A joint NCBI and EMBL-EBI transcript set for clinical genomics and research.

Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE1 and RefSeq2 launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref. 3) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation.

Database resources of the National Center for Biotechnology Information.

The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for most of these databases. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, SciENcv, the NIH Comparative Genomics Resource (CGR), NCBI Virus, SRA, RefSeq, foreign contamination screening tools, Taxonomy, iCn3D, ClinVar, GTR, MedGen, dbSNP, ALFA, ClinicalTrials.gov, Pathogen Detection, antimicrobial resistance resources, and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.

RefSeq Functional Elements as experimentally assayed nongenic reference standards and functional interactions in human and mouse.

Eukaryotic genomes contain many nongenic elements that function in gene regulation, chromosome organization, recombination, repair, or replication, and mutation of those elements can affect genome function and cause disease. Although numerous epigenomic studies provide high coverage of gene regulatory regions, those data are not usually exposed in traditional genome annotation and can be difficult to access and interpret without field-specific expertise. The National Center for Biotechnology Information (NCBI) therefore provides RefSeq Functional Elements (RefSeqFEs), which represent experimentally validated human and mouse nongenic elements derived from the literature. The curated data set is comprised of richly annotated sequence records, descriptive records in the NCBI Gene database, reference genome feature annotation, and activity-based interactions between nongenic regions, target genes, and each other. The data set provides succinct functional details and transparent experimental evidence, leverages data from multiple experimental sources, is readily accessible and adaptable, and uses a flexible data model. The data have multiple uses for basic functional discovery, bioinformatics studies, genetic variant interpretation; as known positive controls for epigenomic data evaluation; and as reference standards for functional interactions. Comparisons to other gene regulatory data sets show that the RefSeqFE data set includes a wider range of feature types representing more areas of biology, but it is comparatively smaller and subject to data selection biases. RefSeqFEs thus provide an alternative and complementary resource for experimentally assayed functional elements, with future data set growth expected.

Database resources of the National Center for Biotechnology Information in 2023.

The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for most of these databases. New resources include the Comparative Genome Resource (CGR) and the BLAST ClusteredNR database. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, IgBLAST, GDV, RefSeq, NCBI Virus, GenBank type assemblies, iCn3D, ClinVar, GTR, dbGaP, ALFA, ClinicalTrials.gov, Pathogen Detection, antimicrobial resistance resources, and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.

Two months outcomes following delirium in the pediatric intensive care unit.

The lasting consequences of delirium in children are not well characterized. This study aimed to compare the two-month outcomes in pediatric intensive care unit (PICU) survivors according to the presence of delirium. Post-hoc analysis of a single-center prospective study of mechanically ventilated (invasive ventilation or non-invasive ventilation) children followed at the CHU Sainte-Justine PICU follow-up clinic two months after PICU discharge, between October 2018 and August 2022. Delirium was defined as one or more Cornell Assessment of Pediatric Delirium (CAPD) scores ≥ 9. Primary outcome was survivors' quality of life and secondary outcomes were sleep and posttraumatic stress and anxiety and depression in parents. Multivariable linear and logistic regression models assessed the independent associations between delirium and outcomes while adjusting for age, sex, comorbidity, diagnosis, severity of illness, PICU length of stay, and invasive mechanical ventilation. Of the 179 children included over a 47 month-period, 117 (65.4%) had delirium. Children with delirium were more commonly intubated (91.5% vs. 30.7%, p < 0.001) and had higher PELOD-2 scores (10 vs. 4, p < 0.001). On multivariable analysis, delirium was associated with a decreased quality of life at 2.3 months post discharge (p = 0.03). The severity of the delirium episode (higher scores of CAPD) was associated with a higher likelihood of sleep disturbances (OR 1.13, p = 0.01) and parental anxiety (OR 1.16, p = 0.01), in addition to lower quality of life (p = 0.03).Conclusions: Two months following their PICU stay, children with delirium had a lower quality of life, suggesting a lasting effect of delirium on children and their families.

Iron Deficiency in Anemic Children Surviving Critical Illness: Post Hoc Analysis of a Single-Center Prospective Cohort in Canada, 2019-2022.

OBJECTIVES: Many children leave the PICU with anemia. The mechanisms of post-PICU anemia are poorly investigated, and treatment of anemia, other than blood, is rarely started during PICU. We aimed to characterize the contributions of iron depletion (ID) and/or inflammation in the development of post-PICU anemia and to explore the utility of hepcidin (a novel iron marker) at detecting ID during inflammation. DESIGN: Post hoc analysis of a single-center prospective study (November 2019 to September 2022). SETTING: PICU, quaternary center, Canada. PATIENTS: Children admitted to PICU with greater than or equal to 48 hours of invasive or greater than or equal to 96 hours of noninvasive ventilation. We excluded patients with preexisting conditions causing anemia or those admitted after cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hematological and iron profiles were performed at PICU discharge on 56 participants of which 37 (37/56) were diagnosed with anemia. Thirty-three children (33/56; 59%) were younger than 2 years. Median Pediatric Logistic Organ Dysfunction score was 11 (interquartile range, 6-16). Twenty-four of the 37 anemic patients had repeat bloodwork 2 months post-PICU. Of those, four (4/24; 16%) remained anemic. Hematologic profiles were categorized as: anemia of inflammation (AI), iron deficiency anemia (IDA), IDA with inflammation, and ID (low iron stores without anemia). Seven (7/47; 15%) had AI at discharge, and one had persistent AI post-PICU. Three patients (3/47; 6%) had IDA at discharge; of which one was lost to follow-up and the other two were no longer anemic but had ID post-PICU. Eleven additional patients developed ID post-PICU. In the exploratory analysis, we identified a diagnostic cutoff value for ID during inflammation from the receiver operating characteristic curve for hepcidin of 31.9 pg/mL. This cutoff would increase the detection of ID at discharge from 6% to 34%. CONCLUSIONS: The burden of ID in children post-PICU is high and better management strategies are required. Hepcidin may increase the diagnostic yield of ID in patients with inflammation.

Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage.

BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU). METHODS: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression. RESULTS: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU. CONCLUSIONS: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages. IMPACT: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage.

Carbon and climate implications of rewetting a raised bog in Ireland.

Peatland rewetting has been proposed as a vital climate change mitigation tool to reduce greenhouse gas emissions and to generate suitable conditions for the return of carbon (C) sequestration. In this study, we present annual C balances for a 5-year period at a rewetted peatland in Ireland (rewetted at the start of the study) and compare the results with an adjacent drained area (represents business-as-usual). Hydrological modelling of the 230-hectare site was carried out to determine the likely ecotopes (vegetation communities) that will develop post-rewetting and was used to inform a radiative forcing modelling exercise to determine the climate impacts of rewetting this peatland under five high-priority scenarios (SSP1-1.9, SS1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5). The drained area (marginal ecotope) was a net C source throughout the study and emitted 157 ± 25.5 g C m-2  year-1 . In contrast, the rewetted area (sub-central ecotope) was a net C sink of 78.0 ± 37.6 g C m-2  year-1 , despite relatively large annual methane emissions post-rewetting (average 19.3 ± 5.2 g C m-2  year-1 ). Hydrological modelling predicted the development of three key ecotopes at the site, with the sub-central ecotope predicted to cover 24% of the site, the sub-marginal predicted to cover 59% and the marginal predicted to cover 16%. Using these areal estimates, our radiative forcing modelling projects that under the SSP1-1.9 scenario, the site will have a warming effect on the climate until 2085 but will then have a strong cooling impact. In contrast, our modelling exercise shows that the site will never have a cooling impact under the SSP5-8.5 scenario. Our results confirm the importance of rapid rewetting of drained peatland sites to (a) achieve strong C emissions reductions, (b) establish optimal conditions for C sequestration and (c) set the site on a climate cooling trajectory.

Characteristics of children admitted to hospital with acute SARS-CoV-2 infection in Canada in 2020.

BACKGROUND: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease. METHODS: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital. RESULTS: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19. INTERPRETATION: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.

PICU Follow-Up Clinic: Patient and Family Outcomes 2 Months After Discharge.

OBJECTIVES: Hospitalization in a PICU is a life-altering experience for children and their families. Yet, little is known about the well-being of these children after their discharge. We are describing the outcome of PICU survivors at a PICU clinic 2 months after discharge. DESIGN: Prospective cohort study. SETTING: PICU and PICU clinic of CHU Sainte-Justine. PATIENTS: Prospective cohort study of children admitted for greater than or equal to 4 days, greater than or equal to 2 days of invasive ventilation, odds ratio greater than or equal to 4 days of noninvasive ventilation at Centre Hospitalier Universitaire Sainte-Justine. PATIENTS: Prospective cohort study of children admitted for greater than or equal to 4 days, greater than or equal to 2 days of invasive ventilation, or greater than or equal to 4 days of noninvasive ventilation at Centre Hospitalier Universitaire Sainte-Justine PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated by a pediatric intensivist 2 months after discharge at the follow-up clinic. They were asked to fill out validated questionnaires. One hundred thirty-two patients were followed from October 2018 to September 2020. The PICU diagnoses were respiratory illness (40.9%), head trauma, and septic shock (7.6%). Average length of PICU stay was 28.5 ± 84.2 days (median 7 d). Sixty-one percent were intubated. Symptoms reported by families were as follows: fatigue (9.9%), sleep disturbances (20.5%), feeding difficulties (12.1%), and voice change and/or stridor (9.8%). Twenty-one percent of school-aged children reported school delays. Twenty-seven children demonstrated communication delays, 45% gross motor function delays, 41% fine motor delays, 37% delays in problem-solving, and 49% delays in personal-social functioning. Quality of Life scores were 78.1 ± 20.5 and 80.0 ± 17.5 for physical and psychosocial aspects, respectively. Fourteen percent of parents reported financial difficulties, 42% reported symptoms of anxiety, 29% symptoms of depression. CONCLUSIONS: PICU survivors and their families experience significant physical and psychosocial morbidities after their critical illness. PICU follow-up is crucial to determine the outcome of these children and develop interventions.

Consensus coding sequence (CCDS) database: a standardized set of human and mouse protein-coding regions supported by expert curation.

The Consensus Coding Sequence (CCDS) project provides a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assembly in genome annotations produced independently by NCBI and the Ensembl group at EMBL-EBI. This dataset is the product of an international collaboration that includes NCBI, Ensembl, HUGO Gene Nomenclature Committee, Mouse Genome Informatics and University of California, Santa Cruz. Identically annotated coding regions, which are generated using an automated pipeline and pass multiple quality assurance checks, are assigned a stable and tracked identifier (CCDS ID). Additionally, coordinated manual review by expert curators from the CCDS collaboration helps in maintaining the integrity and high quality of the dataset. The CCDS data are available through an interactive web page (https://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi) and an FTP site (ftp://ftp.ncbi.nlm.nih.gov/pub/CCDS/). In this paper, we outline the ongoing work, growth and stability of the CCDS dataset and provide updates on new collaboration members and new features added to the CCDS user interface. We also present expert curation scenarios, with specific examples highlighting the importance of an accurate reference genome assembly and the crucial role played by input from the research community.

Le diagnostic et la prise en charge du sepsis grave chez le patient pédiatrique.

Le sepsis est une réponse inflammatoire systémique à une infection présumée ou démontrée. Puisque c'est une cause importante de morbidité et de mortalité, plusieurs sociétés professionnelles ont lancé des initiatives ces dernières années, lesquelles ont débouché sur la rédaction de directives pour déceler le sepsis et le traiter rapidement. Les principaux aspects des directives les plus récentes sont résumés dans le présent point de pratique. Ils incluent la détection de changements à l'état clinique et aux signes vitaux qui doivent évoquer la possibilité de sepsis, tels que la fièvre, la tachycardie et des modifications de la perfusion périphérique, de même que la stabilisation initiale des voies respiratoires, de la respiration et de la circulation. Ils englobent également l'administration opportune d'une thérapie antimicrobienne, l'utilisation de bolus liquidiens et de médicaments vasoactifs et des considérations particulières chez les patients atteints de troubles médicaux sous-jacents, comme l'emploi de corticoïdes pour traiter une possible insuffisance surrénalienne découlant d'une suppression de l'axe hypothalamo-surrénalien. Deux modifications sont apportées aux directives précédentes, soit une réévaluation clinique après chaque bolus liquidien en raison de la crainte d'une surcharge hydrique et le remplacement de la dopamine comme agent vasoactif initial chez les patients pédiatriques hypotendus par de l'adrénaline ou de la noradrénaline en fonction du contexte clinique. Le présent point de pratique porte principalement sur la prise en charge du sepsis chez les nourrissons plus âgés, les enfants et les adolescents.

Diagnosis and management of severe sepsis in the paediatric patient.

Sepsis is a systemic inflammatory response to suspected or proven infection. Given its importance in terms of morbidity and mortality, a number of initiatives by several professional societies in recent years have led to the development of guidelines for the recognition and timely management of sepsis. The principal elements of the most recent guidelines are summarized in this practice point. These elements include recognition of changes in clinical condition and vital signs, such as fever, tachycardia, and changes in peripheral perfusion, which should raise concern for sepsis; initial stabilization of airway, breathing, and circulation; timely administration of empiric antimicrobial therapy; use of fluid boluses and vasoactive medications; and specific considerations in patients with underlying medical conditions, such as the use of corticosteroids for possible adrenal insufficiency due to hypothalamic-adrenal suppression. Two changes from previous guidelines are the concern for fluid overload, implying the need for clinical re-assessment after administration of each fluid bolus, and the removal of dopamine as the initial vasoactive agent for use in hypotensive paediatric patients, with recommendations for the use of epinephrine or norepinephrine as dictated by the clinical context. This practice point focuses primarily on sepsis management in older infants, children, and youth.

Care for Dying Children and Their Families in the PICU: Promoting Clinician Education, Support, and Resilience.

OBJECTIVES: To describe the consequences of workplace stressors on healthcare clinicians in PICU, and strategies for personal well-being, and professional effectiveness in providing high-quality end-of-life care. DATA SOURCES: Literature review, clinical experience, and expert opinion. STUDY SELECTION: A sampling of foundational and current evidence was accessed. DATA SYNTHESIS: Narrative review and experiential reflection. CONCLUSIONS: The well-being of healthcare clinicians in the PICU influences the day-to-day quality and effectiveness of patient care, team functioning, and the retention of skilled individuals in the PICU workforce. End-of-life care, including decision making, can be complicated. Both are major stressors for PICU staff that can lead to adverse personal and professional consequences. Overresponsiveness to routine stressors may be seen in those with moral distress, and underresponsiveness may be seen in those with compassion fatigue or burnout. Ideally, all healthcare professionals in PICU can rise to the day-to-day workplace challenges-responding in an adaptive, effective manner. Strategies to proactively increase resilience and well-being include self-awareness, self-care, situational awareness, and education to increase confidence and skills for providing end-of-life care. Reactive strategies include case conferences, prebriefings in ongoing preidentified situations, debriefings, and other postevent meetings. Nurturing a culture of practice that acknowledges the emotional impacts of pediatric critical care work and celebrates the shared experiences of families and clinicians to build resilient, effective, and professionally fulfilled healthcare professionals thus enabling the provision of high-quality end-of-life care for children and their families.

Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation.

The RefSeq project at the National Center for Biotechnology Information (NCBI) maintains and curates a publicly available database of annotated genomic, transcript, and protein sequence records (http://www.ncbi.nlm.nih.gov/refseq/). The RefSeq project leverages the data submitted to the International Nucleotide Sequence Database Collaboration (INSDC) against a combination of computation, manual curation, and collaboration to produce a standard set of stable, non-redundant reference sequences. The RefSeq project augments these reference sequences with current knowledge including publications, functional features and informative nomenclature. The database currently represents sequences from more than 55,000 organisms (>4800 viruses, >40,000 prokaryotes and >10,000 eukaryotes; RefSeq release 71), ranging from a single record to complete genomes. This paper summarizes the current status of the viral, prokaryotic, and eukaryotic branches of the RefSeq project, reports on improvements to data access and details efforts to further expand the taxonomic representation of the collection. We also highlight diverse functional curation initiatives that support multiple uses of RefSeq data including taxonomic validation, genome annotation, comparative genomics, and clinical testing. We summarize our approach to utilizing available RNA-Seq and other data types in our manual curation process for vertebrate, plant, and other species, and describe a new direction for prokaryotic genomes and protein name management.

Effect of a Pediatric Early Warning System on All-Cause Mortality in Hospitalized Pediatric Patients: The EPOCH Randomized Clinical Trial.

Importance: There is limited evidence that the use of severity of illness scores in pediatric patients can facilitate timely admission to the intensive care unit or improve patient outcomes. Objective: To determine the effect of the Bedside Paediatric Early Warning System (BedsidePEWS) on all-cause hospital mortality and late admission to the intensive care unit (ICU), cardiac arrest, and ICU resource use. Design, Setting, and Participants: A multicenter cluster randomized trial of 21 hospitals located in 7 countries (Belgium, Canada, England, Ireland, Italy, New Zealand, and the Netherlands) that provided inpatient pediatric care for infants (gestational age ≥37 weeks) to teenagers (aged ≤18 years). Participating hospitals had continuous physician staffing and subspecialized pediatric services. Patient enrollment began on February 28, 2011, and ended on June 21, 2015. Follow-up ended on July 19, 2015. Interventions: The BedsidePEWS intervention (10 hospitals) was compared with usual care (no severity of illness score; 11 hospitals). Main Outcomes and Measures: The primary outcome was all-cause hospital mortality. The secondary outcome was a significant clinical deterioration event, which was defined as a composite outcome reflecting late ICU admission. Regression analyses accounted for hospital-level clustering and baseline rates. Results: Among 144 539 patient discharges at 21 randomized hospitals, there were 559 443 patient-days and 144 539 patients (100%) completed the trial. All-cause hospital mortality was 1.93 per 1000 patient discharges at hospitals with BedsidePEWS and 1.56 per 1000 patient discharges at hospitals with usual care (adjusted between-group rate difference, 0.01 [95% CI, -0.80 to 0.81 per 1000 patient discharges]; adjusted odds ratio, 1.01 [95% CI, 0.61 to 1.69]; P = .96). Significant clinical deterioration events occurred during 0.50 per 1000 patient-days at hospitals with BedsidePEWS vs 0.84 per 1000 patient-days at hospitals with usual care (adjusted between-group rate difference, -0.34 [95% CI, -0.73 to 0.05 per 1000 patient-days]; adjusted rate ratio, 0.77 [95% CI, 0.61 to 0.97]; P = .03). Conclusions and Relevance: Implementation of the Bedside Paediatric Early Warning System compared with usual care did not significantly decrease all-cause mortality among hospitalized pediatric patients. These findings do not support the use of this system to reduce mortality. Trial Registration: clinicaltrials.gov Identifier: NCT01260831.

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death-Summary Report.

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada. METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory determination of death literature. Input from these sources drove drafting of actionable questions and Good Practice Statements, as defined by the Grading of Recommendations Assessment, Development, and Evaluation group. We performed additional literature reviews for all actionable questions. Evidence was assessed for quality using Grading of Recommendations Assessment, Development, and Evaluation and then formulated into evidence profiles that informed recommendations through the evidence-to-decision framework. Recommendations were revised through consensus among members of seven topic-specific working groups and finalized during meetings of working group leads and the planning committee. External review was provided by pediatric, critical care, and critical care nursing professional societies and patient partners. RESULTS: We generated 63 Good Practice Statements and seven Grading of Recommendations Assessment, Development, and Evaluation recommendations covering 1) ethics, consent, and withdrawal of life-sustaining therapy, 2) eligibility, 3) withdrawal of life-sustaining therapy practices, 4) ante and postmortem interventions, 5) death determination, 6) neonatal pediatric donation after circulatory determination of death, 7) cardiac and innovative pediatric donation after circulatory determination of death, and 8) implementation. For brevity, 48 Good Practice Statement and truncated justification are included in this summary report. The remaining recommendations, detailed methodology, full Grading of Recommendations Assessment, Development, and Evaluation tables, and expanded justifications are available in the full text report. CONCLUSIONS: This process showed that rigorous, transparent clinical practice guideline development is possible in the domain of pediatric deceased donation. Application of these recommendations will increase access to pediatric donation after circulatory determination of death across Canada and may serve as a model for future clinical practice guideline development in deceased donation.

Multiyear greenhouse gas balances at a rewetted temperate peatland.

Drained peat soils are a significant source of greenhouse gas (GHG) emissions to the atmosphere. Rewetting these soils is considered an important climate change mitigation tool to reduce emissions and create suitable conditions for carbon sequestration. Long-term monitoring is essential to capture interannual variations in GHG emissions and associated environmental variables and to reduce the uncertainty linked with GHG emission factor calculations. In this study, we present GHG balances: carbon dioxide (CO2 ), methane (CH4 ) and nitrous oxide (N2 O) calculated for a 5-year period at a rewetted industrial cutaway peatland in Ireland (rewetted 7 years prior to the start of the study); and compare the results with an adjacent drained area (2-year data set), and with ten long-term data sets from intact (i.e. undrained) peatlands in temperate and boreal regions. In the rewetted site, CO2 exchange (or net ecosystem exchange (NEE)) was strongly influenced by ecosystem respiration (Reco ) rather than gross primary production (GPP). CH4 emissions were related to soil temperature and either water table level or plant biomass. N2 O emissions were not detected in either drained or rewetted sites. Rewetting reduced CO2 emissions in unvegetated areas by approximately 50%. When upscaled to the ecosystem level, the emission factors (calculated as 5-year mean of annual balances) for the rewetted site were (±SD) -104 ± 80 g CO2 -C m-2  yr-1 (i.e. CO2 sink) and 9 ± 2 g CH4 -C m-2  yr-1 (i.e. CH4 source). Nearly a decade after rewetting, the GHG balance (100-year global warming potential) had reduced noticeably (i.e. less warming) in comparison with the drained site but was still higher than comparative intact sites. Our results indicate that rewetted sites may be more sensitive to interannual changes in weather conditions than their more resilient intact counterparts and may switch from an annual CO2 sink to a source if triggered by slightly drier conditions.