Development of the Malay digit triplet test via headphones and telephones as a national hearing screening tool in Malaysia

Introduction: This study aimed to develop a self-administered hearing screening test using digit triplets in Malay (MDTT) to be used as a national hearing screening tool via internet and telephone landlines in Malaysia. Methods: Recordings of disyllabic Malay digits by a female Malay native speaker were used together with a speech shaped stationary noise (TSN). The test stimuli were normalized using responses from twenty normal hearing native Malay speakers. The data were used to produce eight equivalent test lists. An additional twenty normal hearing native Malay speakers were recruited to test the lists equivalency. Forty six listeners with varying levels of hearing were recruited to validate the tests. ROC analysis was done to identify the pass and refer cut-off limits. Results: No statistical differences were found between lists for both test conditions. The evaluation in fixed SNRs resulted in a mean speech reception threshold (SRT) of -11.3 ± 0.34 dB SNR for headphone and -10.24 ± 0.1 dB SNR for telephone applications. A significant main effect of type of transducer was observed in both normal and hearing impaired groups. The cut off for refer, sensitivity and specificity for the tests using telephones are (-5.8dB, 80.8%, 95%) and headphones (-9.8dB, 80.8%, 100%). Conclusions: The MDTT was successfully developed and the normative values are comparable to other versions of the digit triplet tests. The MDTT showed high sensitivity and specificity and can be made available to any Malay speaking public via telephone and internet

Airflow rates and breathlessness recovery from submaximal exercise in healthy adults: prospective, randomised, cross-over study

Objectives Facial airflow from a hand-held fan may reduce breathlessness severity and hasten postexertion recovery. Data from randomised controlled trials are limited and the optimal airflow speed remains unknown. We aimed to determine the effect of different airflow speeds on recovery from exercise-induced breathlessness.Methods A prospective, randomised, cross-over design. Ten healthy participants (seven male; mean age 29±4 years; height 175±9 cm; body mass 76.9±14.1 kg) completed six bouts of 4 min of exercise. During the first 5 min of a 20 min recovery phase, participants received one of five airflow speeds by holding a fan ~15 cm from their face, or no fan control, administered in random order. Fan A had an internal blade, and fan B had an external blade. Breathlessness was measured using a numerical rating scale (NRS) at minute intervals for the first 10 min, and facial skin temperature was recorded using a thermal imaging camera (immediately postexertion and 5 min recovery).Results Nine participants completed the trial. A significant main effect for airflow speed (p=0.016, ηp2=0.285) and interaction effect for airflow speed over time (p=0.008, ηp2=0.167) suggest that the airflow speed modifies breathlessness during recovery from exercise. Fan speeds of 1.7 m/s or greater increased the speed of recovery from breathlessness compared with control (p<0.05) with the highest airflow speeds (2.5 m/s and 3.3 m/s) giving greatest facial cooling.Conclusion Higher airflow rates (1.7 m/s or greater) reduced self-reported recovery times from exercise-induced breathlessness and reduced facial temperature

Anzeige der von den Lehrern des Collegii Carolini in dem Winterhalbjahre von Michaelis 1857 bis Ostern 1858 zu haltenden Vorlesungen und anzustellenden Uebungen

BACKGROUND: The identification of patients with advanced liver fibrosis secondary to non-alcoholic fatty liver disease (NAFLD) remains challenging. Using non-invasive liver fibrosis tests (NILT) in primary care may permit earlier detection of patients with clinically significant disease for specialist review, and reduce unnecessary referral of patients with mild disease. We constructed an analytical model to assess the clinical and cost differentials of such strategies.METHODS: A probabilistic decisional model simulated a cohort of 1000 NAFLD patients over 1 year from a healthcare payer perspective. Simulations compared standard care (SC) (scenario 1) to: Scenario 2: FIB-4 for all patients followed by Enhanced Liver Fibrosis (ELF) test for patients with indeterminate FIB-4 results; Scenario 3: FIB-4 followed by fibroscan for indeterminate FIB-4; Scenario 4: ELF alone; and Scenario 5: fibroscan alone. Model estimates were derived from the published literature. The primary outcome was cost per case of advanced fibrosis detected.RESULTS: Introduction of NILT increased detection of advanced fibrosis over 1 year by 114, 118, 129 and 137% compared to SC in scenarios 2, 3, 4 and 5 respectively with reduction in unnecessary referrals by 85, 78, 71 and 42% respectively. The cost per case of advanced fibrosis (METAVIR ≥F3) detected was £25,543, £8932, £9083, £9487 and £10,351 in scenarios 1, 2, 3, 4 and 5 respectively. Total budget spend was reduced by 25.2, 22.7, 15.1 and 4.0% in Scenarios 2, 3, 4 and 5 compared to £670 K at baseline.CONCLUSION: Our analyses suggest that the use of NILT in primary care can increases early detection of advanced liver fibrosis and reduce unnecessary referral of patients with mild disease and is cost efficient. Adopting a two-tier approach improves resource utilization.</p

The development of a fast method for recording schroeder-phase masking functions

Schroeder-phase masking complexes have been used in many psychophysical experiments to examine the phase curvature of cochlear filtering at characteristic frequencies, and other aspects of cochlear nonlinearity. In a normal nonlinear cochlea, changing the “scalar factor” of the Schroeder-phase masker from −1 through 0 to +1 results in a marked difference in the measured masked thresholds, whereas this difference is reduced in ears with damaged outer hair cells. Despite the valuable information it may give, one disadvantage of the Schroeder-phase masking procedure is the length of the test – using the conventional three-alternative forced-choice technique to measure a masking function takes around 45 min for one combination of probe frequency and intensity. As an alternative, we have developed a fast method of recording these functions which uses a Békésy tracking procedure. Testing at 500 Hz in normal hearing participants, we demonstrate that our fast method: i) shows good agreement with the conventional method; ii) shows high test-retest reliability; and iii) shortens the testing time to 8 min

The use of a fast method for recording schroeder-phase masking functions to estimate cochlear phase curvature

Until relatively recently, the influence of signal phase on human perception has largely been disregarded. However, findings in the last 20 years have shown that altering the phase characteristics of Schroeder harmonic complexes changes their ability to mask other sounds (Kohlrausch &amp; Sander, 1995).The difference in masking produced by different phases of Schroeder complexes is thought to be contributed by the interaction between the phase curvature of the auditory filter and nonlinear cochlear processing. Our aim in this study was to demonstrate the potential use of our newly developed fast method for recording Schroeder-phase masking functions to estimate basilar membrane phase curvature. Schroeder-phase masking functions at 75 dB A masker level were recorded in six normal-hearing participants for 250 Hz, 500 Hz, 1000 Hz, and 2000 Hz using various fundamental frequencies and numbers of masker components. Cochlear phase curvature was estimated from the location of minima in Schroeder-phase masking functions. The estimated auditory filter phase curvature was negative at all tested frequencies, and approached zero as frequency increased. Scaling symmetry was not exhibited for frequencies &lt;500 Hz. Phase curvature estimates at low frequencies contradicted estimates from animal studies, but were consistent with previous Schroeder-phase masking studies in humans (Kohlrausch &amp; Sander, 1995; Oxenham &amp; Dau, 2001; Lentz &amp; Leek, 2001), indicating significant interspecies differences. Our findings suggest that the newly developed fast method of Schroeder-phase masking, with its 80% reduction in test time, may be a useful tool for psychophysical estimation of auditory filter phase curvature

A fast method for the psychophysical estimation of nonlinear cochlear function using schroeder-phase masking

The power spectrum model of masking (Patterson and Moore, 1986) assumes that the masking ability of a sound is affected only by the frequency and intensity of the masker, but not the phase. The well-documented difference in masking produced by different phases of Schroeder- phase harmonic complexes the ("phase effect") is thought to be contributed by the phase curvature of the auditory filter and nonlinear cochlear processing (Kohlrausch &amp; Sander, 1995). We have recently developed a fast method for recording Schroeder-phase masking functions in humans which takes 8 minutes of testing time rather than the 45 minutes taken by the conventional three alternative forced choice (3AFC) method. We demonstrate here the reliability of this new method and its potential use in measuring cochlear non-linearity. Schroeder-phase masking functions were measured in 38 normal hearing and 15 hearing impaired participants using the conventional and fast methods. Results from our fast method agreed well with those from the conventional 3AFC method. We also used the fast method to measure functions at 0.25, 0.5, 1, 2, and 4 kHz at 45 and 75 dB A masker levels in normal hearing and hearing impaired participants, and found significantly reduced phase effects at low presentation levels and in participants with SNHL compared to normal hearing participants (p&lt;0.05), consistent with reductions in cochlear nonlinearity in those conditions. With an 80% reduction of testing time as compared to the conventional method, the fast method has great potential to aid future studies estimating nonlinear cochlear function

Facilitating treatment of HCV in primary care in regional Australia: Closing the access gap

Background: Australia has unrestricted access to direct-acting antivirals (DAA) for hepatitis C virus (HCV) treatment. In order to increase access to treatment, primary care providers are able to prescribe DAA after fibrosis assessment and specialist consultation. Transient elastography (TE) is recommended prior to commencement of HCV treatment; however, TE is rarely available outside secondary care centres in Australia and therefore a requirement for TE could represent a barrier to access to HCV treatment in primary care. Objectives: In order to bridge this access gap, we developed a community-based TE service across the Sunshine Coast and Wide Bay areas of Queensland. Design: Retrospective analysis of a prospectively recorded HCV treatment database. Interventions: A nurse-led service equipped with two mobile Fibroscan units assesses patients in eight locations across regional Queensland. Patients are referred into the service via primary care and undergo nurse-led TE at a location convenient to the patient. Patients are discussed at a weekly multidisciplinary team meeting and a treatment recommendation made to the referring GP. Treatment is initiated and monitored in primary care. Patients with cirrhosis are offered follow-up in secondary care. Results: 327 patients have undergone assessment and commenced treatment in primary care. Median age 48 years (IQR 38-56), 66% male. 57% genotype 1, 40% genotype 3; 82% treatment naïve; 10% had cirrhosis (liver stiffness >12.5 kPa). The majority were treated with sofosbuvir-based regimens. 26% treated with 8-week regimens. All patients had treatment prescribed and monitored in primary care. Telephone follow-up to confirm sustained virological response (SVR) was performed by clinic nurses. 147 patients remain on treatment. 180 patients have completed treatment. SVR data were not available for 19 patients (lost to follow-up). Intention-to-treat SVR rate was 85.5%. In patients with complete data SVR rate was 95.6%. Conclusion: Community-based TE assessment facilitates access to HCV treatment in primary care with excellent SVR rates

Dysregulation of club cell biology in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic fibrotic lung disease with an irreversible decline of lung function. "Bronchiolization", characterized by ectopic appearance of airway epithelial cells in the alveolar regions, is one of the characteristic features in the IPF lung. Based on the knowledge that club cells are the major epithelial secretory cells in human small airways, and their major secretory product uteroglobin (SCGB1A1) is significantly increased in both serum and epithelial lining fluid of IPF lung, we hypothesize that human airway club cells contribute to the pathogenesis of IPF. By assessing the transcriptomes of the single cells from human lung of control donors and IPF patients, we identified two SCGB1A1+ club cell subpopulations, highly expressing MUC5B, a significant genetic risk factor strongly associated with IPF, and SCGB3A2, a marker heterogeneously expressed in the club cells, respectively. Interestingly, the cellular proportion of SCGB1A1+MUC5B+ club cells was significantly increased in IPF patients, and this club cell subpopulation highly expressed genes related to mucous production and immune cell chemotaxis. In contrast, though the cellular proportion did not change, the molecular phenotype of the SCGB1A1+SCGB3A2high club cell subpopulation was significantly altered in IPF lung, with increased expression of mucins, cytokine and extracellular matrix genes. The single cell transcriptomic analysis reveals the cellular and molecular heterogeneity of club cells, and provide novel insights into the biological functions of club cells in the pathogenesis of IPF

Modulation of pulmonary fibrosis by IL-13Rα2

Pulmonary fibrosis is a progressive and fatal disease that involves the remodeling of the distal airspace and the lung parenchyma, which results in compromised gas exchange. The median survival time once diagnosed is less than three years. Interleukin (IL)-13 has been shown to play a role in a number of inflammatory and fibrotic diseases. IL-13 modulates its effector functions via a complex receptor system that includes the IL-4 receptor (R) α, IL-13Rα1, and the IL-13Rα2. IL-13Rα1 binds IL-13 with low affinity, yet, when it forms a complex with IL-4α, it binds with much higher affinity, inducing the effector functions of IL-13. IL-13Rα2 binds IL-13 with high affinity but has a short cytoplasmic tail and has been shown to act as a nonsignaling decoy receptor. Transfection of fibroblasts and epithelial cells with IL-13Rα2 inhibited the IL-13 induction of soluble collagen, TGF-β, and CCL17. Adenoviral overexpression of IL-13Rα2 in the lung reduced bleomycin-induced fibrosis. Our work shows that overexpression of IL-13Rα2 inhibits the IL-13 induction of fibrotic markers in vitro and inhibits bleomycin-induced pulmonary fibrosis. In summary our study highlights the antifibrotic nature of IL-13Ra2