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Purpose Neurally adjusted ventilatory assist (NAVA) is a ventilatory mode that tailors the level of assistance delivered by the ventilator to the electromyographic activity of the diaphragm. The objective of this study was to compare NAVA and pressure support ventilation (PSV) in the early phase of weaning from mechanical ventilation. Methods A multicentre randomized controlled trial of 128 intubated adults recovering from acute respiratory failure was conducted in 11 intensive care units. Patients were randomly assigned to NAVA or PSV. The primary outcome was the probability of remaining in a partial ventilatory mode (either NAVA or PSV) throughout the first 48 h without any return to assist-control ventilation. Secondary outcomes included asynchrony index, ventilator-free days and mortality. Results In the NAVA and PSV groups respectively, the proportion of patients remaining in partial ventilatory mode throughout the first 48 h was 67.2 vs. 63.3 % ( P  = 0.66), the asynchrony index was 14.7 vs. 26.7 % ( P  < 0.001), the ventilator-free days at day 7 were 1.0 day [1.0–4.0] vs. 0.0 days [0.0–1.0] ( P  < 0.01), the ventilator-free days at day 28 were 21 days [4–25] vs. 17 days [0–23] ( P  = 0.12), the day-28 mortality rate was 15.0 vs. 22.7 % ( P  = 0.21) and the rate of use of post-extubation noninvasive mechanical ventilation was 43.5 vs. 66.6 % ( P  < 0.01). Conclusions NAVA is safe and feasible over a prolonged period of time but does not increase the probability of remaining in a partial ventilatory mode. However, NAVA decreases patient–ventilator asynchrony and is associated with less frequent application of post-extubation noninvasive mechanical ventilation. Trial Registration. clinicaltrials.gov Identifier: NCT02018666.

Young healthy adults can hear tones up to at least 20 kHz. However, clinical audiometry, by which hearing loss is diagnosed, is limited at high frequencies to 8 kHz. Evidence suggests there is salient information at extended high frequencies (EHFs; 8 to 20 kHz) that may influence speech intelligibility, but whether that information is used in challenging listening conditions remains unknown. Difficulty understanding speech in noisy environments is the most common concern people have about their hearing and usually the first sign of age-related hearing loss. Digits-in-noise (DIN), a widely used test of speech-in-noise perception, can be sensitized for detection of high-frequency hearing loss by low-pass filtering the broadband masking noise. Here, we used standard and EHF audiometry, self-report, and successively higher cutoff frequency filters (2 to 8 kHz) in a DIN test to investigate contributions of higher-frequency hearing to speech-in-noise perception. Three surprising results were found. First, 74 of 116 “normally hearing,” mostly younger adults had some hearing loss at frequencies above 8 kHz. Early EHF hearing loss may thus be an easily measured, preventive warning to protect hearing. Second, EHF hearing loss correlated with self-reported difficulty hearing in noise. Finally, even with the broadest filtered noise (≤8 kHz), DIN hearing thresholds were significantly better (P < 0.0001) than those using broadband noise. Sound energy above 8 kHz thus contributes to speech perception in noise. People with “normal hearing” frequently report difficulty hearing in challenging environments. Our results suggest that one contribution to this difficulty is EHF hearing loss.

Niemann-Pick disease, type C1 (NPC1) is a lysosomal storage disorder characterised by progressive neurodegeneration. In preclinical testing, 2-hydroxypropyl-β-cyclodextrins (HPβCD) significantly delayed cerebellar Purkinje cell loss, slowed progression of neurological manifestations, and increased lifespan in mouse and cat models of NPC1. The aim of this study was to assess the safety and efficacy of lumbar intrathecal HPβCD. In this open-label, dose-escalation phase 1–2a study, we gave monthly intrathecal HPβCD to participants with NPC1 with neurological manifestation at the National Institutes of Health (NIH), Bethesda, MD, USA. To explore the potential effect of 2-week dosing, three additional participants were enrolled in a parallel study at Rush University Medical Center (RUMC), Chicago, IL, USA. Participants from the NIH were non-randomly, sequentially assigned in cohorts of three to receive monthly initial intrathecal HPβCD at doses of 50, 200, 300, or 400 mg per month. A fifth cohort of two participants received initial doses of 900 mg. Participants from RUMC initially received 200 or 400 mg every 2 weeks. The dose was escalated based on tolerance or safety data from higher dose cohorts. Serum and CSF 24(S)-hydroxycholesterol (24[S]-HC), which serves as a biomarker of target engagement, and CSF protein biomarkers were evaluated. NPC Neurological Severity Scores (NNSS) were used to compare disease progression in HPβCD-treated participants relative to a historical comparison cohort of 21 NPC1 participants of similar age range. Between Sept 21, 2013, and Jan 19, 2015, 32 participants with NPC1 were assessed for eligibility at the National Institutes of Health. 18 patients were excluded due to inclusion criteria not met (six patients), declined to participate (three patients), pursued independent expanded access and obtained the drug outside of the study (three patients), enrolled in the RUMC cohort (one patient), or too late for the trial enrolment (five patients). 14 patients were enrolled and sequentially assigned to receive intrathecal HPβCD at a starting dose of 50 mg per month (three patients), 200 mg per month (three patients), 300 mg per month (three patients), 400 mg per month (three patients), or 900 mg per month (two patients). During the first year, two patients had treatment interrupted for one dose, based on grade 1 ototoxicity. All 14 patients were assessed at 12 months. Between 12 and 18 months, one participant had treatment interrupted at 17 months due to hepatocellular carcinoma, one patient had dose interruption for 2 doses based on caregiver hardship and one patient had treatment interrupted for 1 dose for mastoiditis. 11 patients were assessed at 18 months. Between Dec 11, 2013, and June 25, 2014, three participants were assessed for eligibility and enrolled at RUMC, and were assigned to receive intrathecal HPβCD at a starting dose of 200 mg every 2 weeks (two patients), or 400 mg every two weeks (one patient). There were no dropouts in this group and all 3 patients were assessed at 18 months. Biomarker studies were consistent with improved neuronal cholesterol homoeostasis and decreased neuronal pathology. Post-drug plasma 24(S)-HC area under the curve (AUC8-72) values, an indicator of neuronal cholesterol homoeostasis, were significantly higher than post-saline plasma 24(S)-HC AUC8-72 after doses of 900 mg (p=0·0063) and 1200 mg (p=0·0037). CSF 24(S)-HC concentrations in three participants given either 600 or 900 mg of HPβCD were increased about two fold (p=0·0032) after drug administration. No drug-related serious adverse events were observed. Mid-frequency to high-frequency hearing loss, an expected adverse event, was documented in all participants. When managed with hearing aids, this did not have an appreciable effect on daily communication. The NNSS for the 14 participants treated monthly increased at a rate of 1·22, SEM 0·34 points per year compared with 2·92, SEM 0·27 points per year (p=0·0002) for the 21 patient comparison group. Decreased progression was observed for NNSS domains of ambulation (p=0·0622), cognition (p=0·0040) and speech (p=0·0423). Patients with NPC1 treated with intrathecal HPβCD had slowed disease progression with an acceptable safety profile. These data support the initiation of a multinational, randomised, controlled trial of intrathecal HPβCD. National Institutes of Health, Dana's Angels Research Trust, Ara Parseghian Medical Research Foundation, Hope for Haley, Samantha's Search for the Cure Foundation, National Niemann-Pick Disease Foundation, Support of Accelerated Research for NPC Disease, Vtesse, Janssen Research and Development, a Johnson & Johnson company, and Johnson & Johnson.

High-frequency oscillatory ventilation has been advocated for hypoxemia accompanying the acute respiratory distress syndrome. In this trial comparing HFOV with conventional ventilation, HFOV had no significant effect on 30-day mortality. The acute respiratory distress syndrome (ARDS) is a severe, diffuse inflammatory lung condition caused by a range of acute illnesses. Mortality in affected patients is high, 1 and survivors may have functional limitations for years. 2 , 3 Although mechanical ventilation can initially be lifesaving in patients with ARDS, it can also further injure the patients' lungs and contribute to death. 4 High-frequency oscillatory ventilation (HFOV) was first used experimentally in the 1970s to minimize the hemodynamic effects of mechanical ventilation. 5 Patients' lungs are held inflated to maintain oxygenation, and carbon dioxide is cleared by small volumes of gas moved in and out of . . .

Background High-flow nasal cannula (HFNC) oxygen therapy is being increasingly used to prevent post-extubation hypoxemic respiratory failure and reintubation. However, evidence to support the use of HFNC in chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure after extubation is limited. This study was conducted to test if HFNC is non-inferior to non-invasive ventilation (NIV) in preventing post-extubation treatment failure in COPD patients previously intubated for hypercapnic respiratory failure. Methods COPD patients with hypercapnic respiratory failure who were already receiving invasive ventilation were randomized to HFNC or NIV at extubation at two large tertiary academic teaching hospitals. The primary endpoint was treatment failure, defined as either resumption of invasive ventilation or switching to the other study treatment modality (NIV for patients in the NFNC group or vice versa). Results Ninety-six patients were randomly assigned to the HFNC group or NIV group. After secondary exclusion, 44 patients in the HFNC group and 42 patients in the NIV group were included in the analysis. The treatment failure rate in the HFNC group was 22.7% and 28.6% in the NIV group—risk difference of − 5.8% (95% CI, − 23.8–12.4%, p  = 0.535), which was significantly lower than the non-inferior margin of 9%. Analysis of the causes of treatment failure showed that treatment intolerance in the HFNC group was significantly lower than that in the NIV group, with a risk difference of − 50.0% (95% CI, − 74.6 to − 12.9%, p  = 0.015). One hour after extubation, the mean respiratory rates of both groups were faster than their baseline levels before extubation ( p  < 0.050). Twenty-four hours after extubation, the respiratory rate of the HFNC group had returned to baseline, but the NIV group was still higher than the baseline. Forty-eight hours after extubation, the respiratory rates of both groups were not significantly different from the baseline. The average number of daily airway care interventions in the NIV group was 7 (5–9.3), which was significantly higher than 6 (4–7) times in the HFNC group ( p  = 0.006). The comfort score and incidence of nasal and facial skin breakdown of the HFNC group was also significantly better than that of the NIV group [7 (6–8) vs 5 (4–7), P  < 0.001] and [0 vs 9.6%, p  = 0.027], respectively. Conclusion Among COPD patients with severe hypercapnic respiratory failure who received invasive ventilation, the use of HFNC after extubation did not result in increased rates of treatment failure compared with NIV. HFNC also had better tolerance and comfort than NIV. Trial registration chictr.org ( ChiCTR1800018530 ). Registered on 22 September 2018, http://www.chictr.org.cn/usercenter.aspx

Test the hypothesis that the center of ventilation, a measure of ventro-dorsal atelectasis, is posterior during supraglottic ventilation indicating better dependent-lung ventilation. Secondarily, we tested the hypothesis that supraglottic ventilation improves oxygenation and carbon dioxide elimination. Supraglottic and subglottic jet ventilation are both used during laryngotracheal surgery. Supraglottic jet ventilation may better prevent atelectasis and provide superior ventilation. Randomized, cross-over trial. Operating rooms. Patients having elective micro-laryngotracheal surgery. Patients were sequentially ventilated for 5 min with one randomly selected type of jet ventilation before being switched to the alternative method. Regional ventilation distribution was estimated using electrical impedance tomography, with arterial oxygenation and carbon dioxide partial pressures being simultaneously evaluated. Thirty patients completed the study. There were no statistically significant or clinically meaningful differences in the center of ventilation with supraglottic and subglottic ventilation. However, ventilation with the supraglottic approach was about 4 % higher in the ventromedial lung region and about 4 % lower in the dorsal lung. Surprisingly, arterial blood oxygenation was considerably worse with supraglottic (173 [156, 199] mmHg) than subglottic ventilation (293 [244, 340] mmHg). Arterial carbon dioxide partial pressure was near 40 mmHg with each approach, although slightly lower with supraglottic jet ventilation. The center of ventilation distribution, a measure of atelectasis, was similar with supraglottic and subglottic jet ventilation. Subglottic jet ventilation improved the dorsal-dependent lung region and provided superior arterial oxygenation. Both techniques effectively eliminated carbon dioxide, with the supraglottic approach demonstrating slightly superior efficacy. •In a cross-over trial, we compared supraglottic and subglottic jet ventilation during open-airway laryngeal surgery.•Jet ventilation did not significantly shift the overall center of ventilation as determined by EIT.•Supraglottic jet ventilation worsened ventilation in dorsal lung regions compared to subglottic jet ventilation by 4 %.•Oxygenation was substantially better with subglottic than supraglottic jet ventilation.•Either type of jet ventilation appears suitable for open-airway laryngeal surgery.

The paper presents the original observation of high frequency Alfvén eigenmode excited by fast minority hydrogen ions accelerated by ion cyclotron range of frequency waves in EAST. The frequency of high frequency Alfvén eigenmodes is around 0.75∼0.8∗ΩH, where ΩH is the cyclotron frequency of hydrogen ions evaluated at the low-field side plasma edge. It tracks the on-axis magnetic field Bt and the edge plasma electron density ne via the Alfvénic relation ω∼Bt∗ne−1/2. The high frequency Alfvén eigenmodes are always accompanied by sub-cyclotron modes in several experiments at EAST, consistent with the high frequency Alfvén eigenmode detected on other conventional tokamaks, namely ASDEX Upgrade and DIII-D. Based on the previous study, these sub-cyclotron modes are consistent with the spectrum splitting produced by toroidal mode numbers (Gorelenkov et al 2003 Nucl. Fusion 43 228). We also found that the location of eigenmode excitation of high frequency Alfvén eigenmode driven by RF-accelerated minority hydrogen ions remains unchanged even though the cyclotron resonance location of hydrogen ions varies with Bt.

The inverted tripole charge structure in thunderstorm over the central Tibetan Plateau was discovered for the first time, primarily through observations from lightning very high frequency interferometer capable of high‐precision lightning channel mapping. The dominant cell exhibited an inverted tripole charge structure initially, characterized by a negative charge region at temperatures near 0°C, a main positive charge region between −30°C and −5°C, and an upper negative charge region at T < −20°C. The cell's rear portion exhibited a normal tripole before detaching, leaving a pure inverted tripole. Dissipation of the lower negative charge transitioned the structure to an inverted dipole, consisting of an upper negative (T < −20°C) and lower positive (T > −20°C). Throughout this thunderstorm, no positive cloud‐to‐ground (+CG) flashes were detected, while five −CG flashes were recorded. Among 109 intracloud (IC) flashes detected, 90% occurred between the upper inverted dipole. Radar reflectivity showed that this thunderstorm was more intense than conventional plateau thunderstorms.

Background High-frequency ventilation (HFV) is commonly used in neonatal intensive care units to provide respiratory support for critically ill neonates. Currently, there is no standardized procedure for weaning from HFV. Two commonly used strategies are transitioning from HFV to conventional mechanical ventilation (CMV) before extubation (HFV-CMV) and extubation after decreasing mean airway pressure during HFV (HFV-HFV). The impact of these strategies on neonatal cerebral oxygenation and hemodynamics remains incompletely understood. Methods We will conduct a prospective, single-center, randomized controlled trial to investigate the effects of two different HFV weaning strategies (HFV-CMV, HFV-HFV) on neonatal cerebral oxygenation and hemodynamics. The patients enrolled in the trial will be randomly allocated to either the HFV-CMV group or the HFV-HFV group in a 1:1 ratio. The primary outcome will be cerebral oxygen saturation (S c O 2 ) before and after the intervention. Second outcomes are cerebral fractional tissue oxygen extraction, heart rate, blood pressure, and the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia. We hypothesize that HFV-CMV results in positive impact on neonatal cerebral oxygenation compared to HFV-HFV. This study aims to identify a better weaning strategy for HFV and contribute evidence-based data to enhance its clinical application in newborns, potentially improving the care and outcomes for neonates receiving HFV. Discussion This study aims to assessing the impact of different HFV weaning strategies on neonatal cerebral oxygenation and hemodynamics, as well as the relationship between the duration of HFV under different strategies and neurological complications, to identify better weaning methods for HFV. We hope to contribute evidence-based data to enhance clinical application of HFV in newborns, potentially improving the care and outcomes for neonates receiving HFV. Trial registration Chinese Clinical Trial Registry: ChiCTR2400088628. Registered on August 22, 2024, https://www.chictr.org.cn/bin/project/edit?pid=235926 .

The response of the quartz crystal microbalance (QCM, also: QCM-D for “QCM with Dissipation monitoring”) to loading with a diverse set of samples is reviewed in a consistent frame. After a brief introduction to the advanced QCMs, the governing equation (the small-load approximation) is derived. Planar films and adsorbates are modeled based on the acoustic multilayer formalism. In liquid environments, viscoelastic spectroscopy and high-frequency rheology are possible, even on layers with a thickness in the monolayer range. For particulate samples, the contact stiffness can be derived. Because the stress at the contact is large, the force is not always proportional to the displacement. Nonlinear effects are observed, leading to a dependence of the resonance frequency and the resonance bandwidth on the amplitude of oscillation. Partial slip, in particular, can be studied in detail. Advanced topics include structured samples and the extension of the small-load approximation to its tensorial version.