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The development and evaluation of medical countermeasures against severe acute respiratory syndrome coronavirus type 2
Get PDFThe SARS-CoV-2 pandemic has demonstrated the need for faster and more efficient ways to produce diagnostics, therapeutics and vaccines against unknown infectious diseases. This study evaluated the ability of a baculovirus expression vector system (BEVS) to produce immunogenic antigens for use in diagnostic tests and to produce monoclonal antibody (mAb) therapies. This study also evaluated a novel approach to vaccine development: targeting antigen to MHC-II via an immunotargeted vaccine (ITV) as well as a viral vectored vaccine.
Using the genetic sequences of SARS-CoV-2, the full-length soluble Spike protein (SS), the S1 domain, receptor binding domain (RBD) and nucleocapsid protein (NP) of SARS-CoV-2 were expressed using the BEVS. These proteins were used to immunize mice to produce mAbs which were proven useful in competitive ELISA development, immunostaining and neutralization of SARS-CoV-2 Wuhan and Delta variants. These mAbs were then further characterized by epitope mapping as well as gene and amino acid sequencing of the variable heavy and light chains.
Two unadjuvanted ITVs using the RBD from SARS-CoV-2 were evaluated for their ability to protect ferrets challenged with SARS-CoV-2. The ITVs elicited neutralizing antibody responses after one immunization whereas an adjuvanted subunit vaccine required a boost. Following challenge, ITV immunized ferrets had lower viral titres in nasal washes and were also bright and responsive throughout the duration of challenge. Ferrets immunized with the adjuvanted vaccine and unvaccinated ferrets experienced symptoms consistent with mild to severe clinical disease.
A Newcastle disease viral vectored vaccine expressing a pre-fusion stabilized spike protein of SARS-CoV-2 was intranasally immunized into ferrets at low and high doses and the sera was tested for neutralization potential. At both high and low doses, the serum was able to neutralize SARS-CoV-2 Wuhan, Delta B.1.617.2 and Omicron BQ.1 variants.
The results from these studies form a basis for further study of these platforms and their potential for implementation in the event of another pandemic as well as for currently circulating viruses in both human and animal populations. This study has the potential to directly contribute to both Canadian and global biosecurity and preparedness.February 202
STRATEGIES TO OPTIMIZE ANTIBIOTIC STEWARDSHIP IN THE OUTPATIENT PEDIATRIC POPULATION: A REVIEW OF THE LITERATURE
No full textIntroduction: About one-third of all antimicrobial prescriptions are clinically unnecessary and
potentially harmful in the outpatient pediatric setting, which is an area that commonly features
physician assistants prescribe medications. Behavioural factors were found to influence
prescription rates.
Purpose of Review: The purpose of this literature review is to present a comprehensive overview
of the best available evidence regarding the effectiveness of strategies to optimize prescribing
behaviours in outpatient pediatric settings.
Methods: 23 articles pertained to five individual stewardship strategies and bundled
interventions. Search terms were created from four main categories. Databases were searched for
articles by title and abstract for highlighting pediatrics/adolescents, outpatient prescription rates,
and effectiveness of antibiotic stewardship strategies. 39 articles were found and 19 articles were
chosen for review. Older studies (pre-2017) and those with adult samples were included if recent
literature on a strategy was scarce and/or datasets were large.
Discussion: Bundled and non-bundled approaches were associated with better first-line antibiotic
prescribing, reduced broad-spectrum antibiotic prescribing, reduced prescribed antibiotic
durations, increased delayed antibiotic prescriptions, and sustained effects in studies with
postintervention periods. However, multiple studies did not utilize a pediatric sample and may
limit its generalizability.
Conclusion: By engaging in more than one behavioural strategy to combat unnecessary
antimicrobial prescriptions, physician assistants in outpatient pediatric settings will be better able
to adhere to the judicious use of antimicrobial prescriptions. More research should be undertaken
that is specific to a pediatric population, within the Canadian context, and involving physician
assistants employed in the community
Establishing cephalometric norms for the Indian population using Steiner's cephalometric analysis
No full textObjective: Current cephalometric norms are based on an untreated Caucasian sample and may not apply to other ethnic groups. It is essential to establish standard norms for different populations.
Aim: To create cephalometric norms for the Indian population by utilizing Steiner’s analysis to aid in diagnosis and treatment planning.
Method: The sample consisted of 200 adult subjects of Indian ethnic origin (100 males and 100 females). To avoid regional bias, samples were collected from four metropolitan cities: Delhi, Mumbai, Calcutta, and Chennai. The primary inclusion criterion required the participants to have a Class I molar relationship and an aesthetically pleasing profile (assessed through intra-oral and extra-oral profile photographs). All the radiographs were traced digitally using Dolphin (version 11.95) in random order by a single operator to reduce bias. Another operator randomly selected and retraced fifty cephalograms to check the operator's reliability and reproducibility. Inter-operator and intra-operator reliability was deemed satisfactory. Steiner’s cephalometric analysis was used to compare each participant's cephalogram, calculating all variables' means and standard deviations. Unpaired t-tests were used to determine differences in variable means between the Indian and Caucasian populations. The probability value (P value) of 0.05 was considered statistically significant.
Results: Significant variations in specific parameters of Steiner’s cephalometric analysis were found between Indian and Caucasian populations. Steiner’s analysis showed a significant increase (P<0.05) in SNA (84°), SNB (82°), SND (79°), U1 to NA (8mm), U1 to NA (28°), L1 to NB (7mm), L1 to NB (28°), and reduced Go-Gn to SN (26°), Interincisal angle (122°), Occ plane to SN (12°) while ANB remained constant.
Conclusions: This study emphasizes the necessity of establishing cephalometric norms for the Indian population. Understanding cephalometric differences in norms for various ethnic groups is critical for customized diagnosis and treatment.October 202
Critical coupling and Floquet in cavity magnonics
No full textWe examine the coupling behavior of a dielectric resonator (DR) and a microstrip line in the microwave regime, with a specific focus on three coupling regimes: over-coupling, critical-coupling, and under-coupling. Through our experiments, we observe that coupled mode theory (CMT) effectively explains the underlying mechanisms governing these three coupling regimes. Among them, critical coupling is of particular interest due to characteristics of the zero transmission magnitude, zero linewidth and infinite group delay.
Besides, Floquet drive, a time-periodic modulation, has recently shown its significance in cavity magnonic systems as it can be a powerful tool for manipulating the coupling strength between magnons and photons. Floquet drive, a periodical drive in time dimension, offers a similar conceptual framework to Bloch's theorem. However, unlike spatial periodicity, which is limited by fabrication constraints, Floquet drive demonstrates its flexibility through periodic modulation in time.
This study merges the concepts of critical coupling and Floquet drive, showcasing concurrent critical couplings from mirror-like sidebands in Floquet coherent cavity magnonics. We demonstrate cavity magnonics in different coupling regimes, confirm sidebands through direct Floquet drive in magnons, and present the over-coupled DR hybridizing with magnons in a Floquet condition. Due to the identical damping rates of the first-order magnon sidebands, the system exhibits a total of four modes, with the linewidths of these modes being identical in pairs. In the case of on-resonance between cavity and magnon, an over-coupled DR ensures linewidth variation between loss and effective gain, thereby guaranteeing the occurrence of critical coupling. Additionally, the identical linewidths in pairs due to Floquet ensure that this critical coupling happens concurrently. We propose achieving four simultaneous critical couplings by finely tuning the DR effective gain rate, suggesting a potential design for a perfect energy-feeding device with multiple bands.February 202
Decision-making and autonomy among participants in early-phase cancer immunotherapy trials: a qualitative study
No full textBackground
Participants considering early-phase cancer clinical trials (CTs) need to understand the unique risks and benefits prior to providing informed consent. This qualitative study explored the factors that influence patients’ decisions about participating in early-phase cancer immunotherapy CTs through the ethical lens of relational autonomy.
Methods
Using an interpretive descriptive design, interviews were conducted with 21 adult patients with advanced cancer who had enrolled in an early-phase CT. Data was analyzed using relational autonomy ethical theory and constant comparative analysis.
Results
The extent to which participants perceived themselves as having a choice to participate in early-phase cancer immunotherapy CTs was a central construct. Perceptions of choice varied according to whether participants characterized their experience as an act of desperation or as an opportunity to receive a novel treatment. Intersecting psychosocial and structural factors influenced participants’ decision making about participating in early-phase cancer immunotherapy trials. These relational factors included: (1) being provided with hope; (2) having trust; (3) having the ability to withdraw; and (4) timing constraints.
Conclusions
Findings highlight the continuum of perceived choice that exists among patients with cancer when considering participation in early-phase cancer immunotherapy CTs. All participants were interpreted as exhibiting some degree of relational autonomy within the psychosocial and structural context of early-phase CT decision making. This study offers insights into the intersection of cancer care delivery, personal beliefs and values, and established CT processes and structures that can inform future practices and policies associated with early-phase cancer immunotherapy CTs to better support patients in making informed decisions
Outside looking in: interpreting gossip appreciation in adults using an observer perspective
No full textMy primary goal was to test two main theories of gossip: the social grooming theory and the cultural learning theory. Participants (N = 197) watched 30-second videos depicting four conditions where a gossip statement or a target present statement contained negative content that was: 1) relevant and violated a norm, 2) relevant and did not violate a norm, 3) irrelevant and violated a norm, or 4) irrelevant and did not violate a norm. Participants rated the speaker’s intent on the following dimensions: 1) sharing information, 2) strengthening relationships, 3) entertaining the listener, and 4) socially influencing the listener. They additionally rated the speaker’s attitude. Participants’ ratings indicated that statements that were relevant to the listener and contained a norm violation were better serving of gossip’s four functions than irrelevant statements without norm violations. However, this was generally the case for both gossip and target present statements with some caveats. Strengthening relationships ratings were increased in gossip conditions, albeit with a small effect size. However, when statements included a norm violation, gossiping increased entertaining and speaker attitude ratings. My findings indicate that both social grooming theory and cultural learning theory capture the main social function features of gossip, with the cultural learning theory having the largest impact Further, these features are impacted by gossip and target present scenarios by either strengthening or dampening the effects depending on the social function being measured.October 202
Simulation of the nanoindentation response in single-crystal magnesium using crystal-plasticity finite element methods
No full textNanoindentation is a widely used technique for characterizing the mechanical properties of materials at the nanoscale by applying controlled force through a sharp indenter and measuring the resulting material deformation. However, it is challenging to access the complex stress states during elastic-plastic deformations occurring beneath the indenter, which are crucial to bridge the microscopic plastic deformation carriers, dislocations and their slip systems, to the macroscopic mechanical behavior of the material. To address this, finite element simulation of nanoindentation is essential. Conventional mate-rial models in finite element software, such as ANSYS, are typically developed for bulk materials and are unable to accurately describe the microscopic plastic behaviors, such as the activation of slip systems in crystalline structures. Crystal plasticity finite element methods (CPFEM), which incorporate slip systems, are currently available only in the ABAQUS CAE finite element software. To further improve efficiency and flexibility of CPFEM, a custom user-defined material subroutine within the ANSYS Parametric Design Language (APDL) platform was developed in this thesis. This method accounts for both elastic and plastic crystal deformation, as well as the crystal plasticity constitutive laws specific to the deformation behaviour of the hexagonal close-packed structure of magnesium.
In this subroutine, the elastic component of the material model was validated against experimental elastic modulus values from the literature, accounting for various crystallographic orientations. The plastic component was validated using Kelley-Hosford plane strain compression test data and compared with the simulation results of Graff et al. The material model was then integrated with the nanoindentation loading conditions, to determine the complex stress states in each element and the load-displacement curves for single-crystal magnesium along c-axis, a-axis, and six other grain orientations. Finally, the activity of basal, prismatic, and pyramidal slip systems was analyzed for each orientation.
This work provides an open-source material subroutine designed to predict the crystallographic dependent mechanical behavior of magnesium. By clarifying the details of microscopic plastic deformation, this tool provides valuable insights for designing advanced magnesium for applications in the aerospace, automotive, and biomedical fields.Fellowship for Educational Purpose by Dr. Yunhua Luo and Dr. Guozhen ZhuFebruary 202
Developing a comparative framework for machine-learning classifying models based on the Emergency Severity Index triage system
No full textEmergency departments are among the most crowded facilities in healthcare premises, where they receive a variety of cases, including critical ones and life-threatening conditions. Arranging the order of received patients and providing timely and efficient care is of utmost importance. This procedure is usually carried out by a nurse who considers the patient’s symptoms and vital signs besides ready resources. Existing literature revealed that there is variability in the accuracy of the triage process inside emergencies for a variety of reasons. Therefore, developing an aid tool based on Machine Learning (ML) algorithms would help mitigate this issue and improve the workflow inside such a crucial setting. This work provides a comparison between several ML-based classifying models that were developed from MIMIC-IV-ED and MIMIC-IV databases. Moreover, it presents insights into hidden patterns that explain some outcomes of subgroups in the examined individuals.February 202
Effectiveness of Online Learning Modules in Changing Patient Management A Literature Review
No full textIntroduction: Online learning modules are increasingly utilized for continuing education to enhance healthcare providers' patient management competencies. However, evidence of sustained practice improvements is limited. This literature review evaluated online learning's effectiveness in changing providers' skills and behaviors for patient care.
Methods: Studies published over 20 years assessing the impact of online modules on diagnosis, treatment recommendations, referrals, or patient outcomes were reviewed. Outcomes of interest were skill decay over time, changes in management practices, and learner's self-reported benefits.
Results: Information acquired from online learning persisted until a year before the gradual decline. Initial gains in diagnosis accuracy and guideline-concordant treatment rates diminished by 12 months. Among nurses, 75% reported lasting confidence improvements in blood loss estimation, but only 42% felt competent in judging severe hemorrhages.
Conclusion: Online learning successfully disseminates foundational knowledge to spur short-term patient management skills. However, sustaining intrinsic practice changes requires recurring boosters and accountability mechanisms. Though beneficial for conveying information, online education should integrate long-term reinforcement strategies to bridge enduring knowing-doing gaps
Custodians of creativity: ethical archiving of artists’ digital records
No full textThe digital age has dramatically reshaped archival practices, requiring novel approaches to preserve and provide access to born digital materials. The opportunities and challenges of the digital age are not only technical, but also ethical. This thesis explores the ethical archiving of artists’ digital records through a case study of the records of Scott Leroux, whose digital archive was entrusted to the University of Manitoba Archives and Special Collections (UMASC). Leroux’s extensive digital footprint, spanning many devices and social media platforms, presented distinct challenges and opportunities in archival work. Ethical considerations in digital preservation are paramount, particularly regarding the management of sensitive content and intellectual property rights. By implementing technical strategies alongside participatory appraisal and arrangement strategies, within a larger feminist ethics of care framework, the integrity and relevance of Leroux’s records are maintained. My study underscores the pivotal role of metadata in making digital records discoverable and usable. Comprehensive metadata was crucial in offering context and ensuring appropriate access to Scott Leroux’s artistic legacy. This thesis promotes the adoption of feminist and decolonial approaches to digital archiving, highlighting the importance of community engagement and radical empathy in archival work.The Hew Graduate Bursary, 45981 and J. Edgar Rea Memorial Bursary, 44916October 202