Variability of Replicates of Intraocular Inflammatory Biomarkers in Ocular Fluid Samples Analyzed with Multiplex Assays.

Purpose: Certain factors such as instrumental and sample processing errors may contribute to variability of ocular biofluid samples when they are run as replicates with multiplex assays. There is a paucity of literature on the variability of replicates in multiplex assays. This study aims to evaluate whether there is significant variability in replicate analyses of multiplex assays. Methods: A total of 152 human ocular biofluid samples (51 aqueous humor and 101 vitreous) were collected and assayed for 27 cytokine biomarker concentrations (pg/mL). Samples were evaluated as replicates (duplicate analysis) at four different time points. Statistical methods including paired samples t-test, 3-way ANOVA, intraclass correlation coefficient (ICC; <0.5-0.75=poor-moderate, 0.75->0.90 =good-excellent reliability), and coefficients of variation (CV) were employed to evaluate for statistical significance, with Bonferroni corrected P=0.002. Results: Among the 4104 biomarker replicate assays for aqueous humor and vitreous, two analytes (PDGF-BB and IL-7) had a statistically significant difference between the sampled concentrations of the replicates in vitreous samples (mean (diff)=2.05, P<0.001, mean (diff)=1.56, P<0.001, respectively). Majority of the ICC values fell within the good-excellent range (86% of samples) with a minority falling in the poor-moderate range (14% of samples). More variability was noted in the vitreous humour, with five analytes (IL-2, IL-10, IL-12(p70), IL-13, IL-17) demonstrating an average ICC of less than 0.5. The CV calculated for each set of replicates suggested that 93% of replicates had an acceptable level of quantitative assay variability (CV<20%). Conclusion: This study demonstrates that the analysis of most biomarkers in ocular fluids may not require the use of replicates. However, certain analytes such as PDGF-BB and IL-7 may require the use of replicates to ensure reliable results. Caution should be taken when applying these findings to other laboratory settings as our study was conducted by an experienced technician using a standardized protocol. In less standardized settings, replicates may be required in order to ensure accuracy of results. These findings may guide researchers with the design of their studies on ophthalmic biomarker analysis.

Reading Speed Using the International Reading Speed Texts in a Normal Canadian Cohort.

Background The International Reading Speed Texts (IReST) are commonly used to measure reading speed, which may be affected in many eye conditions. They were originally tested in a younger British population. Our study evaluates IReST in a normal Canadian population. Methodology A normal Canadian cohort in Ontario was prospectively recruited with age >14 years, education >9 years, English as the primary language, and best-corrected visual acuity >20/25 distance and >N8 near in each eye. Participants with eye conditions and neurological/cognitive problems were excluded. Each participant consecutively read two IReST passages (passages 1 and 8). Reading speed in words per minute (WPM) was calculated. One-sample t-test was used to compare our cohort to published IReST standards. Results A total of 112 participants were included (35 male, 77 female). The mean age was 40 ± 17 years (14-18 years: 12; 18-35 years: 34; 35-60 years: 53; 60-75 years: 13). The mean reading speed for passage 1 was 211 ± 33 WPM compared to the published IReST standard of 236 ± 29 WPM (p < 0.0001). The mean reading speed for passage 8 was 218 ± 34 WPM compared to the IReST standard of 237 ± 24 WPM (p < 0.0001). Thus, our cohort read slower for both passages compared to IReST standards. The mean reading speed for passages 1 and 8 was the highest for the 14-18-year (231 and 239, respectively) and the lowest for the 60-75-year group (195 and 192, respectively). Conclusions Normal older populations have slower reading compared to younger populations. The slower reading in our cohort may also be because the passages were in British rather than in Canadian English. It is important that the IReST is evaluated in different populations to ensure reliable comparison standards for future research.

Health Care Students' Perspectives on Artificial Intelligence: Countrywide Survey in Canada.

BACKGROUND: Artificial intelligence (AI) is no longer a futuristic concept; it is increasingly being integrated into health care. As studies on attitudes toward AI have primarily focused on physicians, there is a need to assess the perspectives of students across health care disciplines to inform future curriculum development. OBJECTIVE: This study aims to explore and identify gaps in the knowledge that Canadian health care students have regarding AI, capture how health care students in different fields differ in their knowledge and perspectives on AI, and present student-identified ways that AI literacy may be incorporated into the health care curriculum. METHODS: The survey was developed from a narrative literature review of topics in attitudinal surveys on AI. The final survey comprised 15 items, including multiple-choice questions, pick-group-rank questions, 11-point Likert scale items, slider scale questions, and narrative questions. We used snowball and convenience sampling methods by distributing an email with a description and a link to the web-based survey to representatives from 18 Canadian schools. RESULTS: A total of 2167 students across 10 different health professions from 18 universities across Canada responded to the survey. Overall, 78.77% (1707/2167) predicted that AI technology would affect their careers within the coming decade and 74.5% (1595/2167) reported a positive outlook toward the emerging role of AI in their respective fields. Attitudes toward AI varied by discipline. Students, even those opposed to AI, identified the need to incorporate a basic understanding of AI into their curricula. CONCLUSIONS: We performed a nationwide survey of health care students across 10 different health professions in Canada. The findings would inform student-identified topics within AI and their preferred delivery formats, which would advance education across different health care professions.

Out of the shadows: Chronic pain in Canadian Armed Forces veterans - Proceedings of a workshop at the 2019 Forum of the Canadian Institute for Military and Veteran Health Research.

This commentary summarizes proceedings of a workshop on chronic pain in military personnel and veterans (released personnel) at the Annual Forum of the Canadian Institute for Military and Veteran Health Research in Gatineau and Ottawa on October 22, 2019. The extent and impact of chronic pain among Canadian Armed Forces (CAF) veterans and their families is significant and has been underappreciated, largely due to limited disclosure by serving and veteran military personnel, stemming from a fear of stigmatization. Living with pain is seen as a fact of life in military cultures, something to be endured and not discussed. Though progress is being made in reducing the stigma of mental illness, the discourse on chronic pain remains censored. This workshop's goal was to bring the discussion of chronic pain out of the shadows in the search for ways to help veterans and active service personnel living with chronic pain. Many points of view were brought forward at this first national Canadian multidisciplinary gathering of researchers, veterans with lived experience, clinicians, and policymakers. A CAF member described his lived experience with constant chronic pain. Clinicians described aspects of chronic pain in military personnel and veterans whom they treat in their clinics. Dr. Ramesh Zacharias described the new Chronic Pain Center of Excellence for Canadian Veterans that will be established with funding from Veterans Affairs Canada. Dr. Norman Buckley highlighted collaboration with the existing Chronic Pain Network funded by the Canadian Institute for Health Research. Audience members identified a diverse variety of issues.

Ce commentaire résume les actes d'un atelier sur la douleur chronique chez le personnel militaire et les anciens combattants (personnel libéré) tenu dans le cadre du Forum annuel de l'Institut canadien de recherche sur la santé des militaires et des vétérans à Gatineau et Ottawa le 22 octobre 2019. L'étendue et l'effet de la douleur chronique chez les anciens combattants des Forces armées canadiennes (FAC) et leurs familles sont importantes et ont été sous-estimées, en grande partie en raison de la divulgation limitée par le personnel militaire en service et les anciens combattants, découlant de la peur de la stigmatisation. Le fait de vivre avec la douleur est considéré comme faisant partie de la vie dans les cultures militaires, quelque chose qu'il faut endurer et dont il ne faut pas discuter. Bien que des progrès aient été réalisés dans la réduction de la stigmatisation de la maladie mentale, le discours sur la douleur chronique continue d'être censuré. L'objectif de cet atelier était de faire sortir de l'ombre la discussion sur la douleur chronique afin de chercher des moyens d'aider les anciens combattants et le personnel de service actif vivant avec la douleur chronique. De nombreux points de vue ont été exprimés lors de cette première rencontre multidisciplinaire nationale canadienne réunissant des chercheurs, des anciens combattants ayant vécu l'expérience de la douleur chronique, des cliniciens et des décideurs. Un membre des FAC a décrit l'expérience de douleur chronique qu'il a vécue. Les cliniciens ont décrit les aspects de la douleur chronique chez le personnel militaire et les anciens combattants qu'ils traitent dans leurs cliniques. Le Dr Ramesh Zacharias a décrit le nouveau Centre d'excellence sur la douleur chronique pour les vétérans canadiens qui sera établi grâce au financement d'Anciens Combattants Canada. Le Dr Norman Buckley a souligné la collaboration avec le Réseau de douleur chronique existant financé par l'Institut canadien de la recherche en santé. Les membres de l'audience ont relevé divers problèmes.

Quantitative assessment of neuromotor function in workers with current low exposure to mercury vapor.

Evaluation of neuromotor function has been used in several epidemiological studies of workers with long-term exposure to mercury vapor (Hg 0). Some recent studies indicate adverse effects at relatively low exposure levels. In the present study, we used sensitive quantitative methods, developed specifically to detect subtle effects of exposure to toxins on motor function. After exclusion of individuals with neurological diseases or other conditions that may affect performance, 43 chloralkali workers with current low exposure to Hg 0, and 22 age-matched referents remained for further analysis. The median urinary mercury concentration in exposed workers was 5.9 microg/g (range 1.3-25) creatinine (microg/gC), while that in referents was 0.7 microg/gC (range 0.2-4.1). The mean exposure time was 15 years, and the median cumulative mercury index was 161 years x microg/gC in exposed workers. A eurythmokinesimeter (EKM) was used to quantify eye-hand coordination, and a diadochokinesimeter, to measure rapid alternating rotation of the forearms. In general, the differences in performance between the exposed workers and the referents were small. Age was associated with a decrease in speed, more tremor, and longer contact duration between the stylus and the metal targets in performance of rapid pointing movements. Smokers had significantly more tremor, and more contacts per event in the EKM test, than nonsmokers. Taking age, shift work, and smoking habits into account, no significant associations with current or cumulative mercury exposure were found for the majority of the outcome variables from the quantitative tests. In general, this study indicates no significant adverse effects of Hg 0 on neuromotor function at the exposure levels studied.

Quantitative tremor assessment in workers with current low exposure to mercury vapor.

Measurement of tremor has been used in several occupational studies of workers with long-term exposure to mercury vapor (Hg(0)). Recent studies indicate an adverse effect even at relatively low exposure levels. In the present study, we used sensitive quantitative methods to assess tremor in chloralkali workers with current low exposure to Hg(0). Neurological examinations and recordings of tremor using both an accelerometer and a laser-based system were conducted in 43 mercury-exposed workers and 22 age-matched referents. The median urinary mercury concentration in exposed workers was 5.9 (1.3-25) microg/g creatinine (microg/gC), while it was 0.7 (0.2-4.1) microg/gC in referents. The mean exposure time was 15 years, and the median cumulative mercury index was 161 years x microg/gC in exposed workers. There were no differences between the exposed workers and the referents in the clinical evaluation of tremor. In the quantitative tremor tests, no associations were found with current or cumulative mercury exposure for the majority of tremor measures. There were indications that exposure to Hg(0) was associated with a lowering of tremor frequency in the non-dominant hand, and a possible interaction with smoking. The differences were small, however, and overall, this study indicates no significant adverse effects on tremor at these exposure levels.

Automatic detection of movement disorders using recordings of rapid alternating movements.

The present work assesses the potential of rapid alternating movement analysis for detecting movement disorders like Parkinson's disease. Rapid alternating wrist movements were recorded by a diadochokinesimeter for patients with Parkinson's disease (n=10) and healthy controls (n=20). An index of irregularity was computed for each individual as the density of jerk singularities (i.e. zero-crossings) during the movements. Several scales of analysis (i.e. "coarseness") were used for detecting the jerk events and two methods were compared for all of these scales: (1) automatic classification by means of a threshold that optimally separates the indexes of irregularity of the patients from those of the controls, and (2) statistical decision (normal or abnormal) based upon a distribution of indexes of irregularity obtained from a large population of normal subjects. The results showed that (1) two scales of analysis were sufficient and that (2) both methods presented similar performances (e.g. sensitivity=1.00, specificity=0.85, efficiency=0.90). However, statistical decision should be preferred because of its simplicity. The possibility of automatic detection of movement disorders from alternating movements is discussed.

Standardization of quantitative tests for preclinical detection of neuromotor dysfunctions in pediatric neurotoxicology.

In the neurotoxicology pediatric domain, few neuromotor tests are specifically designed to be sensitive enough for the early detection of subtle deficits in voluntary and involuntary movements. In research and clinical domains, an effort is done to objectify or quantify the qualitative aspects of a movement (pattern of movement) in predicting neurological problems. This study aimed to standardize quantitative motor measures initially developed for adults and adapted to the evaluation of preschoolers. The sample consisted of 110 healthy children aged 4-6. The following quantitative neuromotor tests were selected: alternating movements and pointing movements (DOCO Microsystèmes Inc., Montréal, Canada), postural tremor, postural sway and simple reaction time (Danish Product Development Ltd., Snekkersten, Denmark). Validation measures included global motor tasks and a neurological examination. Results indicate adequate test-retest reliability and complementarities amongst the selected voluntary and involuntary measures. Both the feasibility and relevance of quantitative neuromotor tests in preschool aged children were established. Results also provide a representation of intra-individual and inter-individual variability within this population. Lastly, the results highlight the importance of developmental factors, behavioral factors and testing conditions in the neuromotor evaluation of young children. The proposed tests could help in the early detection of children at risk for motor dysfunctions following neurotoxic exposure. The tests can also be used for the follow up of various conditions relating to motor functions (cerebral palsy, muscular dystrophy, preterm infants) and in the evaluation of the effects of medication.

Neuromotor effects of acute ethanol inhalation exposure in humans: a preliminary study.

Ethanol (ETOH) is added to unleaded gasoline to decrease environmental levels of carbon monoxide from automobiles emissions. Therefore, addition of ETOH in reformulated fuel will most likely increase and the involuntarily human exposure to this chemical will also increase. This preliminary study was undertaken to evaluate the possible neuromotor effects resulting from acute ETOH exposure by inhalation in humans. Five healthy non-smoking adult males, with no history of alcohol abuse, were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of ETOH (0, 250, 500 and 1,000 ppm in air) for six hours. Reaction time, body sway, hand tremor and rapid alternating movements were measured before and after each exposure session by using the CATSYS 7.0 system and a diadochokinesimeter. The concentrations of ETOH in blood and in alveolar air were also measured. ETOH was not detected in blood nor in alveolar air when volunteers were exposed to 250 and 500 ppm, but at the end of exposure to 1,000 ppm, blood and alveolar air concentrations were 0.443 mg/100ml and 253.1 ppm, respectively. The neuromotor tests did not show conclusively significant differences between the exposed and non-exposed conditions. In conclusion, this study suggests that acute exposure to ethanol at 1,000 ppm or lower or to concentrations that could be encountered upon refueling is not likely to cause any significant neuromotor alterations in healthy males.