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This study explores the ways that youth make sense of the United Nations Sustainable Development Goals and how context informs the scope and nature of youth-led local civic action. Using an embedded case study approach, this study focuses on the Cultivating Pathways to Sustainability project, which engages scores of young people in the state of Vermont, U.S.A. Data for this study was drawn from observations and interviews of middle and high school students and teachers from 18 participating schools. The study’s findings show the value of intermediaries as catalysts for civic action, demonstrate ways of linking global policy with local civic action, and show how a youth-adult partnership model can deepen the meaning and implementation of civic action.

Objectives: We implemented front-line loop-mediated isothermal amplification (LAMP)–based malaria screening in our nonendemic multicenter health region to reduce reliance on microscopy without sacrificing diagnostic efficiency. We aimed to evaluate changes in test volumes, positivity rates, turnaround times, and approximate labor time savings resulting from implementation of LAMP-based malaria testing to assess the efficacy of the novel testing algorithm in our regional hub-and-spoke testing model. Methods: We reviewed data generated from institutional malaria testing between 2016 and 2019, having implemented LAMP in October 2018 as a front-line screening test for all malaria investigations from our hub facility and investigations from satellite facilities with negative rapid diagnostic tests (RDTs) and microscopy. Results: Blood film microscopy and RDT workloads decreased substantially in the year following LAMP implementation (by 90% and 46%, respectively,) despite similar numbers of patients tested and positivity rates for malaria compared with historical data. LAMP turnaround times (TATs) were comparable to historical TATs for RDTs, and TATs for RDTs and thick films did not increase with the change in workflow. Conclusions: LAMP was successfully implemented in our multicenter health region malaria diagnostic algorithm, significantly reducing reliance on microscopic evaluations and RDT and providing substantial labor time savings without compromising TATs.

Hemophagocytosis refers to ingestion of hematopoietic elements or mature blood cells by another cell, typically by cells conventionally associated with phagocytic capacity. Although the finding of hemophagocytosis as a prominent feature in a patient’s bone marrow might prompt consideration of a hemophagocytic syndrome (HPS) such as hemophagocytic lymphohistiocytosis (HLH) in a clinician’s or pathologist’s differential diagnosis, this morphologic feature can be nonspecific in the absence of other clinical and laboratory features of pathologic immune activation, which is the sine qua non of HPS/HLH. We describe three patients whose clinical presentations included transfusion-dependent anemia and whose bone marrow aspirates showed unexpectedly brisk hemophagocytosis of mature red blood cells. Despite striking morphologic hemophagocytosis, no patient met criteria for diagnosis of an HPS. Transfusion-associated hemophagocytosis and hyperferritinemia must be carefully distinguished from HLH through clinical and laboratory assessment. Biomarkers of pathologic immune activation are important diagnostic aids.

Objectives Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) caused by ADAMTS13 deficiency with mortality of up to 90% in the absence of treatment, typically therapeutic plasma exchange (TPE). TTP presents similarly to other TMAs in which TPE is ineffective and associated with morbidity and additional costs. Thus, we sought to assess clinical and laboratory parameters differentiating TTP from other TMAs in our institution’s catchment population. Methods We reviewed 8 years of data from a Canadian provincial apheresis center, including 100 patients with suspected TMA who underwent ADAMTS13 testing, 35 of whom were diagnosed with TTP. We assessed clinical and laboratory parameters to identify discriminators of TTP and assigned PLASMIC TTP prediction scores. Results We observed a higher frequency of neurologic symptoms, more severe thrombocytopenia, and less creatinine elevation in TTP relative to other TMAs. High PLASMIC scores (6-7 points) had 83% sensitivity and 88% specificity for TTP diagnoses; however, ADAMTS13 activity testing was required for correct diagnoses in 14 cases. Conclusions Clinical and laboratory parameters including PLASMIC scoring may lead to misdiagnosis in some cases of TMA. ADAMST13 activity testing provides definitive diagnosis of TTP, supporting the role of rapid turnaround ADAMTS13 testing for appropriate treatment of TMAs.

Background In March 2020, a state of emergency was declared to facilitate organized responses to the coronavirus disease 2019 (COVID‐19) pandemic in British Columbia, Canada. Emergency blood management committees (EBMCs) were formed regionally and provincially to coordinate transfusion service activities and responses to possible national blood shortages. Study Design and Methods We describe the responses of transfusion services to COVID‐19 in regional health authorities in British Columbia through a collaborative survey, contingency planning meeting minutes, and policy documents, including early trends observed in blood product usage. Results Early strategic response policies were developed locally in collaboration with members of the provincial EBMC and focused on three key areas: utilization management strategies, stakeholder engagement (collaboration with frequent users of the transfusion service, advance notification of potential inventory shortage plans, and development of blood triage guidance documents), and laboratory staffing and infection control procedures. Reductions in transfusion volumes were observed beginning in mid‐March 2020 for red blood cells and platelets relative to the prepandemic baseline (27% and 26% from the preceding year, respectively). There was a slow gradual return toward baseline beginning one month later; no product shortage issues were experienced. Conclusion Provincial collaborative efforts facilitated the development of initiatives focused on minimizing potential COVID‐19–related disruptions in transfusion services in British Columbia. While there have been no supply issues to date, the framework developed early in the pandemic should facilitate timely responses to possible disruptions in future waves of infection.

Background B-lymphoblastic leukemia (B-ALL) is the most common childhood malignancy, and its diagnosis requires immunophenotypically demonstrating blast B cell lineage differentiation. Expression of myeloperoxidase (MPO) in B-ALL is well-described and it has been recognized that a diagnosis of mixed phenotype acute leukemia should be made cautiously if MPO expression is the sole myeloid feature in these cases. We sought to determine whether MPO expression in pediatric B-ALL was associated with differences in laboratory, immunophenotypic, or clinical features. Methods We reviewed clinical, diagnostic bone marrow flow cytometry, and laboratory data for all new B-ALL diagnoses at our pediatric institution in 5 years. Cases were categorized as MPO positive (MPO+) or negative (MPO-) using a threshold of ≥20% blasts expressing MPO at intensity greater than the upper limit of normal lymphocytes on diagnostic bone marrow flow cytometry. Results A total of 148 cases were reviewed, 32 of which (22%) were MPO+. MPO+ B-ALL was more frequently hyperdiploid and less frequently harbored ETV6-RUNX1; no MPO+ cases had KMT2A rearrangements or BCR-ABL1. Although not significantly so, MPO+ B-ALL was less likely than MPO- B-ALL to have positive end-of-induction minimal residual disease studies (9.4 and 24%, respectively), but relapse rates and stem cell transplantation rates were similar between groups. Aberrant expression of other more typically myeloid markers was similar between these groups. Conclusion In our study cohort, MPO+ B-ALL showed minimal residual disease persistence less often after induction chemotherapy but otherwise had similar clinical outcomes to MPO- B-ALL, with similar rates of additional myeloid antigen aberrancy.

The cover image is based on the Clinical Message Chronic lymphocytic leukemia with progressive anemia secondary to development of composite lymphoma by Habib Moshref Razavi, James England, Jeffrey Craig et al., https://doi.org/10.1002/ccr3.2656. [Image: see text]

INTRODUCTION Activated partial thromboplastin time (PTT) coagulation waveforms produced by optical detection system coagulation analyzers provide additional potentially useful and routinely underutilized information for the evaluation of a patient's coagulation system. We aimed to identify features of PTT coagulation waveforms, available for all PTT assays performed in our hospital laboratories, that may prove useful in directing early investigations in patients with unexplained prolonged PTT. METHODS We retrospectively reviewed 211 PTT coagulation waveforms from patient testing and categorized them based on the underlying hemostatic abnormality: normal, therapeutic anticoagulation, lupus anticoagulant, congenital factor deficiency, or acquired factor VIII inhibitor. We compared quantitative waveform parameters and the frequency of qualitatively abnormal double-peaked first derivative waveform curves between these groups. RESULTS Partial thromboplastin time and derivative curve maxima and minima differed significantly between acquired factor VIII inhibitors and other diagnostic categories, and the second derivative curve minimum demonstrated the highest area under the receiver operator characteristic curve for identification of acquired factor VIII inhibitors (0.860; maximum accuracy: 79.5% for 2Dmin> -39.3 mAbs/s2 [sensitivity 90.5%; specificity 77.2%]). The presence of an abnormal double-peaked first derivative curve had a sensitivity of 83.3% and specificity of 81.6% for identification of acquired factor VIII inhibitors in cases with PTT >50 seconds. CONCLUSION Partial thromboplastin time coagulation waveform analysis can aid in identification of patients with acquired factor VIII inhibitors and may be of clinical utility in directing early laboratory investigations to identify patients at risk of severe bleeding without prompt intervention.

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy (TMA) resulting from severe ADAMTS13 deficiency, which is generally treated with therapeutic plasma exchange (PLEX). Although ADAMTS13 activity is often assayed to differentiate TTP from TMAs not requiring PLEX, technical and logistical constraints often limit rapid turnaround of results, with PLEX initiated based on clinical suspicion of TTP while awaiting ADAMTS13 activity results. We estimated the potential reduction in plasma product use if rapid turnaround ADAMTS13 activity testing were available in our centre. Methods: We reviewed medical records for all Vancouver General Hospital patients with ADAMTS13 activity testing since assay implementation. Patients receiving PLEX but ultimately diagnosed with a disease not requiring PLEX were identified as "potentially avoidable PLEX" (paPLEX), and their plasma product exposures and related blood product costs were estimated. Laboratory results, ADAMTS13 activity, and PLASMIC scores (a validated clinical tool for TTP diagnosis) of this group were compared to those of newly diagnosed TTP patients (N=35). Results: We identified 16 paPLEX patients, including TMAs secondary to malignant hypertension, infection, hemolytic uremic syndrome, illicit drug use, autoimmune renal disease, and malignancy (Table 1). These patients underwent 104 total PLEX cycles (3-12 per patient, median 6), involving 1,428 plasma units (28-199 per patient, median 71.5) and estimated product-associated costs of $187,759 CAD ($140,889 USD). Median platelet counts were significantly lower in TTP than the paPLEX group (7x109/L versus 38x109/L), as was serum creatinine (98µmol/L versus 224µmol/L). PLASMIC scores indicating low or intermediate likelihood of TTP were observed in 63% of patients receiving paPLEX and 17% of patients with TTP. All patients with TTP had ADAMTS13 activity < 10%, while all patients receiving paPLEX had ADAMTS13 activity ≥ 30%. Conclusions: Unnecessary PLEX carries significant patient blood product exposure risks and system costs that may be circumvented if TTP can be reliably distinguished from other TMAs at the time of initial presentation. In our cohort, ADAMTS13 activity results provided clear separation of these groups and improved upon TTP diagnosis by clinical judgement and PLASMIC scores. Rapid turnaround of ADAMTS13 activity testing results has the potential to reduce the unnecessary costs and blood product exposures resulting from PLEX administration to patients with non-TTP TMAs. Figure 1 Disclosures Smith: Alexion: Other: Participated in an advisory board without receiving financial compensation.

Deterioration of hematologic parameters in lymphoma patients is often attributed to disease progression, comorbidities, or treatment effects. Second primary malignancies occur at increased frequency in CLL and must also be considered.

[Figure][1] An 11-year-old girl was diagnosed with gray platelet syndrome (GPS) with compound heterozygous NBEAL2 mutations after presenting with recurrent epistaxis and thrombocytopenia. Bone marrow examination was performed to evaluate for myelofibrosis. Her blood film demonstrated

Huntington's disease (HD) is caused by an expansion of cytosine-adenine-guanine (CAG) repeats within the coding region of the HD gene, which expresses the protein huntingtin and is characterized by selective degeneration of specific neuronal populations, mainly in the striatum and the cortex. The mechanisms that account for this selective neuronal death are multifaceted, but oxidative stress might play an important role in this process. To determine whether changes in the intracellular redox state will result in oxidative damage to cellular macromolecules with disease progression, we analyzed levels of lipid peroxidation (with the thiobarbituric acid reactive substances [TBARS] assay) and protein carbonyl formation (using the 2,4-dinitrophenylhydrazine reaction) in the cerebellum, cerebral cortex, prefrontal cortex, striatum, and hippocampus of the YAC128 HD mouse model at 3, 6, and 12 months of age. With the exception of a transient increase in protein carbonyl levels in the YAC128 prefrontal cortex at 6 months of age, levels of lipid peroxidation and protein oxidation were not significantly different between YAC128 mice and their age-matched wild-type counterparts in any of the brain regions analyzed up to 12 months of age. However, age-related increases in oxidative stress were observed in various brain regions. These results suggest that lipid and protein oxidative damage is not a major contributor to neurodegeneration in the YAC128 brain up to 12 months of age.

American Journal of Education (AJE) es una de las once revistas más importantes en el campo de la educación y publica nuevos trabajos de investigación en un amplio espectro de disciplinas educativas. Con sede en la Pennsylvania State University, la revista trabaja con editores asociados de toda la nación y con un consejo asesor de académicos sénior. También cuenta con un foro online (AJE Forum) gestionado por el consejo editorial estudiantil. El mayor problema que afronta la revista es cómo difundir eficazmente la investigación revisada por pares para que llegue a un público amplio, incluidos gestores, responsables políticos, reformadores y educadores. Dadas las limitaciones de los recursos universitarios, la revista ha explorado nuevas vías para difundir información sobre sus artículos a través de las redes sociales, y continúa evaluando la mejor forma de analizar el impacto de los artículos publicados en contextos académicos y políticos. The American Journal of Education (AJE) is one of 11 core journals identified in the field of education and publishes new research across abroad range of educational disciplines. Located at Penn State, the journal is supported by associate editors from around the nation as well as an advisory board of senior scholars. The journal also supports an online forum (AJE Forum) that is managed by the student editorial board. The major issue facing the journal is how to effectively disseminate peer-reviewed research to a broad audience that includes administrators, policy makers, reform advocates and educators. Given the limitations of university resources, the journal has experimented with new ways to disseminate information about its articles via social media and continues to assess how best to monitor the impact of journal articles in academic and policy contexts.

[Figure][1] A 3-day-old boy with a known family history of von Willebrand disease (VWD) type 2B was found to have marked thrombocytopenia on automated blood count (platelet count, 7 × 109/L). Examination of the peripheral blood showed numerous aggregates of large well-granulated platelets

Introduction: B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy and its diagnosis depends on flow cytometry. Aberrant antigen expression is common in B-ALL and can be useful in both diagnosis and minimal residual disease (MRD) assessment. CD49f (α6 integrin) is commonly overexpressed in lymphoblasts of B-ALL relative to benign B lymphoblasts, and research suggests a role for CD49f in central nervous system (CNS) invasion in B-ALL. We aimed to characterize clinical and laboratory features associated with lymphoblast CD49f expression in pediatric B-ALL. Methods: We reviewed clinical and laboratory features, including diagnostic and day 29 (D29) MRD bone marrow aspirate flow cytometry, for patients newly diagnosed with B-ALL at our pediatric centre using current diagnostic flow cytometry panels implemented in 2013. CD49f positivity (CD49f+) was defined as greater than 20% of leukemic blasts expressing CD49f at fluorescence intensity greater than the upper limit of an internal lymphocyte population. MRD studies were considered positive with leukemic blasts ≥0.01% of mononuclear cells. Frequency of CD49f+ and CD49f median fluorescence intensity (MFI) were compared between groups defined by recurrent cytogenetic abnormalities, molecular abnormalities detected by comparative genomic hybridization, CNS involvement at diagnosis, and occurrence of relapse by Chi-square, Fisher exact, Kruskal-Wallis, and Mann-Whitney testing. Results: 158 patients were reviewed with median age at diagnosis of 56 months (range 4 to 225 months) and median 33 months follow-up (range 1 to 67 months). 82 patients had CD49f+ B-ALL (median 62.2% CD49f+ blasts, CD49f MFI 3.4) and 76 patients had CD49f negative (CD49f-) B-ALL (median 3.7% CD49f+ blasts, CD49f MFI 0.8). CD49f+ and CD49f- cases did not differ significantly in median age at diagnosis (CD49f+, 51 months; CD49f-, 64.5 months) or presenting white blood cell count (CD49f+, 8.7x109/L; CD49f-, 8.8x109/L). 24 patients had CNS involvement at diagnosis, with which CD49f expression status was not significantly associated (CD49f+, 17.1%; CD49f-, 13.4%). Median CD49f MFI (1.8 CNS negative; 1.3 CNS positive) and proportion of CD49f+ leukemic blasts (27.8% CNS negative; 15.8% CNS positive) did not significantly differ between patients presenting with or without CNS involvement. Recurrent cytogenetic abnormalities associated significantly with CD49f status (p=0.001): CD49f+ associated with higher frequency of ETV6-RUNX1 (36.6% of CD49f+ and 11.8% of CD49f-; p=0.0004) and lower frequency (without statistical significance) of KMT2A rearrangement, hypodiploidy (each 1.2% CD49f+; 6.6% CD49f-), intrachromosomal amplification of chromosome 21, and TCF3-PBX1 (neither of which occurred in patients with CD49f+). Copy number abnormalities detectable by comparative genomic hybridization in CDKN2A, CDKN2B, PAX5, IKZF1, BTG1, ERG, TP53, RB1, EBF1, and CRLF2 did not differ in frequency between patients with CD49f+ and CD49f-. D29 MRD data were available for 154 patients, 32 of whom had positive MRD results. Frequency of D29 MRD positivity was not significantly associated with CD49f expression status at diagnosis (19.7% CD49f+; 21.9% CD49f-). Relapse occurred in ten patients and its occurrence was not associated with CD49f expression status at diagnosis (4.9% CD49f+; 7.9% CD49f-). Nine patients had evaluable relapse flow cytometry data, with three demonstrating increased proportions of CD49f+ blasts (1.5- to 3.2-fold increase from diagnosis), two demonstrating similar proportions, and three demonstrating decreased proportions of CD49f+ blasts (1.9- to 25-fold decrease from diagnosis). Two had new CNS involvement at relapse (one patient with 27% CD49f+ blasts at diagnosis and 1.1% at relapse; one patient with 93.3% CD49f+ blasts at diagnosis and 99.5% at relapse) and one had CNS involvement at diagnosis without involvement at relapse (with 12.8% CD49f+ blasts at diagnosis and 12.1% at relapse). Conclusion: Using the aforementioned criteria for flow cytometry data analysis, CD49f positivity in pediatric B-ALL was not associated with increased frequency of CNS involvement at diagnosis, day 29 MRD positivity, or relapse. CD49f expression patterns changed inconsistently in patients experiencing relapse and positivity or negativity at diagnosis or relapse was not clearly associated with CNS involvement at relapse. Disclosures No relevant conflicts of interest to declare.

Background The consumption of alcohol during pregnancy can result in abnormal fetal development and impaired brain function in humans and experimental animal models. Depending on the pattern of consumption, the dose, and the period of exposure to ethanol (EtOH), a variety of structural and functional brain deficits can be observed. Methods This study compared the effects of EtOH exposure during distinct periods of brain development on oxidative damage and endogenous antioxidant status in various brain regions of adult female and male Sprague Dawley rats. Pregnant dams and neonatal rats were exposed to EtOH during one of the following time windows: between gestational days (GDs) 1 and 10 (first trimester equivalent); between GDs 11 and 21 (second trimester equivalent); or between postnatal days (PNDs) 4 and 10 (third trimester equivalent). Results EtOH exposure during any of the 3 trimester equivalents significantly increased lipid peroxidation in both the cornus ammonis (CA) and dentate gyrus (DG) subregions of the hippocampus, while also decreasing the levels of the endogenous antioxidant glutathione in the hippocampal CA and DG subregions as well as the prefrontal cortex of young adult animals (PND 60). Conclusions These results indicate that EtOH exposure during restricted periods of brain development can have long-term consequences in the adult brain by dysregulating its redox status. This dysfunction may underlie, at least in part, the long-term alterations in brain function associated with fetal alcohol spectrum disorders.