Phosphorylated biomarkers are crucial for our understanding of drug mechanism of action and dose selection during clinical trials, particularly for drugs that target protein kinases, such as DNA-damage-response (DDR) inhibitors. However, tissue fixation conditions needed to preserve DDR-specific phospho-biomarkers have not been previously investigated. Using xenograft tissues and tightly controlled formalin fixation conditions, we assessed how preanalytical factors affect phosphorylated DDR biomarkers pRAD50(Ser635), ɣH2AX(Ser139), pKAP1(Ser824), and non-phosphorylated biomarkers cMYC and ATM. Cold ischemia times ranged from 15 min to 6 hr, and the fixation duration ranged from 24 hr to 4 weeks. Epitopes pRAD50 and pKAP1 appeared the most labile assessed with staining loss after just 15 min of cold ischemia time, while ATM was more robust showing consistent expression up to 1 hr of cold ischemia. Notably, ɣH2AX expression was lost with formalin fixation over 48 hr. The use of core needle biopsies where possible and novel fixation methods such as the 2-step temperature-controlled formalin approach may improve phosphorylated biomarker preservation; however, practical challenges may affect wider clinical application. The most essential tissue-processing step when downstream analysis includes DDR phosphorylated biomarkers is immediate tissue submersion in formalin, without delay, upon excision from the patient, followed by room temperature fixation for 24 hr.

Background: Behaviour change interventions influence behaviour through causal processes called “mechanisms of action” (MoAs). Reports of such interventions and their evaluations often use inconsistent or ambiguous terminology, creating problems for searching, evidence synthesis and theory development. This inconsistency includes the reporting of MoAs. An ontology can help address these challenges by serving as a classification system that labels and defines MoAs and their relationships. The aim of this study was to develop an ontology of MoAs of behaviour change interventions. Methods: To develop the MoA Ontology, we (1) defined the ontology’s scope; (2) identified, labelled and defined the ontology’s entities; (3) refined the ontology by annotating (i.e., coding) MoAs in intervention reports; (4) refined the ontology via stakeholder review of the ontology’s comprehensiveness and clarity; (5) tested whether researchers could reliably apply the ontology to annotate MoAs in intervention evaluation reports; (6) refined the relationships between entities; (7) reviewed the alignment of the MoA Ontology with other relevant ontologies, (8) reviewed the ontology’s alignment with the Theories and Techniques Tool; and (9) published a machine-readable version of the ontology. Results: An MoA was defined as “a process that is causally active in the relationship between a behaviour change intervention scenario and its outcome behaviour”. We created an initial MoA Ontology with 261 entities through Steps 2-5. Inter-rater reliability for annotating study reports using these entities was α=0.68 (“acceptable”) for researchers familiar with the ontology and α=0.47 for researchers unfamiliar with it. As a result of additional revisions (Steps 6-8), 21 further entities were added to the ontology resulting in 282 entities organised in seven hierarchical levels. Conclusions: The MoA Ontology extensively captures MoAs of behaviour change interventions. The ontology can serve as a controlled vocabulary for MoAs to consistently describe and synthesise evidence about MoAs across diverse sources.

Background: Behaviour change interventions influence behaviour through causal processes called “mechanisms of action” (MoAs). Reports of such interventions and their evaluations often use inconsistent or ambiguous terminology. This includes the reporting of MoAs, creating challenges for searching, evidence synthesis and theory development. An ontology can help address these challenges by serving as a classification system that labels and defines classes for MoAs and their relationships. Aim: To develop an ontology of MoAs of behaviour change interventions.Methods: To develop the MoA Ontology, we (1) defined the ontology’s scope; (2) identified, labelled and defined the ontology’s classes; (3) refined the ontology by annotating (i.e., coding) MoAs in intervention reports; (4) refined the ontology via stakeholder review of the ontology’s comprehensiveness and clarity; (5) tested whether researchers could reliably apply the ontology to annotate MoAs in intervention reports; (6) refined the relationships between classes; (7) reviewed the alignment of the MoA Ontology with relevant ontologies, (8) reviewed the ontology’s alignment with the Theories and Techniques Project; and (9) published the ontology and created a machine-readable version.Results: An MoA was defined as “a process that is causally active in the relationship between a behaviour change intervention scenario and its outcome behaviour”. We created an initial MoA Ontology with 261 classes through Steps 2-5. Inter-rater reliability for annotating study reports using these classes was α=0.68 (“acceptable”) for researchers familiar with the ontology and α=0.47 for researchers unfamiliar with it. As a result of additional revisions (Steps 6-8), 21 further classes were added to the ontology resulting in 282 classes organised into seven hierarchical levels.Conclusions and implications: The MoA Ontology extensively captures MoAs of behaviour change interventions. The ontology can serve as a controlled vocabulary for MoAs to consistently describe and synthesise evidence about MoAs across diverse sources.

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Evidence suggests a consistent correlation between vision impairments, social isolation, and cognitive decline. The National Eye Institute reports that African Americans have an increased risk of developing certain vision impairments such as cataracts, glaucoma, and diabetic retinopathy. At the same time, older African Americans often receive care from family members and this family care may act as a buffer against social isolation and resulting cognitive decline. Using data from 737 African Americans that participated in waves 5, 6, and 7 of the National Health and Aging Trends Study (NHATS), we explored associations between vision impairment, social isolation, and cognitive functioning. Results showed that vision impairment at round 5 was related to increased social isolation, and higher social isolation at round 5 was related to decreased delayed word recall scores at the same wave. No significant longitudinal associations were found between these constructs. Findings suggest that concurrent associations exist between sensory impairments, social isolation, and cognitive functioning, but that these relationships are not robust across time. Despite support provided by unpaid family caregivers, African American older adults with vision impairment are at an increased risk for concurrent social and cognitive challenges. It may be that family support of those with sensory impairments helps so that these impairments aren’t related to social isolation or cognitive functioning across time. Researchers and clinicians could benefit older African Americans with sensory impairments by providing and encouraging support during early stages of vision loss.