116 research outputs found
Permeability of the blood-brain barrier predicts no evidence of disease activity at two years after natalizumab or fingolimod treatment in relapsing-remitting multiple sclerosis
Get PDFOBJECTIVE: To investigate if blood-brain barrier (BBB) permeability, as measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), can provide early detection of sub-optimal treatment response in relapsing-remitting multiple sclerosis (RRMS).METHODS: 35 RRMS patients starting on fingolimod or natalizumab, drugs with a common effect of decreasing lymphocyte influx into the CNS, were scanned with DCE-MRI at 3T prior to treatment and at three and six-months post-treatment. We calculated the influx constant Ki , a measure of BBB permeability, using the Patlak model. Sub-optimal treatment response was defined as loss of no evidence of disease activity (NEDA-3) status after two years of treatment.RESULTS: Subjects with loss of NEDA status at 2 years had a 51% higher mean Ki in normal-appearing white matter (NAWM) measured after six months of treatment, compared to subjects with maintained NEDA status (mean difference 0.06 (CI 0.02-0.09) ml/100g/min; p=0.002). Ki in NAWM at 6 months was a good predictor of loss of NEDA status at two years (AUC 0.84, CI 0.70-0.99; p=0.003) and a value above 0.136 ml/100/g/min yielded an odds ratio of 12.4 for sub-optimal treatment response at 2 years, with a sensitivity of 73% and a specificity of 82%.INTERPRETATION: Our results suggest that BBB permeability as measured by DCE-MRI reliably predicts sub-optimal treatment response and is a surrogate marker of the state of health of the BBB. We find a predictive threshold for disease activity, which is remarkably identical in clinically isolated syndrome as previously reported and established RRMS as investigated here
Insights from DCE-MRI:blood–brain barrier permeability in the context of MS relapses and methylprednisolone treatment
No full textBackground: Detecting multiple sclerosis (MS) relapses remains challenging due to symptom variability and confounding factors, such as flare-ups and infections. Methylprednisolone (MP) is used for severe relapses, decreasing the number of contrast-enhancing lesions on MRI. The influx constant (Ki) derived from dynamic contrast-enhanced MRI (DCE-MRI), a marker of blood–brain barrier (BBB) permeability, has shown promise as a predictor of disease activity in relapsing–remitting MS (RRMS).Objectives: To investigate the predictive value of Ki in relation to clinical MS relapses and MP treatment, comparing its performance with traditional MRI markers.Methods: We studied 20 RRMS subjects admitted for possible relapse, using DCE-MRI on admission to assess Ki in normal-appearing white matter (NAWM) via the Patlak model. Mixed-effects modeling compared the predictive accuracy of Ki, the presence of contrast-enhancing lesions (CEL), evidence of brain lesions (EBL; defined as the presence of CEL or new T2 lesions), and MP treatment on clinical relapse events. Five models were evaluated, including combinations of Ki, CEL, EBL, and MP, to determine the most robust predictors of clinical relapse. Model performance was assessed using accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), with bootstrapped confidence intervals.Results: Superior predictive accuracy was demonstrated with the inclusion of EBL and Ki, alongside MP treatment (AIC = 66.12, p = 0.006), outperforming other models with a classification accuracy of 83% (CI: 73–92%), sensitivity of 78% (CI: 60–94%), and specificity of 86% (CI: 74–97%). This model showed the highest combined PPV (78%, CI: 60–94%) and NPV (86%, CI: 74–98%) compared to models with EBL or CEL alone, suggesting an added value of Ki in enhancing predictive reliability.Conclusion: These results support the use of Ki alongside conventional MRI imaging metrics, to improve clinical relapse prediction in RRMS. The findings underscore the utility of Ki as a marker of MS-related neuroinflammation, with potential for integration into relapse monitoring protocols. Further validation in larger cohorts is recommended to confirm the model’s generalizability and clinical application.Background: Detecting multiple sclerosis (MS) relapses remains challenging due to symptom variability and confounding factors, such as flare-ups and infections. Methylprednisolone (MP) is used for severe relapses, decreasing the number of contrast-enhancing lesions on MRI. The influx constant (Ki) derived from dynamic contrast-enhanced MRI (DCE-MRI), a marker of blood–brain barrier (BBB) permeability, has shown promise as a predictor of disease activity in relapsing–remitting MS (RRMS). Objectives: To investigate the predictive value of Ki in relation to clinical MS relapses and MP treatment, comparing its performance with traditional MRI markers. Methods: We studied 20 RRMS subjects admitted for possible relapse, using DCE-MRI on admission to assess Ki in normal-appearing white matter (NAWM) via the Patlak model. Mixed-effects modeling compared the predictive accuracy of Ki, the presence of contrast-enhancing lesions (CEL), evidence of brain lesions (EBL; defined as the presence of CEL or new T2 lesions), and MP treatment on clinical relapse events. Five models were evaluated, including combinations of Ki, CEL, EBL, and MP, to determine the most robust predictors of clinical relapse. Model performance was assessed using accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), with bootstrapped confidence intervals. Results: Superior predictive accuracy was demonstrated with the inclusion of EBL and Ki, alongside MP treatment (AIC = 66.12, p = 0.006), outperforming other models with a classification accuracy of 83% (CI: 73–92%), sensitivity of 78% (CI: 60–94%), and specificity of 86% (CI: 74–97%). This model showed the highest combined PPV (78%, CI: 60–94%) and NPV (86%, CI: 74–98%) compared to models with EBL or CEL alone, suggesting an added value of Ki in enhancing predictive reliability. Conclusion: These results support the use of Ki alongside conventional MRI imaging metrics, to improve clinical relapse prediction in RRMS. The findings underscore the utility of Ki as a marker of MS-related neuroinflammation, with potential for integration into relapse monitoring protocols. Further validation in larger cohorts is recommended to confirm the model’s generalizability and clinical application.</p
Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis
No full textBackground: in relapsing-remitting multiple sclerosis (RRMS), early disease control reduces the risk of permanent disability. The blood-brain barrier (BBB) is compromised in MS, and its permeability is a potential biomarker.Objective: to investigate BBB permeability measured by MRI as a marker of alemtuzumab efficacy.Methods: patients with RRMS initiating alemtuzumab treatment were recruited prospectively. BBB permeability was assessed as the Patlak-derived influx constant (Ki) by dynamic contrast-enhanced MRI before and 6, 12, and 18 months after the first course of alemtuzumab. No Evidence of Disease Activity-3 (NEDA-3) status was ascertained two years after treatment initiation.Results: patients who maintained NEDA-3 status at two years (n = 7) had a larger decrease in Ki between baseline and six months (-0.029 ml/100 g/min [CI -0.005 to -0.053]) and between baseline and 12 months in normal appearing white matter (0.043 [CI 0.022 to -0.065]), than those who experienced disease activity (n = 8). ROC curve analysis of the Ki change between baseline and 12 months in NAWM predicted a loss of NEDA status at 2 years with 86% sensitivity and 86% specificity (AUC 0.98, p = 0.002).Conclusion: BBB permeability predicted alemtuzumab efficacy at two years, indicating that BBB permeability is a biomarker of treatment response in RRMS
An investigation of ship propeller fatigue
No full textMechanical, Maritime and Materials EngineeringMechanical, Maritime and Materials Engineerin
Wind engineering study of One Williams Center, Tulsa
Get PDFCER74-75JAP-JEC25.Includes bibliographical references.December 1974.For Skilling, Helle, Christiansen and Robertson.Supported by Skilling, Helle, Christiansen and Robertson
Wind engineering study of Federal Reserve Bank, Richmond
No full textCER73-74JAP-JEC8.For Skilling, Helle, Christiansen and Robertson.August 1973
Den Skjulte Stemme - En nærsproglig analyse af novellen Globryllup
No full textProjektet er en nærsproglig analyse af novellen Globryllup af Helle Helle. I denne analyse anvendes primært Simon Borchmanns funktionelle tekstteori (herunder hans katalysebegreb) til at identificere de sproglige valg der entydiggør forskellige læsninger af novellen. Jeg-fortælleren i Globryllup er en meget underinformativ fortæller. Til at påvise dette anvendes blandt andet Paul Grices teori om samarbejdsprincippet og implikatur. På grund af jeg-fortællerens underinformative adfærd er man som læser så at sige nødt til at lede mellem linjerne efter en sammenhæng mellem jeg-fortællerens handlinger og underliggende hensigter. Til dette benyttes Algirdas J. Greimas’ isotopi-begreb for at tydeliggøre hvordan to fortællerstemmer i novellen udlægger jegets handlinger igennem to forskellige betydningsfelter. De to fortællerstemmer betegner vi som den eksplicitte og den implicitte fortæller, i og med vi tager udgangspunkt i Wayne C. Booths begreb om ‘the implied author’ og et LOC-begreb som anvendes af en sammenslutning af skandinaviske polyfonister (herunder Henning Nølke).Projektet er en nærsproglig analyse af novellen Globryllup af Helle Helle. I denne analyse anvendes primært Simon Borchmanns funktionelle tekstteori (herunder hans katalysebegreb) til at identificere de sproglige valg der entydiggør forskellige læsninger af novellen. Jeg-fortælleren i Globryllup er en meget underinformativ fortæller. Til at påvise dette anvendes blandt andet Paul Grices teori om samarbejdsprincippet og implikatur. På grund af jeg-fortællerens underinformative adfærd er man som læser så at sige nødt til at lede mellem linjerne efter en sammenhæng mellem jeg-fortællerens handlinger og underliggende hensigter. Til dette benyttes Algirdas J. Greimas’ isotopi-begreb for at tydeliggøre hvordan to fortællerstemmer i novellen udlægger jegets handlinger igennem to forskellige betydningsfelter. De to fortællerstemmer betegner vi som den eksplicitte og den implicitte fortæller, i og med vi tager udgangspunkt i Wayne C. Booths begreb om ‘the implied author’ og et LOC-begreb som anvendes af en sammenslutning af skandinaviske polyfonister (herunder Henning Nølke)
Wind-tunnel study of Pittsburgh Plate Glass headquarters
Get PDFFor Skilling, Helle, Christiansen and Robertson, P.C.June 1980.CER79-80JAP-JEC65.Includes bibliographical references
How to Close the Loop on Catheters: Exploring limitations and opportunities at the end-of-life of single-use catheters
No full textWhile lives are saved through the use of medical devices; they have a significant negative impact on the environment. In particular single-use medical devices make up a large part of the healthcare sector’s negative environmental impact as they contribute significantly to generating more medical waste and greenhouse gas emissions. Approximately 90% of medical waste consists of single-use products or components. The incineration of medical waste is still common practice, leading to harmful environmental and human health effects. Additionally, devices that could potentially be recycled, reused, or repurposed in another way to help close the loop of a product’s life cycle are incinerated instead, which sustains and fuels the unsustainable linear economic model. This research aims to identify opportunities at the end-of-life of single-use catheters that could sustain value and limit the amounts of medical waste produced. A method is presented that supports approaching this aim, called the recovery assessment tool for single-use catheters. The presented method allows for identifying components of a catheter that limit or provide opportunities for recovery purposes at the end-of-life. Two protocols have been developed to guide this process. The first protocol covers the dismantling process to explore the build-up of a catheter and separate components to establish a Bill of Materials. The second protocol describes the procedure that was followed to analyse a catheter. The Bill of Materials is used as an input to assess a catheter at the sub-assembly and component level. The assessment evaluates a catheter on three types of indices: disassembly indices, hygienic recovery indices and material recovery indices. The outcome of the assessment is a graphical visualization that highlights areas of attention for recovery. By interpreting these results using the explanations given with each index, components can be identified that limit or provide opportunities for recovery purposes at the end-of-life of single-use catheters. Two single-use catheters of Philips were assessed as a case study with the proposed methodology. A Bill of Materials for each catheter was established with the results of a material investigation in the lab. The results of the case studies led to several limitations and opportunities. The first limitation is that cleaning catheters can be challenging, given their long tubular shape and the fact that almost all components and sub-assemblies cannot be disassembled and reassembled again. This limitation may impede recovery options since catheters must be cleaned and sterilised after use if considered for recovery purposes because they come into contact with blood. Additionally, catheters are lightweight devices, meaning they make up only a small amount of the piles of medical waste produced daily. Still, catheters are high-value devices; therefore, any form of recovery is valuable. Opportunities for recovery at the end-of-life of catheters have also been identified. It was determined that catheters contain valuable metals that could be recovered to reduce medical waste, sustain value and potentially decrease the demand to collect raw materials. Also, most of the materials used in the case studied catheters seem compatible with ethylene oxide sterilisation which provides an opportunity for recovery; however, this must be thoroughly validated. Finally, it is suggested to reconsider the design or build-up of a catheter. Investigating opportunities for a hybrid design and exploring the possibility of recovery of functional modules for new catheters at the end-of-life are suggested. The outcomes of this research indicate that closing the loop on single-use catheters is a complex problem in terms of circularity due to their hygienic criticality and light weight compared to the waste produced daily per hospital bed. The amount of medical waste produced due to the use of catheters is only the tip of the iceberg.Biomedical Engineerin
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