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HARVEST

University of Saskatchewan's Repository for Research, Scholarship, and Artistic Work

Welcome to HARVEST, the repository for research, scholarship, and artistic work created by the University of Saskatchewan community. Browse our collections below or find out more and submit your work.

 

Recent Submissions

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Development of targeted radioimmunotherapy for osteosarcoma using a comparative oncology approach
(2024-02-23) Prabaharan, Chandra Bose; Uppalapati, Maruti; Dadachova, Ekaterina; Kalra, Jay; Fonge, Humphrey; Freywald, Andrew; Valerie, MacDonald Dickinson; Dickinson, Ryan; Vorobyeva, Anzhelika
This study sheds light on the potential of developing targeted antibody-based therapies for osteosarcoma (OS) - a malignant bone tumor that affects both canines and humans. Researchers focused on a cation-independent mannose-6-phosphate/insulin-like growth factor-2 receptor (IGF2R), known for its overexpression in various OS cell lines. They utilised phage display libraries to create antibodies that recognise IGF2R in human, canine, and murine models, including a promising antibody named IF3. The antibodies were then radiolabeled and characterised in vitro and in vivo using patientderived tumor models in SCID mice. The results demonstrated the specific binding of these antibodies to tumours and their potential for effective tumour uptake, which are crucial aspects of antibody-based radioimmunotherapy (RIT). An innovative aspect of the study involved using 177Lu-labeled IF3 in mice with canine-patient-derived tumors, which showed high uptake in both the tumor and spleen, leading to significant inhibition of tumor growth. However, the study also revealed spleen-associated toxicity, indicating the need for careful clinical evaluation in future applications. The findings from the use of IF3, both in its radiolabeled form and various animal models, hold promise for developing targeted antibodybased therapies for OS in both humans and canines. Further modifications to IF3 were made by engineering an amino acid substitution in the Fc region and creating IF3δ, demonstrating the potential for FcRn-mediated endocytosis and recycling. However, biodistribution studies in mice revealed unexpected spleen and bone accumulation, highlighting the distinct pharmacokinetics between mouse models and potential human and canine applications. Lastly, we used a cell-based phage display method to identify CB01, an antibody that selectively binds to OS cell lines with minimal affinity to normal cells. CB01's interaction with glycosaminoglycans (GAGs) revealed the crucial role of glycans in OS and posits GAGs as novel therapeutic targets. MicroSPECT/CT imaging underlined CB01's efficacy in tumor targeting and biodistribution, emphasising its potential in precise cancer treatment through RIT. In conclusion, this study makes significant strides in understanding and treating osteosarcoma, introducing novel therapeutic approaches and insights into the roles of IGF2R and GAGs in cancer progression. The development of IF3 and CB01 antibodies represents a promising advancement in targeted therapies, offering hope for improved management and treatment efficacy in osteosarcoma across species.
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ANTIMICROBIAL PEPTIDES INSPIRED BY STAPHYLOCOCCAL PHENOL SOLUBLE MODULIN d-TOXINS
(2024-02-22) Deeyagahage, Hiruni Kathyana; Ruzzini, Tony; Vederas, John; Chelico, Linda; Siqueira, Walter; Leung, Adelaine; Rubin, Joe
The abstract of this item is unavailable due to an embargo.
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OPTIMAL HOME OXYGEN FLOW RATE FOR INFANTS WITH BRONCHOPULMONARY DYSPLASIA
(2024-02-20) Imran, Ahmad Ali; Adamko, Darryl; Daspal, Sibasis; Aneed, Anas El; Lawson, Joshua; Montgomery, Julia
INTRODUCTION: Bronchopulmonary dysplasia (BPD) is one of the most common morbidities related to preterm birth. Infants with moderate BPD are discharged on supplemental oxygen to maintain oxygen saturation between 90-96%, avoiding both hypoxia and hyperoxia, each with its own morbidity. Pulse oximetry (POX) is used to measure oxygenation in the blood. Near-infrared spectroscopy (NIRS) is a potential method to measure cerebral oxygenation and brain perfusion. To the best of our knowledge, there is a lack of normalized data for NIRS values in neonate infants going home with or without oxygen. We proposed that with combination of NIRS and pulse oximetry we could better identify a safe oxygen flow rate/concentration for babies with BPD. In doing so, we also sought to determine what the normative values of NIRS are in premature infants. METHODS: This was a prospective cohort study approved by the Bioethics Board, University of Saskatchewan. Infants were recruited from the NICU, Jim Pattison Children’s Hospital after obtaining written informed consent. One group (Control group, n=22) of relatively healthy preterm infants were recruited for NIRS measurements in relation to standard POX. We then compared NIRS and POX values on varying flow rates (0.03, 0.06, 0.12 L/Min) for moderate BPD infants going on home oxygen (n=10). RESULTS: Of the control infants in room air, the average POX value was 97.8% with SD ± 1.661 and SEM ± 0.006. The average time of hypoxia with POX below 90% was 3.5%, while time above 96% was 96.5%. The average NIRS value was 78.24% with SD ± 7.705 and SEM ± 0.027. The NIRS values for this group showed time at <60% was 1.4% of the time, 60%-80% was 50.75% and >80% was 47.9%. As expected, the difference of means between POX and NIRS (POX – NIRS) was 19.56% with the 95% confidence interval of 19.503 to 19.61. Cohen's correlation coefficient was 0.02 between the two variables Pulse Oximetry and Near-Infrared Spectroscopy. One-sided and two-sided p-tests values were 0.00. For the group on oxygen, at the flow rate of 0.03 lpm the average time with POX <90% was 2.35%, with 90-96% was 15.52% and with > 96% was 82.13 %. Time for this group with NIRS values <60% were 0.01%, 60%-80% were 58.5% and > 80% were 41.5%. At oxygen flow rate of 0.06 lpm, the average time with POX <90% was 1.43%, 90-96% was 6.08% and > 96% was 92.49%. Time for this group with NIRS values <60% was 0.6%, 60%-80% was 65% and > 80% was 34.4%. At oxygen flow rate of 0.12 lpm, the average time with POX <90% was 1.46%, 90-96% was 11.54% and > 96% was 87.00%. Time for this flow rate with NIRS values <60% was 0.2%, 60%-80% was 64% and > 80% was 34.8%. Individually, we did not see POX desaturation events associate with NIRS desaturations. CONCLUSION: As expected, there is an approximate difference of 19.5% between the POX and NIRS values with POX being higher that NIRS in healthy infants. Individually, we could not find any correlation between POX and NIRS values for hypoxia events. On average, we did not see a dose response correlation between oxygen flow rate and time spent in the hyperoxemic range across different flow rates by POX or cerebral NIRS. While NIRS could play an important adjunct role in the NICU for brain oxygen saturation, NIRS data cannot serve as a stand-alone monitoring tool.
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Analogue Computer Simulation of a Dragline
(1962-10) Ochitwa, David W.; Nikiforuk, P.N.
The purpose of this project was to derive a mathematical model which could describe the complete operation of a Marion Type 7800 dragline. This model could then be used for subsequent optimization studies leading perhaps to the fully automatic control of the digging operation. The dragline electrical equipment consisting of rototrols, generators and motors was, simulated on an analogue computer. The resulting steady state operations agreed very well with those of the actual dragline. Accurate definition of the load motion was difficult due to its highly nonlinear nature. Simulation of the nonlinear motion was made possible by the use of relays which altered the operating conditions as the analogue dragline cycle progressed. The results obtained indicate that a mathematical analysis, aided by an analogue computer, could be used to study dragline performance.
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Large Language Models vs. Stack Overflow Solutions in Addressing Android Permission-Related Challenges
(2024-01-17) Oishwee, Sahrima Jannat; Codabux, Zadia; Stakhanova, Natalia; Dutchyn, Christopher; Jin, Lingling
The abstract of this item is unavailable due to an embargo.
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Effectiveness of Whole Egg Versus Whey Protein Powder During Resistance Training
(2024-02-12) Onwukwe, Victor Maduabuchi; Chilibeck, Phil D; Candow, Darren G; Zello, Gordon A
The primary purpose was to compare the effectiveness of whole egg versus whey protein powder during 12 weeks of resistance training (RT) on lean tissue mass, and the secondary variables of muscle thickness, muscular strength, and blood glucose in resistance-trained adults. Seventy-one resistance-trained adults were randomly assigned to one of 3 groups while participating in a resistance-training program; Whole egg (WE; n = 23), whey protein (WP; n = 25), and placebo (PL; n = 23). Resistance training consisted of a three-day split (i.e., three days of training where separate muscle groups were trained for 1-1.5 hours each day interspersed with one day rest) for 12 weeks. All groups consumed the supplements (delivering 0.4 g/kg/d protein for WE and WP groups and 0.4 g/kg/d carbohydrate for PL) divided into boluses immediately after resistance training and 1 hour later. Before and after 12 weeks of resistance training and protein supplementation, lean tissue mass, fat mass, total body weight, body fat percentage (Dual Energy X-ray Absorptiometry [DXA]), muscle thickness (B-mode Ultrasound), muscle strength (bench press, leg press, knee extension), and fasting blood glucose level (glucometer) were assessed. There were no group x time x sex or group x time interactions for any of the dependent variables. There were time main effects, as expected for a resistance training program, with increases in lean tissue mass, muscle thickness measures, and strength measures (p < .05). When sex was removed as a factor to improve statistical power, there was a group x time interaction for bench press strength (p = 0.011). Bonferroni post-hoc testing showed that the change in bench press strength for the whole egg group (mean = 10.71, SD = 6.39 kg) was significantly different from the control group (mean = 5.56, SD = 7.65 kg) (p = .049), and the whey protein group (mean = 4.77, SD = 6.69 kg) (p = .015). In conclusion, neither whole egg nor whey protein powder supplementation improved body composition or strength during resistance training except for a greater increase in strength in the bench press with whole egg powder supplementation.
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A Fault-Tolerant Design on Convolution Neural Networks by Applying Reconfigurable Processing Element Arrays
(2024-02-09) Jin, Chen; Chen, Li; Ko, Seok-Bum; Zhang, Chris
Convolutional neural networks (CNNs) implemented on field programmable gate arrays (FPGAs) have garnered significant interest due to their superior performance and flexibility, particularly during the inference phase following CNN model training on other platforms. The ability to customize the programmable logic (PL) section of the FPGA is the key factor driving the aforementioned performance and flexibility advantages. Moreover, recent trends in research have indicated that the parallel design of multiple processing element (PE) groups is becoming increasingly popular for implementing complex CNN designs. This approach offers a significant advantage over single PE or flat implementations, as it results in higher performance levels. However, increasing the number of PEs in a design can result in an elevated Single Event Upset (SEU) rate for designs operating in radiation environments. This is due to the vulnerability of the configuration memories in SRAM-based FPGAs. While memory refreshing can eliminate errors, the CNN may still produce incorrect results before SEUs are rectified. To address this issue, Triple Modular Redundancy (TMR) techniques are commonly employed to ensure correct operations. Nevertheless, this approach incurs at least 200% overhead in terms of resources, which can render it unsuitable for many complex neural networks that have high resource requirements. To address the resource limitations of TMR techniques, FPGA vendors offer Dynamic Partial Reconfiguration (DPR) methods that enable the repair of SEUs in specific regions of the configuration memories through partial refreshing without the need for additional hardware resources in the FPGAs. DPR allows for the reconfiguration of a portion of the FPGA while the rest of the device continues to operate normally. This technique can also be applied to TMR-protected CNN designs to reduce refreshing time. However, it does not alleviate the area overhead associated with TMR methods. In this thesis, a CNN was designed and implemented in a FPGA with multiple parallel PE array groups serving as computing engines, with each group working independently. Prior to the start of computation, self-testing was performed on each PE array to verify its functionality. If any faults were detected, DPR was conducted to correct the errors in the configuration memory of the affected PE array.The experiments in this thesis evaluated the performance of a single PE group without any reinforcement design as a control group using both error injection and laser experiments. Subsequently, more PE groups were added to determine whether the system could handle more SEUs or laser pulses before an error occurred. In the result, for non-critical errors where the CNN incorrectly estimates the percentage of a given output number, adding DPR can result in a 13.8 times improvement in cross-section. In cases where the CNN makes critical errors and predicts the input number incorrectly, adding DPR can improve the cross-section by 25 times. Additionally, the overall accuracy of the CNN remains consistently above 99% even after a large number of laser pulse or fault injections, indicating the robustness and reliability of the model. The key novelty of this study is the use of DPR to improve the overall fault tolerance of the entire CNN by taking advantage of the parallel processing capability of the PE arrays to perform data processing without faulty PE arrays. This approach significantly reduces area overhead compared to TMR methods. Experimental results demonstrated the effectiveness of the proposed method.
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Cultural Continuity as a Pathway for Métis Peoples Health Promotion: A Descriptive Phenomenological Approach
(2024-02-09) Diaz Vega, Maria Jose; Groot , Gary; Carr, Tracey; Turner , Tara; Barreno , Leonzo; Janzen , Bonnie
The Métis Peoples, a distinct group of Indigenous Peoples in Canada, have historically faced adverse consequences from colonialism. Disconnection from their land, cultural suppression, and loss of cultural identity have had adverse effects on the health outcomes and overall well-being of the Métis population. Considering the critical importance of cultural continuity as a health-protective factor for Métis people, this thesis explored Métis people's lived experiences of culture and cultural continuity and the connection with health and well-being. The present thesis used secondary data from a research project titled "Preventing Cancer Through Métis Cultural Revitalization: A Framework for Saskatchewan." Data included twenty four semi-structured interviews with Métis citizens (12 females and 12 males, average age of 47 years) regarding their health and culture. Descriptive phenomenology was used to guide the secondary analysis of the interview data. The analysis revealed that some participants discussed cultural disconnection, while others emphasized active participation in Métis culture, which resulted in the promotion of cultural aspects such as traditional practices, language, and connection to the land. These elements were essential for re-establishing identity, nurturing a deeper connection to heritage, and potentially providing health benefits, including stress relief, a sense of belonging, and pride. The findings contribute to a greater understanding of the role of culture and cultural continuity in promoting health and well-being among Métis people. The results are an addition that could guide future research endeavors with other Métis communities that aim to explore health promotion through cultural continuity.
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PROTEOGLYCAN MODULATION OF BMP SIGNALLING IN ENDOCHONDRAL AND INTRAMEMBRANOUS OSSIFICATION: INSIGHTS FROM ZEBRAFISH CRANIOFACIAL AND FIN REGENERATION
(2024-02-09) Koosha, Elham; boughner, Julia; Eskiw, Christopher; Papagerakis, Petros; Collins, Michelle; Graf, Daniel
During the early stages of embryo development, the formation of the skeletal system is carefully controlled by specialized growth factors that are secreted locally. One such group of growth factors is known as bone morphogenetic proteins (BMPs), which serve multiple functions and play crucial roles in the maturation of cartilage and the differentiation of osteoblasts. To transmit the BMP signals from the cell membrane receptors to the nucleus, two pathways are involved: the canonical Smad pathway and the noncanonical p38 mitogen-activated protein kinase (MAPK) pathway. The extracellular regulation of BMP signalling occurs through interactions with proteoglycans (PGs) present in the extracellular matrix (ECM). These PGs generally modulate the efficiency of binding between the ligands and their receptors. During the process of endochondral ossification, which involves bone formation through cartilage, chondrocytes (cartilage cells) produce an ECM abundant in PGs. Following the formation of cartilage, bone formation occurs in the surrounding perichondrium as certain chondrocytes express Indian hedgehog (Ihh), a factor that induces osteoblasts, while undergoing a precisely regulated maturation process. Interestingly, the PG-rich ECM somehow inhibits the maturation of cartilage, including cellular hypertrophy and the expression of Ihh and Col10a1 genes. Given that BMPs are known to promote cartilage maturation, I hypothesize that PGs normally act as inhibitors of BMP signalling. To investigate this hypothesis, using various experimental manipulations we evaluated BMP signalling in chondrocytes of both wild-type zebrafish and zebrafish with a mutation in the PG gene fam20b-/-, which encodes a kinase responsible for phosphorylating xylose in the GAG side chain. The results showed that the levels of phosphorylated Smad1/5/9 (p-Smad1/5/9) were increased only when mutant fam20b chondrocytes secreted PGs, while the phosphorylation of p38 (p-p38) remained unaffected. As anticipated, the levels of p-Smad1/5/9 decreased in chondrocytes treated with DMH1, an inhibitor of the BMP receptor kinase domain, and in chondrocytes of zebrafish with a dominant-negative BMP receptor (dnBMPR). Only treatment with DMH1, and not the dnBMPR condition, reduced p-p38 levels in the chondrocytes. However, in both DMH1-treated and dnBMPR zebrafish the expression of two markers of chondrocyte maturation, ihha and col10a1, was decreased, and formation of perichondral bone was diminished. Next, to confirm the regulatory role of PGs in BMP-dependent cartilage maturation and in the timing of endochondral ossification, we were able to rescue the early expression of ihha and col10a1 genes as well as the formation of perichondral bone in fam20b mutant zebrafish by treating them with either DMH1 or dnBMPR. These rescue findings supported the hypothesis that PGs normally inhibit canonical BMP-dependent cartilage maturation, thereby influencing the rate and onset time of endochondral ossification. Additionally, we hypothesized that PGs typically inhibit BMP signalling during the process of intramembranous (or dermal) ossification, where bone tissue develops directly from mesenchymal cells without the presence of a cartilage precursor. We investigated the development of dermal bones in the craniofacial region of zebrafish to further test our hypothesis. Using a Tg(5xBMPRE-Xla.Id3:GFP)ir1189 transgenic zebrafish line that exhibits green fluorescent protein (GFP) expression in response to BMP signalling, the involvement of BMP signalling in the development of ossified dermal elements was confirmed. However, when embryos were treated with DMH1, the development of craniofacial dermal bone remained unchanged. While most craniofacial dermal bones of fam20b-/- zebrafish showed no discernible differences in their formation during embryonic development, we did observe an early initiation of dermal bone formation derived from the perichondrium, specifically in the dentary and quadrate bones. To test the hypothesis further, the process of fin regeneration was used as an additional model for investigating intramembranous ossification. Through the analysis of GFP expression in two BMP-responsive reporter lines, namely Tg(5xBMPRE-Xla.Id3:GFP)ir1189 and Tg(BMPRE:EGFP)pt510, a relationship was observed, linking the GFP signal as an indicator to the development of bony rays during fin regeneration. Furthermore, regeneration of caudal fin dermal bony rays in fam20b-/- zebrafish was not impaired. In adult zebrafish, the repercussions of DMH1 treatment were clear as it significantly hindered the regenerative capacity of adult fins, supporting the involvement of BMP signalling in this process. Overall, this study demonstrates the inhibitory role of PGs in BMP signalling during cartilage maturation and the influence of PGs on the rate and onset time of endochondral ossification. Furthermore, this study unveils a novel observation, the early formation of dermal bones originating from the perichondrium in fam20b-/- zebrafish mutants.
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Water Futures for the World We Want
(University of Saskatchewan, 2019) Schuster Wallace, Corinne; Sandford, Robert William; Merrill, S
Executive Summary Achievement of Goal 6 is central to the achievement of the Sustainable Development Agenda The global water cycle literally floods the earth on a seasonal basis. Global warming and subsequent climate change is affecting this seasonal redistribution as well as the form in which water falls from the sky – as rain, snow, or ice. The world is aware that water can increasingly be loved or loathed: it is critical for existence of life and central to our quality of life, while also being responsible for poor health and death from waterborne diseases. Its absence causes droughts, and too much in too short a time causes floods. Water is a cornerstone of economic growth, essential for energy production, and equally as important for ecosystems. More frequent extreme weather events associated with too much or too little water have become threat-multipliers that are undermining social, economic, and political stability In many instances, water security and climate stability can be seen as two sides of the same coin. Many of the impacts of climate disruption are, and will continue to be, expressed through effects on water. Water, and the ways in which it is used, vary significantly between countries Even in areas where it is abundant, degradation of water quality can ultimately mean that water resources are insufficient. Groundwater resources are particularly important and vulnerable. In many places in the world accelerating hydro-climatic changes are putting greater pressure on already deteriorating water quantity and quality. Climate change is not the only stressor on our water resources. Population growth, urbanization, land use changes including deforestation and degradation, changing diets, and expanding societal wealth also impact the quality and quantity of surface and groundwater resources. Canada is not a water secure country This is evidenced through recent catastrophic experiences with floods, drought, fires, and toxic algae blooms. The cost of floods and droughts for families, towns and cities, the insurance sector, businesses, agriculture, and ultimately the Federal Government, are skyrocketing. Moreover, Canadian lakes and rivers support diverse plant and animal habitats, forests, tourism, recreation, agriculture, transportation, and essential ecosystem services such as water purification. However, these are not easily valued and therefore not valued enough. Canada’s water availability is disproportionately spread over a vast country spanning multiple ecozones, of which some, like the Canadian prairies, are semi-arid Most fresh water drains to the north, while most people live in the south. The Canadian economy remains highly dependent on resource extraction, processing and transportation of oil and gas, ore, and pulp and paper, as well as intensive agriculture for crop and livestock production. All of these sectors are both heavily reliant on water availability, and have costs to the natural environment and our water resources that are not always fully recognized or completely mitigated. Climate change is exacerbating water insecurity in Canada Temperature increases in Canada are among the highest in the world. This warming is already having a substantial impact on Canada’s cold-dominated hydrological cycle. Hydrologic shifts, especially between snowmelt- and rainfall-driven streams and rivers and subsequent changes in peak water flows have consequences for agricultural productivity, hydropower generation, and floods and droughts. Weather events are becoming more extreme, traditional animal territories are changing, and pathogen ranges are expanding. Jurisdictional fragmentation, territoriality, and inequities make it difficult to generate and implement a common water management vision in Canada Portfolios such as agriculture, health, water and wastewater treatment are shared between multiple agencies and levels of government, and water itself flows across municipal, provincial, territorial, and sometimes national boundaries. Inequities also exist with respect to who experiences the impacts of these challenges and who is most vulnerable to them. Indigenous communities, women and girls, and natural ecosystems are being left behind in pursuit of economic progress. In the absence of a coherent vision of itself at its future sustainable best, Canada as a nation remains mired in divisiveness on matters of energy policy, resource development, and action on climate change. There is considerable opportunity for Canada to coordinate the activities of its water sector Through the example of good and responsible management of its waters, based on strong science and evidence, Canada can improve its own water management and play a prominent leadership role in meeting water-related targets of the Sustainable Development Agenda. Opportunities exist through leadership, example, and knowledge mobilization. Canada possesses a modern water industry, world-leading water technologies, professionally managed water service provision, and world-class transformative water research. The strengths of our water sector, however, have not been optimally harnessed and fully orchestrated for future national interest. Water cooperation, in particular, is poised to become a major instrument that can be used to prevent conflict while at the same time strengthening international stability and promoting peace. Major gaps still exist if we are to meet the ambitious yet necessary Goals of the 2030 Agenda Based on an analysis of reports, syntheses, and activities to date, previous recommendations, the SDG targets, and the challenges associated with meeting and measuring the SDGs nationally and internationally from a variety of sources, we offer recommendations for action in research, practice, and leadership. This report is intended as a blueprint for more coordination between research, policy, and practice between Canadian water researchers, the Canadian government, and other initiatives around the world that will intentionally fill the gaps identified as necessary to achieve a water future for the world we want. There are huge opportunities for Canada on the national and global stage in these areas. Given the right business model and access to support and resources, there is significant capacity within the Canadian water sector to deliver water technology, management, capacity, and predictive tools to emerging markets, particularly in developing countries, to accelerate greatly needed sustainable water resources management. There is an urgent need to ensure the sustainability of natural bio-diversity-based Earth system function Presently, there is a huge and growing gap between our understanding of the problems and implementation and practice. These gaps can be bridged by recognition of the link between water, peace, security, and human and planetary health and the SDGs can be a catalyst whereby we organize our intentions and our actions to get there. This report synthesizes current undertakings, gaps, and opportunities through research, practice, and leadership to shape sustainability starting with our water future. There is huge opportunity for university research and leadership to contribute to this water future Research networks should continue to remind all of the risks and threats posed to future stability by poverty, inequality, injustice, failed governance, climate change, and the massive involuntary human migration that are already beginning to follow in their collective wake. Ideally, however, universities should go beyond just talking about the SDGs and their importance, as they are largely doing now. They are uniquely poised to be showing the country and the world what the SDGs mean and how to implement them. The challenges, as always, lie in generating transformative and sustainable change that is more than the sum of individual programs, projects, and activities, even when they have scientific value in and of themselves. As such, a commitment to leadership is essential to realize these actions and to leverage them to become greater than the sum of their parts.