Τετάρτη 7 Δεκεμβρίου 2022

Characterizing the Relationship Between Reflection and Distortion Otoacoustic Emissions in Normal-Hearing Adults

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AbstractOtoacoustic emissions (OAEs) arise from one (or a combination) of two basic generation mechanisms in the cochlea: nonlinear distortion and linear reflection. As a result of having distinct generation processes, these two classes of emissions may provide non-redundant information about hair-cell integrity and show distinct sensitivities to cochlear pathology. Here, we characterize the relationship between reflection and distortion emissions in normal hearers across a broad frequency and stimulus-level space using novel analysis techniques. Furthermore, we illustrate the promise of this approach in a small group of individuals with mild-moderate hearing loss. A "joint-OAE profile" was created by measuring interleaved swept-tone stimulus-frequency OAEs (SFOAEs) and 2f1-f2 distorti...
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No Reduction in the 226-Hz Probe Tone Acoustic Reflex Amplitude Following Severe Inner Hair Cell Loss in Chinchillas

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AbstractThe relationship between the middle ear acoustic reflex (AR) and inner hair cell (IHC) loss is currently unknown. Given that IHC are believed to convey nearly all acoustic information to the central auditory nervous system, it has been assumed that loss of IHC would significantly impact the AR. To evaluate this relationship, we assessed the presence and amplitude of the AR in chinchillas before and after treatment with carboplatin, an anticancer drug that reliably and selectively destroys IHC in this species. Baseline measures of hearing sensitivity, including auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAE), were assessed and then re-evaluated following carboplatin treatment. Post-carboplatin ABR thresholds and DPOAE were found to b...
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A Computational Model of a Single Auditory Nerve Fiber for Electric-Acoustic Stimulation

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AbstractCochlear implant (CI) recipients with preserved acoustic low-frequency hearing in the implanted ear are a growing group among traditional CI users who benefit from hybrid electric-acoustic stimulation (EAS). However, combined ipsilateral electric and acoustic stimulation also introduces interactions between the two modalities that can affect the performance of EAS users. A computational model of a single auditory nerve fiber that is excited by EAS was developed to study the interaction between electric and acoustic stimulation. Two existing models of sole electric or acoustic stimulation were coupled to simulate responses to combined EAS. Different methods of combining both models were implemented. In the coupled model variant, the refractoriness of the simulated fiber leads to sup...
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Main Causal Agents of Occupational Asthma

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Abstract
Objectives
The definition of work-related Asthma (WRA) has changed in recent years and new etiologies and agents have been identified. The aim of this study is to describe the main causal agents of WRA in France in the period 2001–2018 in the main work sectors.
Methods
Data were collected from the French national network of occupational health surveillance and prevention [Réseau National de Vigilance et de Prévention des Pathologies Professionnelles (RNV3P)], Data between 2001 and 2018 with at least a probable or certain association with one occupational agent, were included.
Results
Work sectors with more cases OF WRA included personal service activities (10.6%), food industry (10.2%) and healthcare activities (7.6%). WRA cases were most frequently related to flour (10%), quaternary ammoniums compounds (5.3%), isocyanates (5.1%) and cleaning products (4.8%).
Conclusion
Occupational exposure to specific ag ents capable of causing WRA is still present, and four agents represent more than 25% of the cases. Actions to prevent respiratory exposure are still relevant.
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Τρίτη 6 Δεκεμβρίου 2022

Risk communication and community preparedness in the context of biotechnological hazards: A case of NBAF

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Applying the Protection Motivation Theory, this study examines factors affecting community preparedness in the context of biotechnological hazards. In particular, residents living nearby the National Bio and Agro-Defence Facility (NBAF), a biosafety level-4 facility currently under construction, were surveyed. The survey assessed residents' perceptions of key risk communication elements, transparency, consistency, and source, as well as risk perception, knowledge, collective efficacy, involvement, civic engagement behaviours, and preparedness perceptions. Results indicate that sources such as local organisations and mass media, as opposed to social media and word-of-mouth, are more reliable and lead to increased knowledge. The structural model suggests that transparent and consistent risk communication leads to community preparedness through knowledge, involvement, risk perception, and collective efficacy. Theoretical implications for the Protection Motivation Theory and practical implications for risk communication regarding biotechnological hazards are discussed.

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Switching certolizumab pegol from a prefilled syringe or autoinjection pen to an AVA® e‐Device in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis patients

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Six months multicentre pilot open label single-arm study to evaluate patient experience, acceptability and satisfaction of switching certolizumab pegol from a prefilled syringe or autoinjection pen to an AVA® e-Device in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis patients

AVA® is a new electromechanical injection device for self-injecting certolizumab pegol (CZP). Thirty four patients were included (28 women) RA 11, PsA 10 and axial axSpA 13. Patients reported >90% adherence assessed with AVA® injection log and the full dose of CZP was injected on all patients with AVA® device. No safety findings related to AVA® CZP administration were identified. AVA® device is an advantageous delivery option for CZP. This study provides further evidence to support that AVA® device is a valid method for switching CZP from syringe or pen with highly preference in patients with RA, PsA and axSpa.


Abstract

What Is Known and Objective

The study aimed to assess acceptability and patient experience of Certolizumab (CZP) self-injection with AVA® and clarify patient device preference after switching CZP from the syringe or auto-injection pen to AVA® in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients.

Method

A multicentre open-label, cross-sectional and prospective study among four Spanish hospitals was performed. Adult RA, PsA, axSpA patients treated for at least 6 months with the CZP syringe or pen were recruited. At the first visit, patients completed Pre-AVA® questionnaire. Patients were instructed on proper administration of CZP by AVA®. After 2 and 6 months of CZP self-injections using the AVA®, patient experience, adherence, preference and safety of each administration was assessed using post-AVA® questionnaire.

Results and Discussion

Thirty four patients were included (28 women). All patients self-administered CZP AVA® the full dose of CZP was injected. Patients reported >90% adherence to CZP AVA® assessed with the injection log. Pain at the injection site was reduced after switching to AVA®. Twenty nine patients preferred CZP AVA® and five patients preferred the CZP pen. No safety-related findings related to AVA® CZP administration were identified.

What Is New and Conclusion

The AVA® is an advantageous delivery option for CZP in patients with RA, PsA, axSpA.

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Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: a phase I, “windowofopportunity” study

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Abstract
Background
The bromodomain and extraterminal protein (BET) inhibitor trotabresib has demonstrated antitumor activity in patients with advanced solid tumors, including high-grade gliomas. CC-90010-GBM-001 (NCT04047303) is a phase I study investigating the pharmacokinetics, pharmacodynamics, and CNS penetration of trotabresib in patients with recurrent high-grade gliomas scheduled for salvage resection.
Methods
Patients received trotabresib 30 mg/day on days 1–4 before surgery, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off after surgery. Primary endpoints were plasma pharmacokinetics and trotabresib concentrations in resected tissue. Secondary and exploratory endpoints included safety, pharmacodynamics, and antitumor activity.
Results
Twenty patients received preoperative trotabresib and underwent resection with no delays or cancellations of surgery; 16 patients received maintenance trot abresib after recovery from surgery. Trotabresib plasma pharmacokinetics were consistent with previous data. Mean trotabresib brain tumor tissue:plasma ratio was 0.84 (estimated unbound partition coefficient [KPUU] 0.37), and modulation of pharmacodynamic markers was observed in blood and brain tumor tissue. Trotabresib was well tolerated; the most frequent grade 3/4 treatment-related adverse event during maintenance treatment was thrombocytopenia (5/16 patients). Sixmonth progression-free survival was 12%. Two patients remain on treatment with stable disease at cycles 25 and 30.
Conclusions
Trotabresib penetrates the blood–brain-tumor barrier in patients with recurrent high-grade glioma and demonstrates target engagement in resected tumor tissue. Plasma pharmacokinetics, blood pharmacodynamics, and safety were comparable with previous results for trotabresib in patients with advanced solid tumors. Investigation of adjuvant trotabresib + temozolomide and concom itant trotabresib + temozolomide + radiotherapy in patients with newly diagnosed glioblastoma is ongoing (NCT04324840).
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