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Abstract Recent advances in 3D printing have enabled the manufacture of porous electrodes which cannot be machined using traditional methods. With micron-scale precision, the pore structure of an electrode can now be designed for optimal energy efficiency, and a 3D printed electrode is not limited to a single uniform porosity. As these electrodes scale in size, however, the total number of possible pore designs can be intractable; choosing an appropriate pore distribution manually can be a complex task. To address this challenge, we adopt an inverse design approach. Using physics-based models, the electrode structure is optimized to minimize power losses in a flow reactor. The computer-generated structure is then printed and benchmarked against homogeneous porosity electrodes. We show how an optimized electrode decreases the power requirements by 16% compared to the best-case homogeneous porosity. Future work could apply this approach to flow batteries, electrolyzers, and fuel cells to accelerate their design and implementation.

Background: Previous research has indicated significant concerns regarding attrition of early career physiotherapists in Australia. Despite the importance of retaining skilled and experienced professionals within the profession, the workplace and workforce intentions of early career physiotherapists remain relatively unexplored., Purpose: The aim of this study was to investigate and explore factors influencing the workplace and workforce intentions of early career physiotherapists in Australia., Methods: The Turnover Intention Theory was used to guide a whole-of-person qualitative exploration through semi-structured interviews with 14 participants. Transcribed interview data was subjected to reflexive thematic analysis., Results: Four themes were generated, constructed as questions to represent participants' temporary holding of intentions: 1) What drives me?; 2) Do my expectations align?; 3) Do my values align?; and 4) What does the future hold?, Conclusion: Early career physiotherapists' perspectives encompass diverse and varied experiences that reflect an alignment, or in some cases a misalignment, of the expectations, values and resulting practices of becoming and being a physiotherapist. Early career physiotherapists experience a range of challenges within their workplaces, including significant experiences of stress, yet they express an underlying commitment to the wider profession.

Purpose: Colorectal cancer screening is recommended starting at age 45, but there has been little research on strategies to promote screening in patients younger than 50., Methods: An outreach program quasi-randomly assigned patients aged 45-50 without recent fecal immunochemical test (FIT), colonoscopy or contraindications to screening to two intervention arms: electronic outreach with email and text (electronic outreach only) versus electronic outreach plus mailed outreach with FIT, an instructional letter and a prepaid return envelope (mailed + electronic outreach). In response to known disparities in screening uptake, all Black patients were assigned to receive mailed + electronic outreach., Results: Among patients quasi-randomly assigned to an intervention (non-Black patients), the 180-day FIT completion rate was 18.8% in the electronic outreach only group (n = 1,318) and 25.0% in the mailed + electronic outreach group (n = 1,364) (difference 6.2% [95% CI 3.0, 9.4]). FIT completion was 16.6% among Black patients (n = 469), 8.4% (95% CI 4.1, 12.6) lower than among non-Black patients also assigned to mailed + electronic outreach., Conclusion: Among patients aged 45-50, mailed + electronic outreach had a greater effect on FIT completion than electronic outreach alone. Crossover between intervention groups likely lead to an underestimation of the effect of mailed outreach., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Precise transformations of natural products (NPs) can fine-tune their physicochemical properties while preserving inherently complex and evolutionarily optimized parent scaffolds. Here, we report an unprecedented lactone-to-lactam transformation on bilobalide, thus improving its stability and paving the way for biological exploration of previously inaccessible chemical space that is highly representative of the parent structure. This late-stage molecular editing of bilobalide enables facile access to a unique library of lactam analogues with altered pharmacology. Through phenotypic screening, we identify BB10 as a hit compound with unexpected inhibition of ferroptotic cell death. We further reveal that BB10 suppresses ferroptosis by restoring the expression of glutathione peroxidase 4 (GPX4) in brain cells. This study highlights that even subtle changes on NP scaffolds can confer new pharmacological properties, inspiring the exploration of simple yet critical transformations on complex NPs., Competing Interests: The authors declare the following competing financial interest(s): B.W.-L.N. is an inventor on a U.S. non-provisional patent application submitted by The Chinese University of Hong Kong that covers the described analogues in this manuscript., (© 2024 The Authors. Published by American Chemical Society.)

Objective: To develop a semiautomated electronic medical record (EMR) system to track pediatric endoscopic procedural adverse event (AE) at a tertiary referral children's hospital., Methods: We developed an automated EMR based query for postprocedure AEs. Main outcome measurements within 30 days of procedure: return to emergency department, return to surgery, unplanned admissions and admissions with longer than intended stays. Events were graded using a recently described classification system for postendoscopy events and tracked for a 36-month period, from January 2017 to December 2019., Results: Development of a semi-automated system was successful in comprehensive identification of endoscopy and sedation related AE. A total of 193 AEs (2%) were identified in all three categories. Seventy cases (0.7%) were noted to be a direct result of an endoscopic procedure. Of these cases, 31 (44%) were noted to be Grade 3, 5 cases (7%) Grade 4, and no Grade 5 AE occured. Higher rates of AE were observed after therapeutic procedures versus diagnostic (2.6% vs. 0.3%, p = <0.00001). AEs related to sedation occurred in 0.5% of procedures with the majority (84%) reported in patients with American Society of Anesthesia classification of 3 or greater., Conclusions: Diagnostic endoscopy remains a safe procedure and risk of both endoscopy and sedation related AE are low. Therapeutic procedures carry a higher risk but are still overwhelmingly safe. Institutional investment in this EMR based system allowed for sustainability and comprehensive tracking of endoscopy related AE., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Infection and lymphopenia are established bendamustine-related complications. The relationship between lymphopenia severity and infection risk, and the role of antimicrobial prophylaxis, is not well described. This multicentre retrospective study analysed infection characteristics and antimicrobial prophylaxis in 302 bendamustine-treated indolent non-Hodgkin lymphoma patients. Lymphopenia (<1 × 10 9 /L) was near universal and time to lymphocyte recovery correlated with cumulative bendamustine dose. No association between lymphopenia severity and duration with infection was observed. Infections occurred in 44% of patients (50% bacterial) with 27% hospitalised; 32% of infections occurred ≥3 months post bendamustine completion. Infection was associated with obinutuzumab and/or maintenance anti-CD20 therapy, prior therapy and advanced stage. Twenty-four opportunistic infections occurred in 21 patients: ten varicella zoster virus (VZV), seven herpes simplex virus (HSV), one cytomegalovirus, one progressive multifocal leucoencephalopathy, one nocardiosis, one Pneumocystis jiroveci pneumonia (PJP) and three other fungal infections. VZV/HSV and PJP prophylaxis were prescribed to 42% and 54% respectively. Fewer VZV/HSV infections occurred in patients receiving prophylaxis (HR 0.14, p = 0.061) while PJP prophylaxis was associated with reduced risk of bacterial infection (HR 0.48, p = 0.004). Our study demonstrates a significant infection risk regardless of lymphopenia severity and supports prophylaxis to mitigate the risk of early and delayed infections., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Homelessness poses complex health obstacles for individuals and communities. Peer and lay health worker programs aim to increase access to health care and improve health outcomes for PEH by building trust and empowering community-based workers. The scope and breadth of peer and lay health worker programs among PEH has not been synthesized. The primary objective of this scoping review is to understand the context (setting, community, condition or disease) encompassing peer and lay health worker programs within the homelessness sector. The secondary objective is to examine the factors that either facilitate or hinder the effectiveness of peer and lay health worker programs when applied to people experiencing homelessness (PEH). We searched CINHAL, Cochrane, Web of Science Core Collection, PsycINFO, Google Scholar and MEDLINE. We conducted independent and duplicate screening of titles and abstracts, and extracted information from eligible studies including study and intervention characteristics, peer personnel characteristics, outcome measures, and the inhibitors and enablers of effective programs. We discuss how peer and lay health work programs have successfully been implemented in various contexts including substance use, chronic disease management, harm reduction, and mental health among people experiencing homelessness. These programs reported four themes of enablers (shared experiences, trust and rapport, strong knowledge base, and flexibility of role) and five themes of barriers and inhibitors (lack of support and clear scope of role, poor attendance, precarious work and high turnover, safety, and mental well-being and relational boundaries). Organizations seeking to implement these interventions should anticipate and plan around the enablers and barriers to promote program success. Further investigation is needed to understand how peer and lay health work programs are implemented, the mechanisms and processes that drive effective peer and lay health work among PEH, and to establish best practices for these programs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mangan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To describe the prevalence of and between-center variations in care practices and clinical outcomes of moderate and late preterm infants (MLPIs) admitted to tertiary Canadian neonatal intensive care units (NICUs)., Study Design: This was a retrospective cohort study including infants born at 32 0/7 through 36 6/7  weeks of gestation and admitted to 25 NICUs participating in the Canadian Neonatal Network between 2015 and 2020. Patient characteristics, process measures represented by care practices, and outcome measures represented by clinical in-hospital and discharge outcomes were reported by gestational age weeks. NICUs were compared using indirect standardization after adjustment for patient characteristics., Results: Among 25 669 infants (17% of MLPIs born in Canada during the study period) included, 45% received deferred cord clamping, 7% had admission hypothermia, 47% received noninvasive respiratory support, 11% received mechanical ventilation, 8% received surfactant, 40% received antibiotics in the first 3 days, 4% did not receive feeding in the first 2 days, and 77% had vascular access. Mortality, early-onset sepsis, late-onset sepsis, or necrotizing enterocolitis occurred in <1% of the study cohort. Median (IQR) length of stay was 14 (9-21) days among infants discharged home from the admission hospital and 5 (3-9) days among infants transferred to community hospitals. Among infants discharged home, 33% were discharged on exclusive breastmilk and 75% on any breastmilk. There were significant variations between NICUs in all process and outcome measures., Conclusions: Care practices and outcomes of MLPIs varied significantly between Canadian NICUs. Standardization of process and outcome quality measures for this population will enable benchmarking and research, facilitating systemwide improvements., Competing Interests: Declaration of Competing Interest Organizational support for the Canadian Neonatal Network (CNN) was provided by the Maternal-Infant Care (MiCare) Research Center at Mount Sinai Hospital in Toronto, Ontario, Canada, and participating hospitals within the CNN. The MiCare research center is supported by the Canadian Preterm Birth Network Grant awarded to P.S. from the Canadian Institutes of Health Research. The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Nasal intermittent positive pressure ventilation (NIPPV) has been shown to be superior to nasal continuous positive airway pressure (CPAP) postextubation in preterm neonates. However, studies have not permitted high CPAP pressures or rescue with other modes. We hypothesized that if CPAP pressures >8 cmH2O and rescue with other modes were permitted, CPAP would be noninferior to NIPPV., Methods: We conducted a pragmatic, comparative-effectiveness, noninferiority study utilizing network-based real-world data from 22 Canadian NICUs. Centers self-selected CPAP or NIPPV as their standard postextubation mode for preterm neonates <29 weeks' gestation. The primary outcome was failure of the initial mode ≤72 hours. Secondary outcomes included failure ≤7 days, and reintubation ≤72 hours and ≤7 days. Groups were compared using a noninferiority adjusted risk-difference (aRD) margin of 0.05, and margin of no difference., Results: A total of 843 infants extubated to CPAP and 974 extubated to NIPPV were included. CPAP was not noninferior (and inferior) to NIPPV for failure of the initial mode ≤72 hours (33.0% vs 26.3%; aRD 0.07 [0.03 to 0.12], Pnoninferiority(NI) = .86), and ≤7 days (40.7% vs 35.8%; aRD 0.09 [0.05 to 0.13], PNI = 0.97). However, CPAP was noninferior (and equivalent) to NIPPV for reintubation ≤72 hours (13.2% vs 16.1%; aRD 0.01 [-0.05 to 0.02], PNI < .01), and noninferior (and superior) for reintubation ≤7 days (16.4% vs 22.8%; aRD -0.04 [-0.07 to -0.001], PNI < .01)., Conclusions: CPAP was not noninferior to NIPPV for failure ≤72 hours postextubation; however, it was noninferior to NIPPV for reintubation ≤72 hours and ≤7 days. This suggests CPAP may be a reasonable initial postextubation mode if alternate rescue strategies are available., (Copyright © 2024 by the American Academy of Pediatrics.)

Objective: To quantify site-specific costs and their association with survival without major morbidity (SWMM) in Canada for neonates <28 weeks of gestation admitted to large tertiary neonatal intensive care units., Methods: We conducted a retrospective analysis of infants born at <28 weeks of gestation and admitted to Canadian Neonatal Network sites from 2010 through 2021. Sites that cared for at least 50 eligible infants by gestational age in weeks over the study period were included. Using a validated costing algorithm that assessed physician, nursing, respiratory therapy, diagnostic imaging, transfusions, procedural, medication, and certain indirect costs, we calculated site and resource-specific costs in 2017 Canadian dollars (CAD) and evaluated their relationship with SWMM., Results: Seven sites with 8180 (range 841-1605) eligible neonates with a mean (SD) gestation of 25.4 [1.3] weeks were included. Survival to discharge or transfer was 85.3% with a mean (SD) length of stay of 75 (46) days. The mean (SD) total and daily costs per neonate varied between $94 992 ($60 283) and $174 438 ($130 501) CAD and $1833 ($916) to $2307 ($1281) CAD, respectively. Between sites, there was no relationship between costs and SWMM., Conclusions: There was marked variation in costs and SWMM between sites in Canada with universal health care. The lack of concordance between both outcomes and costs among sites may provide possibilities for outcomes improvement and cost containment., Competing Interests: Declaration of Competing Interest This study was supported by a grant from the Canadian Institutes of Health Research (CIHR) funding the Canadian Preterm Birth Network (CPTBN) (PBN 150642). Organizational support for the CPTBN and the Canadian Neonatal Network was provided by the Maternal-infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by Mount Sinai Hospital and the contribution of participating sites within Canada. The funders played no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the writing, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Optimization of nutrition prior to inflammatory bowel disease (IBD)-related surgery could improve outcomes. The aim of this study was to assess the perioperative nutrition status and management of children undergoing intestinal resection for treatment of their IBD., Methods: We identified all patients with IBD who underwent primary intestinal resection. We identified malnutrition using established criteria and methods of nutrition provision at various time points (preoperative outpatient evaluation, admission, and postoperative outpatient follow-up) for elective cases (who underwent their procedure at a scheduled admission) and urgent cases (who underwent an unplanned surgical intervention). We also recorded data on postsurgical complications., Results: A total of 84 patients were identified in this single-center study (male sex: 40%, mean age: 14.5 years, Crohn's disease: 65%). Thirty-four patients (40%) had some degree of malnutrition. Prevalence of malnutrition in the urgent and elective cohorts was similar (48% vs 36%; P = 0.37). Of these patients, 29 (34%) were noted to be on some type of nutrition supplementation prior to surgery. Postoperatively, BMI z scores increased (-0.61 vs -0.42; P = 0.0008), but the percentage of patients who were malnourished did not change from preoperative status (40% vs 40%; P = 0.10). Despite this, use of nutrition supplementation was only noted in 15 (17%) patients at postoperative follow-up. Complications were not associated with nutrition status., Conclusion: Utilization of supplemental nutrition decreased postprocedure despite no change in malnutrition prevalence. These findings support the development of a pediatric-specific perioperative nutrition protocol in the setting of IBD-related surgery., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Objectives: To implement an early rehabilitation bundle in two Canadian PICUs., Design and Setting: Implementation study in the PICUs at McMaster Children's Hospital (site 1) and London Health Sciences (site 2)., Patients: All children under 18 years old admitted to the PICU were eligible for the intervention., Interventions: A bundle consisting of: 1) analgesia-first sedation; 2) delirium monitoring and prevention; and 3) early mobilization., Measurements and Main Results: Primary outcomes were the duration of implementation, bundle compliance, process of care, safety, and the factors influencing implementation. Secondary endpoints were the impact of the bundle on clinical outcomes such as pain, delirium, iatrogenic withdrawal, ventilator-free days, length of stay, and mortality. Implementation occurred over 26 months (August 2018 to October 2020). Data were collected on 1,036 patients representing 4,065 patient days. Bundle compliance was optimized within 6 months of roll-out. Goal setting for mobilization and level of arousal improved significantly (p < 0.01). Benzodiazepine, opioid, and dexmedetomidine use decreased in site 1 by 23.2% (95% CI, 30.8-15.5%), 26.1% (95% CI, 34.8-17.4%), and 9.2% (95% CI, 18.2-0.2%) patient exposure days, respectively, while at site 2, only dexmedetomidine exposure decreased significantly by 10.5% patient days (95% CI, 19.8-1.1%). Patient comfort, safety, and nursing workload were not adversely affected. There was no significant impact of the bundle on the rate of delirium, ventilator-free days, length of PICU stay, or mortality. Key facilitators to implementation included institutional support, unit-wide practice guidelines, dedicated PICU educators, easily accessible resources, and family engagement., Conclusions: A rehabilitation bundle can improve processes of care and reduce patient sedative exposure without increasing patient discomfort, nursing workload, or harm. We did not observe an impact on short-term clinical outcomes. The efficacy of a PICU-rehabilitation bundle requires ongoing study. Lessons learned in this study provide evidence to inform rehabilitation implementation in the PICU setting., Competing Interests: Drs. Choong’s and Cupiodo’s institutions received funding from the Alternate Funding Plan (AFP) Innovation Fund: Hamilton Academic Health Sciences Organization. Drs. Fraser’s and Martin’s institutions received funding from the AFP Innovation Fund: Academic Medical Organization of Southwestern Ontario. Dr. Choong’s institution received funding from Hamilton Health Sciences Foundation. Drs. Choong and Kennedy received funding from McMaster University. Dr. Cameron received funding from London Health Sciences Center. Dr. Kennedy received funding from Pediatric Critical Care Medicine; he disclosed work for hire. Dr. Kho’s institution received funding from the Canadian Institutes of Health Research, Canada Research Chairs, and Canada Foundation for Innovation; she disclosed that Restorative Therapies loaned three RT300 supine cycle ergometers for an ongoing research project. Dr. Simpson received funding from Hamilton Health Sciences-McMaster Children’s Hospital. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background and Objectives: Research on outcomes of prematurity frequently examines neurodevelopment in the toddler years as an end point, but the age range at examination varies. We aimed to evaluate whether the corrected age (CA) at Bayley-III assessment is associated with rates of developmental delay in extremely preterm children., Methods: This retrospective cohort study included children born at <29 weeks' gestation who were admitted in the Canadian Neonatal Network between 2009 and 2017. The primary outcomes were significant developmental delay (Bayley-III score <70 in any domain) and developmental delay (Bayley-III score <85 in any domain). To assess the association between CA at Bayley-III assessment and developmental delay, we compared outcomes between 2 groups of children: those assessed at 18 to 20 months' CA and 21-24 months., Results: Overall, 3944 infants were assessed at 18-20 months' CA and 881 at 21-24 months. Compared with infants assessed at 18-20 months, those assessed at 21-24 months had higher odds of significant development delay (20.0% vs 12.5%; adjusted odds ratio, 1.75; 95% confidence interval [CI], 1.41-2.13) and development delays (48.9% vs 41.7%, adjusted odds ratio 1.33; 95% CI, 1.11-1.52). Bayley-III composite scores were on average 3 to 4 points lower in infants evaluated at 21-24 months' CA (for instance, adjusted mean difference and 95% CI for language: 3.49 [2.33-4.66]). Conversely, rates of cerebral palsy were comparable (4.6% vs 4.7%) between the groups., Conclusions: Bayley-III assessments performed at 21-24 months' CA were more likely to diagnose a significant developmental delay compared with 18- to 20-month assessments in extremely preterm children., (Copyright © 2024 by the American Academy of Pediatrics.)

Objective: To compare neonatal and early-childhood outcomes of twins and singletons born preterm and explore the association of chorionicity with outcomes., Study Design: This was a national retrospective cohort study of singleton and twin infants admitted at 23 0/7 -28 6/7 weeks to level III neonatal intensive care units in Canada (2010-2020). The primary neonatal outcome was a composite of neonatal death or severe neonatal morbidities. The primary early-childhood outcome was a composite of death or significant neurodevelopmental impairment., Results: The study cohort included 3554 twin and 12 815 singleton infants. Twin infants born at 23 0/7 -25 6/7  weeks had a greater risk of the composite neonatal outcome (adjusted risk ratio 1.04, 95% CI 1.01-1.07). However, these differences were limited to the subgroups of same-sex and monochorionic twin pregnancies. Twin infants of 23 0/7 -25 6/7  weeks were also at an increased risk of the composite early-childhood outcome (adjusted risk ratio 1.22, 95% CI 1.09-1.37). Twin infants of 26 0/7 -28 6/7  weeks were not at an increased risk of adverse neonatal outcomes or the composite early-childhood outcome compared with singleton infants., Conclusions: Among infants born at 23 0/7 -25 6/7  weeks, twins have a greater risk of adverse neonatal outcomes and the composite early-childhood outcome than singleton infants. However, the increased risk of adverse neonatal outcomes is mostly limited to monochorionic twins and may thus be driven by complications related to monochorionic placentation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To report the clinical manifestations, response to antiviral treatment, and long-term visual outcomes of cytomegalovirus endotheliitis in a Canadian population., Design: Retrospective case series., Participants: A total of 9 eyes of 7 patients referred to a cornea subspecialty clinic in a major Canadian centre with corneal endotheliitis., Methods: A retrospective review of all patients presenting with corneal endotheliitis to 1 corneal surgeon was completed. Patients underwent anterior chamber biopsy with positive cytomegalovirus polymerase chain reaction. All patients received systemic valganciclovir for a minimum of 3 months. Primary outcomes included visual acuity, intraocular pressure control, medication dependence, and corneal status., Results: The average follow-up was 76.4 ± 11.8 months. Two patients had bilateral disease. Corneal manifestations included linear, disciform, and circinate patterns of endotheliitis. Best-corrected visual acuity improved from a mean of 0.48 ± 0.19 logMAR at presentation to 0.24 ± 0.11 logMAR at last follow-up. Intraocular pressure decreased from a peak of 35 ± 3.1 mm Hg to 14.2 ± 4.3 mm Hg. Antiglaucoma medications were reduced from 2.6 ± 0.45 to 0.89 ± 0.29 agents. Two eyes required endothelial transplantation. Valganciclovir therapy was well tolerated by all patients; at the time of last follow-up, all patients were stable on low-dose valganciclovir at an average dose of 1395 mg per week., Conclusions: Cytomegalovirus is an uncommon but clinically significant cause of corneal endotheliitis that must be considered in the differential diagnosis of corneal endotheliitis, even in the immunocompetent population. Our results support prior findings that this entity responds robustly to oral valganciclovir and demonstrate for the first time the efficacy of chronic low-dose antiviral maintenance therapy., (Copyright © 2022. Published by Elsevier Inc.)

Background: Although a few case reports have shown that immune checkpoint inhibitors (ICIs) are potential inducers of capillary leak syndrome (CLS), an incidental finding cannot be ruled out. The aim of this study was to describe the clinical characteristics of ICI-induced CLS through a systematic review and to assess a potential safety signal., Methods: Medline/PubMed, Embase, and Reactions Weekly were screened, and a global disproportionality study was performed using the World Health Organization pharmacovigilance database through January 15, 2023. A signal of disproportionate reporting was defined as a Bayesian information component (IC) with a 95% credibility interval (CrI) lower boundary that exceeds 0., Results: A total of 47 cases of ICI-associated CLS were included, 14 from the systematic review (of 61 screened articles) and 33 from VigiBase (of 34,058,481 reports of adverse drug reactions). The median time to CLS onset from the start of ICI was 12 weeks (interquartile range 8-49, n = 24). A total of 57% (8/14) of patients experienced an immune-related adverse event (irAE) before CLS. A fatal outcome was reported in 23% (7/31) of patients. A significant overreporting of CLS was found with ICIs compared with all other drugs (IC 2.4, 95% CrI from 1.8 to 2.8)., Conclusion: This study showed a significant signal of disproportionality reporting for ICI-induced CLS, characterized by a long time to onset, and compared with the idiopathic form of the disease with a less abrupt onset and a less consistent hemoconcentration pattern., (© 2023 The Association for the Publication of the Journal of Internal Medicine.)

Anaerobic digestion (AD) has emerged as a promising technology for diverting the organic waste from the landfills along with the production of clean energy. AD is a microbial-driven biochemical process wherein the plethora of microbial communities participate in converting the putrescible organic matter into biogas. Nevertheless, the AD process is susceptible to the external environmental factors such as presence of physical (microplastics) and chemical (antibiotics, pesticides) pollutants. The microplastics (MPs) pollution has received recent attention due to the increasing plastic pollution in terrestrial ecosystems. This review was aimed for holistic assessment of impact of MPs pollution on AD process to develop efficient treatment technology. First, the possible pathways of MPs entry into the AD systems were critically evaluated. Further, the recent literature on the experimental studies pertaining to the impact of different types of MPs at different concentrations on the AD process was reviewed. In addition, several mechanisms such as direct exposure of MPs on the microbial cells, indirect impact of MPs through the leaching of toxic chemicals and reactive oxygen species (ROS) formation on AD process were elucidated. Besides, the risk possessed by the increase of antibiotic resistance genes (ARGs) after the AD process due to the MPs stress on microbial communities were discussed. Overall, this review deciphered the severity of MPs pollution on AD process at different levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We developed and implemented a method-independent, fully numerical, finite difference approach to calculating nuclear magnetic resonance shieldings, using gauge-including atomic orbitals. The resulting capability can be used to explore non-standard methods, given only the energy as a function of finite-applied magnetic fields and nuclear spins. For example, standard second-order Møller-Plesset theory (MP2) has well-known efficacy for 1H and 13C shieldings and known limitations for other nuclei such as 15N and 17O. It is, therefore, interesting to seek methods that offer good accuracy for 15N and 17O shieldings without greatly increased compute costs, as well as exploring whether such methods can further improve 1H and 13C shieldings. Using a small molecule test set of 28 species, we assessed two alternatives: κ regularized MP2 (κ-MP2), which provides energy-dependent damping of large amplitudes, and MP2.X, which includes a variable fraction, X, of third-order correlation (MP3). The aug-cc-pVTZ basis was used, and coupled cluster with singles and doubles and perturbative triples [CCSD(T)] results were taken as reference values. Our κ-MP2 results reveal significant improvements over MP2 for 13C and 15N, with the optimal κ value being element-specific. κ-MP2 with κ = 2 offers a 30% rms error reduction over MP2. For 15N, κ-MP2 with κ = 1.1 provides a 90% error reduction vs MP2 and a 60% error reduction vs CCSD. On the other hand, MP2.X with a scaling factor of 0.6 outperformed CCSD for all heavy nuclei. These results can be understood as providing renormalization of doubles amplitudes to partially account for neglected triple and higher substitutions and offer promising opportunities for future applications., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Genomic testing is already used by blood collection agencies (BCAs) to identify rare blood types and ensure the best possible matching of blood. With ongoing technological developments, broader applications, such as the identification of genetic markers relevant to blood donor health, will become feasible. However, the perspectives of blood donors (and potential blood donors) on routine genomic testing of donor blood are under-researched., Study Design and Methods: Eight online Focus Groups were conducted: four with donors and four with non-donors. Participants were presented with three hypothetical scenarios about the current and possible future applications of genomic testing: Performing rare blood type testing; identifying donors with genetic markers associated with iron metabolism; and identifying donors with genetic markers associated with bowel cancer., Results: Testing to identify rare blood types was perceived to be an appropriate application for the BCA to undertake, while identifying markers associated with iron metabolism and cancer genetic markers were only partially supported. Participants raised concerns about the boundaries of acceptable testing and the implications of testing for privacy, data security, and health insurance. Perspectives of donors and non-donors on all scenarios were similar., Discussion: The principles of who benefits from genomic testing and the perceived role of BCAs were key in shaping participants' perspectives. Participants generally agreed that testing should be directly related to blood donation or be of benefit to the recipient or donor. Findings indicate that consent and communication are key to the acceptability of current and expanded genomic testing., (© 2022 Australian Red Cross Lifeblood. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

This paper presents a systematic study of applying composite method approximations with locally dense basis sets (LDBS) to efficiently calculate NMR shielding constants in small and medium-sized molecules. The pcSseg- n series of basis sets are shown to have similar accuracy to the pcS- n series when n ≥ 1 and can slightly reduce computational costs. We identify two different LDBS partition schemes that perform very effectively for density functional calculations. We select a large subset of the recent NS372 database containing 290 H, C, N, and O shielding values evaluated by reference methods on 106 molecules to carefully assess methods of the high, medium, and low computational costs to make practical recommendations. Our assessment covers conventional electronic structure methods (density functional theory and wave function) with global basis calculations, as well as their use in one of the satisfactory LDBS approaches, and a range of composite approaches, also with and without LDBS. Altogether 99 methods are evaluated. On this basis, we recommend different methods to reach three different levels of accuracy and time requirements across the four nuclei considered.

Acquired hypogammaglobulinemia is common in chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). No previous systematic reviews (SRs) have compared different approaches to infection prevention. We sought to assess the efficacy and safety of prophylactic immunoglobulin, antibiotics, and vaccination in these patients. We performed an SR and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of prophylactic immunoglobulin, antibiotics, and vaccination in adult patients with hematological malignancies commonly associated with acquired hypogammaglobulinemia, specifically, CLL, NHL, and MM. We searched PubMed (MEDLINE), EMBASE, and Cochrane Registry up to 9 January 2021. Results for dichotomous data were expressed as relative risk (RR) with 95% confidence interval (CI) and pooled in a random-effects model. This review was registered with PROSPERO CRD42017070825. From 10 576 studies screened, there were 21 completed RCTs and 1 ongoing. Of these, 8 evaluated prophylactic immunoglobulin (n = 370; 7 published before 2000), 5 evaluated prophylactic antibiotics (n = 1587), 7 evaluated vaccination (n = 3996), and 1 compared immunoglobulin to antibiotics (n = 60). Prophylactic immunoglobulin reduced the risk of clinically documented infection (CDI) by 28% (n = 2 trials; RR, 0.72; 95% CI, 0.54-0.96), and vaccination reduced the risk by 63% (RR, 0.37; 95% CI, 0.30-0.45). Prophylactic antibiotics did not reduce the risk. No intervention reduced all-cause mortality. Prophylactic immunoglobulin and antibiotics increased the risk of adverse events. Findings should be interpreted with caution, given the high risk of bias in many studies. There is a clear need for high-quality contemporary trials to establish the effectiveness of different approaches to preventing infection., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Chinese medicinal herbal residues (CMHRs) are known for their antipathogenic properties due to the presence of bioactive compounds. Hence, CMHRs could be used as a potential resource to produce biofertilizer with antipathogenic properties for agricultural applications. In this study, a novel approach was used by utilizing the waste-derived biofertilizer, i.e., CMHRs compost (CMHRC) as a nutrient supplier as well as an organic bioagent against Alternaria solani (A. solani) and Fusarium oxysporum (F. oxysporum) on tomato (Lycopersicon esculentum) and Chinese cabbage (Brassica rapa subsp. Chinensis) plants. The experiments were conducted under greenhouse conditions using locally collected acidic soil wherein 2%, 5% and 10% CMHRC (dry weight) along with 5% food waste compost were used as treatments. In addition, only soil and soil with phytopathogens were used as control treatments. The results suggested that amending the compost into acidic soil significantly increased the pH to a neutral level along with enhanced uptake of nutrients. Among all the treatments, 5% CMHRs compost addition increased the tomato plant biomass production to 4.9 g/pot (dry weight) compared to 2.2 g/pot in control. A similar trend was observed in Chinese cabbage plants and the improved plant biomass production could be attributed to the combined effect of strong nutrient absorption ability by healthy roots and enhanced nutrient supply. At 5% CMHRC application rate, the nitrogen uptake by tomato and Chinese cabbage plants increased by 78% and 62%, respectively, whereas phosphorous uptake increased by 75% and 25%, respectively. The reduction in A. solani by 48% and F. oxysporum by 54% in the post-harvested soil of 5% CMHRC treatment against the control demonstrated the anti-phytopathogenic efficiency of CMHRC compost. Hence, the present study illustrates the beneficiary aspects of utilizing CMHRs to produce biofertilizer with anti-phytopathogenic properties which can be safely used for tomato and Chinese cabbage plant growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

The annual increase of waste activated sludge (WAS) has become an urgent problem to be solved in sewage plants worldwide. Anaerobic digestion (AD) of WAS is an attractive choice to maximize the resource utilization rate. Nevertheless, the disintegration of sludge complex polymers is difficult, resulting in a low bioconversion rate. Potassium ferrate (PF), as a green oxidant with strong oxidizing property, has attracted great attention in WAS pretreatment recently. The effects of PF pretreatment on WAS hydrolysis and its dosage-response on methane production were investigated in the present study. Results show that as PF dosage raise from 0 to 50 g-K 2 FeO 4 / kg-TS (total solids), the methane yield enhanced significantly by 40.3% from 0.083 to 0.12 L/g-VS added (volatile solids). Nevertheless, the further increase in PF dosage resulted in decreased methane production. Especially with the PF dosage of 500 g-K 2 FeO 4 / kg-TS, methane production is even slightly lower than the control reactor without PF oxidation. The mechanism analysis showed that although the dissolution of polysaccharides and proteins was enhanced with the high dosage of PF, the accompanying released humic-like substances and high concentration of ferric ions should be the main reasons inhibiting methane production.

To improve the dose efficiency of K 2 FeO 4 in waste activated sludge (WAS) treatment, pH regulation on K 2 FeO 4 pretreatment and acidogenic fermentation was investigated. Four pretreatments were compared, i.e. pH3 + 50 g/kg-TS, pH10 + 50 g/kg-TS, neutral pH + 50 g/kg-TS and neutral pH + 100 g/kg-TS (without pH adjustment). The higher short chain fatty acids (SCFAs) yield and phosphorous dissolution rate was found under the condition of pH 10.0. In pH10 + 50 g/kg-TS, the maximum concentration of SCFAs was 5591 mg-COD/L, which yield was 22.6 times higher than that of the neutral pH + 50 g/kg-TS (237 mg COD/L). The acidogenic fermentation period could be shortened to 5 days and acetic acid accounted for 70 % of SCFAs. Furthermore, PO 4 3- -P in the hydrolysate (346.5 mg/L) accounted for 47.59 % of TP, which is easier to be recovered by chemical precipitation. Therefore, a more economical and feasible utilization mode of potassium ferrate was proposed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Point-of-care ultrasound (POCUS) is a growing part of internal medicine training programs. Dedicated POCUS rotations are emerging as a particularly effective tool in POCUS training, allowing for longitudinal learning and emphasizing both psychomotor skills and the nuances of clinical integration. In this descriptive paper, we set out to review the state of POCUS rotations in Canadian Internal Medicine training programs., Results: We identify five programs currently offering a POCUS rotation. These rotations are offered over two to thirteen blocks each year, run over one to four weeks and support one to four learners. Across all programs, these rotations are set up as a consultative service that offers POCUS consultation to general internal medicine inpatients, with some extension of scope to the hospitalist service or surgical subspecialties. The funding model for the preceptors of these rotations is predominantly fee-for-service using consultation codes, in addition to concomitant clinical work to supplement income. All but one program has access to hospital-based archiving of POCUS exams. Preceptors dedicate ten to fifty hours to the rotation each week and ensure that all trainee exams are reviewed and documented in the patient's medical records in the form of a consultation note. Two of the five programs also support a POCUS fellowship. Only two out of five programs have established learner policies. All programs rely on In-Training Evaluation Reports to provide trainee feedback on their performance during the rotation., Conclusions: We describe the different elements of the POCUS rotations currently offered in Canadian Internal Medicine training programs. We share some lessons learned around the elements necessary for a sustainable rotation that meets high educational standards. We also identify areas for future growth, which include the expansion of learner policies, as well as the evolution of trainee assessment in the era of competency-based medical education. Our results will help educators that are endeavoring setting up POCUS rotations achieve success., (© 2022. The Author(s).)

Purpose: To evaluate change in the severity of hypoxic-ischemic encephalopathy (HIE) and associated morbidities between pre- and during COVID-19 pandemic periods in Canada., Methods: We conducted a retrospective cohort study extracting the data from level-3 NICUs participating in Canadian Neonatal Network (CNN). The primary outcome was a composite of death in the first week after birth and/or stage 3 HIE (Sarnat and Sarnat). Secondary outcomes included rate and severity of HIE among admitted neonates, overall mortality, brain injury on magnetic resonance imaging (MRI), neonates requiring resuscitation, organ dysfunction, and therapeutic hypothermia (TH) usage. We included 1591 neonates with gestational age ≥ 36 weeks with HIE during the specified periods: pandemic cohort from April 1st to December 31st of 2020; pre-pandemic cohort between April 1st and December 31st of 2017, 2018, and 2019. We calculated the odds ratio (OR) and confidence intervals (CI)., Results: We observed no significant difference in the primary outcome (15% vs. 16%; OR 1.08; 95%CI 0.78-1.48), mortality in the first week after birth (6% vs. 6%; OR 1.10, 95%CI 0.69-1.75), neonates requiring resuscitation, organ dysfunction, TH usage, or rate of brain injury. In the ad hoc analysis, per 1000 live births, there was an increase in the rate of infants with HIE and TH use., Conclusions: Severity of HIE, associated morbidities, and mortality were not significantly different during the pandemic lockdown compared to a pre-pandemic period in Canada. Anticipated risks and difficulties in accessing healthcare have not increased the mortality and morbidities in neonates with HIE in Canada., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sox17 gene expression is essential for both endothelial and endodermal cell differentiation. To better understand the genetic basis for the expression of multiple Sox17 mRNA forms, we identified and performed CRISPR/Cas9 mutagenesis of two evolutionarily conserved promoter regions (CRs). The deletion of the upstream and endothelial cell-specific CR1 caused only a modest increase in lympho-vasculogenesis likely via reduced Notch signaling downstream of SOX17. In contrast, the deletion of the downstream CR2 region, which functions in both endothelial and endodermal cells, impairs both vascular and endodermal development causing death by embryonic day 12.5. Analyses of 3D chromatin looping, transcription factor binding, histone modification, and chromatin accessibility data at the Sox17 locus and surrounding region further support differential regulation of the two promoters during the development., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

During mitosis, individual microtubules make attachments to chromosomes via a specialized protein complex called the kinetochore to faithfully segregate the chromosomes to daughter cells. Translocation of kinetochores on the lateral surface of the microtubule has been proposed to contribute to high fidelity chromosome capture and alignment at the mitotic midzone, but has been difficult to observe in vivo because of spatial and temporal constraints. To overcome these barriers, we used total internal reflection fluorescence (TIRF) microscopy to track the interactions between microtubules, kinetochore proteins, and other microtubule-associated proteins in lysates from metaphase-arrested Saccharomyces cerevisiae . TIRF microscopy and cryo-correlative light microscopy and electron tomography indicated that we successfully reconstituted interactions between intact kinetochores and microtubules. These kinetochores translocate on the lateral microtubule surface toward the microtubule plus end and transition to end-on attachment, whereupon microtubule depolymerization commences. The directional kinetochore movement is dependent on the highly processive kinesin-8, Kip3. We propose that Kip3 facilitates stable kinetochore attachment to microtubule plus ends through its abilities to move the kinetochore laterally on the surface of the microtubule and to regulate microtubule plus end dynamics., Competing Interests: JT, JW, DS, AM, DD, GB No competing interests declared, (© 2022, Torvi, Wong et al.)

Peripheral T-cell lymphoma (PTCL) is a rare, heterogenous malignancy with dismal outcomes at relapse. Hypomethylating agents (HMA) have an emerging role in PTCL, supported by shared mutations with myelodysplasia (MDS). Response rates to azacitidine in PTCL of follicular helper cell origin are promising. Guadecitabine is a decitabine analogue with efficacy in MDS. In this phase II, single-arm trial, PTCL patients received guadecitabine on days 1-5 of 28-day cycles. Primary end points were overall response rate (ORR) and safety. Translational sub-studies included cell free plasma DNA sequencing and functional genomic screening using an epigenetically-targeted CRISPR/Cas9 library to identify response predictors. Among 20 predominantly relapsed/refractory patients, the ORR was 40% (10% complete responses). Most frequent grade 3-4 adverse events were neutropenia and thrombocytopenia. At 10 months median follow-up, median progression free survival (PFS) and overall survival (OS) were 2.9 and 10.4 months respectively. RHOA G17V mutations associated with improved PFS (median 5.47 vs. 1.35 months; Wilcoxon p = 0.02, Log-Rank p = 0.06). 4/7 patients with TP53 variants responded. Deletion of the histone methyltransferase SETD2 sensitised to HMA but TET2 deletion did not. Guadecitabine conveyed an acceptable ORR and toxicity profile; decitabine analogues may provide a backbone for future combinatorial regimens co-targeting histone methyltransferases., (© 2022. The Author(s).)

This study explores the natural history of vestibular, trigeminal and lower cranial nerve schwannomas (VS, TS, LCNS) in patients with Neurofibromatosis type 2 (NF2), to understand how pathogenic variants (PVs) of the NF2 gene affect tumour burden and growth rate, via a retrospective analysis of a UK NF2 centre database and imaging. VS, TS and LCNS location and size were measured in accordance with a standardised protocol. PVs were categorised in accordance with the UK NF2 Genetic Severity Score (GSS). 153 patients (age 5-82) had 458 schwannomas, of which 362 were previously untreated comprising: 204 VS, 93 TS, and 65 LCNS (IX, X, XI). 322 schwannomas had sequential imaging allowing growth rate analysis with a mean follow-up of 45 months. VS were universally present, and bilateral in 146/153 cases. 65% of tumours grew >2 mm during the study period at mean rate 2.0 mm/year. Significant association was found between increasing GSS and growth rate. TS occurred in 66/153 patients (bilateral in 27/153); 31% of tumours showed growth (mean 1.8 mm/yr). Significant increase in tumour prevalence was noted with increasing GSS. LCNS were found in 47/153 patients (bilateral in 19/153); 27% of tumours showed growth (mean 1.9 mm/yr). The trend for increased prevalence with increasing GSS did not reach significance. VS growth rate was significantly influenced by GSS and they were much more likely to grow than TS and LCNS. TS prevalence also correlated with increasing GSS., (© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)

Objective: To compare short term respiratory outcomes in preterm infants treated with bovine lipid extract surfactant or poractant alfa., Study Design: Prospective comparative effectiveness cohort study of infants <32 weeks' gestational age requiring surfactant in thirteen centers. Each center provided bovine lipid extract surfactant for a set period of time in the year 2019 and then changed to poractant alfa for the remainder of the year. The primary outcome was total duration of respiratory support., Result: 968 infants were included. 494 received bovine lipid extract surfactant and 474 received poractant alfa. No difference was observed in the total duration of respiratory support (mechanical ventilation or non-invasive) (median 38 vs 40.5 days), need to re-dose surfactant, bronchopulmonary dysplasia, survival to discharge, or length of admission., Conclusion: In this pragmatic study, we did not identify any difference in short term outcomes between the groups based on the type of surfactant received., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

In the past decades, considerable attention has been directed toward anaerobic digestion (AD), which is an effective biological process for converting diverse organic wastes into biogas, volatile fatty acids (VFAs), biohydrogen, etc. The microbial bioprocessing takes part during AD is of substantial significance, and one of the crucial approaches for the deep and adequate understanding and manipulating it toward different products is process microbiology. Due to highly complexity of AD microbiome, it is critically important to study the involved microorganisms in AD. In recent years, in addition to traditional methods, novel molecular techniques and meta-omics approaches have been developed which provide accurate details about microbial communities involved AD. Better understanding of process microbiomes could guide us in identifying and controlling various factors in both improving the AD process and diverting metabolic pathway toward production of selective bio-products. This review covers various platforms of AD process that results in different final products from microbiological point of view. The review also highlights distinctive interactions occurring among microbial communities. Furthermore, assessment of these communities existing in the anaerobic digesters is discussed to provide more insights into their structure, dynamics, and metabolic pathways. Moreover, the important factors affecting microbial communities in each platform of AD are highlighted. Finally, the review provides some recent applications of AD for the production of novel bio-products and deals with challenges and future perspectives of AD.

Objectives: People experiencing homelessness are at increased risk of SARS-CoV-2 infection. This study reports the point prevalence of SARS-CoV-2 infection during testing conducted at sites serving people experiencing homelessness in Toronto during the first wave of the COVID-19 pandemic. We also explored the association between site characteristics and prevalence rates., Methods: The study included individuals who were staying at shelters, encampments, COVID-19 physical distancing sites, and drop-in and respite sites and completed outreach-based testing for SARS-CoV-2 during the period April 17 to July 31, 2020. We examined test positivity rates over time and compared them to rates in the general population of Toronto. Negative binomial regression was used to examine the relationship between each shelter-level characteristic and SARS-CoV-2 positivity rates. We also compared the rates across 3 time periods (T1: April 17-April 25; T2: April 26-May 23; T3: May 24-June 25)., Results: The overall prevalence of SARS-CoV-2 infection was 8.5% (394/4657). Site-specific rates showed great heterogeneity with infection rates ranging from 0% to 70.6%. Compared to T1, positivity rates were 0.21 times lower (95% CI: 0.06-0.75) during T2 and 0.14 times lower (95% CI: 0.04-0.44) during T3. Most cases were detected during outbreak testing (384/394 [97.5%]) rather than active case finding., Conclusion: During the first wave of the pandemic, rates of SARS-CoV-2 infection at sites for people experiencing homelessness in Toronto varied significantly over time. The observation of lower rates at certain sites may be attributable to overall time trends, expansion of outreach-based testing to include sites without known outbreaks, and/or individual site characteristics., (© 2021. The Author(s).)

The hepatitis C virus (HCV) is a common cause of chronic liver disease and liver cancer worldwide. Despite advances in curative therapies for HCV, the incidence of new infections is not decreasing at the expected rate to hit the World Health Organization (WHO) target for the elimination of HCV by 2030. In fact, there are still more new cases of infection in the United States and worldwide than are being cured. The reasons for the rise in new cases include poor access to care and the opioid epidemic. The clinical burden of HCV requires a multimodal approach to eradicating the infection. Vaccination would be an excellent tool to prevent incidence of new infections; however, the genetic diversity of HCV and its ability to generate quasispecies within an infected host make creating a broadly reactive vaccine difficult. Multiple vaccine candidates have been identified, but to date, there has not been a target that has led to a broadly reactive vaccine, though several of the candidates are promising. Additionally, the virus is very difficult to culture and testing candidates in humans or chimpanzees is ethically challenging. Despite the multiple barriers to creating a vaccine, vaccination still represents an important tool in the fight against HCV.

Bronchopulmonary dysplasia (BPD) is the most prevalent and clinically significant complication of prematurity. Accurate identification of at-risk infants would enable ongoing intervention to improve outcomes. Although postnatal exposures are known to affect an infant's likelihood of developing BPD, most existing BPD prediction models do not allow risk to be evaluated at different time points, and/or are not suitable for use in ethno-diverse populations. A comprehensive approach to developing clinical prediction models avoids assumptions as to which method will yield the optimal results by testing multiple algorithms/models. We compared the performance of machine learning and logistic regression models in predicting BPD/death. Our main cohort included infants <33 weeks' gestational age (GA) admitted to a Canadian Neonatal Network site from 2016 to 2018 ( n = 9,006) with all analyses repeated for the <29 weeks' GA subcohort ( n = 4,246). Models were developed to predict, on days 1, 7, and 14 of admission to neonatal intensive care, the composite outcome of BPD/death prior to discharge. Ten-fold cross-validation and a 20% hold-out sample were used to measure area under the curve (AUC). Calibration intercepts and slopes were estimated by regressing the outcome on the log-odds of the predicted probabilities. The model AUCs ranged from 0.811 to 0.886. Model discrimination was lower in the <29 weeks' GA subcohort (AUCs 0.699-0.790). Several machine learning models had a suboptimal calibration intercept and/or slope (k-nearest neighbor, random forest, artificial neural network, stacking neural network ensemble). The top-performing algorithms will be used to develop multinomial models and an online risk estimator for predicting BPD severity and death that does not require information on ethnicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Khurshid, Coo, Khalil, Messiha, Ting, Wong and Shah.)

Competing Interests: The authors report no conflicts of interest.