bluuebunny/crossref_metadata_2025 huggingface dataset:
Vowel intelligibility in clear speech produced by electrolaryngeal speakers
Authors: Cox Steven R. , Raphael Lawrence J. , Doyle Philip C.
Published: November 2017

This study assessed vowel intelligibility when electrolaryngeal (EL) speakers were instructed to use clear speech (CS). Eighteen consonant-vowel-consonant words containing /i/, /ɪ/, /ɛ/, and /æ/ were spoken by 10 laryngectomees in habitual speech (HS) and CS conditions. A total of 4,320 words across both speech conditions were recorded and then transcribed by 12, naïve listeners. Results indicate that vowel intelligibility was 85.4% (range = 77.8% to 90.6%) when EL speakers used HS compared to 82.7% (range = 75.0% to 92.8%) in CS. This finding suggests that CS does not facilitate improved vowel intelligibility for EL speakers. Future research will seek explanations for the lack of a CS benefit by examining the acoustic changes that occur when EL speakers use CS.
Intelligibility of sinewave consonants
Authors: Hillenbrand James , Clark Michael J.
Published: November 2017

A good deal of experimental work has assessed the intelligibility of sinewave speech (SWS), synthesized by mixing sinusoids that follow the formants of natural utterances. While SWS is clearly intelligible at some level, most SWS work has been conducted using sentences, whose intelligibility is affected by many factors in addition to those related to recognition at the phonetic level. Earlier work [Hillenbrand et al., J. Acoust. Soc. Am, 129, 3991–4000] measuring the intelligibility of SWS vowels in isolated syllables reported an identification rate of 55%, far above chance but ~40 percentage points lower that of the original signals. The present work tested the intelligibility of SWS versions of 23 consonant types in CV and VCV syllables with three vowel types ([ɑ i u]) spoken by one man and one woman. SW signals were generated from unedited envelope peaks rather than formants. Intelligibility averaged across 59 listeners was 59%, with large variability across both listeners (sd = 9.9) and, especially, consonant type (sd = 23.4). Recognition at the feature level was 65.5% for place, 78.4% for manner, 90.0% for voicing. Voicing results are especially striking given that SWS is fully aperiodic, and the fact that the representation of spectral shape in SWS is necessarily coarse.
Delayed effects of speech and non-speech stimuli on sibilant categorization
Authors: Chodroff Eleanor , Wilson Colin
Published: November 2017

Adaptation to the speech of a novel talker can involve at least two types of mechanism: phonetic learning (e.g., Samuel & Kraljic, 2009) and spectral contrast (e.g., Lotto & Kluender, 1998). While phonetic learning persists over long time periods, auditory effects such as spectral contrast have been demonstrated to occur for sounds that are temporally adjacent or separated by brief delays (e.g., 1.3s; Holt, 2005). The present study examined whether phonetic and auditory mechanisms can be distinguished by introducing a substantially longer delay between exposure and test. Five exposure conditions were examined across participants: exposure to syllables beginning with a relatively high or low COG [z], exposure to white noise matched in LTAS to the high or low COG [z]-initial syllables, and a baseline (no exposure) condition. Following exposure, participants performed a one-back image repetition detection task for 15 minutes, and then categorized members of the same 10-point [ʃ]-[s] continuum over 6 blocks. In comparison to baseline, exposure to speech had a significant and expected influence on sibilant categorization (e.g., the [ʃ]-[s] boundary shifted toward [s] following high COG [z] exposure). Speech and non-speech exposures were compared to determine whether spectral contrast is a viable explanation for long-lasting sibilant adaptation.
Segmenting words from bilingual speech: Evidence from 8- and 10-month-olds
Authors: Orena Adriel John , Polka Linda
Published: November 2017

Previous studies show that young monolingual infants use language-specific cues to segment words from multiword utterances in their native language. However, little is known about how infants deal with the segmentation challenge in bilingual environments. Here, we examined the word segmentation abilities of young infants in a mixed dual-language task. Infants were familiarized with an English-French passage containing a target word in each language, and were then tested on their recognition of those target words. Results confirm that 8-month-old monolingual infants show language-specific patterns in word segmentation: English- and French-monolingual infants segmented in their native language, but not in the other unfamiliar language. As a group, 8- and 10-month-old bilingual infants showed positive evidence of segmentation in both of their native languages. However, closer inspection of the data suggests that bilingual infants are only able to segment in the language in which they receive more exposure. Taken together, these results suggest a dose-response relationship between speech input and word segmentation: that is, more input in a language gives infants more opportunities to learn about how word boundaries are denoted in that language. This study also addresses the possible roles of attention and code-mixing on the development of word segmentation abilities.
Speech recognition and word learning in 24-month-olds: The roles of non-native speech and familiar words
Authors: Blanco Cynthia P. , Waxman Sandra R.
Published: November 2017

After 18 months of age, infants’ lexical representations are sufficiently flexible to recognize acoustically unfamiliar productions as variants of familiar words (Best et al., 2009; Mulak et al., 2013). For novel words, 24-month-olds still have trouble generalizing from native to non-native pronunciations, although exposure to the accent improves recognition (Schmale et al., 2011, 2012; White & Aslin, 2011). In the present study, we tested how quickly 24-month-olds could use exposure and familiar words to learn the meanings of novel words, on-line, when listening to Spanish-accented speech. In the exposure phase, twenty-four-month-olds heard a novel word embedded in a dialogue that either contained linguistic cues to the referent’s animacy (The vep is eating) or was uninformative (The vep is right here). Infants then saw two pictures at test, one animate and one inanimate, and were asked to find the vep. Looking time to the two potential referents here was compared to performance with native-accented speech (Ferguson et al., under review). Infants hearing Spanish-accented speech struggled to learn the referents of novel words, but differences also emerged between the accent conditions for familiar target words. Infants are slower to access the meanings of familiar words when hearing non-native speech.
Echolocating dolphins as opportunistic signal sources for observing fine structure in the impulse responses of acoustic scatterers
Authors: Ferguson Eric L. , Williams Stefan B. , Jin Craig T. , Ferguson Brian G.
Published: November 2017

Echolocating dolphins emit wideband acoustic signals as sequences of short duration pulses or clicks. Often, the waveforms of the clicks (especially during a buzz phase) have simple shapes that resemble a Ricker wavelet or a Gaussian modulated sinusoidal pulse. The main energy lobe of the pulse is of short duration (about 20 microseconds) with an inverted monopulse shape indicating a rarefaction (negative pressure pulse). An experimental bistatic active sonar system is configured in which a dolphin’s biological sonar transmissions are coupled with a wide aperture receiving array. The acoustic transmissions of free-ranging Indo-Pacific bottlenose (Tursiops aduncus) dolphins are sampled every 4 microseconds at three collinear hydrophones having an interelement spacing of 14 m and located 1 m above the sea floor in shallow water of depth 20 m. Insonification of the seafloor and sea surface boundaries by the short-duration pulses reveals fine structure in the observed forward scattering impulse responses of the boundaries. Features (or highlights) in the forward scattering impulse responses are measured to within a fraction of a microsecond leading to precise localization of the scatterer using the modified wavefront curvature passive ranging method. Also, it will be shown that a similar result is observed for a scatterer in the water column that was moving rapidly with respect to the echolocating dolphin.
Array invariant-based localization using ships of opportunity
Authors: Byun Gihoon , kim Jea Soo , Cho Chomgun , Song Hee-Chun , Byun Sung-Hoon
Published: November 2017

The array invariant (AI) proposed for robust source-range estimation with minimal knowledge of the environment in shallow water is based on the dispersion characteristics in ideal waveguides. This approach involves plane wave beamforming, utilizing coherent multiple arrivals separated in beam angle and travel time, referred to as “beam-time migration.” To resolve multipath arrivals in beam-time domain, AI requires either an impulsive source or Green’s function typically estimated from a known probe signal. For unknown source waveforms, it is possible to estimate the Green’s function using a ray-based blind deconvolution (RBD) which also utilizes simple conventional beamforming. Recently, the cascade of RBD and AI has been demonstrated for a towed source at 50-m depth broadcasting communication waveforms [J. Acoust. Soc. Am. 141, 3270–3273 (2017)]. Rather than the towed source, this study focuses on the feasibility of tracking a ship radiating random and anisotropic noise. The combination of RBD and AI is demonstrated to localize a ship of opportunity (200–900 Hz) along a track at ranges of 1.8–3.4 km and a 16-element, 56-m long vertical array in approximately 100-m deep shallow water.
Acoustic propagation from the Canadian Basin to the Chukchi Shelf
Authors: Ballard Megan S. , Sagers Jason D. , Lin Ying-Tsong , Badiey Mohsen , Worcester Peter F. , Pecknold Sean
Published: November 2017

The Pacific Arctic Region, encompassing the Bering, Chukchi, Western Beaufort, and Eastern Siberian shelves and seas, has experienced decadal changes in atmospheric conditions, seasonal sea-ice coverage, and seawater temperature. In the summer of 2016, the Canada Basin Acoustic Propagation Experiment (CANAPE) was conducted to understand the changing soundscape and to explore the use of acoustic signals as a remote sensing tool in the modern Arctic. During the experiment, low-frequency signals from five tomographic sources located in the Canada Basin were recorded by a short vertical line array of hydrophones deployed from a research vessel. The recordings were made at seven stations located in the Canada Basin, on the continental rise, and on the Chukchi Shelf. The propagation distances ranged from 50 km to 500 km, and the propagation conditions changed from ducted by the Beaufort Lens in the basin to upward refracting on the continental shelf. Multiple measurements of the sound speed profile were acquired at each station to characterize the temporal and spatial variability of the sound speed field. This talk examines the range-dependent measurements and explains the observed variability in the received signals through propagation modeling. [Work sponsored by ONR.]
Experimental characterization of the Green’s function in a room using sparse reconstruction principles
Authors: Fernandez-Grande Efren , Christiansen Rasmus Ellebæk
Published: November 2017

Measuring the Green’s function over the entire volume of a room would typically require an unfeasible number of measurements, due to requirements on spatial sampling. To alleviate the need for excessive measurements, sparse reconstruction methods can be employed, as they make it possible to reconstruct a seemingly undersampled signal. The present study proposes a method for acquiring experimentally the Green’s function in a room by measuring directly the mode shapes of the room, based on the conception that any mode can be expanded into a number of propagating waves. If the modes are described in the wavenumber domain (as a plane-wave expansion), sparse reconstruction methods can be employed, under the implicit assumption that each mode shape is represented as the superposition of a small number of plane waves. In addition, it is assumed that the medium is source-free and homogeneous. The methodology is examined numerically and verified experimentally, based on measurements in a lightly damped rectangular room.
Sound isolation of large transformers mounted on raised floors
Authors: Campanella Angelo J.
Published: November 2017

Transformers for substation service mounted on elevated floors often cause spurious sound to be transmitted to the spaces below it. Magnetostriction vibration of the massive iron core at 120 Hz and its harmonics drives the supporting floor to emit sound into the spaces below. Contemporary vibration isolation design fails to prescribe the proper isolation method since the mass of that transformer considerably exceeds that of the participating mass of the concrete floor. A vibration isolation paradigm is proposed of a two-body system in inertial space; the participating mass of the concrete floor being the second active body; the virtual mass of the pair along with the spring stiffness determines the resonance frequency. The ratio of that resonant frequency to that to be isolated is a measure of the expected isolation. For good isolation, the resonant frequency should be 1/10th that of the vibration to be isolated. The floor participating mass is approximated as a square one-half wavelength of the thin concrete slab bending wave. Recent case history supporting this model is described.
Ultrasonic cavitation-enabled treatment for therapy of hypertrophic cardiomyopathy: Proof-of-principle
Authors: Miller Douglas , Lu Xiaofang , Dou Chunyan , Zhu Yiying I. , Fabiilli Mario L. , Owens Gabe E. , Kripfgans Oliver D.
Published: November 2017

Ultrasound myocardial cavitation enabled treatment (MCET) creates scattered microlesions in the myocardium, which can be accumulated to produce a desired macrolesion. MCET was applied to the SS-16BN rat model of hypertrophic cardiomyopathy (HCM) for proof-of-principle as a means for myocardial reduction. A focused ultrasound transducer was targeted using 10 MHz imaging (10S, GE Vivid 7) to the left ventricular wall of anesthetized rats in a warmed water bath. Pulse bursts of 4 MPa peak rarefactional pressure amplitude were intermittently triggered 1:8 heartbeats during 10 min infusion of a microbubble suspension. Methylprednisolone was given to reduce initial inflammation and Losartan was given to improve healing. MCET significantly reduced the targeted wall thickness (n = 11) at 28 d post treatment by 16.2% (P<0.01) relative to shams (n = 8), with myocardial strain rate and endocardial border displacement reduced by 34% and 29%, respectively. This demonstrates sufficient effect for a therapeutic outcome similar to surgical myectomy or alcohol ablation. Premature ECG complexes and plasma troponin measurements at the time of treatment were found to be useful to gauge optimal and suboptimal treatments, and thus aid in achieving a desired impact. With clinical translation, MCET therapy should fill the need for a new non-invasive HCM therapy option.
An efficient boundary element solver for trans-abdominal high-intensity focused ultrasound treatment planning
Authors: Gélat Pierre , Haqshenas Seyyed Reza , Betcke Timo , van 't Wout Elwin , Saffari Nader
Published: November 2017

High-intensity focused ultrasound (HIFU) is a promising treatment modality for the non-invasive ablation of pathological tissue in many organs, including the liver. Since many patients are not suitable candidates for liver surgery, the possibility to locally deposit thermal energy in a non-invasive way would bear significant clinical impact. Optimal treatment planning strategies based on high-performance computing numerical methods are expected to form a vital component of a successful clinical outcome in which healthy tissue is preserved and optimal focusing achieved, thus compensating for soft tissue heterogeneity and the presence of ribs. The boundary element method (BEM) is an effective approach for this purpose because only the boundaries of the ribs and soft tissue regions require discretization, as opposed to standard approaches which require the entire volume around the ribcage to be meshed. A Galerkin discretized Burton-Miller formulation used in combination with preconditioning and matrix compression techniques was applied to compute the acoustic field generated by a focused array transducer in the presence of a layer of abdominal fat, a human ribcage model and liver tissue. The results demonstrate the effectiveness of this dedicated BEM algorithm for trans-abdominal HIFU treatment planning.
Focused-ultrasound mediated anti-alpha-synuclein antibody delivery for the treatment of Parkinson’s disease
Authors: Zhang Hairong , Sanchez Carlos S. , Kwon Nancy , Jackson-Lewis Vernice R. , Przedborski Serge , Konofagou Elisa
Published: November 2017

Parkinson’s disease (PD) is associated with the selective death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While the specific cause of the neuronal loss remains elusive, the abnormal accumulation of alpha synuclein (α-syn), a major constituent of Lewy bodies, is considered to play a central role in the pathology of PD. Previous studies have shown the potential of immunotherapy with antibodies against α-syn, but such treatments remain ineffective due to the presence of the blood-brain barrier (BBB), which hinders most therapeutic agents to diffuse to the brain parenchyma. Therefore, in this study, we used focused ultrasound (FUS) in conjunction with microbubbles to transiently and noninvasively open the BBB and deliver anti-α-syn monoclonal antibodies (mAb) to the brains of transgenic PD mouse models. Preliminary histological findings demonstrate that the FUS promotes the delivery of anti-α-syn mAb to the transgenic mice overexpressing the human A53T or A30P α-synuclein. We hypothesize that weekly FUS treatments with mAb will help ameliorate histopathological deficits such as alpha-synuclein and Lewy bodies represented in these mouse models of PD. Ongoing work aims to explore the potential of FUS-mediated drug delivery to achieve both neuroprotection and neurorestoration for the treatment of Parkinson’s disease.
Stress corrosion crack imaging in stainless steel using the time reversed elastic nonlinearity diagnostic and nonlinear resonant ultrasound spectroscopy
Authors: Anderson Brian E. , Young Sarah M. , Hogg Stephen M. , Gregg Joshua F.
Published: November 2017

Spent nuclear fuel is often stored in stainless steel canisters in the United States. Stainless steel is susceptible to Stress Corrosion Cracking (SCC). This presentation will discuss progress on the use of the Time Reversed Elastic Nonlinearity Diagnostic (TREND) and Nonlinear Resonant Ultrasound Spectroscopy (NRUS) to determine whether SCC is present and attempt to quantify the depth of the cracking. NRUS is the measurement of the amplitude dependence of a sample’s resonance frequency, which occurs because of a softening of the elastic modulus in damaged media. NRUS provides a global indication of damage in a sample. TREND employs time reversal acoustics, which focuses wave energy at various points of interest to excite localized high amplitude. The amplitude dependence of this localized energy allows pointwise inspection of a sample. [This work was funded by the Nuclear Energy University Program of the U.S. Department of Energy through a subcontract from Los Alamos National Laboratory.]
The role of nonlinear ultrasound in the diagnosis of early-stage damage in heterogeneous materials
Authors: Kim Gun , Yun Tae Sup , Kim Jin-Yeon , Kurtis Kimberly , Jacobs Laurence
Published: November 2017

Predictable noninvasive evaluation of engineering materials requires a more reliable sensing technique capable of providing quantitative information of early stage damage. Nonlinear ultrasound (NLU) is a promising candidate because it provides a direct measure of the nonlinear elastic behavior of materials. NLU excels in the direction and quantification of damage that originates at or beneath the material’s microscale. This talk will present a procedure for the second harmonic generation (SHG) measurements using nonlinear Rayleigh surface waves. This technique quantifies material nonlinearity through the acoustic nonlinearity parameter, β. Specifically, microscale material characterization of physical/chemical phenomena in heterogeneous materials will be reviewed by means of the acoustic nonlinearity parameter, β. The results reveal how the SHG technique can provide the quantitative relationship between the acoustic nonlinearity parameter and the damage state of these materials. Last, new strategies for the application of the SHG technique will be discussed with an emphasis on bio-engineering materials and rocks.
Broadband acoustic wave experiments in borehole configurations
Authors: Fan Huajun , Smeulders David
Published: November 2017

A borehole in the ground may penetrate rocks which are porous, permeable, and fractured. Pressure transients in the borehole will therefore cause viscous fluid to flow into and out of the wall of the borehole. This forced flow consumes some energy and affects the phase velocity of the waves traveling along the fluid column. These two effects can be evaluated to extract information about the rocks adjacent to the borehole, which is of paramount importance for the oil and gas industry. This work discusses laboratory wave experiments in a 7.5 m long vertical shock tube. Rock samples containing a vertical borehole and pre-fabricated fracture configurations are installed in the test section and filled with water. The shock tube generates broadband pressure transients in the borehole. These are measured in the borehole at variable depth by means of a sliding pressure probe. In this way borehole microseismograms are constructed from repetitive wave experiments. Borehole wave modes are identified using coherence analysis. It is found that the presence of fractures significantly influences the transmission and reflection of borehole waves over the fracture zone. Moreover, there is a strong correlation between fracture aperture and borehole acoustic properties.
The perception of English Vowels by Korean Native Speakers: Concerning the influence of the manner of articulation for consonants following vowels
Authors: Han Heesun , Nozawa Takeshi
Published: November 2017

The purpose of this study is to explore the perception of English vowels by Korean native speakers. It focuses on difficulty levels of perception for English vowels in relation to the sound environment. The sound environment is determined by differences in the manner of articulation of consonants following vowels. The experiment consists of 24 test words formed with six American English vowels(/i, ɪ, ɛ, æ, ɑ, ʌ/) embedded in four different sound environments (/hVt/, /pVt/, /pVn/, /pVl/). The experiment compares two words paired for each sound environment, examining judgment accuracy for each combination and the influence of sound environments. Twenty Korean native speakers in their 20s or 30s participated in the experiment. The results found that participants could rarely differentiate /i/ and /ɪ/, and /ɛ /and /æ/ in all sound environments. Moreover, judgment accuracy was lower overall for the /pVn/ and /pVl/ environments. For /pVl/, in particular, Korean native speakers misjudged /ʌ/ as /ɑ/, confirming that difficulty levels differed according to the sound environments.
Effects of clear speech and language background on multimodal perception of English fricatives
Authors: Cho Sylvia , Jongman Allard , Wang Yue , Sereno Joan A.
Published: November 2017

Research shows that acoustic modifications in clearly enunciated fricative consonants (relative to the plain, conversational productions) facilitate auditory fricative perception. However, clear-speech effects on visual fricative perception have received less attention. A comparison of auditory and visual (facial) clear-fricative perception is particularly interesting since sibilant fricatives in English are more auditorily salient while non-sibilants are more visually salient. This study thus examines clear-speech effects on audio-visual perception of English sibilant and non-sibilant fricatives. Native English perceivers and non-native perceivers with different L1 fricative inventories (Mandarin, Korean) identified clear and plain fricative-vowel syllables in audio-only (AO), visual-only (VO), and audio-visual (AV) modes. The results across perceiver groups and speech styles showed an overall visual benefit and auditory dominance (AV>AO>VO). Comparisons of styles revealed clear-speech benefits in AO across fricatives and groups, but different patterns were noted in the visual conditions. In VO and AV, clear speech helped the more visually salient non-sibilant identification for native perceivers; however, clear-speech benefits were less prominent in non-natives’ perception of the non-sibilants, which are non-existent in their L1s. These findings are discussed in terms of the relative audio-visual weighting that benefits perception in clear speech as a function of input saliency and perceiver experience.
Methods of unwrapping phase ambiguity and selecting direct sounds in an ultra short baseline positioning system
Authors: Liu Xuyan , Zou Nan , Zhang Yifeng
Published: November 2017

This paper presents a novel method to unwrap phase ambiguity and an expert system to select the direct sound from several reflecting pulses in an USBL positioning system. Generally, in the crossed-shaped USBL array, unwrapping ambiguity in the long edge is based on the absence of ambiguity in the short edge, where the array spacing is less than half-wavelength. However, if the positioning system works at a high frequency, which results in the short-edge phase ambiguity, the classical method to unwrap long-edge ambiguity will fail. This paper proposes a sector searching method for this scenario. It utilizes all combinations of two edges to solve all possible target orientations, and takes the mode as the final result. Additionally, hydrophones receive multi-path reflections besides the direct sound in practical application. The expert system is particularly used for selecting the direct sound correctly, which seriously effects the positioning precision. It contains series of criteria to evaluate the quality of each pulse and considers the pulse with the best quality as the direct sound. Simulation and field experiment results prove that the proposed methods are feasible and can achieve good accuracy. Keywords: USBL; phase ambiguity; expert system; and direct sound.
Vocalizing in chimpanzees is influenced by social-cognitive processes
Authors: Crockford Catherine , Wittig Roman M. , Zuberbühler Klaus
Published: November 2017

A study in wild chimpanzees shows that cognition-influenced vocalizing is not only a human trait but also occurs in chimpanzees.
Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis
Authors: Menachery Vineet D. , Gralinski Lisa E. , Mitchell Hugh D. , Dinnon Kenneth H. , Leist Sarah R. , Yount Boyd L. , Graham Rachel L. , McAnarney Eileen T. , Stratton Kelly G. , Cockrell Adam S. , Debbink Kari , Sims Amy C. , Waters Katrina M. , Baric Ralph S.
Published: November 2017

Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2′
O
-MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. Importantly, other approaches targeting other conserved pan-CoV functions have not yet proven effective against MERS-CoV, illustrating the broad applicability of targeting viral 2′
O
-MTase function across CoVs.
Inhibition of Retrograde Transport Limits Polyomavirus Infection
In Vivo
Authors: Maru Saumya , Jin Ge , Desai Dhimant , Amin Shantu , Shwetank  , Lauver Matthew D. , Lukacher Aron E.
Published: November 2017

PyVs can cause significant morbidity and mortality in immunocompromised individuals. No clinically efficacious anti-PyV therapeutic agents are available. A recently identified inhibitor of retrograde transport, Retro-2
cycl
, blocks movement of PyV virion-containing vesicles from early endosomes to the endoplasmic reticulum, an early step in the PyV life cycle. Retro-2
cycl
and its derivatives have been shown to inhibit infection by human PyVs in tissue culture. Here, we demonstrate that a derivative of Retro-2
cycl
, Retro-2.1, reduces infection by MuPyV in the kidneys of acutely infected mice. Mimicking the common clinical scenario of PyV resurgence, we further show that MuPyV levels increase in the kidneys of immunocompromised, persistently infected mice and that this increase is inhibited by Retro-2.1. These data provide the first evidence for control of a natural PyV infection
in vivo
by administration of an inhibitor of retrograde transport.
Rare cause of adrenal insufficiency
Authors: Hii Justin WS , Page Michael M , Wesseldine Andrew
Published: November 2017

A 72-year-old man presented with weight loss, night sweats and haemoptysis and was hypotensive. CT imaging showed rapidly enlarging bilateral adrenal masses, and he was found to have primary adrenal insufficiency. An adrenal gland biopsy revealed the rare diagnosis of primary adrenal lymphoma. This unique case highlights possible rare causes of adrenal masses and adrenal insufficiency, their investigation and management principles.
Comparison among adjuvant treatments for primary pterygium: a network meta-analysis
Authors: Fonseca Ellen Carrara , Rocha Eduardo Melani , Arruda Gustavo Viani
Published: November 2017

Purpose

Pterygium is a frequent ocular disease, where the major challenge is the high level of recurrence after its surgical removal. We performed a network meta-analysis to identify, among several adjuvant treatments for primary pterygium, which is the best to prevent recurrence.

Methods

A search was conducted using PubMed, Scientific Electronic Library Online, Latin American and Caribbean Centre on Health Sciences and Cochrane Eyes and Vision Group Trials Register between 1993 and 2015 for randomisedclinical trials (RCTs) comparing adjuvant treatments following primary pterygium surgery.

Results

24 RCTs that studied 1815 eyes of 1668 patients were included and allowed direct and indirect comparison among 14 interventions through network meta-analysis. The rank from the best to worse treatment to prevent recurrence is: conjunctival autograft + ciclosporin 0.05% eye drops, bare sclera + intraoperativemitomycin C (MMC) <0.02%, bare sclera + beta therapy (2500 cGy single dose), conjunctival autograft + beta therapy (1000 cGy single dose), bare sclera + MMC 0.02% eye drops, conjunctival autograft, bare sclera + intraoperative MMC >0.02%, bare sclera + ciclosporin 0.05% eye drops, bare sclera + intraoperative 5-fluorouracil 5%, amniotic membrane transplantation, bare sclera + intraoperative MMC 0.02%, conjunctival autograft + bevacizumab 0.05% eye drops, bare sclera + bevacizumab 0.05% eye drops and bare sclera alone.

Conclusion

The best adjuvant treatment to prevent recurrence after primary pterygium surgery is the association of conjunctival autograft and ciclosporin 0.05% eye drops. Bare sclera technique alone should be discontinued since it is associated with high recurrence rates.
Unequal cluster sizes in stepped-wedge cluster randomised trials: a systematic review
Authors: Kristunas Caroline , Morris Tom , Gray Laura
Published: November 2017

Objectives

To investigate the extent to which cluster sizes vary in stepped-wedge cluster randomised trials (SW-CRT) and whether any variability is accounted for during the sample size calculation and analysis of these trials.

Setting

Any, not limited to healthcare settings.

Participants

Any taking part in an SW-CRT published up to March 2016.

Primary and secondary outcome measures

The primary outcome is the variability in cluster sizes, measured by the coefficient of variation (CV) in cluster size. Secondary outcomes include the difference between the cluster sizes assumed during the sample size calculation and those observed during the trial, any reported variability in cluster sizes and whether the methods of sample size calculation and methods of analysis accounted for any variability in cluster sizes.

Results

Of the 101 included SW-CRTs, 48% mentioned that the included clusters were known to vary in size, yet only 13% of these accounted for this during the calculation of the sample size. However, 69% of the trials did use a method of analysis appropriate for when clusters vary in size. Full trial reports were available for 53 trials. The CV was calculated for 23 of these: the median CV was 0.41 (IQR: 0.22–0.52). Actual cluster sizes could be compared with those assumed during the sample size calculation for 14 (26%) of the trial reports; the cluster sizes were between 29% and 480% of that which had been assumed.

Conclusions

Cluster sizes often vary in SW-CRTs. Reporting of SW-CRTs also remains suboptimal. The effect of unequal cluster sizes on the statistical power of SW-CRTs needs further exploration and methods appropriate to studies with unequal cluster sizes need to be employed.
‘When it goes back to my normal I suppose’: a qualitative study using online focus groups to explore perceptions of ‘control’ among people with eczema and parents of children with eczema in the UK
Authors: Howells Laura M , Chalmers Joanne R , Cowdell Fiona , Ratib Sonia , Santer Miriam , Thomas Kim S
Published: November 2017

Objective

To inform the development of a core outcome set for eczema by engaging with people with eczema and parents of children with eczema to understand their experiences and understanding of the concept ‘eczema control’.

Design

37 participants took part in a total of six semi-structured online focus groups held in a typed chatroom with 5–7 participants per group. Three groups involved adults with eczema and three groups involved parents of children with eczema. Framework analysis was used for data analysis.

Setting

A community-based sample was recruited from across the UK via social media and email.

Participants

19 adults aged 17–61 years (15/19 female, 16/19 white) and 18 parents of children with eczema aged 9 months–17 years (9/18 female, 18/19 white).

Results

Four main themes were identified:(1) ‘Commonalities and differences in the experiences of control’: a reduction in symptoms such as itch and sleep loss characterised eczema control, but what level was acceptable differed across participants;(2) ‘Eczema control goes beyond the skin’: psychological factors, social factors, the constant scratching and the impact on everyday activities are a variety of ways an individual can be impacted;(3) ‘Stepping up and down of treatment’: participants’ stepped-up treatment in response to loss of control, but several factors complicated this behaviour. Control needed to be maintained after stepped-up treatment ended to be acceptable; and (4) ‘How to measure control’: self-report was generally preferred to allow frequent measurements and to capture unobservable features. Although most thought their eczema needed to be measured frequently, many also felt that this was not always realistic or desirable.

Conclusions

‘Eczema control’ is a complex experience for people with eczema and parents of children with the condition. These experiences could have important implications on how long-term control should be measured in eczema clinical trials and clinical practice.
Prevalence of diabetic retinopathy in children and young people living with diabetes: protocol for a systematic review
Authors: Ibanez-Bruron Maria Carolina , Solebo Ameenat L , Cumberland Phillippa M , Rahi Jugnoo S
Published: November 2017

Introduction

The frequency of diabetes mellitus in childhood is increasing. Thus, more children and young people are at risk of developing diabetic retinopathy and diabetes related visual impairment. However, there is no consensus on optimal screening strategies for the paediatric population reflecting the lack of clarity about the current burden of disease in this group. We aim to estimate the prevalence of diabetic retinopathy in children and young people living with types 1 or 2 diabetes, and to investigate potential sources of heterogeneity in this figure so as to inform screening strategies for this population.

Methods and analysis

PubMed and EMBASE will be searched from 1995 to 2016 using the OvidSP platform with no language restriction. Additionally, manual review of the references lists of included articles will be conducted. Two investigators will independently screen titles and abstracts for potential eligibility. Studies which report prevalence of diabetic retinopathy among general populations of children and young people with types 1 or 2 diabetes will be included. Pooled prevalence estimates of diabetic retinopathy reported in studies with sample size greater than 200 participants will be calculated by the random effect model. Forest plots will be used to summarise individual and pooled estimates of the prevalence. Heterogeneity between studies will be assessed using theI2statistic and explored through meta-regressions and subgroup analyses if the necessary data are available.

Ethics and dissemination

Ethics approval is not required as this is a review of anonymised published data. We will report the findings of this systematic review in a peer-reviewed journal, and share it with the relevant professionals including health authorities through our Diabetic Eye disease in Childhood Study collaborative network.

Clinical trail registration

PROSPERO (CRD42017067178).
A qualitative study of patient involvement in medicines management after hospital discharge: an under-recognised source of systems resilience
Authors: Fylan Beth , Armitage Gerry , Naylor Deirdre , Blenkinsopp Alison
Published: November 2017

Introduction

There are risks to the safety of medicines management when patient care is transferred between healthcare organisations, for example, when a patient is discharged from hospital. Using the theoretical concept of resilience in healthcare, this study aimed to better understand the proactive role that patients can play in creating safer, resilient medicines management at a common transition of care.

Methods

Qualitative interviews with 60 cardiology patients 6 weeks after their discharge from 2 UK hospitals explored patients’ experiences with their discharge medicines. Data were initially subjected to an inductive thematic analysis and a subsequent theory-guided deductive analysis.

Results

During interviews 23 patients described medicines management resilience strategies in two main themes: identifying system vulnerabilities; and establishing self-management strategies. Patients could anticipate problems in the system that supplied them with medicines and took specific actions to prevent them. They also identified when errors had occurred both before and after medicines had been supplied and took corrective action to avoid harm. Some reported how they had not foreseen problems or experienced patient safety incidents. Patients recounted how they ensured information about medicines changes was correctly communicated and acted upon, and described their strategies to enhance their own reliability in adherence and resource management.

Conclusion

Patients experience the impact of vulnerabilities in the medicines management system across the secondary–primary care transition but many are able to enhance system resilience through developing strategies to reduce the risk of medicines errors occurring. Consequently, there are opportunities—with caveats—to elicit, develop and formalise patients’ capabilities which would contribute to safer patient care and more effective medicines management.
Effectiveness and efficiency of different weight machine-based strength training programmes for patients with hip or knee osteoarthritis: a protocol for a quasi-experimental controlled study in the context of health services research
Authors: Krauss Inga , Müller Gerhard , Steinhilber Benjamin , Haupt Georg , Janssen Pia , Martus Peter
Published: November 2017

Introduction

Osteoarthritis is a chronic musculoskeletal disease with a major impact on the individual and the healthcare system. As there is no cure, therapy aims for symptom release and reduction of disease progression. Physical exercises have been defined as a core treatment for osteoarthritis. However, research questions related to dose response, sustainability of effects, economic efficiency and safety are still open and will be evaluated in this trial, investigating a progressive weight machine-based strength training.

Methods and analysis

This is a quasi-experimental controlled trial in the context of health services research. The intervention group (n=300) is recruited from participants of an offer for insurants of a health insurance company suffering from hip or knee osteoarthritis. Potential participants of the control group are selected and written to from the insurance database according to predefined matching criteria. The final statistical twins from the control responders will be determined via propensity score matching (n=300). The training intervention comprises 24 supervised mandatory sessions (2/week) and another 12 facultative sessions (1/week). Exercises include resistance training for the lower extremity and core muscles by use of weight machines and small training devices. The training offer is available at two sites. They differ with respect to the weight machines in use resulting in different dosage parameters. Primary outcomes are self-reported pain and function immediately after the 12-week intervention period. Health-related quality of life, self-efficacy, cost utility and safety will be evaluated as secondary outcomes. Secondary analysis will be undertaken with two strata related to study site. Participants will be followed up 6, 12 and 24 months after baseline.

Trial registration number

German Clinical Trial Register DRKS00009257. Pre-results.
Cyanotic congenital heart disease following fertility treatments in the United States from 2011 to 2014
Authors: Shamshirsaz Alireza A , Bateni Zhoobin H , Sangi-haghpeykar Haleh , Arian Sara E , Erfani Hadi , Shamshirsaz Amir A , Abuhamad Alfred , Fox Karin A , Ramin Susan M , Moaddab Amirhossein , Maskatia Shiraz A , Salmanian Bahram , Lopez Keila N , Hosseinzadeh Pardis , Schutt Amy K , Nassr Ahmed A , Espinoza Jimmy , Dildy Gary A , Belfort Michael A , Clark Steven L
Published: November 2017

Objective

To examine the risk for cyanotic congenital heart diseases (CCHDs) among live births in the USA, resulting from various forms of infertility treatments.

Methods

This study is a cross-sectional analysis of live births in the USA from 2011 to 2014. Infertility treatments are categorised into two of the following groups on birth certificates: assisted reproductive technology (ART) fertility treatment (surgical egg removal; eg, in vitro fertilisation and gamete intrafallopian transfer) and non-ART fertility treatment (eg, medical treatment and intrauterine insemination). We compared the risk for CCHD in ART and non-ART fertility treatment groups with those infants whose mothers received no documented fertility treatment and were naturally conceived (NC).

Results

Among 14 242 267 live births from 2011 to 2014, a total of 101 494 live births were in the ART and 81 242 resulted from non-ART fertility treatments. CCHD prevalence in ART, non-ART and NC groups were 393/100 892 (0.39%), 210/80 884 (0.26%) and 10 749/14 020 749 (0.08%), respectively. As compared with naturally conceiving infants, risk for CCHD was significantly higher among infants born in ART (adjusted relative risk (aRR) 2.4, 95% CI 2.1 to 2.7) and non-ART fertility treatment groups (aRR 1.9, 95% CI 1.6 to 2.2). Absolute risk increase in CCHD due to ART and non-ART treatments were 0.03% and 0.02%, respectively. A similar pattern was observed when the analysis was restricted to twins, newborns with birth weights under 1500 g and gestational age of less than 32 weeks.

Conclusions

Our findings suggest an increased risk for CCHD in infants conceived after all types of infertility treatment.
Variations in rotation of the aortic root and membranous septum with implications for transcatheter valve implantation
Authors: Tretter Justin T , Mori Shumpei , Saremi Farhood , Chikkabyrappa Sathish , Thomas Kristen , Bu Fang , Loomba Rohit S , Alsaied Tarek , Spicer Diane E , Anderson Robert H
Published: November 2017

Objective

It is intuitive to suggest that knowledge of the variation in the anatomy of the aortic root may influence the outcomes of transcatheter implantation of the aortic valve (TAVI). We have now assessed such variation.

Methods

We used 26 specimens of normal hearts and 78 CT data sets of adults with a mean age of 64±15 years to measure the dimensions of the membranous septum and to assess any influence played by rotation of the aortic root, inferring the relationship to the atrioventricular conduction axis.

Results

The aortic root was positioned centrally in the majority of both cohorts, although with significant variability. For the cadaveric hearts, 14 roots were central (54%), 4 clockwise-rotated (15%) and 8 counterclockwise-rotated (31%). In the adult CT cohort, 44 were central (56%), 21 clockwise-rotated (27%) and 13 counterclockwise-rotated (17%). A mean angle of 15.5° was measured relative to the right fibrous trigone in the adult CT cohort, with a range of −32° to 44.7°. The dimensions of the membranous septum were independent of rotation. Fibrous continuity between the membranous septum and the right fibrous trigone increased with counterclockwise to clockwise rotation, implying variation in the relationship to the atrioventricular conduction axis.

Conclusions

The central fibrous body is wider, providing greater fibrous support, in the setting of clockwise rotation of the aortic root. Individuals with this pattern may be more vulnerable to conduction damage following TAVI. Knowledge of such variation may prove invaluable for risk stratification.
Potential Approaches to Prevent Hypoglycemia-Associated Autonomic Failure
Authors: Lontchi-Yimagou Eric , You Jee Young , Carey Michelle , Gabriely Ilan , Shamoon Harry , Hawkins Meredith
Published: November 2017

Clear health benefits are associated with intensive glucose control in type 1 diabetes mellitus (T1DM). However, maintaining near-normal glycemia remains an elusive goal for many patients, in large part owing to the risk of severe hypoglycemia. In fact, recurrent episodes of hypoglycemia lead to ‘hypoglycemia-associated autonomic failure’ (HAAF), characterized by defective counter-regulatory responses to hypoglycemia. Extensive studies to understand the mechanisms underlying HAAF have revealed multiple potential etiologies, suggesting various approaches to prevent the development of HAAF. In this review, we present an overview of the literature focused on pharmacological approaches that may prevent the development of HAAF. The purported underlying mechanisms of HAAF include: 1) central mechanisms (opioid receptors, ATP-sensitive K+(KATP) channels, adrenergic receptors, serotonin selective receptor inhibitors, γ-aminobuyric acid receptors, N-methyl D-aspartate receptors); 2) hormones (cortisol, estrogen, dehydroepiandrosterone (DHEA) or DHEA sulfate, glucagon-like peptide-1) and 3) nutrients (fructose, free fatty acids, ketones), all of which have been studied vis-à-vis their ability to impact the development of HAAF. A careful review of the current literature reveals many promising therapeutic approaches to treat or reduce this important limitation to optimal glycemic control.