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Item type: Item , Global land use implications of dietary trends(Public Library of Science, 2018-08-08) Rizvi, Sarah; Pagnutti, Chris; Fraser, Evan; Bauch, Chris T.; Anand, MadhurGlobal food security and agricultural land management represent two urgent and intimately related challenges that humans must face. We quantify the changes in the global agricultural land footprint if the world were to adhere to the dietary guidelines put forth by the United States Department of Agriculture (USDA), while accounting for the land use change incurred by import/export required to meet those guidelines. We analyze data at country, continental, and global levels. USDA guidelines are viewed as an improvement on the current land-intensive diet of the average American, but despite this our results show that global adherence to the guidelines would require 1 gigahectare of additional land—roughly the size of Canada—under current agricultural practice. The results also show a strong divide between Eastern and Western hemispheres, with many Western hemisphere countries showing net land sparing under a USDA guideline diet, while many Eastern hemisphere countries show net land use increase under a USDA guideline diet. We conclude that national dietary guidelines should be developed using not just health but also global land use and equity as criteria. Because global lands are a limited resource, national dietary guidelines also need to be coordinated internationally, in much the same way greenhouse gas emissions are increasingly coordinated.Item type: Item , Franklin expedition lead exposure: New insights from high resolution confocal x-ray fluorescence imaging of skeletal microstructure(Public Library of Science, 2018-08-23) Swanston, Treena; Varney, Tamara L.; Kozachuk, Madalena; Choudhury, Sanjukta; Bewer, Brian; Coulthard, Ian; Keenleyside, Anne; Nelson, Andrew; Martin, Ronald R.; Stenton, Douglas R.; Cooper, David M. L.In the summer of 1845, under the command of Sir John Franklin, 128 officers and men aboard Royal Navy ships HMS Erebus and HMS Terror sailed into Lancaster Sound and entered the waters of Arctic North America. The goal of this expedition was to complete the discovery of a northwest passage by navigating the uncharted area between Barrow Strait and Simpson Strait. Franklin and his crew spent the first winter at Beechey Island, where three crewmen died and were buried. In September 1846, the ships became stranded in ice off the northwest coast of King William Island, where they remained until April 1848. At that time, the crew, reduced to 105, deserted the ships and retreated south along the island’s western and southern shores in a desperate attempt to reach the mainland and via the Back River, to obtain aid at a Hudson’s Bay Company Post. Sadly, not one individual survived. Previous analyses of bone, hair, and soft tissue samples from expedition remains found that crewmembers’ tissues contained elevated lead (Pb) levels, suggesting that Pb poisoning may have contributed to their demise; however, questions remain regarding the timing and degree of exposure and, ultimately, the extent to which the crewmembers may have been impacted. To address this historical question, we investigated three hypotheses. First, if elevated Pb exposure was experienced by the crew during the expedition, we hypothesized that those sailors who survived longer (King William Island vs. Beechey Island) would exhibit more extensive uptake of Pb in their bones and vice versa. Second, we hypothesized that Pb would be elevated in bone microstructural features forming at or near the time of death compared with older tissue. Finally, if Pb exposure played a significant role in the failure of the expedition we hypothesized that bone samples would exhibit evidence of higher and more sustained uptake of Pb than that of a contemporary comparator naval population from the 19th century. To test these hypotheses, we analyzed bone and dental remains of crew members and compared them against samples derived from the Royal Navy cemetery in Antigua. Synchrotron-based high resolution confocal X-ray fluorescence imaging was employed to visualize Pb distribution within bone and tooth microstructures at the micro scale. The data did not support our first hypothesis as Pb distribution within the samples from the two different sites was similar. Evidence of Pb within skeletal microstructural features formed near the time of death lent support to our second hypothesis but consistent evidence of a marked elevation in Pb levels was lacking. Finally, the comparative analysis with the Antigua samples did not support the hypothesis that the Franklin sailors were exposed to an unusually high level of Pb for the time period. Taken all together our skeletal microstructural results do not support the conclusion that Pb played a pivotal role in the loss of Franklin and his crew.Item type: Item , Spatial statistical tools for genome-wide mutation cluster detection under a microarray probe sampling system(Public Library of Science, 2018-09-25) Luo, Bin; Edge, Alanna K.; Tolg, Cornelia; Turley, Eva A.; Dean, C. B.; Hill, Kathleen A.; Kulperger, R. J.Mutation cluster analysis is critical for understanding certain mutational mechanisms relevant to genetic disease, diversity, and evolution. Yet, whole genome sequencing for detection of mutation clusters is prohibitive with high cost for most organisms and population surveys. Single nucleotide polymorphism (SNP) genotyping arrays, like the Mouse Diversity Genotyping Array, offer an alternative low-cost, screening for mutations at hundreds of thousands of loci across the genome using experimental designs that permit capture of de novo mutations in any tissue. Formal statistical tools for genome-wide detection of mutation clusters under a microarray probe sampling system are yet to be established. A challenge in the development of statistical methods is that microarray detection of mutation clusters is constrained to select SNP loci captured by probes on the array. This paper develops a Monte Carlo framework for cluster testing and assesses test statistics for capturing potential deviations from spatial randomness which are motivated by, and incorporate, the array design. While null distributions of the test statistics are established under spatial randomness via the homogeneous Poisson process, power performance of the test statistics is evaluated under postulated types of Neyman-Scott clustering processes through Monte Carlo simulation. A new statistic is developed and recommended as a screening tool for mutation cluster detection. The statistic is demonstrated to be excellent in terms of its robustness and power performance, and useful for cluster analysis in settings of missing data. The test statistic can also be generalized to any one dimensional system where every site is observed, such as DNA sequencing data. The paper illustrates how the informal graphical tools for detecting clusters may be misleading. The statistic is used for finding clusters of putative SNP differences in a mixture of different mouse genetic backgrounds and clusters of de novo SNP differences arising between tissues with development and carcinogenesis.Item type: Item , Beyond the Lab: Integrated Biosensing Platforms for Point-of-Care Diagnostics and Continuous Monitoring in Blood, Skin, and Brain(University of Waterloo, 2026-05-13) Keyvani, FatemehConventional disease diagnosis and health monitoring rely on centralized laboratory testing that requires invasive biofluid collection, complex processing, and specialized equipment. These methods are costly, time-consuming, and provide only intermittent data, limiting their utility for timely decision-making. This thesis addresses these challenges by developing advanced biosensing platforms that combine minimally invasive sampling with different detection modalities to enable point-of-care (POC) diagnostics and continuous monitoring. The overarching vision is to enable on-site biomarker quantification and continuous monitoring of disease-relevant indicators. The first platform focuses on POC screening for cervical cancer (CC), a disease that disproportionately affects women in low- and middle-income countries due to limited access to screening. We developed an Integrated Microfluidic Electrochemical Assay for Cervical Cancer (IMEAC), a low-cost and user-friendly system that combines a force-free plasma separation module with a graphene oxide-based electrochemical biosensor. The plasma separator isolates high-purity plasma directly from whole blood, while the biosensor employs sequence-specific probes to detect circulating tumor nucleic acid. The second platform expands the concept of decentralized diagnostics toward general clinical biomarker monitoring. We designed a hydrogel microneedle (HMN)–based assay capable of sampling interstitial fluid (ISF) in a minimally invasive manner. The extracted ISF is analyzed using a graphene oxide–nucleic acid (GO.NA) fluorescence biosensor, enabling real-time detection of clinically relevant biomarkers. This system was complemented with a portable fluorescence detector, yielding a complete and user-friendly POC solution. Building upon these foundations, the third platform centers on therapeutic drug monitoring (TDM), a clinical necessity for optimizing treatment efficacy. We developed a hybrid microneedle–flexible electrode biosensor (HMN-Flex) capable of real-time monitoring of two widely used antibiotics: vancomycin and gentamicin. The HMN array extracts dermal ISF and delivers it to an electrode, where target antibiotic concentrations are quantified electrochemically. The HMN-Flex system was validated in-vivo using rat models, with pharmacokinetic profiles showing strong concordance with conventional blood-based assays. The fourth platform translates the principles of minimally invasive, continuous biosensing into the neurocritical care environment. Patients with external ventricular drains (EVDs) require close monitoring of cerebrospinal fluid (CSF) to detect complications such as infection and drain malfunction. We developed NeuroSense, a multiplexed sensing platform that integrates seamlessly with standard EVD systems to provide continuous, real-time monitoring of CSF. NeuroSense provides measurements of CSF glucose, lactate, pH, and flow rate, thus reporting about potential infection and EVD malfunction. Taken together, the works presented in this thesis demonstrate how integrating novel sampling strategies, nanomaterial-enabled biosensors, and system-level design with interdisciplinary advances in microfluidics, microneedles, and electrochemical and optical sensing can overcome intrinsic limitations of laboratory-based diagnostics. These platforms establish a technological foundation for next-generation healthcare systems that prioritize accessibility, timeliness, and personalization, with the potential to improve patient outcomes in high-resource clinical settings and expand access to quality care in underserved regions worldwide.Item type: Item , When too much isn't enough: Does current food production meet global nutritional needs?(Public Library of Science, 2018-10-23) Bahadur KC, Krishna; Dias, Goretty M.; Veeramani, Anastasia; Swanton, Clarence J.; Fraser, David; Steinke, Dirk; Lee, Elizabeth; Wittman, Hannah; Farber, Jeffrey M.; Dunfield, Kari; McCann, Kevin; Anand, Madhur; Campbell, Malcolm; Rooney, Neil; Raine, Nigel E.; Van Acker, Rene; Hanner, Robert; Pascoal, Samantha; Sharif, Shayan; Benton, Tim G.; Graser, Evan D. G.Sustainably feeding the next generation is often described as one of the most pressing “grand challenges” facing the 21st century. Generally, scholars propose addressing this problem by increasing agricultural production, investing in technology to boost yields, changing diets, or reducing food waste. In this paper, we explore whether global food production is nutritionally balanced by comparing the diet that nutritionists recommend versus global agricultural production statistics. Results show that the global agricultural system currently overproduces grains, fats, and sugars while production of fruits and vegetables and protein is not sufficient to meet the nutritional needs of the current population. Correcting this imbalance could reduce the amount of arable land used by agriculture by 51 million ha globally but would increase total land used for agriculture by 407 million ha and increase greenhouse gas emissions. For a growing population, our calculations suggest that the only way to eat a nutritionally balanced diet, save land and reduce greenhouse gas emissions is to consume and produce more fruits and vegetables as well as transition to diets higher in plant-based protein. Such a move will help protect habitats and help meet the Sustainable Development Goals.