Background Lesion-symptom mapping(LSM)is a statistical technique to investigate the population-specific relationship between structural integrity and post-stroke clinical outcome.In clinical practice,patients are comm...Background Lesion-symptom mapping(LSM)is a statistical technique to investigate the population-specific relationship between structural integrity and post-stroke clinical outcome.In clinical practice,patients are commonly evaluated using the National Institutes of Health Stroke Scale(NIHSS),an 11-domain clinical score to quantitate neurological deficits due to stroke.So far,LSM studies have mostly used the total NIHSS score for analysis,which might not uncover subtle structure–function relationships associated with the specific sub-domains of the NIHSS evaluation.Thus,the aim of this work was to investigate the feasibility to perform LSM analyses with sub-score information to reveal category-specific structure–function relationships that a total score may not reveal.Methods Employing a multivariate technique,LSM analyses were conducted using a sample of 180 patients with NIHSS assessment at 48-hour post-stroke from the ESCAPE trial.The NIHSS domains were grouped into six categories using two schemes.LSM was conducted for each category of the two groupings and the total NIHSS score.Results Sub-score LSMs not only identify most of the brain regions that are identified as critical by the total NIHSS score but also reveal additional brain regions critical to each function category of the NIHSS assessment without requiring extensive,specialised assessments.Conclusion These findings show that widely available sub-scores of clinical outcome assessments can be used to investigate more specific structure–function relationships,which may improve predictive modelling of stroke outcomes in the context of modern clinical stroke assessments and neuroimaging.展开更多
The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases....The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.展开更多
Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web o...Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB 展开更多
Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ...Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction.展开更多
Autonomous systems are an emerging AI technology functioning without human intervention underpinned by the latest advances in intelligence,cognition,computer,and systems sciences.This paper explores the intelligent an...Autonomous systems are an emerging AI technology functioning without human intervention underpinned by the latest advances in intelligence,cognition,computer,and systems sciences.This paper explores the intelligent and mathematical foundations of autonomous systems.It focuses on structural and behavioral properties that constitute the intelligent power of autonomous systems.It explains how system intelligence aggregates from reflexive,imperative,adaptive intelligence to autonomous and cognitive intelligence.A hierarchical intelligence model(HIM)is introduced to elaborate the evolution of human and system intelligence as an inductive process.The properties of system autonomy are formally analyzed towards a wide range of applications in computational intelligence and systems engineering.Emerging paradigms of autonomous systems including brain-inspired systems,cognitive robots,and autonomous knowledge learning systems are described.Advances in autonomous systems will pave a way towards highly intelligent machines for augmenting human capabilities.展开更多
How distinct transcriptional programs are enacted to generate cellular heterogeneity and plasticity,and enable complex fate decisions are important open questions.One key regulator is the cell’s epigenome state that ...How distinct transcriptional programs are enacted to generate cellular heterogeneity and plasticity,and enable complex fate decisions are important open questions.One key regulator is the cell’s epigenome state that drives distinct transcriptional programs by regulating chromatin accessibility.Genome-wide chromatin accessibility measurements can impart insights into regulatory sequences(in)accessible to DNA-binding proteins at a single-cell resolution.This review outlines molecular methods and bioinformatic tools for capturing cell-to-cell chromatin variation using single-cell assay for transposase-accessible chromatin using sequencing(scATAC-seq)in a scalable fashion.It also covers joint profiling of chromatin with transcriptome/proteome measurements,computational strategies to integrate multi-omic measurements,and predictive bioinformatic tools to infer chromatin accessibility from single-cell transcriptomic datasets.Methodological refinements that increase power for cell discovery through robust chromatin coverage and integrate measurements from multiple modalities will further expand our understanding of gene regulation during homeostasis and disease.展开更多
Neuropathic pain is a long term and common pain disorder in clinics that is refractory to treatment,however,the neural substrates and underlying mechanisms are poorly understood.Using the com bination of neuronal mapp...Neuropathic pain is a long term and common pain disorder in clinics that is refractory to treatment,however,the neural substrates and underlying mechanisms are poorly understood.Using the com bination of neuronal mapping,optogenetics,chemogenetics,eletrophysiological recording,in vivo fiber photometry and behavioral testing,we previously identified a new neural circuit of BLA-mPFC-vIPAG and its key role in encoding and modulation of the spared nerve injury(SNI)-induced neuropathic pain..Here we report that the V M-vlOFC-vIPAG circuit modulates neuropathic pain and dissects the underlying mechanisms at cellular and circuitry level.展开更多
BACKGROUND Patients leaving the intensive care unit(ICU)often experience gaps in care due to deficiencies in discharge communication,leaving them vulnerable to increased stress,adverse events,readmission to ICU,and de...BACKGROUND Patients leaving the intensive care unit(ICU)often experience gaps in care due to deficiencies in discharge communication,leaving them vulnerable to increased stress,adverse events,readmission to ICU,and death.To facilitate discharge communication,written summaries have been implemented to provide patients and their families with information on medications,activity and diet restrictions,follow-up appointments,symptoms to expect,and who to call if there are questions.While written discharge summaries for patients and their families are utilized frequently in surgical,rehabilitation,and pediatric settings,few have been utilized in ICU settings.AIM To develop an ICU specific patient-oriented discharge summary tool(PODS-ICU),and pilot test the tool to determine acceptability and feasibility.METHODS Patient-partners(i.e.,individuals with lived experience as an ICU patient or family member of an ICU patient),ICU clinicians(i.e.,physicians,nurses),and researchers met to discuss ICU patients’specific informational needs and design the PODS-ICU through several cycles of discussion and iterative revisions.Research team nurses piloted the PODS-ICU with patient and family participants in two ICUs in Calgary,Canada.Follow-up surveys on the PODS-ICU and its impact on discharge were administered to patients,family participants,and ICU nurses.RESULTS Most participants felt that their discharge from the ICU was good or better(n=13;87.0%),and some(n=9;60.0%)participants reported a good understanding of why the patient was in ICU.Most participants(n=12;80.0%)reported that they understood ICU events and impacts on the patient’s health.While many patients and family participants indicated the PODS-ICU was informative and useful,ICU nurses reported that the PODS-ICU was“not reasonable”in their daily clinical workflow due to“time constraint”.CONCLUSION The PODS-ICU tool provides patients and their families with essential information as they discharge from the ICU.This tool has the potential to engage and empower 展开更多
基金funded by the Heart and Stroke Foundation of Canada Grant in aid(G-17-0018368)the Canada Research Chairs programthe River Fund at Calgary Foundation.
文摘Background Lesion-symptom mapping(LSM)is a statistical technique to investigate the population-specific relationship between structural integrity and post-stroke clinical outcome.In clinical practice,patients are commonly evaluated using the National Institutes of Health Stroke Scale(NIHSS),an 11-domain clinical score to quantitate neurological deficits due to stroke.So far,LSM studies have mostly used the total NIHSS score for analysis,which might not uncover subtle structure–function relationships associated with the specific sub-domains of the NIHSS evaluation.Thus,the aim of this work was to investigate the feasibility to perform LSM analyses with sub-score information to reveal category-specific structure–function relationships that a total score may not reveal.Methods Employing a multivariate technique,LSM analyses were conducted using a sample of 180 patients with NIHSS assessment at 48-hour post-stroke from the ESCAPE trial.The NIHSS domains were grouped into six categories using two schemes.LSM was conducted for each category of the two groupings and the total NIHSS score.Results Sub-score LSMs not only identify most of the brain regions that are identified as critical by the total NIHSS score but also reveal additional brain regions critical to each function category of the NIHSS assessment without requiring extensive,specialised assessments.Conclusion These findings show that widely available sub-scores of clinical outcome assessments can be used to investigate more specific structure–function relationships,which may improve predictive modelling of stroke outcomes in the context of modern clinical stroke assessments and neuroimaging.
基金Supported by the Lejoie-Lake Fellowship(to Camara-Lemarroy CR)awarded by the Hotchkiss Brain Institute
文摘The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.
文摘Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB
文摘Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction.
基金supported in part by the Department of National Defence’s Innovation for Defence Excellence and Security(IDEa S)Program,Canadathrough the Project of Auto Defence Towards Trustworthy Technologies for Autonomous Human-Machine Systems,NSERCthe IEEE SMC Society Technical Committee on Brain-Inspired Systems(TCBCS)。
文摘Autonomous systems are an emerging AI technology functioning without human intervention underpinned by the latest advances in intelligence,cognition,computer,and systems sciences.This paper explores the intelligent and mathematical foundations of autonomous systems.It focuses on structural and behavioral properties that constitute the intelligent power of autonomous systems.It explains how system intelligence aggregates from reflexive,imperative,adaptive intelligence to autonomous and cognitive intelligence.A hierarchical intelligence model(HIM)is introduced to elaborate the evolution of human and system intelligence as an inductive process.The properties of system autonomy are formally analyzed towards a wide range of applications in computational intelligence and systems engineering.Emerging paradigms of autonomous systems including brain-inspired systems,cognitive robots,and autonomous knowledge learning systems are described.Advances in autonomous systems will pave a way towards highly intelligent machines for augmenting human capabilities.
基金a Cancer Research Society award(Scholarships for the New Generation of Scientists).NJB was supported by Multiple Myeloma Research Foundation.ATS was supported by the National Institutes of Health(NIHGrant No.K08CA230188)+2 种基金the Parker Institute for Cancer Immunotherapy,a Cancer Research Institute Technology Impact Award,a Career Award for Medical Scientists from the Burroughs Wellcome Fund,and the Human Vaccines Project Michelson Prize.HJ and WZ were supported by the National Human Genome Research Institute of NIH(Grant Nos.R01HG009518 and R01HG010889)JAS was supported by an Alberta Children’s Hospital Research Institute Postdoctoral Fellowship.AJ was supported by an Alberta Innovates Summer Studentship.JB was supported by Canadian Institutes of Health Research(PJT-401394)Calgary Firefighters Burn Treatment Society.
文摘How distinct transcriptional programs are enacted to generate cellular heterogeneity and plasticity,and enable complex fate decisions are important open questions.One key regulator is the cell’s epigenome state that drives distinct transcriptional programs by regulating chromatin accessibility.Genome-wide chromatin accessibility measurements can impart insights into regulatory sequences(in)accessible to DNA-binding proteins at a single-cell resolution.This review outlines molecular methods and bioinformatic tools for capturing cell-to-cell chromatin variation using single-cell assay for transposase-accessible chromatin using sequencing(scATAC-seq)in a scalable fashion.It also covers joint profiling of chromatin with transcriptome/proteome measurements,computational strategies to integrate multi-omic measurements,and predictive bioinformatic tools to infer chromatin accessibility from single-cell transcriptomic datasets.Methodological refinements that increase power for cell discovery through robust chromatin coverage and integrate measurements from multiple modalities will further expand our understanding of gene regulation during homeostasis and disease.
文摘Neuropathic pain is a long term and common pain disorder in clinics that is refractory to treatment,however,the neural substrates and underlying mechanisms are poorly understood.Using the com bination of neuronal mapping,optogenetics,chemogenetics,eletrophysiological recording,in vivo fiber photometry and behavioral testing,we previously identified a new neural circuit of BLA-mPFC-vIPAG and its key role in encoding and modulation of the spared nerve injury(SNI)-induced neuropathic pain..Here we report that the V M-vlOFC-vIPAG circuit modulates neuropathic pain and dissects the underlying mechanisms at cellular and circuitry level.
文摘BACKGROUND Patients leaving the intensive care unit(ICU)often experience gaps in care due to deficiencies in discharge communication,leaving them vulnerable to increased stress,adverse events,readmission to ICU,and death.To facilitate discharge communication,written summaries have been implemented to provide patients and their families with information on medications,activity and diet restrictions,follow-up appointments,symptoms to expect,and who to call if there are questions.While written discharge summaries for patients and their families are utilized frequently in surgical,rehabilitation,and pediatric settings,few have been utilized in ICU settings.AIM To develop an ICU specific patient-oriented discharge summary tool(PODS-ICU),and pilot test the tool to determine acceptability and feasibility.METHODS Patient-partners(i.e.,individuals with lived experience as an ICU patient or family member of an ICU patient),ICU clinicians(i.e.,physicians,nurses),and researchers met to discuss ICU patients’specific informational needs and design the PODS-ICU through several cycles of discussion and iterative revisions.Research team nurses piloted the PODS-ICU with patient and family participants in two ICUs in Calgary,Canada.Follow-up surveys on the PODS-ICU and its impact on discharge were administered to patients,family participants,and ICU nurses.RESULTS Most participants felt that their discharge from the ICU was good or better(n=13;87.0%),and some(n=9;60.0%)participants reported a good understanding of why the patient was in ICU.Most participants(n=12;80.0%)reported that they understood ICU events and impacts on the patient’s health.While many patients and family participants indicated the PODS-ICU was informative and useful,ICU nurses reported that the PODS-ICU was“not reasonable”in their daily clinical workflow due to“time constraint”.CONCLUSION The PODS-ICU tool provides patients and their families with essential information as they discharge from the ICU.This tool has the potential to engage and empower
