factor (VEGF) was increased. In HUVECS, matrix metalloproteinase-2 (MMP2), VEGF, angiopoietin-2 (ANG2), platelet-derived growth factor beta (PDGFB), placental growth factor (PlGF), and sFLT1 were increased. In syncytialized BeWo cells, VEGF, MMP2, PDGFB, PlGF, and sFLT1 secretion were increased. Placental pericytes and HUVECS colocalized to vessel sprouts in the 3-D sprouting assay. DISCUSSION: Hypoxic conditions altered placental pericyte, endothelial, and syncytialized BeWo secretion of angiogenic factors. We speculate that pericyte dropout and, by extension, the loss of pericyte-derived angiogenic factors in hypoxic conditions may contribute to compromised fetal vascular development observed in placental pathologies.

Expanding the genetic and phenotypic landscape of replication factor C complex-related disorders: RFC4 deficiency is linked to a multisystemic disorder.

The precise regulation of DNA replication is vital for cellular division and genomic integrity. Central to this process is the replication factor C (RFC) complex, encompassing five subunits, which loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. While RFC1's role in cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is known, the contributions of RFC2-5 subunits on human Mendelian disorders is largely unexplored. Our research links bi-allelic variants in RFC4, encoding a core RFC complex subunit, to an undiagnosed disorder characterized by incoordination and muscle weakness, hearing impairment, and decreased body weight. We discovered across nine affected individuals rare, conserved, predicted pathogenic variants in RFC4, all likely to disrupt the C-terminal domain indispensable for RFC complex formation. Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression. Our integrated approach of combining in silico, structural, cellular, and functional analyses establishes compelling evidence that bi-allelic loss-of-function RFC4 variants contribute to the pathogenesis of this multisystemic disorder. These insights broaden our understanding of the RFC complex and its role in human health and disease.

Clinical and demographic moderators of self-care and hospitalizations in pre-coronary artery bypass grafting patients: A cross-sectional study.

AIM: To examine the influence of clinical and demographic factors on self-care behaviour and hospitalization rates among patients with coronary heart disease awaiting coronary artery bypass grafting. BACKGROUND: Appropriate self-care behaviour can improve the management of patients with coronary heart disease and reduce hospitalization rates among those awaiting coronary artery bypass graft surgery. However, little is known about the influence of clinical and demographic factors on self-care or hospitalizations in this population. DESIGN: A cross-sectional study. METHODS: A convenience sample of 99 participants diagnosed with coronary heart disease awaiting coronary artery bypass grafting surgery were recruited from an outpatient clinic of a public tertiary hospital in southern Thailand. Data were collected on clinical (left ventricular ejection fraction, symptom severity and comorbid disease) and demographic (age, education level and marital status) factors, self-care behaviour and hospitalization rates. Path analysis using LISREL was performed to examine the influence of self-care on hospitalizations, with clinical and demographic factors as moderators. RESULTS: Path analysis showed that clinical and demographic factors accounted for nearly half of the variance (46%) in self-care, and that self-care accounted for nearly half of the variance (48%) in hospitalization rates. CONCLUSION: Our findings demonstrate that clinical and demographic factors play an important role in self-care behaviour, and in turn hospitalization rates of pre-coronary artery bypass graft surgery patients. It is suggested that the period pre-surgery is an ideal time to introduce programmes designed to bolster self-care and minimize uncertainty among this patient population and that nurses are well-positioned to do so. REPORTING METHOD: Study methods and results reported in adherence to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: Patients contributed their consent, time and data to the study.

Sodium-glucose cotransporter 2 inhibitors reduce the risk of incident type 2 diabetes in people with heart failure without diabetes: An analysis of real-world, cohort data.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is), used as a glucose-lowering therapy in people with type 2 diabetes (T2D), have significant cardiorenal benefits, reducing hospitalization for heart failure (HF) and cardiovascular mortality in patients with and without T2D. Recent clinical trial evidence suggests their potential utility in preventing incident T2D among the high-risk HF populations. Therefore, we aimed to assess whether this finding was reproducible in a real-world setting. METHODS: We performed a retrospective cohort analysis of 484 643 patients with HF, without baseline diabetes, prescribed either angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers with/without SGLT2is (treatment, n = 42 018; reference, n = 442 625) across 95 global health care organizations, using a large real-world ecosystem. Propensity score matching balanced arms 1:1 for confounders (n = 39 168 each arm). Subgroup analysis further evaluated the impact on patients with prediabetes and the efficacy of dapagliflozin/empagliflozin, specifically, on incident T2D and secondary outcomes, including all-cause mortality, acute pulmonary oedema and hospitalization. RESULTS: Treatment with SGLT2is significantly reduced incident T2D {hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.63, 0.75]} in patients with HF. The analysis of patients with prediabetes found that SGLT2is further reduced incident T2D [HR 0.62 (95% CI 0.45, 0.80)]. The magnitude of reduction in incident T2D was higher in patients prescribed dapagliflozin [HR 0.47 (95% CI 0.39, 0.56)] versus empagliflozin [HR 0.81 (95% CI 0.70, 0.93)]. CONCLUSION: Treatment with SGLT2is in patients with HF was associated with a reduced risk of incident T2D, most strikingly in people with prediabetes.

Insulin sensitivity and insulin secretion in adults with Friedreich's Ataxia: the role of skeletal muscle.

INTRODUCTION: Friedreich's Ataxia (FRDA) is a multi-system disorder caused by frataxin deficiency. FRDA-related diabetes mellitus (DM) is common. Frataxin supports skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, a mediator of insulin sensitivity. Our objective was to test the association between skeletal muscle health and insulin sensitivity and secretion in adults with FRDA without DM. METHODS: Case-control study (NCT02920671). Glucose and insulin metabolism (stable-isotope oral glucose tolerance tests), body composition (dual-energy x-ray absorptiometry), physical activity (self-report), and skeletal muscle OXPHOS capacity (creatine chemical exchange saturation transfer MRI) were assessed. RESULTS: Participants included 11 individuals with FRDA (4 female), median age 27y (IQR 23, 39), BMI 26.9kg/m2 (24.1, 29.4), and 24 controls (11 female), 29y (26, 39), 24.4kg/m2 (21.8, 27.0). Fasting glucose was higher in FRDA (91 vs. 83mg/dL (5.0 vs. 4.6mmol/L), p<0.05). Individuals with FRDA had lower insulin sensitivity (WBISI 2.8 vs. 5.3, p<0.01), higher post-prandial insulin secretion (insulin secretory rate iAUC 30-180 minutes, 24,652 vs. 17,858, p<0.05), and more suppressed post-prandial endogenous glucose production (-0.9% vs. 26.9% of fasting EGP, p<0.05). In regression analyses, lower OXPHOS and inactivity explained some of the difference in insulin sensitivity. More visceral fat contributed to lower insulin sensitivity independent of FRDA. Insulin secretion accounting for sensitivity (disposition index) was not different. CONCLUSIONS: Lower mitochondrial OXPHOS capacity, inactivity, and visceral adiposity contribute to lower insulin sensitivity in FRDA. Higher insulin secretion appears compensatory, and when inadequate, could herald DM. Further studies are needed to determine if muscle- or adipose-focused interventions could delay FRDA-related DM.

"It's just part of who I am " Living with chronic headache: voices from the CHESS trial, a qualitative study.

BACKGROUND: Between 2015 and 2019 the Chronic Headache Education and Self-management Study (CHESS) developed and tested a supportive self-management approach that aimed to improve outcomes for people with chronic migraine or chronic tension type headache with/without episodic migraine. However, a paucity of qualitative research which explored the lived experiences of people with chronic headache was evidenced. In response, we undertook to explore the experiences of living with chronic headaches of people who participated in the CHESS study. METHODS: We adopted qualitative methodologies, inviting participants in the CHESS study to participate in semi-structured interviews. In phase 1 (feasibility study), a thematic analysis was conducted. In phase 2 (main CHESS trial), interviews were informed by topic guides developed from our learning from the phase 1 interviews. Pen portrait methodology and thematic analysis was employed allowing us to explore the data longitudinally. RESULTS: Phase 1, 15 interviews (10 female) age range 29 to 69 years (median 47 years) revealed the complexities of living with chronic headache. Six overarching themes were identified including the emotional impact and the nature of their headaches. Phase 2, included 66 interviews (26 participants; median age group 50s (range 20s-60s); 20 females. 14 were interviewed at three points in time (baseline, 4 and 12 months) Through an iterative process four overlapping categories of headache impact emerged from the data and were agreed: i) 'I will not let headaches rule my life'; ii) 'Headaches rule my life'; iii) 'Headaches out of control-something needs to change'; and iv) 'Headaches controlled-not ruling my life'. One of these categories was assigned to each pen portrait at each timepoint. The remaining 12 participants were interviewed at two time points during a year; pen portraits were again produced. Analysis revealed that the headache impact categories developed above held true in this sample also providing some validation of the categories. CONCLUSIONS: These data give an insight into the complexities of living with chronic headache. Chronic headache is unpredictable, permeating all aspects of an individual's life; even when an individual feels that their headache is controlled and not interfering, this situation can rapidly change. It shows us that more work needs to be done both medically and societally to help people living with this often-hidden condition. TRIAL REGISTRATION: ISRCTN79708100.

Biomanufacturing of value-added chemicals from lignin.

Lignin valorization faces persistent biomanufacturing challenges due to the heterogeneous and toxic carbon substrates derived from lignin depolymerization. To address the heterogeneous nature of aromatic feedstocks, plant cell wall engineering and 'lignin first' pretreatment methods have recently emerged. Next, to convert the resulting aromatic substrates into value-added chemicals, diverse microbial host systems also continue to be developed. This includes microbes that (1) lack aromatic metabolism, (2) metabolize aromatics but not sugars, and (3) co-metabolize both aromatics and sugars, each system presenting unique pros and cons. Considering the intrinsic complexity of lignin-derived substrate mixtures, emerging and non-model microbes with native metabolism for aromatics appear poised to provide the greatest impacts on lignin valorization via biomanufacturing.

Factors That Impact Time to Athletic Trainer Evaluation Following Acute Injury Among Secondary School Athletes: A Report from the Athletic Trainin Practice-Based Research Network.

CONTEXT: Immediate athletic trainer (AT) availability for acute injuries is essential as worse long-term outcomes are associated with delays in receiving medical care. Several factors have been found to influence AT availability between secondary schools, but few studies have evaluated how medical coverage varies between athlete groups. OBJECTIVE: The purpose of this project was to identify factors that impact the time to AT evaluation following acute sport-related injury in secondary school setting. DESIGN: Cross-Sectional Study. SETTING: Retrospective analysis of de-identified patient records via the Athletic Training Practice-Based Research Network. PATIENTS: High school athletes diagnosed with an acute sport related injury during in-season play from 2010-2023. MAIN OUTCOME MEASURE: Time to AT evaluation was measured as the number of days between injury onset, reported by the patient, to AT evaluation. RESULTS: This report consists of 17,354 patient cases representing 20 different sports. Overall, 46.9% (n=8,138) of patients who sustained an injury during in-season play were evaluated by an AT the same day (range=0-14days). Significant group differences were reported for sex (p <. 001), setting (p <. 001), and sport level (p < .01), with females and in-game injuries associated with longer times to AT evaluation. Freshmen were evaluated sooner than JV (p < .01) and varsity (p < .001) athletes. No difference was observed between JV and varsity athletes (p=0.34). CONCLUSIONS: Almost half of patients received medical care within 24 hours following an acute injury during in-season play, highlighting how qualified health care is accessible for many student athletes through ATs in the secondary school setting. Differences in time to AT evaluation may be attributable to sex discrepancies in immediate medical coverage between sports and injury reporting patterns among athletes.

Gene Expression Changes Associated With Recurrence After Gross Total Resection of Newly Diagnosed World Health Organization Grade 1 Meningioma.

BACKGROUND AND OBJECTIVE: Patients who undergo gross total resection (GTR) of Central Nervous System World Health Organization (WHO) grade 1 meningioma constitute a "low-risk" group, but some low-risk meningiomas can recur despite reassuring clinical and histological features. In this study, gene expression values in newly diagnosed WHO grade 1 meningiomas that had undergone GTR were evaluated for their association with recurrence. METHODS: This was a retrospective, international, multicenter cohort study that included WHO grade 1 meningiomas that underwent GTR, as first treatment, based on postoperative magnetic resonance imaging. Normalized gene expression values from a previously validated 34-gene panel were evaluated for their association with recurrence. Kaplan-Meier, multivariable Cox proportional hazard analyses, and K-means clustering were performed to assess the association of genes of interest with recurrence and identify molecular subgroups among clinically and histologically low-risk meningiomas. RESULTS: In total, 442 patients with WHO grade 1 meningiomas that underwent GTR and had available gene expression profiling data were included in the study. The median follow-up was 5.0 years (interquartile range 2.6-7.7 years), local recurrence occurred in 36 patients (8.1%), 5-year local freedom from recurrence was 90.5%, and median time to recurrence was 2.9 years (range 0.5-10.7 years). Eleven genes were associated with local recurrence, including lower expression of ARID1B, ESR1, LINC02593, PGR, and TMEM30B and higher expression of CDK6, CDKN2C, CKS2, KIF20A, PGK1, and TAGLN. Of these genes, PGK1 had the largest effect size. K-means clustering based on these 11 genes distinguished 2 molecular groups of clinically and histologically low-risk meningiomas with significant differences in local freedom from recurrence (hazard ratio 2.5, 95% CI 1.2-5.1, P = .016). CONCLUSION: Gene expression profiling may help to identify newly diagnosed WHO grade 1 meningiomas that have an elevated risk of recurrence despite GTR.

Osteochondral Allograft Transplantation to the Capitellum: Technical Considerations of a Mega Osteochondritis Dissecans Technique.

Osteochondritis dissecans of the elbow is a rare but debilitating pathology typically found in the adolescent repetitive overhead athlete. In the setting of unstable lesions, mechanical symptoms, or deteriorating function despite appropriate conservative management, surgical osteochondral allograft transplantation of the capitellum is a viable option for even large lesions (>10 mm), with minimal morbidity and good return of function. We describe a technique for performing a large osteochondral allograft transplantation of the capitellum.

Loss of genetic variation and ancestral sex determination system in North American northern pike characterized by whole-genome resequencing.

The northern pike Esox lucius is a freshwater fish with low genetic diversity but ecological success throughout the Northern Hemisphere. Here we generate an annotated chromosome-level genome assembly of 941 Mbp in length with 25 chromosome-length scaffolds. We then genotype 47 northern pike from Alaska through New Jersey at a genome-wide scale and characterize a striking decrease in genetic diversity along the sampling range. Individuals west of the North American Continental Divide have substantially higher diversity than those to the east (e.g., Interior Alaska and St. Lawrence River have on average 181K and 64K heterozygous SNPs per individual, or a heterozygous SNP every 5.2 kbp and 14.6 kbp, respectively). Individuals clustered within each population with strong support, with numerous private alleles observed within each population. Evidence for recent population expansion was observed for a Manitoba hatchery and the St. Lawrence population (Tajima's D = -1.07 and -1.30, respectively). Several chromosomes have large regions with elevated diversity, including LG24, which holds amhby, the ancestral sex determining gene. As expected amhby was largely male-specific in Alaska and the Yukon and absent southeast to these populations, but we document some amhby(-) males in Alaska and amhby(+) males in the Columbia River, providing evidence for a patchwork of presence of this system in the western region. These results support the theory that northern pike recolonized North America from refugia in Alaska and expanded following deglaciation from west to east, with probable founder effects resulting in loss of both neutral and functional diversity (e.g., amhby).

Determining the Key Education Priorities Related to Heart Failure Care in Nursing Homes: A Modified Delphi Approach.

There is currently a limited understanding of what nurses in nursing homes view as the key education priorities to support their ability to provide the appropriate care for residents with heart failure (HF). A modified Delphi technique was utilized to gain a consensus on the key education priorities for nurses working in nursing homes in Northern Ireland. An initial list of items (n = 58), across 19 domains, was generated using the findings of a scoping review and stakeholder interviews, and a review of available clinical guidelines. Two rounds of surveys were undertaken. Items were presented using a 5-point Likert scale, with an additional exercise in the second round to rank the domains in order of importance. Fifty-four participants completed the first-round survey and 34 (63%) returned to complete the second. The findings highlight the importance of providing nurses in nursing home settings with general HF education and the delivery of person-centered care. Participants perceived education around technology for the management of HF and quality improvement or research methodologies associated with HF in nursing homes as lower priorities. This study illuminates key priorities from nursing home nurses regarding HF education that are applicable to this care setting.

Surgeon- and hospital-level variation in wait times for scheduled non-urgent surgery in Ontario, Canada: A cross-sectional population-based study.

BACKGROUND: Canadian health systems fare poorly in providing timely access to elective surgical care, which is crucial for quality, trust, and satisfaction. METHODS: We conducted a cross-sectional analysis of surgical wait times for adults receiving non-urgent cataract surgery, knee arthroplasty, hip arthroplasty, gallbladder surgery, and non-cancer uterine surgery in Ontario, Canada, between 2013 and 2019. We obtained data from the Wait Times Information System (WTIS) database. Inter- and intra-hospital and surgeon variations in wait time were described graphically with caterpillar plots. We used non-nested 3-level hierarchical random effects models to estimate variation partition coefficients, quantifying the proportion of wait time variance attributable to surgeons and hospitals. RESULTS: A total of 942,605 procedures at 107 healthcare facilities, conducted by 1,834 surgeons, were included in the analysis. We observed significant intra- and inter-provider variations in wait times across all five surgical procedures. Inter-facility median wait time varied between six-fold for gallbladder surgery and 15-fold for knee arthroplasty. Inter-surgeon variation was more pronounced, ranging from a 17-fold median wait time difference for cataract surgery to a 216-fold difference for non-cancer uterine surgery. The proportion of variation in wait times attributable to facilities ranged from 6.2% for gallbladder surgery to 23.0% for cataract surgery. In comparison, surgeon-related variation ranged from 16.0% for non-cancer uterine surgery to 28.0% for cataract surgery. IMPLICATIONS: There is extreme variability in surgical wait times for five common, high-volume, non-urgent surgical procedures. Strategies to address surgical wait times must address the variation between service providers through better coordination of supply and demand. Approaches such as single-entry models could improve surgical system performance.

Short-term dietary changes are reflected in the cerebral content of adult ring-billed gulls.

Omega-3 long-chain polyunsaturated fatty acids (n3-LCPUFAs) are produced primarily in aquatic ecosystems and are considered essential nutrients for predators given their structural role in vertebrates' cerebral tissues. Alarmingly, with urbanization, many aquatic animals now rely on anthropogenic foods lacking n3-LCPUFAs. In this study undertaken in Newfoundland (Canada), we tested whether recent or longer term diet explains the cerebral fatty acid composition of ring-billed gulls (Larus delawarensis), a seabird that now thrives in cities. During the breeding season, cerebral levels of n3-LCPUFAs were significantly higher for gulls nesting in a natural habitat and foraging on marine food (mean ± s.d.: 32 ± 1% of total identified fatty acids) than for urban nesters exploiting rubbish (27 ± 1%). Stable isotope analysis of blood and feathers showed that urban and natural nesters shared similar diets in autumn and winter, suggesting that the difference in cerebral n3-LCPUFAs during the breeding season was owing to concomitant and transient differences in diet. We also experimentally manipulated gulls' diets throughout incubation by supplementing them with fish oil rich in n3-LCPUFAs, a caloric control lacking n3-LCPUFAs, or nothing, and found evidence that fish oil increased urban nesters' cerebral n3-LCPUFAs. These complementary analyses provide evidence that the brain of this seabird remains plastic during adulthood and responds to short-term dietary changes.