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Venetoclax in Combination with Obinutuzumab in Previously Untreated Fit Patients with Chronic Lymphocytic Leukemia: A Canadian Cost-Utility Analysis
Get PDFBackground/Objective: Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder diagnosed in Canada and is associated with a significant economic burden. This study evaluates the cost effectiveness of fixed-treatment duration venetoclax plus obinutuzumab (VEN + O) for previously untreated, fit CLL patients in Canada, for whom this therapy is not universally reimbursed provincially.
Methods: A three-state partitioned survival model was developed using data from the CLL13 trial and a Bayesian network meta-analysis. Health states included progression-free, progressed disease, and death. A lifetime horizon (40-year) was used and a 1.5% discount rate was applied to costs and effects. Costs included drug acquisition, administration, monitoring, adverse events, subsequent treatment, and terminal care. Utility values were derived from previous NICE technology appraisals in CLL. Extensive sensitivity and scenario analyses were conducted.
Results: VEN + O was associated with lower total costs and higher quality-adjusted life years and thus dominant compared with ibrutinib, zanubrutinib, and fludarabine plus cyclophosphamide plus rituximab. Compared with acalabrutinib and venetoclax plus ibrutinib, the incremental cost-utility ratios (ICURs) were in the south-west quadrant and substantially above a CA$50,000/QALY willingness-to-pay threshold, meaning VEN + O was cost effective versus these comparators. VEN + O was cost effective versus bendamustine plus rituximab. Extensive sensitivity and scenario analyses confirmed the robustness of these results.
Conclusions: This analysis demonstrates that VEN + O, a 12-month fixed duration treatment, is a cost-effective option for previously untreated fit CLL patients in Canada. VEN + O offers potential health benefits and cost savings when compared with relevant comparator treatments
Breadmaking Potential of Andean Roots and Tuber Starches from Ahipa (Pachyrhizus ahipa), Oca (Oxalis tuberosa), and Arracacha (Arracacia xanthorrhiza)
Get PDFAim is to explore the breadmaking potential for gluten-free goods of non-conventional starches from Andean crops ahipa, oca, and arracacha. Their characteristics and performance in breadmaking are compared with those of cassava, taken as a reference for conventional gluten-free root starch. Physicochemical properties of breads are studied along with the pasting and thermal properties, composition, and α-amylase hydrolysis of starches. Arracacha starch has the lowest amylose content (2.4%) and the highest water hydration (1.4 g g−1). Its batter shows adequate proofing, but the bread is highly adhesive, with dense crumb. Ahipa starch paste has the lowest peak, trough and final viscosities determined by rapid visco analyzer, and the highest hydrolysis rate (kRVA = 2.30 min−1). Its batter exhibits, along with oca, the highest volume increase during fermentation (193–197%), but structure collapses in the oven and no alveoli are observed in the crumb. Conversely, oca forms a crumb structure similar to cassava, but with higher cell density (131 alveoli cm−2), cohesiveness (0.95), and resilience (0.65) than the latter (71 alveoli cm−2, 0.88, and 0.45, respectively). Oca starch has lower pasting temperature (64 °C) and the starch paste has similar hydrolysis rate (kRVA = 1.92 min−1) compared to cassava (71.9 °C and 2.08 min−1, respectively), making it a suitable option for providing gluten-free yeast-leavened breads with improved technological properties and a comparable glycemic index
Dispossession, violence, resistance: First Nations and Mapuche women in the face of settler colonial patriarchy
Get PDFLand dispossession by European colonizers in what we know as North, Central, and South America brought about the erasure of Indigenous cultures, traditions, and languages across the region, including First Nations in Canada and the Mapuche people in Chile, whose resistance against settler colonialism continues to resonate today. This paper presents a comparative analysis of First Nations and Mapuche women's experiences within colonial patriarchy, using an interdisciplinary approach by integrating a review and analysis of historical, feminist, and decolonizing secondary sources. Using settler colonialism as a framework, the first section reviews the European processes of colonization and the settler-Indigenous relations to the land and property rights in what is now Canada and Chile, comparing the colonial methods of land dispossession and unveiling how the attempts to control First Nations and Mapuche people through their lands were part of these settler-colonial projects. The second section uses patriarchal colonialism and cuerpo-territorio to understand how colonial assimilation policies and systemic marginalization relate to direct forms of violence against Indigenous women. From the structural issues behind missing and murdered Indigenous women and girls (MMIWG) in Canada to militarized violence against Mapuche communities in Chile, it explores the continuous impact of colonial policies on Indigenous women. Finally, based on research on First Nations women's activism and Mapuche women's efforts within and beyond their communities, the last section will examine how Indigenous women have organized and challenged colonial patriarchy. This section will provide insight into how Indigenous women have fought against oppressive systems historically and what this means for decolonizing the present and future.May 202
“We really need to surround people with care:” a qualitative examination of service providers’ perspectives on barriers to HIV care in Manitoba, Canada
Get PDFAbstract Objective To identify barriers to HIV care from the perspectives of HIV service providers in Manitoba (MB), Canada during the 2020–2022 period of the COVID-19 pandemic. Methods In this qualitative study, we conducted semi-structured interviews with HIV service providers between October 2022 and January 2023. Purposive sampling was used to include a cross-section of 27 providers (clinicians, nurses, social workers, pharmacists, program managers, and health education facilitators). The main themes explored in the interviews included: (1) provider roles and organization; (2) facilitators and barriers to HIV care; (3) harm reduction and sexually transmitted and blood-borne infections prevention practices; (4) impacts of the COVID-19 pandemic on HIV care and providers and (5) policies related to HIV care in Manitoba. Results Using a Social Ecological Model of Health framework, our analysis of service provider interviews identified barriers at four different levels: (1) structural level barriers, including limitations to public health and social support systems, geographic barriers, and policy inefficiencies; (2) socio-cultural/community level barriers, such as experiences of racism, stigma and discrimination leading to people living with HIV’s (PLHIV) reduced trust in the health care system; (3) institutional level barriers, which describe how lack of primary care for PLHIV, limitations to the HIV care delivery model in Manitoba, and system capacity limitations have created missed opportunities for linkage to HIV care; and (4) intrapersonal barriers that reflect how the interaction of structural, socio-cultural, and institutional level barriers challenge providers’ role performance and exacerbate risk of burnout and moral distress. Conclusions Our findings demonstrate how multi-level barriers intersect to create challenges for both PLHIV and providers, limiting where and how people receive HIV care and impeding providers’ ability to perform their roles and provide effective, consistent HIV care. Given the key role of HIV providers in facilitating care, structural, social/community, and institutional changes are needed, as is further research to examine structural causes of burnout to develop meaningful interventions that support service providers’ mental health and well-being
Modelling thermal characteristics of cocoa butter using a feed-forward artificial neural network based on multilayer perceptron
Get PDFCocoa butter is the most important ingredient of chocolate, which determines its melting behaviour. Variations in the melting characteristics of cocoa butter can profoundly affect the performance and suitability for their industrial utilisation. Over time, researchers have been attempting to establish a logical relationship between cocoa butter’s unique thermal properties and the amount of saturated to unsaturated fatty acids in mono, di and triglycerides, and fatty acids (as major components), and free fatty acids, soap, primary oxidation products, minerals, moisture, phospholipids, tocopherols, unsaponifiable matters and metals (as minor components) found in cocoa butter. In this research, the thermal behaviours of thirteen samples of cocoa butter with different origins were investigated using isothermal differential scanning calorimetry. The cocoa butters starting temperature of crystallisation, temperature of maximum heat release, temperature of completed crystallisation and the enthalpy of heat release during recrystallisation were evaluated. In addition, the chemical composition (moisture, acidity, peroxide, minerals and soap content), fatty acid and triacylglycerol composition were used to establish an MLP-ANN with fourteen input neurons connected by two flexible, sigmoid activation function layers. The back-propagation was used to train the artificial neural network (ANN) structure and optimise the error of prediction. The study showed that the MLP algorithm can predict the thermal behaviour of CB samples with trace error, regardless of plant growth and extract process condition
Evaluating health system performance for key populations during public health emergencies: a longitudinal analysis of HIV service use by female sex workers in Nairobi, Kenya during COVID-19
Get PDFFemale sex workers face existing challenges with HIV healthcare access due to structural factors (e.g., stigma, violence) and COVID-19 established further unprecedented challenges. A retrospective longitudinal design (February 2019-March 2023) was done using an interrupted time series analysis (ITS) to assess the impact of restrictions/their removal on visit numbers and Generalized Linear Models (GLM) compared patterns across the seven Sex Work Outreach Program (SWOP) clinics, with SWOP City serving as a reference clinic. The ITS analyses revealed significant variability in visit numbers across clinics and service-types due to COVID-19 restrictions. An initial decline in visits corresponded with restrictions which was followed by a rebound. HIV testing significantly dropped at some clinics, such as SWOP Majengo (estimate= -5.408, p<0.001), while ART visits remained stable. GLM analysis showed variation across clinics; for instance, condom distribution visits were significantly lower at SWOP Donholm (estimate= -0.997, p<0.001) and SWOP Langata (estimate= -0.662, p=0.022) compared to SWOP City. Findings highlight the need for adaptable health systems to sustain essential services for marginalized populations during public health emergencies. While treatment services remained stable, prevention and support services were more affected. Strengthening resilience in HIV programming requires flexible outreach strategies, adaptable clinic models, and addressing structural healthcare gaps. Possible recommendations for strengthening resilience in HIV health programming for future emergencies includes re-visiting current outreach strategies, developing flexible models and protocols that equip clinics to be accessible during future disruptions, and addressing structural gaps in healthcare to increase the engagement of female sex workers. This work also establishes a foundation for future research to be done at the patient-level to understand the specific challenges female sex workers faced when accessing these services due to the pandemic. By identifying any service gaps, this project can help support evidence-based strategies to develop inclusive and resilient public health approaches for key populations.May 202
A feminist perspective of the differentiated impacts of climate change, adaptation and women’s roles in coastal agriculture in Bangladesh
Get PDFThis thesis research, conducted in Kaliganj Upazila, Satkhira District, Bangladesh, aims to i) identify the key factors driving differentiated climate change impacts on various income groups, particularly women; ii) examine local agricultural adaptation strategies with a focus on women's engagement; and iii) explore the challenges women face in adapting to climate change in agriculture. A mixed-methods approach, using a feminist lens, was employed and data collection involved surveys, focus group discussions (FGDs), key informant interviews (KIIs), and participant observations Data were analyzed using Microsoft Excel and thematic categorization, and presented through tables, graphs, and descriptive narration. The findings reveal that women, minorities, and lower socioeconomic groups experience adverse impacts of climate change disproportionately, which are exacerbated by systemic gender disparities and existing social inequalities related to age and minority status. The study highlights the cyclical relationship between climate change and gender inequality, where one reinforces the other. It also identifies coastal agricultural adaptation strategies, such as alternate income sources, salt- and drought-tolerant crops, hybrid high-yielding crops, and rainwater harvesting. Women’s critical role in agriculture is emphasized, while revealing barriers such as limited land rights, wage gaps, gender norms, lack of gender-sensitive technologies, and restricted access to resources. The study also underscores the significance of external social factors in shaping farmers’ adaptive capacity. Recommendations include providing gender-sensitive disaster shelters, accessible credit facilities and agricultural interventions, and creating awareness programs to address gender and social disparities. The study also calls for gender-responsive and inclusive adaptation policies, fostering women and minorities’ participation in decision-making, and ensuring access to education and resources for adaptive capacity.University of Manitoba Graduate FellowshipMay 202
A scoping review on early childhood caries and inequalities using the Sustainable Development Goal 10 framework
Get PDFAbstract Background Social inequalities contribute to health disparities. This study aimed to map evidence on early childhood caries (ECC) related to the United Nations' Sustainable Development Goal 10 (SDG 10). Methods A scoping review was conducted in May 2024 following the PRISMA-ScR guidelines. A literature search was performed in PubMed, Web of Science, and CINAHL for studies published in English and addressing population level social inequalities. Studies measuring individual level of social inequalities were excluded as they were covered by other SDGs. However, studies incorporating individual measures as additional measures of population level social inequality were included. Retrieved papers were summarized, inductively analysed and a conceptual framework linking SDG 10 was developed. Results Of 452 studies retrieved, 42 met the inclusion criteria. Studies measured inequality among groups (deprivation, family income, indigenous communities, ethnicity, minority status) [14 studies], institutions (type of school, nursery or school facility, school poverty index, public primary health care units) [five studies], and inequality in communities (neighbourhood socio-economic status, Human Development Index, employment rate, income inequality, sanitary sewer and water supply, residents/household ratio, urban vs rural vs remote rural, accessibility index, location index, the slope index of inequality) [24 studies]. These levels of social inequalities were linked to higher prevalence of ECC; social and economic policies contributed to widening inequalities in ECC severity; and although effective interventions targeted at at-risk populations could reduce dental health disparities, study interventions differed by deprivation status. Six studies (14.3%) addressed SDG 10.1, 33 (78.6%) addressed SDG 10.2, 11 (26.2%) addressed SDG 10.3, and three (7.1%) addressed SDG 10.4. Fourteen studies (33.3%) addressed a combination of SDGs. The conceptual framework highlights the role of structural inequalities stemming from the cumulative impact of institutional decisions and systemic inequalities. Conclusion This scoping review underscores the profound influence of social inequality on ECC through interactions between multi-level factors. Further research is needed to explore the links between ECC and other SDG 10 targets, especially in low- and lower-middle-income countries
Scanning photoelectrochemical microscopy and its application to living cells
Get PDFLiving cell electrochemistry enables the non-invasive qualitative and quantitative measurement of metabolite and biomarker flux from individual or groups of cells. Scanning electrochemical microscopy (SECM) is an electroanalytical technique that allows for real-time detection of species flux from living cells. This thesis emphasizes the importance of maintaining optimal physiological conditions during SECM and explores the advancement of SECM to scanning photoelectrochemical microscopy (SPECM) for studying living cells. The first part of this thesis investigates the effects of experimental parameters such as temperature, media composition, and light on cellular electrochemical signals. It is shown that maintaining ideal physiological conditions is crucial for reliable SECM and SPECM data. Studies on Adenocarcinoma cervical cancer (HeLa) cells across different temperature ranges reveal inconsistent cellular electrochemical reactivity with small deviations from physiological temperature. However, HeLa cells demonstrate enhanced and stable electrochemical signals when cultured in serum-free media under constant light exposure.
To advance SECM to SPECM, the integration of optical fiber (OF) probes is explored to enhance both electrochemical and spectroscopic capabilities. A new, easy-to-fabricate micro-optical ring electrode (MORE) is introduced, with its functionality assessed through electrochemical analysis, numerical modeling, scanning electron microscopy (SEM), and spectroelectrochemistry. The MORE, integrated into SPECM, is used for localized irradiation and as an electrochemical sensor for quantitative analysis of single algal cells. This proof-of-concept demonstrates the potential of applying SPECM to mammalian cells. SPECM is further applied to skin cells for the detection of reactive oxygen species (ROS) and melanin production, which are elevated in response to external stimuli. Overall, a comprehensive exploration of the application of SPECM to mammalian cell studies is investigated with suggestions for future research, highlighting its potential in diverse applications.May 202
A synchrophasor stream processing pipeline architecture for near-real-time applications
Get PDFSince their introduction, synchrophasor measurement networks have been steadily growing and
are expected to continue growing as distribution Phasor Measurement Units (PMU) become
mainstream. Moreover, recent advances in data-driven methods, in contrast to traditional
synchrophasor applications, introduce more demanding data requirements. Together, these factors
create the need to research data engineering methods for handling synchrophasor data at a large
scale. This research investigates the use of a stream processing framework to build synchrophasor
applications and proposes a novel reconfigurable synchrophasor data pipeline for near-real-time
applications. The processing pipeline is part of a larger system which comprises data collection at
the substation level, data ingestion, processing and a centralized metadata registry. In addition, to
overcome some of the technical, cybersecurity and economic challenges of traditional PMU
networks, the system is developed using open-source, off-the-shelf technologies and is deployed
to a cloud provider. Lastly, the system is tested using a real-time simulation, the data is collected
by multiple agents and forwarded to the cloud using different data rates to assess its performance
in terms of the latency.May 202