Showing papers by "Queen's University published in 2022"

Prospects and applications of photonic neural networks

Abstract: Neural networks have enabled applications in artificial intelligence through machine learning, and neuromorphic computing. Software implementations of neural networks on conventional computers that...

On the design evolution of hip implants: A review

Abstract: This manuscript reviews the development of femoral stem prostheses in the biomedical field. After a brief introduction on the development of these prostheses and the associated problems, we describe the standard design of these systems. We review the different materials, constructions, and surfaces used in the development of femoral stems, in order to solve and avoid various problems associated with their use. Femoral stem prostheses have undergone substantial changes and design optimizations since their introduction. Common materials include stainless steel, cobalt–chromium alloy, titanium alloy, and composites. The structural development of femoral stem prostheses, including their length, shape, porosity, and functional gradient construction, is also reviewed. The performance of these prostheses is affected not only by individual factors, but also by the synergistic combination of multiple effects; therefore, several aspects need to be optimized. The main purpose of this study is to summarize various strategies for the material and construction optimization of femoral stem prostheses, and to provide a reference for the combined optimization of their performance. Substantial research is still needed to develop prostheses emulating the behavior of a real human femoral stem.

Omicron and S‐gene target failure cases in the highest COVID‐19 case rate region in Canada—December 2021

Abstract: As the newly detected SARS-CoV-2 B.1.1.529 variant (Omicron) rapidly spreads worldwide, the Kingston, Frontenac, Lennox & Addington (KFL&A) region has had record-setting COVID-19 case numbers, with 1574 active cases as of December 21, 2021—a higher case rate than any other region in Canada (Figure 1). The Omicron variant was classified as a variant of concern by the World Health Organization on November 26, 2021.1 One of its 50+ mutations reduces PCR amplification of the S gene, allowing for S gene target failure (SGTF) to be used as an Omicron marker while awaiting sequencing.2 The rate of detection of Omicron has been faster than other strains in previous pandemic waves, suggesting Omicron may have the ability for faster growth.3 From December 3, the detection of the first case of Omicron in the KFL&A region, until December 21, 2021, there have been 1063 Omicron cases that were either confirmed or suspected.1 A total of 59% of these cases were 18–24 years old while 27% were 25–39 years old. This has corresponded with the main outbreak environments being in Postsecondary education (N = 64) and food and beverage settings (N = 106), with considerable overlap between these settings. There have only been three cases in the 70+ age group and no hospitalizations. There have been no deaths to-date in KFL&A due to Omicron. Initial modeling estimates have placed the Re for Omicron in KFL&A at 1.5 (90% credible interval: 0.78–2.34; modeling estimates conducted with R and the EpiNow2 package). In confirmed and suspect Omicron cases, 9.6% were asymptomatic. For symptomatic cases, the most common symptoms reported were nasal congestion (73%), cough (65%), headaches (54%), sore throat (48%). Of note, only 10% reported shortness of breath. Frequencies of symptom combinations between any two symptoms are displayed in Figure 2. Outside of 45 individuals not yet old enough to be double-vaccinated, 31 cases were unvaccinated, 19 cases were partially vaccinated,2 and 64 cases had unknown vaccination status. The remainder of cases were at least double-vaccinated.3 There was a median of 22 weeks between second dose and symptom onset. There were also 13 Omicron cases in individuals with a third dose: four received their booster 32–35 days before onset, two received theirs 15 days before onset, and seven cases received their booster <14 days before onset. There have been 12 confirmed reinfections with Omicron; all were symptomatic and double-vaccinated.4 These cases had a mix between suspect wild-type, alpha, and delta variants at first infection. Given the rapid propagation of the Omicron variant as well as the incidence of immune escape in double-vaccinated individuals, everyone must continue to remain cautious and vigilant in a time of rapid case surge. This includes physical distancing, limiting nonessential travel and gatherings, proper respiratory and hand hygiene, robust personal protective equipment, and adhering to testing and isolation requirements based on symptoms. Getting a booster vaccine, as able, may be an effective way to prevent breakthrough infections. Postsecondary education institutions and food and beverage settings remain high-risk transmission environments most likely due to reduced physical distancing and higher frequency of unmasking behavior. Strong collaboration and communication between public officials and citizens are needed to ensure a unified approach to mitigating community spread. All the persons and organizations affected by the COVID-19 pandemic; staff at KFL&A Public Health, including the investigators, nurses, case and contact management team, and assessment center personnel; staff at the Kingston Health Sciences Centre and the local Public Health Ontario Laboratory. This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors received no financial support for the research, authorship, and/or publication of this article. The authors declare there are no conflict of interests. The authors alone are responsible for the content and writing of the article. The authors confirm that the data supporting the findings of this study are available within the article. Derived data supporting the findings of this study are available from the corresponding author [THG] on request The authors confirm that the data supporting the findings of this study are available within the article. Derived data supporting the findings of this study are available from the corresponding author [THG] on request

Efficiency Improved Multi-Source Inverter for Hybrid Energy Storage Systems in Electric Vehicle Application

Abstract: Multisource inverters (MSIs) as a new approach for the integration of the energy and the power sources in electric vehicle applications have gained considerable attraction. Such structures offer the active control of the dc sources without using any dc/dc converters or magnetic elements, which reduces the weight, and the volume of the power electronics interface between the sources and the load. Moreover, high power density and improved efficiency due to the elimination of the magnetics are the other significant features of an MSI. This article proposes a novel three-phase MSI for integration and active control of a high-voltage dc source and a low-voltage dc source. The proposed MSI structure employs a smaller number of semiconductor devices at the current path in various operating modes in comparison to the previously published counterparts, which results in an improved efficiency operation. Performance of the proposed MSI using a modified space vector modulation technique for all possible operating modes is verified through simulations and experiments on a laboratory prototype

Mitochondria in human neutrophils mediate killing of Staphylococcus aureus

Abstract: Neutrophils play a role in innate immunity and are critical for clearance of Staphylococcus aureus. Current understanding of neutrophil bactericidal effects is that NADPH oxidase produces reactive oxygen species (ROS), mediating bacterial killing. Neutrophils also contain numerous mitochondria; since these organelles lack oxidative metabolism, their function is unclear. We hypothesize that mitochondria in human neutrophils contribute to the bactericidal capacity of S. aureus.and Findings: Using human neutrophils isolated from healthy volunteers (n = 13; 7 females, 6 males), we show that mitochondria are critical in the immune response to S. aureus. Using live-cell and fixed confocal, and transmission electron microscopy, we show mitochondrial tagging of bacteria prior to ingestion and surrounding of phagocytosed bacteria immediately upon engulfment. Further, we demonstrate that mitochondria are ejected from intact neutrophils and engage bacteria during vital NETosis. Inhibition of the mitochondrial electron transport chain at Complex III, but not Complex I, attenuates S. aureus killing by 50 ± 7%, comparable to the NADPH oxidase inhibitor apocynin. Similarly, mitochondrial ROS scavenging using MitoTEMPO attenuates bacterial killing 112 ± 60% versus vehicle control. Antimycin A treatment also reduces mitochondrial ROS production by 50 ± 12% and NETosis by 53 ± 5%.We identify a previously unrecognized role for mitochondria in human neutrophils in the killing of S. aureus. Inhibition of electron transport chain Complex III significantly impairs antimicrobial activity. This is the first demonstration that vital NETosis, an early event in the antimicrobial response, occurring within 5 min of bacterial exposure, depends on the function of mitochondrial Complex III. Mitochondria join NADPH oxidase as bactericidal ROS generators that mediate the bactericidal activities of human neutrophils.

Inhibition of Ferroptosis Attenuates Glutamate Excitotoxicity and Nuclear Autophagy in a CLP Septic Mouse Model

Abstract: Sepsis-associated encephalopathy (SAE) often manifests in severe diffuse cerebral dysfunction due to an aberrant systemic immune response to infection. The underlying pathophysiology of SAE is not entirely understood but is likely a multifactorial process that involves disruption in cell death mechanism. Ferroptosis is a novel form of programmed cell death characterized by iron accumulation and lipid peroxidation, leading to inflammatory cascade and glutamate release. We hypothesized that ferroptosis is involved in the glutamate-mediated excitotoxic neuron injury during the uncontrolled neural inflammatory process of SAE. Inhibiting ferroptosis with ferrostatin-1 (Fer-1) could alleviate glutamate excitotoxicity and reduce neuron death of SAE, potentially improving prognosis. We found that in the cecal ligation and puncture (CLP) sepsis model, ferroptosis occurred increasingly in the cerebrum, characterized by glutathione-dependent antioxidant enzyme glutathione peroxidase 4 (GPX4) inactivation, transferrin upregulation, mitochondria shrink and malondialdehyde (MDA) increased. Fer-1 treatment downregulated cerebral ferroptosis and alleviated glutamate excitotoxicity via dampening system xc-(SXC) and glutamate receptor N-methyl-D-asperate receptor subunit 2. Combined with an observed reduction in calcium transporter PLCG and PLCB activation, these processes ultimately protected the integrities of synapses and neurons during SAE. Fer-1 treatment also rescued sepsis-induced nuclear autophagy and improved the behaviors of tail suspension test and novel object recognition test in septic mice. Conclusively, our results suggested that inhibition of ferroptosis could attenuate glutamate excitotoxicity and SAE outcomes.

100 YEARS OF VITAMIN D: Historical aspects of vitamin D

Abstract: Vitamin D has many physiological functions including upregulation of intestinal calcium and phosphate absorption, mobilization of bone resorption, renal reabsorption of calcium as well as actions on a variety of pleiotropic functions. It is believed that many of the hormonal effects of vitamin D involve a 1,25-dihydroxyvitamin D3-vitamin D receptor-mediated transcriptional mechanism involving binding to the cellular chromatin and regulating hundreds of genes in many tissues. This comprehensive historical review provides a unique perspective of the many steps of the discovery of vitamin D and its deficiency disease, rickets, stretching from 1650 until the present. The overview is divided into four distinct historical phases which cover the major developments in the field and in the process highlighting the: (a) first recognition of rickets or vitamin D deficiency; (b) discovery of the nutritional factor, vitamin D and its chemical structure; (c) elucidation of vitamin D metabolites including the hormonal form, 1,25-dihydroxyvitamin D3; (d) delineation of the vitamin D cellular machinery, functions and vitamin D-related diseases which focused on understanding the mechanism of action of vitamin D in its many target cells.

Quantifying Power in Silicon Photonic Neural Networks

Abstract: Due to challenging efficiency limits facing conventional and unconventional electronic architectures, information processors based on photonics have attracted renewed interest. Research communities have yet to settle on definitive techniques to describe the performance of this class of information processors. Photonic systems are different from electronic ones, and the existing concepts of computer performance measurement cannot necessarily apply. In this paper, we quantify the power use of photonic neural networks with state-of-the-art and future hardware. We derive scaling laws, physical limits, and platform platform performance metrics. We find that overall performance takes on different dominant scaling laws depending on scale, bandwidth, and resolution, which means that energy efficiency characteristics of a photonic processor can be completely described by no less than seven performance metrics over the range of relevant operating domains. The introduction of these analytical strategies provides a much needed foundation and reference for quantitative roadmapping and commercial value assignment for silicon photonic neural networks.

Progression-free survival: it is time for a new name

Abstract: Progression-free survival refers to the time from randomisation or initiation of treatment to the occurrence of disease progression or death. Disease progression is defined by the Response Evaluation Criteria in Solid Tumors as an increase in the sum of maximum tumour diameters of at least 20%, the development of any new lesions, or an unequivocal increase in non-measurable malignant disease. 1 Eisenhauer EA Therasse P Bogaerts J et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009; 45: 228-247 Google Scholar These criteria were originally developed to categorise the outcomes of new cancer treatments in phase 2 studies and facilitate the advancement of promising therapies to phase 3 trials. As an endpoint that is subject to several sources of bias 2 Gutman SI Piper M Grant MD Basch E Oliansky DM Aronson N Progression-free survival: what does it mean for psychological well-being or quality of life? Methods Research Report No. 13-EHC074-EF. Agency for Healthcare Research and Quality, Rockville, MD2013 Google Scholar and that does not directly measure how a patient feels or functions, or how long a patient lives, progression-free survival was not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. 3 Booth CM Eisenhauer EA Progression-free survival: meaningful or simply measurable?. J Clin Oncol. 2012; 30: 1030-1033 Google Scholar However, over the past two decades, it has become the most common primary endpoint in oncology clinical trials. 4 Del Paggio JC Berry JS Hopman WM et al. Evolution of the randomized clinical trial in the era of precision oncology. JAMA Oncol. 2021; 7: 728-734 Google Scholar From a clinical perspective, a distinction between a patient with a tumour that grows by 21% and a patient with a tumour that grows by 19% seems unlikely. However, in most contemporary randomised controlled trials, these patients would be classified differently. We are concerned that progression-free survival has been widely accepted by the oncology community as an endpoint, without consideration of its limitations as a measure of meaningful impact for patients. 5 Gyawali B Hey SP Kesselheim AS Evaluating the evidence behind the surrogate measures included in the FDA's table of surrogate endpoints as supporting approval of cancer drugs. EClinicalMedicine. 2020; 21100332 Google Scholar As described elsewhere, in addition to many methodological concerns about the use of progression-free survival as a primary endpoint, 3 Booth CM Eisenhauer EA Progression-free survival: meaningful or simply measurable?. J Clin Oncol. 2012; 30: 1030-1033 Google Scholar we are deeply worried about how the term survival in this phrase can influence clinical practice and patient choices. We propose replacing the phrase progression-free survival with a less ambiguous term: progression-free interval.

Diagnostic Armamentarium of Infectious Keratitis: A Comprehensive Review

Abstract: Infectious keratitis (IK) represents the leading cause of corneal blindness worldwide, particularly in developing countries. A good outcome of IK is contingent upon timely and accurate diagnosis followed by appropriate interventions. Currently, IK is primarily diagnosed on clinical grounds supplemented by microbiological investigations such as microscopic examination with stains, and culture and sensitivity testing. Although this is the most widely accepted practice adopted in most regions, such an approach is challenged by several factors, including indistinguishable clinical features shared among different causative organisms, polymicrobial infection, long diagnostic turnaround time, and variably low culture positivity rate. In this review, we aim to provide a comprehensive overview of the current diagnostic armamentarium of IK, encompassing conventional microbiological investigations, molecular diagnostics (including polymerase chain reaction and mass spectrometry), and imaging modalities (including anterior segment optical coherence tomography and in vivo confocal microscopy). We also highlight the potential roles of emerging technologies such as next-generation sequencing, artificial intelligence-assisted platforms. and tele-medicine in shaping the future diagnostic landscape of IK.

100 YEARS OF VITAMIN D: Historical aspects of vitamin D.

Abstract: Vitamin D has many physiological functions including upregulation of intestinal calcium and phosphate absorption, mobilization of bone resorption, renal reabsorption of calcium as well as actions on a variety of pleiotropic functions. It is believed that many of the hormonal effects of vitamin D involve a 1,25-dihydroxyvitamin D3-vitamin D receptor-mediated transcriptional mechanism involving binding to the cellular chromatin and regulating hundreds of genes in many tissues. This comprehensive historical review provides a unique perspective of the many steps of the discovery of vitamin D and its deficiency disease, rickets, stretching from 1650 until the present. The overview is divided into four distinct historical phases which cover the major developments in the field and in the process highlighting the: (a) first recognition of rickets or vitamin D deficiency; (b) discovery of the nutritional factor, vitamin D and its chemical structure; (c) elucidation of vitamin D metabolites including the hormonal form, 1,25-dihydroxyvitamin D3; (d) delineation of the vitamin D cellular machinery, functions and vitamin D-related diseases which focused on understanding the mechanism of action of vitamin D in its many target cells.

100 YEARS OF VITAMIN D: Historical aspects of vitamin D.

Abstract: Vitamin D has many physiological functions including upregulation of intestinal calcium and phosphate absorption, mobilization of bone resorption, renal reabsorption of calcium as well as actions on a variety of pleiotropic functions. It is believed that many of the hormonal effects of vitamin D involve a 1,25-dihydroxyvitamin D3-vitamin D receptor-mediated transcriptional mechanism involving binding to the cellular chromatin and regulating hundreds of genes in many tissues. This comprehensive historical review provides a unique perspective of the many steps of the discovery of vitamin D and its deficiency disease, rickets, stretching from 1650 until the present. The overview is divided into four distinct historical phases which cover the major developments in the field and in the process highlighting the: (a) first recognition of rickets or vitamin D deficiency; (b) discovery of the nutritional factor, vitamin D and its chemical structure; (c) elucidation of vitamin D metabolites including the hormonal form, 1,25-dihydroxyvitamin D3; (d) delineation of the vitamin D cellular machinery, functions and vitamin D-related diseases which focused on understanding the mechanism of action of vitamin D in its many target cells.

100 YEARS OF VITAMIN D: Historical aspects of vitamin D.

Abstract: Vitamin D has many physiological functions including upregulation of intestinal calcium and phosphate absorption, mobilization of bone resorption, renal reabsorption of calcium as well as actions on a variety of pleiotropic functions. It is believed that many of the hormonal effects of vitamin D involve a 1,25-dihydroxyvitamin D3-vitamin D receptor-mediated transcriptional mechanism involving binding to the cellular chromatin and regulating hundreds of genes in many tissues. This comprehensive historical review provides a unique perspective of the many steps of the discovery of vitamin D and its deficiency disease, rickets, stretching from 1650 until the present. The overview is divided into four distinct historical phases which cover the major developments in the field and in the process highlighting the: (a) first recognition of rickets or vitamin D deficiency; (b) discovery of the nutritional factor, vitamin D and its chemical structure; (c) elucidation of vitamin D metabolites including the hormonal form, 1,25-dihydroxyvitamin D3; (d) delineation of the vitamin D cellular machinery, functions and vitamin D-related diseases which focused on understanding the mechanism of action of vitamin D in its many target cells.

Systematic review with meta-analysis of diagnostic test accuracy for COVID-19 by mass spectrometry.

Abstract: Background The global COVID-19 pandemic has led to extensive development in many fields, including the diagnosis of COVID-19 infection by mass spectrometry. The aim of this systematic review and meta-analysis was to assess the accuracy of mass spectrometry diagnostic tests developed so far, across a wide range of biological matrices, and additionally to assess risks of bias and applicability in studies published to date. Method 23 retrospective observational cohort studies were included in the systematic review using the PRISMA-DTA framework, with a total of 2858 COVID-19 positive participants and 2544 controls. Risks of bias and applicability were assessed via a QUADAS-2 questionnaire. A meta-analysis was also performed focusing on sensitivity, specificity, diagnostic accuracy and Youden's Index, in addition to assessing heterogeneity. Findings Sensitivity averaged 0.87 in the studies reviewed herein (interquartile range 0.81–0.96) and specificity 0.88 (interquartile range 0.82–0.98), with an area under the receiver operating characteristic summary curve of 0.93. By subgroup, the best diagnostic results were achieved by viral proteomic analyses of nasopharyngeal swabs and metabolomic analyses of plasma and serum. The performance of other sampling matrices (breath, sebum, saliva) was less good, indicating that these protocols are currently insufficiently mature for clinical application. Conclusions This systematic review and meta-analysis demonstrates the potential for mass spectrometry and ‘omics in achieving accurate test results for COVID-19 diagnosis, but also highlights the need for further work to optimize and harmonize practice across laboratories before these methods can be translated to clinical applications.