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Baseline lung allograft dysfunction after lung transplantation: Risk factors, imaging, and quality of life
No full textIntroduction
Baseline lung allograft dysfunction (BLAD) is a physiologic state in double lung transplant recipients where lung function fails to normalize and is associated with an increased risk of death after transplant. However, the risk factors and causes remain unknown, as does the association with patient-important outcomes such as quality of life and exercise capacity. One potential contributing factor to BLAD physiology may be reduced diaphragm function, which can be affected postoperatively due to phrenic nerve injury, ventilation-associated atrophy, or medication effects. Objectives
We sought to determine whether BLAD after lung transplant was associated with changes in diaphragm structure and function, and whether patients with BLAD had lower quality of life and exercise capacity. Methods
We performed two studies. First, we conducted a prospective observational cohort study of patients sequentially double-lung transplanted in our program over a 1-year period from June 2023 through May 2024. We defined BLAD as failure to reach normal function, defined as both a forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) to reach > 80% predicted of a healthy reference population’s lung function on two consecutive tests > 3 weeks apart. We tested diaphragm function at 3-months post-transplant via ultrasonography and mean inspiratory pressure (MIP) measurements. We measured diaphragm thickness, thickening fraction, and excursion during tidal, deep, and sniff breath maneuvers. We compared these values in patients meeting criteria for BLAD at 3-months post-transplant, to patients with normal function using Wilcoxon rank sum tests and linear regression, adjusting for age at transplant, sex at birth, and primary lung disease. Second, we conducted a retrospective cohort study of patients who underwent double lung transplant from January 2004 to October 2018 who completed 1-year post-transplant Short Form 36 (SF-36) health-related quality of life questionnaires as well as six-minute walk distance (6MWD) testing to measure exercise capacity. We tested the relationship between BLAD status and SF-36 physical component summary scores and 6MWD using linear regression, adjusting for age at transplant, sex at birth, and primary lung disease. Results
In the prospective study, we included 56 patients, mainly transplanted for interstitial lung disease (ILD, 69%), 28 (50%) of whom met criteria for BLAD. Patients with BLAD had lower diaphragm excursion on deep breathing (p=0.0227) and sniff test (p=0.0143). There were no differences in thickness or thickening fraction. BLAD was associated with both MIP% predicted (p=0.0047), deep breath excursion (p=0.0210), and sniff test (p=0.0469) in multivariable linear regression models. In the retrospective study, 264 patients were included, 96 (36%) of whom met criteria for BLAD. Patients with ILD as indication for transplant, and those who received older, female, and heavy smoking donors were at increased risk of BLAD. BLAD was associated with lower SF-36 scores (p=0.0025) and 6MWD (p=0.0008) at 1-year post-transplant in multivariable linear regression models. Conclusion
BLAD was associated with lower diaphragm function but not structure at 3-months post-transplant, suggesting respiratory muscle function could be contributing to BLAD physiology in some cases. We are planning follow-up measurements at 1-year post-transplant in this cohort to assess the dynamics of diaphragm function and BLAD over time. BLAD was also associated with reduced HRQL and 6MWD scores at 1-year post-lung transplant in adjusted models, suggesting that poor post-transplant lung function is related to or could be contributing to lower HRQL and exercise capacity in lung recipients. Taken together, these findings give us additional insights into the nature and implications of BLAD and may suggest preventative and therapeutic strategies
Digital Resilience of ePortfolios During and Beyond the COVID-19 Pandemic: Lessons for the Future
No full textImpact of processing and chemical composition of Western Canadian ingredients in pigs
No full textFeed represents about two thirds of the total cost of pork production. Western Canadian ingredients such as lentil , canola meal (CM), and barley grain offer alternatives to conventional energy and protein sources fed to swine. Lentil, rich in starch and protein, may serve as alternative feed energy and protein source. While substituting soybean meal (SBM) with CM lowers feed cost, its greater fibre and anti-nutritional factor (ANF) content may impair nutrient utilization. Hull-less barley cultivars with fermentable carbohydrates may enhance gut health; however, barley grain inclusion in starter pig diets is limited due to its relatively high fibre content that may reduce nutrient digestion and growth performance. This thesis investigated the roles of lentil, CM, and barley grain in swine diets, focusing on their effects on nutrient utilization, growth performance, body composition and retention of energy, protein, and lipids. Additionally, effects of interactions among these ingredients, dietary fibre, starch, and processing technologies (e.g., extrusion, steam explosion) on metabolite profiles and energy efficiency to improve nutrient use, growth performance, and sustainability in swine production systems were explored.
In Chapter 2, ileal-cannulated grower pigs were fed lentil-based diets supplemented with either soybean meal (SBM) or fish meal (FM) as protein sources, with each diet subjected to extrusion or not. Feeding FM diets resulted in greater apparent ileal digestibility (AID) of dry matter (DM), gross energy (GE), and amino acids (AA) than the SBM diets. Extrusion increased the AID of crude protein (CP) and most AA, and the digestible energy (DE) value of lentil-based diets containing either SBM or FM. In chapter 3, two studies determined effects of steam-explosion on nutrient and energy digestibility in solvent-extracted Brassica napus canola meal in grower pigs and diet nutrient digestibility and growth performance in weaned pigs. Steam-explosion reduced ileal digestibility of CP, most indispensable AA and GE of canola meal in grower pigs. Dietary inclusion of 200 g canola meal/kg to replace SBM reduced average daily feed intake (ADFI), but not average daily gain (ADG), and thus increased gain-to-feed ratio (G:F) in weaned pigs. Steam-explosion of canola meal reduced dietary ATTD of CP and increased ADFI, but not ADG or G:F of weaned pigs. In chapters 4 and 5, low-fermentable, hulled barley grain (LFB) and high fermentable, hull-less barley grain cultivars (high β-glucan HFBB; high amylose HFAB) replaced low-fermentable, wheat grain in weaned pig diets. In Chapter 4, a fifth test diet was formulated using steam-exploded LFB. In Chapter 5, a diet with reduced NE value was formulated using LFB. Feeding barley grain to replace wheat grain reduced diet ATTD of GE and CP but did not affect growth performance in weaned pigs. However, hulled or hull-less barley to replace wheat grain did not affect AID of GE and CP, but high-amylose hull-less barley reduced AID of β-glucan and starch. Regardless of fermentable carbohydrates content, dietary inclusion of barley to replace wheat grain did not affect total SCFA concentrations in cecal and colonic digesta, virulence factor levels of enterotoxigenic Escherichia coli in ileal and colonic digesta, or body composition. However, high dietary fermentable carbohydrates reduced empty body weight (empty BW) and increased hindgut weight and digesta butyric and propionic acid concentration. Feeding a LFB with reduced NE value while maintaining SID AA content did not affect growth, empty BW, and organ weights, whereas steam explosion of LFB did not increase dietary energy, protein digestibility or growth performance in weaned pigs.
In conclusion, extrusion increased the feeding value of lentil-based diets. Steam-explosion reduced the nutritional value of CM in grower and nursery pigs. Feeding diets containing 200 g CM/kg, balanced for NE and SID AA to replace SBM, maintained ADG and improved G:F in weaned pigs. Feeding barley diets, regardless of fermentability or energy density, maintained growth performance and carcass weight, with fermentable carbohydrates favoring hindgut fermentation and cecal butyric acid production. Feed processing and balancing diets based on available energy and AA to match their supply and requirements can maintain growth performance and may lower feed cost when feeding protein- and fibre-rich alternative feed ingredient
Studies on Microwave and Millimeter-Wave FMCW Radars for Imaging and Tracking Applications
No full textFrequency modulated continuous wave (FMCW) radars are increasingly used across diverse applications that demand detection, localization, and tracking, including autonomous vehicles, biomedical imaging, non-contact medical measurements, vital sign monitoring in rescue operations, through-wall imaging, security and surveillance, human tracking, gait analysis, and material inspection. In all such applications, high resolution is a critical requirement that guarantees the radar system’s effectiveness.
Fine range resolution is achievable through a broad RF sweep bandwidth over which the radar operates. Cross-range resolution is improved through two classes of methods, i.e., synthetic aperture radar (SAR) and multiple-input multiple-output (MIMO) radar system. The purpose of this research is to study both structures and propose effective solutions to the challenges in each case.
The first part of this thesis presents a low-cost, easily-implementable, and portable S-band FMCW SAR system with broad frequency coverage for short-range imaging applications. Design considerations and radar performance metrics are discussed in detail while investigating systematic and nonsystematic performance-limiting factors.
A signal processing procedure based on a closed-form comprehensive mathematical model is introduced to characterize the impact of the nonlinear frequency sweep on radar performance. Based on the proposed model, the nonlinearity is compensated using the time-resampling technique and without needing a reference response.
However, achieving accurate target localization requires more than just nonlinearity compensation. In particular, calibration plays a crucial role in enhancing the accuracy of radar measurements. Single-zone calibration alone fails to provide sufficient accuracy when multiple targets are widely distributed across the azimuth. To address this, a range- and angle-dependent calibration scheme is introduced, offering a more precise mitigation of second-order effects that are otherwise challenging to model mathematically. Detecting less reflective targets in the presence of a strong scatterer is challenging. A range-gating method based on a tunable active bandpass filter (BPF) is proposed to improve the radar system’s sensitivity by suppressing the dominant reflection and enhancing the weaker scatterer. The results are verified by developing SAR images of targets in free space and through a residential wall. Many modern radar applications require very fi ne angular resolution and high up-date rates demanding for a different radar structure at higher frequency ranges with faster chirp rates. In the second part of this thesis a fast-chirp MIMO FMCW radar sensor is used and array processing algorithms for such applications are developed. A specific focus is given to estimating the impinged signals’ direction of arrival (DoA) using the MIMO radar system as a crucial step in modern radar applications. Estimating DoA when there are more reflectors than sensor count is a challenge. This thesis offers a new insight into the problem and proposes an efficient yet straightforward solution. The proposed method focuses on increasing the degree of freedom (DoF) in the data processing stage, offering a practical solution against limitations imposed by traditional approaches which address this issue through customized antenna array designs, in which the results have primarily been evaluated numerically and thus require further practical investigation. The proposed method, however, provides an effective solution without expanding and complicating the antenna array geometry. The thesis put forward an approach based on 2D multiple signal classification (MUSIC), joint with 2D forward-backward spatial smoothing (FBBS) technique enabling localizing more targets than the number of sensors. The proposed method’s effectiveness is verified through simulations and measurements under different practical scenarios, preceded by a comparative study of the popular DoA estimation techniques
Genomic Instability and DNA Damage Regulate Dendritic Cell Mediated Anti-Tumor Immunity Through Distinctive Cytosolic DNA Structures in Colorectal Cancer
No full textBackground. Cancer genomes are characterized by instability, with significant levels of DNA damage and mutation due to DNA repair defects. In colorectal cancer (CRC), defects in mismatch repair define the microsatellite instable (MSI) subtype, with stronger immunogenicity and better prognosis than the more common chromosomally instable (CIN) subtype. The mechanisms behind these differences remain unknown, but their understanding could identify therapeutic strategies to improve the prognosis of CIN CRC patients. The cGAS/STING pathway detects foreign DNA in the cytosol, leading to production of type I interferon and induction of innate and adaptive immune responses. In cancer, cGAS/STING also recognizes self cytosolic DNA (cyDNA) in the form of micronuclei or free DNA fragments generated by endogenous or treatment-induced DNA damage. cGAS/STING is required for the full efficacy of DNA damaging therapies like radiation, and our lab previously identified this pathway as a key player in the increased cytotoxic T cell infiltration characteristic of MSI CRCs. However, we were unable to detect a difference in the concentration of cyDNA between MSI and CIN CRC cells.
Hypothesis. I hypothesize that different forms of endogenous or external sources of DNA damage produce cyDNA with sequence and/or structural patterns that influence cGAS/STING activation and overall anti-tumor cytotoxic T cell responses.
Results. First, to examine the effects and composition of cyDNA, I developed a protocol to isolate cyDNA from cells. With this method, I isolated cyDNA from MC38 CRC cells, patient organoids, and dendritic cells (DCs) without any detectable mitochondrial contamination. Next, I aimed to determine whether different types of genomic instability, such as MSI vs CIN, or DNA damaging therapies produced cyDNA that was differentially capable of activating cGAS/STING. Using MC38 cells with previously developed CRISPR mutations in Mlh1 to model MSI, and Kras to model CIN, I isolated cyDNA for stimulation of DCs, a key responder to cGAS/STING pathway activation that coordinates innate and adaptive immune responses. At equal concentration, MSI cyDNA induced higher STING and DC-mediated cytotoxic T cell activation compared to CIN cyDNA. Similar results were observed with cyDNA isolated from patient organoids. Stimulations with cyDNA isolated following radiation or oxaliplatin treatment showed that these DNA damaging therapies also produce highly stimulatory cyDNA. Next, I aimed to characterize specific changes in cyDNA composition that affect cGAS/STING signaling. Next generation sequencing identified an enrichment for microsatellite sequences in MSI cyDNA. I then determined that microsatellites induce higher activation of cGAS/STING, and thereby cytotoxic T cells, by DCs compared to scrambled sequences through improved binding to cGAS. Transfer of DCs activated with microsatellite rich DNAs into mice bearing orthotopic CIN tumors led to improved cytotoxic T cell infiltration and activation, showing that microsatellite rich cyDNAs can be used to directly improve anti-tumor immune responses in CIN CRCs. Finally, I aimed to examine the role of DNA structure in the sensing of MSI and CIN cyDNA. Structural prediction analysis and atomic force microscopy showed that MSI cyDNA is enriched in G-quadruplexes (G4s). I found that G4s are highly effective at activating cGAS/STING and cytotoxic T cells through DCs and show that this can be replicated in CIN cyDNA through treatment with G4 stabilizing agents. I also evaluated the role of micronuclei in MSI vs CIN cyDNA. DCs stimulated with MSI or CIN micronuclei show higher cGAS/STING activation, and thereby cytotoxic T cell infiltration, from MSI micronuclei compared to CIN at equal DNA concentration. Additionally, despite similar effects on cGAS/STING activation in vitro, transfer of micronuclei or free cyDNA stimulated DCs into orthotopic CRC bearing mice showed a role for micronuclei in immunosuppression, with increased Treg activation and IL10 production compared to free cyDNA. Notably, micronuclei are linked to CIN, indicating a possible mechanism for the poor immunogenicity of CIN CRCs. Significance. Understanding the mechanisms underlying the improved cytotoxic T cell responses in MSI CRCs allows for development of therapies to improve the anti-tumor immunity and prognosis of poorly immunogenic tumors like CIN CRCs. Here I show that highly stimulatory cyDNA sequences can be used as STING agonists to activate DCs and stimulate improved anti-tumor T cell responses in CIN tumors. These DNAs could be used therapeutically to improve cytotoxic T cell infiltration for combination with immune checkpoint inhibitor therapies to improve patient care
Social fragmentation and maternal mental health: a longitudinal analysis of depression and anxiety among pregnant women and mothers in Alberta, Canada
No full textBackground: Maternal mental health is a significant public health concern, particularly during the perinatal period when depression and anxiety are prevalent. In Canada, approximately 23% of postpartum mothers report symptoms of depression or anxiety. Social fragmentation, characterized by weakened social ties and community cohesion, has been linked to mental health challenges. However, its impact on maternal well-being remains underexplored, particularly within the Canadian context.
Objective: This study examines the association between neighborhood social fragmentation and maternal depression and anxiety, among mothers in Calgary, Alberta. The research aims to investigate whether higher levels of social fragmentation correspond with increased risks of depressive and anxiety symptoms.
Methods: Using data from the All Our Families (AOF) cohort, this study analyzed 1,693 mothers from 158 neighborhoods, collected across four time points from early pregnancy (<25 weeks’ gestation) to one year postpartum. Social fragmentation was measured using the Congdon Index, derived from the 2006 Canadian Census. Multilevel growth curve modeling was employed to evaluate the relationship between social fragmentation and maternal depression and anxiety, while accounting for individual- and area-level covariates. Sensitivity analyses were performed to examine the robustness of the results.
Results: Contrary to initial hypotheses, those who lived in neighbourhood with the highest level of neighborhood social fragmentation were significantly associated with lower depressive symptoms among mothers in the fully adjusted model (regression coefficient β = -0.76, 95% CI: -1.43, -0.08). This inverse relationship was not observed for anxiety symptoms (regression coefficient β = -1.01, 95% CI: -2.45, 0.44), suggesting that the social and contextual factors influencing depression and anxiety may differ. When depressive and anxiety symptoms were analyzed as dichotomous outcomes, no significant associations were found.
Conclusion: These findings challenge conventional assumptions that social fragmentation uniformly predicts negative mental health outcomes. Instead, they underscore the nuanced relationship between social environment and maternal mental health, suggesting that fragmented neighborhoods may possess protective factors that warrant further exploration. Future research should aim to contextualize social fragmentation measures and investigate the community dynamics that might contribute to maternal resilience in fragmented settings
In Pursuit of Truth: Challenging Colonial Narratives in Canadian Legislation with wâhkôhtowin and Other Indigenous Perspectives
No full textNationwide events that gained global attention have prompted the Canadian government to engage in reconciliatory efforts to promote the revitalization of Indigenous languages. The resultant Indigenous Languages Act appears to address the issues that have been highlighted in the media over the past several decades. The discourse and rhetoric surrounding the Indigenous Languages Act suggest that the government has implemented legislation that effectively recognizes and reconciles past injustices towards Indigenous peoples. I argue that this oversimplifies the colonial-Indigenous relationship, glosses over the reasons why Indigenous languages are endangered in the first place, and presents only one side of the story. The methods I used to explore my concerns consisted of close readings and discourse analysis of past legislation and events that flowed from these laws. Indigenous methodologies and theorists guided my research, and I drew from Indigenous voices broadly and the Cree worldview of wâhkôhtowin specifically to provide Indigenous perspectives. My research found that legislation and other colonial constructs use possessive logics to maintain the status quo and benefit white patriarchal sovereignty, which is rarely beneficial to Indigenous peoples. I have shown that the missing pieces of Canadian history lie in wâhkôhtowin and the voices of Indigenous peoples, who provide the rest of the story, challenge colonial narratives, and amend history with the truth. Because discourse shapes reality, the consequence of this strictly colonial narrative is the continued dis-representation of history that ignores the lived experiences of Indigenous peoples and leaves mainstream society unaware of the true history of Canada. Despite federal claims of redress, my research found that the Indigenous Languages Act falls short of reconciliation and that only structural change will begin to address the loss of Indigenous languages. Meaningful reconciliation begins with engaging Indigenous perspectives and embracing cultural cornerstones such as wâhkôhtowin
Mental Health Professionals' Competence and Current Practices Responding to Suicidality in Individuals with FASD
No full textPeople with Fetal Alcohol Spectrum Disorder (FASD) experience elevated rates of mental health challenges compared to the general population. Of particular concern are the elevated rates of suicidality consistently reported among people with FASD. Despite these high prevalence rates, there are currently no FASD-informed or FASD-specific suicide assessment and intervention measures or practices. Given the elevated rates of suicidality among people with FASD, it is likely that they work with diverse mental health professionals (MHPs) to support their mental health. MHPs are therefore tasked with providing care to people with FASD experiencing suicidality in the absence of evidence to inform their assessment and intervention practices. The current study aimed to 1) examine whether MHPs feel competent to support individuals with FASD experiencing suicidality, 2) what factors influence their competence, willingness to assess
and treat suicidality, and 3) what current practices MHPs are using to support people with FASD experiencing suicidality. Diverse MHPs (e.g., psychologists, counsellors, social workers, etc.) were recruited across Canada. 39 MHPs completed an online survey, including the Suicide
Competency Inventory and questions pertaining to MHPs’ knowledge about FASD, attitudes
about FASD, and current clinical practices related to supporting individuals with FASD
experiencing suicidality. The results indicated that the MHPs in the current sample reported high levels of competence, willingness to assess, and willingness to treat suicidality. MHPs who had received more suicide-specific training reported higher perceived competence and willingness to treat suicidality. MHPs who believed that people with FASD could lead purposeful lives with suitable supports and resources and who had worked with fewer clients with FASD experiencing suicidality reported a greater willingness to assess suicidality. These results highlight that suicide
assessment and intervention are distinct clinical practices predicted by unique factors. Further, the attitudes MHPs have about their clients with FASD impact their clinical practices related to
suicide assessment. The current study provides initial insights into factors that can be targeted by specific training and professional development programs to increase professional competencies and prepare MHPs to effectively support people with FASD experiencing suicidality. In particular, it is important for professional training programs and professional development efforts to foster positive attitudes about FASD and target unique underlying skills relating to suicide assessment and intervention
Vernon-John Gibbins - Abstract 76 - Innovate Conference 2025
No full textClinical course failure in nursing is often attributed to students' deficits in knowledge, skills, and abilities. Little attention is given to students’ perceptions of why they struggled