587 research outputs found

    Seizures as an Atypical Feature of Beal’s Syndrome

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    Congenital contractural arachnodactyly, commonly known as Beal’s syndrome, is an extremely rare genetic disorder caused by mutations in the fibrillin-2 (FBN2) gene located on chromosome 5q23. It is an autosomal dominant inherited connective tissue disorder characterised by a Marfan-like body habitus, contractures, abnormally shaped ears and kyphoscoliosis. We report a seven-year-old Omani male who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2014 with seizures. He was noted to have certain distinctive facial features and musculoskeletal manifestations; he was subsequently diagnosed with Beal’s syndrome. Sequencing of the FBN2 gene revealed that the patient had a novel mutation which was also present in his mother; however, she had only a few facial features indicative of Beal’s syndrome and no systemic involvement apart from a history of childhood seizures. To the best of the authors’ knowledge, this is the first report of Beal’s syndrome with seizure symptoms as a potential feature

    Phosphatidylinositol-4,5 Bisphosphate Produced by PIP5K(gamma) Regulates Gelsolin, Actin Assembly, and Adhesion Strength of N-Cadherin Junctions

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    Phosphoinositides regulate several actin-binding proteins but their role at intercellular adhesions has not been defined. We found that phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) was generated at sites of N-cadherin–mediated intercellular adhesion and was a critical regulator of intercellular adhesion strength. Immunostaining for PI(4,5)P2 or transfection with GFP-PH-PLCδ showed that PI(4,5)P2 was enriched at sites of N-cadherin adhesions and this enrichment required activated Rac1. Isoform-specific immunostaining for type I phosphatidylinositol 4-phosphate 5 kinase (PIP5KI) showed that PIP5KIγ was spatially associated with N-cadherin–Fc beads. Association of PIP5KIγ with N-cadherin adhesions was in part dependent on the activation of RhoA. Transfection with catalytically inactive PIP5KIγ blocked the enrichment of PI(4,5)P2 around beads. Catalytically inactive PIP5KIγ or a cell-permeant peptide that mimics and competes for the PI(4,5)P2-binding region of the actin-binding protein gelsolin inhibited incorporation of actin monomers in response to N-cadherin ligation and reduced intercellular adhesion strength by more than twofold. Gelsolin null fibroblasts transfected with a gelsolin severing mutant containing an intact PI(4,5)P2 binding region, demonstrated intercellular adhesion strength similar to wild-type transfected controls. We conclude that PIP5KIγ-mediated generation of PI(4,5)P2 at sites of N-cadherin contacts regulates intercellular adhesion strength, an effect due in part to PI(4,5)P2-mediated regulation of gelsolin

    OR.107. TIM-1 Plays a Crucial Role in the Expansion of Autopathogneic T-Cells and Regulation of Autoimmunity [abstract only]

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    T-cell immunoglobulin and mucin (TIM) family Members are differentially expressed on Th1 and Th2 cells. Polymorphisms of TIM-1 have been associated with susceptibility to asthma; however, its role in regulating autoimmunity has not been studied. Here, we have used an agonistic antiTIM-1 antibody (Ab, Clone 3B3) which has previously been shown to costimulate T-cell activation and expansion, to analyze the role of TIM-1 in the development and regulation of experimental autoimmune encephalomyelitis (EAE). Treatment with 3B3 dramatically enhances the severity of EAE as well as the frequency of encephalitogenic CD4+ T-cells and the production of IFN-g and IL-17 by these cells. Furthermore, administration of 3B3 breaks self-tolerance and induces EAE in the disease resistant B10.S strain. We have utilized another anti-TIM-1 Ab (RMT1-10) that does not costimulate T-cell activation in vitro. In contrast to 3B3, treatment with RMT1-10 inhibits the development of EAE and reduces the frequency of encephalitogenic CD4+ T-cells with a commensurate decrease in the production of IFN-g and IL-17. Treatment with RMT1-10 causes CD4+ T-cells to produce more IL-4 and IL-10. We provide evidence that both 3B3 and RMT1-10 bind to the same epitope in the Ig domain of TIM-1, but the binding affinity of 3B3 is much higher than that of RMT1-10. These data suggest that TIM-1 engagement with the agonistic Ab, along with TcR ligation, costimulates T-cell expansion with pro-inflammatory IFN-g and IL-17 production resulting in the breakdown of self-tolerance and development of autoimmunity, whereas blocking anti-TIM-1 Ab causes a decrease in the autopathogenic Th1/ThIL-17 responses. This study demonstrates that TIM-1 is a key cell surface molecule that regulates effector T-cell response and depending on hopw the molecule is engaged, autoimmune responses can be either enhanced or inhibited in vivo

    A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

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    Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment

    Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function

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    It has been suggested that T cell immunoglobulin mucin (Tim)-1 expressed on T cells serves to positively costimulate T cell responses. However, crosslinking of Tim-1 by its ligand Tim-4 resulted in either activation or inhibition of T cell responses, thus raising the issue of whether Tim-1 can have a dual function as a costimulator. To resolve this issue, we tested a series of monoclonal antibodies specific for Tim-1 and identified two antibodies that showed opposite functional effects. One anti–Tim-1 antibody increased the frequency of antigen-specific T cells, the production of the proinflammatory cytokines IFN-γ and IL-17, and the severity of experimental autoimmune encephalomyelitis. In contrast, another anti–Tim-1 antibody inhibited the generation of antigen-specific T cells, production of IFN-γ and IL-17, and development of autoimmunity, and it caused a strong Th2 response. Both antibodies bound to closely related epitopes in the IgV domain of the Tim-1 molecule, but the activating antibody had an avidity for Tim-1 that was 17 times higher than the inhibitory antibody. Although both anti–Tim-1 antibodies induced CD3 capping, only the activating antibody caused strong cytoskeletal reorganization and motility. These data indicate that Tim-1 regulates T cell responses and that Tim-1 engagement can alter T cell function depending on the affinity/avidity with which it is engaged

    Air quality and urban sustainable development: the application of machine learning tools

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    [EN] Air quality has an efect on a population¿s quality of life. As a dimension of sustainable urban development, governments have been concerned about this indicator. This is refected in the references consulted that have demonstrated progress in forecasting pollution events to issue early warnings using conventional tools which, as a result of the new era of big data, are becoming obsolete. There are a limited number of studies with applications of machine learning tools to characterize and forecast behavior of the environmental, social and economic dimensions of sustainable development as they pertain to air quality. This article presents an analysis of studies that developed machine learning models to forecast sustainable development and air quality. Additionally, this paper sets out to present research that studied the relationship between air quality and urban sustainable development to identify the reliability and possible applications in diferent urban contexts of these machine learning tools. To that end, a systematic review was carried out, revealing that machine learning tools have been primarily used for clustering and classifying variables and indicators according to the problem analyzed, while tools such as artifcial neural networks and support vector machines are the most widely used to predict diferent types of events. The nonlinear nature and synergy of the dimensions of sustainable development are of great interest for the application of machine learning tools.Molina-Gómez, NI.; Díaz-Arévalo, JL.; López Jiménez, PA. (2021). Air quality and urban sustainable development: the application of machine learning tools. International Journal of Environmental Science and Technology. 18(4):1-18. https://doi.org/10.1007/s13762-020-02896-6S118184Al-Dabbous A, Kumar P, Khan A (2017) Prediction of airborne nanoparticles at roadside location using a feed–forward artificial neural network. Atmos Pollut Res 8:446–454. https://doi.org/10.1016/j.apr.2016.11.004Antanasijević D, Pocajt V, Povrenović D, Ristić M, Perić-Grujić A (2013) PM10 emission forecasting using artificial neural networks and genetic algorithm input variable optimization. Sci Total Environ 443:511–519. https://doi.org/10.1016/j.scitotenv.2012.10.110Brink H, Richards JW, Fetherolf M (2016) Real-world machine learning. Richards JW, Fetherolf M (eds) Manning Publications Co. Berkeley, CA. https://www.manning.com/books/real-world-machine-learning. Accessed 26 Apr 2020Cervone G, Franzese P, Ezber Y, Boybeyi Z (2008) Risk assessment of atmospheric emissions using machine learning. Nat Hazard Earth Syst 8:991–1000. https://doi.org/10.5194/nhess-8-991-2008Chen S, Kan G, Li J, Liang K, Hong Y (2018) Investigating China’s urban air quality using big data, information theory, and machine learning. Pol J Environ Stud 27:565–578. https://doi.org/10.15244/pjoes/75159Corani (2005) Air quality prediction in Milan: feed-forward neural networks, pruned neural networks and lazy learning. Ecol Model 185:513–529. https://doi.org/10.1016/j.ecolmodel.2005.01.008Cruz C, Gómez A, Ramírez L, Villalva A, Monge O, Varela J, Quiroz J, Duarte H (2017) Calidad del aire respecto de metales (Pb, Cd, Ni, Cu, Cr) y relación con salud respiratoria: caso Sonora, México. Rev Int Contam Ambient 33:23–34. https://doi.org/10.20937/RICA.2017.33.esp02.02de Hoogh K, Héritier H, Stafoggia M, Künzli N, Kloog I (2018) Modelling daily PM2.5 concentrations at high spatio-temporal resolution across Switzerland. Environ Pollut 233:1147–1154. https://doi.org/10.1016/j.envpol.2017.10.025Franceschi F, Cobo M, Figueredo M (2018) Discovering relationships and forecasting PM10 and PM2.5 concentrations in Bogotá, Colombia, using Artificial Neural Networks, Principal Component Analysis, and k-means clustering. Atmos Pollut Res 9:912–922. https://doi.org/10.1016/j.apr.2018.02.006García N, Combarro E, del Coz J, Montañes E (2013) A SVM-based regression model to study the air quality at local scale in Oviedo urban area (Northern Spain): a case study. Appl Math Comput 219:8923–8937. https://doi.org/10.1016/j.amc.2013.03.018Gibert K, Sànchez-Màrre M, Sevilla B (2012) Tools for environmental data mining and intelligent decision support. In iEMSs. Leipzig, Germany. http://www.iemss.org/society/index.php/iemss-2012-proceedings. Accessed 26 Nov 2018Gibert K, Sànchez-Marrè M, Izquierdo J (2016) A survey on pre-processing techniques: relevant issues in the context of environmental data mining. Ai Commun 29:627–663. https://doi.org/10.3233/AIC-160710Gounaridis D, Chorianopoulos I, Koukoulas S (2018) Exploring prospective urban growth trends under different economic outlooks and land-use planning scenarios: the case of Athens. Appl Geogr 90:134–144. https://doi.org/10.1016/j.apgeog.2017.12.001Holloway J, Mengersen K (2018) Statistical machine learning methods and remote sensing for sustainable development goals: a review. Remote Sens 10:1–21. https://doi.org/10.3390/rs10091365Ifaei P, Karbassi A, Lee S, Yoo Ch (2017) A renewable energies-assisted sustainable development plan for Iran using techno-econo-socio-environmental multivariate analysis and big data. Energy Convers Manag 153:257–277. https://doi.org/10.1016/j.enconman.2017.10.014Kadiyala A, Kumar A (2017a) Applications of R to evaluate environmental data science problems. Environ Prog Sustain 36:1358–1364. https://doi.org/10.1002/ep.12676Kadiyala A, Kumar A (2017b) Vector time series-based radial basis function neural network modeling of air quality inside a public transportation bus using available software. Environ Prog Sustain 36:4–10. https://doi.org/10.1002/ep.12523Karimian H, Li Q, Wu Ch, Qi Y, Mo Y, Chen G, Zhang X, Sachdeva S (2019) Evaluation of different machine learning approaches to forecasting PM2.5 mass concentrations. Aerosol Air Qual Res 19:1400–1410. https://doi.org/10.4209/aaqr.2018.12.0450Krzyzanowski M, Apte J, Bonjour S, Brauer M, Cohen A, Prüss-Ustun A (2014) Air pollution in the mega-cities. Curr Environ Health Rep 1:185–191. https://doi.org/10.1007/s40572-014-0019-7Lässig K, Morik (2016) Computat sustainability. Springer, Berlin. https://doi.org/10.1007/978-3-319-31858-5Li Y, Wu Y-X, Zeng Z-X, Guo L (2006) Research on forecast model for sustainable development of economy-environment system based on PCA and SVM. In: Proceedings of the 2006 international conference on machine learning and cybernetics, vol 2006. IEEE, Dalian, China, pp 3590–3593. https://doi.org/10.1109/ICMLC.2006.258576Liu B-Ch, Binaykia A, Chang P-Ch, Tiwari M, Tsao Ch-Ch (2017) Urban air quality forecasting based on multi- dimensional collaborative support vector regression (SVR): a case study of Beijing-Tianjin-Shijiazhuang. PLoS ONE 12:1–17. https://doi.org/10.1371/journal.pone.0179763Lubell M, Feiock R, Handy S (2009) City adoption of environmentally sustainable policies in California’s Central Valley. J Am Plan Assoc 75:293–308. https://doi.org/10.1080/01944360902952295Ma D, Zhang Z (2016) Contaminant dispersion prediction and source estimation with integrated Gaussian-machine learning network model for point source emission in atmosphere. J Hazard Mater 311:237–245. https://doi.org/10.1016/j.jhazmat.2016.03.022Madu C, Kuei N, Lee P (2017) Urban sustainability management: a deep learning perspective. Sustain Cities Soc 30:1–17. https://doi.org/10.1016/j.scs.2016.12.012Mellos K (1988) Theory of eco-development. In: Perspectives on ecology. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-19598-5_4Ni XY, Huang H, Du WP (2017) Relevance analysis and short-term prediction of PM2.5 concentrations in Beijing based on multi-source data. Atmos Environ 150:146–161. https://doi.org/10.1016/j.atmosenv.2016.11.054Oprea M, Dragomir E, Popescu M, Mihalache S (2016) Particulate matter air pollutants forecasting using inductive learning approach. Rev Chim 67:2075–2081Paas B, Stienen J, Vorländer M, Schneider Ch (2017) Modelling of urban near-road atmospheric PM concentrations using an artificial neural network approach with acoustic data input. Environments 4:1–25. https://doi.org/10.3390/environments4020026Pandey G, Zhang B, Jian L (2013) Predicting submicron air pollution indicators: a machine learning approach. Environ Sci Proc Impacts 15:996–1005. https://doi.org/10.1039/c3em30890aPeng H, Lima A, Teakles A, Jin J, Cannon A, Hsieh W (2017) Evaluating hourly air quality forecasting in Canada with nonlinear updatable machine learning methods. Air Qual Atmos Health 10:195–211. https://doi.org/10.1007/s11869-016-0414-3Pérez-Ortíz M, de La Paz-Marín M, Gutiérrez PA, Hervás-Martínez C (2014) Classification of EU countries’ progress towards sustainable development based on ordinal regression techniques. Knowl Based Syst 66:178–189. https://doi.org/10.1016/j.knosys.2014.04.041Phillis Y, Kouikoglou V, Verdugo C (2017) Urban sustainability assessment and ranking of cities. Comput Environ Urban 64:254–265. https://doi.org/10.1016/j.compenvurbsys.2017.03.002Saeed S, Hussain L, Awan I, Idris A (2017) Comparative analysis of different statistical methods for prediction of PM2.5 and PM10 concentrations in advance for several hours. Int J Comput Sci Netw Secur 17:45–52Sayegh A, Munir S, Habeebullah T (2014) Comparing the performance of statistical models for predicting PM10 concentrations. Aerosol Air Qual Res 14:653–665. https://doi.org/10.4209/aaqr.2013.07.0259Shaban K, Kadri A, Rezk E (2016) Urban air pollution monitoring system with forecasting models. IEEE Sens J 16:2598–2606. https://doi.org/10.1109/JSEN.2016.2514378Sierra B (2006) Aprendizaje automático conceptos básicos y avanzados Aspectos prácticos utilizando el software Weka. Madrid Pearson Prentice Hall, MadridSingh K, Gupta S, Rai P (2013) Identifying pollution sources and predicting urban air quality using ensemble learning methods. Atmos Environ 80:426–437. https://doi.org/10.1016/j.atmosenv.2013.08.023Song L, Pang S, Longley I, Olivares G, Sarrafzadeh A (2014) Spatio-temporal PM2.5 prediction by spatial data aided incremental support vector regression. In: International joint conference on neural networks. IEEE, Beijing, pp 623–630. https://doi.org/10.1109/IJCNN.2014.6889521Souza R, Coelho G, da Silva A, Pozza S (2015) Using ensembles of artificial neural networks to improve PM10 forecasts. Chem Eng Trans 43:2161–2166. https://doi.org/10.3303/CET1543361Suárez A, García PJ, Riesgo P, del Coz JJ, Iglesias-Rodríguez FJ (2011) Application of an SVM-based regression model to the air quality study at local scale in the Avilés urban area (Spain). Math Comput Model 54:453–1466. https://doi.org/10.1016/j.mcm.2011.04.017Tamas W, Notton G, Paoli C, Nivet M, Voyant C (2016) Hybridization of air quality forecasting models using machine learning and clustering: an original approach to detect pollutant peaks. Aerosol Air Qual Res 16:405–416. https://doi.org/10.4209/aaqr.2015.03.0193Toumi O, Le Gallo J, Ben Rejeb J (2017) Assessment of Latin American sustainability. Renew Sustain Energy Rev 78:878–885. https://doi.org/10.1016/j.rser.2017.05.013Tzima F, Mitkas P, Voukantsis D, Karatzas K (2011) Sparse episode identification in environmental datasets: the case of air quality assessment. Expert Syst Appl 38:5019–5027. https://doi.org/10.1016/j.eswa.2010.09.148United Nations, Department of Economic and Social Affairs (2019) World urbanization prospects The 2018 Revision. New York. https://doi.org/10.18356/b9e995fe-enWang B (2019) Applying machine-learning methods based on causality analysis to determine air quality in China. Pol J Environ Stud 28:3877–3885. https://doi.org/10.15244/pjoes/99639Wang X, Xiao Z (2017) Regional eco-efficiency prediction with support vector spatial dynamic MIDAS. J Clean Prod 161:165–177. https://doi.org/10.1016/j.jclepro.2017.05.077Wang W, Men C, Lu W (2008) Online prediction model based on support vector machine. Neurocomputing 71:550–558. https://doi.org/10.1016/j.neucom.2007.07.020WCED (1987) Report of the world commission on environment and development: our common future: report of the world commission on environment and development. WCED, Oslo. https://doi.org/10.1080/07488008808408783Weizhen H, Zhengqiang L, Yuhuan Z, Hua X, Ying Z, Kaitao L, Donghui L, Peng W, Yan M (2014) Using support vector regression to predict PM10 and PM2.5. In: IOP conference series: earth and environmental science, vol 17. IOP. https://doi.org/10.1088/1755-1315/17/1/012268WHO (2016) OMS | La OMS publica estimaciones nacionales sobre la exposición a la contaminación del aire y sus repercusiones para la salud. WHO. http://www.who.int/mediacentre/news/releases/2016/air-pollution-estimates/es/. Accesed 26 Nov 2018Yeganeh N, Shafie MP, Rashidi Y, Kamalan H (2012) Prediction of CO concentrations based on a hybrid partial least square and support vector machine model. Atmos Environ 55:357–365. https://doi.org/10.1016/j.atmosenv.2012.02.092Zalakeviciute R, Bastidas M, Buenaño A, Rybarczyk Y (2020) A traffic-based method to predict and map urban air quality. Appl Sci. https://doi.org/10.3390/app10062035Zeng L, Guo J, Wang B, Lv J, Wang Q (2019) Analyzing sustainability of Chinese coal cities using a decision tree modeling approach. Resour Policy 64:101501. https://doi.org/10.1016/j.resourpol.2019.101501Zhan Y, Luo Y, Deng X, Grieneisen M, Zhang M, Di B (2018) Spatiotemporal prediction of daily ambient ozone levels across China using random forest for human exposure assessment. Environ Pollut 233:464–473. https://doi.org/10.1016/j.envpol.2017.10.029Zhang Y, Huan Q (2006) Research on the evaluation of sustainable development in Cangzhou city based on neural-network-AHP. In: Proceedings of the fifth international conference on machine learning and cybernetics, vol 2006. pp 3144–3147. https://doi.org/10.1109/ICMLC.2006.258407Zhang Y, Shang W, Wu Y (2009) Research on sustainable development based on neural network. In: 2009 Chinese control and decision conference. IEEE, pp 3273–3276. https://doi.org/10.1109/CCDC.2009.5192476Zhou Y, Chang F-J, Chang L-Ch, Kao I-F, Wang YS (2019) Explore a deep learning multi-output neural network for regional multi-step-ahead air quality forecasts. J Clean Prod 209:134–145. https://doi.org/10.1016/j.jclepro.2018.10.24

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

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    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty
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