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Touzene, A. R., and K. Day. "On Directed Edge-Disjoint Spanning Trees in Product Networks, An Algorithmic Approach." Journal of Engineering Research [TJER] 11, no. 2 (December 1, 2014): 79. http://dx.doi.org/10.24200/tjer.vol11iss2pp79-88.
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In (Ku et al. 2003), the authors have proposed a construction of edge-disjoint spanning trees EDSTs in undirected product networks. Their construction method focuses more on showing the existence of a maximum number (n1+n2-1) of EDSTs in product network of two graphs, where factor graphs have respectively n1 and n2 EDSTs. In this paper, we propose a new systematic and algorithmic approach to construct (n1+n2) directed routed EDST in the product networks. The direction of an edge is added to support bidirectional links in interconnection networks. Our EDSTs can be used straightforward to develop efficient collective communication algorithms for both models store-and-forward and wormhole.
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McEvoy, Matthew D., William R. Hand, Marjorie P. Stiegler, Amy N. DiLorenzo, Jesse M. Ehrenfeld, Kenneth R. Moran, Robert Lekowski, et al. "A Smartphone-based Decision Support Tool Improves Test Performance Concerning Application of the Guidelines for Managing Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy." Anesthesiology 124, no. 1 (January 1, 2016): 186–98. http://dx.doi.org/10.1097/aln.0000000000000885.
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Abstract Background The American Society of Regional Anesthesia and Pain Medicine (ASRA) consensus statement on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy is the standard for evaluation and management of these patients. The authors hypothesized that an electronic decision support tool (eDST) would improve test performance compared with native physician behavior concerning the application of this guideline. Methods Anesthesiology trainees and faculty at 8 institutions participated in a prospective, randomized trial in which they completed a 20-question test involving clinical scenarios related to the ASRA guidelines. The eDST group completed the test using an iOS app programmed to contain decision logic and content of the ASRA guidelines. The control group completed the test by using any resource in addition to the app. A generalized linear mixed-effects model was used to examine the effect of the intervention. Results After obtaining institutional review board’s approval and informed consent, 259 participants were enrolled and randomized (eDST = 122; control = 137). The mean score was 92.4 ± 6.6% in the eDST group and 68.0 ± 15.8% in the control group (P < 0.001). eDST use increased the odds of selecting correct answers (7.8; 95% CI, 5.7 to 10.7). Most control group participants (63%) used some cognitive aid during the test, and they scored higher than those who tested from memory alone (76 ± 15% vs. 57 ± 18%, P < 0.001). There was no difference in time to completion of the test (P = 0.15) and no effect of training level (P = 0.56). Conclusions eDST use improved application of the ASRA guidelines compared with the native clinician behavior in a testing environment.
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Pawa, S., K. Van Aarsen, A. Dukelow, D. Lizotte, and M. Zheng. "MP04: Interim analysis of the impact of the Emergency Department Transformation System on ambulance offload delay." CJEM 19, S1 (May 2017): S66. http://dx.doi.org/10.1017/cem.2017.170.
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Introduction: Emergency Department Systems Transformation (EDST) is a bundle of Toyota Production System based interventions implemented in two London, Canada tertiary care Emergency Departments (ED) between April 2014 and July 2016 to improve patient care by increasing value and reducing waste. Some of the 17 primary interventions included computerized physician order entry optimization, staff schedule realignment, physician scorecards, and a novel initial assessment process. Offload delays are associated with longer hospital length of stay and delayed admission, and may increase morbidity and mortality. Delays also result in fewer circulating ambulances in the community. CIHI sets a benchmark of 30 minutes as an acceptable offload target. It is possible that EDST may have impacted offload times. Methods: Middlesex-London EMS provided offload times. Data was collected from London Health Sciences Centre including daily ED visit volumes, ED occupancy, offload nursing hours, and site variation. A binomial logistic regression analysis was performed to determine the impact of interventions and confounding variables on the proportion of patients meeting CIHI benchmark. A chi-square analysis was done comparing proportion of patients meeting the benchmark in the first 3 months versus the last 3 months to identify overall impact of EDST to date. Results: Increased offload nursing hours had a positive impact (p<0.001) on the proportion of offload times meeting the CIHI benchmark while increased ED visit volume and hospital inpatient volume had a significant negative impact (p<0.001). At both ED sites, the proportion of patients meeting the offload target ranged from 58-83% over the timeframe. There was a significant increase in the proportion of patients meeting the benchmark from the first quarter to the last quarter (69.6% vs 75.0%; 95% CI 3.45% to 7.38%, p=0.000). Specific interventions had varying degrees of impact on offload times. Conclusion: The proportion of patients meeting the benchmark offload time varied over the study timeframe but significantly increased with EDST implementation. Offload times are one of many outcomes we aim to improve with EDST and it remains an ongoing process as new interventions continue to be implemented. Once transformation is complete, future studies will focus on the impact of EDST on all ED flow metrics, and patient and provider satisfaction.
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Danby, S., K. Van Aarsen, M. Columbus, and A. Dukelow. "LO06: Effects of emergency department system transformation (EDST) on patient experience of emergency department visits." CJEM 20, S1 (May 2018): S8. http://dx.doi.org/10.1017/cem.2018.68.
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Introduction: Emergency Department Systems Transformation (EDST) is a bundle of Toyota Production System based interventions partially implemented in two Canadian tertiary care Emergency Departments (ED) between June 2014- July 2016 with the goal to improve patient care by increasing value and reducing waste. Some of the 17 primary interventions included computerized physician order entry optimization, staff schedule realignment, physician scorecards and a novel initial assessment process. Some interventions have only been partially implemented due to persistent access block. This project was designed to examine the effect of partial EDST implementation on patient experience of emergency department visits. Patient satisfaction has been linked to improved patient outcomes, improved adherence to physician instruction, and improved provider satisfaction. Methods: Semi structured interviews were conducted over three distinct time periods (summer 2015, 2016 and 2017) to encompass progressive levels of EDST implementation. The interviews focused on the patients perceptions in each of 4 stages of their ED visit - Check-in, assessment, reassessment, and disposition. Patients were asked a list of positive (respected, listened to, supported, safe) and negative (in pain, worried, confused, frustrated) emotions frequently experienced and asked if they felt any of these emotions during their ED stay. Open ended questions were also asked about their overall visit. Descriptive statistics were calculated as differences in the proportion of patients feeling each emotion across timeframes. The open-ended question was coded by two reviewers as positive, negative or mixed. A kappa score was calculated to determine reviewer agreement. Results: 987 interviews were completed. In general, the proportion of patients feeling negative emotions remained consistent while positive emotions increased as EDST implementation progressed. For open-ended responses, the percentage of overtly positive experiences increased significantly from 2015 to 2017 (p=0.006), while overtly negative experiences did not significantly change. Reviewers agreed in the coding of the open-ended responses in 97.6% of surveys. The kappa score for reviewer agreement was 0.96 (95%CI 0.94-0.98) indicating almost perfect agreement. Conclusion: Partial implementation of EDST positively impacted patients experience of emergency department visits.
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Tsuei, J. J., F. M. K. Lam, and Pesus Chou. "Clinical applications of the EDST." IEEE Engineering in Medicine and Biology Magazine 15, no. 3 (1996): 67–75. http://dx.doi.org/10.1109/51.499761.
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Stanczak, Magda, Teresa Fras, Ludovic Blanc, Piotr Pawlowski, and Alexis Rusinek. "Blast-Induced Compression of a Thin-Walled Aluminum Honeycomb Structure—Experiment and Modeling." Metals 9, no. 12 (December 15, 2019): 1350. http://dx.doi.org/10.3390/met9121350.
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The presented discussion concerns the behavior of a thin-walled hexagonal aluminum honeycomb structure subjected to blast loading. The shock wave affecting the structure is generated by detonation of the C4 charge in an explosive-driven shock tube (EDST). The EDST set-up is an instrumented device that makes it possible to study blast effects in more stable and repeatable conditions than those obtained in a free-air detonation. The formation of folds characteristic of a honeycomb deformation in the axial compression distributes the initial loading over a time period, which is considered as an efficient method of energy dissipation. The test configuration is modeled in the Ls-Dyna explicit code, which enables analysis of the mechanisms of energy absorption that accompanies structural deformation under a blast loading. The conclusions reached in the performed experimental and numerical investigation can be applied to the modeling and optimization of cellular structures used to mitigate blast loadings.
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Dukelow, A., K. Van Aarsen, C. MacDonald, and V. Dagnone. "P036: Interim analysis of the impact of the emergency department transformation system on flow metrics." CJEM 20, S1 (May 2018): S69. http://dx.doi.org/10.1017/cem.2018.234.
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Introduction: Emergency Department Systems Transformation (EDST) is a bundle of Toyota Production System based interventions implemented in two Canadian tertiary care Emergency Departments (ED) between June 2014 to July 2016. The goals were to improve patient care by increasing value and reducing waste. Longer times to physician initial assessment (PIA), ED length of stays (LOS) and times to inpatient beds are associated with increased patient morbidity and potentially mortality. Some of the 17 primary interventions included computerized physician order entry optimization, staff schedule realignment, physician scorecards and a novel initial assessment process ED access block has limited full implementation of EDST. An interim analysis was conducted to assess impact of interventions implemented to date on flow metrics. Methods: Daily ED visit volumes, boarding at 7am, time to PIA and LOS for non-admitted patients were collected from April 2014 -June 2016. Volume and boarding were compared from first to last quarter using an independent samples median test. Linear regression for each variable versus time was conducted to determine unadjusted relationships. PIA, LOS for non-admitted low acuity (Canadian Triage and Acuity Scale (CTAS) 4,5) and non-admitted high acuity (CTAS 1,2,3) patients were subsequently adjusted for volume and/or boarding to control for these variables using a non-parametric correlation. Results: Overall, median ED boarding decreased at University Hospital (UH) (14.0 vs 6.0, p<0.01) and increased at Victoria Hospital (VH) (17.0 vs 21.0, p<0.01) from first to last quarter. Median ED volume increased significantly at UH from first to last quarter (129.0 vs 142.0, p<0.01) but remained essentially unchanged at VH. 90th percentile LOS for non-admitted low acuity patients significantly decreased at UH (adjusted rs=-0.24, p<0.01) but did not significantly change at VH. For high acuity patients 90th percentile LOS significantly decreased at both hospitals (UH: adjusted rs=-0.23, p<0.01; VH: adjusted rs=-0.21, p<0.01). 90th percentile time to PIA improved slightly but significantly in both EDs (UH: adjusted rs=-0.10, p<0.01; VH: adjusted rs=-0.18, p<0.01). Conclusion: Persistent ED boarding impacted the ability to fully implement the EDST model of care. Partial EDST implementation has resulted in improvement in PIA at both LHSC EDs. At UH where ED boarding decreased, LOS metrics improved significantly even after controlling for boarding.
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Kuo-Gen Chen. "Applying quantum interference to EDST medicine testing." IEEE Engineering in Medicine and Biology Magazine 15, no. 3 (1996): 64–66. http://dx.doi.org/10.1109/51.499760.
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A., Ademuyiwa J., and Adetunji A. A. "Impact of Some Economic Variables on the Real Gross Domestic Product of Nigeria." Budapest International Research and Critics Institute (BIRCI-Journal) : Humanities and Social Sciences 2, no. 4 (November 6, 2019): 12–19. http://dx.doi.org/10.33258/birci.v2i4.563.
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The influences of External Debt Service (EDS), External Debt Stock (EDSt), Government Expenditure (GE), Inflation Rate (InfR), Interest Rate (IntR) and Exchange Rate (ExR) of Nigeria on the Real Gross Domestic Product (RGDP) are examined. Results of the analysis using Stepwise Regression (Backward Elimination and Forward Selection) reveals that GE, EDS, and IntR have positive significant contributions to the RGDP of the country compared to other variables considered.
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Sun, Baoli, Luciana L. Prates, and Peiqiang Yu. "Interactive Curve-Linear Relationship Between Alteration of Carbohydrate Macromolecular Structure Traits in Hulless Barley (Hordeum vulgare L.) Grain and Nutrient Utilization, Biodegradation and Bioavailability." International Journal of Molecular Sciences 20, no. 6 (March 18, 2019): 1366. http://dx.doi.org/10.3390/ijms20061366.
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The aim of this study was to reveal an interactive curve-linear relationship between altered carbohydrate macromolecular structure traits of hulless barley cultivars and nutrient utilization, biodegradation, as well as bioavailability. The cultivars had different carbohydrate macromolecular traits, including amylose (A), amylopectin (AP), and β-glucan contents, as well as their ratios (A:AP). The parameters assessed included: (1) chemical and nutrient profiles; (2) protein and carbohydrate sub-fractions partitioned by the Cornell Net Carbohydrate and Protein System (CNCPS); (3) total digestible nutrients (TDN) and energy values; and (4) in situ rumen degradation kinetics of nutrients and truly absorbed nutrient supply. The hulless barley samples were analyzed for starch (ST), crude protein (CP), total soluble crude protein (SCP), etc. The in situ incubation technique was performed to evaluate the degradation kinetics of the nutrients, as well as the effective degradability (ED) and bypass nutrient (B). Results showed that the carbohydrates (g/kg DM) had a cubic relationship (p < 0.05), with the A:AP ratio and β-glucan level; while the starch level presented a quadratic relationship (p < 0.05), with the A:AP ratio and cubic relationship (p < 0.05), with β-glucan level. The CP and SCP contents had a cubic relationship (p < 0.05) with the A:AP ratio and β-glucan level. The altered carbohydrate macromolecular traits were observed to have strongly curve-linear correlations with protein and carbohydrate fractions partitioned by CNCPS. For the in situ protein degradation kinetics, there was a quadratic effect of A:AP ratio on the rumen undegraded protein (RUP, g/kg DM) and a linear effect of β-glucan on the bypass protein (BCP, g/kg DM). The A:AP ratio and β-glucan levels had quadratic effects (p < 0.05) on BCP and EDCP. For ST degradation kinetics, the ST degradation rate (Kd), BST and EDST showed cubic effects (p < 0.05) with A:AP ratio. The β-glucan level showed a cubic effect on EDST (g/kg DM) and a quadratic effect on BST (g/kg ST or g/kg DM) and EDST (g/kg DM). In conclusion, alteration of carbohydrate macromolecular traits in hulless barley significantly impacted nutrient utilization, metabolic characteristics, biodegradation, and bioavailability. Altered carbohydrate macromolecular traits curve-linearly affected the nutrient profiles, protein and carbohydrate fractions, total digestible nutrient, energy values, and in situ degradation kinetics.
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Stanczak, M., T. Fras, L. Blanc, P. Pawlowski, and A. Rusinek. "Numerical and experimental study on mechanical behaviour of the AlSi10Mg aluminium structures manufactured additively and subjected to a blast wave." EPJ Web of Conferences 250 (2021): 02017. http://dx.doi.org/10.1051/epjconf/202125002017.
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The paper is related to energy absorptive properties of additively manufactured metallic cellular structures. The samples of Honeycomb, Auxetic, rhomboidal Lattice and a regular Foam are subjected to a dynamic compression due to the blast tests. The cuboidal samples are manufactured by the Direct Metal Laser Sintering (DMLS) method using AlSi10Mg aluminium powder. The experimental tests are performed by means of an Explosive Driven Shock Tube (EDST). The measured results of the transmitted forces in relation to the shortening of the samples allow to analyse the deformation processes of each selected geometry. In addition, the evaluation of the structural responses leads to identification of the structure properties, such as the equivalent stress over equivalent strain or the energy absorption per a unit of mass. Moreover, the process of compression is modelled numerically using the explicit code LS-DYNA R9.0.1. The obtained simulations provide the complete analysis of the experimentally observed mechanisms.
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Bal, Harshawardhan P., and Janendra K. Batra. "Human Pancreatic Ribonuclease. Deletion of the Carboxyl-Terminal EDST Extension Enhances Ribonuclease Activity and Thermostability." European Journal of Biochemistry 245, no. 2 (April 15, 1997): 465–69. http://dx.doi.org/10.1111/j.1432-1033.1997.t01-1-00465.x.
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Love, Andrew J., Valérie Laval, Chiara Geri, Janet Laird, A. Deri Tomos, Mark A. Hooks, and Joel J. Milner. "Components of Arabidopsis Defense- and Ethylene-Signaling Pathways Regulate Susceptibility to Cauliflower mosaic virus by Restricting Long-Distance Movement." Molecular Plant-Microbe Interactions® 20, no. 6 (June 2007): 659–70. http://dx.doi.org/10.1094/mpmi-20-6-0659.
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We analyzed the susceptibility of Arabidopsis mutants with defects in salicylic acid (SA) and jasmonic acid (JA)/ethylene (ET) signaling to infection by Cauliflower mosaic virus (CaMV). Mutants cpr1-1 and cpr5-2, in which SA-dependent defense signaling is activated constitutively, were substantially more resistant than the wild type to systemic infection, implicating SA signaling in defense against CaMV. However, SA-deficient NahG, sid2-2, eds5-1, and pad4-1 did not show enhanced susceptibility. A cpr5 eds5 double mutant also was resistant, suggesting that resistance in cpr5 may function partially independently of SA. Treatment of cpr5 and cpr5 eds5, but not cpr1, with salicyl-hydroxamic acid, an inhibitor of alternative oxidase, partially restored susceptibility to wild-type levels. Mutants etr1-1, etr1-3, and ein2-1, and two mutants with lesions in ET/JA-mediated defense, eds4 and eds8, also showed reduced virus susceptibility, demonstrating that ET-dependent responses also play a role in susceptibility. We used a green fluorescent protein (GFP)-expressing CaMV recombinant to monitor virus movement. In mutants with reduced susceptibility, cpr1-1, cpr5-2, and etr1-1, CaMV-GFP formed local lesions similar to the wild type, but systemic spread was almost completely absent in cpr1 and cpr5 and was substantially reduced in etr1-1. Thus, mutations with enhanced systemic acquired resistance or compromised ET signaling show diminished long-distance virus movement.
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Khanuja, Harmeet Kaur, and Dr D. S. Adane. "Forensic Analysis of Databases by Combining Multiple Evidences." INTERNATIONAL JOURNAL OF COMPUTERS & TECHNOLOGY 7, no. 3 (June 10, 2013): 654–63. http://dx.doi.org/10.24297/ijct.v7i3.3446.
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The information security for securing enterprise databases from internal and external attacks and violations of mutual policy is an interminable struggle. With the growing number of attacks and frauds, the organizations are finding it difficult to meet various regulatory compliance requirements such as SOX, HIPAA, and state privacy laws. The aim here is to develop a methodology which monitors the database transactions on continuous basis and to make a decision whether the database transactions are legitimate or suspicious by combining multiple evidences gathered. The suspicious transactions can then be used for forensic analysis to reconstruct the illegal activity carried out in an organization. This can be achieved by incorporating information accountability in Database Management System. Information accountability means, the information usage should be transparent so that it is possible to determine whether a use is appropriate under a given set of rules. We focus on effective information accountability of data stored in high-performance databases through database forensics which collects and analyses database transactions collected through various sources and artifacts like data cache, log files, error logs etc. having volatile or non-volatile characteristics within high performance databases. The information and multiple evidences collected are then analyzed using an Extended Dempster-Shafer theory(EDST). It  combines multiple such evidences and an initial belief is computed for suspected transactions which can be further used for reconstructing the activity in database forensics process.
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Battikh, Dalia, Safwan El El Assad, Thang Manh Hoang, Bassem Bakhache, Olivier Deforges, and Mohamad Khalil. "Comparative Study of Three Steganographic Methods Using a Chaotic System and Their Universal Steganalysis Based on Three Feature Vectors." Entropy 21, no. 8 (July 30, 2019): 748. http://dx.doi.org/10.3390/e21080748.
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In this paper, we firstly study the security enhancement of three steganographic methods by using a proposed chaotic system. The first method, namely the Enhanced Edge Adaptive Image Steganography Based on LSB Matching Revisited (EEALSBMR), is present in the spatial domain. The two other methods, the Enhanced Discrete Cosine Transform (EDCT) and Enhanced Discrete Wavelet transform (EDWT), are present in the frequency domain. The chaotic system is extremely robust and consists of a strong chaotic generator and a 2-D Cat map. Its main role is to secure the content of a message in case a message is detected. Secondly, three blind steganalysis methods, based on multi-resolution wavelet decomposition, are used to detect whether an embedded message is hidden in the tested image (stego image) or not (cover image). The steganalysis approach is based on the hypothesis that message-embedding schemes leave statistical evidence or structure in images that can be exploited for detection. The simulation results show that the Support Vector Machine (SVM) classifier and the Fisher Linear Discriminant (FLD) cannot distinguish between cover and stego images if the message size is smaller than 20% in the EEALSBMR steganographic method and if the message size is smaller than 15% in the EDCT steganographic method. However, SVM and FLD can distinguish between cover and stego images with reasonable accuracy in the EDWT steganographic method, irrespective of the message size.
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Berrocal-Lobo, Marta, and Antonio Molina. "Ethylene Response Factor 1 Mediates Arabidopsis Resistance to the Soilborne Fungus Fusarium oxysporum." Molecular Plant-Microbe Interactions® 17, no. 7 (July 2004): 763–70. http://dx.doi.org/10.1094/mpmi.2004.17.7.763.
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Ethylene response factor 1 (ERF1) is a transcriptional factor from Arabidopsis thaliana that regulates plant resistance to the necrotrophic fungi Botrytis cinerea and Plectosphaerella cucumerina and whose overexpression enhances resistance to these fungi. Here, we show that ERF1 also mediates Arabidopsis resistance to the soilborne fungi Fusarium oxysporum sp. conglutinans and F. oxysporum f. sp. lycopersici, because its constitutive expression in Arabidopsis confers enhanced resistance to these pathogens. Expression of ERF1 was upregulated after inoculation with F. oxysporum f. sp. conglutinans, and this response was blocked in ein2-5 and coi1-1 mutants, impaired in the ethylene (ET) and jasmonic acid (JA) signal pathways, respectively, which further indicates that ERF1 is a downstream component of ET and JA defense responses. The signal transduction network controlling resistance to F. oxysporum fungi was explored using signaling-defective mutants in ET (ein2-5), JA (jar1-1), and salicylic acid (SA) (NahG, sid2-1, eds5-1, npr1-1, pad4-1, eds1-1, and pad2-1) transduction pathways. This analysis revealed that Arabidopsis resistance to F. oxysporum requires the ET, JA, and SA signaling pathways and the NPR1 gene, although it is independent of the PAD4 and EDS1 functions.
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Kragt, J. J., J. M. Nielsen, F. AH van der Linden, B. MJ Uitdehaag, and C. H. Polman. "How similar are commonly combined criteria for EDSS progression in multiple sclerosis?" Multiple Sclerosis Journal 12, no. 6 (November 2006): 782–86. http://dx.doi.org/10.1177/1352458506070931.
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Introduction Measuring disease progression is an important aspect of multiple sclerosis (MS) clinical trials. Commonly applied disability endpoints include time to clinically meaningful Expanded Disability Status Scale (EDSS) change, or the number of patients in whom such a change has occurred. Typically, clinically meaningful EDSS change has been defined as a change of 1.0 point on Kurtzke’s EDSS in patients with an entry EDSS score of 5.5 or lower, or 0.5 point in patients with a higher EDSS score. Our goal was to evaluate whether these changes can be considered as similar. Therefore, we compared EDSS changes to corresponding changes in the Guy’s Neurological Disability Scale (GNDS), which is a measure of patient perceived disability, and the Multiple Sclerosis Functional Composite (MSFC), which is an examination-based quantitative scoring of neurological impairment. Methods From a large longitudinal database, we selected two groups of patients with a clinically meaningful change in EDSS score according to the usual criteria: patients with EDSS change]/1.0 for baseline EDSS 5/5.5 and patients with EDSS change]/0.5 for baseline EDSS]/6.0. We compared changes in GNDS sum score and in MSFC score between both groups. Results In the group with baseline EDSS]/6.0, GNDS and MSFC changes were higher than in patients with baseline EDSS 5/5.5. The difference in change was 1.00 (95% confidence interval (CI): / 0.35 to 2.36) for the GNDS and 0.412 (95% CI: 0.300-0.525) for the MSFC. Conclusion Our results indicate that a 0.5 point EDSS change in patients with baseline EDSS / 6.0 cannot be considered equal to a 1.0 point change in patients with baseline EDSS 5/5.5.
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Cho, Joong-Yang, Keun-Sik Hong, Ho Jin Kim, Su-Hyun Kim, Ju-Hong Min, Nam-Hee Kim, Suk-Won Ahn, et al. "Disability weight for each level of the Expanded Disability Status Scale in multiple sclerosis." Multiple Sclerosis Journal 20, no. 9 (January 7, 2014): 1217–23. http://dx.doi.org/10.1177/1352458513518259.
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Background: The Expanded Disability Status Scale (EDSS) is the most widely employed ordinal disability scale in multiple sclerosis (MS). However, how far apart the individual EDSS levels are along the disability spectrum has not been formally quantified. Objectives: The objective of this paper is to generate refined disability weights (DWs) for each of the ordinal EDSS levels. Methods: We performed the person trade-off (PTO) procedure to derive DWs of five representative EDSS categories (2, 4, 6, 7 and 9), and DWs of the remaining EDSS categories were assigned by linear interpolation. The modified Delphi process was used to achieve consensus among raters. Results: DWs were 0.021 for EDSS 2, 0.199 for EDSS 4, 0.313 for EDSS 6, 0.617 for EDSS 7, and 0.926 for EDSS 9. Panel members achieved a high degree of consensus for each DW, as indicated by low coefficients of variation. Conclusions: Our DWs confirmed that EDSS is an ordinal scale with highly variable intervals. The availability of DW for each EDSS level allows direct comparison of each MS outcome state with other health states and provides a foundation for the estimation of the disability-adjusted life-years lost of individual patients.
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Bove, Riley, Carolyn Bevan, Elizabeth Crabtree, Chao Zhao, Refujia Gomez, Priya Garcha, John Morrissey, et al. "Toward a low-cost, in-home, telemedicine-enabled assessment of disability in multiple sclerosis." Multiple Sclerosis Journal 25, no. 11 (August 24, 2018): 1526–34. http://dx.doi.org/10.1177/1352458518793527.
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Background: Remote assessment of neurological disability in people with multiple sclerosis (MS) could improve access to clinical care and efficiency of clinical research. Objective: To develop and validate a telemedicine-based MS disability examination that does not require an in-home examiner. Methods: Adults with MS were recruited after a standardized in-person Expanded Disability Status Scale (EDSS) evaluation, and within 1 week underwent a blinded televideo-enabled EDSS examination with a different clinician. EDSS and tele-EDSS scores were compared. Results: Overall, 41 adults participated (mean (standard deviation (SD)) age: 47.0 years (11.6); median EDSS: 2 (range: 0–7)); 37 required no in-home assistance for the tele-EDSS evaluation (e.g. help positioning camera). Mean difference between EDSS and tele-EDSS was 0.34 (95% confidence interval (CI): 0.07–0.61). For 88% of evaluations, tele-EDSS and EDSS scores were within 1 point (similar to reported in-person inter-rater differences). Unweighted kappa for agreement within 0.5 point was 0.72. Correlation for individual functional systems (FS) ranged from modest (vision: 0.37) to high (bowel/bladder: 0.79). Overall correlation between EDSS and tele-EDSS was 0.89 ( p < 0.0001); and 0.98 ( p < 0.0001) at EDSS range: 4–7. Conclusion: In this proof of principle study, disability evaluation in mild to moderate MS is feasible using telemedicine without an aide at the patient’s location.
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Saccà, Francesco, Teresa Costabile, Antonio Carotenuto, Roberta Lanzillo, Marcello Moccia, Chiara Pane, Cinzia Valeria Russo, et al. "The EDSS integration with the Brief International Cognitive Assessment for Multiple Sclerosis and orientation tests." Multiple Sclerosis Journal 23, no. 9 (November 3, 2016): 1289–96. http://dx.doi.org/10.1177/1352458516677592.
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Objective: Despite cognitive tests have been validated in multiple sclerosis (MS), a neuropsychological evaluation is not implemented in the Expanded Disability Status Scale (EDSS) scoring. Methods: We used the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and orientation tests (OTs) to measure the cerebral functional system (CFS) score and to evaluate its impact on the EDSS. We compared EDSS calculated as usual (Native-EDSS) and after the use of the BICAMS and OT (NPS-EDSS). Results: We tested 604 MS patients with BICAMS, OTs, and EDSS. In all, 384 patients (63.6%) had at least one altered test at the BICAMS. Older age, lower education, higher Native-EDSS, and male gender were independently associated with at least one impaired BICAMS test. Native-EDSS was different from NPS-EDSS (−0.112; p < 0.001) in 99 patients (16%). When considering patients with a Native-EDSS ⩽ 4.0, the proportion of miscalculated EDSS was 25%. Conclusion: The use of brief neuropsychological tests leads to a more accurate CFS assessment in two-thirds of MS patients, and a more accurate EDSS calculation in 25% of patients with a score ⩽4.0. This may help clinicians to better recognize cognitive impairment in everyday clinical practice, especially in the case of isolated cognitive worsening.
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Cheng, E. M., R. D. Hays, L. W. Myers, G. W. Ellison, M. Beckstrand, and B. G. Vickrey. "Factors related to agreement between self-reported and conventional Expanded Disability Status Scale (EDSS) scores." Multiple Sclerosis Journal 7, no. 6 (December 2001): 405–10. http://dx.doi.org/10.1177/135245850100700610.
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Background: Although the Expanded Disability Status Scale (EDSS) remains a widely used scale for evaluating impairments in people with multiple sclerosis (MS), EDSS assessments are infeasible in certain situations. A self-administered version of the EDSS would be potentially usefulif it yielded similar results as the conventional physician-based version. Methods: We developed a self-administered patient questionnaire to obtain ratings of neurologic impairments, and developed algorithms to estimate EDSS scores. We mailed the questionnaires to all new consecutive patients scheduled to be seen at an MS clinic. Questionnaires were completed prior to the visit, and traditional EDSS ratings were made by one of two neurologists at the visit. One hundred and forty-six pairs of patient questionnaires and physician EDSS assessments were obtained. Results: Kappa values for agreement between the physician's EDSS scores and the questionnaire-derived scores were 0.13 (for exact agreement), 0.39 (+0.5 EDSS steps), and 0.56 (+1.0 EDSS steps). A scatterplot showed that agreement was best at EDSS scores 53.0 and 45.0. Better agreement was obtained when patients had a higher level of education, and when the physician was more certain of the diagnosis of MS. Conclusions: While the self-assessed EDSS scores do not agree highly enough to take the place of conventional EDSS scores, they may be sufficient for MS trial screening or for assessing outcomes across broad categories of disability.
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Bowen, James, Laura Gibbons, Ann Gianas, and George H. Kraft. "Self-administered Expanded Disability Status Scale with functional system scores correlates well with a physician-administered test." Multiple Sclerosis Journal 7, no. 3 (June 2001): 201–6. http://dx.doi.org/10.1177/135245850100700311.
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Background: Patient-administered measures are needed to assess disability cost-effectively in large epidemiological studies. Setting: An outpatient clinic in a large multiple sclerosis center. Methods: A self-administered EDSS questionnaire was developed (EDSS-S). Consecutive patients with clinically definite multiple sclerosis completed the EDSS-S (n=95). During the same visit, a physician completed an EDSS (EDSS-P). Scores below 4.0 were determined using functional system (FS) scores. Scores above 4.0 were calculated by two methods, using gait alone and using gait and functional system scores combined. Results: EDSS-P scores ranged from 0-9.5 (mean 5.1, median 5.0, 78% female, age 17-78, mean age 45). Mean EDSS-P, EDSS-S and intraclass correlation coefficients of agreement were: EDSS using ambulation alone (4.6, 5.1, 0.89), EDSS using ambulation and FS scores (4.6, 5.3, 0.87), bowel/bladder FS scores (1.6, 1.7, 0.79), pyramidal FS scores (2.1, 2.4, 0.67), sensory FS scores (1.6, 2.1, 0.60), cerebellar FS scores (1.1, 1.6, 0.55), brainstem FS scores (0.5, 1.2, 0.45), vision FS scores (1.9, 1.3, 0.38), cerebral FS scores (0.6, 2.3, 0.27). Conclusions: Very good correlation was seen between patient and physician scores for EDSS and the bowel/bladder FS score. Four other FS scores correlated moderately. In general, patients scored themselves more disabled than physicians.
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Wang, Xin, Hiromichi Tanaka, Masanori Baba, and Yung-chi Cheng. "Retention of Metabolites of 2′,3′-Didehydro-3′-Deoxy-4′-Ethynylthymidine, a Novel Anti-Human Immunodeficiency Virus Type 1 Thymidine Analog, in Cells." Antimicrobial Agents and Chemotherapy 53, no. 8 (May 26, 2009): 3317–24. http://dx.doi.org/10.1128/aac.00302-09.
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ABSTRACT 2′,3′-Didehydro-3′-deoxy-4′-ethynylthymidine (4′-Ed4T), a novel thymidine analog, has more potent anti-human immunodeficiency virus type 1 (HIV-1) activity than its progenitor, stavudine (d4T). The profile of the intracellular metabolites of 4′-Ed4T was qualitatively similar to that of zidovudine (AZT) but not to that of d4T, while after drug removal it showed more persistent anti-HIV activity than AZT or d4T in cell culture. When CEM cells were exposed to various concentrations of 4′-Ed4T, 4′-Ed4T was efficiently taken up by the cells and was readily phosphorylated to 4′-Ed4T monophosphate (4′-Ed4TMP), 4′-Ed4T diphosphate (4′-Ed4TDP), and 4′-Ed4T triphosphate (4′-Ed4TTP). Most importantly, 4′-Ed4TTP, the active metabolite of 4′-Ed4T, persisted significantly longer than 4′-Ed4TDP and 4′-Ed4TMP after drug removal. We further investigated the efflux profiles of 4′-Ed4T in the comparison with those of AZT in CEM cells. After drug removal, both 4′-Ed4T and AZT were effluxed from the cells in a time- and temperature-dependent manner. However, the efflux of 4′-Ed4T from cells was much less efficient than that of AZT. 4′-Ed4T was effluxed from cells only in its nucleoside form, while AZT was effluxed from cells in both its nucleoside and monophosphate forms. The mechanism-of-action study showed that the efflux of 4′-Ed4T or AZT nucleoside might be due to unknown nucleoside transporters which were not related to the equilibrative nucleoside transporters, while the efflux of AZT monophosphate might be due to multidrug resistance protein 4 (MRP4/ABCC4). The results demonstrated that no detectable 4′-Ed4TMP efflux and the less efficient efflux of 4′-Ed4T nucleoside from cells might be one of the biochemical determinants of its persistent antiviral activity in cell culture.
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Wang, Jun, Shulan Li, and Bingshu He. "Chinese physicians’ attitudes toward eco-directed sustainable prescribing from the perspective of ecopharmacovigilance: a cross-sectional study." BMJ Open 10, no. 6 (June 2020): e035502. http://dx.doi.org/10.1136/bmjopen-2019-035502.
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IntroductionEco-directed sustainable prescribing (EDSP) is an effective upstream way to reduce the environmental footprints of active pharmaceutical ingredients (APIs), a kind of emerging contaminants, from the patients’ excretion. EDSP is one of the key steps in the programme of ecopharmacovigilance (EPV), a drug administration route on API pollution.ObjectiveTo assess the attitudes of physicians prescribing medicines regarding EDSP from the perspective of EPV.DesignA cross-sectional study conducted from March 2019 to June 2019.Setting5 government general hospitals in Hubei province, China.Participants405 physicians were randomly selected and 262 valid questionnaires were obtained.Outcome measuresA self-developed questionnaire, which inquired about the participant characteristics, perceptions and attitudes toward API pollution, EPV and EDSP from an EPV perspective, was emailed to collect data from physicians.ResultsMost physicians agreed the existence of APIs in environment, worried about the potential environmental and ecological risks of API residues, supported the effectiveness and necessity of EDSP under an EPV perspective in decreasing environmental exposure of excreted APIs, and showed their willingness to participate in the EDSP practices. Nevertheless, no respondent identified the environmental impacts as the aspects regarding medicines affecting his(her) prescription decision, none was satisfied with knowledge on EDSP and showed confidence toward EDSP. The most important barrier to the effective implementation of EDSP was identified as ‘poor awareness of EDSP and EPV‘. Most responding physicians (97%) reported that they held the wait-and-see or conservative attitudes towards EDSP practice. The biggest concerns in low-dose prescribing and prescribing of drugs possessing environment-friendly excretion profiles, two EDSP approaches, were the possible negative impact on therapeutic outcomes and too complicated and professional drug evaluation process, respectively.ConclusionsChinese physicians had positive attitudes towards EDSP from the perspective of EPV. However, their environmental consciousness during prescribing and the related education were insufficient.
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Ravnborg, M., M. Blinkenberg, F. Sellebjerg, M. Ballegaard, S. Helweg Larsen, and P. Soelberg Sørensen. "Responsiveness of the Multiple Sclerosis Impairment Scale in comparison with the Expanded Disability Status Scale." Multiple Sclerosis Journal 11, no. 1 (February 2005): 81–84. http://dx.doi.org/10.1191/1352458505ms1120oa.
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The Multiple Sclerosis Impairment Scale (MSIS) is a measure of accumulated deficits assessed by means of a standard neurological examination. We compared the responsiveness of the MSIS with that of the Expanded Disability Status Scale (EDSS). We reviewed 4300 records collected systematically from 1995 to 2003 and identified 534 patients who had clinically definite multiple sclerosis and had had at least two clinical assessments with a time interval of 2-5 years. The rate of deterioration was significantly higher on the MSIS than on the EDSS. The annualized change in EDSS exhibited a maximum at baseline EDSS 4 and a subsequent rapid decline at higher baseline EDSS, while the annualized change in MSIS was fairly stable over a wide middle range of baseline MSIS. The variance of the annualized change in EDSS fluctuated markedly between the baseline EDSS categories, being highest at baseline EDSS 2, while the variance of the annualized change in MSIS was stable. The study indicates that the responsiveness of the MSIS is better than that of the EDSS in terms of both magnitude and stability over the range of measurement.
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Markowitz, Clyde E., Mary D. Hughes, Daniel D. Mikol, Lisa Shi, MerriKay Oleen-Burkey, and Douglas R. Denney. "Expanded Disability Status Scale Calculator for Handheld Personal Digital Assistant: Reliability Study." International Journal of MS Care 10, no. 2 (January 1, 2008): 33–39. http://dx.doi.org/10.7224/1537-2073-10.2.33.
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Through a standard neurological examination, the Expanded Disability Status Scale (EDSS) score is traditionally determined by a pen-and-paper method. The objectives of this study were to compare the interrater/method reliability of EDSS scores obtained through the pen-and-paper method with those obtained with the EDSS Calculator, evaluate test-retest reliability of the EDSS Calculator, and examine the validity of EDSS Calculator scores through correlation with the Ambulation Index (AI). During a single office visit, 62 subjects with multiple sclerosis (MS) from six study centers had disability levels evaluated by separate raters using the EDSS calculator and pen-and-paper methods in random order. Seven days later, subjects returned for reevaluation with the EDSS Calculator; AI was also evaluated. Mean EDSS scores for the sample were 3.5 ± 2.2 with the calculator and 3.4 ± 2.0 (range 0–8) with the traditional method. Interrater reliability between scores with the two methods was high (κ = 0.84; confidence interval [CI], 0.74–0.94). Test-retest reliability with the calculator was also high (κ = 0.93; CI, 0.86–0.996). Correlation between disability scores from the EDSS Calculator and AI was 0.73 (P <.001). Relative to the pen-and paper method, the EDSS Calculator was found to be highly reliable and provide valid results when measuring disability in MS patients.
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Miller, Aaron, Vincent Spada, Dorothy Beerkircher, and Rivka Riven Kreitman. "Long-term (up to 22 years), open-label, compassionate-use study of glatiramer acetate in relapsing—remitting multiple sclerosis." Multiple Sclerosis Journal 14, no. 4 (January 21, 2008): 494–99. http://dx.doi.org/10.1177/1352458507085029.
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To evaluate the safety and efficacy of long-term glatiramer acetate (GA) therapy, 46 patients with relapsing—remitting multiple sclerosis (RRMS) were treated for up to 22 years in an ongoing, open-label study. Kurtzke expanded disability status scale (EDSS) was measured every six months, relapses were reported at occurrence and patients self-reported adverse events (AEs). At GA initiation, disease durations ranged from 0—20 years (median 6.0 years) and at data cut-off (October 2004), GA therapy duration ranged from 1—22 years (median 12.0 years). Mean EDSS score increased 0.9 ± 1.9 from the pretreatment score (3.0 ± 1.8; P = 0.076). Only 10/28 (36%) patients with baseline EDSS <4.0 had a last observed value ≥ 4.0 and 8/34 (24%) with entry EDSS < 6.0 reached EDSS ≥ 6.0. A majority (57%) maintained improved or unchanged EDSS scores. Annualized relapse rate decreased to 0.1 ± 0.2 from 2.9 ± 1.4 prestudy ( P < 0.0001). Of the 18 remaining patients in October 2004 (average disease duration 23 years), 17% with baseline EDSS scores < 4.0 reached EDSS ≥ 4.0 and 28% with baseline scores < 6.0 reached EDSS ≥ 6.0. Adverse events were similar to those reported in short-term clinical trials. This study shows a low rate of relapses and EDSS progression in RRMS patients on GA for up to 22 years. Multiple Sclerosis 2008; 14: 494—499. http://msj.sagepub.com
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Patwardhan, M. B., D. B. Matchar, G. P. Samsa, D. C. McCrory, R. G. Williams, and T. T. Li. "Cost of multiple sclerosis by level of disability: a review of literature." Multiple Sclerosis Journal 11, no. 2 (April 2005): 232–39. http://dx.doi.org/10.1191/1352458505ms1137oa.
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We performed a review of the economic literature to identify what is known about the relationship between Expanded Disability Status Scale (EDSS) categories and cost of multiple sclerosis (MS). We sought cohort studies of patients with multiple sclerosis that described the costs attributed to each EDSS score and utilized specific inclusion criteria for the selection of 10 studies. We found that both direct and indirect costs rise continuously with increasing EDSS category, and this rise is qualitatively exponential. The rise in indirect costs appears at lower EDSS scores. The cost of a relapse occurring in any given EDSS category exceeds that associated with that particular EDSS category. Few studies comprehensively assessed the entire spectrum of the costs, and much of the literature is based on EDSS categories in coarse groupings. In spite of several variations between studies, one important conclusion that we can draw is that rise in cost is positively correlated to scores on the EDSS categories, and therefore agents with a capacity to prevent or arrest the rate of MS progression may affect the overall cost of MS.
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Zhang, J., E. Waubant, G. Cutter, JS Wolinsky, and D. Leppert. "Composite end points to assess delay of disability progression by MS treatments." Multiple Sclerosis Journal 20, no. 11 (March 27, 2014): 1494–501. http://dx.doi.org/10.1177/1352458514527180.
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Background: The Expanded Disability Status Scale (EDSS) has low sensitivity and reliability for detecting sustained disability progression (SDP) in multiple sclerosis (MS) trials. Objective: This study evaluated composite disability end points as alternatives to EDSS alone. Methods: SDP rates were determined using 96-week data from the Olympus trial (rituximab in patients with primary progressive MS). SDP was analyzed using composite disability end points: SDP in EDSS, timed 25-foot walk test (T25FWT), or 9-hole peg test (9HPT) (composite A); SDP in T25FWT or 9HPT (composite B); SDP in EDSS and (T25FWT or 9HPT) (composite C); and SDP in any two (EDSS, T25FWT, and 9HPT) (composite D). Results: Overall agreements between EDSS and other disability measures in defining SDP were 66%−73%. Composite A showed similar treatment effect estimate versus EDSS alone with much higher SDP rates. Composite B, C, and D all showed larger treatment effect estimate with different or similar SDP rates versus EDSS alone. Using composite A (24-week confirmation only), B, C, or D could reduce sample sizes needed for MS trials. Conclusion: Composite end points including multiple accepted disability measures could be superior to EDSS alone in analyzing disability progression and should be considered in future MS trials.
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Kaufmann, Marco, Claude Vaney, Laura Barin, Xinglu Liu, and Viktor von Wyl. "Long-term worsening of different body functions in persons with progressive multiple sclerosis." Multiple Sclerosis Journal - Experimental, Translational and Clinical 6, no. 4 (October 2020): 205521732096451. http://dx.doi.org/10.1177/2055217320964514.
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Background It is unclear whether EDSS is responsive to disability worsening in advanced MS. Objective To explore the dynamics of disability worsening in persons with advanced-stage MS (EDSS ≥5.5) using three disability worsening definitions (EDSS, Rivermead Mobility Index (RMI), 9-Hole Peg Test (9-HPT)). Methods EDSS-, RMI- and 9-HPT-based disability worsening were assessed over a minimum of two years in a cohort of 286 persons with advanced MS attending inpatient rehabilitation using Kaplan-Meier Curves and multivariable Cox regression. Furthermore, the correspondence between EDSS-, RMI- and 9-HPT-based disability worsening was analyzed. Results Disability progression was observed in 49% (9-HPT), 52% (EDSS) and 53% (RMI), with 9-HPT-based worsening slightly lagging behind. The Multiple Sclerosis Severity Score (MSSS) was the only consistent factor predicting disability worsening based on all three definitions (EDSS: hazard ratio 1.48 [1.30;1.68]; RMI: 1.12 [0.99;1.27]; 9-HPT: 1.36 [1.18;1.57]). Correspondence between EDSS and the other definitions (9-HPT and RMI) was 44.3% and 55.7% at time of EDSS progression and 65.1% and 72.5% overall, respectively. Conclusion In persons with advanced-stage MS, half still developed disability worsening in different functional systems over a median of 6 years. MSSS seems a valid predictor for disability worsening in all three outcome measures in advanced MS.
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Rojas, Juan Ignacio, Liliana Patrucco, Cristina Besada, Laura Bengolea, and Edgardo Cristiano. "Brain atrophy at onset and physical disability in multiple sclerosis." Arquivos de Neuro-Psiquiatria 70, no. 10 (October 2012): 765–68. http://dx.doi.org/10.1590/s0004-282x2012001000003.
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The aim of this study was to investigate if brain atrophy in multiple sclerosis (MS) patients during the disease onset predicts long term disability. METHODS: MS patients with follow-up time of at least 7 years from disease onset and with baseline and second magnetic resonance 12 months later were included to measure brain atrophy. Expanded Disability Status Scale (EDSS) was categorized in three groups, EDSS=0, EDSS=1 and 2.5 and EDSS>2.5, and used as disability measure. RESULTS: Twenty-six patients were included. Mean atrophy during the first year in patients that reached an EDSS≥3 was -0.76±0.45 %, in patients with an EDSS between 1 and 2.5 was -0.59±0.56, while in patients with an EDSS of 0 it was -0.38±0.42 (p=0.003). DISCUSSION: Brain atrophy rates during the first year of disease were predictive of disease progression in our population.
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Alonso, Ricardo N., Maria B. Eizaguirre, Berenice Silva, Maria C. Pita, Cecilia Yastremiz, Sandra Vanotti, Fernando Cáceres, and Orlando Garcea. "Brain Function Assessment of Patients with Multiple Sclerosis in the Expanded Disability Status Scale." International Journal of MS Care 22, no. 1 (January 1, 2020): 31–35. http://dx.doi.org/10.7224/1537-2073.2018-084.
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Abstract Background: There is no consensus regarding assessment of the brain function functional system (FS) of the Expanded Disability Status Scale (EDSS) in patients with multiple sclerosis (MS). We sought to describe brain function FS assessment criteria used by Argentinian neurologists and, based on the results, propose redefined brain function FS criteria. Methods: A structured survey was conducted of 113 Argentinian neurologists. Considering the survey results, we decided to redefine the brain function FS scoring using the Brief International Cognitive Assessment for MS (BICAMS) battery. For 120 adult patients with MS we calculated the EDSS score without brain function FS (basal EDSS) and compared it with the EDSS score after adding the modified brain function FS (modified EDSS). Results: Of the 93 neurologists analyzed, 14% reported that they did not assess brain function FS, 35% reported that they assessed it through a nonstructured interview, and the remainder used other tools. Significant differences were found in EDSS scores before and after the inclusion of BICAMS (P < .001). Redefining the brain function FS, 15% of patients modified their basal EDSS score, as did 20% of those with a score of 4.0 or less. Conclusions: The survey results show the importance of unifying the brain function FS scoring criteria in calculating the EDSS score. While allowing more consistent brain function FS scoring, including the modified brain function FS led to a change in EDSS score in many patients, particularly in the lower range of EDSS scores. Considering the relevance of the EDSS for monitoring patients with MS and for decision making, it is imperative to further validate the modified brain function FS scoring.
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Dujmovic, Irena, Simon Demetz, Alban Millonig, and Florian Deisenhammer. "The effect of fatigability on expanded disability status scale components in multiple sclerosis." Srpski arhiv za celokupno lekarstvo 144, no. 5-6 (2016): 262–65. http://dx.doi.org/10.2298/sarh1606262d.
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Introduction. The Expanded Disability Status Scale (EDSS) is the most widely used disability measure in multiple sclerosis (MS). The effect of fatigability on EDSS components has been underreported to date. Objective We investigated daytime variability in EDSS score and EDSS components - functional scores (FS) and walking distance (WD) up to 500 m, in MS patients who underwent a standardized fatiguing exercise. Methods. Twenty-four patients with relapsing-remitting MS (n = 7), secondary-progressive MS (n = 8) and primary-progressive MS (n = 9) were included. Exclusion criteria were as follows: current MS relapse, infection/fever/flu-like symptoms, conditions prohibiting safe exercise testing, current medication affecting fatigue. One trained examiner performed baseline (BL) and follow-up (FU) assessments (FU1 after a standardized fatiguing exercise, FU2 after rest) over a single day. EDSS score change of ?1 point if BL EDSS score was <5.5 or of ?0.5 point if BL EDSS score was ?5.5 were considered clinically meaningful. Results. In progressive MS subtypes, WD decreased at FU1, but recovered at FU2, more so in secondaryprogressive MS subgroup with the highest BL EDSS score. Although BL EDSS scores (median, 5.0; range 4.0-6.5) and FS remained relatively stable over repeated assessments in the total group, a clinically meaningful transitory post-exercise EDSS score increase was observed in three patients with progressive MS. Conclusion. WD seems to be more influenced by fatigability than the total EDSS score, more so in patients with progressive MS and higher disability. WD should be assessed after rest and this strategy should be implemented into protocols of clinical trials recruiting patients with progressive MS phenotypes.
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Ysrraelit, Celica, Fernando Caceres, Andres Villa, Marcela Parada Marcilla, Jorge Blanche, Marcos Burgos, Ignacio Casas Parera, et al. "ENCOMS: Argentinian survey in cost of illness and unmet needs in multiple sclerosis." Arquivos de Neuro-Psiquiatria 72, no. 5 (May 2014): 337–43. http://dx.doi.org/10.1590/0004-282x20140016.
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The objective of the study was to assess the cost of multiple sclerosis (MS) patients in Argentina categorized by disease severity using a societal perspective.Method:Cross-sectional study including MS patients from 21 MS centers in 12 cities of Argentina. Patients were stratified by disease severity using the expanded disability status scale (EDSS) (group 1 with EDSS score between 0 and 3; group 2 with EDSS >3 and <7; group 3 with EDSS ≥7). Direct and indirect costs were analyzed for the second quarter of 2012 from public sources and converted to US Dollars.Results:266 patients were included. Mean annual cost per MS patient was USD 36,025 (95%CI 31,985-38,068) for patients with an EDSS between 0-3; USD 40,705 (95%CI 37,199-46,300) for patients with EDSS >3 and <7, and USD 50,712 (95%CI 47,825-62,104) for patients with EDSS ≥7.Conclusions:This is the first Argentine study evaluating the costs of MS considering disease severity.
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Garcia-Hernandez, Carlos, Alberto Fernández, and Francesc Serratosa. "Learning the Edit Costs of Graph Edit Distance Applied to Ligand-Based Virtual Screening." Current Topics in Medicinal Chemistry 20, no. 18 (August 24, 2020): 1582–92. http://dx.doi.org/10.2174/1568026620666200603122000.
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Background: Graph edit distance is a methodology used to solve error-tolerant graph matching. This methodology estimates a distance between two graphs by determining the minimum number of modifications required to transform one graph into the other. These modifications, known as edit operations, have an edit cost associated that has to be determined depending on the problem. Objective: This study focuses on the use of optimization techniques in order to learn the edit costs used when comparing graphs by means of the graph edit distance. Methods: Graphs represent reduced structural representations of molecules using pharmacophore-type node descriptions to encode the relevant molecular properties. This reduction technique is known as extended reduced graphs. The screening and statistical tools available on the ligand-based virtual screening benchmarking platform and the RDKit were used. Results: In the experiments, the graph edit distance using learned costs performed better or equally good than using predefined costs. This is exemplified with six publicly available datasets: DUD-E, MUV, GLL&GDD, CAPST, NRLiSt BDB, and ULS-UDS. Conclusion: This study shows that the graph edit distance along with learned edit costs is useful to identify bioactivity similarities in a structurally diverse group of molecules. Furthermore, the target-specific edit costs might provide useful structure-activity information for future drug-design efforts.
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Ford, C. C., K. P. Johnson, R. P. Lisak, H. S. Panitch, G. Shifroni, and J. S. Wolinsky. "A prospective open-label study of glatiramer acetate: over a decade of continuous use in multiple sclerosis patients." Multiple Sclerosis Journal 12, no. 3 (June 2006): 309–20. http://dx.doi.org/10.1191/135248506ms1318oa.
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A decade of continuous glatiramer acetate (GA) use by relapsing remitting multiple sclerosis (RRMS) patients was evaluated in this ongoing, prospective study, and the neurological status of ‘Withdrawn’ patients was assessed at a 10-year long-term follow-up (LTFU) visit. Modified intention-to-treat (mITT, n=232) patients received ≥ 1 GA dose since 1991; ‘Ongoing’ patients ( n=108) continued in November 2003. Of 124 patients, 50 Withdrawn patients returned for LTFU. Patients were evaluated every six months (EDSS). Mean GA exposure was 6.99, 10.1 and 4.26 years for mITT, Ongoing, and Withdrawn/LTFU patients, respectively. While on GA, mITT relapse rates declined from 1.18/year prestudy to ∼1 relapse/5 years; median time to ≥ 1 EDSS point increase was 8.8 years; mean EDSS change was 0.739±1.66 points; 58% had stable/improved EDSS scores; and 24, 11 and 3% reached EDSS 4, 6 and 8, respectively. For Ongoing patients, EDSS increased 0.509±1.65; 62% were stable/improved; and 24, 8 and 1% reached EDSS 4, 6 and 8, respectively. For Withdrawn patients at 10-year LTFU, EDSS increased 2.249±1.86; 28% were stable/improved; and 68, 50 and 10% reached EDSS 4, 6 and 8, respectively. While on GA nearly all patients (mean disease duration 15 years) remained ambulatory. At LTFU, Withdrawn patients had greater disability than Ongoing patients.
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Chitnis, Tanuja, Greg Aaen, Anita Belman, Leslie Benson, Mark Gorman, Manu S. Goyal, Jennifer S. Graves, et al. "Improved relapse recovery in paediatric compared to adult multiple sclerosis." Brain 143, no. 9 (August 18, 2020): 2733–41. http://dx.doi.org/10.1093/brain/awaa199.
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Abstract Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack. Adult patients with multiple sclerosis (n = 632) were identified from the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham study (CLIMB), and paediatric patients (n = 132) from the US Network of Paediatric Multiple Sclerosis Centers (NPMSC) registry. Change in EDSS was defined as the difference in EDSS between attack and follow-up. Change in EDSS at follow-up compared to baseline was significantly lower in children compared to adults (P = 0.001), as were several functional system scores. Stratification by decade at onset for change in EDSS versus age found for every 10 years of age, EDSS recovery is reduced by 0.15 points (P < 0.0001). A larger proportion of children versus adults demonstrated improvement in EDSS following an attack (P = 0.006). For every 10 years of age, odds of EDSS not improving increase by 1.33 times (P < 0.0001). Younger age is associated with improved recovery from relapses. Age-related mechanisms may provide novel therapeutic targets for disability accrual in multiple sclerosis.
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Skjerbæk, Anders Guldhammer, Finn Boesen, Thor Petersen, Peter Vestergaard Rasmussen, Egon Stenager, Michael Nørgaard, Peter Feys, Marie Louise Kjeldgaard-Jørgensen, Lars Grøndahl Hvid, and Ulrik Dalgas. "Can we trust self-reported walking distance when determining EDSS scores in patients with multiple sclerosis? The Danish MS hospitals rehabilitation study." Multiple Sclerosis Journal 25, no. 12 (August 20, 2018): 1653–60. http://dx.doi.org/10.1177/1352458518795416.
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Background: In multiple sclerosis (MS), the Expanded Disability Status Scale (EDSS) reflects disease severity. Although parts of the EDSS are dependent on actual walking distance, self-reported statements are often applied. Objectives: The purpose of the present study was, therefore, to compare self-reported walking distance to actual walking distance to outline how this influences EDSS scoring. Methods: MS patients with EDSS 4.0–7.5 ( n = 273) were included from the Danish MS hospitals rehabilitation study ( n = 427). All patients subjectively classified their maximal walking distance according to one of seven categories (>500; 300–499; 200–299; 100–199; 20–99; 5–19; 0–4 m). Subsequently, actual maximal walking distance was assessed and EDSS was determined from both self-reported walking distance (EDSSself-report) and actual walking distance (EDSSactual). Results: In 145 patients (53%), self-reported walking distance was misclassified when compared to the actual walking distance. Misclassification was more frequent in patients using walking aids (64% vs. 44%, p < 0.05) and in patients with primary progressive MS (69%, p < 0.05). Misclassification of walking distance corresponded to incorrect EDSS scores (EDSSself-report vs EDSSactual) of ⩾0.5 point in 24%. Conclusion: In MS patients with EDSS 4.0–7.5, 53% misclassified their walking distance yielding incorrect EDSS scores in 24%. Therefore, correct EDSS determination must be based on measurement of actual walking distance.
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Bosma, Libertje VAE, Jolijn J. Kragt, Dirk L. Knol, Chris H. Polman, and Bernard MJ Uitdehaag. "Clinical scales in progressive MS: predicting long-term disability." Multiple Sclerosis Journal 18, no. 3 (August 25, 2011): 345–50. http://dx.doi.org/10.1177/1352458511419880.
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Background: To determine which short-term changes on clinical scales including the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg test (9HPT) and Guy’s Neurological Disability Scale (GNDS) are most predictive of long-term outcome of disability as rated by the EDSS in progressive multiple sclerosis (MS). Methods: From a longitudinal database, all progressive patients, both primary (PP) and secondary (SP), were selected on the basis of at least two complete examinations being available within a time interval of 1–2 years (short-term change). All patients who fulfilled the selection criteria were invited for a third visit after an interval of at least 3 years (long-term outcome). We used ordinal logistic regression to see which early changes were most predictive of the long-term EDSS. Results: 181 patients fulfilled the selection criteria. Early change on EDSS and T25FW were the best predictors of long-term EDSS; both were significant predictors in a ‘single predictor’ model. Early EDSS change was a slightly stronger single predictor (R2 0.38, Wald χ2 42.65, p < 0.001) compared with early T25FW change (R2 0.27, Wald χ2 12.35, p < 0.001). Adding early T25FW change to early EDSS change in a ‘combined predictor’ model improved prediction ( p = 0.036). Conclusion: Both early change on EDSS and T25FW predict long-term EDSS with comparable strength. Early change on T25FW adds significant independent information and improves the prediction model with early EDSS change only. Therefore we support the use of early T25FW examinations in future clinical trials in progressive MS.
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Hyyrö, Heikki, and Shunsuke Inenaga. "Dynamic RLE-Compressed Edit Distance Tables Under General Weighted Cost Functions." International Journal of Foundations of Computer Science 29, no. 04 (June 2018): 623–45. http://dx.doi.org/10.1142/s0129054118410083.
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Kim and Park [A dynamic edit distance table, J. Disc. Algo., 2:302–312, 2004] proposed a method (KP) based on a “dynamic edit distance table” that allows one to efficiently maintain unit cost edit distance information between two strings [Formula: see text] of length [Formula: see text] and [Formula: see text] of length [Formula: see text] when the strings can be modified by single-character edits to their left or right ends. This type of computation is useful e.g. in cyclic string comparison. KP uses linear time, [Formula: see text], to update the distance representation after each single edit. Recently Hyyrö et al. [Incremental string comparison, J. Disc. Algo., 34:2-17, 2015] presented an efficient method for maintaining the dynamic edit distance table under general weighted edit distance, running in [Formula: see text] time per single edit, where [Formula: see text] is the maximum weight of the cost function. The work noted that the [Formula: see text] space requirement, and not the running time, may be the main bottleneck in using the dynamic edit distance table. In this paper we take the first steps towards reducing the space usage of the dynamic edit distance table by RLE compressing [Formula: see text] and [Formula: see text]. Let [Formula: see text] and [Formula: see text] be the lengths of RLE compressed versions of [Formula: see text] and [Formula: see text], respectively. We propose how to store the dynamic edit distance table using [Formula: see text] space while maintaining the same time complexity as the previous methods for uncompressed strings.
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Cohen, Y. C., S. Hassin-Baer, L. Olmer, R. Barishev, Y. Goldhammer, L. Freedman, and B. Mozes. "MS-CANE: a computer-aided instrument for neurological evaluation of patients with multiple sclerosis: enhanced reliability of expanded disability status scale (EDSS) assessment." Multiple Sclerosis Journal 6, no. 5 (October 2000): 355–61. http://dx.doi.org/10.1177/135245850000600511.
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Kurtzke's EDSS remains the most widely-used measure for clinical evaluation of MS patients. However, several studies have demonstrated the limited reliability of this tool. We introduce a computerized instrument, MS-CANE (Multiple Sclerosis Computer-Aided Neurological Examination), for clinical evaluation and follow up of patients with multiple sclerosis (MS) and to compare its reliability to that of conventional Expanded Disability Status Scale (EDSS) assessment. We developed a computerized interactive instrument, based on the following principles: structured gathering of neurological findings, reduction of compound notions to their basic components, use of precise definitions, priority setting and automated calculations of EDSS and functional systems scores. An expert panel examined the consistency of MS-CANE with Kurtzke's specifications. To determine the effect of MS-CANE on the reliability of EDSS assessment, 56 MS patients underwent paired conventional EDSS and MS-CANE-based evaluations. The inter-observer agreement in both methods was determined and compared using the kappa statistic. The expert panel judged the tool to be compatible with the basic concepts of Kurtzke's EDSS. The use of MS-CANE increased the reliability of EDSS assessment: Kappa statistic was found to be 0.42 (i.e. moderate agreement) for conventional EDSS assessment versus 0.69 (i.e. substantial agreement) for MS-CANE (P=0.002). We conclude that the use of this tool may contribute towards a standardized and reliable assessment of EDSS. Within clinical trials, this could increase the power to detect effects, thus reducing trial duration and the cohort size required.
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Zhang, Jiameng, Emmanuelle Waubant, Gary Cutter, Jerry S. Wolinsky, and Robert Glanzman. "EDSS variability before randomization may limit treatment discovery in primary progressive MS." Multiple Sclerosis Journal 19, no. 6 (October 1, 2012): 775–81. http://dx.doi.org/10.1177/1352458512459685.
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Background: Baseline Expanded Disability Status Scale (EDSS) is usually based on a single measurement. Here we evaluated whether using a baseline EDSS derived from two pre-treatment measurements improves the detection of progression events and the ability to demonstrate a therapeutic effect in delaying MS disability progression. Methods: Real data from OLYMPUS, a phase II/III randomized, placebo-controlled trial of rituximab in patients with primary progressive multiple sclerosis (PPMS), as well as simulated data were analyzed. Several definitions of baseline EDSS were used to capture sustained disability progression (SDP) events. Variations in the EDSS were estimated by linear mixed-effect models. Results: Selecting the higher of two baseline EDSS scores lowered the number of SDP events in both treatment groups, so decreasing sensitivity, and reduced the number of false SDP events, so increasing specificity. Conversely, selecting the lower of two baseline scores increased sensitivity but decreased specificity. Increased power (~7% based on the simulation study) was observed when the average of screening and Week 0 EDSS scores was used for baseline. Conclusion: Baseline EDSS derived from two pre-treatment EDSS measurements may enhance the ability of detecting a therapeutic effect in slowing disability progression in PPMS. This strategy could be implemented in future clinical trials of patients with MS.
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Lavorgna, L., S. Bonavita, D. Ippolito, R. Lanzillo, G. Salemi, F. Patti, P. Valentino, et al. "Clinical and magnetic resonance imaging predictors of disease progression in multiple sclerosis: a nine-year follow-up study." Multiple Sclerosis Journal 20, no. 2 (July 9, 2013): 220–26. http://dx.doi.org/10.1177/1352458513494958.
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Objective: The objective of this paper is to identify clinical or magnetic resonance imaging (MRI) predictors of long-term clinical progression in a large cohort of multiple sclerosis (MS) patients. Methods: A total of 241 relapsing–remitting (RR) MS patients were included in a nine-year follow-up (FU) study. The reference MRIs were acquired at baseline (BL) as part of a multicenter, cross-sectional, clinical-MRI study. Volumetric MRI metrics were measured by a fully automated, operator-independent, multi-parametric segmentation method. Clinical progression was evaluated as defined by: conversion from RR to secondary progressive (SP) disease course; progression of Expanded Disability Status Scale (EDSS); achievement and time to reach EDSS 4. Results: We concluded that conversion from RR to SP (OR 0.79; CI 0.7–0.9), progression of EDSS (OR 0.85; CI 0.77–0.93), achievement of EDSS 4 (OR 0.8; CI 0.7–0.9), and time to reach EDSS 4 (HR 0.88; CI 0.82–0.94) were all predicted by BL gray matter (GM) volume and, except for progression of EDSS, by BL EDSS (respectively: (OR 2.88; CI 1.9–4.36), (OR 2.7; CI 1.7–4.2), (HR 3.86; CI 1.94–7.70)). Conclusions: BL GM volume and EDSS are the best long-term predictors of disease progression in RRMS patients with a relatively long and mild disease.
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Freilich, Jonatan, Ali Manouchehrinia, Mark Trusheim, Lynn G. Baird, Sophie Desbiens, Ernst Berndt, and Jan Hillert. "Characterization of annual disease progression of multiple sclerosis patients: A population-based study." Multiple Sclerosis Journal 24, no. 6 (May 8, 2017): 786–94. http://dx.doi.org/10.1177/1352458517706252.
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Background: Previous research characterizing factors influencing multiple sclerosis (MS) disease progression has typically been based on time to disease milestones (Kaplan–Meier, Cox hazard regression, etc.). A limitation of these methods is the handling of the often large groups of patients not reaching the milestone. Objective: To characterize clinical factors influencing MS disease progression as annual transitions from each Expanded Disability Status Scale (EDSS). Method: The annual progression of 11,964 patients from the Swedish MS Registry was analysed with 10 multinomial logistic regressions, that is, one for transition from each full EDSS with explanatory variables age, sex, age at onset, time in current EDSS, highest prior EDSS, MS course and treatment. Results: All factors (except sex) investigated had statistically significant impacts on transitions from at least one EDSS. However, significance and size of the effect are dependent on the EDSS state of the patient. Greater age, longer time in a state, highest prior EDSS, having progressive MS and treatment had significant impacts, whereas age at onset had minor impact. Conclusion: Our study confirms that established factors associated with MS disease worsening in time to disease milestones also have impacts on annual progression. This approach adds granularity to what EDSS these factors have an influence.
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Koch, Marcus W., Jop Mostert, Bernard Uitdehaag, and Gary Cutter. "Clinical outcome measures in SPMS trials: An analysis of the IMPACT and ASCEND original trial data sets." Multiple Sclerosis Journal 26, no. 12 (September 13, 2019): 1540–49. http://dx.doi.org/10.1177/1352458519876701.
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Background: Still too little is known about the natural history of clinical outcome measures beyond the Expanded Disability Status Scale (EDSS), such as the timed 25-foot walk (T25FW) and nine-hole peg test (9HPT) in secondary progressive multiple sclerosis (SPMS). Objective: To describe progression on the EDSS, T25FW, 9HPT, and their combinations. To investigate the association of the baseline characteristics age, sex, EDSS, T25FW, gadolinium-enhancing lesions, and relapse activity with EDSS and T25FW progression. Methods: Using original trial data from the placebo arms of the IMPACT and ASCEND randomized controlled trials, we describe disability progression (with and without 3- or 6-month confirmation). We investigated the association of selected baseline characteristics with EDSS and T25FW progression over 2 years using binary logistic regression. Results: T25FW was the single outcome measure with the largest proportion of patients progressing, followed by EDSS and 9HPT. EDSS and T25FW at baseline were associated with EDSS and T25FW progression in both data sets. Age and relapse activity were only mild and inconsistent predictors, while sex and gadolinium enhancement at baseline did not predict disability progression in either data set. Conclusion: Our analyses inform the selection of primary outcome measures as well as inclusion criteria for clinical trials in SPMS.
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Grima, D. T., G. W. Torrance, G. Francis, G. Rice, A. J. Rosner, and L. Lafortune. "Cost and health related quality of life consequences of multiple sclerosis." Multiple Sclerosis Journal 6, no. 2 (April 2000): 91–98. http://dx.doi.org/10.1177/135245850000600207.
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Objectives: To (i) quantify the cost of multiple sclerosis (MS) to the Canadian health care system and society; (ii) measure health utility in MS patients, and (iii) examine the influence of disability on patient utility and health care costs.Materials and methods: A comprehensive patient survey and chart review of relapsing MS patient in remission, relapse and recalling a relapse.Results: Annual remission costs increased with EDSS level ($7596 at EDSS 1, $33 206 at EDSS 6). At all EDSS levels the largest costs were due to inability to work, which increased with EDSS. The average relapse cost for all EDSS levels was $1367. An inverse correlation was found between EDSS level and patient utility for patient in remission and relapse. The decrease in remission health utility from EDSS I to 6 was 0.24, which is 25% greater than the difference in health status between an average 25 and 85 year-old.Conclusions: This study demonstrates that MS produces substantial health care cost and reductions in patient quality of life and ability to work, losses that can be avoided or delayed if disease progression is slowed. These data provide health-care decision-makers with the opportunity to consider the full impact of MS when faced with budget allocation decisions.
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Prados, Nicolás, Rocío Quiroga, Cinzia Caligara, Myriam Ruiz, Víctor Blasco, Antonio Pellicer, and Manuel Fernández-Sánchez. "Elective single versus double embryo transfer: live birth outcome and patient acceptance in a prospective randomised trial." Reproduction, Fertility and Development 27, no. 5 (2015): 794. http://dx.doi.org/10.1071/rd13412.
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The purpose of this study was to determine which strategy of embryo transfer has a better trade-off in live birth delivery rate versus multiple pregnancy considering patient acceptance: elective single embryo transfer (eSET) or elective double embryo transfer (eDET). In all, 199 women <38 years of age undergoing their first IVF treatment in a private centre were included in a prospective open-label randomised controlled trial. Patients were randomised into four groups: (1) eSET on Day 3; (2) eSET on Day 5; (3) eDET on Day 3; and (4) eDET on Day 5. Per patient, main analysis included acceptance of assigned group, as well as multiple and live birth delivery rates of the fresh cycle. Secondary analysis included the rates of subsequent cryotransfers and the theoretical cumulative success rate. Of 98 patients selected for eSET, 40% refused and preferred eDET. The live birth delivery rate after eDET was significantly higher after eDET versus eSET (65% vs 42%, respectively; odds ratio = 1.6, 95% confidence interval 1.1–2.1). No multiple births were observed after eSET, compared with 35% after eDET. Although live birth delivery is higher with eDET, the increased risk of multiple births is avoided with eSET. Nearly half the patients refused eSET even after having been well informed about its benefits.
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Pan, Yanhui, Faqiong Zhao, and Baizhao Zeng. "Electrochemical sensors of octylphenol based on molecularly imprinted poly(3,4-ethylenedioxythiophene) and poly(3,4-ethylenedioxythiophene–gold nanoparticles)." RSC Advances 5, no. 71 (2015): 57671–77. http://dx.doi.org/10.1039/c5ra08094k.
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Two molecularly imprinted electrochemical sensors are fabricated by using EDOT and EDOT–AuNPs as monomers, respectively. The sensors show good analytical performance for OP sensing. Note: graphene nanoribbons (GNRs), 3,4-ethylenedioxythiophene (EDOT), 4-tert-octyl-phenol (OP).
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Nagane, Samadhan, Peter Sitarik, Yuhang Wu, Quintin Baugh, Shrirang Chhatre, Junghyun Lee, and David C. Martin. "Functionalized Polythiophene Copolymers for Electronic Biomedical Devices." MRS Advances 5, no. 18-19 (2020): 943–56. http://dx.doi.org/10.1557/adv.2020.3.
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ABSTRACTWe continue to investigate the design, synthesis, and characterization of electrically and ionically active conjugated polythiophene copolymers for integrating a variety of biomedical devices with living tissue. This paper will describe some of our most recent results, including the development of several new monomers that can tailor the surface chemistry, adhesion, and biointegration of these materials with neural cells. Our efforts have focused on copolymers of 3,4 ethylenedioxythiophene (EDOT), functionalized variants of EDOT (including EDOT-acid and the trifunctional EPh), and dopamine (DOPA). The resulting PEDOT-based copolymers have electrical, optical, mechanical, and adhesive properties that can be precisely tailored by fine tuning the chemical composition and structure. Here we present results on EDOT-dopamine bifunctional monomers and their corresponding polymers. We discuss the design and synthesis of an EDOT-cholesterol that combines the thiophene with a biological moiety known to exhibit surface-active behaviour. We will also introduce EDOT-aldehyde and EDOT-maleimide monomers and show how they can be used as the starting point for a wide variety of functionalized monomers and polymers.
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Lapin, Dmitry, Deepak D. Bhandari, and Jane E. Parker. "Origins and Immunity Networking Functions of EDS1 Family Proteins." Annual Review of Phytopathology 58, no. 1 (August 25, 2020): 253–76. http://dx.doi.org/10.1146/annurev-phyto-010820-012840.
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The EDS1 family of structurally unique lipase-like proteins EDS1, SAG101, and PAD4 evolved in seed plants, on top of existing phytohormone and nucleotide-binding–leucine-rich-repeat (NLR) networks, to regulate immunity pathways against host-adapted biotrophic pathogens. Exclusive heterodimers between EDS1 and SAG101 or PAD4 create essential surfaces for resistance signaling. Phylogenomic information, together with functional studies in Arabidopsis and tobacco, identify a coevolved module between the EDS1–SAG101 heterodimer and coiled-coil (CC) HET-S and LOP-B (CCHELO) domain helper NLRs that is recruited by intracellular Toll-interleukin1-receptor (TIR) domain NLR receptors to confer host cell death and pathogen immunity. EDS1–PAD4 heterodimers have a different and broader activity in basal immunity that transcriptionally reinforces local and systemic defenses triggered by various NLRs. Here, we consider EDS1 family protein functions across seed plant lineages in the context of networking with receptor and helper NLRs and downstream resistance machineries. The different modes of action and pathway connectivities of EDS1 family members go some way to explaining their central role in biotic stress resilience.