Enlisting Students to Transcribe Historical Climate and Weather Data For Research: Building Knowledge Translation Via Classroom-Based Citizen Science

DRAW (Data Rescue: Archives & Weather) is a citizen science project that asks the Canadian public to take part in transcribing millions of meteorological observations recorded between 1871 and 1963 at McGill University’s Observatory in Montreal, Quebec, which was demolished in 1963. We examine how classroom-based curricula can integrate citizen science so youth can learn more about their community via engagement with the local history of weather conditions and impacts. Conducted in March 2018, this research examined knowledge translation during a three-week course module through written reflections, classroom video footage, exit interviews, and a final group research assignment. We worked with 21 students—16- to 20-year-olds enrolled in a social science research methods course at Dawson College, a two-year collège d\u27enseignement général et professionnel (college of general and vocational education) that attracts local students and is a funded part of education in the province of Quebec. We found knowledge translation was facilitated by student engagement with their community’s history and appreciation for aiding credible scientific research. Knowledge translation suffered from attempts to include archival records that could be difficult to find, access, and read. Our work showed that citizen science, as a vehicle for community engagement and scientific literacy, requires considerable contextualization, for example, the use of frequently asked questions, tutorials, and blogs for context, and historical context to ensure knowledge translation takes place

Cerebral blood volume lesion extent predicts functional outcome in patients with vertebral and basilar artery occlusion

Background CT perfusion may improve diagnostic accuracy in posterior circulation stroke. The posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) on Computed Tomography Angiography source images (CTA-SI) predicts functional outcome in patients with basilar artery occlusion. Aims We assessed the prognostic value of pc-ASPECTS on CT perfusion in patients with vertebral and basilar artery occlusion (VBAO) in comparison with CTA-SI. Methods Whole-brain CT perfusion from consecutive stroke patients with VBAO at four stroke centers was retrospectively analyzed. pc-ASPECTS - a 10-point score assessing hypoattenuation on CTA-SI - was calculated from CT perfusion parameters as focally reduced cerebral blood flow or cerebral blood volume, focally increased time to peak of the deconvolved tissue residue function (Tmax) or mean transit time. Two investigators independently reviewed the images. Reliability was assessed with intraclass correlation coefficient. Good outcome was defined as modified Rankin scale ≤3 at three months. Results We included 60 patients with VBAO. After assessment of four CT perfusion maps simultaneously, area-under-ROC curve (AROC) was 0.83 (95%CI 0.72-0.93) for cerebral blood volume, 0.76 (95%CI 0.64-0.89) for cerebral blood flow, 0.77 (95%CI 0.64-0.89) for Tmax, 0.70 (95%CI 0.56-0.84) for mean transit time versus area-under-ROC curve 0.64 (95%CI 0.50-0.79) for CTA-SI. Cerebral blood volume had greater accuracy compared with CTA-SI for poor outcome (p = 0.04). In logistic regression analysis, cerebral blood volume pc-ASPECTS≤8 was independently associated with poor outcome (OR 9.3 95%CI 2.2-41; p = 0.003, adjusted for age and clinical severity). Inter-rater agreement was substantial for cerebral blood volume pc-ASPECTS (intraclass correlation coefficient 0.82 95%CI 0.71-0.90 versus 0.67 for CTA-SI 95%CI 0.43-0.81). Conclusions Cerebral blood volume pc-ASPECTS may identify VBAO patients at higher risk of disability

Cerebral blood volume lesion extent predicts functional outcome in patients with vertebral and basilar artery occlusion

Background: CT perfusion may improve diagnostic accuracy in posterior circulation stroke. The posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) on Computed Tomography Angiography source images (CTA-SI) predicts functional outcome in patients with basilar artery occlusion. Aims: We assessed the prognostic value of pc-ASPECTS on CT perfusion in patients with vertebral and basilar artery occlusion (VBAO) in comparison with CTA-SI. Methods: Whole-brain CT perfusion from consecutive stroke patients with VBAO at four stroke centers was retrospectively analyzed. pc-ASPECTS – a 10-point score assessing hypoattenuation on CTA-SI – was calculated from CT perfusion parameters as focally reduced cerebral blood flow or cerebral blood volume, focally increased time to peak of the deconvolved tissue residue function (Tmax) or mean transit time. Two investigators independently reviewed the images. Reliability was assessed with intraclass correlation coefficient. Good outcome was defined as modified Rankin scale ≤3 at three months. Results: We included 60 patients with VBAO. After assessment of four CT perfusion maps simultaneously, area-under-ROC curve (AROC) was 0.83 (95%CI 0.72–0.93) for cerebral blood volume, 0.76 (95%CI 0.64–0.89) for cerebral blood flow, 0.77 (95%CI 0.64–0.89) for Tmax, 0.70 (95%CI 0.56–0.84) for mean transit time versus area-under-ROC curve 0.64 (95%CI 0.50–0.79) for CTA-SI. Cerebral blood volume had greater accuracy compared with CTA-SI for poor outcome (p = 0.04). In logistic regression analysis, cerebral blood volume pc-ASPECTS≤8 was independently associated with poor outcome (OR 9.3 95%CI 2.2–41; p = 0.003, adjusted for age and clinical severity). Inter-rater agreement was substantial for cerebral blood volume pc-ASPECTS (intraclass correlation coefficient 0.82 95%CI 0.71–0.90 versus 0.67 for CTA-SI 95%CI 0.43–0.81). Conclusions: Cerebral blood volume pc-ASPECTS may identify VBAO patients at higher risk of disability

Maternal exposure to urinary polycyclic aromatic hydrocarbons (PAH) in pregnancy and childhood asthma in a pooled multi-cohort study

Background: Prenatal exposure to polycyclic aromatic hydrocarbons (PAH) may increase risk of pediatric asthma, but existing human studies are limited. Objectives: We estimated associations between gestational PAHs and pediatric asthma in a diverse US sample and evaluated effect modification by child sex, maternal asthma, and prenatal vitamin D status. Methods: We pooled two prospective pregnancy cohorts in the ECHO PATHWAYS Consortium, CANDLE and TIDES, for an analytic sample of N = 1296 mother–child dyads. Mono-hydroxylated PAH metabolites (OH-PAHs) were measured in mid-pregnancy urine. Mothers completed the International Study on Allergies and Asthma in Childhood survey at child age 4–6 years. Poisson regression with robust standard errors was used to estimate relative risk of current wheeze, current asthma, ever asthma, and strict asthma associated with each metabolite, adjusted for potential confounders. We used interaction models to assess effect modification. We explored associations between OH-PAH mixtures and outcomes using logistic weighted quantile sum regression augmented by a permutation test to control Type 1 errors. Results: The sociodemographically diverse sample spanned five cities. Mean (SD) child age at assessment was 4.4 (0.4) years. While there was little evidence that either individual OH-PAHs or mixtures were associated with outcomes, we observed effect modification by child sex for most pairs of OH-PAHs and outcomes, with adverse associations specific to females. For example, a 2-fold increase in 2-hydroxy-phenanthrene was associated with current asthma in females but not males (RRfemale = 1.29 [95 % CI: 1.09, 1.52], RRmale = 0.95 [95 % CI: 0.79, 1.13]; pinteraction = 0.004). There was no consistent evidence of modification by vitamin D status or maternal asthma. Discussion: This analysis, the largest cohort study of gestational PAH exposure and childhood asthma to date, suggests adverse associations for females only. These preliminary findings are consistent with hypothesized endocrine disruption properties of PAHs, which may lead to sexually dimorphic effects

Prenatal polycyclic aromatic hydrocarbon exposure and asthma at age 8–9 years in a multi-site longitudinal study

Abstract Background and aim Studies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in socio-demographically diverse participants from the ECHO PATHWAYS multi-cohort consortium. Methods We included 1,081 birth parent–child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8–9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression. Results The prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically significant. Conclusions In a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8–9 years, though some adverse associations were observed among girls

Differential modulation of Alzheimer's disease amyloid β-peptide accumulation by diverse classes of metal ligands

Biometals have an important role in AD (Alzheimer's disease) and metal ligands have been investigated as potential therapeutic agents for treatment of AD. In recent studies the 8HQ (8-hydroxyquinoline) derivative CQ (clioquinol) has shown promising results in animal models and small clinical trials; however, the actual mode of action in vivo is still being investigated. We previously reported that CQ–metal complexes up-regulated MMP (matrix metalloprotease) activity in vitro by activating PI3K (phosphoinositide 3-kinase) and JNK (c-jun N-terminal kinase), and that the increased MMP activity resulted in enhanced degradation of secreted Aβ (amyloid β) peptide. In the present study, we have further investigated the biochemical mechanisms by which metal ligands affect Aβ metabolism. To achieve this, we measured the effects of diverse metal ligands on cellular metal uptake and secreted Aβ levels in cell culture. We report that different classes of metal ligands including 8HQ and phenanthroline derivatives and the sulfur compound PDTC (pyrrolidine dithiocarbamate) elevated cellular metal levels (copper and zinc), and resulted in substantial loss of secreted Aβ. Generally, the ability to inhibit Aβ levels correlated with a higher lipid solubility of the ligands and their capacity to increase metal uptake. However, we also identified several ligands that potently inhibited Aβ levels while only inducing minimal change to cellular metal levels. Metal ligands that inhibited Aβ levels [e.g. CQ, 8HQ, NC (neocuproine), 1,10-phenanthroline and PDTC] induced metal-dependent activation of PI3K and JNK, resulting in JNK-mediated up-regulation of metalloprotease activity and subsequent loss of secreted Aβ. The findings in the present study show that diverse metal ligands with high lipid solubility can elevate cellular metal levels resulting in metalloprotease-dependent inhibition of Aβ. Given that a structurally diverse array of ligands was assessed, the results are consistent with the effects being due to metal transport rather than the chelating ligand interacting directly with a receptor

Identification of concordant plasma lipid signatures in Alzheimer’s disease: Validation between two independent studies of Alzheimer’s disease

Background: Changes to lipid metabolism are tightly coupled to the onset and pathology of Alzheimer’s disease (AD). Lipidomics has allowed for unprecedented characterisation of the lipidome within biological systems. To explore the lipid dysregulation associated with AD, we utilised our expanded lipidomics platform, examining 569 lipid species across 32 lipid classes, and applied it to the Australian Imaging, Biomarker & Lifestyle Study of Ageing (AIBL) study and the Alzheimer\u27s Disease Neuroimaging Initiative (ADNI) study. Method: We examined over 4000 samples between the AIBL and ADNI studies. Baseline samples comprises of 1112 and 804 from the AIBL and ADNI respectively. Univariate associations between lipids and AD were examined using logistic or linear regressions accounting for variables including anthropometric measures and APOE genotype. Cox regression analysis was used to identify lipids associated with future onset of AD from baseline samples. We utilised a fixed effect model to meta analyse the results, identifying lipids which are concordantly associated between the two studies. Result: Exploratory analysis of the data identified strong associations between plasma lipids and AD risk factors such as age (increasing acylcarnitine species), sex (sphingoid base specific) and APOE genotype (ether lipids). Combined meta‐analysis of the two cohorts identified lipid class and subclass‐specific associations with incident and established AD. In the fully adjusted analysis (anthropometric measures, APOE genotype, clinical lipids and medication), a total of 218 species were associated with established AD and 71 with incident AD after correction for FDR. Sphingomyelin, ceramide, ganglioside, plasmalogen and other ether lipids were concordantly associated with AD and its risk factors in both studies. In particular, ether lipids were consistently associated with both established and future AD independent of their subclass (plasmalogen vs non‐plasmalogen) highlighting impairment of peroxisomal function at the earliest stages of AD. Whole lipid class associations were seen with phosphatidylethanolamine and triglyceride, despite adjustments for clinical lipids, implicating dysregulation in liver lipid metabolism. Conclusion: By leveraging off two independent studies, we were able to highlight concordant associations between lipids and both established and incident AD. The significantly broader coverage of the lipidome from our platform provides new hypotheses and directions for future research