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      Multidisciplinary Tinnitus Research: Challenges and Future Directions From the Perspective of Early Stage Researchers

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          Abstract

          Tinnitus can be a burdensome condition on both individual and societal levels. Many aspects of this condition remain elusive, including its underlying mechanisms, ultimately hindering the development of a cure. Interdisciplinary approaches are required to overcome long-established research challenges. This review summarizes current knowledge in various tinnitus-relevant research fields including tinnitus generating mechanisms, heterogeneity, epidemiology, assessment, and treatment development, in an effort to highlight the main challenges and provide suggestions for future research to overcome them. Four common themes across different areas were identified as future research direction: (1) Further establishment of multicenter and multidisciplinary collaborations; (2) Systematic reviews and syntheses of existing knowledge; (3) Standardization of research methods including tinnitus assessment, data acquisition, and data analysis protocols; (4) The design of studies with large sample sizes and the creation of large tinnitus-specific databases that would allow in-depth exploration of tinnitus heterogeneity.

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          The hospital anxiety and depression scale.

          A self-assessment scale has been developed and found to be a reliable instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The anxiety and depressive subscales are also valid measures of severity of the emotional disorder. It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.
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            The UK Biobank resource with deep phenotyping and genomic data

            The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
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              Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L)

              Purpose This article introduces the new 5-level EQ-5D (EQ-5D-5L) health status measure. Methods EQ-5D currently measures health using three levels of severity in five dimensions. A EuroQol Group task force was established to find ways of improving the instrument’s sensitivity and reducing ceiling effects by increasing the number of severity levels. The study was performed in the United Kingdom and Spain. Severity labels for 5 levels in each dimension were identified using response scaling. Focus groups were used to investigate the face and content validity of the new versions, including hypothetical health states generated from those versions. Results Selecting labels at approximately the 25th, 50th, and 75th centiles produced two alternative 5-level versions. Focus group work showed a slight preference for the wording ‘slight-moderate-severe’ problems, with anchors of ‘no problems’ and ‘unable to do’ in the EQ-5D functional dimensions. Similar wording was used in the Pain/Discomfort and Anxiety/Depression dimensions. Hypothetical health states were well understood though participants stressed the need for the internal coherence of health states. Conclusions A 5-level version of the EQ-5D has been developed by the EuroQol Group. Further testing is required to determine whether the new version improves sensitivity and reduces ceiling effects.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                11 June 2021
                2021
                : 13
                : 647285
                Affiliations
                [1] 1Department of Psychiatry and Psychotherapy, University of Regensburg , Regensburg, Germany
                [2] 2Centre National de la Recherche Scientifique, Aix-Marseille University , Marseille, France
                [3] 3Hearing Sciences, Mental Health and Clinical Neurosciences, School of Medicine, University of Nottingham , Nottingham, United Kingdom
                [4] 4Otology & Neurotology Group CTS 495, Department of Genomic Medicine, GENYO - Centre for Genomics and Oncological Research Pfizer/University of Granada/Junta de Andalucía, PTS , Granada, Spain
                [5] 5Department of Otorhinolaryngology and Head & Neck Surgery, University Medical Center Utrecht , Utrecht, Netherlands
                [6] 6Department of Clinical and Experimental Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University , Utrecht, Netherlands
                [7] 7Cochlear Technology Centre , Mechelen, Belgium
                [8] 8Laboratory of Lifestyle Epidemiology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS , Milan, Italy
                [9] 9Hearing Systems, Department of Health Technology, Technical University of Denmark , Lyngby, Denmark
                [10] 10Oticon A/S , Smoerum, Denmark
                [11] 11Interacoustics Research Unit , Lyngby, Denmark
                [12] 12Institute of Databases and Information Systems, Ulm University , Ulm, Germany
                [13] 13Department of Otorhinolaryngology Head and Neck Surgery, Antwerp University Hospital , Edegem, Belgium
                [14] 14Department of Translational Neurosciences, Faculty of Medicine and Health Sciences, Antwerp University , Wilrijk, Belgium
                [15] 15WS Audiology , Lynge, Denmark
                [16] 16Ear Institute, University College London , London, United Kingdom
                [17] 17University of Zurich , Zurich, Switzerland
                [18] 18Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich , Zurich, Switzerland
                [19] 19Experimental Health Psychology, Faculty of Psychology and Neuroscience, Maastricht University , Maastricht, Netherlands
                [20] 20Health Psychology Research Group, Faculty of Psychology and Educational Sciences, University of Leuven , Leuven, Belgium
                [21] 21Department of Otorhinolaryngology, Head and Neck Surgery, University of Groningen, University Medical Center Groningen , Groningen, Netherlands
                [22] 22Graduate School of Medical Sciences (Research School of Behavioral and Cognitive Neurosciences), University of Groningen , Groningen, Netherlands
                [23] 23Institute of Distributed Systems, Ulm University , Ulm, Germany
                [24] 24Radiological Sciences, Mental Health and Clinical Neurosciences, School of Medicine, University of Nottingham , Nottingham, United Kingdom
                [25] 25Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham , Nottingham, United Kingdom
                [26] 26Chair of Neuropsychology, Department of Psychology, University of Zurich , Zurich, Switzerland
                [27] 27Department of Physiology and Pharmacology, Experimental Audiology Laboratory, Karolinska Institutet , Stockholm, Sweden
                [28] 28Nottingham Biomedical Research Centre, National Institute for Health Research , Nottingham, United Kingdom
                Author notes

                Edited by: Daniel Ortuño-Sahagún, University of Guadalajara, Mexico

                Reviewed by: Haúla Faruk Haider, CUF Infante Santo Hospital, Portugal; Don J. McFerran, Colchester Hospital University NHS Foundation Trust, United Kingdom

                *Correspondence: Eleni Genitsaridi eleni.genitsaridi@ 123456nottingham.ac.uk
                Jorge Piano Simoes jorge.simoes@ 123456ukr.de

                †These authors have contributed equally to this work and share first and senior authorship

                Article
                10.3389/fnagi.2021.647285
                8225955
                34177549
                ac99cfff-8182-4a60-a111-6ca5f3ff0bf9
                Copyright © 2021 Simoes, Daoud, Shabbir, Amanat, Assouly, Biswas, Casolani, Dode, Enzler, Jacquemin, Joergensen, Kok, Liyanage, Lourenco, Makani, Mehdi, Ramadhani, Riha, Santacruz, Schiller, Schoisswohl, Trpchevska and Genitsaridi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 December 2020
                : 19 March 2021
                Page count
                Figures: 0, Tables: 3, Equations: 0, References: 342, Pages: 24, Words: 23381
                Funding
                Funded by: H2020 Marie Sklodowska-Curie Actions 10.13039/100010665
                Award ID: 722046
                Award ID: 764604
                Award ID: 848261
                Categories
                Neuroscience
                Review

                Neurosciences
                tinnitus,review,heterogeneity,standardization,interdisciplinary collaborations,big data,treatment development

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