Three decades of Canadian marine harmful algal events: Phytoplankton and phycotoxins of concern to human and ecosystem health.

Spatial and temporal trends of marine harmful algal events in Canada over the last three decades were examined using data from the Harmful Algal Event Database (HAEDAT). This database contains the most complete record of algal blooms, phycotoxins and shellfish harvesting area closures in Canada since 1987. This 30-year review of 593 Canadian HAEDAT records from 1988 to 2017, together with other Canadian data and publications, shows that recurring harmful algal events have been widespread throughout both the Atlantic and Pacific coastal regions. The 367 paralytic shellfish toxin (PST) reports revealed annual and frequent recurrence throughout both the Atlantic and Pacific regions, including multi-year PST events in the Bay of Fundy, the Estuary and Gulf of St. Lawrence and the Strait of Georgia. The 70 amnesic shellfish toxin (AST) records revealed no recognizable trend, as these events were usually area specific and did not recur annually. The increasing frequency of diarrhetic shellfish toxin (DST) events over the period of this review, in total 59 records, can be at least partially explained by increased sampling effort. Marine species mortalities caused by harmful algae (including diatoms, dictyochophytes, dinoflagellates, and raphidophytes), were a common occurrence in the Pacific region (87 reports), but have been reported much less frequently in the Atlantic region (10 reports). Notable Canadian records contained in HAEDAT include the first detection worldwide of amnesic shellfish poisoning (ASP), attributed to the production of domoic acid (an AST) by a diatom (Pseudo-nitzschia multiseries) in Prince Edward Island in 1987. The first proven case of diarrhetic shellfish poisoning (DSP) in Canada and North America was recorded in 1990, and the first closures of shellfish harvesting due to DST (associated with the presence of Dinophysis norvegica) occurred in Nova Scotia in 1992, followed by closures in Newfoundland and Labrador in 1993. In 2008, mass mortalities of fishes, birds and mammals in the St. Lawrence Estuary were caused by Alexandrium catenella and high levels of PST. During 2015, the Pacific coast experienced a large algal bloom that extended from California to Alaska. It resulted in the closure of several shellfish harvesting areas in British Columbia due to AST, produced by Pseudo-nitzschia australis. Data from the Canadian Arctic coast is not included in HAEDAT. However, because of the emerging importance of climate change and increased vessel traffic in the Arctic, information on the occurrence of harmful algal species (pelagic and sympagic = sea ice-associated) in that region was compiled from relevant literature and data. The results suggest that these taxa may be more widespread than previously thought in the Canadian Arctic. Information in HAEDAT was not always robust or complete enough to provide conclusions about temporal trends. Compilation of spatial and temporal information from HAEDAT and other records is nevertheless important for evaluating the potential role of harmful algae as a stressor on Canadian marine ecosystems, and will support the next step: developing a knowledge gap analysis that will establish research priorities for determining their consequences on human and ecosystem health.

Use of Thromboelastography to Predict Thrombotic Complications in Pediatric and Neonatal Extracorporeal Membranous Oxygenation.

The objectives of this study were to investigate the correlation between thromboelastography (TEG) and conventional measures of anticoagulation, and to determine optimum values for citrated kaolin TEG R time (TEG RCK) and anti-Xa activity that would minimize both bleeding and thrombotic complications in pediatric and neonatal patients requiring extracorporeal membranous oxygenation (ECMO). A retrospective chart review of patients requiring veno-venous (VV) and venoarterial (VA) ECMO was performed. Combined medical and cardiac ICU within a single-center, tertiary care, freestanding, children's hospital. Non-pregnant patients <18 years and >2 kilograms requiring VV or VA ECMO from July 2013 through July 2015. Anti-Xa (OR = 0.62, 95% CI 0.53-0.72, p < .001) and TEG RCK (OR = 1.19, 95% CI 1.07-1.34, p = .003) were the only independent predictors for a significant thrombotic event. Receiver operating characteristic curves and traditional epidemiological data (sensitivity, specificity, PPV, NPV) were used to determine optimal target Anti-Xa and TEG RCK values. No independent predictors for significant bleeding events were identified in this cohort. A anti-Xa activity of .25 IU/mL (sensitivity = 81%, specificity = 67%, PPV = 81%, NPV = 58%) and TEG RCK time of 17.85 minutes (sensitivity = 84%, specificity = 68%, PPV = 82%, NPV = 59%) were established as the optimal thresholds for preventing thrombotic events. Anti-Xa and TEG RCK were independent predictors of thrombosis in this cohort of pediatric and neonatal ECMO patients. Targeting an anti-Xa activity greater than .25 IU/mL and a TEG RCK greater than 17.85 minutes may minimize the risk of thrombosis in pediatric and neonatal ECMO patients. Future investigation should evaluate targets for anti-Xa and TEG RCK, which additionally minimize the risk of significant bleeding in this patient population.

The Use of Recombinant Antithrombin III in Pediatric and Neonatal ECMO Patients.

A retrospective review of 77 pediatric and neonatal extracorporeal membranous oxygenation (ECMO) patients who received recombinant antithrombin III (ATIII) for ATIII activity greater than 80% was conducted. Anticoagulation management was per institutional protocol. An ATIII activity greater than 80% was targeted. Diagnosis, reason for ECMO cannulation, blood product usage, heparin dosing, ATIII activity and doses, thrombotic and bleeding complications, hours on ECMO, and mortality were recorded. We calculated patient-level summary statistics and assessed differences between groups using χ tests (categorical variables) and Wilcoxon rank sum tests (continuous variables). Hierarchical generalized linear models were developed to model bleeding and thrombotic complications. The majority (n = 75) received venoarterial ECMO and had cardiac diagnoses (n = 62). Antithrombin III activity was below 80% for an average of 5.2 hours per patient. Antithrombin III activity less than 80% was not associated with thrombotic complications (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 0.97-1.06, p = 0.86). Antithrombin III activity greater than 80% was not associated with bleeding complications (OR = 1.06, 95% CI = 1.01-1.11, p = 0.44). Duration of ECMO was an independent predictor of thrombotic complications (OR = 1.08, 95% CI = 1.02-1.11, p = 0.02). There were no independent predictors of bleeding complications. Antithrombin III activity correlated with anti Xa activity (r = 0.367, p < 0.001) but not with other measures of anticoagulation or with heparin dose (r = 0.16, p = 0.165). ATIII activity was not associated with bleeding, thrombosis, or heparin dose. Antithrombin III activity was associated with anti Xa activity but not with traditional measures of anticoagulation. Antithrombin III replacement for an activity less than 80% did not increase bleeding.

Age-related changes in the composition, the molecular stoichiometry and the stability of proteoglycan aggregates extracted from human articular cartilage.

The heterogeneity of the components of proteoglycan aggregates, their stoichiometry within the aggregate and the aggregates' stability was investigated in normal human articular cartilage specimens (age-range newborn to 63 years). Proteoglycans were extracted from tissue by sequentially extracting them with PBS alone, PBS containing oligosaccharides of hyaluronan, and PBS containing solutions of increasing guanidinium chloride concentration (1 M, 2 M, 3 M and 4 M). A high proportion of each of the components of the proteoglycan aggregate, i.e. uronic acid, sulphated glycosaminoglycan, hyaluronan binding domain of aggrecan (G1-domain), link protein (LP) and hyaluronan, was extracted from immature cartilage by PBS alone and PBS containing oligosaccharides of hyaluronan. This was in marked contrast to adult cartilage, which required high concentrations of guanidinium chloride for the efficient extraction of these components. The molar ratios of total G1-domain:LP and the G1-domain associated with aggrecan:LP also differed markedly between immature and mature cartilage and between each of the sequential extracts. The concentration of LP was less than that of the G1-domain in all extracts of cartilage from individuals over 13 years, but this was particularly noticeable in the 1 M guanidinium chloride extracts, and it was surmised that a deficiency in LP produces unstable aggregates in situ. The fragmentation of LP, which is known to occur with advancing age, did not influence the extractability of LP, and fragments were present in each of the sequential extracts. Therefore the generally accepted model of proteoglycan aggregation presented in the literature, which is mostly derived from analysis of immature animal cartilage, cannot be used to describe the structure and organization of aggregates in adult human articular cartilage, where a heterogeneous population of complexes exist that have varying degrees of stability.