Genetics and Evolution of Bird Migration.

Bird migration has long been a subject of fascination for humankind and is a behavior that is both intricate and multifaceted. In recent years, advances in technology, particularly in the fields of genomics and animal tracking, have enabled significant progress in our understanding of this phenomenon. In this review, we provide an overview of the latest advancements in the genetics of bird migration, with a particular focus on genomics, and examine various factors that contribute to the evolution of this behavior, including climate change. Integration of research from the fields of genomics, ecology, and evolution can enhance our comprehension of the complex mechanisms involved in bird migration and inform conservation efforts in a rapidly changing world.

Post-COVID-19 Condition in Children 6 and 12 Months After Infection.

Importance: There is a need to understand the long-term outcomes among children infected with SARS-CoV-2. Objective: To quantify the prevalence of post-COVID-19 condition (PCC) among children tested for SARS-CoV-2 infection in pediatric emergency departments (EDs). Design, Setting, and Participants: Multicenter, prospective cohort study at 14 Canadian tertiary pediatric EDs that are members of the Pediatric Emergency Research Canada network with 90-day, 6-month, and 12-month follow-up. Participants were children younger than 18 years who were tested for SARS-CoV-2 infection between August 2020 and February 2022. Data were analyzed from May to November 2023. Exposure: The presence of SARS-CoV-2 infection at or within 14 days of the index ED visit. Main Outcomes and Measures: Presence of symptoms and QoL reductions that meet the PCC definition. This includes any symptom with onset within 3 months of infection that is ongoing at the time of follow-up and affects everyday functioning. The outcome was quantified at 6 and 12 months following the index ED visit. Results: Among the 5147 children at 6 months (1152 with SARS-CoV-2 positive tests and 3995 with negative tests) and 5563 children at 12 months (1192 with SARS-CoV-2 positive tests and 4371 with negative tests) who had sufficient data regarding the primary outcome to enable PCC classification, the median (IQR) age was 2.0 (0.9-5.0) years, and 2956 of 5563 (53.1%) were male. At 6-month follow-up, symptoms and QoL changes consistent with the PCC definition were present in 6 of 1152 children with positive SARS-CoV-2 tests (0.52%) and 4 of 3995 children with negative SARS-CoV-2 tests (0.10%; absolute risk difference, 0.42%; 95% CI, 0.02% to 0.94%). The PCC definition was met at 12 months by 8 of 1192 children with positive SARS-CoV-2 tests (0.67%) and 7 of 4371 children with negative SARS-CoV-2 tests (0.16%; absolute risk difference, 0.51%; 95% CI, 0.06 to 1.08%). At 12 months, the median (IQR) PedsQL Generic Core Scale scores were 98.4 (90.0-100) among children with positive SARS-CoV-2 tests and 98.8 (91.7-100) among children with negative SARS-CoV-2 tests (difference, -0.3; 95% CI, -1.5 to 0.8; P = .56). Among the 8 children with SARS-CoV-2 positive tests and PCC at 12-month follow-up, children reported respiratory (7 of 8 patients [88%]), systemic (3 of 8 patients [38%]), and neurologic (1 of 8 patients [13%]) symptoms. Conclusions and Relevance: In this cohort study of children tested for SARS-CoV-2 infection in Canadian pediatric EDs, although children infected with SARS-CoV-2 reported increased chronic symptoms, few of these children developed PCC, and overall QoL did not differ from children with negative SARS-CoV-2 tests.

Whole-genome survey reveals extensive variation in genetic diversity and inbreeding levels among peregrine falcon subspecies.

In efforts to prevent extinction, resource managers are often tasked with increasing genetic diversity in a population of concern to prevent inbreeding depression or improve adaptive potential in a changing environment. The assumption that all small populations require measures to increase their genetic diversity may be unwarranted, and limited resources for conservation may be better utilized elsewhere. We test this assumption in a case study focused on the peregrine falcon (Falco peregrinus), a cosmopolitan circumpolar species with 19 named subspecies. We used whole-genome resequencing to generate over two million single nucleotide polymorphisms (SNPs) from multiple individuals of all peregrine falcon subspecies. Our analyses revealed extensive variation among subspecies, with many island-restricted and nonmigratory populations possessing lower overall genomic diversity, elevated inbreeding coefficients (F ROH)-among the highest reported, and extensive runs of homozygosity (ROH) compared to mainland and migratory populations. Similarly, the majority of subspecies that are either nonmigratory or restricted to islands show a much longer history of low effective population size (N e). While mutational load analyses indicated an increased proportion of homozygous-derived deleterious variants (i.e., drift load) among nonmigrant and island populations compared to those that are migrant or reside on the mainland, no significant differences in the proportion of heterozygous deleterious variants (i.e., inbreeding load) was observed. Our results provide evidence that high levels of inbreeding may not be an existential threat for some populations or taxa. Additional factors such as the timing and severity of population declines are important to consider in management decisions about extinction potential.

A rare finding of bilateral facial canal meningoceles involving the tympanic segment in suspected idiopathic intracranial hypertension.

Meningoceles are a common radiological feature found in cases of idiopathic intracranial hypertension (IIH). Rarely, they can affect the facial canal within the petrous temporal bone, leading to symptoms such as facial nerve palsy, hearing loss or meningitis. This is the first case report that describes bilateral facial canal meningoceles involving the tympanic segment of the canal. Prominent Meckel's caves were also seen on MRI, a feature commonly associated with IIH.

Understanding elite rugby league players' experience of collision, effective contact coaching techniques, and player contact psychology: A focus group study.

The current study performed a series of online focus groups to understand elite rugby league players' experiences of collision. Eighteen rugby league players comprising different playing positions from four teams were recruited to participate in a series of online focus groups, via the Microsoft Team's platform, facilitated by a moderator. Players were competing in Europe's elite rugby league competition, the European Super League (ESL), during the 2021 season. All focus group data were transcribed, coded and analysed using reflexive thematic analysis guide to ensure robust exploring, interpreting and reporting through pattern-based analysis. The findings are split into five key themes: 1) the three-man tackle - the perceived optimal defensive strategy with simultaneous contact, 2) not all collisions are the same; matchplay events change the collision intensity, 3) bracing and blindsiding - two factors that influence experiences of collision and concussion, 4) coaching philosophies and orientations, 5) psychological readiness for collision. Collision sports have an inherent risk of injury; however, in some players' subjective experiences, there are collision types that have a greater association with risk or intensity (blind-sided collisions or long closing distances). It is essential that future research comprehends the effects of these collision types and the further themes.

Canadian Anaphylaxis Network-Predicting Recurrence after Emergency Presentation for Allergic REaction (CAN-PREPARE): a prospective, cohort study protocol.

INTRODUCTION: Anaphylaxis is a severe, potentially fatal multiorgan system manifestation of an allergic reaction. The highest incidence of anaphylaxis is in children and adolescents. Biphasic anaphylaxis (BA) is defined as the recurrence of allergic symptoms after resolution of an initial reaction. It has been reported to occur in 10%-20% of cases within 1-48 hours from the onset of the initial reaction. The dilemma for physicians is determining which patients with resolved anaphylaxis should be observed for BA and for how long. Guidelines for duration of postanaphylaxis monitoring vary, are based on limited evidence and can have unintended negative impacts on patient safety, quality of life and healthcare resources. The objectives of this study are to derive a prognostic model for BA and to develop a risk-scoring system that informs disposition decisions of children who present to emergency departments (ED) with anaphylaxis. METHODS AND ANALYSIS: This prospective multicentre cohort study will enrol 1682 patients from seven paediatric EDs that are members of the Paediatric Emergency Research Canada network. We will enrol patients younger than 18 years of age with an allergic reaction meeting anaphylaxis diagnostic criteria. Trained ED research assistants will screen, obtain consent and prospectively collect study data. Research assistants will follow patients during their ED visit and ascertain, in conjunction with the medical team, if the patient develops BA. A standardised follow-up survey conducted following study enrolment will determine if a biphasic reaction occurred after ED disposition. Model development will conform to the broad principles of the PROGRESS (Prognosis Research Strategy) framework and reporting will follow the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis Statement. ETHICS AND DISSEMINATION: Ethics approval has been received from all participating centres. Our dissemination plan focuses on informing clinicians, policy makers and parents of the results through publication in peer-reviewed journals and broadcasting on multiple media platforms. TRIAL REGISTRATION NUMBER: NCT05135377.

Arctic introgression and chromatin regulation facilitated rapid Qinghai-Tibet Plateau colonization by an avian predator.

The Qinghai-Tibet Plateau (QTP), possesses a climate as cold as that of the Arctic, and also presents uniquely low oxygen concentrations and intense ultraviolet (UV) radiation. QTP animals have adapted to these extreme conditions, but whether they obtained genetic variations from the Arctic during cold adaptation, and how genomic mutations in non-coding regions regulate gene expression under hypoxia and intense UV environment, remain largely unknown. Here, we assemble a high-quality saker falcon genome and resequence populations across Eurasia. We identify female-biased hybridization with Arctic gyrfalcons in the last glacial maximum, that endowed eastern sakers with alleles conveying larger body size and changes in fat metabolism, predisposing their QTP cold adaptation. We discover that QTP hypoxia and UV adaptations mainly involve independent changes in non-coding genomic variants. Our study highlights key roles of gene flow from Arctic relatives during QTP hypothermia adaptation, and cis-regulatory elements during hypoxic response and UV protection.

How safe are paediatric emergency departments? A national prospective cohort study.

BACKGROUND: Despite the high number of children treated in emergency departments, patient safety risks in this setting are not well quantified. Our objective was to estimate the risk and type of adverse events, as well as their preventability and severity, for children treated in a paediatric emergency department. METHODS: Our prospective, multicentre cohort study enrolled children presenting for care during one of 168 8-hour study shifts across nine paediatric emergency departments. Our primary outcome was an adverse event within 21 days of enrolment which was related to care provided at the enrolment visit. We identified 'flagged outcomes' (such as hospital visits, worsening symptoms) through structured telephone interviews with patients and families over the 21 days following enrolment. We screened admitted patients' health records with a validated trigger tool. For patients with flags or triggers, three reviewers independently determined whether an adverse event occurred. RESULTS: We enrolled 6376 children; 6015 (94%) had follow-up data. Enrolled children had a median age of 4.3 years (IQR 1.6-9.8 years). One hundred and seventy-nine children (3.0%, 95% CI 2.6% to 3.5%) had at least one adverse event. There were 187 adverse events in total; 143 (76.5%, 95% CI 68.9% to 82.7%) were deemed preventable. Management (n=98, 52.4%) and diagnostic issues (n=36, 19.3%) were the most common types of adverse events. Seventy-nine (42.2%) events resulted in a return emergency department visit; 24 (12.8%) resulted in hospital admission; and 3 (1.6%) resulted in transfer to a critical care unit. CONCLUSION: In this large-scale study, 1 in 33 children treated in a paediatric emergency department experienced an adverse event related to the care they received there. The majority of events were preventable; most were related to management and diagnostic issues. Specific patient populations were at higher risk of adverse events. We identify opportunities for improvement in care.

Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.

Importance: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. Objectives: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. Design, Setting, and Participants: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. Exposure: SARS-CoV-2 detected via nucleic acid testing. Main Outcomes and Measures: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. Results: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

Outcomes of SARS-CoV-2-Positive Youths Tested in Emergency Departments: The Global PERN-COVID-19 Study.

Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized. Objective: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED). Design, Setting, and Participants: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. Exposures: Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing. Main Outcomes and Measures: Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death. Results: Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%). Conclusions and Relevance: In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.

A Target Population Derived Method for Developing a Competency Standard in Radiograph Interpretation.

CONSTRUCT: For assessing the skill of visual diagnosis such as radiograph interpretation, competency standards are often developed in an ad hoc method, with a poorly delineated connection to the target clinical population. BACKGROUND: Commonly used methods to assess for competency in radiograph interpretation are subjective and potentially biased due to a small sample size of cases, subjective evaluations, or include an expert-generated case-mix versus a representative sample from the clinical field. Further, while digital platforms are available to assess radiograph interpretation skill against an objective standard, they have not adopted a data-driven competency standard which informs educators and the public that a physician has achieved adequate mastery to enter practice where they will be making high-stakes clinical decisions. APPROACH: Operating on a purposeful sample of radiographs drawn from the clinical domain, we adapted the Ebel Method, an established standard setting method, to ascertain a defensible, clinically relevant mastery learning competency standard for the skill of radiograph interpretation as a model for deriving competency thresholds in visual diagnosis. Using a previously established digital platform, emergency physicians interpreted pediatric musculoskeletal extremity radiographs. Using one-parameter item response theory, these data were used to categorize radiographs by interpretation difficulty terciles (i.e. easy, intermediate, hard). A panel of emergency physicians, orthopedic surgeons, and plastic surgeons rated each radiograph with respect to clinical significance (low, medium, high). These data were then used to create a three-by-three matrix where radiographic diagnoses were categorized by interpretation difficulty and significance. Subsequently, a multidisciplinary panel that included medical and parent stakeholders determined acceptable accuracy for each of the nine cells. An overall competency standard was derived from the weighted sum. Finally, to examine consequences of implementing this standard, we reported on the types of diagnostic errors that may occur by adhering to the derived competency standard. FINDINGS: To determine radiograph interpretation difficulty scores, 244 emergency physicians interpreted 1,835 pediatric musculoskeletal extremity radiographs. Analyses of these data demonstrated that the median interpretation difficulty rating of the radiographs was -1.8 logits (IQR -4.1, 3.2), with a significant difference of difficulty across body regions (p < 0.0001). Physician review classified the radiographs as 1,055 (57.8%) as low, 424 (23.1%) medium or 356 (19.1%) high clinical significance. The multidisciplinary panel suggested a range of acceptable scores between cells in the three-by-three table of 76% to 95% and the sum of equal-weighted scores resulted in an overall performance-based competency score of 85.5% accuracy. Of the 14.5% diagnostic interpretation errors that may occur at the bedside if this competency standard were implemented, 9.8% would be in radiographs of low-clinical significance, while 2.5% and 2.3% would be in radiographs of medium or high clinical significance, respectively. CONCLUSION(S): This study's novel integration of radiograph selection and a standard setting method could be used to empirically drive evidence-based competency standard for radiograph interpretation and can serve as a model for deriving competency thresholds for clinical tasks emphasizing visual diagnosis.

Evaluation of injectable nucleus augmentation materials for the treatment of intervertebral disc degeneration.

Back pain affects a person's health and mobility as well as being associated with large health and social costs. Lower back pain is frequently caused by degeneration of the intervertebral disc. Current operative and non-operative treatments are often ineffective and expensive. Nucleus augmentation is designed to be a minimally invasive method of restoring the disc to its native healthy state by restoring the disc height, and mechanical and/or biological properties. The majority of the candidate materials for nucleus augmentation are injectable hydrogels. In this review, we examine the materials that are currently under investigation for nucleus augmentation, and compare their ability to meet the design requirements for this application. Specifically, the delivery of the material into the disc, the mechanical properties of the material and the biological compatibility are examined. Recommendations for future testing are also made.

The Community Health and Social Medicine Incubator: a service-learning framework for medical student-led projects.

The Community Health and Social Medicine (CHASM) Incubator is a social impact venture that gives medical and other health care students the opportunity to develop initiatives that sustainably promote health equity for, and in partnership with, community partners and historically marginalized communities. Students learn how to develop projects with project management curricula, are paired with community health mentors, and are given seed micro-financing. As the first community health incubator driven by medical students, CHASM provides a framework for students interested in implementing sustainable solutions to local health disparities which extends the service-learning opportunities offered in existing curricula.

L'incubateur CHASM (Community Health and Social Medicine) est une initiative visant à créer un impact social en donnant aux étudiants en médecine et des autres sciences de la santé la possibilité de développer des initiatives durables en collaboration avec des partenaires communautaires et des communautés historiquement marginalisées. CHASM met en valeur l'équité en matière de santé. Les étudiants apprennent à élaborer des projets via un cursus de gestion de projet, sont jumelés à des mentors en santé communautaire et bénéficient de micro-financement de départ. Ce premier incubateur de santé communautaire mené par des étudiants en médecine fournit un cadre aux étudiants qui souhaitent mettre en œuvre des solutions durables aux inégalités en matière de santé. Il élargit également les possibilités d'apprentissage par le service offertes dans les cursus existants.

CLiP, catheter and line position dataset.

Correct catheter position is crucial to ensuring appropriate function of the catheter and avoid complications. This paper describes a dataset consisting of 50,612 image level and 17,999 manually labelled annotations from 30,083 chest radiographs from the publicly available NIH ChestXRay14 dataset with manually annotated and segmented endotracheal tubes (ETT), nasoenteric tubes (NET) and central venous catheters (CVCs).

Split-enzyme immunoassay to monitor EGFR-HER2 heterodimerization on cell surfaces.

Over 30,000 protein-protein interactions with pathological implications have been identified; yet, discovering and investigating drugs that target these specific interactions is greatly limited by the inability to monitor native protein-protein interactions (PPIs) efficiently. The two most frequently used tools to monitor PPIs, resonance-energy transfer (RET) assays and protein complementation assays (PCA), face significant limitations. RET assays have a narrow working range of 10 to 50 Å, while PCA require permanent attachment of a reporter probe to a protein of interest by chemical conjugation or genetic engineering. We developed a non-invasive assay platform to measure PPIs without modifications to the proteins of interest and is functional at a greater working range than RET assays. We demonstrate our approach by monitoring the EGFR-HER2 heterodimerization on relevant cell surfaces, utilizing various EGFR- and HER2-specific binders (e.g., Fab, DARPin, and VHH) fused with small fragments of a tri-part split-luciferase derived from NanoLuc®. Following independent binding of the binder fusions to their respective targets, the dimerization of EGFR and HER2 induces complementation of the luciferase fragments into a functional native structure, producing glow-type luminescence. We have confirmed the functionality of the platform to monitor EGFR-HER2 dimerization induction and inhibition. STATEMENT OF SIGNIFICANCE: We describe a platform technology for rapid monitoring of protein-protein interactions (PPIs). Our approach is uses a luciferase split into three parts - two short peptide "tags" and a large third fragment. Each of the short peptides can be fused to antibodies which bind to domains of a target antigens which orients the two tags and facilitates refolding of an active enzyme. To our knowledge this is the first example of a split-enzyme used to monitor PPIs without requiring any modification of the target proteins. We demonstrate our approach on the important PPI of HER2 and EGFR. Significantly, we quantify stimulation and inhibition of these partners, opening the possibility of using our approach to assess potential drugs without engineering cells.

Effect of the COVID-19 Pandemic on Patient Volumes, Acuity, and Outcomes in Pediatric Emergency Departments: A Nationwide Study.

OBJECTIVES: The aim of this study was to quantify the effect of the COVID-19 pandemic on pediatric emergency department (ED) utilization and outcomes. METHODS: This study is an interrupted-time-series observational study of children presenting to 11 Canadian tertiary-care pediatric EDs. Data were grouped into weeks in 3 study periods: prepandemic (January 1, 2018-January 27, 2020), peripandemic (January 28, 2020-March 10, 2020), and early pandemic (March 11, 2020-April 30, 2020). These periods were compared with the same time intervals in the 2 preceding calendar years. Primary outcomes were number of ED visits per week. The secondary outcomes were triage acuity, hospitalization, intensive care unit (ICU) admission, mortality, length of hospital stay, ED revisits, and visits for trauma and mental health concerns. RESULTS: There were 577,807 ED visits (median age, 4.5 years; 52.9% male). Relative to the prepandemic period, there was a reduction [-58%; 95% confidence interval (CI), -63% to -51%] in the number of ED visits during the early-pandemic period, with concomitant higher acuity. There was a concurrent increase in the proportion of ward [odds ratio (OR), 1.39; 95% CI, 1.32-1.45] and intensive care unit (OR, 1.20; 95% CI, 1.01-1.42) admissions, and trauma-related ED visits among children less than 10 years (OR, 1.51; 95% CI, 1.45-1.56). Mental health-related visits in children declined in the early-pandemic period (in <10 years, -60%; 95% CI, -67% to -51%; in children ≥10 years: -56%; 95% CI, -63% to -47%) relative to the pre-COVID-19 period. There were no differences in mortality or length of stay; however, ED revisits within 72 hours were reduced during the early-pandemic period (percent change: -55%; 95% CI, -61% to -49%; P < 0.001). CONCLUSIONS: After the declaration of the COVID-19 pandemic, dramatic reductions in pediatric ED visits occurred across Canada. Children seeking ED care were sicker, and there was an increase in trauma-related visits among children more than 10 years of age, whereas mental health visits declined during the early-pandemic period. When faced with a future pandemic, public health officials must consider the impact of the illness and the measures implemented on children's health and acute care needs.

Homogeneous Immunoassay Using a Tri-Part Split-Luciferase for Rapid Quantification of Anti-TNF Therapeutic Antibodies.

Anti-TNF therapeutics bind and sequester tumor necrosis factor (TNF) to prevent downstream signaling and are clinically important in the treatment of several autoimmune diseases. Effective treatment with these drugs requires frequent therapeutic drug monitoring (TDM). Current analytical methods, including reporter gene assay (RGA), enzyme-linked immunosorbent assay (ELISA), and mobility shift assay (MSA), can be technically rigorous, slow, and expensive. These qualities prevent the implementation of point-of-care testing and ultimately limit the frequency and utility of monitoring. An assay simple enough to be performed in the clinic would enable increased TDM frequency, more accurate dosing, and improved patient outcomes. Toward this end, we developed a homogeneous immunoassay based on a tri-part split-luciferase system for "add-and-read" detection of anti-TNF therapeutics. In our platform, two small fragments of the split-luciferase, called ß9 and ß10, are each fused to a different interacting protein. The binding of each of these proteins to anti-TNF antibodies forces the split-luciferase components into proximity where they reform the active luciferase. We identified the fusion proteins, ß9-protein A (ß9-A) and ß10-TNF, as promising binding pairs. We systematically adjusted assay conditions to optimize the signal/background (S/B) ratio, limit of detection (LOD), and percent recovery. The assay has a large dynamic range (0.5-32 µg/mL) and is sensitive enough to monitor both subtherapeutic and supratherapeutic serum concentrations of anti-TNF antibodies, as demonstrated in clinical samples.

Re-introduction of the Saker Falcon (Falco cherrug) in Bulgaria - preliminary results from the ongoing establishment phase by 2020.

Considered extinct as breeding species in the early 2000s, the Saker Falcon was recovered when the first active nest from the new history of the species in Bulgaria was discovered in 2018, formed of two birds that were re-introduced back in 2015. Currently, there is only one confirmed wild breeding pair in the country - the male from 2015 with a female changed in 2020, released again as a part of the programme, in 2016. This is a report on the preliminary results and analysis of the ongoing establishment phase of the re-introduction of the Saker Falcon (Falco cherrug) in Bulgaria - first ever performed for this species in the country and globally. The period studied is 2015-2020. Following the re-introduction activities started in 2011, the current phase is defined by standardised methodology and a unified approach. Analysed and presented are methods for captive breeding and hacking, the breeding performance of the falcons, the number of released individuals, data from the post-fledging dependence period and a model of population growth.