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Acoustic Wave Sensor Detection of an Ovarian Cancer Biomarker with Antifouling Surface Chemistry
Get PDFOvarian cancer (OC) must be detected in its early stages when the mortality rate is the lowest to provide patients with the best chance of survival. Lysophosphatidic acid (LPA) is a critical OC biomarker since its levels are elevated across all stages and increase with disease progression. This paper presents an LPA assay based on a thickness shear mode acoustic sensor with dissipation monitoring that involves a new thiol molecule 3-(2-mercaptoethanoxy)propanoic acid (HS-MEG-COOH). HS-MEG-COOH is an antifouling linker that provides (a) antifouling properties for gold substrates and (b) linking ability via its terminal carboxylic acid functional group. The antifouling ability of HS-MEG-COOH was tested in whole human serum. The new molecule was applied to the LPA assay in conjunction with a spacer molecule, 2-(2-mercaptoethoxy)ethan-1-ol (HS-MEG-OH), in a 1:1 v/v ratio. HS-MEG-COOH was covalently linked to gelsolin–actin, a protein complex probe that dissociates due to LPA-binding. LPA was detected in phosphate-buffered saline and undiluted human serum and achieved a low limit of detection (1.0 and 0.7 μM, respectively) which was below the concentration of LPA in healthy individuals. The antifouling properties of HS-MEG-COOH and the detection of LPA demonstrate the ability of the sensor to successfully identify the early-stage OC biomarker in undiluted human serum
Oncolytic Viruses and Immunotherapy for the Treatment of Uveal Melanoma and Retinoblastoma: The Current Landscape and Novel Advances
Get PDFIntraocular malignant tumors are rare; however, they can cause serious life-threatening complications. Uveal melanoma (UM) and retinoblastoma (RB) are the most common intraocular tumors in adults and children, respectively, and come with a great disease burden. For many years, several different treatment modalities for UM and RB have been proposed, with chemotherapy for RB cases and plaque radiation therapy for localized UM as first-line treatment options. Extraocular extension, recurrence, and metastasis constitute the major challenges of conventional treatments. To overcome these obstacles, immunotherapy, which encompasses different treatment options such as oncolytic viruses, antibody-mediated immune modulations, and targeted immunotherapy, has shown great potential as a novel therapeutic tool for cancer therapy. These anti-cancer treatment options provide numerous advantages such as selective cancer cell death and the promotion of an anti-tumor immune response, and they prove useful in preventing vision impairment due to macular and/or optic disc involvement. Numerous factors such as the vector choice, route of administration, dosing, and patient characteristics must be considered when engineering an oncolytic virus or other forms of immunotherapy vectors. This manuscript provides an in-depth review of the molecular design of oncolytic viruses (e.g., virus capsid proteins and encapsulation technologies, vectors for delivery, cell targeting) and immunotherapy. The most recent advances in preclinical- and clinical-phase studies are further summarized. The recent developments in virus-like drug conjugates (i.e., AU011), oncolytic viruses for metastatic UM, and targeted immunotherapies have shown great results in clinical trials for the future clinical application of these novel technologies in the treatment algorithm of certain intraocular tumors
Long-term biodiversity erosion: Limited co-existence of the Eurasian zebra mussel and native mussels in a North American river after 25 years
Get PDFNorth American unionid mussel populations have experienced significant mortality due to competition and fouling by the Eurasian zebra mussel Dreissena polymorpha (Pallas 1771). Habitats whose water chemistry is suboptimal for the zebra mussel could plausibly serve as refugia in which unionids and zebra mussels co-exist. The Richelieu River, invaded by the zebra mussel in the mid-1990s, has a mean calcium concentration (~18 mg L-1) believed insufficient for supporting a zebra mussel population capable of severely damaging unionids. Using a 25-year dataset, we tested how unionid diversity and abundance have changed along with zebra mussel fouling levels in the river over time. Local unionid populations suffered major declines across sites regardless of their distance from the river’s headwaters, Lake Champlain—a constant source of zebra mussel larvae. Over the past 25 years, unionid diversity and abundance have eroded to a similar extent and followed a similar timeline of initial rapid population decline as has been observed in invaded calcium-rich habitats. We hypothesize that sustained exposure to zebra mussel fouling and food competition has produced a limited co-existence in which long-term impacts of zebra mussels have accrued.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
The Temporal Dimension of Life History: Case Studies of Time Allocation in Individual Female Reptiles
Get PDFTime and energy are finite, and their allocation influences organismal fitness and life history trade-offs. To understand mechanisms regulating life history, we must consider the complex relationship among environment, time and energy allocation, and fitness. Female animals limit population growth rates, making their time allocation important for linking individual processes and behaviors to higher ecological scales. Despite its significance, quantification of time allocation in females is understudied, with most studies focusing on energetics. However, studies directly examining life history trade-offs in the context of time allocation have provided valuable insight. Using reptiles as model organisms, we present case studies on Timber Rattlesnakes (Crotalus horridus, Linnaeus, 1758) and Canyon lizards (Sceloporus merriami, Stejneger, 1904) to illustrate the link between environmental factors, female time allocation, and life history. While quantifying time allocation is challenging as a result of delineating behaviors occurring simultaneously, accessing animals, and requiring a significant amount of a researcher’s time, recent technological advancements have increased accessibility. Understanding the temporal aspects of life history is essential for developing effective conservation strategies and predicting species responses to climate change. Insights into how females allocate both time and energy have significant implications for ecological theory and conservation initiatives.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
Evaluating the Nutritional Quality of School Food Programs in Canada Compared to National Nutritional Guidelines
Get PDFWhile the potential of school food programs (SFPs) to influence healthy eating behaviors and improve child health outcomes is recognized globally, Canada currently lacks a well-established nationally coordinated and funded SFP. Instead, the fragmented nature of SFPs across Canada has resulted in a limited understanding of their nutritional quality. This study builds upon prior research assessing the characteristics of Canadian SFPs and aims to provide a baseline of SFP nutritional quality before federal policy implementation to identify priority areas for improvement in the current school food landscape. SFP menu data was collected from a diverse sample of school food providers. The mean content of nutrients of public health concern were calculated and two indices of dietary quality representing adherence to national nutrition guidelines were applied to SFP menu data: Healthy Eating Food Index 2019 (HEFI-2019) and Healthy Eating Index Canada (HEI-C) 2010. Nutritional quality results from 67 SFPs serving over 20% of Canadian schools revealed approximately 51% adherence to the 2019 and 2007 Canada’s Food Guides, indicating similar adherence to national dietary guidelines as in the broader population. Snacks tended to be high in total sugars but low in protein and sodium was high across all meal types. Given the limited resources available to SFPs in Canada, these findings indicate that although school food providers are serving relatively healthful choices, a federally harmonized school food policy and program (including the development of national school food guidelines) can further improve the state of school food in Canada and its nutritional quality.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
Current Prognostic Biomarkers for Peripheral Arterial Disease: A Comprehensive Systematic Review of the Literature
Get PDFBackground: Peripheral arterial disease (PAD) is a chronic atherosclerotic disease characterized by atheromatous plaque buildup within arteries of the lower limbs. It can lead to claudication, skin ulcerations, and, in severe cases, chronic limb-threatening ischemia, requiring amputation. There are several plasma protein biomarkers that have been suggested as prognostic markers for adverse events, including major adverse cardiovascular and limb events. However, the clinical benefit and ability to clinically adapt these biomarkers remains uncertain due to inconsistent findings possibly related to heterogenous study designs and differences in methodology. Objectives: This review aims to evaluate the current literature on the prognostic value of plasma protein biomarkers for PAD, their predictive ability for PAD-related adverse outcomes, and their potential roles in guiding PAD management. Methods: To address these challenges, we conducted a systematic review of MEDLINE, Embase, and Cochrane CENTRAL libraries of the current literature (2010–2024). Results: We found 55 studies that evaluated the prognostic value of 44 distinct plasma proteins across various pathophysiological processes. These included markers of immunity and inflammation, markers of metabolism, cardiac biomarkers, markers of kidney function, growth factors and hormones, markers of coagulation and platelet function, extracellular matrix and tissue remodeling proteins, and transport proteins. This review summarizes the existing evidence for prognostic protein plasma biomarkers for PAD and their association with adverse events related to PAD. Conclusions: With this review, we hope to provide a comprehensive list of the prognostic markers and their value as prognostic biomarkers to guide clinical decision making in these patients
Challenges in NorSand to model CSD stress paths and proposed modifications
Get PDFNorSand is a widely used constitutive model in geotechnical engineering. This study identifies challenges in simulating stress-relief stress paths, such as constant shear drained (CSD) loading, using NorSand, and proposes modifications to address them. These stress paths are particularly relevant in dam and tailings storage facility (TSF) engineering, as evidenced by case history failures. An experimental dataset of triaxial and CSD tests on a mine tailings material is used to highlight stress-relief mechanisms and contextualize the challenges associated with the flow rule, hardening rules, and the planar inner cap geometry in the standard NorSand model. The proposed modifications, informed by experimental observations on instability onset and strain evolution during CSD tests, introduce a new inner cap geometry, a modified flow rule, and a refined hardening rule. Their effectiveness is evaluated through comparisons between experimental and numerical responses, demonstrating that the updated model reproduces the experimentally observed patterns. Additionally, the performance of the updated NorSand model in a system-level simulation of a dam subjected to a rising water table, a stress-relief scenario, is also illustrated, further highlighting the role of the proposed modifications. More broadly, this study contributes to performance-based assessments of dam systems, aligning with modern engineering standards.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
Numerical Analysis of Cold Spray Process for Creation of Pin Fin Geometries
Get PDFA numerical study was performed to analyze the particle deposition of a cold spray process for the preparation of nickel electrocatalysts used in the Hydrogen Evolution Reaction (HER). The study focused on the creation of fin-shaped geometries with an optimal porosity on the electrode surface using a mask located between the nozzle exit and the substrate. Computational Fluid Dynamics (CFD) was performed on a three-dimensional high-pressure nozzle, with nickel powder used as the injection feedstock. The behavior of particles was effectively modeled through a two-way coupled Eulerian–Lagrangian approach. As per the parametric study, four masks of varying wire thicknesses and opening sizes were investigated. The masks were placed at 4 mm increments from the nozzle exit, with the substrate placed at standoff distances (SODs) of 10 mm and 20 mm. To capture the effects of the gas inlet operating conditions, two different nozzle inlet conditions were analyzed (2 MPa and 400 °C, 4 MPa and 800 °C). It was found that the nozzle inlet operating condition had the most significant impact, as it relates to the particle velocity and powder deposition. The high-pressure operating condition resulted in a deposition efficiency (DE) greater than 99.9% for all the test cases, with nearly all the impacted particles depositing on the substrate. For the medium-pressure operating condition, the DE increased linearly as the mask SOD was increased, due to the increase in the particle velocity upon impact
Barriers and Facilitators to Delivering Multifactorial Risk Assessment and Communication for Personalized Breast Cancer Screening: A Qualitative Study Exploring Implementation in Canada
Get PDFMany jurisdictions are considering a shift to risk-stratified breast cancer screening; however, evidence on the feasibility of implementing it on a population scale is needed. We conducted a prospective cohort study in the PERSPECTIVE I&I project to produce evidence on risk-stratified breast screening and recruited 3753 participants to undergo multifactorial risk assessment from 2019–2021. This qualitative study explored the perspectives of study personnel on barriers and facilitators to delivering multifactorial risk assessment and risk communication. One focus group and three one-on-one interviews were conducted and a thematic analysis conducted which identified five themes: (1) barriers and facilitators to recruitment for multifactorial risk assessment, (2) barriers and facilitators to completion of the risk factor questionnaire, (3) additional resources required to implement multifactorial risk assessment, (4) the need for a person-centered approach, and (5) and risk literacy. While risk assessment and communication processes were successful overall, key barriers were identified including challenges with collecting comprehensive breast cancer risk factor information and limited resources to execute data collection and risk communication activities on a large scale. Risk assessment and communication processes will need to be optimized for large-scale implementation to ensure they are efficient but robust and person-centered
Acquisition of Variation in the Use of alors, donc, fait que by Advanced French-as-a-Second-Language Learners in Ontario, Canada
Get PDFThis study examines the acquisition of sociolinguistic variation in the use of French connectors alors/donc/fait que ‘so’ by two groups of advanced French-as-a-second language (FL2) learners in Ontario: (i) high school French Immersion (FI) students and (ii) university students. It considers two types of functions fulfilled by these connectors: (i) the grammatical function of expressing consequence between two clauses and (ii) a range of discursive functions, a dual focus not present in previous research, which considered only one or the other of these two types of functions. Our study shows that: (i) although these two FL2 groups’ use of the connectors is distant from the norms of FL1 speech, the university students achieve a more advanced level of acquisition of this case of variation than do the FI students, reflecting the positive effect of continued learning of French at the postsecondary level; (ii) ‘level of opportunities to interact in French with native speakers’ has a greater positive impact on the acquisition of alors/donc/fait que than ‘time spent learning French’; and (iii) both groups of students evidence incomplete acquisition of the linguistic constraints of connector choice