Pathfinders: Realizing Reconciliation Through Lessons Learned

In 2016, a group of Indigenous and non-Indigenous scholars came together to imagine a better world through a bold approach to education at the Werklund School of Education. This imagining took the form of a newly designed graduate pathway program which focused on meaningfully and actively responding to Canada’s Truth and Reconciliation Commission’s (TRC) (2015) 94 Calls to Action. Central to the design of our program is the inclusion of a capstone service-learning project that asks graduate students to bring together Indigenous and non-Indigenous groups in designing and delivering projects of mutual benefit. In sharing insights from their respective learning journeys, our students reveal the complexities and challenges of reconciliatory work but also its many rewards. Further, in sharing these courageous acts, we hope to inspire others to take action

Association between Statin Use and Balance in Older Adults

ABSTRACT: Background: Several medications have been associated with an increased risk of balance deficits and greater likelihood to sustain a fall, representing a large health and economic issue. Statins are regularly prescribed to prevent strokes and heart attacks, but their impact on balance is unknown. The aim of this paper was to determine whether statin use is associated with poorer balance performances in older adults. Methods: All participants, one group taking statins (n = 34), and the other group not taking statins (n = 31), completed a balance assessment with their eyes closed and their eyes opened on a MatScan Pressure Sensing Mat. Center of Pressure (CoP) velocity, peak-to-peak distance, and standard deviation were collected in both anteroposterior (AP) and mediolateral (ML) directions. Multiple linear regression analyses were performed for each balance outcome, testing the statin use status as a predictor and controlling for appropriate factors including participants characteristics, lipid profile, and cardiovascular disease. Results: After controlling for confounding factors, statin use significantly predicted both CoP ML-Amplitude (beta = 0.638, p = 0.004) and ML-Velocity (beta = 0.653, p = 0.002) in the eyes-opened condition. Conclusions: The present study detected a negative association between statin use and balance control in the ML direction, suggesting that caution should be taken when prescribing statins in older adults, as this could decrease ML stability and ultimately increase fall and fracture risks

Comparison of Illumina and 454 Deep Sequencing in Participants Failing Raltegravir-Based Antiretroviral Therapy

Background: The impact of raltegravir-resistant HIV-1 minority variants (MVs) on raltegravir treatment failure is unknown. Illumina sequencing offers greater throughput than 454, but sequence analysis tools for viral sequencing are needed. We evaluated Illumina and 454 for the detection of HIV-1 raltegravir-resistant MVs. Methods: A5262 was a single-arm study of raltegravir and darunavir/ritonavir in treatment-naïve patients. Pre-treatment plasma was obtained from 5 participants with raltegravir resistance at the time of virologic failure. A control library was created by pooling integrase clones at predefined proportions. Multiplexed sequencing was performed with Illumina and 454 platforms at comparable costs. Illumina sequence analysis was performed with the novel snp-assess tool and 454 sequencing was analyzed with V-Phaser. Results: Illumina sequencing resulted in significantly higher sequence coverage and a 0.095% limit of detection. Illumina accurately detected all MVs in the control library at ≥0.5% and 7/10 MVs expected at 0.1%. 454 sequencing failed to detect any MVs at 0.1% with 5 false positive calls. For MVs detected in the patient samples by both 454 and Illumina, the correlation in the detected variant frequencies was high (R2 = 0.92, P<0.001). Illumina sequencing detected 2.4-fold greater nucleotide MVs and 2.9-fold greater amino acid MVs compared to 454. The only raltegravir-resistant MV detected was an E138K mutation in one participant by Illumina sequencing, but not by 454. Conclusions: In participants of A5262 with raltegravir resistance at virologic failure, baseline raltegravir-resistant MVs were rarely detected. At comparable costs to 454 sequencing, Illumina demonstrated greater depth of coverage, increased sensitivity for detecting HIV MVs, and fewer false positive variant calls

Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection

Deep sequencing technologies have the potential to transform the study of highly variable viral pathogens by providing a rapid and cost-effective approach to sensitively characterize rapidly evolving viral quasispecies. Here, we report on a high-throughput whole HIV-1 genome deep sequencing platform that combines 454 pyrosequencing with novel assembly and variant detection algorithms. In one subject we combined these genetic data with detailed immunological analyses to comprehensively evaluate viral evolution and immune escape during the acute phase of HIV-1 infection. The majority of early, low frequency mutations represented viral adaptation to host CD8+ T cell responses, evidence of strong immune selection pressure occurring during the early decline from peak viremia. CD8+ T cell responses capable of recognizing these low frequency escape variants coincided with the selection and evolution of more effective secondary HLA-anchor escape mutations. Frequent, and in some cases rapid, reversion of transmitted mutations was also observed across the viral genome. When located within restricted CD8 epitopes these low frequency reverting mutations were sufficient to prime de novo responses to these epitopes, again illustrating the capacity of the immune response to recognize and respond to low frequency variants. More importantly, rapid viral escape from the most immunodominant CD8+ T cell responses coincided with plateauing of the initial viral load decline in this subject, suggestive of a potential link between maintenance of effective, dominant CD8 responses and the degree of early viremia reduction. We conclude that the early control of HIV-1 replication by immunodominant CD8+ T cell responses may be substantially influenced by rapid, low frequency viral adaptations not detected by conventional sequencing approaches, which warrants further investigation. These data support the critical need for vaccine-induced CD8+ T cell responses to target more highly constrained regions of the virus in order to ensure the maintenance of immunodominant CD8 responses and the sustained decline of early viremia

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions

English

The release of the Canadian Truth and Reconciliation Report in 2015 has prompted research and pedagogy that focuses on Indigenous education, updated teaching standards, and re-designed curriculum; however, experiences of teachers who have been called to act in the service of reconciliation have received minimal research attention. This study found that although the majority of educators believe in the necessity of this work, few are taking steps towards reconciliation through their work as educators. This study utilized an explanatory mixed method approach to gather survey and interview data into the reconciliatory practices, challenges, and successes experienced by grades 4-9 teachers. Overall, findings of this research suggest that educators who are committed to reconciliation, self-reflection, and collaboration are more likely to incorporate aspects of reconciliatory pedagogy into their teaching. This study informs teacher practice, pre-service teacher training, professional development, and ultimately aims to move the dialogue about reconciliation forward within Canadian education.La publication du Rapport de la Commission de vérité et reconciliation du Canada en 2015 a suscité des recherches et une pédagogie axée sur l'éducation Indigène, des normesd'enseignement mises à jour et un curriculum reformulé; cependant, les expériences des enseignants qui ont été appelés à agir au service de la réconciliation n'ont reçu qu'une attentionminime. Cette étude a révélé que, bien que la majorité des éducateurs croient en la nécessité de ce travail, peu prennent des mesures vers la réconciliation par leur travail d’éducateur. Cetteétude a utilisé une approche explicative à méthodes mixtes pour recueillir des données d'enquêtes et d'entrevues sur les pratiques de réconciliation, les défis et les succès rencontrés par lesenseignants de la 4e à la 9e année. Au total, les résultats de cette recherche suggèrent que les éducateurs qui se sont engagés à la susceptibles d'incorporer des aspects de la pédagogie de laréconciliation dans leur enseignement. Cette étude renseigne la pratique des enseignants, la formation initiale des enseignants, le perfectionnement professionnel et vise ultimement à faire avancer le dialogue sur la réconciliation au sein de l'éducation canadienne.réconciliation, à l'autoréflexion et à la collaboration sont plu

Sexual partnership concurrency and age disparities associated with sexually transmitted infection and risk behavior in rural communities in Kenya and Uganda.

ObjectivesWe examined sex-specific associations of partner age disparity and relationship concurrency with Neisseria gonorrhoeae and/or Chlamydia trachomatis (NG/CT) infection, higher-risk relationships, and condom use as proxies for HIV risk.MethodsData were collected in 2016 from 2179 adults in 12 communities in Uganda and Kenya. Logistic regression models examined associations of age disparity and relationship concurrency with NG/CT infection, condom use, and higher-risk (commercial sex and other higher-risk) relationships in the past 6 months, controlling for covariates.ResultsPartner age and relationship concurrency were associated with NG/CT infection in women but not men. Relative to women in age-disparate relationships, women in both age-disparate and age-homogeneous relationships had higher odds of NG/CT infection (adjusted odds ratio [aOR]=3.82, 95% confidence interval [CI]: 1.46-9.98). Among men and women, partnership concurrency was associated with higher-risk partnerships. In addition, relative to those with a single age-homogeneous partner, those with concurrent age-homogeneous partners had higher odds of condom use (men: aOR=2.85, 95% CI: 1.89-4.31; women: aOR=2.99, 95% CI: 1.52-5.89). Concurrent age-disparate partnerships were associated with condom use among men only (aOR=4.02, 95% CI: 2.54-6.37).ConclusionFindings underscore the importance of targeted HIV prevention efforts for couples in age-disparate and concurrent relationships

Steady-state visual evoked potentials in children with neurofibromatosis type 1:associations with behavioral rating scales and impact of psychostimulant medication

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder often associated with cognitive dysfunctions, including a high occurrence of deficits in visuoperceptual skills. The neural underpinnings of these visuoperceptual deficits are not fully understood. We used steady-state visual evoked potentials (SSVEPs) to investigate possible alterations in the synchronization of neural activity in the occipital cortex of children with NF1. METHODS: SSVEPs were measured using electroencephalography and compared between children with NF1 (n = 28) and neurotypical controls (n = 28) aged between 4 and 13 years old. SSVEPs were recorded during visual stimulation with coloured icons flickering at three different frequencies (6 Hz, 10 Hz, and 15 Hz) and analyzed in terms of signal-to-noise ratios. A mixed design ANCOVA was performed to compare SSVEP responses between groups at the three stimulation frequencies. Pearson’s correlations with levels of intellectual functioning as well as with symptoms of ADHD, ASD and emotional/behavioral problems were performed. The impact of psychostimulant medication on the SSVEP responses was analyzed in a subset of the NF1 group (n = 8) with paired t-tests. RESULTS: We observed reduced signal-to-noise ratios of the SSVEP responses in children with NF1. The SSVEP responses were negatively correlated with symptoms of inattention and with symptoms of emotional/behavioral problems in the NF1 group. The SSVEP response generated by the lowest stimulation frequency (i.e., 6 Hz) was rescued with the intake of psychostimulant medication. CONCLUSIONS: Impaired processing of rhythmic visual stimulation was evidenced in children with NF1 through measures of SSVEP responses. Those responses seem to be more reduced in children with NF1 who exhibit more symptoms of inattention and emotional/behavioral problems in their daily life. SSVEPs are potentially sensitive electrophysiological markers that could be included in future studies investigating the impact of medication on brain activity and cognitive functioning in children with NF1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-022-09452-y