Sleep: the sound of a local alarm clock.

Besides the master clock located in the suprachiasmatic nucleus (SCN) of the brain, additional clocks are distributed across the central nervous system and the body. The role of these 'secondary' clocks remains unclear. A new study shows that the lack of an internal clock in histamine neurons profoundly perturbs sleep.

Comprehensive measures of sound exposures in cinemas using smart phones

OBJECTIVES Sensorineural hearing loss from sound overexposure has a considerable prevalence. Identification of sound hazards is crucial, as prevention, due to a lack of definitive therapies, is the sole alternative to hearing aids. One subjectively loud, yet little studied, potential sound hazard is movie theaters. This study uses smart phones to evaluate their applicability as a widely available, validated sound pressure level (SPL) meter. Therefore, this study measures sound levels in movie theaters to determine whether sound levels exceed safe occupational noise exposure limits and whether sound levels in movie theaters differ as a function of movie, movie theater, presentation time, and seat location within the theater. DESIGN Six smart phones with an SPL meter software application were calibrated with a precision SPL meter and validated as an SPL meter. Additionally, three different smart phone generations were measured in comparison to an integrating SPL meter. Two different movies, an action movie and a children's movie, were measured six times each in 10 different venues (n = 117). To maximize representativeness, movies were selected focusing on large release productions with probable high attendance. Movie theaters were selected in the San Francisco, CA, area based on whether they screened both chosen movies and to represent the largest variety of theater proprietors. Measurements were analyzed in regard to differences between theaters, location within the theater, movie, as well as presentation time and day as indirect indicator of film attendance. RESULTS The smart phone measurements demonstrated high accuracy and reliability. Overall, sound levels in movie theaters do not exceed safe exposure limits by occupational standards. Sound levels vary significantly across theaters and demonstrated statistically significant higher sound levels and exposures in the action movie compared to the children's movie. Sound levels decrease with distance from the screen. However, no influence on time of day or day of the week as indirect indicator of film attendance could be found. CONCLUSIONS Calibrated smart phones with an appropriate software application as used in this study can be utilized as a validated SPL meter. Because of the wide availability, smart phones in combination with the software application can provide high quantity recreational sound exposure measurements, which can facilitate the identification of potential noise hazards. Sound levels in movie theaters decrease with distance to the screen, but do not exceed safe occupational noise exposure limits. Additionally, there are significant differences in sound levels across movie theaters and movies, but not in presentation time.

Interferon-free treatment of chronic hepatitis C with faldaprevir, deleobuvir and ribavirin: SOUND-C3, a Phase 2b study.

BACKGROUND & AIMS The safety and efficacy of the interferon-free combination of faldaprevir (NS3/A4 protease inhibitor), deleobuvir (BI 207127, non-nucleoside polymerase inhibitor), and ribavirin in treatment-naïve patients chronically infected with HCV genotype-1 was explored. METHODS SOUND-C3 was a multicenter, open-label Phase 2b study. Treatment-naïve patients chronically infected with HCV genotype-1a (IL28B CC genotype only; n = 12) and genotype-1b (n = 20) were assigned to 16 weeks of treatment with faldaprevir 120 mg once daily, deleobuvir 600 mg twice daily, and weight-based ribavirin. Patients with compensated liver disease, including cirrhosis, were eligible for inclusion in this study. The primary endpoint was sustained virological response 12 weeks after completion of therapy. RESULTS Sustained virological response rates 12 weeks after completion of therapy were 17% and 95% in patients infected with HCV genotype-1a and genotype-1b respectively. All four patients with cirrhosis achieved sustained virological response 12 weeks after completion of therapy. The most frequently reported adverse events of at least moderate intensity were anaemia (16%), nausea, vomiting and fatigue (9% each). Three (9%) patients discontinued because of adverse events. CONCLUSIONS The interferon-free regimen of faldaprevir, deleobuvir and ribavirin was efficacious in patients infected with genotype-1b and generally well tolerated.

Details of left ventricular radial wall motion supporting the ventricular theory of the third heart sound obtained by cardiac MR.

OBJECTIVE Obtaining new details of radial motion of left ventricular (LV) segments using velocity-encoding cardiac MRI. METHODS Cardiac MR examinations were performed on 14 healthy volunteers aged between 19 and 26 years. Cine images for navigator-gated phase contrast velocity mapping were acquired using a black blood segmented κ-space spoiled gradient echo sequence with a temporal resolution of 13.8 ms. Peak systolic and diastolic radial velocities as well as radial velocity curves were obtained for 16 ventricular segments. RESULTS Significant differences among peak radial velocities of basal and mid-ventricular segments have been recorded. Particular patterns of segmental radial velocity curves were also noted. An additional wave of outward radial movement during the phase of rapid ventricular filling, corresponding to the expected timing of the third heart sound, appeared of particular interest. CONCLUSION The technique has allowed visualization of new details of LV radial wall motion. In particular, higher peak systolic radial velocities of anterior and inferior segments are suggestive of a relatively higher dynamics of anteroposterior vs lateral radial motion in systole. Specific patterns of radial motion of other LV segments may provide additional insights into LV mechanics. ADVANCES IN KNOWLEDGE The outward radial movement of LV segments impacted by the blood flow during rapid ventricular filling provides a potential substrate for the third heart sound. A biphasic radial expansion of the basal anteroseptal segment in early diastole is likely to be related to the simultaneous longitudinal LV displacement by the stretched great vessels following repolarization and their close apposition to this segment.

“But look: we have sat here too long”: Hilary Mantel’s tightrope walk of present-tense usage

Even after Hilary Mantel has won the Man Booker prize two times in a row with Wolf Hall and Bring up the Bodies, her novelistic account of the life of Thomas Cromwell, her intriguing decision to write these historical novels in the present tense gave cause to surprisingly little extended comment beyond a perfunctory nod to its evocation of immediacy. This presents not only a lacunae in the discussion about Mantel’s novels, but is also symptomatic for a change in the contemporary critical evaluation of present-tense narration in general. If present-tense narration once used to be a marker for experimental daring and might even have implied a certain hostility towards fictionality, Mantel’s novels give ample evidence that literary sensibilities have changed. In order to understand the scope and nature of this change, my paper puts Mantel’s use of the present tense in the context of both the historical development of present-tense usage and the ample contemporary landscape of present-tense narration. This allows me to show that the complexities of present-tense usage belie a reduction of its effect to an evocation of immediacy. Rather, I argue, Mantel uses it for a delicate tightrope walk between proximity and distance, history and fiction, authenticity and imagination.

Computed Ultrasound Tomography in Echo Mode for Imaging Speed of Sound Using Pulse-Echo Sonography: Proof of Principle

The limitations of diagnostic echo ultrasound have motivated research into novel modalities that complement ultrasound in a multimodal device. One promising candidate is speed of sound imaging, which has been found to reveal structural changes in diseased tissue. Transmission ultrasound tomography shows speed of sound spatially resolved, but is limited to the acoustically transparent breast. We present a novel method by which speed-of-sound imaging is possible using classic pulse-echo equipment, facilitating new clinical applications and the combination with state-of-the art diagnostic ultrasound. Pulse-echo images are reconstructed while scanning the tissue under various angles using transmit beam steering. Differences in average sound speed along different transmit directions are reflected in the local echo phase, which allows a 2-D reconstruction of the sound speed. In the present proof-of-principle study, we describe a contrast resolution of 0.6% of average sound speed and a spatial resolution of 1 mm (laterally) × 3 mm (axially), suitable for diagnostic applications.

Full correction for spatially distributed speed-of-sound in echo ultrasound based on measuring aberration delays via transmit beam steering

Aberrations of the acoustic wave front, caused by spatial variations of the speed-of-sound, are a main limiting factor to the diagnostic power of medical ultrasound imaging. If not accounted for, aberrations result in low resolution and increased side lobe level, over all reducing contrast in deep tissue imaging. Various techniques have been proposed for quantifying aberrations by analysing the arrival time of coherent echoes from so-called guide stars or beacons. In situations where a guide star is missing, aperture-based techniques may give ambiguous results. Moreover, they are conceptually focused on aberrators that can be approximated as a phase screen in front of the probe. We propose a novel technique, where the effect of aberration is detected in the reconstructed image as opposed to the aperture data. The varying local echo phase when changing the transmit beam steering angle directly reflects the varying arrival time of the transmit wave front. This allows sensing the angle-dependent aberration delay in a spatially resolved way, and thus aberration correction for a spatially distributed volume aberrator. In phantoms containing a cylindrical aberrator, we achieved location-independent diffraction-limited resolution as well as accurate display of echo location based on reconstructing the speed-of-sound spatially resolved. First successful volunteer results confirm the clinical potential of the proposed technique.

Documenting sound change with smartphone apps

Crowdsourcing linguistic phenomena with smartphone applications is relatively new. Apps have been used to train acoustic models for automatic speech recognition (de Vries et al. 2014) and to archive endangered languages (Iwaidja Inyaman Team 2012). Leemann and Kolly (2013) developed a free app for iOS—Dialäkt Äpp (DÄ) (>78k downloads)—to document language change in Swiss German. Here, we present results of sound change based on DÄ data. DÄ predicts the users’ dialects: for 16 variables, users select their dialectal variant. DÄ then tells users which dialect they speak. Underlying this prediction are maps from the Linguistic Atlas of German-speaking Switzerland (SDS, 1962-2003), which documents the linguistic situation around 1950. If predicted wrongly, users indicate their actual dialect. With this information, the 16 variables can be assessed for language change. Results revealed robustness of phonetic variables; lexical and morphological variables were more prone to change. Phonetic variables like to lift (variants: /lupfə, lʏpfə, lipfə/) revealed SDS agreement scores of nearly 85%, i.e., little sound change. Not all phonetic variables are equally robust: ladle (variants: /xælə, xællə, xæuə, xæɫə, xæɫɫə/) exhibited significant sound change. We will illustrate the results using maps that show details of the sound changes at hand.