The Institute of Medical Science (IMS) was established as an institute within the School of Graduate Studies at the University of Toronto in 1968 to serve as a graduate unit for the Clinical Departments in the Faculty...The Institute of Medical Science (IMS) was established as an institute within the School of Graduate Studies at the University of Toronto in 1968 to serve as a graduate unit for the Clinical Departments in the Faculty of Medicine. In this role,the IMS offers a doctoral stream program in medical science leading to the Master of Science and Doctor of Philosophy degrees. Translational research,as a means of moving new discovery to improvement in patient outcome,has become a central theme of graduate education in our Institute. To this end,we have developed a curriculum offering which is intended to provide all new students with a defined skill set relevant to Translational Research and at the same time,to provide students with flexible offerings which would enhance their specific research programs. The course,spread over two years,will have three separate components:(1) there will be lectures focusing on research fundamentals and the basics of translational research; (2) there will be student presentations to hone presentation skills and get valuable feedback from fellow students and faculty mentors; (3) there will be elective modules,where students can select from a number of course offerings in order to round out training. These modules include subjects such as the fundamentals of clinical trials,the basics of qualitative research,an approach to the role of proteomics and genomics in research and the business of science. As part of this modular program,we have created a program 'clinical exposure for non-clinicians' with the hope that graduate students will be able to gain some understanding of the clinical relevance of their research activities. Over time,these modular offerings will be expanded based on a needs assessment from our students. The presentation will describe the IMS and its mission and will overview the structure and content of this course offering.展开更多
Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-...Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.展开更多
This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally ...This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.展开更多
Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lyci...Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.展开更多
Since its introduction,discontinuous deformation analysis(DDA)has been widely used in different areas of rock mechanics.By dividing large blocks into subblocks and introducing artificial joints,DDA can be applied to r...Since its introduction,discontinuous deformation analysis(DDA)has been widely used in different areas of rock mechanics.By dividing large blocks into subblocks and introducing artificial joints,DDA can be applied to rock fracture simulation.However,parameter calibration,a fundamental issue in discontinuum methods,has not received enough attention in DDA.In this study,the parameter calibration of DDA for intact rock is carefully studied.To this end,a subblock DDA with Voronoi tessellation is presented first.Then,a modified contact constitutive law is introduced,in which the tensile and shear meso-strengths are modified to be independent of the bond lengths.This improvement can prevent the unjustified preferential failure of short edges.A method for imposing confining pressure is also introduced.Thereafter,sensitivity analysis is performed to investigate the influence of the calculated parameters and meso-parameters on the mechanical properties of modeled rock.Based on the sensitivity analysis,a unified calibration procedure is suggested for both cases with and without confining pressure.Finally,the calibration procedure is applied to two examples,including a biaxial compression test.The results show that the proposed Voronoi-based DDA can simulate rock fracture with and without confining pressure very well after careful parameter calibration.展开更多
Use of gold nanoparticles(GNPs)in medicine is an emerging field of translational research with vast clinical implications and exciting therapeutic potential.However,the safety of using GNPs in human subjects is an imp...Use of gold nanoparticles(GNPs)in medicine is an emerging field of translational research with vast clinical implications and exciting therapeutic potential.However,the safety of using GNPs in human subjects is an important question that remains unanswered.This study reviews over 20 clinical trials focused on GNP safety and aims to summarize all the clinical studies,completed and ongoing,to identify whether GNPs are safe to use in humans as a therapeutic platform.In these studies,GNPs were implemented as drug delivery devices,for photothermal therapy,and utilized for their intrinsic therapeutic effects by various routes of delivery.These studies revealed no major safety concerns with the use of GNPs;however,the number of trials and total patient number remains limited.Multi-dose,multicenter blinded trials are required to deepen our understanding of the use of GNPs in clinical settings to facilitate translation of this novel,multifaceted therapeutic device.Expanding clinical trials will require collaboration between clinicians,scientists,and biotechnology companies.展开更多
The words one chooses to describe personal pain mirror current usage, but may also hold echoes of an individual’s lived experience. They may provide clues to the origin of physical symptoms that are medically hard to...The words one chooses to describe personal pain mirror current usage, but may also hold echoes of an individual’s lived experience. They may provide clues to the origin of physical symptoms that are medically hard to explain. The aim of this commentary is to propose, on the basis of the available literature, that verbal metaphors can prove effective in the psychotherapy of such conditions. I provide a case history of a 45 year old woman referred to psychiatry because of extreme ‘burning’ pain in her mouth and tongue. She had been to numerous doctors, had undergone a variety of tests, had tried many medical treatments, and had been prescribed a number of different pharmaceutical agents. She had changed her diet, done her daily dental mouth exercises, drunk a lot of water, but the burning continued and interfered, with her job(she was a teacher), her friendships, and her everyday life. This made her angry and recalcitrant to therapy, but the metaphor ‘burning with rage,’ as applicable to her pain, worked to establish a good alliance that led to a decrease of symptoms. Burning Mouth Syndrome is a medically unexplained condition of complex etiology that psychotherapy alone cannot reverse. The literature bears out, however, that the use of metaphors can help to open avenues of psychological exploration that accelerate adaptation to pain and improve quality life.展开更多
Dynamic tensile failure is a common phenomenon in deep rock practices,and thus accurately evaluating the dynamic tensile responses of rocks under triaxial pressures is of great significance.The Brazilian disc(BD)test ...Dynamic tensile failure is a common phenomenon in deep rock practices,and thus accurately evaluating the dynamic tensile responses of rocks under triaxial pressures is of great significance.The Brazilian disc(BD)test is the suggested method by the International Society for Rock Mechanics and Rock Engineering(ISRM)for measuring both the static and dynamic tensile strengths of rock-like materials.However,due to the overload phenomenon and the complex preloading conditions,the dynamic tensile strengths of rocks measured by the BD tests tend to be overestimated.To address this issue,the dynamic BD tensile strength(BTS)of Fangshan marble(FM)under different preloading conditions were measured through a triaxial split Hopkinson pressure bar(SHPB).The fracture onset in BD specimen was captured through a strain gage around the disc center.The discrepancy between the traditional tensile strength(TTS,determined by the peak load P_(f) of the BD specimen)and the nominal tensile strength(NTS,obtained from the load P_(i) when the diametral fracture commences in the tested BD specimen)was applied to quantitatively evaluating the overload phenomenon.The Griffith criterion was used to rectify the calculation of the tensile stress at the disc center under triaxial stress states.The results demonstrate that the overload ratio(s)increases with the loading rate(σ)and decreases with the hydrostatic pressure(σ_(s)).The TTS corrected by the Griffith criterion is independent of theσ_(s)due to the overload phenomenon,while the NTS corrected by the Griffith criterion is sensitive to both the andσ.Therefore,it is essential to modify the tensile stress in dynamic confined BD tests using both the overload correction and the Griffith criterion rectification to obtain the accurate dynamic BTS of rocks.展开更多
Engineering disasters(e.g.rock slabbing and rockburst)of the tunnel groups induced by the transient excavation of an adjacent tunnel threaten the stability of the existing tunnel,especially for those excavated by usin...Engineering disasters(e.g.rock slabbing and rockburst)of the tunnel groups induced by the transient excavation of an adjacent tunnel threaten the stability of the existing tunnel,especially for those excavated by using the drill and blast tunneling(D&B).However,the dynamic response and failure mechanism of surrounding rocks of the existing tunnel caused by adjacent transient excavation are not clear due to the difficulty in conducting field tests and laboratory experiments.Therefore,a novel transient unloading experimental system for deep tunnel excavation was proposed in this study.The real stress path and the unloading rate can be reproduced by using this proposed system.The experiments were conducted for observing the dynamic response of the existing tunnel induced by adjacent transient excavation under different lateral pressure coefficients l(?0.4,0.6,0.8,1,1.2,1.4,1.6,1.8)with a polymethyl methacrylate(PMMA)specimen.The propagation of the impact wave and unloading surface wave was detected through the digital image correlation(DIC)analysis.The reflection of the unloading surface wave on the incident side of the existing tunnel(tunnel-E)was observed and analyzed.Moreover,the dynamic characteristics of the stress redistribution,the particle displacement and vibration velocity of surrounding rocks of tunnel-E were analyzed and summarized.In addition,the Mohr-Coulomb(MeC)failure criterion with tension cut-off was adopted to evaluate the stability of the existing tunnel under adjacent transient excavation.The results indicate that the incident side of the existing tunnel under the dynamic disturbance of transient excavation of an adjacent tunnel was more prone to fail,followed by the shadow side and the top/bottom side.展开更多
Marine equipments such as marine risers and oil pipelines operate in complex underwater environments and are usually attached by animals,plants and microorganisms.The attachment of marine fouling organisms will accele...Marine equipments such as marine risers and oil pipelines operate in complex underwater environments and are usually attached by animals,plants and microorganisms.The attachment of marine fouling organisms will accelerate the corrosion damage of offshore structure and greatly reduce the service life.Studies have shown that non-smooth bionic surfaces with specific microstructures can inhibit fouling formation.Based on the idea of bionics,this paper proposes a new type of underwater flexible fretting texture,which is a composite material prepared by mixing graphene and silicone rubber,and modified by pulsed laser to construct a hexagonal bionic surface texture.Under the impact of specific water flow,the flexible texture can produce an angular displacement around 8°and a linear displacement in the amplitude range of 165μm,and the inhibition rate of fouling biological diatoms up to 97.5%,which can effectively avoid the occurrence of marine biological fouling.The results provide a new idea for the surface protection of marine structures,which is of great significance for the development of marine industry.展开更多
The anisotropy induced by rock bedding structures is usually manifested in the mechanical behaviors and failure modes of rocks.Brazilian tests are conducted for seven groups of shale specimens featuring different bedd...The anisotropy induced by rock bedding structures is usually manifested in the mechanical behaviors and failure modes of rocks.Brazilian tests are conducted for seven groups of shale specimens featuring different bedding angles. Acoustic emission (AE) and digital image correlation (DIC) technologies are used to monitor the in-situ failure of the specimens. Furthermore, the crack morphology of damaged samples is observed through scanning electron microscopy (SEM). Results reveal the structural dependence on the tensile mechanical behavior of shales. The shale disk exhibits compression in the early stage of the experiment with varying locations and durations. The location of the compression area moves downward and gradually disappears when the bedding angle increases. The macroscopic failure is well characterized by AE event location results, and the dominant frequency distribution is related to the bedding angle. The b-value is found to be stress-dependent.The crack turning angle between layers and the number of cracks crossing the bedding both increase with the bedding angle, indicating competition between crack propagations. SEM results revealed that the failure modes of the samples can be classified into three types:tensile failure along beddings with shear failure of the matrix, ladder shear failure along beddings with tensile failure of the matrix, and shear failure along multiple beddings with tensile failure of the matrix.展开更多
Interparticle adhesion force has a controlling effect on the physical and mechanical properties of planetary regolith and rocks.The current research on the adhesion force of planetary regolith and rock particles has b...Interparticle adhesion force has a controlling effect on the physical and mechanical properties of planetary regolith and rocks.The current research on the adhesion force of planetary regolith and rock particles has been primarily based on the assumption of smooth spherical particles to calculate the intergranular adhesion force;this approach lacks consideration for the adhesion force between irregular shaped particles.In our study,an innovative approach was established to directly measure the adhesion force between the arbitrary irregular shaped particles;the probe was modified using simulated lunar soil particles that were a typical representation of planetary regolith.The experimental results showed that for irregular shaped mineral particles,the particle size and mineral composition had no significant influence on the interparticle adhesion force;however,the complex morphology of the contact surface predominantly controlled the adhesion force.As the contact surface roughness increased,the adhesion force gradually decreased,and the rate of decrease gradually slowed;these results were consistent with the change trend predicted via the theoretical models of quantum electrodynamics.Moreover,a theoretical model to predict the adhesion force between the irregular shaped particles was constructed based on Rabinovich’s theory,and the prediction results were correlated with the experimental measurements.展开更多
The effective treatment of patients with cancer hinges on the delivery of therapeutics to a tumor site.Nanoparticles provide an essential transport system.We present 5 principles to consider when designing nanoparticl...The effective treatment of patients with cancer hinges on the delivery of therapeutics to a tumor site.Nanoparticles provide an essential transport system.We present 5 principles to consider when designing nanoparticles for cancer targeting:(a)Nanoparticles acquire biological identity in vivo,(b)organs compete for nanoparticles in circulation,(c)nanoparticles must enter solid tumors to target tumor components,(d)nanoparticles must navigate the tumor microenvironment for cellular or organelle targeting,and(e)size,shape,surface chemistry,and other physicochemical properties of nanoparticles influence their transport process to the target.This review article describes these principles and their application for engineering nanoparticle delivery systems to carry therapeutics to tumors or other disease targets.展开更多
To theeditor:The incidence of depression and obesity is on the rise,posing significant public health concerns.While the literature largely supports a positive correlation between depression and body mass index(BMI),I2...To theeditor:The incidence of depression and obesity is on the rise,posing significant public health concerns.While the literature largely supports a positive correlation between depression and body mass index(BMI),I2 earlier studies have suggested an inverse relationship or indicated a lack of association between depression and obesity.展开更多
The shear behavior is regarded as the dominant property of rock joints and is dramatically affected by the joint surface roughness.To date,the effect of surface roughness on the shear behavior of rock joints under sta...The shear behavior is regarded as the dominant property of rock joints and is dramatically affected by the joint surface roughness.To date,the effect of surface roughness on the shear behavior of rock joints under static or cyclic loading conditions has been extensively studied,but such effect under impact loading conditions keeps unclear.To address this issue,a series of impact shear tests was performed using a novel-designed dynamic experimental system combined with the digital image correlation(DIC)technique.The dynamic shear strength,deformability and failure mode of the jointed specimens with various joint roughness coefficients(JRC)are comprehensively analyzed.Results show that the shear strength and shear displacement characteristics of the rock joint under the impact loading keep consistent with those under static loading conditions.However,the temporal variations of shear stress,slip displacement and normal displacement under the impact loading conditions show obviously different behaviors.An elastic rebound of the slip displacement occurs during the impact shearing and its value increases with increasing joint roughness.Two identifiable stages(i.e.compression and dilation)are observed in the normal displacement curves for the rougher rock joints,whereas the joints with small roughness only manifest normal compression displacement.Besides,as the roughness increases,the maximum compression tends to decrease,while the maximum dilation gradually increases.More-over,the microstructural analysis based on scanning electron microscope(SEM)suggests that the roughness significantly affects the characteristics of the shear fractured zone enclosing the joint surface.展开更多
Background and Purpose: With the unexpectedly rapid increase in the prevalence of types of diabetes worldwide, this chronic disease is no longer being viewed as a systemic health issue, but also treated as the start o...Background and Purpose: With the unexpectedly rapid increase in the prevalence of types of diabetes worldwide, this chronic disease is no longer being viewed as a systemic health issue, but also treated as the start of the deadly disease. As the sixth complication of diabetes, periodontitis is a chronic inflammatory condition that leads directly and indirectly to a severer condition of diabetes via its underlying mechanisms. Interestingly, both diseases are not been fully identified in their bidirectional relationships by researchers. Thus, healthcare agencies must pay appropriate attention. This literature review paper aims to investigate and discuss dentists’ role in modulating environmental and epigenetic determinants in the oral health of diabetic patients based on the bidirectional relationship between these diseases, their prevalence and how treatment of one disease affects the other. Methods: The authors conducted electronic searches in PubMed, Google Scholar, One Search UofT, ScienceDirect, and the National Library of Medicine. The paper also included gray literature from government resources related to the topic. The paper will review the epidemiology, pathogenesis, and epigenetics of both diabetes and periodontal disease and their functions with each other. Results: The literature has consistently shown that diabetes and periodontal disease have responded to the formation and severity of each other. Patients with pre- and diabetes have potentially higher risks of causing periodontal disease and other complications if adequate diagnosis and treatment are not involved timely. The combination of risk factors, including individual, social, environmental, and genetic, play a crucial role in the development of diabetes and the severity of periodontitis. Conclusions: Based on the results, the collaboration between dentists and other healthcare practitioners is inevitable in the overall development of treatment for both diseases. With the proper and updated knowledge, dentists can benefit patients’ overall physical conditions through strategic intervention in diabetes patients.展开更多
The field of exercise-oncology has evolved significantly over the past 30 years.Numerous studies have examined the role of structured exercise interventions—often incorporating aerobic or resistance training at moder...The field of exercise-oncology has evolved significantly over the past 30 years.Numerous studies have examined the role of structured exercise interventions—often incorporating aerobic or resistance training at moderate-to-vigorous intensities,sometimes in conjunction with multi-modal strategies—for individuals living with and beyond cancer.展开更多
Objective:Smart insufflation(SI)techniques relying on valve and membrane-free insufflation are increasing in usage.Although considerable literature exists demonstrating the benefits of SI on procedural ease and patien...Objective:Smart insufflation(SI)techniques relying on valve and membrane-free insufflation are increasing in usage.Although considerable literature exists demonstrating the benefits of SI on procedural ease and patient outcomes,there remains a paucity describing the financial impact of these devices.The purpose of this study was to determine the financial and efficiency impact of these devices on the operating room and inpatient wards of a hospital.Methods:A discrete event simulation model representing a typical mid-sized North American hospital comparing SI to traditional insufflation(TI)was generated.The National Surgical Quality Improvement database from 2015 to 2019 was used to populate the model with data supplemented from the literature.Outcomes included length of stay(LOS),duration of surgery(DOS),annual procedure volume,profit,return on investment(ROI),and gross profit margin(GPM).From the literature review,DOS savings were 10e32 minutes/case,while LOS savings were 0e3 days/case.Results:Implementation of an SI led to an increase in annual throughput of 42e346(4.4%e36.6%)cases for all procedures and 38 to 297(4.3%e33.3%)cases for complex procedures.LOS was found to be decreased by 175e614(18.3%e64.2%)days for all procedures and 231 to 614(35.6%e77.9%)cases for complex procedures with the implementation of an SI.Together,this resulted in an increase in net profit of$104,685 per annum.The ROI of SI over the TI device was>1000%,and the GPM for the TI was 90.0%,while the GPM for the SI was 71.7%.Conclusion:Despite the initial financial investment being greater,the implementation of SI offsets these expenses and yields significant financial benefits.Our study demonstrates the financial benefits of SI over TI and illustrates how granular operational and financial analyses of technologies are essential to aid in sound healthcare procurement decision making.展开更多
Colloidal quantum dots(CQDs)are of great interest to photovoltaic(PV)technologies as they possess the benefits of solution-processability,size-tunability,and roll-to-roll manufacturability,as well as unique capabiliti...Colloidal quantum dots(CQDs)are of great interest to photovoltaic(PV)technologies as they possess the benefits of solution-processability,size-tunability,and roll-to-roll manufacturability,as well as unique capabilities to harvest near-infrared(NIR)radiation.During the last decade,lab-scale CQD solar cells have achieved rapid improvement in the power conversion efficiency(PCE)from~1%to 18%,which will potentially exceed 20%in the next few years and approach the performance of other PV technologies,such as perovskite solar cells and organic solar cells.In the meanwhile,CQD solar cells exhibit long lifetimes either under shelf storage or continuous operation,making them highly attractive to industry.However,in order to meet the industrial requirements,mass production techniques are necessary to scale up the fabrication of those lab devices into large-area PV modules,such as roll-to-toll coating.This paper reviews the recent developments of large-area CQD solar cells with a focus on various fabrication methods and their principles.It covers the progress of typical large-area coating techniques,including spray coating,blade coating,dip coating,and slot-die coating.It also discusses next steps and new strategies to accomplish the ultimate goal of the low-cost large-area fabrication of CQD solar cells and emphasizes how artificial intelligence or machine learning could facilitate the developments of CQD solar cell research.展开更多
Discontinuities are often considered as important factors responsible for the instability caused by shear failure in engineering rock mass,and energy-driven instability is the root cause of rock failure.However,few st...Discontinuities are often considered as important factors responsible for the instability caused by shear failure in engineering rock mass,and energy-driven instability is the root cause of rock failure.However,few studies focus on the energy evolution during the failure process using a three-dimensional(3D)numerical model.In this study,a series of laboratory direct shear tests on rock-like samples is numer-ically simulated using bonded particle models(BPMs)with multiple combinations of discontinuous in the particle flow code(PFC3D),in which the location and size of the particles conform to the uniform distribution.The effects of joint row number and inclination on the stress-strain characteristics and failure mode of rock were studied from the perspective of microcrack growth and energy evolution.The results showed that,when the number of joint rows Nr>1,the shear failure region does not change with the increase of Nr for the type B(2-columnn multiple-row at center)and the type C(2-column multiple-row at edge)as compared to the type A(1-column multiple-row at center)joint models.Notably,joints significantly increase the post-peak energy dissipation but have little effect on the proportion of energy before the peak.Friction consumes most of the energy while kinetic energy accounts for less than 1%of total energy during the shear process.Peak elastic strain energy follows the variation trend of peak shear displacement.The development and accumulation of microcracks directly affect the energy dissipation,and there is a significant linear relationship between the cumulative number of critical microcracks and the critical dissipated energy at the failure,when the dip direction of joints is opposite to the shear direction,more microcracks will be accumulated at the peak time,resulting in more energy dissipation.The results contribute to deeply understanding the shear failure process of non-persistent jointed mass.展开更多
文摘The Institute of Medical Science (IMS) was established as an institute within the School of Graduate Studies at the University of Toronto in 1968 to serve as a graduate unit for the Clinical Departments in the Faculty of Medicine. In this role,the IMS offers a doctoral stream program in medical science leading to the Master of Science and Doctor of Philosophy degrees. Translational research,as a means of moving new discovery to improvement in patient outcome,has become a central theme of graduate education in our Institute. To this end,we have developed a curriculum offering which is intended to provide all new students with a defined skill set relevant to Translational Research and at the same time,to provide students with flexible offerings which would enhance their specific research programs. The course,spread over two years,will have three separate components:(1) there will be lectures focusing on research fundamentals and the basics of translational research; (2) there will be student presentations to hone presentation skills and get valuable feedback from fellow students and faculty mentors; (3) there will be elective modules,where students can select from a number of course offerings in order to round out training. These modules include subjects such as the fundamentals of clinical trials,the basics of qualitative research,an approach to the role of proteomics and genomics in research and the business of science. As part of this modular program,we have created a program 'clinical exposure for non-clinicians' with the hope that graduate students will be able to gain some understanding of the clinical relevance of their research activities. Over time,these modular offerings will be expanded based on a needs assessment from our students. The presentation will describe the IMS and its mission and will overview the structure and content of this course offering.
基金supported by the Robert Campeau Family Foundation/Dr.C.H.Tator Chair in Brain and Spinal Cord Research(to MGF)。
文摘Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.
文摘This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.
基金supported by the National Natural Science Foundation of China,No.81671347(to KL)the Science and Technology Program of Guangzhou of China,No.202007030012(to KFS and KL)the Science and Technology Program of Guangzhou of China,No 202102020735(to RW).
文摘Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.
基金The authors would like to thank the National Natural Science Foundation of China(Grant Nos.51879184 and 52079091)for funding this work.
文摘Since its introduction,discontinuous deformation analysis(DDA)has been widely used in different areas of rock mechanics.By dividing large blocks into subblocks and introducing artificial joints,DDA can be applied to rock fracture simulation.However,parameter calibration,a fundamental issue in discontinuum methods,has not received enough attention in DDA.In this study,the parameter calibration of DDA for intact rock is carefully studied.To this end,a subblock DDA with Voronoi tessellation is presented first.Then,a modified contact constitutive law is introduced,in which the tensile and shear meso-strengths are modified to be independent of the bond lengths.This improvement can prevent the unjustified preferential failure of short edges.A method for imposing confining pressure is also introduced.Thereafter,sensitivity analysis is performed to investigate the influence of the calculated parameters and meso-parameters on the mechanical properties of modeled rock.Based on the sensitivity analysis,a unified calibration procedure is suggested for both cases with and without confining pressure.Finally,the calibration procedure is applied to two examples,including a biaxial compression test.The results show that the proposed Voronoi-based DDA can simulate rock fracture with and without confining pressure very well after careful parameter calibration.
基金supported by grants from Canadian Institutes of Health Research(Grant Nos.:MOP-42546,MOP-119514,PJT148847).
文摘Use of gold nanoparticles(GNPs)in medicine is an emerging field of translational research with vast clinical implications and exciting therapeutic potential.However,the safety of using GNPs in human subjects is an important question that remains unanswered.This study reviews over 20 clinical trials focused on GNP safety and aims to summarize all the clinical studies,completed and ongoing,to identify whether GNPs are safe to use in humans as a therapeutic platform.In these studies,GNPs were implemented as drug delivery devices,for photothermal therapy,and utilized for their intrinsic therapeutic effects by various routes of delivery.These studies revealed no major safety concerns with the use of GNPs;however,the number of trials and total patient number remains limited.Multi-dose,multicenter blinded trials are required to deepen our understanding of the use of GNPs in clinical settings to facilitate translation of this novel,multifaceted therapeutic device.Expanding clinical trials will require collaboration between clinicians,scientists,and biotechnology companies.
文摘The words one chooses to describe personal pain mirror current usage, but may also hold echoes of an individual’s lived experience. They may provide clues to the origin of physical symptoms that are medically hard to explain. The aim of this commentary is to propose, on the basis of the available literature, that verbal metaphors can prove effective in the psychotherapy of such conditions. I provide a case history of a 45 year old woman referred to psychiatry because of extreme ‘burning’ pain in her mouth and tongue. She had been to numerous doctors, had undergone a variety of tests, had tried many medical treatments, and had been prescribed a number of different pharmaceutical agents. She had changed her diet, done her daily dental mouth exercises, drunk a lot of water, but the burning continued and interfered, with her job(she was a teacher), her friendships, and her everyday life. This made her angry and recalcitrant to therapy, but the metaphor ‘burning with rage,’ as applicable to her pain, worked to establish a good alliance that led to a decrease of symptoms. Burning Mouth Syndrome is a medically unexplained condition of complex etiology that psychotherapy alone cannot reverse. The literature bears out, however, that the use of metaphors can help to open avenues of psychological exploration that accelerate adaptation to pain and improve quality life.
基金We acknowledge the funding support from the National Natural Science Foundation of China(Grant Nos.42141010,51879184 and 12172253).
文摘Dynamic tensile failure is a common phenomenon in deep rock practices,and thus accurately evaluating the dynamic tensile responses of rocks under triaxial pressures is of great significance.The Brazilian disc(BD)test is the suggested method by the International Society for Rock Mechanics and Rock Engineering(ISRM)for measuring both the static and dynamic tensile strengths of rock-like materials.However,due to the overload phenomenon and the complex preloading conditions,the dynamic tensile strengths of rocks measured by the BD tests tend to be overestimated.To address this issue,the dynamic BD tensile strength(BTS)of Fangshan marble(FM)under different preloading conditions were measured through a triaxial split Hopkinson pressure bar(SHPB).The fracture onset in BD specimen was captured through a strain gage around the disc center.The discrepancy between the traditional tensile strength(TTS,determined by the peak load P_(f) of the BD specimen)and the nominal tensile strength(NTS,obtained from the load P_(i) when the diametral fracture commences in the tested BD specimen)was applied to quantitatively evaluating the overload phenomenon.The Griffith criterion was used to rectify the calculation of the tensile stress at the disc center under triaxial stress states.The results demonstrate that the overload ratio(s)increases with the loading rate(σ)and decreases with the hydrostatic pressure(σ_(s)).The TTS corrected by the Griffith criterion is independent of theσ_(s)due to the overload phenomenon,while the NTS corrected by the Griffith criterion is sensitive to both the andσ.Therefore,it is essential to modify the tensile stress in dynamic confined BD tests using both the overload correction and the Griffith criterion rectification to obtain the accurate dynamic BTS of rocks.
基金supported by the National Natural Science Foundation of China(Grant Nos.42141010,51879184 and 12172253).
文摘Engineering disasters(e.g.rock slabbing and rockburst)of the tunnel groups induced by the transient excavation of an adjacent tunnel threaten the stability of the existing tunnel,especially for those excavated by using the drill and blast tunneling(D&B).However,the dynamic response and failure mechanism of surrounding rocks of the existing tunnel caused by adjacent transient excavation are not clear due to the difficulty in conducting field tests and laboratory experiments.Therefore,a novel transient unloading experimental system for deep tunnel excavation was proposed in this study.The real stress path and the unloading rate can be reproduced by using this proposed system.The experiments were conducted for observing the dynamic response of the existing tunnel induced by adjacent transient excavation under different lateral pressure coefficients l(?0.4,0.6,0.8,1,1.2,1.4,1.6,1.8)with a polymethyl methacrylate(PMMA)specimen.The propagation of the impact wave and unloading surface wave was detected through the digital image correlation(DIC)analysis.The reflection of the unloading surface wave on the incident side of the existing tunnel(tunnel-E)was observed and analyzed.Moreover,the dynamic characteristics of the stress redistribution,the particle displacement and vibration velocity of surrounding rocks of tunnel-E were analyzed and summarized.In addition,the Mohr-Coulomb(MeC)failure criterion with tension cut-off was adopted to evaluate the stability of the existing tunnel under adjacent transient excavation.The results indicate that the incident side of the existing tunnel under the dynamic disturbance of transient excavation of an adjacent tunnel was more prone to fail,followed by the shadow side and the top/bottom side.
基金financially supported by the National Natural Science Foundation of China(Grant No.51975586)。
文摘Marine equipments such as marine risers and oil pipelines operate in complex underwater environments and are usually attached by animals,plants and microorganisms.The attachment of marine fouling organisms will accelerate the corrosion damage of offshore structure and greatly reduce the service life.Studies have shown that non-smooth bionic surfaces with specific microstructures can inhibit fouling formation.Based on the idea of bionics,this paper proposes a new type of underwater flexible fretting texture,which is a composite material prepared by mixing graphene and silicone rubber,and modified by pulsed laser to construct a hexagonal bionic surface texture.Under the impact of specific water flow,the flexible texture can produce an angular displacement around 8°and a linear displacement in the amplitude range of 165μm,and the inhibition rate of fouling biological diatoms up to 97.5%,which can effectively avoid the occurrence of marine biological fouling.The results provide a new idea for the surface protection of marine structures,which is of great significance for the development of marine industry.
基金financially supported by the National Natural Science Foundation of China (No.51934003)the Major Science and Technology Special Project of Yunnan Province,China(Nos.202102AF080001 and 202102AG050024)。
文摘The anisotropy induced by rock bedding structures is usually manifested in the mechanical behaviors and failure modes of rocks.Brazilian tests are conducted for seven groups of shale specimens featuring different bedding angles. Acoustic emission (AE) and digital image correlation (DIC) technologies are used to monitor the in-situ failure of the specimens. Furthermore, the crack morphology of damaged samples is observed through scanning electron microscopy (SEM). Results reveal the structural dependence on the tensile mechanical behavior of shales. The shale disk exhibits compression in the early stage of the experiment with varying locations and durations. The location of the compression area moves downward and gradually disappears when the bedding angle increases. The macroscopic failure is well characterized by AE event location results, and the dominant frequency distribution is related to the bedding angle. The b-value is found to be stress-dependent.The crack turning angle between layers and the number of cracks crossing the bedding both increase with the bedding angle, indicating competition between crack propagations. SEM results revealed that the failure modes of the samples can be classified into three types:tensile failure along beddings with shear failure of the matrix, ladder shear failure along beddings with tensile failure of the matrix, and shear failure along multiple beddings with tensile failure of the matrix.
基金supported by the National Natural Science Foundation of China(Nos.U22A20166,52104141,12172230 and U2013603)the Department of Science and Technology of Guangdong Province(No.2019ZT08G315)the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515012654).
文摘Interparticle adhesion force has a controlling effect on the physical and mechanical properties of planetary regolith and rocks.The current research on the adhesion force of planetary regolith and rock particles has been primarily based on the assumption of smooth spherical particles to calculate the intergranular adhesion force;this approach lacks consideration for the adhesion force between irregular shaped particles.In our study,an innovative approach was established to directly measure the adhesion force between the arbitrary irregular shaped particles;the probe was modified using simulated lunar soil particles that were a typical representation of planetary regolith.The experimental results showed that for irregular shaped mineral particles,the particle size and mineral composition had no significant influence on the interparticle adhesion force;however,the complex morphology of the contact surface predominantly controlled the adhesion force.As the contact surface roughness increased,the adhesion force gradually decreased,and the rate of decrease gradually slowed;these results were consistent with the change trend predicted via the theoretical models of quantum electrodynamics.Moreover,a theoretical model to predict the adhesion force between the irregular shaped particles was constructed based on Rabinovich’s theory,and the prediction results were correlated with the experimental measurements.
基金I acknowledge Canadian Institute of Health Research grants FDN159932 and MOP-1301431Canadian Foundation for Innovation,Natural Sciences and Engineering Research Council of Canada,and Canada Research Chairs Program grant 950-223824.
文摘The effective treatment of patients with cancer hinges on the delivery of therapeutics to a tumor site.Nanoparticles provide an essential transport system.We present 5 principles to consider when designing nanoparticles for cancer targeting:(a)Nanoparticles acquire biological identity in vivo,(b)organs compete for nanoparticles in circulation,(c)nanoparticles must enter solid tumors to target tumor components,(d)nanoparticles must navigate the tumor microenvironment for cellular or organelle targeting,and(e)size,shape,surface chemistry,and other physicochemical properties of nanoparticles influence their transport process to the target.This review article describes these principles and their application for engineering nanoparticle delivery systems to carry therapeutics to tumors or other disease targets.
文摘To theeditor:The incidence of depression and obesity is on the rise,posing significant public health concerns.While the literature largely supports a positive correlation between depression and body mass index(BMI),I2 earlier studies have suggested an inverse relationship or indicated a lack of association between depression and obesity.
基金We acknowledge the funding support from the National Natural Science Foundation of China(Grant Nos.51879135 and 51879184)the Natural Sciences and Engineering Research Council of Canada(NSERC)through the Discovery Grant No.72031326.
文摘The shear behavior is regarded as the dominant property of rock joints and is dramatically affected by the joint surface roughness.To date,the effect of surface roughness on the shear behavior of rock joints under static or cyclic loading conditions has been extensively studied,but such effect under impact loading conditions keeps unclear.To address this issue,a series of impact shear tests was performed using a novel-designed dynamic experimental system combined with the digital image correlation(DIC)technique.The dynamic shear strength,deformability and failure mode of the jointed specimens with various joint roughness coefficients(JRC)are comprehensively analyzed.Results show that the shear strength and shear displacement characteristics of the rock joint under the impact loading keep consistent with those under static loading conditions.However,the temporal variations of shear stress,slip displacement and normal displacement under the impact loading conditions show obviously different behaviors.An elastic rebound of the slip displacement occurs during the impact shearing and its value increases with increasing joint roughness.Two identifiable stages(i.e.compression and dilation)are observed in the normal displacement curves for the rougher rock joints,whereas the joints with small roughness only manifest normal compression displacement.Besides,as the roughness increases,the maximum compression tends to decrease,while the maximum dilation gradually increases.More-over,the microstructural analysis based on scanning electron microscope(SEM)suggests that the roughness significantly affects the characteristics of the shear fractured zone enclosing the joint surface.
文摘Background and Purpose: With the unexpectedly rapid increase in the prevalence of types of diabetes worldwide, this chronic disease is no longer being viewed as a systemic health issue, but also treated as the start of the deadly disease. As the sixth complication of diabetes, periodontitis is a chronic inflammatory condition that leads directly and indirectly to a severer condition of diabetes via its underlying mechanisms. Interestingly, both diseases are not been fully identified in their bidirectional relationships by researchers. Thus, healthcare agencies must pay appropriate attention. This literature review paper aims to investigate and discuss dentists’ role in modulating environmental and epigenetic determinants in the oral health of diabetic patients based on the bidirectional relationship between these diseases, their prevalence and how treatment of one disease affects the other. Methods: The authors conducted electronic searches in PubMed, Google Scholar, One Search UofT, ScienceDirect, and the National Library of Medicine. The paper also included gray literature from government resources related to the topic. The paper will review the epidemiology, pathogenesis, and epigenetics of both diabetes and periodontal disease and their functions with each other. Results: The literature has consistently shown that diabetes and periodontal disease have responded to the formation and severity of each other. Patients with pre- and diabetes have potentially higher risks of causing periodontal disease and other complications if adequate diagnosis and treatment are not involved timely. The combination of risk factors, including individual, social, environmental, and genetic, play a crucial role in the development of diabetes and the severity of periodontitis. Conclusions: Based on the results, the collaboration between dentists and other healthcare practitioners is inevitable in the overall development of treatment for both diseases. With the proper and updated knowledge, dentists can benefit patients’ overall physical conditions through strategic intervention in diabetes patients.
文摘The field of exercise-oncology has evolved significantly over the past 30 years.Numerous studies have examined the role of structured exercise interventions—often incorporating aerobic or resistance training at moderate-to-vigorous intensities,sometimes in conjunction with multi-modal strategies—for individuals living with and beyond cancer.
基金funding to conduct this study was provided by a research innovation grant provided by CONMED Corporation(#IRB 22-0113-C).
文摘Objective:Smart insufflation(SI)techniques relying on valve and membrane-free insufflation are increasing in usage.Although considerable literature exists demonstrating the benefits of SI on procedural ease and patient outcomes,there remains a paucity describing the financial impact of these devices.The purpose of this study was to determine the financial and efficiency impact of these devices on the operating room and inpatient wards of a hospital.Methods:A discrete event simulation model representing a typical mid-sized North American hospital comparing SI to traditional insufflation(TI)was generated.The National Surgical Quality Improvement database from 2015 to 2019 was used to populate the model with data supplemented from the literature.Outcomes included length of stay(LOS),duration of surgery(DOS),annual procedure volume,profit,return on investment(ROI),and gross profit margin(GPM).From the literature review,DOS savings were 10e32 minutes/case,while LOS savings were 0e3 days/case.Results:Implementation of an SI led to an increase in annual throughput of 42e346(4.4%e36.6%)cases for all procedures and 38 to 297(4.3%e33.3%)cases for complex procedures.LOS was found to be decreased by 175e614(18.3%e64.2%)days for all procedures and 231 to 614(35.6%e77.9%)cases for complex procedures with the implementation of an SI.Together,this resulted in an increase in net profit of$104,685 per annum.The ROI of SI over the TI device was>1000%,and the GPM for the TI was 90.0%,while the GPM for the SI was 71.7%.Conclusion:Despite the initial financial investment being greater,the implementation of SI offsets these expenses and yields significant financial benefits.Our study demonstrates the financial benefits of SI over TI and illustrates how granular operational and financial analyses of technologies are essential to aid in sound healthcare procurement decision making.
基金supported by the National Natural Science Foundation of China under Grants No.11774304,No.61905206,No.12064048,and No.11804294.
文摘Colloidal quantum dots(CQDs)are of great interest to photovoltaic(PV)technologies as they possess the benefits of solution-processability,size-tunability,and roll-to-roll manufacturability,as well as unique capabilities to harvest near-infrared(NIR)radiation.During the last decade,lab-scale CQD solar cells have achieved rapid improvement in the power conversion efficiency(PCE)from~1%to 18%,which will potentially exceed 20%in the next few years and approach the performance of other PV technologies,such as perovskite solar cells and organic solar cells.In the meanwhile,CQD solar cells exhibit long lifetimes either under shelf storage or continuous operation,making them highly attractive to industry.However,in order to meet the industrial requirements,mass production techniques are necessary to scale up the fabrication of those lab devices into large-area PV modules,such as roll-to-toll coating.This paper reviews the recent developments of large-area CQD solar cells with a focus on various fabrication methods and their principles.It covers the progress of typical large-area coating techniques,including spray coating,blade coating,dip coating,and slot-die coating.It also discusses next steps and new strategies to accomplish the ultimate goal of the low-cost large-area fabrication of CQD solar cells and emphasizes how artificial intelligence or machine learning could facilitate the developments of CQD solar cell research.
基金supported by the National Natural Science Foundation of China(Grant No.41825018)the Second Tibetan Plateau Scientific Expedition and Research Program(STEP)(Grant No.2019QZKK0904).
文摘Discontinuities are often considered as important factors responsible for the instability caused by shear failure in engineering rock mass,and energy-driven instability is the root cause of rock failure.However,few studies focus on the energy evolution during the failure process using a three-dimensional(3D)numerical model.In this study,a series of laboratory direct shear tests on rock-like samples is numer-ically simulated using bonded particle models(BPMs)with multiple combinations of discontinuous in the particle flow code(PFC3D),in which the location and size of the particles conform to the uniform distribution.The effects of joint row number and inclination on the stress-strain characteristics and failure mode of rock were studied from the perspective of microcrack growth and energy evolution.The results showed that,when the number of joint rows Nr>1,the shear failure region does not change with the increase of Nr for the type B(2-columnn multiple-row at center)and the type C(2-column multiple-row at edge)as compared to the type A(1-column multiple-row at center)joint models.Notably,joints significantly increase the post-peak energy dissipation but have little effect on the proportion of energy before the peak.Friction consumes most of the energy while kinetic energy accounts for less than 1%of total energy during the shear process.Peak elastic strain energy follows the variation trend of peak shear displacement.The development and accumulation of microcracks directly affect the energy dissipation,and there is a significant linear relationship between the cumulative number of critical microcracks and the critical dissipated energy at the failure,when the dip direction of joints is opposite to the shear direction,more microcracks will be accumulated at the peak time,resulting in more energy dissipation.The results contribute to deeply understanding the shear failure process of non-persistent jointed mass.
