A Parent's Autoethnography: Examining My Experiences and Identity as Parent, Educator, and Researcher While Teaching Literacy to My Adolescent Sons Who Have Autism and Use Augmentative and Alternative Communication

This autoethnography was completed from my unique perspective as a mother to two adolescent sons with autism spectrum disorder (ASD) who have complex communication needs and use augmentative and alternative communication (AAC) to communicate. Although literacy is a human right (Ontario Human Rights Commission, 2022a), it often has been overlooked in my sons’ self-contained classrooms in high school. As my sons’ parent and educator, I gathered my reflections, observations, descriptions, journals, lesson plans, and artifacts to examine the experiences I encountered in developing their literacy. Initially, I conducted a pilot project based on Erickson and Koppenhaver’s (2007) Children With Disabilities: Reading and Writing the Four Blocks® Way, the results of which guided my planning in teaching literacy with an adaptation of the more recent Comprehensive Literacy for All: Teaching Students With Significant Disabilities to Read and Write (Erickson & Koppenhaver, 2020). I coded by hand each line of the collected data to extract categories and then streamline these into the meaningful themes to respond to my two research questions: (a) What are the experiences of a parent educator who has been teaching literacy awareness and skills to her adolescent sons who both have autism and use AAC devices? (b) Does the experience shape her identity as a parent, educator, and researcher? Thematic findings pertaining to the first question revealed experiences related to planning and questioning and my own transformational learning and mindshift. Thematic findings related to the second question include: Parental concerns; Educator: advocating and imposter syndrome; Researcher: Lesson planning and questioning; and Transformational learning and mindshift. Findings are discussed in light of the literature on experiences of parents as educators of children with exceptionalities. The study also presents implications for theory, practice, and research, as well as limitations and future directions

Laboratory Medicine is Faced with the Evolution of Medical Practice

Laboratory medicine and clinical medicine are co-dependent components of medicine. Laboratory medicine functions most effectively when focused through a clinical lens. Me dical practice as a whole undergoes change. New drugs, treatments and changes in management strategies are introduced. New techniques, new technologies and new tests are developed. These changes may be either clinically or laboratory initiated, and so their introduction requires dialogue and interaction between clinical and laboratory medicine specialists. Treatment monitoring is integral to laboratory medicine, varying from direct drug measurement to monitoring cholesterol levels in response to treatment. The current trend to »personalised medicine« is an extension of this process with the development of companion diagnostics. Technological innovation forms part of modern laboratory practice. Introduction of new technology both facilitates standard laboratory approaches and permits introduction of new tests and testing strategies previously confined to the research laboratory only. The revolution in cardiac biomarker testing has been largely a laboratory led change. Flexibility in service provision in response to changing clinical practice or evolving technology provides a significant laboratory management challenge in the light of increasing expectations, shifts in population demographics and constraint in resource availability. Laboratory medicine practitioners are adept at meeting these challenges. One thing remains constant, that there will be a constant need laboratory medicine to meet the challenges of novel clinical challenges from infectious diseases to medical conditions developing from lifestyle and longevity

Cardiac troponin and natriuretic peptide analytical interferences from hemolysis and biotin: educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC C-CB).

Two interferences recently brought to the forefront as patient safety issues include hemolysis (hemoglobin) and biotin (vitamin B7). The International Federation for Clinical Chemistry Committee on Cardiac Biomarkers (IFCC-CB) obtained input from a majority of cTn and NP assay manufacturers to collate information related to high-sensitivity (hs)-cTnI, hs-cTnT, contemporary, and POC cTn assays, and NP assays interferences due to hemolysis and biotin. The information contained in these tables was designed as educational tools to aid laboratory professionals and clinicians in troubleshooting cardiac biomarker analytical results that are discordant with the clinical situation

Analytical considerations in deriving 99th percentile upper reference limits for high-sensitivity cardiac troponin assays: Educational recommendations from the IFCC committee on clinical application of cardiac bio-markers

The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers provides evidence-based educational documents to facilitate uniform interpretation and utilization of cardiac biomarkers in clinical laboratories and practice. The committee’s goals are to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay in clinical practice. Measurement of high-sensitivity cardiac troponin (hs-cTn) assays is a cornerstone in the clinical evaluation of patients with symptoms and/or signs of acute cardiac ischemia. To define myocardial infarction, the Universal Definition of Myocardial Infarction requires patients who manifest with features suggestive of acute myocardial ischemia to have at least one cTn concentration above the sex-specific 99th percentile upper reference limit (URL) for hs-cTn assays and a dynamic pattern of cTn concentrations to fulfill the diagnostic criteria for MI. This special report provides an overview of how hs-cTn 99th percentile URLs should be established, including recommendations about prescreening and the number of individuals required in the reference cohort, how statistical analysis should be conducted, optimal preanalytical and analytical protocols, and analytical/biological interferences or confounds that can affect accurate determination of the 99th percentile URLs. This document also provides guidance and solutions to many of the issues posed.publishedVersio

Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT

Ubiquitin-dependent mechanisms have emerged as essential regulatory elements controlling cellular levels of Smads and TGFß-dependent biological outputs such as epithelial–mesenchymal transition (EMT). In this study, we identify a HECT E3 ubiquitin ligase known as WWP2 (Full-length WWP2-FL), together with two WWP2 isoforms (N-terminal, WWP2-N; C-terminal WWP2-C), as novel Smad-binding partners. We show that WWP2-FL interacts exclusively with Smad2, Smad3 and Smad7 in the TGFß pathway. Interestingly, the WWP2-N isoform interacts with Smad2 and Smad3, whereas WWP2-C interacts only with Smad7. In addition, WWP2-FL and WWP2-C have a preference for Smad7 based on protein turnover and ubiquitination studies. Unexpectedly, we also find that WWP2-N, which lacks the HECT ubiquitin ligase domain, can also interact with WWP2-FL in a TGFß-regulated manner and activate endogenous WWP2 ubiquitin ligase activity causing degradation of unstimulated Smad2 and Smad3. Consistent with our protein interaction data, overexpression and knockdown approaches reveal that WWP2 isoforms differentially modulate TGFß-dependent transcription and EMT. Finally, we show that selective disruption of WWP2 interactions with inhibitory Smad7 can stabilise Smad7 protein levels and prevent TGFß-induced EMT. Collectively, our data suggest that WWP2-N can stimulate WWP2-FL leading to increased activity against unstimulated Smad2 and Smad3, and that Smad7 is a preferred substrate for WWP2-FL and WWP2-C following prolonged TGFß stimulation. Significantly, this is the first report of an interdependent biological role for distinct HECT E3 ubiquitin ligase isoforms, and highlights an entirely novel regulatory paradigm that selectively limits the level of inhibitory and activating Smads

High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people with acute chest pain: a systematic review and cost-effectiveness analysis.

BACKGROUND: Early diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions for chest pain have an AMI. High-sensitivity cardiac troponin (hs-cTn) assays may allow rapid rule-out of AMI and avoidance of unnecessary hospital admissions and anxiety. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of hs-cTn assays for the early (within 4 hours of presentation) rule-out of AMI in adults with acute chest pain. METHODS: Sixteen databases, including MEDLINE and EMBASE, research registers and conference proceedings, were searched to October 2013. Study quality was assessed using QUADAS-2. The bivariate model was used to estimate summary sensitivity and specificity for meta-analyses involving four or more studies, otherwise random-effects logistic regression was used. The health-economic analysis considered the long-term costs and quality-adjusted life-years (QALYs) associated with different troponin (Tn) testing methods. The de novo model consisted of a decision tree and Markov model. A lifetime time horizon (60 years) was used. RESULTS: Eighteen studies were included in the clinical effectiveness review. The optimum strategy, based on the Roche assay, used a limit of blank (LoB) threshold in a presentation sample to rule out AMI [negative likelihood ratio (LR-) 0.10, 95% confidence interval (CI) 0.05 to 0.18]. Patients testing positive could then have a further test at 2 hours; a result above the 99th centile on either sample and a delta (Δ) of ≥ 20% has some potential for ruling in an AMI [positive likelihood ratio (LR+) 8.42, 95% CI 6.11 to 11.60], whereas a result below the 99th centile on both samples and a Δ of < 20% can be used to rule out an AMI (LR- 0.04, 95% CI 0.02 to 0.10). The optimum strategy, based on the Abbott assay, used a limit of detection (LoD) threshold in a presentation sample to rule out AMI (LR- 0.01, 95% CI 0.00 to 0.08). Patients testing positive could then have a further test at 3 hours; a result above the 99th centile on this sample has some potential for ruling in an AMI (LR+ 10.16, 95% CI 8.38 to 12.31), whereas a result below the 99th centile can be used to rule out an AMI (LR- 0.02, 95% CI 0.01 to 0.05). In the base-case analysis, standard Tn testing was both most effective and most costly. Strategies considered cost-effective depending upon incremental cost-effectiveness ratio thresholds were Abbott 99th centile (thresholds of < £6597), Beckman 99th centile (thresholds between £6597 and £30,042), Abbott optimal strategy (LoD threshold at presentation, followed by 99th centile threshold at 3 hours) (thresholds between £30,042 and £103,194) and the standard Tn test (thresholds over £103,194). The Roche 99th centile and the Roche optimal strategy [LoB threshold at presentation followed by 99th centile threshold and/or Δ20% (compared with presentation test) at 1-3 hours] were extendedly dominated in this analysis. CONCLUSIONS: There is some evidence to suggest that hs-CTn testing may provide an effective and cost-effective approach to early rule-out of AMI. Further research is needed to clarify optimal diagnostic thresholds and testing strategies. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005939. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Antibody-mediated interferences affecting cardiac troponin assays:recommendations from the IFCC Committee on Clinical Applications of Cardiac Biomarkers

The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results

Tiul1 and TGIF are Involved in Downregulation of TGFβ1-induced IgA Isotype Expression

TGF-β1 is well known to induce Ig germ-line α (GLα) transcription and subsequent IgA isotype class switching recombination (CSR). Homeodomain protein TG-interacting factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin ligase 1 (Tiul1) are implicated in the negative regulation of TGF-β signaling. In the present study, we investigated the roles of Tiul1 and TGIF in TGFβ1-induced IgA CSR. We found that over-expression of Tiul1 decreased TGFβ1-induced GLα promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Likewise, overexpression of TGIF also diminished GLα promoter activity and further strengthened the inhibitory effect of Tiul1, suggesting that Tiul1 and TGIF can down-regulate TGFβ1-induced GLα expression. In parallel, overexpression of Tiul1 decreased the expression of endogenous IgA CSR-predicitive transcripts (GLTα, PSTα, and CTα) and TGFβ1-induced IgA secretion, but not GLTγ3 and IgG3 secretion. Here, over-expressed TGIF further strengthened the inhibitory effect of Tiul1. These results suggest that Tiul1 and TGIF act as negatively regulators in TGFβ1-induced IgA isotype expression