The MLL-Menin Interaction is a Therapeutic Vulnerability in <em>NUP98</em>-rearranged AML

\ua9 2023 Wolters Kluwer Health. All rights reserved. Chromosomal translocations involving the NUP98 locus are among the most prevalent rearrangements in pediatric acute myeloid leukemia (AML). AML with NUP98 fusions is characterized by high expression of HOXA and MEIS1 genes and is associated with poor clinical outcome. NUP98 fusion proteins are recruited to their target genes by the mixed lineage leukemia (MLL) complex, which involves a direct interaction between MLL and Menin. Here, we show that therapeutic targeting of the Menin-MLL interaction inhibits the propagation of NUP98-rearrranged AML both ex vivo and in vivo. Treatment of primary AML cells with the Menin inhibitor revumenib (SNDX-5613) impairs proliferation and clonogenicity ex vivo in long-term coculture and drives myeloid differentiation. These phenotypic effects are associated with global gene expression changes in primary AML samples that involve the downregulation of many critical NUP98 fusion protein-target genes, such as MEIS1 and CDK6. In addition, Menin inhibition reduces the expression of both wild-type FLT3 and mutated FLT3-ITD, and in combination with FLT3 inhibitor, suppresses patient-derived NUP98-r AML cells in a synergistic manner. Revumenib treatment blocks leukemic engraftment and prevents leukemia-associated death of immunodeficient mice transplanted with NUP98::NSD1 FLT3-ITD-positive patient-derived AML cells. These results demonstrate that NUP98-rearranged AMLs are highly susceptible to inhibition of the MLL-Menin interaction and suggest the inclusion of AML patients harboring NUP98 fusions into the clinical evaluation of Menin inhibitors

A review on approaches to solving Poisson’s equation in projection-based meshless methods for modelling strongly nonlinear water waves

Three meshless methods, including incompressible smooth particle hydrodynamic (ISPH), moving particle semi-implicit (MPS) and meshless local Petrov–Galerkin method based on Rankine source solution (MLPG_R) methods, are often employed to model nonlinear or violent water waves and their interaction with marine structures. They are all based on the projection procedure, in which solving Poisson’s equation about pressure at each time step is a major task. There are three different approaches to solving Poisson’s equation, i.e. (1) discretizing Laplacian directly by approximating the second-order derivatives, (2) transferring Poisson’s equation into a weak form containing only gradient of pressure and (3) transferring Poisson’s equation into a weak form that does not contain any derivatives of functions to be solved. The first approach is often adopted in ISPH and MPS, while the third one is implemented by the MLPG_R method. This paper attempts to review the most popular, though not all, approaches available in literature for solving the equation

Description of combined ARHSP/JALS phenotype in some patients with SPG11 mutations

Background: SPG11 mutations can cause autosomal recessive hereditary spastic paraplegia (ARHSP) and juvenile amyotrophic lateral sclerosis (JALS). Because these diseases share some clinical presentations and both can be caused by SPG11 mutations, it was considered that definitive diagnosis may not be straight forward. Methods: The DNAs of referred ARHSP and JALS patients were exome sequenced. Clinical data of patients with SPG11 mutations were gathered by interviews and neurological examinations including electrodiagnosis (EDX) and magnetic resonance imaging (MRI). Results: Eight probands with SPG11 mutations were identified. Two mutations are novel. Among seven Iranian probands, six carried the p.Glu1026Argfs*4-causing mutation. All eight patients had features known to be present in both ARHSP and JALS. Additionally and surprisingly, presence of both thin corpus callosum (TCC) on MRI and motor neuronopathy were also observed in seven patients. These presentations are, respectively, key suggestive features of ARHSP and JALS. Conclusion: We suggest that rather than ARHSP or JALS, combined ARHSP/JALS is the appropriate description of seven patients studied. Criteria for ARHSP, JALS, and combined ARHSP/JALS designations among patients with SPG11 mutations are suggested. The importance of performing both EDX and MRI is emphasized. Initial screening for p.Glu1026Argfs*4 may facilitate SPG11 screenings in Iranian patients. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LL

The completion of the Mammalian Gene Collection (MGC)

Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transcripts that have one or more PubMed publications, in addition to clones for more than 6300 rat genes. These high-quality MGC clones and their sequences are accessible without restriction to researchers worldwide

Evidence for Transcript Networks Composed of Chimeric RNAs in Human Cells

The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5′ and 3′ transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network

A Hybrid Fuzzy Multi-criteria Decision Making Model to Evaluate the Overall Performance of Public Emergency Departments: A Case Study

[EN] Performance evaluation is relevant for supporting managerial decisions related to the improvement of public emergency departments (EDs). As different criteria from ED context and several alternatives need to be considered, selecting a suitable Multicriteria Decision-Making (MCDM) approach has become a crucial step for ED performance evaluation. Although some methodologies have been proposed to address this challenge, a more complete approach is still lacking. This paper bridges this gap by integrating three potent MCDM methods. First, the Fuzzy Analytic Hierarchy Process (FAHP) is used to determine the criteria and sub-criteria weights under uncertainty, followed by the interdependence evaluation via fuzzy Decision-Making Trial and Evaluation Laboratory(FDEMATEL). The fuzzy logic is merged with AHP and DEMATEL to illustrate vague judgments. Finally, the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) is used for ranking EDs. This approach is validated in a real 3-ED cluster. The results revealed the critical role of Infrastructure (21.5%) in ED performance and the interactive nature of Patient safety (C+R =12.771). Furthermore, this paper evidences the weaknesses to be tackled for upgrading the performance of each ED.Ortiz-Barrios, M.; Alfaro Saiz, JJ. (2020). A Hybrid Fuzzy Multi-criteria Decision Making Model to Evaluate the Overall Performance of Public Emergency Departments: A Case Study. International Journal of Information Technology & Decision Making. 19(6):1485-1548. https://doi.org/10.1142/S0219622020500364S14851548196Lord, K., Parwani, V., Ulrich, A., Finn, E. B., Rothenberg, C., Emerson, B., … Venkatesh, A. K. (2018). Emergency department boarding and adverse hospitalization outcomes among patients admitted to a general medical service. The American Journal of Emergency Medicine, 36(7), 1246-1248. doi:10.1016/j.ajem.2018.03.043Sørup, C. M., Jacobsen, P., & Forberg, J. L. (2013). Evaluation of emergency department performance – a systematic review on recommended performance and quality-in-care measures. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 21(1). doi:10.1186/1757-7241-21-62Farokhi, S., & Roghanian, E. (2018). Determining quantitative targets for performance measures in the balanced scorecard method using response surface methodology. Management Decision, 56(9), 2006-2037. doi:10.1108/md-08-2017-0772Ortiz Barrios, M. A., & Felizzola Jiménez, H. (2016). Use of Six Sigma Methodology to Reduce Appointment Lead-Time in Obstetrics Outpatient Department. Journal of Medical Systems, 40(10). doi:10.1007/s10916-016-0577-3Sunder M., V., Ganesh, L. S., & Marathe, R. R. (2018). A morphological analysis of research literature on Lean Six Sigma for services. International Journal of Operations & Production Management, 38(1), 149-182. doi:10.1108/ijopm-05-2016-0273Bergeron, B. P. (2017). Performance Management in Healthcare. doi:10.4324/9781315102214Santos, S. P., Belton, V., Howick, S., & Pilkington, M. (2018). Measuring organisational performance using a mix of OR methods. Technological Forecasting and Social Change, 131, 18-30. doi:10.1016/j.techfore.2017.07.028Ho, W., & Ma, X. (2018). The state-of-the-art integrations and applications of the analytic hierarchy process. European Journal of Operational Research, 267(2), 399-414. doi:10.1016/j.ejor.2017.09.007Dargi, A., Anjomshoae, A., Galankashi, M. R., Memari, A., & Tap, M. B. M. (2014). Supplier Selection: A Fuzzy-ANP Approach. Procedia Computer Science, 31, 691-700. doi:10.1016/j.procs.2014.05.317Jing, M., Jie, Y., Shou-yi, L., & Lu, W. (2015). Application of fuzzy analytic hierarchy process in the risk assessment of dangerous small-sized reservoirs. International Journal of Machine Learning and Cybernetics, 9(1), 113-123. doi:10.1007/s13042-015-0363-4Samanlioglu, F., Taskaya, Y. E., Gulen, U. C., & Cokcan, O. (2018). A Fuzzy AHP–TOPSIS-Based Group Decision-Making Approach to IT Personnel Selection. International Journal of Fuzzy Systems, 20(5), 1576-1591. doi:10.1007/s40815-018-0474-7CHEN, M.-F., TZENG, G.-H., & TANG, T.-I. (2005). FUZZY MCDM APPROACH FOR EVALUATION OF EXPATRIATE ASSIGNMENTS. International Journal of Information Technology & Decision Making, 04(02), 277-296. doi:10.1142/s0219622005001520Gul, M., Celik, E., Gumus, A. T., & Guneri, A. F. (2016). Emergency department performance evaluation by an integrated simulation and interval type-2 fuzzy MCDM-based scenario analysis. European J. of Industrial Engineering, 10(2), 196. doi:10.1504/ejie.2016.075846Jovčić, Průša, Dobrodolac, & Švadlenka. (2019). A Proposal for a Decision-Making Tool in Third-Party Logistics (3PL) Provider Selection Based on Multi-Criteria Analysis and the Fuzzy Approach. Sustainability, 11(15), 4236. doi:10.3390/su11154236Saaty, T. L., & Vargas, L. G. (2012). Models, Methods, Concepts & Applications of the Analytic Hierarchy Process. International Series in Operations Research & Management Science. doi:10.1007/978-1-4614-3597-6Vargas, L. G. (2016). Voting with Intensity of Preferences. International Journal of Information Technology & Decision Making, 15(04), 839-859. doi:10.1142/s0219622016400058Lee, K.-C., Tsai, W.-H., Yang, C.-H., & Lin, Y.-Z. (2018). An MCDM approach for selecting green aviation fleet program management strategies under multi-resource limitations. Journal of Air Transport Management, 68, 76-85. doi:10.1016/j.jairtraman.2017.06.011Labib, A., & Read, M. (2015). A hybrid model for learning from failures: The Hurricane Katrina disaster. Expert Systems with Applications, 42(21), 7869-7881. doi:10.1016/j.eswa.2015.06.020Hosseini, S., & Khaled, A. A. (2016). A hybrid ensemble and AHP approach for resilient supplier selection. Journal of Intelligent Manufacturing, 30(1), 207-228. doi:10.1007/s10845-016-1241-yZavadskas, E. K., Govindan, K., Antucheviciene, J., & Turskis, Z. (2016). Hybrid multiple criteria decision-making methods: a review of applications for sustainability issues. Economic Research-Ekonomska Istraživanja, 29(1), 857-887. doi:10.1080/1331677x.2016.1237302Lolli, F., Balugani, E., Ishizaka, A., Gamberini, R., Butturi, M. A., Marinello, S., & Rimini, B. (2019). On the elicitation of criteria weights in PROMETHEE-based ranking methods for a mobile application. Expert Systems with Applications, 120, 217-227. doi:10.1016/j.eswa.2018.11.030De Almeida Filho, A. T., Clemente, T. R. N., Morais, D. C., & de Almeida, A. T. (2018). Preference modeling experiments with surrogate weighting procedures for the PROMETHEE method. European Journal of Operational Research, 264(2), 453-461. doi:10.1016/j.ejor.2017.08.006Sun, G., Guan, X., Yi, X., & Zhou, Z. (2018). An innovative TOPSIS approach based on hesitant fuzzy correlation coefficient and its applications. Applied Soft Computing, 68, 249-267. doi:10.1016/j.asoc.2018.04.004Frazão, T. D. C., Camilo, D. G. G., Cabral, E. L. S., & Souza, R. P. (2018). Multicriteria decision analysis (MCDA) in health care: a systematic review of the main characteristics and methodological steps. BMC Medical Informatics and Decision Making, 18(1). doi:10.1186/s12911-018-0663-1Ortiz-Barrios, M. A., Herrera-Fontalvo, Z., Rúa-Muñoz, J., Ojeda-Gutiérrez, S., De Felice, F., & Petrillo, A. (2018). An integrated approach to evaluate the risk of adverse events in hospital sector. Management Decision, 56(10), 2187-2224. doi:10.1108/md-09-2017-0917Al Salem, A. A., & Awasthi, A. (2018). Investigating rank reversal in reciprocal fuzzy preference relation based on additive consistency: Causes and solutions. Computers & Industrial Engineering, 115, 573-581. doi:10.1016/j.cie.2017.11.027Aires, R. F. de F., & Ferreira, L. (2019). A new approach to avoid rank reversal cases in the TOPSIS method. Computers & Industrial Engineering, 132, 84-97. doi:10.1016/j.cie.2019.04.023Emrouznejad, A., & Yang, G. (2018). A survey and analysis of the first 40 years of scholarly literature in DEA: 1978–2016. Socio-Economic Planning Sciences, 61, 4-8. doi:10.1016/j.seps.2017.01.008Arya, A., & Yadav, S. P. (2017). Development of FDEA Models to Measure the Performance Efficiencies of DMUs. International Journal of Fuzzy Systems, 20(1), 163-173. doi:10.1007/s40815-017-0325-yMufazzal, S., & Muzakkir, S. M. (2018). A new multi-criterion decision making (MCDM) method based on proximity indexed value for minimizing rank reversals. Computers & Industrial Engineering, 119, 427-438. doi:10.1016/j.cie.2018.03.045Kaliszewski, I., & Podkopaev, D. (2016). Simple additive weighting—A metamodel for multiple criteria decision analysis methods. Expert Systems with Applications, 54, 155-161. doi:10.1016/j.eswa.2016.01.042Mousavi-Nasab, S. H., & Sotoudeh-Anvari, A. (2018). A new multi-criteria decision making approach for sustainable material selection problem: A critical study on rank reversal problem. Journal of Cleaner Production, 182, 466-484. doi:10.1016/j.jclepro.2018.02.062Chen, Z., Ming, X., Zhang, X., Yin, D., & Sun, Z. (2019). A rough-fuzzy DEMATEL-ANP method for evaluating sustainable value requirement of product service system. Journal of Cleaner Production, 228, 485-508. doi:10.1016/j.jclepro.2019.04.145Jumaah, F. M., Zadain, A. A., Zaidan, B. B., Hamzah, A. K., & Bahbibi, R. (2018). Decision-making solution based multi-measurement design parameter for optimization of GPS receiver tracking channels in static and dynamic real-time positioning multipath environment. Measurement, 118, 83-95. doi:10.1016/j.measurement.2018.01.011Singh, A., & Prasher, A. (2017). Measuring healthcare service quality from patients’ perspective: using Fuzzy AHP application. Total Quality Management & Business Excellence, 30(3-4), 284-300. doi:10.1080/14783363.2017.1302794Otay, İ., Oztaysi, B., Cevik Onar, S., & Kahraman, C. (2017). Multi-expert performance evaluation of healthcare institutions using an integrated intuitionistic fuzzy AHP&DEA methodology. Knowledge-Based Systems, 133, 90-106. doi:10.1016/j.knosys.2017.06.028Awasthi, A., Govindan, K., & Gold, S. (2018). Multi-tier sustainable global supplier selection using a fuzzy AHP-VIKOR based approach. International Journal of Production Economics, 195, 106-117. doi:10.1016/j.ijpe.2017.10.013Gul, M., Guneri, A. F., & Nasirli, S. M. (2018). A fuzzy-based model for risk assessment of routes in oil transportation. International Journal of Environmental Science and Technology, 16(8), 4671-4686. doi:10.1007/s13762-018-2078-zKazancoglu, Y., Kazancoglu, I., & Sagnak, M. (2018). Fuzzy DEMATEL-based green supply chain management performance. Industrial Management & Data Systems, 118(2), 412-431. doi:10.1108/imds-03-2017-0121Abdullah, L., & Zulkifli, N. (2015). Integration of fuzzy AHP and interval type-2 fuzzy DEMATEL: An application to human resource management. Expert Systems with Applications, 42(9), 4397-4409. doi:10.1016/j.eswa.2015.01.021Ashtiani, M., & Azgomi, M. A. (2016). A hesitant fuzzy model of computational trust considering hesitancy, vagueness and uncertainty. Applied Soft Computing, 42, 18-37. doi:10.1016/j.asoc.2016.01.023Zyoud, S. H., & Fuchs-Hanusch, D. (2017). A bibliometric-based survey on AHP and TOPSIS techniques. Expert Systems with Applications, 78, 158-181. doi:10.1016/j.eswa.2017.02.016Scholz, S., Ngoli, B., & Flessa, S. (2015). Rapid assessment of infrastructure of primary health care facilities – a relevant instrument for health care systems management. BMC Health Services Research, 15(1). doi:10.1186/s12913-015-0838-8Ivlev, I., Vacek, J., & Kneppo, P. (2015). Multi-criteria decision analysis for supporting the selection of medical devices under uncertainty. European Journal of Operational Research, 247(1), 216-228. doi:10.1016/j.ejor.2015.05.075Kovacs, E., Strobl, R., Phillips, A., Stephan, A.-J., Müller, M., Gensichen, J., & Grill, E. (2018). Systematic Review and Meta-analysis of the Effectiveness of Implementation Strategies for Non-communicable Disease Guidelines in Primary Health Care. Journal of General Internal Medicine, 33(7), 1142-1154. doi:10.1007/s11606-018-4435-5Morley, C., Unwin, M., Peterson, G. M., Stankovich, J., & Kinsman, L. (2018). Emergency department crowding: A systematic review of causes, consequences and solutions. PLOS ONE, 13(8), e0203316. doi:10.1371/journal.pone.0203316Hermann, R. M., Long, E., & Trotta, R. L. (2019). Improving Patients’ Experiences Communicating With Nurses and Providers in the Emergency Department. Journal of Emergency Nursing, 45(5), 523-530. doi:10.1016/j.jen.2018.12.001Hawley, K. L., Mazer-Amirshahi, M., Zocchi, M. S., Fox, E. R., & Pines, J. M. (2015). Longitudinal Trends in U.S. Drug Shortages for Medications Used in Emergency Departments (2001-2014). Academic Emergency Medicine, 23(1), 63-69. doi:10.1111/acem.12838Stang, A. S., Crotts, J., Johnson, D. W., Hartling, L., & Guttmann, A. (2015). Crowding Measures Associated With the Quality of Emergency Department Care: A Systematic Review. Academic Emergency Medicine, 22(6), 643-656. doi:10.1111/acem.12682Chanamool, N., & Naenna, T. (2016). Fuzzy FMEA application to improve decision-making process in an emergency department. Applied Soft Computing, 43, 441-453. doi:10.1016/j.asoc.2016.01.007Farup, P. G. (2015). Are measurements of patient safety culture and adverse events valid and reliable? Results from a cross sectional study. BMC Health Services Research, 15(1). doi:10.1186/s12913-015-0852-xCarter, E. J., Pouch, S. M., & Larson, E. L. (2013). The Relationship Between Emergency Department Crowding and Patient Outcomes: A Systematic Review. Journal of Nursing Scholarship, 46(2), 106-115. doi:10.1111/jnu.12055Ebben, R. H. A., Siqeca, F., Madsen, U. R., Vloet, L. C. M., & van Achterberg, T. (2018). Effectiveness of implementation strategies for the improvement of guideline and protocol adherence in emergency care: a systematic review. BMJ Open, 8(11), e017572. doi:10.1136/bmjopen-2017-017572Innes, G. D., Sivilotti, M. L. A., Ovens, H., McLelland, K., Dukelow, A., Kwok, E., … Chochinov, A. (2018). Emergency overcrowding and access block: A smaller problem than we think. CJEM, 21(2), 177-185. doi:10.1017/cem.2018.446Di Somma, S., Paladino, L., Vaughan, L., Lalle, I., Magrini, L., & Magnanti, M. (2014). Overcrowding in emergency department: an international issue. Internal and Emergency Medicine, 10(2), 171-175. doi:10.1007/s11739-014-1154-8Uthman, O. A., Walker, C., Lahiri, S., Jenkinson, D., Adekanmbi, V., Robertson, W., & Clarke, A. (2018). General practitioners providing non-urgent care in emergency department: a natural experiment. BMJ Open, 8(5), e019736. doi:10.1136/bmjopen-2017-019736Razzak, J. A., Baqir, S. M., Khan, U. R., Heller, D., Bhatti, J., & Hyder, A. A. (2013). Emergency and trauma care in Pakistan: a cross-sectional study of healthcare levels. Emergency Medicine Journal, 32(3), 207-213. doi:10.1136/emermed-2013-202590Dart, R. C., Goldfrank, L. R., Erstad, B. L., Huang, D. T., Todd, K. H., Weitz, J., … Anderson, V. E. (2018). Expert Consensus Guidelines for Stocking of Antidotes in Hospitals That Provide Emergency Care. Annals of Emergency Medicine, 71(3), 314-325.e1. doi:10.1016/j.annemergmed.2017.05.021Mkoka, D. A., Goicolea, I., Kiwara, A., Mwangu, M., & Hurtig, A.-K. (2014). Availability of drugs and medical supplies for emergency obstetric care: experience of health facility managers in a rural District of Tanzania. BMC Pregnancy and Childbirth, 14(1). doi:10.1186/1471-2393-14-108Beck, M. J., Okerblom, D., Kumar, A., Bandyopadhyay, S., & Scalzi, L. V. (2016). Lean intervention improves patient discharge times, improves emergency department throughput and reduces congestion. Hospital Practice, 44(5), 252-259. doi:10.1080/21548331.2016.1254559Morais Oliveira, M., Marti, C., Ramlawi, M., Sarasin, F. P., Grosgurin, O., Poletti, P.-A., … Rutschmann, O. T. (2018). Impact of a patient-flow physician coordinator on waiting times and length of stay in an emergency department: A before-after cohort study. PLOS ONE, 13(12), e0209035. doi:10.1371/journal.pone.0209035Vermeulen, M. J., Stukel, T. A., Boozary, A. S., Guttmann, A., & Schull, M. J. (2016). The Effect of Pay for Performance in the Emergency Department on Patient Waiting Times and Quality of Care in Ontario, Canada: A Difference-in-Differences Analysis. Annals of Emergency Medicine, 67(4), 496-505.e7. doi:10.1016/j.annemergmed.2015.06.028Singh, S., Lin, Y.-L., Nattinger, A. B., Kuo, Y.-F., & Goodwin, J. S. (2015). Variation in readmission rates by emergency departments and emergency department providers caring for patients after discharge. Journal of Hospital Medicine, 10(11), 705-710. doi:10.1002/jhm.2407Källberg, A.-S., Göransson, K. E., Florin, J., Östergren, J., Brixey, J. J., & Ehrenberg, A. (2015). Contributing factors to errors in Swedish emergency departments. International Emergency Nursing, 23(2), 156-161. doi:10.1016/j.ienj.2014.10.002Riga, M., Vozikis, A., Pollalis, Y., & Souliotis, K. (2015). MERIS (Medical Error Reporting Information System) as an innovative patient safety intervention: A health policy perspective. Health Policy, 119(4), 539-548. doi:10.1016/j.healthpol.2014.12.006Norman, G. R., Monteiro, S. D., Sherbino, J., Ilgen, J. S., Schmidt, H. G., & Mamede, S. (2017). The Causes of Errors in Clinical Reasoning. Academic Medicine, 92(1), 23-30. doi:10.1097/acm.0000000000001421Lisbon, D., Allin, D., Cleek, C., Roop, L., Brimacombe, M., Downes, C., & Pingleton, S. K. (2014). Improved Knowledge, Attitudes, and Behaviors After Implementation of TeamSTEPPS Training in an Academic Emergency Department. American Journal of Medical Quality, 31(1), 86-90. doi:10.1177/1062860614545123Li, L., Georgiou, A., Vecellio, E., Eigenstetter, A., Toouli, G., Wilson, R., & Westbrook, J. I. (2015). The Effect of Laboratory Testing on Emergency Department Length of Stay: A Multihospital Longitudinal Study Applying a Cross‐classified Random‐effect Modeling Approach. Academic Emergency Medicine, 22(1), 38-46. doi:10.1111/acem.12565Telem, D. A., Yang, J., Altieri, M., Patterson, W., Peoples, B., Chen, H., … Pryor, A. D. (2016). Rates and Risk Factors for Unplanned Emergency Department Utilization and Hospital Readmission Following Bariatric Surgery. Annals of Surgery, 263(5), 956-960. doi:10.1097/sla.0000000000001536Rigobello, M. C. G., Carvalho, R. E. F. L. de, Guerreiro, J. M., Motta, A. P. G., Atila, E., & Gimenes, F. R. E. (2017). The perception of the patient safety climate by professionals of the emergency department. International Emergency Nursing, 33, 1-6. doi:10.1016/j.ienj.2017.03.003Farmer, B. (2016). Patient Safety in the Emergency Department. Emergency Medicine, 48(9), 396-404. doi:10.12788/emed.2016.0052Liu, H.-C., You, J.-X., Zhen, L., & Fan, X.-J. (2014). A novel hybrid multiple criteria decision making model for material selection with target-based criteria. Materials & Design, 60, 380-390. doi:10.1016/j.matdes.2014.03.071Kou, G., Ergu, D., & Shang, J. (2014). Enhancing data consistency in decision matrix: Adapting Hadamard model to mitigate judgment contradiction. European Journal of Operational Research, 236(1), 261-271. doi:10.1016/j.ejor.2013.11.035Keshavarz Ghorabaee, M., Amiri, M., Zavadskas, E. K., & Antucheviciene, J. (2017). Supplier evaluation and selection in fuzzy environments: a review of MADM approaches. Economic Research-Ekonomska Istraživanja, 30(1), 1073-1118. doi:10.1080/1331677x.2017.1314828Barrios, M. A. O., De Felice, F., Negrete, K. P., Romero, B. A., Arenas, A. Y., & Petrillo, A. (2016). An AHP-Topsis Integrated Model for Selecting the Most Appropriate Tomography Equipment. International Journal of Information Technology & Decision Making, 15(04), 861-885. doi:10.1142/s021962201640006xYeh, D.-Y., & Cheng, C.-H. (2016). Performance Management of Taiwan’s National Hospitals. International Journal of Information Technology & Decision Making, 15(01), 187-213. doi:10.1142/s0219622014500199Chen, T.-Y. (2014). An Interactive Signed Distance Approach for Multiple Criteria Group Decision-Making Based on Simple Additive Weighting Method with Incomplete Preference Information Defined by Interval Type-2 Fuzzy Sets. International Journal of Information Technology & Decision Making, 13(05), 979-1012. doi:10.1142/s0219622014500229Gou, X., Xu, Z., & Liao, H. (2019). Hesitant Fuzzy Linguistic Possibility Degree-Based Linear Assignment Method for Multiple Criteria Decision-Making. International Journal of Information Technology & Decision Making, 18(01), 35-63. doi:10.1142/s0219622017500377Saksrisathaporn, K., Bouras, A., Reeveerakul, N., & Charles, A. (2016). Application of a Decision Model by Using an Integration of AHP and TOPSIS Approaches within Humanitarian Operation Life Cycle. International Journal of Information Technology & Decision Making, 15(04), 887-918. doi:10.1142/s0219622015500261Hsiao, B., & Chen, L.-H. (2019). Performance Evaluation for Taiwanese Hospitals by Multi-Activity Network Data Envelopment Analysis. International Journal of Information Technology & Decision Making, 18(03), 1009-1043. doi:10.1142/s0219622018500165Saaty, T. L., & Ergu, D. (2015). When is a Decision-Making Method Trustworthy? Criteria for Evaluating Multi-Criteria Decision-Making Methods. International Journal of Information Technology & Decision Making, 14(06), 1171-1187. doi:10.1142/s021962201550025xChang, K.-H., Chang, Y.-C., & Lee, Y.-T. (2014). Integrating TOPSIS and DEMATEL Methods to Rank the Risk of Failure of FMEA. International Journal of Information Technology & Decision Making, 13(06), 1229-1257. doi:10.1142/s0219622014500758Yeh, T.-M., & Huang, Y.-L. (2014). Factors in determining wind farm location: Integrating GQM, fuzzy DEMATEL, and ANP. Renewable Energy, 66, 159-169. doi:10.1016/j.renene.2013.12.003Ortíz, M. A., Felizzola, H. A., & Isaza, S. N. (2015). A contrast between DEMATEL-ANP an

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

sharma et al. define a new primary atopic disorder caused by heterozygous gain-of-function variants in STAT6. this results in severe, early-onset allergies, and is seen in 16 patients from 10 families. Anti-IL-4R &amp; alpha; antibody and JAK inhibitor treatment were highly effective.STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. we have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. the cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). all patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and T(H)2 skewing. Precision treatment with the anti-IL-4R &amp; alpha; antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. this study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder

Effect of early and current Helicobacter pylori infection on the risk of anaemia in 6.5-year-old Ethiopian children

Background: Epidemiological and clinical studies in high income countries have suggested that Helicobacter pylori (H. pylori) may cause anaemia, but evidence is lacking from low income countries.We examined associations between H. pylori infection in early childhood and anaemia at the age of 6.5 years in an Ethiopian birth cohort. Methods: In 2011/12, 856 children (85.1 % of the 1006 original singletons in a population-based birth cohort) were followed up at age six and half. An interviewer-led questionnaire administered to mothers provided information on demographic and lifestyle variables. Haemoglobin level and red cell indices were examined using an automated haematological analyzer (Cell Dyn 1800, Abbott, USA), and stool samples analyzed for H. pylori antigen. The independent effects of H. pylori infection (measured at age 3.5 and 6.5 years) on anaemia, haemoglobin level, and red cell indices (measured at age 6.5 years) were determined using multiple logistic and linear regression. Results: The prevalence of anemia was 34.8 % (257/739), and the mean (SD) haemoglobin concentration was 11.8 (1.1) gm/dl. Current H. pylori infection at age 6.5 years was positively, though not significantly related to prevalence of anaemia (adjusted OR, 95 % CI, 1.15; 0.69, 1.93, p = 0.59). Any H. pylori infection up to age 6.5 years was significantly associated with an increased risk of anaemia at age 6.5 (adjusted OR, 95 % CI, 1.68; 1.22, 2.32, p = 0.01). A significant reduction in haemoglobin concentration and red cell indices was also observed among children who had any H. pylori infection up to age 6.5 (Hb adjusted β = −0.19, 95 % CI, −0.35 to −0.03, p = 0.01; MCV adjusted β = −2.22, 95 % CI, −3.43 to −1.01, p = 0.01; MCH adjusted β = −0.63, 95 % CI, −1.15 to - 0.12, p = 0.01; and MCHC adjusted β = −0.67, 95 % CI, −1.21 to −0.14, p = 0.01), respectively. Conclusion: This study provides further evidence from a low income country that any H. pylori infection up to age 6.5 is associated with higher prevalence of anaemia, and reduction of haemoglobin level and red cell indices at age 6.5