III/V-on-lithium niobate amplifiers and lasers

We demonstrate electrically pumped, heterogeneously integrated lasers on thin-film lithium niobate, featuring electro-optic wavelength tunability. (C) 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

Occupational Noise, Smoking, and a High Body Mass Index are Risk Factors for Age-related Hearing Impairment and Moderate Alcohol Consumption is Protective: A European Population-based Multicenter Study

A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment

Deafness mutation mining using regular expression based pattern matching

<p>Abstract</p> <p>Background</p> <p>While keyword based queries of databases such as Pubmed are frequently of great utility, the ability to use regular expressions in place of a keyword can often improve the results output by such databases. Regular expressions can allow for the identification of element types that cannot be readily specified by a single keyword and can allow for different words with similar character sequences to be distinguished.</p> <p>Results</p> <p>A Perl based utility was developed to allow the use of regular expressions in Pubmed searches, thereby improving the accuracy of the searches.</p> <p>Conclusion</p> <p>This utility was then utilized to create a comprehensive listing of all DFN deafness mutations discussed in Pubmed records containing the keywords "human ear".</p

Spectrum of Genetic Changes in Patients with Non-Syndromic Hearing Impairment and Extremely High Carrier Frequency of 35delG GJB2 Mutation in Belarus

The genetic nature of sensorineural hearing loss (SNHL) has so far been studied for many ethnic groups in various parts of the world. The single-nucleotide guanine deletion (35delG) of the GJB2 gene coding for connexin 26 was shown to be the main genetic cause of autosomal recessive deafness among Europeans. Here we present the results of the first study of GJB2 and three mitochondrial mutations among two groups of Belarusian inhabitants: native people with normal hearing (757 persons) and 391 young patients with non-syndromic SNHL. We have found an extremely high carrier frequency of 35delG GJB2 mutation in Belarus −5.7%. This point deletion has also been detected in 53% of the patients with SNHL. The 312del14 GJB2 was the second most common mutation in the Belarus patient cohort. Mitochondrial A1555G mt-RNR1 substitution was found in two SNHL patients (0.55%) but none were found in the population cohort. No individuals carried the A7445G mutation of mitochondrial mt-TS1. G7444A as well as T961G substitutions were detected in mitochondrial mt-RNR1 at a rate of about 1% both in the patient and population cohorts. A possible reason for Belarusians having the highest mutation carrier frequency in Europe 35delG is discussed

A cohort of 17 patients with kyphoscoliotic Ehlers-Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history.

PurposeIn 2012 we reported in six individuals a clinical condition almost indistinguishable from PLOD1-kyphoscoliotic Ehlers-Danlos syndrome (PLOD1-kEDS), caused by biallelic mutations in FKBP14, and characterized by progressive kyphoscoliosis, myopathy, and hearing loss in addition to connective tissue abnormalities such as joint hypermobility and hyperelastic skin. FKBP14 is an ER-resident protein belonging to the family of FK506-binding peptidyl-prolyl cis-trans isomerases (PPIases); it catalyzes the folding of type III collagen and interacts with type III, type VI, and type X collagens. Only nine affected individuals have been reported to date.MethodsWe report on a cohort of 17 individuals with FKBP14-kEDS and the follow-up of three previously reported patients, and provide an extensive overview of the disorder and its natural history based on clinical, biochemical, and molecular genetics data.ResultsBased on the frequency of the clinical features of 23 patients from the present and previous cohorts, we define major and minor features of FKBP14-kEDS. We show that myopathy is confirmed by histology and muscle imaging only in some patients, and that hearing impairment is predominantly sensorineural and may not be present in all individuals.ConclusionOur data further support the extensive clinical overlap with PLOD1-kEDS and show that vascular complications are rare manifestations of FKBP14-kEDS

A Discourse Analysis of Pilgrimage Reviews

This paper is the first to provide an account of the discursive features of online consumer reviews of pilgrimage sites. Drawing from pilgrimage studies and narrativity theory in consumer research, we explore how consumers communicate the spiritual and material aspects of pilgrimage experiences by examining a corpus of 833 consumer reviews on TripAdvisor of the most sacred pilgrimage sites of the world’s major five faith groups. Pilgrims include analytical discursive features to communicate the material aspect of their consumption experience. They reserve narration for spiritual transformation and the experience of strong emotions. Moreover, review ratings are only reflective of the spiritual aspect of their consumption experience. As such, our research complements previous studies by highlighting the material, physical aspect of this extraordinary consumption experience

Candidate gene resequencing in a large bicuspid aortic valve-associated thoracic aortic aneurysm cohort: SMAD6 as an important contributor

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6, and MAT2A. Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3) or in syndromic (e.g., TGFBR1/2, TGFB2/3) or non-syndromic (e.g., ACTA2) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort (n = 441; BAV in addition to an aortic root or ascendens diameter = 4.0 cm in adults, or a Z-score = 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation (n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 (p = 0.002), with 2.5% (n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype

Computational Models of HIV-1 Resistance to Gene Therapy Elucidate Therapy Design Principles

Gene therapy is an emerging alternative to conventional anti-HIV-1 drugs, and can potentially control the virus while alleviating major limitations of current approaches. Yet, HIV-1's ability to rapidly acquire mutations and escape therapy presents a critical challenge to any novel treatment paradigm. Viral escape is thus a key consideration in the design of any gene-based technique. We develop a computational model of HIV's evolutionary dynamics in vivo in the presence of a genetic therapy to explore the impact of therapy parameters and strategies on the development of resistance. Our model is generic and captures the properties of a broad class of gene-based agents that inhibit early stages of the viral life cycle. We highlight the differences in viral resistance dynamics between gene and standard antiretroviral therapies, and identify key factors that impact long-term viral suppression. In particular, we underscore the importance of mutationally-induced viral fitness losses in cells that are not genetically modified, as these can severely constrain the replication of resistant virus. We also propose and investigate a novel treatment strategy that leverages upon gene therapy's unique capacity to deliver different genes to distinct cell populations, and we find that such a strategy can dramatically improve efficacy when used judiciously within a certain parametric regime. Finally, we revisit a previously-suggested idea of improving clinical outcomes by boosting the proliferation of the genetically-modified cells, but we find that such an approach has mixed effects on resistance dynamics. Our results provide insights into the short- and long-term effects of gene therapy and the role of its key properties in the evolution of resistance, which can serve as guidelines for the choice and optimization of effective therapeutic agents