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Predicting estimated glomerular filtration rate slope among adult patients with IgA nephropathy in Manitoba
Full text linkBackground: As the most common cause of glomerulonephritis worldwide, immunoglobulin A nephropathy (IgAN) represents an important cause of kidney failure. Traditional epidemiologic research and clinical trials have focused on the onset of kidney failure, or a profound decrease in the estimated glomerular filtration rate (eGFR), as a primary outcome. Over short follow up, some patients with IgAN may appear low risk, yet recent epidemiologic data suggest that few avoid kidney failure in their lifetime. The rate of decline in eGFR (eGFR slope) over a 2-year period has emerged as a surrogate endpoint in trials, and a method to identify high-risk patients earlier. However, no tools currently exist to predict eGFR slope in patients with IgAN. We aimed to develop and validate a prediction model for 2-year eGFR slope using clinical and pathological data in patients with IgAN.
Methods: Adult patients with biopsy-proven IgAN from 2002 to 2021 were identified from the Manitoba Glomerular Diseases Registry. Registry data were linked to demographic, laboratory, physician claims, and drug dispensing data from the Manitoba Population Research Data Repository. Mixed-effects linear regression models were fit to predict eGFR slope, with random intercept and slope; candidate fixed effect covariates included time, age, sex, index eGFR, proteinuria, the change in proteinuria and eGFR from biopsy to index, the time from nephrology visit to biopsy, prescription of glucocorticoids, the presence of hypertension, presence of diabetes, Oxford S, T, and C scores. Two-way interaction terms with time were tested for proteinuria, index eGFR, glucocorticoid prescription, change in eGFR from biopsy to index, and Oxford S, T, and C scores. Model performance was evaluated using marginal R2, conditional R2 and root mean squared error. Predictions were evaluated using calibration and Bland-Altman plots. Internal validation was performed with 10-fold cross validation.
Results: A total of 181 patients were included in the study cohort. The median age was 41 years (interquartile range, IQR 31, 54). Included patients were high risk; median eGFR at biopsy was 58 mL/min/1.73 m2 (IQR 35-86), while median proteinuria at biopsy was 1.73 g/day (IQR 1.06, 2.95). The “parsimonious model” including fixed effects for time, age, sex, index eGFR and proteinuria, with two-way interaction terms for time with both index eGFR and proteinuria, as well as random intercept and slope for each patient, was selected as the final model. In this model, higher index proteinuria was significantly associated with faster eGFR decline (-1.47 mL/min/1.73 m2/year, SE 0.66, p = 0.009). Model fit was excellent, with conditional R2 of 0.95. In the development dataset, predictions were accurate, with 88% of predicted slopes within 1 mL/min/1.73 m2/year of the observed slope. However, marginal predictions were inaccurate and poorly calibrated; only 11% of marginal predicted slopes were within 1 mL/min/1.73 m2/year of the observed slope, with calibration slope 1.58 (95% confidence interval 0.71, 2.44). Cross-validation revealed poor generalizability, with marked deterioration in conditional predictions, while marginal predictions were more stable, but remained inaccurate.
Significance: Accurate prediction of eGFR slope could enable earlier risk stratification, facilitating earlier and more personalized treatment decisions in IgAN. Our findings highlight both the promise and the limitations of slope prediction; while models achieved excellent in-sample accuracy, they relied heavily on patient-specific random effects for accuracy, a property that does not generalize well to new patients. The results underscore the challenges of slope prediction in a heterogeneous disease and suggest that larger, more homogeneous cohorts, combined with models capable of estimating random effects using previously observed data, may improve out-of-sample predictive performance.February 202
Behavioral divergence in a changing Arctic: Novel insights into the movement ecology of Eastern Beaufort Sea belugas from historical tracking data
Full text linkThe Eastern Beaufort Sea (EBS) population undertakes an annual migration from their summering grounds in the western Canadian Arctic to their winter range in the Chukchi and Bering Seas. EBS belugas were instrumented with satellite-linked transmitters in the shallow waters of the Mackenzie Delta over the course of the 1990s, 2000s and 2010s in collaboration with Inuvialuit communities. This thesis aggregated these datasets to examine the range and diversity of EBS beluga movements at two different scales. First, dynamic Brownian Bridge Movement Models (dBBMMs) were used to re-establish seasonal ranges and high-use areas across the annual migration cycle. Evidence of individual stopovers on bathymetric features, together with a potential fall staging area in the Chukchi Sea, suggests that EBS belugas depend on a network of sites across their annual range to support long-distance movements. Second, variation in summer space use was quantified, individuals with similar summer movements were clustered, and the link between space use and migration timing was examined. Three main summering groups were identified, and targeted distinct high-use areas and were generally associated with different individual traits: A group of mature males departed from the Mackenzie Estuary by mid-July and travelled to Viscount Melville Sound, a mixed group remained in the Amundsen Gulf and travelled between nearshore and offshore sites throughout the season, while a smaller, mixed group targeted the Beaufort Sea slope and similarly returned to the Estuary before migrating. Fall migration timing varied between and within groups, suggesting that summer space use, individual variation and external drivers influence the date of departure. These findings highlight avenues for future research on EBS beluga space use, migration timing, population structure and abundance that may better account for the presence of spatially and temporally segregated groups.ArcticNet
Fisheries and Oceans CanadaFebruary 202
International Humanitarian Law under the light of the right to a healthy, clean and sustainable environment: the role of human rights in the proportionality principle
Full text linkIt is an undeniable fact that international and non-international armed conflicts have become a threat to a healthy, clean and sustainable environment, creating long-term and often irreversible impacts for current and future generations. While the right to a healthy, clean and sustainable environment has been recognized and is increasingly being developed nationally, regionally, and internationally, the law governing armed conflicts, International Humanitarian Law, is not yet well-equipped to protect the natural environment.
The present thesis examines the role of the right to a healthy, clean, and sustainable environment in the proportionality principle. The main question is what the role and relevance of the right to a healthy, clean, and sustainable environment is in proportionality assessment. The innovation of this thesis lies in the intersection and application of this right during armed conflicts, addressing how the right to a healthy, clean, and sustainable environment can make a difference in the assessment of the proportionality principle. Another focal point of this thesis is examining the status of the mentioned right in international human rights law. Drawing from this analysis, this research examines the interaction between international humanitarian law and international human rights law.
The overall aim is to provide greater protection for the environment during armed conflicts. A doctrinal research method with a human rights approach is used in this thesis. Findings of this research will contribute to the discourse on the protection of the environment during armed conflicts.February 202
Identifying molecular mechanisms of cationic antimicrobial tolerance in Klebsiella pneumoniae and antibiotic cross-resistance
No full textAntimicrobial resistance (AMR) generally focuses on antibiotics, however, bacterial adaptation to disinfectant and antiseptic biocides is comparatively understudied, despite growing evidence of resistance emerging. Cationic antimicrobial (CAs) biocides are widely used and environmentally persistent, imposing significant selective pressure that promotes bacterial adaptation. CA-resistant bacteria have also demonstrated cross-resistance to other biocides and antibiotics, suggesting that excessive CA use may contribute to the development of broader AMR.
This thesis investigates the adaptation of Klebsiella pneumoniae DSM 6135 to three CAs: benzalkonium chloride (BZK), chlorhexidine (CHX), and colistin (CST) to identify genetic alterations shared and uniquely induced after prolonged CA exposure and to determine any antimicrobial cross-resistance phenotypes. This study revealed that CAs rapidly promoted stable CA-resistant phenotypes, as indicated by minimum inhibitory concentration (MIC) values >4-fold higher than those of the wild type (WT). CHX- and BZK-adapted isolates exhibited reduced growth relative to the WT, attributable to deleterious single-nucleotide variant mutations associated with each CA adaptation. All CA-adapted K. pneumoniae isolates exhibited cross-resistance to multiple CAs and diverse antibiotics, in contrast to previous findings in E. coli K-12, where CA adaptation conferred limited cross-resistance. Notably, CHX- and CST-adapted isolates generally showed broader antibiotic cross-resistance than BZK-adapted isolates. Whole-genome sequencing (WGS) identified a complex network of mutations with few genes consistently altered across all isolate types, namely KEB-L, ROP-L, and yfcD, implicating these as potential key determinants of CA resistance. Additional mutations arising from CA adaptation affected pathways related to lipid metabolism, efflux, protein synthesis, and cellular transport, as well as novel changes in hypothetical genes with unknown functions, that could be further explored in future studies.
These findings demonstrate that K. pneumoniae can rapidly acquire CA resistance through diverse genetic routes, that often appear to be specific for the CA used during adaptation. All CA adaptations resulted in cross-resistance to antibiotics and other antiseptics. This study emphasizes the need to limit CA overuse and highlights novel genetic targets for further study to elucidate their contributions to AMR through CA resistance mechanisms.February 202
Down to earth: an arts-based Matryoshka of critical place inquiries in Winnipeg, Manitoba
Full text linkThis manuscript-based dissertation embodies a conceptual format of a Matryoshka (nesting figures), which shares multiple multi-year critical place inquiries (Tuck & McKenzie, 2018) into Winnipeg, Manitoba, and a journey through a/r/tography (Irwin, 2004, 2013; Irwin, Lasczik, Sinner, Triggs, 2024; Leggo & Irwin, 2014; Springgay, Irwin, & Kind, 2005). The Matryoshka activates an assemblage of interconnected topics such as Indigenous sovereignty, historical removals and displacements, the Truth and Reconciliation Commission of Canada (2015) and the National Inquiry into Missing and Murdered Indigenous Women and Girls (2019).
I have linked four manuscripts (consisting of one chapter prepared for publication, one published journal article, and two published book chapters), which share stories and analysis of working with land art installations (soilwork) in urban locations with Indigenous significance in the city. Manuscript 1 is titled “Unearthing Truths” and analyzes an abstract artwork I created by sifting soil around my children’s shoes at my home as a response to the discovery of unmarked graves of children that did not come home from Indian Residential Schools. Manuscript 2 is titled “Homeland” and documents the creation and impact of a larger-than-life scale soil portrait I constructed of Louis Riel at Upper Fort Garry on a corporately sponsored and re-branded historical location. Manuscript 3, “Murky Waters”, documents the creation of an intricate soil spiral on snow around the public commemorative monument to Murdered and Missing Indigenous Women and Girls. Manuscript 4, “Red River Removals”, analyzes a series of bold Métis symbols I sequenced repeatedly at Riel House, a Parks Canada national historical site, and that is accompanied by haunting footprints as a way of remembering a connection to water.
Embedded within this dissertation (referred to as the Matryoshka of manuscripts) are perspectives of land, place, and art that shift towards relationality (Donald, 2012, 2021; Tynan, 2021; Wilson, 2008). The artwork I created in and between each manuscript represents a visible negotiation of differing knowledge systems through an a/r/tographic embodiment of ethical space (Ermine, 2007). I layer methodologies as part of a journey towards understanding place and addressing two main research questions: 1) How can critical place and arts-based inquiries with pop-up soil art installations support (public engagement and teacher education with) decolonizing educational praxis in settler-colonial systems? and 2) What does earth-based art (soilwork) offer as an emerging methodology? Additionally, I frame both initiating and linking questions to value the dynamic and cyclical quality of learning from land and the layered interactions and power of place.
I share three horizons of soilwork that create unique topography within the creative realm of arts-based research, and which unearths the methodological potentialities of soil to understand what a localized version of decolonization means in this powerful prairie place. This dissertation takes an undisciplined approach (hooks, 2004; Kulchyski, 2002) to embrace the embodiment of the arts and anticolonial approaches that blur the boundaries between topics in ways that resist settler colonialism and challenge what research should look like. Methods include public provocations, poetic soil compositions, walking, and guided participatory workshops with teachers. The visual data of individual and collaborative soilwork installations and praxis form living links to give life to the conceptual framework of this dissertation. Overall, this dissertation contributes to anticolonial arts-based research and illustrates a process of understanding ethical space that provides the groundwork for interdisciplinary research collaborations. Grounding this research in the relational process of earth-based art gives understandings of settler colonial tracks (Veracini, 2011) and has revealed new accessible modes of addressing complex topics that disrupt dominant research progression and paradigms. Soil speaks to the stories of places, and I present soil sensibilities as new renderings of a/r/tography which connect to place and led towards relational research endeavours.February 202
Diverting waters: examining the potential for community-based strategic environmental assessment of small hydropower projects in the Upper Kullu Valley, India
Full text linkThis research explores the potential for implementing community-based strategic environmental assessment (CBSEA) using the development of micro and mini hydropower (MHP) in the Upper Kullu Valley of Himachal Pradesh, India as a case example. CBSEA provides an alternative to traditional assessment tools because the process is conducted by community members, ensuring their concerns and local knowledge are considered, while also engaging community members in strategic thinking. CBSEA has been studied little, so my work explored if and how a CBSEA could be implemented in a local context.
A case study approach involving projects in the Upper Kullu Valley was undertaken to consider the promise of CBSEA in this context. Data were collected through a document review, semi-structured interviews with stakeholders, and observation of community events and existing MHP projects over the course of three months. A thematic analysis revealed the various roles of community members and decision makers in MHP development, such as through the no objection certificate process for the Panchayat and Forest Rights Committee. Also identified were potential barriers and enablers to implementing a CBSEA, such as a lack of awareness surrounding MHP development, a desire for involvement in decisions, and evidence of strategic thinking. Participants further identified concerns about the potential cumulative effects of MHP projects on water availability and flooding.
Given the potential revealed in the data for CBSEA, a framework for its implementation was developed using five main themes to encompass the barriers and enablers identified. These include considering cumulative impacts, increasing participant engagement, ensuring adequate government support, providing educational support and training to community members, and improving the reliability of decision-making processes. Given the research findings, focusing on these five themes would allow for a CBSEA to be implemented in the Upper Kullu Valley.February 202
Genetic discrimination: a critical discourse analysis of legislation in North America
Full text linkMy research examines the legal and societal dimensions of genetic discrimination in North America, focusing on the Genetic Information Non-Discrimination Act in the U.S. and the Genetic Non-Discrimination Act in Canada. Using Fairclough’s Critical Discourse Analysis and Pistor’s theory of legal coding, I explore how legal frameworks and discursive practices in North America construct genetic information as a governable object that is protected, rendered usable, and valuable within biomedical innovation. Amid advances in genomic technologies and rising concerns over data misuse, legislative efforts have emerged to protect individuals. However, such protections are narrow in scope, primarily covering employment and health insurance. By analyzing legal texts, policy documents, and media narratives, this research illustrates how genetic information is discursively constructed as a form of capital, turning patients into health consumers and economic value sources. It also highlights how discourses of self-responsibility and empowerment often mask deeper neoliberal logics of autonomous individuals and the commodification of genetic data. Through a multilevel examination of this phenomenon at textual, discursive, and social levels, my dissertation reveals how genetic discrimination laws protect against certain harms while simultaneously legitimizing the marketization of genetic data. My research also illustrates the dual role of legislation that protects individuals from discrimination while embedding genetic data within the structures of market mechanisms. The findings contribute to ongoing debates about privacy, health equity, and the use of genetic information.February 202
Towards a collective understanding of fraction as quotient and a deeper mathematical knowledge for teaching
Full text linkResearch conducted in many countries has shown that teaching and learning fractions is a challenge for students and teachers (Cramer et al., 2002; Kieran, 1976; Lamon, 2007; Moss & Case, 1999; Tian & Siegler, 2018; Van Steenbrugge et al., 2014). One proposed cause of limited fractional understanding is an overemphasis on part-whole and an under emphasis on the four other interpretations of fractions in curriculum standards and learning activities (Charalambous & Pitta-Pantazi, 2007; Cramer et al., 2002; Lamon, 2007). Quotient, one of the five interpretations, is argued to be important as it is linked to multiplicative structures (Lamon, 2007), magnitude (Johanning & Mamer, 2014) and cardinality (Cooper et al., 2012). In this study, I used a methodology informed by hermeneutic phenomenology to analyse the K-8 mathematics curriculum standards and support documents in the province of Manitoba, Canada and found little explicit attention to the quotient interpretation. I also facilitated three interactive inquiry sessions with a small group of experienced Grades 4-8 teachers to explore their understanding of the quotient interpretation of fractions. Analysis of the transcripts and artifacts from the sessions revealed seven features which seemed to impact the development of mathematical knowledge for teaching (MKT) of fraction as quotient: problem-solving contexts, the quotient notation and generalization, re-defining quotient as more than the answer to a division question, difficulty describing fraction as quotient, lack of focus on fractions as relationships, working with indefinite amounts, and curriculum standards and support materials. Recommendations for schools, divisions, and Manitoba Education to support teachers with the concept of fraction as quotient are made and areas of future research are identified.February 202
The effect of integrated crop management (ICM) on crop-weed competition, weed phenology and weed seed dormancy
Full text linkIntegrated Crop Management (ICM) is a holistic framework that integrates soil, nutrient, pest, and weed management to improve agricultural sustainability and productivity. However, limited information exists on how combining nitrogen fertilization strategies with cultural weed control influences crop–weed competition, weed phenology, and weed seed dormancy in Western Canadian wheat systems. Field experiments were conducted in 2023 and 2024 at Carman, Manitoba, and Kernen, Saskatchewan, using a split-plot RCB design with four replicates. Treatments consisted of a four-factor factorial combination of nitrogen fertilizer timing (fall vs. spring application), fertilizer placement (broadcast vs. side-banding), fertilizer rate (full vs. half rate), and weed management strategy (integrated weed management, (IWM) vs. standard management). IWM included narrow row spacing (15 cm), high crop density (400 plants m⁻²), and early seeding, whereas standard management used wider row spacing (30 cm), lower crop density (200 plants m⁻²), and late seeding. The study evaluated ICM effects on crop–weed competition, weed phenology, and weed seed dormancy of wild oats (Avena fatua L.), volunteer canola (Brassica napus L.), and redroot pigweed (Amaranthus retroflexus L.). Across site-years, weed density and biomass were reduced by up to 66% and 73%, respectively, under side-banded, half-rate nitrogen combined with IWM compared with broadcast, full-rate nitrogen under standard management during favorable growing conditions at Carman in 2024. Weed height was reduced under IWM during dry conditions in 2023; however, under favorable moisture conditions in 2024, weed height increased in IWM plots, particularly under full-rate nitrogen. Flowering duration was shortened for wild oats and volunteer canola under IWM, resulting in reduced reproductive windows. Total weed seed production declined by up to 93% under full-rate nitrogen, side-banding with IWM relative to broadcasting, full-rate nitrogen with standard management. In large seeds category of wild oats, IWM exhibited lower dormancy, particularly under full-rate N. These reductions in weed pressure translated into substantial wheat yield gains, with IWM increasing grain yield by up to 140% compared with standard management across experiments. Overall, integrating weed management with nitrogen management strengthens crop competitiveness, alters weed phenology and seed dormancy, and improves wheat productivity.MITACS Accelerate;
Title- The Effect of Integrated Crop Management on Weed Phenology and Weed Persistence, Funder ID- 58357
UMGF(University of Manitoba Graduate Fellowship).February 202
Polygenicity of cognitive ability and educational attainment in multiple sclerosis
Full text linkAbstract
Background: Lower educational attainment is associated with higher risk of multiple sclerosis (MS). In those with MS, cognition may be impaired. Cognitive ability and educational attainment are both heritable traits, with the latest large genome-wide association studies identifying >200 and >1,000 genomic loci associated with these traits, respectively but these studies did not investigate these traits in people with MS. Polygenic scores (PGS) consider the cumulative effects of multiple genes on a trait. Studies have not yet examined the association of the PGS for cognitive ability and educational attainment, specifically in persons with MS (pwMS).
Objectives: In PwMS, I aimed to determine whether (a) a cognitive ability PGS is positively associated with information processing speed and (b) an educational attainment PGS is positively associated with years of education and education level.
Methods: I used existing data from three cohorts: a study of psychiatric comorbidity in MS from Canada (IMID); an American 3-arm, multi-center, Phase III clinical trial on combination disease modifying therapy for MS (CombiRx); and the UK Biobank (UKB), a population-based study of 502,655 individuals. PwMS completed various of measures of information processing speed: Symbol Digit Modalities Test (IMID), Paced Auditory Serial Addition Test (CombiRx) or
Digit Symbol Substitution Test (UKB) and reported their number of years of education (IMID, UKB) or highest education level achieved (all cohorts). I generated the PGS for cognitive ability and educational attainment based on the largest genome-wide association studies of both traits using SBayesR, and standardized to mean=0, standard deviation=1. I tested the association of the cognitive ability PGS with information processing speed and then the educational attainment PGS with education years or level in PwMS using regression. Analyses were completed by cohort and then pooled together using fixed-effect meta-analysis.
Results: I included 2092 PwMS of European genetic ancestry (213 IMID, 602 US, 1,277 UK). The average age and sex were similar across cohorts. Meta-analyses revealed in PwMS, higher cumulative cognitive ability PGS was associated with higher information processing speed (beta per standard deviation [SD]=0.59 standard error [SE]=0.23, P=0.01). Likewise, higher cumulative genetic score for educational attainment was associated with more years of education (beta per SD=0.56, SE=0.10, P<0.001) in PwMS (excluding US cohort) or higher education (beta per SD=0.39, SE=0.06, P<0.001). The variance explained by PGS were similar to non-MS cohorts (range cognitive ability PGS R2: 0.035-0.094, educational attainment PGS R2: 0.034-0.15).
Conclusions: Polygenicity for higher cognitive functioning and educational attainment were associated with information processing speed and education in PwMS, respectively. This study was able to show associations found in the MS population were consistent with similar studies done in general, non-MS populations.Advanced Degrees in Medicine UofM (MD/MSc)
United States of America Department of DefenseFebruary 202