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BACKGROUND: Since 2012, the APHAB is part of the quality agreement for statutory insured patients in hearing aid fitting (HAF). So far, individual results could be interpreted by using percentile curves only, but not for the improvement quotient and the cumulated benefit. The presented study should close this gap.âMoreover, it should be clarified if an individual constancy within percentile exists. METHODS: Using the data of 6861 hearing aid fitted patients from a database, we calculated the benefit by improvement quotient and cumulated benefit for different age-classes and percentile-groups and presented by a heatmap.âIndividual constancy of percentile would be calculated using Spearman's rank correlation. RESULTS: The average benefit was 21.41. The average of the improvement quotient was 41.01. It was significantly higher (44.36â%) in subjects younger than the average (27.26 years ± 11.86) than in the elderly (37.66â%). It decreased in cases of lower APHAB-scores before HAF concerning the percentile-group, ranging from 23.22â% to 52.07â%. Spearman's rank coefficient for the APHAB benefit was 0.285, Cohen's effect size was small. The correlation between the APHAB-score before HAF and the cumulated benefit was 0.582 and the improvement quotient was 0.270. CONCLUSIONS: An individual constancy within percentile before and after HAF was not detectable. Nevertheless, some relationships of the improvement quotient and the age resp.âpercentile-groups could be demonstrated. The benefit of HAF was less in older subjects with lower APHAB-scores and best in young subjects with higher APHAB-scores before HAF.
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Auxiliares de Audição , Idoso , Testes Auditivos , Humanos , Inquéritos e QuestionáriosRESUMO
Poly- and perfluoroalkyl substances (PFAS) are contaminants of emerging Arctic concern and are present in the marine environments of the polar regions. Their input to and fate within the marine cryosphere are poorly understood. We conducted a series of laboratory experiments to investigate the uptake, distribution, and release of 10 PFAS of varying carbon chain length (C4-C12) in young sea ice grown from artificial seawater (NaClsolution). We show that PFAS are incorporated into bulk sea ice during ice formation and regression analyses for individual PFAS concentrations in bulk sea ice were linearly related to salinity (r2 = 0.30 to 0.88, n = 18, p < 0.05). This shows that their distribution is strongly governed by the presence and dynamics of brine (high salinity water) within the sea ice. Furthermore, long-chain PFAS (C8-C12), were enriched in bulk ice up to 3-fold more than short-chain PFAS (C4-C7) and NaCl. This suggests that chemical partitioning of PFAS between the different phases of sea ice also plays a role in their uptake during its formation. During sea ice melt, initial meltwater fractions were highly saline and predominantly contained short-chain PFAS, whereas the later, fresher meltwater fractions predominantly contained long-chain PFAS. Our results demonstrate that in highly saline parts of sea ice (near the upper and lower interfaces and in brine channels) significant chemical enrichment (ε) of PFAS can occur with concentrations in brine channels greatly exceeding those in seawater from which it forms (e.g., for PFOA, εbrine = 10 ± 4). This observation has implications for biological exposure to PFAS present in brine channels, a common feature of first-year sea ice which is the dominant ice type in a warming Arctic.
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Fluorocarbonos , Camada de Gelo , Regiões Árticas , Monitoramento Ambiental , Fluorocarbonos/análise , Água do MarRESUMO
Despite the high and preferential expression of p38γ MAPK in the myocardium, little is known about its function in the heart. The aim of the current study was to elucidate the physiologic and biochemical roles of p38γ in the heart. Expression and subcellular localization of p38 isoforms was determined in mouse hearts. Comparisons of the cardiac function and structure of wild-type and p38γ knockout (KO) mice at baseline and after abdominal aortic banding demonstrated that KO mice developed less ventricular hypertrophy and that contractile function is better preserved. To identify potential substrates of p38γ, we generated an analog-sensitive mutant to affinity tag endogenous myocardial proteins. Among other proteins, this technique identified calpastatin as a direct p38γ substrate. Moreover, phosphorylation of calpastatin by p38γ impaired its ability to inhibit the protease, calpain. We have identified p38γ as an important determinant of the progression of pathologic cardiac hypertrophy after aortic banding in mice. In addition, we have identified calpastatin, among other substrates, as a novel direct target of p38γ that may contribute to the protection observed in p38γKO mice.-Loonat, A. A., Martin, E. D., Sarafraz-Shekary, N., Tilgner, K., Hertz, N. T., Levin, R., Shokat, K. M., Burlingame, A. L., Arabacilar, P., Uddin, S., Thomas, M., Marber, M. S., Clark, J. E. p38γ MAPK contributes to left ventricular remodeling after pathologic stress and disinhibits calpain through phosphorylation of calpastatin.
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Proteínas de Ligação ao Cálcio/metabolismo , Calpaína/metabolismo , Proteína Quinase 12 Ativada por Mitógeno/metabolismo , Remodelação Ventricular/fisiologia , Animais , Calpaína/genética , Ecocardiografia , Eletroforese em Gel de Poliacrilamida , Células HEK293 , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Proteína Quinase 12 Ativada por Mitógeno/genética , Fosforilação , Isoformas de Proteínas , Espectrometria de Massas em Tandem , Remodelação Ventricular/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The reaction of TMP-NH2 [TMP = m,m-(CF3)2-C6H3] with 2 equiv of n-BuLi led to the in situ formation of Li2[N-TMP], which, after the addition of BiCl3, formed a [Cl-Bi(µ3-N-TMP)]4-type heterocubane in up to 30% yield. Transmetalation reactions, thought of as alternatives, starting from the analogous tin-nitrogen heterocubane [Sn(µ3-N-TMP)]4 and BiCl3 resulted in the isolation of a complex reaction mixture from which different Bi-N and Bi-Sn-N cage compounds could be isolated. The structures of all cage compounds that contain bismuth are discussed, and the thermodynamics of the formation of [Cl-Bi(µ3-N-TMP)]4 are highlighted. In an attempt to isolate Li2[N-TMP], generated in situ from TMP-NH2 and 2 equiv of n-BuLi, it was possible to isolate a lithium salt with a negatively charged lithium cluster of the type [Li9(N-TMP)5F]2- with an unusual Li9N5F skeleton.
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BACKGROUND: Questionnaires measuring the subjective outcome of hearing aid benefit are used in diagnostics of hearing loss additionally. Since 2012, the APHAB is part of the quality agreement for statutory insured patients in hearing aid fitting. Actually, calculating the benefit by the given formula (improvement quotient A) causes distortion by patients with negative results. In general, these dues to misinterpretation of the results. In this study, we proposed two alternative ways of calculation and compared the results together. METHODS: Using the data of 6861 hearing aid fitted patients from a database, we calculated the benefit by A and two new formulas (improvement quotient B and cumulated benefit) and compared the results together. RESULTS: The average for A was -29.02â% (SD ±â47.94) and a minimum of -637.93â%. The average for B was -13.42â% (SD ±â13.14) and a minimum of -78,63. No relevant differences by calculating the improvement quotients between A and B occurred. The average APHAB-score (EC-, BN-, and RV-subscale) was 50.70 before and 29.29 after hearing aid fitting, the average of the cumulated benefit was 21.41. CONCLUSIONS: Quotient B avoids the intrinsic potential of distortion of A in favor of patients with negative results in hearing aid benefit. It would be useful for the further developing of the quality agreement if B in exchange for A and, in addition, the cumulated benefit should be used.
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Surdez , Auxiliares de Audição , Perda Auditiva , Humanos , Ajuste de Prótese , Inquéritos e QuestionáriosRESUMO
The fate of persistent organic pollutants in sea ice is a poorly researched area and yet ice serves as an important habitat for organisms at the base of the marine foodweb. This study presents laboratory-controlled experiments to investigate the mechanisms governing the fate of organic contaminants in sea ice grown from artificial seawater. Sea ice formation was shown to result in the entrainment of chemicals from seawater, and concentration profiles in bulk ice generally showed the highest levels in both the upper (ice-atmosphere interface) and lower (ice-ocean interface) ice layers, suggesting their incorporation and distribution is influenced by brine advection. Results from a 1-D sea ice brine dynamics model supported this, but also indicated that other processes may be needed to accurately model low-polarity compounds in sea ice. This was reinforced by results from a melt experiment, which not only showed chemicals were more enriched in saltier brine, but also revealed that chemicals are released from sea ice at variable rates. We use our results to demonstrate the importance of processes related to the occurrence and movement of brine for controlling chemical fate in sea ice which provides a pathway for exposure to ice-associated biota at the base of the pelagic food web.
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Poluentes Ambientais , Camada de Gelo , Regiões Árticas , Atmosfera , Ecossistema , Água do MarRESUMO
The reaction of HN3 with the strong Lewis acid B(C6 F5 )3 led to the formation of a very labile HN3 â B(C6 F5 )3 adduct, which decomposed to an aminoborane, H(C6 F5 )NB(C6 F5 )2 , above -20 °C with release of molecular nitrogen and simultaneous migration of a C6 F5 group from boron to the nitrogen atom. The intermediary formation of azide-borane adducts with B(C6 F5 )3 was also demonstrated for a series of organic azides, RN3 (R=Me3 Si, Ph, 3,5-(CF3 )2 C6 H3 ), which also underwent Staudinger-like decomposition along with C6 F5 group migration. In accord with experiment, computations revealed rather small barriers towards nitrogen release for these highly labile azide adducts for all organic substituents except R=Me3 Si (m.p.â 120 °C, Tdec =189 °C). Hydrolysis of the aminoboranes provided C6 F5 -substituted amines, HN(R)(C6 F5 ), in good yields.
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A dichloro-cycloazatriphosphane that incorporates a cyclic NP3 backbone could be synthesized using knowledge gained from the chemistry of N2 P2 and P4 ring systems. It fills the gap between the congeneric compounds [ClP(µ-NR)]2 and [ClP(µ-PR)]2 (R=sterically demanding substituent), and thus contributes to the systematic development of nitrogen-phosphorus chemistry in general. The title compound was studied with respect to its formation via a labile aminodiphosphene, which readily underwent different rearrangement reactions depending on the solvent. All compounds were fully characterized by experimental and computational methods.
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OBJECTIVE: The vascular endothelial growth factor (VEGF) receptor Flk1 is essential for vascular development, but the signaling and transcriptional pathways by which its expression is regulated in endothelial cells remain unclear. Although previous studies have identified 2 Flk1 regulatory enhancers, these are dispensable for Flk1 expression, indicating that additional enhancers contribute to Flk1 regulation in endothelial cells. In the present study, we sought to identify Flk1 enhancers contributing to expression in endothelial cells. APPROACH AND RESULTS: A region of the 10th intron of the Flk1 gene (Flk1in10) was identified as a putative enhancer and tested in mouse and zebrafish transgenic models. This region robustly directed reporter gene expression in arterial endothelial cells. Using a combination of targeted mutagenesis of transcription factor-binding sites and gene silencing of transcription factors, we found that Gata and Ets factors are required for Flk1in10 enhancer activity in all endothelial cells. Furthermore, we showed that activity of the Flk1in10 enhancer is restricted to arteries through repression of gene expression in venous endothelial cells by the Notch pathway transcriptional regulator Rbpj. CONCLUSIONS: This study demonstrates a novel mechanism of arterial-venous identity acquisition, indicates a direct link between the Notch and VEGF signaling pathways, and illustrates how cis-regulatory diversity permits differential expression outcomes from a limited repertoire of transcriptional regulators.
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Artérias/metabolismo , Células Endoteliais/metabolismo , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Neovascularização Fisiológica , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Veias/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Artérias/embriologia , Sítios de Ligação , Elementos Facilitadores Genéticos , Fatores de Transcrição GATA/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Inativação Gênica , Genes Reporter , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Íntrons , Camundongos Transgênicos , Mutagênese Sítio-Dirigida , Mutação , Proteínas Proto-Oncogênicas c-ets/metabolismo , Receptores Notch/metabolismo , Fatores de Transcrição SOX/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Veias/embriologia , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
This work describes the synthesis and full characterization of elusive chloropnictenium ion salts of the type [(R)Ar*N(SiMe)ECl][A] ((R)Ar* = 2,6-(CHPh2)-4-R-C6H2, R = Me, tBu; E = Sb, Bi; A(-) = GaCl4, Al(OCH(CF3)2)4). In these species the cation is significantly stabilized by weak arene interactions to flanking phenyl groups of the (R)Ar* moiety. In this context the bonding situation has been studied by computational means and the reactivity towards the Lewis base 4-dimethylaminopyridine (dmap) was investigated.
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In people recovering from COVID-19, there is concern regarding potential long-term pulmonary sequelae and associated impairment of functional capacity. Data published thus far indicate that spirometric indices appear to be generally well preserved, but that a defect in diffusing capacity (DLco) is a prevalent abnormality identified on follow-up lung function; present in 20-30% of those with mild to moderate disease and 60% in those with severe disease. Reductions in total lung capacity were commonly reported. Functional capacity is also often impaired, with data now starting to emerge detailing walk test and cardiopulmonary exercise test outcome at follow-up. In this review, we evaluate the published evidence in this area, to summarise the impact of COVID-19 infection on pulmonary function and relate this to the clinico-radiological findings and disease severity.
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This article provides an overview of outstanding sessions that were (co)organised by the Allied Respiratory Professionals Assembly during the European Respiratory Society International Congress 2020, which this year assumed a virtual format. The content of the sessions was mainly targeted at allied respiratory professionals, including respiratory function technologists and scientists, physiotherapists, and nurses. Short take-home messages related to spirometry and exercise testing are provided, highlighting the importance of quality control. The need for quality improvement in sleep interventions is underlined as it may enhance patient outcomes and the working capacity of healthcare services. The promising role of digital health in chronic disease management is discussed, with emphasis on the value of end-user participation in the development of these technologies. Evidence on the effectiveness of airway clearance techniques in chronic respiratory conditions is provided along with the rationale for its use and challenges to be addressed in future research. The importance of assessing, preventing and reversing frailty in respiratory patients is discussed, with a clear focus on exercise-based interventions. Research on the impact of disease-specific fear and anxiety on patient outcomes draws attention to the need for early assessment and intervention. Finally, advances in nursing care related to treatment adherence, self-management and patients' perspectives in asthma and chronic obstructive pulmonary disease are provided, highlighting the need for patient engagement and shared decision making. This highlights article provides readers with valuable insight into the latest scientific data and emerging areas affecting clinical practice of allied respiratory professionals.
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Thermal ion retarding potential analyzers (RPAs) are used to measure in situ auroral ionospheric plasma parameters. This article analyzes data from a low-resource RPA in order to quantify the capability of the sensor. The RPA collects a sigmoidal current-voltage (I-V) curve, which depends on a non-linear combination of Maxwellian plasma parameters, so a forward-modeling procedure is used to match the best choice plasma parameters for each I-V curve. First, the procedure is used, given constraining information about the flow moment, to find scalar plasma parameters-ion temperature, ion density, and spacecraft sheath potential-for a single I-V curve interpreted in the context of a Maxwellian plasma distribution. Second, two azimuthally separated I-V curves from a single sensor on the spinning spacecraft are matched, given constraining information on density and sheath potential, to determine the bulk plasma flow components. These flows are compared to a high-fidelity, high-resource flow diagnostic. In both cases, the procedure's sensitivity to variations in constraining diagnostics is tested to ensure that the matching procedure is robust. Finally, a standalone analysis is shown, providing plasma scalar and flow parameters using known payload velocity and International Reference Ionosphere density as input information. The results show that the sensor can determine scalar plasma measurements as designed, as well as determine plasma DC flows to within hundreds of m/s error compared to a high-fidelity metric, thus showing their capability to replace higher-resource methods for determining DC plasma flows when coarse-resolution measurements at in situ spatial scales are suitable.
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Various tin(ii) compounds such as Mes*2Sn (Mes* = 2,4,6-tri-tert-butylphenyl), Sn[N(SiMe3)2]2 and TerSnCl (Ter = 2,6-bis(2,4,6-trimethylphenyl)phenyl) could be readily oxidised by organic azides to release N2, forming nitrogen-tin compounds. Depending on the used Sn(ii) compound, the reactions with two equivalents of azide led to the formation of tetrazastannoles (R2N4SnR'2) or cyclo-distannadiazanes [R2Sn(µ-NR')]2. The reactivity was independent of the electronic situation of the organic azide. Additionally, Mes*2Sn formed an amido-azido compound of the type R(R')Sn(N(SiMe3)2)N3 in the presence of Me3SiN3. Presumably, the corresponding tetrazastannole was formed in the first step followed by a ring opening reaction. The same holds true for the reaction of Sn[N(SiMe3)2]2 with Me3SiN3 while TerSnCl showed no reaction in the presence of Me3SiN3, even after prolonged heating.
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The reaction of lithium N-trimethylsilyl-amides of the type RN(SiMe3)Li with bismuth(iii) chloride yielded mono-, di- or triaminobismuthanes depending on the sterical demand of the anilide ligand R and the used stoichiometry. For the bulky Mes* substituent the reaction with BiCl3 resulted in the formation of a C-C coupling product as the main product besides a small amount of the expected Mes*N(SiMe3)BiCl2.