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The Evolving Landscape of Radioisotopes in Modern Medicine
Full text linkIntroduction After decades of development, an increasing repertoire of radioisotopes are experiencing rapid growth in demand, both for diagnostic molecular imaging (MI), but also targeted radionuclide therapy (TRT) – two modalities with great potential for the identification and treatment of difficult-to-treat diseases, including micro-metastatic cancers, antibiotic-resistant bacterial infections and viral infections. Clinical MI agents (specifically PET and SPECT radiotracers) were dominated for years by a small group of short-lived, main-group positron-, and metallic single-photon emitting radioisotopes. However, recent advances in technologies in and around solid targets and metal isotope production are now enabling cyclotron centres to produce and distribute many emerging and important radionuclides for clinical use. On the TRT front, recent clinical results demonstrating the efficacy of beta- and alpha-emitting radiopharmaceuticals toward advanced, metastatic disease have triggered a global pursuit for new drugs. Couple this with increasing supply of promising alpha-, beta- and Auger-emitting radionuclides, personalized diagnostic, therapeutic and theranostic medicine is closer to reality now than ever before. Researchers at facilities such as TRIUMF are playing an active and important role in developing and translating new technologies that are paving the way for the discovery and translation of radioisotopes and radiopharmaceuticals that will ultimately enable the paradigm of personalized molecular medicine. Description of the Work or Project Many of the ~1400 medical cyclotrons around the world today operate between 16 and 24 MeV [1], an ideal range for producing, among others, isotopes including 99mTc [2,3], 68Ga [4], 64Cu and 89Zr [5]. Efforts at TRIUMF have led to the development of a solid target transfer and irradiation system, and solid target processing chemistry which has demonstrated a high-yield, automated method for producing GBq-TBq quantities of these isotopes using up to 500 μA of ~13-22 MeV protons. Fully automated dissolution/separation processes along with regulatory filings now allow for cyclotron-produced materials to substitute for other sources used in the clinic today. On the therapeutic isotope front TRIUMF is scaling-up processes to produce 225Ac via the high-energy proton irradiation of 232Th, with the aim of implementing a scalable and routine production operation capable of supporting multiple clinical trials [6]. Targets containing 0.5 mm thick, 11 g thorium foils were irradiated to12,500 μAh with ~450 MeV protons using TRIUMF’s 500 MeV Isotope Production Facility (IPF), producing GBq quantities of 225Ac, 225Ra, 228Th, 212Pb, among a number of other alpha-emitting isotopes of interest [7]. A discussion will include recent experiences with target chemistry automation, product quality control, and Th-spallation waste handling and disposal. Conclusions This presentation will provide a summary update on the development and implementation of several newer technologies toward direct cyclotron-production of various emerging radionuclides across a fleet of 13 to 520 MeV cyclotrons located at TRIUMF and its partner institutions. References [1] Accelerator Knowledge Portal https://nucleus.iaea.org/sites/accelerators/Pages/Cyclotron.aspx [2] Beaver, J.E., Hupf, H.B. (1971). J Nucl Med. 12(11), 739–41. PMID 5113635 [3] Bénard, F. et al. (2014). J.Nucl.Med. 55(6), 1017-22. https://doi.org/10.2967/jnumed.113.133413 [4] Thisgaard, H. et al. (2021). EJNMMI Radiopharmacy and Chemistry. 6:1. https://doi.org/10.1186/s41181-020-00114-9 [5] Oehlke, E. et al. (2015). Nucl. Med. Biol. 42, 842-49. http://dx.doi.org/10.1016/j.nucmedbio.2015.06.005 [6] Robertson, A.K.H. et al. (2020). Inorg. Chem. 59(17), pp. 12156-165. https://doi.org/10.1021/acs.inorgchem.0c01081 [7] Robertson A.K.H., Kunz, P., Hoehr, C., Schaffer, P. (2020). Physics Review C, 102, 044613. https://journals.aps.org/prc/abstract/10.1103/PhysRevC.102.04461
Indigenous Women’s Experiences of Colonial Violence by the Canadian Legal System in the Context of their Intimate Partner Violence Relationships
Full text linkContemporary violence against Indigenous women (VAIW) is enacted through a comprehensive range of state agencies designed to oppress Indigenous peoples so they cannot challenge settler colonial dominion. One such state agency is that of the Canadian Legal System (CLS). Tasked with upholding the authority of the settler colonial state, the CLS enacts institutional and structural violence to reproduce conditions of marginalization and oppression of Indigenous people. One avenue in which this violence is enacted is found in inadequate CLS response to epidemic rates of VAIW. Despite multiple calls to action and justice which specifically name the CLS, rates of VAIW remain high, particularly rates of intimate partner violence (IPV) against Indigenous women. As the CLS is the de facto response to violent victimization and IPV, Indigenous women are forced to turn to an institution that has demonstrated indifference to their victimization.
This thesis investigates Indigenous women’s’ experience of colonial violence by and through the CLS in the context of their IPV relationship. Using an Indigenous feminist framework to critically analyze 30 Indigenous women’s narratives of seeking out the CLS to address their IPV victimization reveals several common experiences. Findings revealed an overarching experience of colonial violence - comprised of and experienced as institutional and structural violence – that has served to reproduce the conditions in which these women initially underwent violence, resulting in more opportunities for their continual victimization and revictimization. CLS inaction to meaningfully address their IPV victimization stemmed from latent bias and assumptions of Indigenous women as culpable, and thus, deserving of the violence they were experiencing. When reporting violence, many reported being met with skepticism about whether they experienced violence at all, and disbelief about the severity of that violence. Whether through inaction or direct action, the CLS contributes to these Indigenous women’s experiences of IPV. It becomes apparent that the CLS’s response to VAIW, particularly IPV against Indigenous women, is a continuation of the settler colonial project of elimination, making it clear that the CLS has no role in addressing IPV and VAIW in Indigenous communities
LITHIUM OROTATE SELECTIVELY INHIBITS GSK3β WITHOUT IMPACT ON INOSITOL SIGNALLING
Full text linkLithium Carbonate (LiCO) has been the standard pharmacological treatment for bipolar disorder (BD) for over half a century because it successfully reduces the manic and depressive
characteristics of BD. Unfortunately, patients often discontinue LiCO treatment due to adverse physiological and cognitive side effects. LiCO treatment is limited by the narrow therapeutic
window where high doses lead to toxicity or increased risk of side effects while lower doses are
considered ineffective. Lithium orotate (LiOr) is an alternative treatment suggested to possess
superior uptake properties compared to LiCO, which may reduce dosing requirements and lessen
cognitive side effects. As LiOr yields higher brain lithium (Li+
) than LiCO due to different
transport mechanisms and is only liberated intracellularly distant from the cell membrane, we
hypothesize that 1) LiOr will be more potent than LiCl and 2) LiOr will selectively inhibit GSK3β
to facilitate long-term potentiation (LTP) while LiCl acts closer to the membrane on N-methyl-D aspartate (NMDA) receptors and the phosphatidylinositol cycle. Dose-dependent LiCl and LiOr effects on synaptic plasticity were assessed in the hippocampal Schaffer collateral-CA1 synapse in male C57BL/6 mouse slices. LTP was induced by theta burst stimulations (TBS) (8 bursts at 5 Hz of 4 high-frequency pulses at 100 Hz repeated three times, 60 seconds apart) at 32℃. Long-term depression (LTD) was induced using a low frequency stimulation (LFS; 1 Hz) for 15 minutes at room temperature. We used typical therapeutic Li+ concentrations between 0.2-1.0 mM to assess Li+ effects on synaptic plasticity. We compared the effects the phosphoinositol cycle had on Li+
-mediated effects on LTP by incubating
slices in myo-inositol for 2-3 hours. We used basic pharmacology to determine the effects LiCl
and LiOr had on GSK3β and NMDA receptors with 3.5 µM AZD2858, a non-specific GSK3Β
inhibitor, and 5 µM DNQX to isolate NMDA currents. We found that LiCl and LiOr differentially affect synaptic plasticity by mediating different
secondary messenger pathways. All concentrations of LiOr influenced synaptic plasticity, but only
higher concentrations of LiCl altered LTP and LTD. We determined that LiCl had a dose dependent effect on the phosphatidylinositol pathway and NMDA receptors, whereas LiOr
consistently increased LTP through inhibition of GSK3β. Therapeutic LiCl concentrations demonstrate a dose-dependent response on synaptic
plasticity, whereas LiOr has a consistent effect at both high and low concentrations. This differential effect could explain the contrasting findings on the effects LiCO has on cognition, as slight changes in Li+ concentration drastically change the synaptic response. This provides clinical
relevancy to BD research as it indicates LiOr is a more beneficial treatment for BD because it can
be prescribed at a lower dose than LiCO with the same effect. This study could influence clinical
Li+ application and may lessen the adverse physiological and cognitive impact associated with Li+
treatment
Therapeutic Potential of Acute Intermittent Hypoxia (AIH) In Early Repair of Decompressed Peripheral Nerves
No full textThe abstract of this item is unavailable due to an embargo
Tipping Points in First Nations' Land Use: Understanding the Impacts of Industrial Development in Northeast British Columbia
Full text linkThis study examines the impact of industrial development on the land use practices of the Saulteau First Nations (SFN) in northeastern British Columbia. Using household surveys and spatial data analysis, the goal is to identify critical tipping points at which industrial activities disrupt SFN members’ traditional harvesting practices.
The 12-month household survey revealed that most of the SFN harvest occurred near the SFN reserve, although some distant locations in the north were used to target specific species. Additionally, the northwest region of the SFN reserve offered better hunting opportunities compared to the east region, which faced extensive oil and gas developments.
Significant constraints to SFN land use were identified as human-induced disturbances, such as industrial development, environmental change, food contamination, and recreational development. Spatial analysis revealed areas of conflict between industrial activities and SFN harvesting practices, particularly near the SFN reserve and municipality centre.
This study proposes an industrial tipping point model and identifies a cessation tipping point (industry density = 0.084 km2/km2) where industrial development significantly hinders SFN's traditional land use practices. The results also highlight the subjective and varied nature of determining a tipping point influenced by specific land use activities and household assets.
The research findings are intended to facilitate constructive dialogue between the SFN community and the provincial government of British Columbia to preserve environmental livelihoods and territorial rights. The study emphasizes the importance of conservation and restoration efforts in core areas of the SFN territory. The insights provided can assist the Regional Strategic Environmental Assessment Project Team in striking a balance between sustainable economic development and the rights of First Nations in the region
“You kind of just have to give up on that dream”: Saskatchewan women’s and men’s experiences with fertility gaps
Full text linkLongitudinal research has shown that women and men are more likely to underachieve, than overachieve, their child number preferences (Quesnel-Valleé & Morgan, 2003). Such discrepancies between preferences and reality are known as fertility gaps (Chesnais, 2000; Phillipov, 2009). This thesis sought to further the qualitative work of Carvalho and colleagues (2018), who demonstrated that individuals in Brazil were often satisfied with their experienced fertility gaps. Using the Model of Dyadic Pathways (Brehm & Schneider, 2019), a context-based approach was taken to explore the unique ways in which women and men experience timing and number gaps. Biographical narrative interviews were conducted in-person or via Zoom with women and men who mostly resided in Saskatchewan, Canada. After applying purposive sampling techniques, the final sample consisted of seven women and seven men who had or wanted (more) children, ranging in age from 27 – 41 years. Interpretative Phenomenological Analysis was used to explore participants’ perceptions of experienced or anticipated fertility gaps.
Participants associated multiple factors with fertility gaps (e.g., infertility, completing education, establishing job stability, and the COVID-19 pandemic) and often made sense of timing and number gaps by explaining their perceived level of control over circumstances that affected their child-related decisions. For example, women and men often expressed an openness to situations that they felt were beyond their control (e.g., romantic relationship formation) and came to accept timing and number gaps despite alternative preferences. Participants also talked about choosing fertility gaps, whether out of necessity or due to strong desires to satisfy other life aspirations first. Some women and men expressed negative feelings towards fertility gaps, such as worry and stress. Though many participants accepted the discrepancies they talked about, they noted a number of supports that would (or did) assist them in their decision-making (e.g., financial, social, and informational support). The results suggest that maintaining and improving policies and practices (e.g., related to childcare, financial incentives, and parental leave) can help people navigate their fluctuating preferences and make decisions about children easier. Having available, accessible, and affordable supports may encourage agency in peoples’ decisions about children, in a way that they can choose whether or not fertility gaps are suitable to them. A provincial needs assessment would be useful to identify how to best support people in Saskatchewan
IMPACT OF CONVENTIONAL AND PRECISION CATTLE MANURE APPLICATION METHODS ON HORMONE CONCENTRATIONS AND ACTIVITIES IN SURFACE WATER AND SOIL
Full text linkWorldwide, agricultural activities such as animal production have intensified to supply nutrients for the growing human population. To satisfy nutritional demands, sustainable strategies must be implemented to enhance agricultural outputs and manage resulting by-products, while securing agricultural and environmental system viability. Intensive animal production can generate vast quantities of animal manure that is concentrated within relatively limited areas. Managing manure is challenging, but management often involves applying manure to agricultural lands. Applying manure to land recycles valuable nutrients and organic matter beneficial for producing crops. However, manure-borne pollutants, such as hormones, can threaten water and soil quality. Specifically, hormones can be readily exported in surface runoff water from manured fields to ecosystems. This thesis compared conventional and precision manure application strategies to determine if either method contributed hormone concentrations and activities to water and soil. For this watershed-scale study, a previously unmanured cropland field adjacent to the University of Saskatchewan Beef Cattle Research and Teaching Unit was used for a study established in 2018. Within the field, three treatment zones of approximately 40 acres each were set up. The three treatments were 1) commercial fertilizer (no manure), 2) conventional, also termed traditional, cattle manure application at constant rate with no setbacks from watershed basin centers, and 3) precision cattle manure application at variable rate with no manure applied in basin centers. During 2019, snowmelt, rainfall runoff, and soil was collected from nine watershed basins within the three field treatment zones. Manure source material was also directly sampled from the windrow pile used for field treatments in May of 2019. In 2021, fecal rectal grabs, pen floor manure, and windrow pile manure were also collected from the cattle feedlot facility where manure was obtained for field treatments. Chemical analyses were combined with in vitro reporter gene assays to assess hormone concentrations and activities in environmental samples and manure materials. Targeted hormonal growth promoting chemicals, and corresponding metabolites, were identified and quantified by liquid chromatography ultra-high resolution mass spectrometry, while hormone activities were assessed by in vitro bioassays. Targeted analytes included trenbolone acetate, 17α-trenbolone, 17β-trenbolone, trendione, melengestrol acetate, and melengestrol. No target analyte concentrations were detected in any water, soil, or windrow pile manure. Fresh rectal feces contained 17α-trenbolone and 17β-trenbolone, while pen floor manure contained 17α-trenbolone. Hormone activities assessed included (anti-)androgenic/glucocorticoid activity and (anti-)estrogenicity. Fresh and pen materials both contained androgenic/glucocorticoid activity, and (anti-)estrogenicity. In contrast, windrow manure samples (collected in 2019, and 2021) were mostly estrogenic and lacked androgenic/glucocorticoid activity. All pre- and post-manure application water samples (snowmelt, and rainfall runoff) were estrogenic. Estrogenic potency was increased in rainfall runoff after conventional application. In contrast, estrogenic potency did not increase in rainfall runoff after precision application. No hormone activities were detected in soil samples collected late August of 2019. Increased estrogenicity in rainfall runoff from the conventional application likely originated from windrow manure uniformly applied across the field, which included the watershed basin centers. These results indicate precision manure application, with setbacks, may protect water from hormone entry. Precision application may be particularly effective if runoff occurs after recent manure-amendment, or before hormones dissipate in manured soils. This thesis supports precision manure application as a viable method to help mitigate hormone export from manure-amended soils to sensitive systems
Exploring the Past: A Retrospective Look at the Experiences of Young Men in High School Physical Education Classes
Full text linkHigh school physical education classes aim to provide young men with the competence and confidence needed to lead a physically active lifestyle (Borghese, 2019; Tanaka et al., 2018). As well, physical education is recognized as a significant contributor to the daily accumulation of moderate to vigorous physical activity among young men (Tanaka et al., 2018). However, a considerable gap exists in the literature regarding what specific factors influence young men to participate during their physical education classes. Using a retrospective, qualitative description study, this research project explored the previous high school physical education experiences of 10 male-identifying students at the University of Saskatchewan. Using two rounds of semi-structured, individual interviews, each participant’s previous physical education experiences were investigated at length. The findings from these individual interviews can be understood through three themes: Us and Them, The Physical Education Teacher: “Him and His Football Boys” and Physical Cultural Capital. Woven throughout these three themes, the findings suggest that several key factors play a role in determining a young man’s participation and engagement in physical education. These key factors include competitiveness, participation in community hockey or on the school football team, relationships with the physical education teacher and accruement of physical cultural capital. The findings of this study support previous research, identifying physical cultural capital as a factor that affects engagement in physical education (Jachyra, 2014). As there is a paucity of research regarding young mens’ experiences with participation in physical education, this study aimed to add relevant information to a topic that lacks sufficient research
Deep Learning Based Computer-aided Detection and Diagnosis Systems for Medical Imaging
No full textThe abstract of this item is unavailable due to an embargo