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Item does not contain fulltext, In this study, we investigated the association of ACAN variants with otosclerosis, a frequent cause of hearing loss among young adults. We sequenced the coding, 5'-UTR and 3'-UTR regions of ACAN in 1497 unrelated otosclerosis cases and 1437 matched controls from six different subpopulations. The association between variants in ACAN and the disease risk was tested through single variant and gene-based association tests. After correction for multiple testing, 14 variants were significantly associated with otosclerosis, ten of which represented independent association signals. Eight variants showed a consistent association across all subpopulations. Allelic odds ratios of the variants identified four predisposing and ten protective variants. Gene-based tests showed an association of very rare variants in the 3'-UTR with the phenotype. The associated exonic variants are all located in the CS domain of ACAN and include both protective and predisposing variants with a broad spectrum of effect sizes and population frequencies. This includes variants with strong effect size and low frequency, typical for monogenic diseases, to low effect size variants with high frequency, characteristic for common complex traits. This single-gene allelic spectrum with both protective and predisposing alleles is unique in the field of complex diseases. In conclusion, these findings are a significant advancement to the understanding of the etiology of otosclerosis.

Item does not contain fulltext, In this study, we investigated the association of ACAN variants with otosclerosis, a frequent cause of hearing loss among young adults. We sequenced the coding, 5'-UTR and 3'-UTR regions of ACAN in 1497 unrelated otosclerosis cases and 1437 matched controls from six different subpopulations. The association between variants in ACAN and the disease risk was tested through single variant and gene-based association tests. After correction for multiple testing, 14 variants were significantly associated with otosclerosis, ten of which represented independent association signals. Eight variants showed a consistent association across all subpopulations. Allelic odds ratios of the variants identified four predisposing and ten protective variants. Gene-based tests showed an association of very rare variants in the 3'-UTR with the phenotype. The associated exonic variants are all located in the CS domain of ACAN and include both protective and predisposing variants with a broad spectrum of effect sizes and population frequencies. This includes variants with strong effect size and low frequency, typical for monogenic diseases, to low effect size variants with high frequency, characteristic for common complex traits. This single-gene allelic spectrum with both protective and predisposing alleles is unique in the field of complex diseases. In conclusion, these findings are a significant advancement to the understanding of the etiology of otosclerosis.

Due to be launched in late 2021, the Imaging X-Ray Polarimetry Explorer (IXPE) is a NASA Small Explorer mission designed to perform polarization measurements in the 2-8 keV band, complemented with imaging, spectroscopy and timing capabilities. At the heart of the focal plane is a set of three polarization-sensitive Gas Pixel Detectors (GPD), each based on a custom ASIC acting as a charge-collecting anode. In this paper we shall review the design, manufacturing, and test of the IXPE focal-plane detectors, with particular emphasis on the connection between the science drivers, the performance metrics and the operational aspects. We shall present a thorough characterization of the GPDs in terms of effective noise, trigger efficiency, dead time, uniformity of response, and spectral and polarimetric performance. In addition, we shall discuss in detail a number of instrumental effects that are relevant for high-level science analysis -- particularly as far as the response to unpolarized radiation and the stability in time are concerned., Comment: To be published in Astroparticle Physics

Due to be launched in late 2021, the Imaging X-Ray Polarimetry Explorer (IXPE) is a NASA Small Explorer mission designed to perform polarization measurements in the 2-8 keV band, complemented with imaging, spectroscopy and timing capabilities. At the heart of the focal plane is a set of three polarization-sensitive Gas Pixel Detectors (GPD), each based on a custom ASIC acting as a charge-collecting anode. In this paper we shall review the design, manufacturing, and test of the IXPE focal-plane detectors, with particular emphasis on the connection between the science drivers, the performance metrics and the operational aspects. We shall present a thorough characterization of the GPDs in terms of effective noise, trigger efficiency, dead time, uniformity of response, and spectral and polarimetric performance. In addition, we shall discuss in detail a number of instrumental effects that are relevant for high-level science analysis -- particularly as far as the response to unpolarized radiation and the stability in time are concerned., Comment: To be published in Astroparticle Physics

Purpose Aims of this research were (a) to investigate higher order linguistic and cognitive skills of Italian children with cochlear implants (CIs); (b) to correlate them with the comprehension of irony, which has never been systematically studied in this population; and (c) to identify the factors that facilitate the development of this competence. Method We tested 28 Italian children with CI (mean chronological age = 101 [SD = 25.60] months, age range: 60–144 months), and two control groups of normal-hearing (NH) peers matched for chronological age and for hearing age, on a series of tests assessing their cognitive abilities (nonverbal intelligence and theory of mind), linguistic skills (morphosyntax and prosody recognition), and irony comprehension. Results Despite having grammatical abilities in line with the group of NH children matched for hearing age, children with CI lag behind both groups of NH peers on the recognition of emotions through prosody and on the comprehension of ironic stories, even if these two abilities were not related. Conclusions This is the first study that targeted irony comprehension in children with CI, and we found that this competence, which is crucial for maintaining good social relationships with peers, is impaired in this population. In line with other studies, we found a correlation between this ability and advanced theory of mind skills, but at the same time, a deeper investigation is needed, to account for the high variability of performance in children with CI.

Disregarding the widely used division of skull base into anterior and lateral, since the skull base should be conceived as a single anatomic structure, it was to our convenience to group all those approaches that run from the antero-lateral, pure lateral and postero-lateral side of the skull base as “Surgery of the lateral skull base”. “50 years of endeavour” points to the great effort which has been made over the last decades, when more and more difficult surgeries were performed by reducing morbidity. The principle of lateral skull base surgery, “remove skull base bone to approach the base itself and the adjacent sites of the endo-esocranium”, was then combined with function preservation and with tailoring surgery to the pathology. The concept that histology dictates the extent of resection, balancing the intrinsic morbidity of each approach was the object of the first section of the present report. The main surgical approaches were described in the second section and were conceived not as a step-by-step description of technique, but as the highlighthening of the surgical principles. The third section was centered on open issues related to the tumor and its treatment. The topic of vestibular schwannoma was investigated with the current debate on observation, hearing preservation surgery, hearing rehabilitation, radiotherapy and the recent efforts to detect biological markers able to predict tumor growth. Jugular foramen paragangliomas were treated in the frame of radical or partial surgery, radiotherapy, partial “tailored” surgery and observation. Surgery on meningioma was debated from the point of view of the neurosurgeon and of the otologist. Endolymphatic sac tumors and malignant tumors of the external auditory canal were also treated, as well as chordomas, chondrosarcomas and petrous bone cholesteatomas. Finally, the fourth section focused on free-choice topics which were assigned to aknowledged experts. The aim of this work was attempting to report the sta

Disregarding the widely used division of skull base into anterior and lateral, since the skull base should be conceived as a single anatomic structure, it was to our convenience to group all those approaches that run from the antero-lateral, pure lateral and postero-lateral side of the skull base as “Surgery of the lateral skull base”. “50 years of endeavour” points to the great effort which has been made over the last decades, when more and more difficult surgeries were performed by reducing morbidity. The principle of lateral skull base surgery, “remove skull base bone to approach the base itself and the adjacent sites of the endo-esocranium”, was then combined with function preservation and with tailoring surgery to the pathology. The concept that histology dictates the extent of resection, balancing the intrinsic morbidity of each approach was the object of the first section of the present report. The main surgical approaches were described in the second section and were conceived not as a step-by-step description of technique, but as the highlighthening of the surgical principles. The third section was centered on open issues related to the tumor and its treatment. The topic of vestibular schwannoma was investigated with the current debate on observation, hearing preservation surgery, hearing rehabilitation, radiotherapy and the recent efforts to detect biological markers able to predict tumor growth. Jugular foramen paragangliomas were treated in the frame of radical or partial surgery, radiotherapy, partial “tailored” surgery and observation. Surgery on meningioma was debated from the point of view of the neurosurgeon and of the otologist. Endolymphatic sac tumors and malignant tumors of the external auditory canal were also treated, as well as chordomas, chondrosarcomas and petrous bone cholesteatomas. Finally, the fourth section focused on free-choice topics which were assigned to aknowledged experts. The aim of this work was attempting to report the sta

Purpose: Ménière disease (MD) is a multifactorial chronic disabling condition characterized by episodic vertigo, ear fullness, and hearing loss. MD patients often complain of aspecific gastrointestinal symptoms associated with autonomic dysregulation, frequently outweighed by the otological manifestations. Dietary modifications have been reported to improve the typical MD symptoms in some cases. Our purpose was to test the urinary levels of lactulose and mannitol (double sugar test) and the fecal calprotectin, both markers of altered intestinal permeability, in subjects with definite MD in an active and inactive stage. Materials and methods: Twenty-six with definite unilateral MD were studied: 14 patients were symptomatic for at least 3 months with moderate to severe vertigo spells and a functional level ≥ 4; 12 patients had been asymptomatic (no vertigo spells) for at least 3 months and had a functional level = 1 at the time of testing. Twenty healthy volunteers were recruited as “control group”. Results: Lactulose and mannitol absorption was significantly increased in the symptomatic M patients compared to the asymptomatic group (p < 0.02 and p < 0.004, respectively) and to the controls. FC were also higher than normal only in the symptomatic group. (p < 0.01). Conclusions: An altered intestinal permeability, according to the two assays, was found only in symptomatic MD patients. The rationale for a possible relationship between MD and intestinal permeability is forwarded. The double-sugar test and FC quantification might be implemented in the MD diagnostic workup

BACKGROUND: The efficacy of intratympanic steroid (ITS) treatment in sudden deafness (SD) remains controversial. To shed light on this issue, we performed a systematic review of randomized controlled trials to assess the overall efficacy of ITS therapy and to clarify whether it is more suitable as a first-line approach (primary treatment) or as a salvage treatment when traditional systemic agents have failed. METHODS: An electronic database search (MEDLINE and PubMed) was performed with the objective of identifying all studies published in the English language between January 1980 and November 2011 on the efficacy of ITS in the treatment of SD. All relevant articles were retrieved, and the related reference lists were reviewed systematically to identify other reports that could be included. Data were synthesized using the Mantel-Haenszel model. Results are expressed as odds ratio (OR) with 95% confidence interval (CI). RESULTS: A total of 11 randomized studies including 472 subjects allocated to ITS and 453 controls were selected. Intratympanic steroid regimens used and treatments administered to controls varied widely across studies. When considering together trials investigating ITS therapy as a primary (n = 4) or salvage (n = 7) treatment, the common OR for recovery was 1.7 (95% CI, 1.3-2.3). When considering them separately, the common ORs for recovery were 0.9 (95% CI, 0.7-1.6) for primary and 2.9 (95% CI, 1.9-4.5) for salvage therapy. CONCLUSION: Intratympanic steroid therapy seems to confer a certain degree of benefit as a salvage but not as a primary treatment of SD. However, further evidence is needed to clarify some yet uncertain aspects, such as the optimal protocol of therapy.

Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65-85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition.