The development of the spiral ganglion in the human foetus

The development of the spiral ganglion was studied in steps sections of 81 human temporal bones. By the 8th week, the spiral ganglion has already separated from the vestibular ganglion. At 13 weeks two distinct populations are observed that correspond to neuron and Schwann cells. At 15 weeks the spiral ganglion has increased its distance from the cochlear duct and is surrounded by mesenchyme near the scala tympani. At 14 weeks a gradual decrease in the nucleus-to-cell area ratio was observed in spiral ganglion neurons that may reflect a morphological adaptation to function. By the 23rd week the modiolus begins to ossify and the spiral ganglion is surrounded by bony trabeculae. The time course of spiral ganglion development follows that of the stria vascularis and organ of Corti, although maturation changes are still observed in the neuronal population even beyond 20 weeks

Relationships between hearing loss and hearing aid usage in real world

Many hearing aids are fitted with multiple programs that the user can choose between in different situations. In the H2020 EVOTION project hundreds of hearing aid users were fitted according to their audiogram with Oticon VAC rationale with four adaptive programs that differed in the noise management profile. The programs differed on how much the noise was attenuated and the threshold at which the device started to remove noise. The hearing aids also transmitted continuous data about the sound environment and the operation of the hearing aid to a dedicated app on a smartphone. The participants had a wide range of hearing losses and was recruited from amongst new and experienced hearing aid users in six different clinics in UK, Greece, and Denmark. The data from the hearing aid users was collected for up to a year to investigate relationships between clinical factors and usage patterns. The data enables a detailed investigation of the complexity of sound environments throughout the day, relation between complexity as function of time to the clinical factors including and beyond the audiogram

Clinical validation of a public health policy-making platform for hearing loss (EVOTION): protocol for a big data study

INTRODUCTION: The holistic management of hearing loss (HL) requires an understanding of factors that predict hearing aid (HA) use and benefit beyond the acoustics of listening environments. Although several predictors have been identified, no study has explored the role of audiological, cognitive, behavioural and physiological data nor has any study collected real-time HA data. This study will collect ‘big data’, including retrospective HA logging data, prospective clinical data and real-time data via smart HAs, a mobile application and biosensors. The main objective is to enable the validation of the EVOTION platform as a public health policy-making tool for HL. METHODS AND ANALYSIS: This will be a big data international multicentre study consisting of retrospective and prospective data collection. Existing data from approximately 35 000 HA users will be extracted from clinical repositories in the UK and Denmark. For the prospective data collection, 1260 HA candidates will be recruited across four clinics in the UK and Greece. Participants will complete a battery of audiological and other assessments (measures of patient-reported HA benefit, mood, cognition, quality of life). Patients will be offered smart HAs and a mobile phone application and a subset will also be given wearable biosensors, to enable the collection of dynamic real-life HA usage data. Big data analytics will be used to detect correlations between contextualised HA usage and effectiveness, and different factors and comorbidities affecting HL, with a view to informing public health decision-making. ETHICS AND DISSEMINATION: Ethical approval was received from the London South East Research Ethics Committee (17/LO/0789), the Hippokrateion Hospital Ethics Committee (1847) and the Athens Medical Center’s Ethics Committee (KM140670). Results will be disseminated through national and international events in Greece and the UK, scientific journals, newsletters, magazines and social media. Target audiences include HA users, clinicians, policy-makers and the general public. TRIAL REGISTRATION NUMBER: NCT03316287; Pre-results

Macroeconomic drivers of baseline scenarios in dynamic CGE models: review and guidelines proposal

For dynamic computable general equilibrium (CGE) modeling, long-term baseline construction is key and depends on the applied methods and the sources of projections considered. For dynamic CGE models, baseline assumptions and base data are both important determinants of results. This paper reviews the assumptions made by 24 modeling teams on baseline macroeconomic drivers, understood as factor accumulation and gross domestic product (GDP) growth. We critically review the various methods, identifying state-of-the-art practices and propose simple guidelines, particularly focusing on consistency between data sources and models, which is intended to help dynamic CGE modelers build their own baselines

The supine moving apprehension test—Reliability and validity among healthy individuals and patients with anterior shoulder instability

Background: Performance-based tests for patients with anterior shoulder dislocation are lacking. This study determined the reliability and validity of the supine moving apprehension test designed to assess the ability to control anterior instability loads. Methods: Thirty-six participants were recruited (18 healthy individuals, and 18 patients following anterior shoulder dislocation). Healthy participants performed the supine moving apprehension test on 2 separate occasions to determine test-retest reliability. Patients completed the supine moving apprehension test and the Western Ontario Shoulder Instability index before and 6 months after surgical stabilization of their shoulder. The presence of anterior apprehension was also documented post-operatively. Results: The supine moving apprehension test demonstrated good test-retest reliability (intraclass correlation coefficient =0.74−0.84). Patients performed 18−30 repetitions less than healthy individuals during the supine moving apprehension test (P \u3c 0.01). A strong correlation was found between supine moving apprehension test scores and Western Ontario Shoulder Instability post-operatively (r=−0.74, P ≤ 0.01). Supine moving apprehension test scores significantly improved among patients following surgery (P \u3c 0.01). Patients with a negative apprehension test post-operatively performed the supine moving apprehension test significantly better than patients with a positive apprehension test (P \u3c 0.01). Conclusions: The supine moving apprehension test is reliable and valid among patients with anterior shoulder dislocation and may serve to assess patients’ ability to control shoulder anterior instability loads

Mining balance disorders' data for the development of diagnostic decision support systems

In this work we present the methodology for the development of the EMBalance diagnostic Decision Support System (DSS) for balance disorders. Medical data from patients with balance disorders have been analysed using data mining techniques for the development of the diagnostic DSS. The proposed methodology uses various data, ranging from demographic characteristics to clinical examination, auditory and vestibular tests, in order to provide an accurate diagnosis. The system aims to provide decision support for general practitioners (GPs) and experts in the diagnosis of balance disorders as well as to provide recommendations for the appropriate information and data to be requested at each step of the diagnostic process. Detailed results are provided for the diagnosis of 12 balance disorders, both for GPs and experts. Overall, the reported accuracy ranges from 59.3 to 89.8% for GPs and from 74.3 to 92.1% for experts

Diagnostic accuracy and usability of the EMBalance decision support system for vestibular disorders in primary care: proof of concept randomised controlled study results

BACKGROUND: Dizziness and imbalance are common symptoms that are often inadequately diagnosed or managed, due to a lack of dedicated specialists. Decision Support Systems (DSS) may support first-line physicians to diagnose and manage these patients based on personalised data. AIM: To examine the diagnostic accuracy and application of the EMBalance DSS for diagnosis and management of common vestibular disorders in primary care. METHODS: Patients with persistent dizziness were recruited from primary care in Germany, Greece, Belgium and the UK and randomised to primary care clinicians assessing the patients with (+ DSS) versus assessment without (- DSS) the EMBalance DSS. Subsequently, specialists in neuro-otology/audiovestibular medicine performed clinical evaluation of each patient in a blinded way to provide the "gold standard" against which the + DSS, - DSS and the DSS as a standalone tool (i.e. without the final decision made by the clinician) were validated. RESULTS: One hundred ninety-four participants (age range 25-85, mean = 57.7, SD = 16.7 years) were assigned to the + DSS (N = 100) and to the - DSS group (N = 94). The diagnosis suggested by the + DSS primary care physician agreed with the expert diagnosis in 54%, compared to 41.5% of cases in the - DSS group (odds ratio 1.35). Similar positive trends were observed for management and further referral in the + DSS vs. the - DSS group. The standalone DSS had better diagnostic and management accuracy than the + DSS group. CONCLUSION: There were trends for improved vestibular diagnosis and management when using the EMBalance DSS. The tool requires further development to improve its diagnostic accuracy, but holds promise for timely and effective diagnosis and management of dizzy patients in primary care. TRIAL REGISTRATION NUMBER: NCT02704819 (clinicaltrials.gov)

EMBalance - validation of a decision support system in the early diagnostic evaluation and management plan formulation of balance disorders in primary care: study protocol of a feasibility randomised controlled trial

BACKGROUND: Balance problems are caused by multiple factors and often lead to falls and related fractures, bringing large socio-economic costs. The complexity of balance control mechanisms, the lack of medical expertise, and the absence of specialised equipment contribute to the delayed or incorrect diagnosis and management ofthese patients. Advances in computer science have allowed the development of computer systems that support clinical diagnosis and treatment decisions based on individualised patient data. The aim of the EMBalance decision support system (DSS) is to support doctors facing this clinical challenge, to make a definitive diagnosis and implement an effective management plan. The EMBalance study will determine the accuracy of this supportive tool when used by non-specialist doctors. This study is funded by the European Union's Seventh Framework Programme. METHODS/DESIGN: EMBalance is a proof-of-concept study designed as a non-commercial, international, multi-centre, single-blind, parallel-group randomised controlled trial to be carried out at four clinical sites in the United Kingdom, Germany, Greece and Belgium. The study is comprised of three stages: internal pilot, phase I (diagnosis) and stage II (management). For this purpose, 200 patients presenting with persistent dizziness (>3 months’ duration) to primary care services will be randomised to either the intervention group (diagnostic assessment with the DSS) or a control group (diagnostic assessment without the DSS). Patients allocated to the intervention group will be assessed by a doctor with the support of the EMBalance DSS, while patients allocated to the control group will receive a visit as per standard practice. Ultimately, all patients’ diagnoses and management plans will be certified by a consultant in neuro-otology. DISCUSSION: EMBalance is the first trial to test the accuracy of a DSS in both the diagnosis of and the management plan for vestibular disorders across the healthcare systems of four different countries. The EMBalance study is the result of a combined effort of engineers and physicians to develop an accurate tool to support non-specialist doctors, with no risk for the patient. This trial will provide reliable information about the benefits of implementing DSSs in primary care while supporting the feasibility of testing the EMBalance algorithms in further research. TRIAL REGISTRATION: ClinicalTrials.gov NCT02704819. Registered 29 February 2016

The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients

BACKGROUND/OBJECTIVES: A dysregulated inflammatory profile plays an important role in coronavirus disease-2019 (COVID-19) pathogenesis. Moreover, the depletion of lymphocytes is typically associated with an unfavourable disease course. We studied the role and impact of p53 and deacetylase Sirtuin 1 (SIRT1) on lymph-monocyte homeostasis and their possible effect on T and B cell signalling. METHODS: Gene expression analysis and flow cytometry were performed on peripheral blood mononuclear cells (PBMC) of 35 COVID-19 patients and 10 healthy donors (HD). Inflammatory cytokines, the frequency of Annexin+ cells among CD3+ T cells and CD19+ B cell subsets were quantified. RESULTS: PBMC from COVID-19 patients had a higher p53 expression, and higher concentrations of plasma proinflammatory cytokines (IL1β, TNF-α, IL8, and IL6) than HD. Deacetylase Sirtuin 1 (SIRT1) expression was significantly decreased in COVID-19 patients and was negatively correlated with p53 (p = 0.003 and r = -0.48). A lower expression of IL-7R and B Cell linker (BLNK), key genes for lymphocyte homeostasis and function, was observed in COVID-19 than in HD. The reduction of IgK and IgL chains was seen in lymphopenic COVID-19 patients. A significant increase in both apoptotic B and T cells were observed. Inflammatory cytokines correlated positively with p53 (IL-1β: r = 0.5 and p = 0.05; IL-8: r = 0.5 and p = 0.05) and negatively with SIRT1 (IL1-β: r = -0.5 and p = 0.04; TNF-α: r = -0.4 and p = 0.04). CONCLUSIONS: Collectively, our data indicate that the inflammatory environment, the dysregulated p53/SIRT1 axis and low expression of IL7R and BLNK may impact cell survival, B cell signalling and antibody production in COVID-19 patients. Further studies are required to define the functional impact of low BLNK/IL7R expression during severe acute respiratory syndrome coronavirus-2 infection