Asymmetric Effects of Economic Growth on Carbon Emissions of Developed Countries: Evidence From Nonlinear Panel Autoregressive Distributed Lag Model

This study explores the asymmetric impact of economic growth on carbon emissions in developed countries by utilizing the panel data for the period 1990 to 2019. The current investigation considers the growth of developed countries to be an essential determinant of CO2 emissions. This study is the first of its kind to reveal the asymmetric connections between GDP and CO2 emissions by using the Westerlund panel co-integration and nonlinear panel auto-regressive distributive lag model. The findings support the fact that the impact of economic growth on CO2 emissions is significantly asymmetric. In the long run, positive GDP shocks will increase CO2 emissions in developed economies. Also, the positive shocks to GDP are correlated with CO2 emissions and other variables in a unidirectional way, except for renewable energy. Based on the given results quite a few policy recommendations were proposed in the concluding portion

Asymmetric Effects of Economic Growth on Carbon Emissions of Developed Countries: Evidence From Nonlinear Panel Autoregressive Distributed Lag Model

This study explores the asymmetric impact of economic growth on carbon emissions in developed countries by utilizing the panel data for the period 1990 to 2019. The current investigation considers the growth of developed countries to be an essential determinant of CO2 emissions. This study is the first of its kind to reveal the asymmetric connections between GDP and CO2 emissions by using the Westerlund panel co-integration and nonlinear panel auto-regressive distributive lag model. The findings support the fact that the impact of economic growth on CO2 emissions is significantly asymmetric. In the long run, positive GDP shocks will increase CO2 emissions in developed economies. Also, the positive shocks to GDP are correlated with CO2 emissions and other variables in a unidirectional way, except for renewable energy. Based on the given results quite a few policy recommendations were proposed in the concluding portion

An Agent-based CBIR System for Medical Images

The growing number of image acquisition and storage systems in the digital world demand for the new retrieval methods. Most of the existing retrieval methods use textual information, which has been mainly entered manually for every image in the image collection. In order to access the images of interest, user gives textual input against which images are retrieved from the image collection. Sometimes, this results in garbage retrieval due the human involvement in the image annotation process. So more efficient image retrieval mechanism is needed. To overcome the issue, other approach which is generally considered is content-based image retrieval (CBIR). CBIR depends on the automatically extracted features for every image in the image collection as well as their storage and comparison upon a query. Therefore, feature extraction technique and their storage space are important aspects of CBIR. In this paper, we design and develop agent-based CBIR system for image retrieval and suggest the best feature extraction technique in terms of less storage space and more accurate search results. Although the proposed image retrieval technique can be used for any type image collection, our work focuses on the medical images

Burden of rare variants in synaptic genes in patients with severe tinnitus: An exome based extreme phenotype study

Background: tinnitus is a heterogeneous condition associated with audiological and/or mental disorders. Chronic, severe tinnitus is reported in 1% of the population and it shows a relevant heritability, according to twins, adoptees and familial aggregation studies. The genetic contribution to severe tinnitus is unknown since large genomic studies include individuals with self-reported tinnitus and large heterogeneity in the phenotype. The aim of this study was to identify genes for severe tinnitus in patients with extreme phenotype. Methods: for this extreme phenotype study, we used three different cohorts with European ancestry (Spanish with Meniere disease (MD), Swedes tinnitus and European generalized epilepsy). In addition, four independent control datasets were also used for comparisons. Whole-exome sequencing was performed for the MD and epilepsy cohorts and whole-genome sequencing was carried out in Swedes with tinnitus. Findings: we found an enrichment of rare missense variants in 24 synaptic genes in a Spanish cohort, the most significant being PRUNE2, AKAP9, SORBS1, ITGAX, ANK2, KIF20B and TSC2 (p < 2E 04), when they were compared with reference datasets. This burden was replicated for ANK2 gene in a Swedish cohort with 97 tinnitus individuals, and in a subset of 34 Swedish patients with severe tinnitus for ANK2, AKAP9 and TSC2 genes (p < 2E 02). However, these associations were not significant in a third cohort of 701 generalized epilepsy individuals without tinnitus. Gene ontology (GO) and gene-set enrichment analyses revealed several pathways and biological processes involved in severe tinnitus, including membrane trafficking and cytoskeletal protein binding in neurons. Interpretation: a burden of rare variants in ANK2, AKAP9 and TSC2 is associated with severe tinnitus. ANK2, encodes a cytoskeleton scaffolding protein that coordinates the assembly of several proteins, drives axonal branching and influences connectivity in neurons

Corrigendum:Multidisciplinary Tinnitus Research: Challenges and Future Directions From the Perspective of Early Stage Researchers (Front. Aging Neurosci., (2021), 13, (647285), 10.3389/fnagi.2021.647285)

In the original article, there was an error. For the sentence “NMDA receptor antagonists (AM-101) have been discontinued in phase III for not meeting endpoints (van de Heyning et al., 2014)” there was a typographical error (phase III should have been phase II). In addition, it was brought to our attention that clinical trials for AM-101 are ongoing. A correction has been made to section 6. Treatment Development, Subsection 6.4. Pharmacology-Based Interventions, paragraph 1. The corrected paragraph is below. A wide variety of therapeutic drugs have been used to relieve tinnitus (Elgoyhen and Langguth, 2010). For acute tinnitus, a dose-dependent reduction in tinnitus intensity was observed with intravenous lidocaine (Trellakis et al., 2006). However, its use is controversial due to its short-lasting response, its potentially life threatening arrhythmogenic side effects, and the low bioavailability of its oral form (Israel et al., 1982; Trellakis et al., 2007; Gil-Gouveia and Goadsby, 2009). A potential goal of pharmacologic tinnitus research could be to identify the mechanism by which lidocaine interferes with tinnitus and mimic this effect using a drug with better tolerance that can be orally administered. For chronic tinnitus, the off-label use of medicines like betahistine (Hall et al., 2018d), anticonvulsants (Hoekstra et al., 2011), and glutamate receptor antagonists have shown little or no effect in clinical trials. Prescription of antidepressants and benzodiazepines is limited to tinnitusassociated comorbidities such as depression, insomnia and anxiety (Langguth et al., 2019). Moreover, three clinical research programs, in the last few years, were discontinued in phase II and III. AMPA antagonist selurampanel (BGG492) has not resulted in a new compound (Cederroth et al., 2018). NMDA receptor antagonists (AM-101) did not meet the primary endpoint of improving minimum masking level in acute tinnitus in a phase II clinical trial but showed improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media (van de Heyning et al., 2014). Many other treatments decreasing tinnitus percept or targeting central auditory processing pathways are at a preclinical phase (Schilder et al., 2019). The modulator of voltage-gated potassium channels (Kv3.1) (AUT00063) was not effective in alleviating tinnitus symptoms (Hall et al., 2019b). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

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

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

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

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

Contribución genética al acúfeno crónico en pacientes de enfermedad de Meniere con fenotipo extremo de acúfeno (MD-TEP)

Sana Amanat was supported by H2020 MSCA-ITN-2016–722046 as PhD student in the Biomedicine Program in Universidad de Granada. This study has been funded by European School of Interdisciplinary Tinnitus (ESIT), H2020 MSCA-ITN-2016–722046 (SA and JALE), the H2020- SC1-2019-848261 (JALE), and the GNP-182 GENDER-Net Co-Plus Fund (JALE). The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/DE18/52010002 (JALE).Introduction: Tinnitus is the perception of noise in the absence of an external acoustic stimulation affecting more than15% of adult population. Severe tinnitus is observed in 1% of the general population. The genetic studies conducted in twins, adoptees and families support a significant heritability. Several studies selecting candidate genes have shown no consistent findings and the evidence to support a genetic contribution to tinnitus is weak and emphasis the need to select an appropriate tinnitus phenotype. Objectives: To identify the genes involved in the development and maintenance of severe tinnitus by selecting individuals with extreme phenotype for tinnitus using exome sequencing and gene burden analyses. The identification of potential pathways and biological processes will be carried out by gene ontology and gene-set enrichment analysis. Methods: Exomes of 59 Meniere disease patients with extreme tinnitus and 32 MD patients without severe tinnitus of Spanish ancestry as internal control were sequenced. For replication cohort, 97 Swedish patients with severe tinnitus were sequenced and a third dataset of 701 patients with genetic generalized epilepsy of European ancestry were included. Minor allele frequency of variants was compared with Non-Finnish European and Spanish reference data sets. Gene ontology and gene-set enrichment was performed to identify the pathways and biological processes. Results: We found an enrichment of rare missense variants in 24 synaptic genes in a Spanish cohort, the most significant being PRUNE2, AKAP9, SORBS1, ITGAX, ANK2, KIF20B and TSC2, when they were compared with reference datasets. This burden was replicated for ANK2 gene in a Swedish cohort with 97 tinnitus individual, and in a subset of 34 Swedish patients with severe tinnitus for ANK2, AKAP9 and TSC2 genes. In addition, the hypothesis-free data driven approach, gene burden analyses revealed ADGRV1 gene and also confirmed the excess of missense variants for ANK2 and TSC2 with tinnitus. However, these associations were not significant in the third cohort of 701 genetic generalized epilepsy individuals without tinnitus. Gene ontology (GO) and gene-set enrichment analyses showed several pathways and biological processes involved in severe tinnitus, including membrane trafficking and cytoskeletal protein binding in neurons. Conclusions: In this Thesis, the potential genes and pathways for severe tinnitus have been identified, suggesting the role of synaptic genes and axon initial branching in the development and maintenance of severe tinnitus. These results could be beneficial for future genetic studies of tinnitus.Introducción: El acúfeno es la percepción de ruido en ausencia de una estimulación acústica externa que afecta a más del 15% de la población adulta. El acúfeno severo está presente en el 1% de la población general. Los estudios genéticos realizados en gemelos, adoptados y familias avalan una heredabilidad significativa. Varios estudios que seleccionaron genes candidatos no han mostrado hallazgos consistentes y la evidencia que respalda una contribución genética al acúfeno es débil y enfatiza la necesidad de seleccionar el fenotipo de acúfeno apropiado. Objetivos: Identificar los genes implicados en el desarrollo y mantenimiento del acúfeno severo mediante la selección de individuos con fenotipo extremo para acúfeno mediante secuenciación del exoma y análisis de carga génica. La identificación de posibles vías y procesos biológicos se llevará a cabo mediante análisis de ontología genética y análisis de enriquecimiento de conjuntos de genes. Métodos: Los exomas de 59 pacientes con enfermedad de Meniere (EM) y fenotipo extremo para acúfenos, y 32 pacientes con EM sin acúfeno grave de ascendencia española fueron secuenciados como control interno. Para la cohorte de replicación, se secuenciaron 97 pacientes suecos con acúfeno severo y se reclutó un tercer conjunto de datos de 701 pacientes con epilepsia genética generalizada de ascendencia europea. La frecuencia de alelos menores de las variantes se comparó con conjuntos de datos de referencia españoles y europeos no finlandeses. Se realizó un análisis de ontología genética y un enriquecimiento de conjuntos de genes para identificar las vías y los procesos biológicos. Resultados: Encontramos un enriquecimiento de variantes raras sin sentido en 24 genes sinápticos en la cohorte española, siendo los más significativos PRUNE2, AKAP9, SORBS1, ITGAX, ANK2, KIF20B y TSC2, cuando se compararon con conjuntos de datos de referencia. Esta carga se replicó para el gen ANK2 en la cohorte sueca con 97 individuos con acúfeno y en un subconjunto de 34 pacientes suecos con acúfeno severo para los genes ANK2, AKAP9 y TSC2. Además, en el enfoque basado en datos sin hipótesis, los análisis de carga genética revelaron el gen ADGRV1 y también confirmaron el exceso de variantes sin sentido para ANK2 y TSC2 en pacientes con acúfeno. Sin embargo, estas asociaciones no fueron significativas en la tercera cohorte de 701 individuos con epilepsia generalizada sin acúfeno. La ontología genética (GO) y los análisis de enriquecimiento de conjuntos de genes mostraron varias vías y procesos biológicos involucrados en el acúfeno severo, incluido el transporte a través de membranas y la unión de proteínas del citoesqueleto en las neuronas. Conclusiones: En esta tesis, se han identificado los genes y las potenciales vías del acúfeno severo, lo cual sugiere que los genes sinápticos y la ramificación inicial del axón juegan un importante papel en el desarrollo y mantenimiento del acúfeno severo. Estos resultados podrían ser beneficiosos para futuros estudios genéticos del acúfeno.Tesis Univ. Granada.H2020 MSCA-ITN-2016–722046European School of Interdisciplinary Tinnitus (ESIT), H2020 MSCA-ITN-2016–722046 (SA and JALE)H2020- SC1-2019-848261 (JALE)GNP-182 GENDER-Net Co-Plus Fund (JALE)“la Caixa” Foundation (ID 100010434), under agreement LCF/PR/DE18/52010002 (JALE

A Systematic Review of Extreme Phenotype Strategies to Search for Rare Variants in Genetic Studies of Complex Disorders

Exome sequencing has been commonly used to characterize rare diseases by selecting multiplex families or singletons with an extreme phenotype (EP) and searching for rare variants in coding regions. The EP strategy covers both extreme ends of a disease spectrum and it has been also used to investigate the contribution of rare variants to the heritability of complex clinical traits. We conducted a systematic review to find evidence supporting the use of EP strategies in the search for rare variants in genetic studies of complex diseases and highlight the contribution of rare variations to the genetic structure of polygenic conditions. After assessing the quality of the retrieved records, we selected 19 genetic studies considering EPs to demonstrate genetic association. All studies successfully identified several rare or de novo variants, and many novel candidate genes were also identified by selecting an EP. There is enough evidence to support that the EP approach for patients with an early onset of a disease can contribute to the identification of rare variants in candidate genes or pathways involved in complex diseases. EP patients may contribute to a better understanding of the underlying genetic architecture of common heterogeneous disorders such as tinnitus or age-related hearing loss.H2020 MSCA-ITN-2016-722046La Caixa Foundation 100010434 LCF/PR/DE18/5201000

Video Retrieval System for Meniscal Surgery to Improve Health Care Services

Meniscal surgery is considered the most general orthopedic process that deals with the treatment of meniscus tears for human health care. It leads to a communal contusion to the cartilage that stabilizes and cushions the knee joints of human beings. Such tears can be classified into different categories based on age group, region, and occupation. Further, a large number of sportsmen and heavy weightlifters even in developed countries are affected by meniscus injuries. These patients are subjected to arthroscopic surgery, and during surgical treatment, the perseverance of meniscus is a very crucial task. Current research provides a significant ratio of meniscal tear patients around the globe, the critical expanse is considered as having strikingly risen with a mean annual of 0.066% due to surgery failure. To decumbent this ratio, an innovative training mechanism is proposed through video retrieval system in this research. This research work is focussed on developing a corpus and video retrieval system for meniscus surgery. Using the proposed system, surgeons can access guidance by watching the videos of surgeries performed by an expert and their seniors. The proposed system is comprised of four approaches to the spatiotemporal methodology to improve health care services. It entails key point, statistical modeling, PCA-scale invariant feature transform (SIFT), and PCA-Gaussian mixture model (GMM) with a combination of sparse-optical flow. The real meniscal surgery dataset is used for testing purposes and evaluation. The results conclude that using PCA-SIFT approach improves the results with an average precision of 0.78