Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Introduction: Patient-reported outcome measures (PROM) are questionnaires that can be used to elicit care outcome information from patients. We sought to develop and validate the first PROM for adult patients without a primary mental health or addictions presentation receiving emergency department (ED) care and who were not hospitalized. Methods: PROM development used a multi-phase process based on national and international guidance (FDA, NQF, ISPOR). Phase 1: ED outcome conceptual framework qualitative interviews with ED patients post-discharge informed four core domains (previously published). Phase 2: Item generation scoping review of the literature and existing instruments identified candidate questions relevant for each domain for inclusion in tool. Phase 3: Cognitive debriefing existing and newly written questions were tested with ED patients post-discharge for comprehension and wording preference. Phase 4: Field and validity testing revised tool pilot tested on a national online survey panel and then again at 2 weeks (test-retest). Phase 5: Final item reduction using a Delphi process involving ED clinicians, researchers, patients and system administrators. Phase 6: Validation - psychometric testing of PROM-ED 1.0. Results: Four core outcome domains were defined in Phase 1: (1) understanding; (2) symptom relief; (3) reassurance and (4) having a plan. The domains informed a review of existing relevant questionnaires and instruments and the writing of additional questions creating an initial long-form questionnaire. Eight patients participated in cognitive debriefing of the long-form questionnaire. Expert clinicians, researchers and patient partners provided input on item refinement and reduction. Four hundred forty-four patients completed a second version of the long-form questionnaire (add in retest numbers) which informed the final item reduction process by a modified Delphi method involving 21 diverse contributors. The questionnaire was validated and underwent final revisions to create the 21 questions that constitute PROM-ED 1.0. Conclusion: Using accepted PROM instrument development methodology, we developed the first outcome questionnaire for use with adult ED patients who are not hospitalized. This questionnaire can be used to systematically gather patient-reported outcome information that could support and inform improvement work in ED care.

Of the radiation types, alpha-(α) particles are of particular interest as they are an environmental concern, predominately due to inhalation of radon and its daughter progeny. Furthermore, α-particle emitters like Americium-241, Plutonium-238 and Polonium-210 have been identified as probable isotopes to be used in radiological dispersal devices. Thus, the identification of potential biomarkers to α-particle radiation exposure would be useful for the development of field deployable bioassays which could be used for human risk assessment and public health protection. Human lung cells were exposed to α-particle radiation and assessed for modulations in protein expression using two-dimensional gel electrophoresis (2D-GE). Concurrently, cell culture supernatants were analyzed for cytokine secretion using a multiplex-27 bead array assay. Cell culture supernatants assessed for cytokine secretion expressed 8 statistically significant cytokines following α-particle exposure, among which VEGF was confirmed to be dose-responsive and not modulated in X-irradiated cells. Analysis of whole cell lysates using 2-D gel electrophoresis showed 15 upregulated and 1 downregulated protein spot, of which 4 were identified by mass spectrometry. These data suggest that α-particle exposure results in the alterations in expression-levels of specific proteins which may be potential biomarkers used further for the development of fast and reliable bioassays.