bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic detail in monolingual and bilingual children’s representations of English and Spanish
Authors: Blanco Cynthia P. , Smiljanic Rajka , Bannard Colin
Published: October 2015

Children must learn to process variations in the pronunciation of their language(s), but they must also learn the social meaning of particular kinds of variation. By preschool, children’s initially overly specific lexical representations have generalized to reflect commonalities in pronunciations, thus allowing children to recognize accented productions as instances of familiar lexical items (Best et al., 2009; Schmale, et al., 2010, 2011, 2012; Stager and Werker, 1997). However, elementary-school-aged children struggle to use the phonetic variation present in accented speech to understand social differences among talkers (Floccia et al., 2009; Girard et al., 2008). In the present study, we investigated children’s ability to associate acoustic cues with a particular language as a function of their language background (monolingual, significant L2 exposure, or bilingual). Children decided whether nonce words containing language-specific sounds were produced by a Spanish speaker or an English speaker. Language-specific cues included phonemes unique to Spanish (/r/) or English (/ɹ, θ/), or sound categories common to both languages but produced differently in each (/l, u/). The categorization patterns and reaction times of the three groups were compared, and results indicate that children with exposure to or proficiency in Spanish categorized the nonce words more accurately than monolinguals.
Accent and fluency in third language acquisition
Authors: Onishi Hiromi
Published: October 2015

This paper examined the influence of L2 on L3 accent and fluency. Target participants were native speakers of Chinese who have studied English as an L2 prior to beginning their study of Japanese as L3. Participants were recorded in L2 and L3, and their speech samples were rated by expert judges of respective language. The judges were asked to rate each speaker based on foreign accentedness and overall fluency. The results from English and Japanese were analyzed using correlation analysis. The result of the correlation analysis showed a positive correlation between accent in L2 and L3, which suggests that, regarding foreign accentedness, the better a speaker performs in L2, the better they also perform in L3. The correlation between L2 and L3 in terms of fluency did not reach significance, mostly due to the fact that fluency rating in English was done mildly by the judges. The result nevertheless showed a clear trend toward positive correlation between the two languages. This study contributes to the area of Third Language Acquisition by supporting the idea that L3 acquisition is qualitatively different from L2 acquisition, and phonological acquisition in L3 is influenced not only by the learner’s L1 but also their L2.
Foreign accentedness of English sentences spoken by Japanese EFL learners and Japanese teachers of English: A first report
Authors: Maeda Natsumi , Yoneyama Kiyoko
Published: October 2015

This study reports the results of a foreign-accented-rating experiment that investigate the foreign accentedness of spoken English sentences by two Japanese groups, Japanese EFL learners and Japanese teachers of English. This study aims first to investigate whether spoken English sentences by Japanese teachers of English are judged less foreign-accented than those by Japanese EFL learners, and second to investigate whether American-English listeners rate spoken English sentences by Japanese speakers more severely than Japanese listeners do. The stimuli were five sentences adopted from Flege, Munro, and McKay (1995) spoken by 33 Japanese EFL learners and 33 Japanese teachers of English. Ten American-English speakers and ten Japanese speakers were asked to rate the stimuli presented visually and auditorily by clicking along a line on the computer screen for their ratings. The participants’ original responses were converted to 10 scales and were submitted to the analyses. The results showed that spoken English sentences by Japanese teachers of English were rated significantly less Japanese-accented than those by Japanese EFL learners. The results further revealed that as in the previous studies, the American-English speakers rated spoken English sentences by two Japanese groups significantly more severely than Japanese speakers. [Work supported by JSPS.]
Production and perception skill developments of Korean coronal obstruents by inexperienced English-speaking learners of Korean
Authors: Park Hanyong
Published: October 2015

The present study investigates how speech production and perception abilities develop in second language learning among learners in a classroom setting. English-speaking students taking a first semester college course in Korean participated in both production and perception tasks. In the production task, the participants read a list of Korean frame sentences with target stimuli consisting of Korean /t t’ th s s’/ with /a/ in CV and VCV. To assess the production accuracy, native Koreans identified the consonants from the learners’ productions. In the perception task, the participants listened to the same corpus of Korean stimuli and identified the consonants with Korean orthography. The data were collected four times over two semesters: Week 5 or 6, and Week 13 or 14 of each semester. Results indicate that the learners’ overall production and perception abilities are correlated to each other in some but not all data collection times. Further analyses show that over two semesters, most learners did not improve much in overall perception abilities. Not much learning occurred either in production or perception for some sounds (e.g., /s/, /s’/). These findings suggest different learning units for production and perception as well as the powerful influence of native language.
Effects of training methods and attention on the identification and discrimination of American English coda nasals by native Japanese listeners
Authors: Nozawa Takeshi
Published: October 2015

The accuracy with which native Japanese listeners identified and discriminated American English coda nasals in /CVN/ context was assessed before and after training. The listeners were divided into four groups, each of which received a different type of training. Two of the four groups were vowel-oriented; one of these groups received vowel identification training (VI), while the other received vowel discrimination training (VD). The other two groups were nasal-oriented. One of the nasal-oriented groups received nasal identification training (NI), and the other received nasal discrimination training (ND). The results revealed that the two nasal-oriented groups made more gains in its ability to identify and discriminate American English coda nasals than the vowel-oriented groups after training. The result implies that identification and discrimination trainings are equally effective in improving listeners’ sensitivity to identify and discriminate American English coda nasals. The two vowel-oriented groups achieved modest improvement in identification and discrimination accuracy, which suggests that repeated exposure to stimuli can enhance listeners' sensitivity even when their attention is not on the target segment.
The effect of informational and energetic masking on foreign-accent adaptation
Authors: Ferracane Elisa , Blanco Cynthia P. , Dubois Michelle , Manrique Andrea , Smiljanic Rajka
Published: October 2015

Speech understanding in noisy environments can be compromised through energetic (EM) and informational (IM) masking. EM reduces intelligibility of target speech through spectro-temporal overlap with the masker at the auditory periphery level. IM refers to the higher-level interference, such as competing attention, linguistic interference, and increased cognitive load. The present study examined the effects of EM and IM on foreign-accent adaptation. Native English listeners heard blocks of sentences produced by native-accented (NA) or foreign-accented (FA) talkers (Korean, Spanish) mixed with speech-shaped noise (SSN) or two-talker, native-accented babble and responded to a visual probe. Preliminary results show that listeners were more accurate and faster in babble compared to SSN. The more successful FA adaptation in the babble condition may be related to the presence of dips in the masker energy or the ability of listeners to successfully separate FA target from the NA background speech. Additionally, the acoustic properties of the target sentences, such as speaking rate and pausing, are examined to understand their effect on FA adaptation in each of the two noise conditions. These findings suggest that IM was less disruptive than EM for FA adaptation even though listeners were processing FA speech with an increased cognitive load.
High frequency p-wave attenuation dispersion in water-saturated granular medium with bimodal grain size distribution
Authors: Yang Haesang , Lee Keunhwa , Seong Woojae
Published: October 2015

Compressional wave attenuation in water-saturated granular medium depends on both the frequency and grain size. In recent series of high frequency measurements on porous medium, such as water-saturated glass beads and marine sediments, the effect of grain size distribution on attenuation has been investigated, and a variety of grain size dependence on attenuation has been reported. Particularly, dispersion relation in the granular medium with bimodal grain size distribution is significantly different from that in the medium with unimodal grain size distribution. In this study, two sets of glass beads experiments employing unimodal and bimodal grain size distributions are performed. In order to examine wave propagation phenomenon in the bimodal grains, the attenuation dispersion is represented as a function of three parameters; porosity, volume fraction of scatterers, and Rayleigh parameter kd. Heuristic dispersion model considering scattering phenomenon will also be discussed for comparison with measurements.
Estimation of cylinder orientation using autonomous underwater vehicle mapping of bistatic scattered fields
Authors: Fischell Erin M. , Schmidt Henrik
Published: October 2015

When an aspect-dependent target is insonified by an acoustic source, distinct features are produced in the resulting bistatic scattered field. These features were exploited in a process for estimating target aspect angles that was demonstrated on a real-world data set using models produced using simulation data. Bistatic scattering data was collected during an experiment in November 2014 in Massachusetts Bay using a ship-based acoustic source producing 7-9kHz LFM chirps and a steel pipe target. The true target orientation was unknown, as the target was dropped from the ship with no rotation control. The Autonomous Underwater Vehicle (AUV) Unicorn, fitted with a 16-element nose array and data acquisition payload, was deployed in broadside data collection behaviors around the target, and the ship was moved to create two target aspects. Scattering data was collected for each target aspect angle. A Support Vector Machine (SVM) regression model was trained using simulated scattering bistatic field data from the OASES-SCATT simulation package. This model was used to estimate the target aspect angles using the real data collected by the AUV during the experiment. The aspect angle estimates were consistent with experimental observations of relative source positioning based on ship position.
Extending the distributed-basis transition matrix for acoustic target scattering to highly oblate elastic objects in free-field
Authors: Lim Raymond
Published: October 2015

In previously presented work, a variant of Waterman’s transition (T) matrix utilizing an ansatz for problematic outgoing basis functions in standard formulations was proposed and demonstrated to improve the stability of free-field acoustic scattering calculations for elongated axisymmetric elastic objects. The ansatz replaced the basis causing instability with a non-local basis consisting of low-order spherical functions made into a complete set by distributing the functions along the axis within the object. Unfortunately, as pointed out by Doicu, et al. [Acoustic & Electromagnetic Scattering Analysis Using Discrete Sources, Academic Press, London, 2000], these bases are not as useful for expanding surface fields on oblate axisymmetric shapes. However, they suggested an alternative basis for such shapes in the form of low-order spherical functions made complete by analytically continuing them into a complex plane of the axial coordinate of the object and distributing them along the imaginary axis of this axial coordinate. This presentation will show how this alternative performs in our T-matrix formulation for highly oblate axisymmetric objects, discuss sources of residual noise, and suggest ways to remediate the noise for such shapes. [Work supported by ONR.]
Modifying Tradition: Examining Organizational Change in Youth Sport
Authors: Legg Julie , Snelgrove Ryan , Wood Laura
Published: October 2015

The purpose of this study was to examine the process of change at the level of youth sport by identifying the impetus for change, responses to change by stakeholders, and factors that constrained or aided the change process. Theoretically, this study builds upon an existing integrative change model. The context of this research is two youth soccer associations in Ontario, Canada, undergoing a long-term structural redesign mandated by the provincial soccer association. Stakeholders from local soccer clubs, as well as the Ontario Soccer Association (N = 20), identified key factors influencing the implementation and success of change. Pressures to change and individual efforts made by board members, coaches, and parents were noted as aiding the change process. Limited collaboration with stakeholders, poor communication, misunderstandings of the change, and constrained organizational capacity negatively affected the change process.
Leaving a lasting impression
Authors: Wong Wei
Published: October 2015

Mesenchymal stem cells can use Fas delivered by exosomes to trigger long-lasting changes in epigenetic programming.
The Relationship between Microbial Community Evenness and Function in Slow Sand Filters
Authors: Haig Sarah-Jane , Quince Christopher , Davies Robert L. , Dorea Caetano C. , Collins Gavin
Published: October 2015

Two full-scale slow sand filters (SSFs) were sampled periodically from April until November 2011 to study the spatial and temporal structures of the bacterial communities found in the filters. To monitor global changes in the microbial communities, DNA from sand samples taken at different depths and locations within the SSFs and at different filters ages was used for Illumina 16S rRNA gene sequencing. Additionally, 15 water quality parameters were monitored to assess filter performance, with functionally relevant microbial members being identified by using multivariate statistics. The bacterial diversity in the SSFs was found to be much larger than previously documented, with community composition being shaped by the characteristics of the SSFs (filter age and depth) and sampling characteristics (month, side, and distance from the influent and effluent pipes). We found that several key genera (
Acidovorax
,
Halomonas
,
Sphingobium
, and
Sphingomonas
) were associated with filter performance. In addition, at the whole-community level, a strong positive correlation was found between species evenness and filter performance. This study is the first to comprehensively characterize the microbial community of SSFs and link specific microbes to water quality parameters. In doing so, we reveal key patterns in microbial community structure that relate to overall community function.

IMPORTANCE
The supply of sustainable, energy-efficient, and safe drinking water to an increasing world population is a huge challenge faced by the water industry. SSFs have been used for hundreds of years to provide a safe and reliable source of potable drinking water, with minimal energy requirements. However, a lack of knowledge pertaining to the treatment mechanisms, particularly the biological processes, underpinning SSF operation has meant that SSFs are still operated as “black boxes.” Understanding these dynamics alongside performance-induced effects associated with operational differences will promote optimized SSF design, maintenance, and operation, creating more efficient and environmentally sustainable filters. Through a spatial-temporal survey of full-scale SSFs at various points of operation, we present the most detailed characterization to date of the functional microbial communities found in SSFs, linking various taxa and community metrics to optimal water quality production.
Direct Target Network of the Neurospora crassa Plant Cell Wall Deconstruction Regulators CLR-1, CLR-2, and XLR-1
Authors: Craig James P. , Coradetti Samuel T. , Starr Trevor L. , Glass N. Louise
Published: October 2015

Fungal deconstruction of the plant cell requires a complex orchestration of a wide array of intracellular and extracellular enzymes. In
Neurospora crassa
, CLR-1, CLR-2, and XLR-1 have been identified as key transcription factors regulating plant cell wall degradation in response to soluble sugars. The XLR-1 regulon was defined using a constitutively active mutant allele, resulting in hemicellulase gene expression and secretion under noninducing conditions. To define genes directly regulated by CLR-1, CLR-2, and XLR-1, we performed chromatin immunoprecipitation and next-generation sequencing (ChIPseq) on epitope-tagged constructs of these three transcription factors. When
N. crassa
is exposed to plant cell wall material, CLR-1, CLR-2, and XLR-1 individually bind to the promoters of the most strongly induced genes in their respective regulons. These include promoters of genes encoding cellulases for CLR-1 and CLR-2 (CLR-1/CLR-2) and promoters of genes encoding hemicellulases for XLR-1. CLR-1 bound to its regulon under noninducing conditions; however, this binding alone did not translate into gene expression and enzyme secretion. Motif analysis of the bound genes revealed conserved DNA binding motifs, with the CLR-2 motif matching that of its closest paralog in
Saccharomyces cerevisiae
, Gal4p. Coimmunoprecipitation studies showed that CLR-1 and CLR-2 act in a homocomplex but not as a CLR-1/CLR-2 heterocomplex.

IMPORTANCE
Understanding fungal regulation of complex plant cell wall deconstruction pathways in response to multiple environmental signals via interconnected transcriptional circuits provides insight into fungus/plant interactions and eukaryotic nutrient sensing. Coordinated optimization of these regulatory networks is likely required for optimal microbial enzyme production.
Impacted Science: Impact Is Not Importance
Authors: Casadevall Arturo , Fang Ferric C.
Published: October 2015

The journal impact factor (IF) exerts a tremendous influence on the conduct of scientists. The obsession with IF has been compared to a medical condition, sometimes referred to as “IF mania” or “impactitis.” Here, we analyze the difference between impact and importance, using examples from the history of science to show that these are not equivalent. If impact does not necessarily equal importance, but scientists are focused on high-impact work, there is a danger that misuse of the IF may adversely affect scientific progress. We suggest five measures to fight this malady: (i) diversify journal club selections, (ii) do not judge science on the publication venue, (iii) reduce the reliance on journal citation metrics for employment and advancement, (iv) discuss the misuse of the IF in ethics courses, and (v) cite the most appropriate sources. If IF mania is indeed a medical condition, the most appropriate course of action may be disimpaction.
Blockade of the Brachial Plexus Abolishes Activation of Specific Brain Regions by Electroacupuncture at Li4: A Functional Mri Study
Authors: Gu Weidong , Jiang Wei , He Jingwei , Liu Songbin , Wang Zhaoxin
Published: October 2015

Objective

Our aim was to test the hypothesis that electroacupuncture (EA) at acupuncture point LI4 activates specific brain regions by nerve stimulation that is mediatied through a pathway involving the brachial plexus.

Methods

Twelve acupuncture naive right-handed volunteers were allocated to receive three sessions of EA at LI4 in a random different order (crossover): (1) EA alone (EA); EA after injection of local anaesthetics into the deltoid muscle (EA+LA); and (3) EA after blockade of the brachial plexus (EA+NB). During each session, participants were imaged in a 3 T MRI scanner. Brain regions showing change in blood oxygen level-dependent (BOLD) signal (activation) were identified. Subjective acupuncture sensation was quantified after functional MRI scanning was completed. Results were compared between the three sessions for each individual, and averaged.

Results

Blockade of the brachial plexus inhibited acupuncture sensation during EA. EA and EA+LA activated the bilateral thalamus, basal ganglia, cerebellum and left putamen, whilst no significant activation was observed during EA+NB. The BOLD signal of the thalamus correlated significantly with acupuncture sensation score during EA.

Conclusions

Blockade of the brachial plexus completely abolishes patterns of brain activation induced by EA at LI4. The results suggest that EA activates specific brain regions through stimulation of the local nerves supplying the tissues at LI4, which transmit sensory information via the brachial plexus.

Trial Registration Number

ChiCTR-OO-13003389.
An unusual case of a patient who presented with haemorrhagic shock following massive subcutaneous haematomas of the lower back due to blunt trauma
Authors: Yumoto Tetsuya , Sato Keiji , Ugawa Toyomu , Ujike Yoshihito
Published: October 2015

An 83-year-old woman with no significant medical history was transferred to our tertiary hospital after being hit by a car and presenting with haemorrhagic shock. Immediate fluid resuscitation was performed; physical, chest/pelvic X-ray and echographic examinations did not detect any major sources of bleeding. However, a contrast-enhanced CT scan revealed multiple regions of significant contrast extravasation in an extensive part of the subcutaneous tissue of the patient's lower back, which is an unusual source of bleeding. Transcatheter arterial embolisation of the lumbar and internal iliac arteries and their branches was carried out. In addition, haemostatic resuscitation was performed for damage control resuscitation, which successfully resolved the patient's haemorrhagic shock.
Application of two versions of the WHO/international society of hypertension absolute cardiovascular risk assessment tools in a rural Bangladeshi population
Authors: Fatema Kaniz , Zwar Nicholas Arnold , Milton Abul Hasnat , Rahman Bayzidur , Ali Liaquat
Published: October 2015

Objectives

To estimate the absolute cardiovascular disease (CVD) risk burden in a remote rural Bangladeshi population using the ‘With’ and ‘Without’ Cholesterol versions of the WHO/International Society of Hypertension (WHO/ISH) CVD risk assessment chart (particularly suitable for low and middle-income countries due to less reliance on laboratory testing) and to evaluate the agreement between the two approaches.

Design

Cross-sectional study using data from a large prospective cohort of the North Bengal Non-Communicable Disease Programme (NB-NCDP) of Bangladesh.

Setting

General rural population from Thakurgaon district of Bangladesh.

Participants

563 individuals who were categorised as having ‘no CVDs’ on screening by a questionnaire-based survey using the ‘WHO CVD-Risk Management Package’ developed in 2002.

Main outcome measures

Absolute CVD risk burden assessed using two versions of the WHO/ISH risk assessment charts for the South-East Asian Region-D.

Results

10-year risk (moderate, high and very high) positivity was present among 21.5% and 20.2% of participants, respectively, using with and without cholesterol versions of the tool. The overall concordance rate for the two versions was 89.5% and they did not differ significantly in estimating the proportion of overall participants having higher levels of CVD. The projected drug requirement, however, showed a significant overestimation in the proportion of participants at both the threshold levels (p<0.002) on using ‘without’ as compared to ‘with’ cholesterol versions.

Conclusions

About one-fifth of the adult population in Bangladesh, even in a remote rural area, seem to be at risk of developing CVDs (25% of them at high risk and 25% at very high risk) within 10 years with males and females being almost equally vulnerable.
Increasing incidence of recent hepatitis C virus infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan
Authors: Tsai Jen-Chih , Hung Chien-Ching , Chang Sui-Yuan , Liu Wen-Chun , Wu Cheng-Hsin , Su Yi-Ching , Wu Pei-Ying , Luo Yu-Zhen , Chang Lan-Hsin , Sun Hsin-Yun , Chang Shan-Chwen
Published: October 2015

Objectives

The incidence of hepatitis C virus (HCV) infection among HIV-negative men who have sex with men (MSM) is rarely investigated in the Asia-Pacific region. We aimed to estimate the incidence rate of and factors associated with recent HCV infection among the clients seeking voluntary counselling and testing (VCT) services for HIV in Taiwan.

Methods

During 2006–2013, 12 143 clients sought VCT services for HIV. Clients with subsequent follow-up tests at an interval of 6 months or longer were included to estimate the incidence rate of HCV seroconversion. Phylogenetic analysis of HCV sequences from VCT clients and HIV-positive patients was performed.

Results

The overall HCV seroprevalence at baseline was 0.3%. Of 2150 clients testing negative for anti-HCV antibody at baseline with a total of 5074.99 person-years of follow-up (PYFU), 17 (0.8%) developed HCV seroconversion, leading to an overall incidence rate of 3.35 per 1000 PYFU (95% CI 1.76 to 4.94), which increased from 2.28 (95% CI 0.05 to 4.51) in 2006–2009, to 3.33 (95% CI 0.86 to 5.80) in 2010 to 2011 and 4.94 per 1000 PYFU (95% CI 0.99 to 8.99) in 2012–2013; the incidence of early syphilis increased from 11.91 to 13.28 and 31.78 per 1000 PYFU in the three corresponding periods. In multivariate analysis, having HIV-positive partners (adjusted HR (AHR) =3.756; 95%CI 1.180 to 11.955) and developing a rapid plasma reagin titre of 4 or greater (AHR=9.978; 95% CI 1.550 to 64.233) were significantly associated with HCV seroconversion.

Conclusions

An increasing trend of recent HCV infection occurs among individuals seeking VCT services in Taiwan. Having HIV-positive partners and having syphilis are independently associated with recent HCV seroconversion.
Understanding burn injuries in Aboriginal and Torres Strait Islander children: protocol for a prospective cohort study
Authors: Ivers Rebecca Q , Hunter Kate , Clapham Kathleen , Coombes Julieann , Fraser Sarah , Lo Serigne , Gabbe Belinda , Hendrie Delia , Read David , Kimble Roy , Sparnon Anthony , Stockton Kellie , Simpson Renee , Quinn Linda , Towers Kurt , Potokar Tom , Mackean Tamara , Grant Julian , Lyons Ronan A , Jones Lindsey , Eades Sandra , Daniels John , Holland Andrew J A
Published: October 2015

Introduction

Although Aboriginal and Torres Strait Islander children in Australia have higher risk of burns compared with non-Aboriginal children, their access to burn care, particularly postdischarge care, is poorly understood, including the impact of care on functional outcomes. The objective of this study is to describe the burden of burns, access to care and functional outcomes in Aboriginal and Torres Strait Islander children in Australia, and develop appropriate models of care.

Methods and analysis

All Aboriginal and Torres Strait Islander children aged under 16 years of age (and their families) presenting with a burn to a tertiary paediatric burn unit in 4 Australian States (New South Wales (NSW), Queensland, Northern Territory (NT), South Australia (SA)) will be invited to participate. Participants and carers will complete a baseline questionnaire; follow-ups will be completed at 3, 6, 12 and 24 months. Data collected will include sociodemographic information; out of pocket costs; functional outcome; and measures of pain, itch and scarring. Health-related quality of life will be measured using the PedsQL, and impact of injury using the family impact scale. Clinical data and treatment will also be recorded. Around 225 participants will be recruited allowing complete data on around 130 children. Qualitative data collected by in-depth interviews with families, healthcare providers and policymakers will explore the impact of burn injury and outcomes on family life, needs of patients and barriers to healthcare; interviews with families will be conducted by experienced Aboriginal research staff using Indigenous methodologies. Health systems mapping will describe the provision of care.

Ethics and dissemination

The study has been approved by ethics committees in NSW, SA, NT and Queensland. Study results will be distributed to community members by study newsletters, meetings and via the website; to policymakers and clinicians via policy fora, presentations and publication in peer-reviewed journals.
Factors influencing long-term outcomes in relapsing–remitting multiple sclerosis: PRISMS-15
Authors: Kappos Ludwig , Kuhle Jens , Multanen Juha , Kremenchutzky Marcelo , Verdun di Cantogno Elisabetta , Cornelisse Peter , Lehr Lorenz , Casset-Semanaz Florence , Issard Delphine , Uitdehaag Bernard M J
Published: October 2015

Aim

An exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) β-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing–remitting multiple sclerosis (RRMS).

Methods

Patients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS-15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN β-1a dose groups, and according to total time receiving sc IFN β-1a as a continuous variable per 5 years of treatment. Potential prognostic factors for outcomes were analysed.

Results

Of 560 patients randomised in PRISMS, 291 returned for PRISMS-15 and 290 (51.8%) were analysed. Higher cumulative dose exposure and longer treatment time appeared to be associated with better outcomes on: annualised relapse rate, number of relapses, time to Expanded Disability Status Scale (EDSS) progression, change in EDSS, proportions of patients with EDSS ≥4 or ≥6, ≤5 relapses and EDSS <4 or <6, and time to conversion to secondary-progressive MS (SPMS). Higher dose exposure was associated with lower proportions of patients with EDSS progression and conversion to SPMS, and longer time on treatment with lower risk of first relapse. Change in EDSS from baseline to 24 months was a strong predictor of evaluated clinical outcomes over 15 years.

Conclusions

These findings suggest that higher cumulative exposure to sc IFN β-1a may be associated with better clinical outcomes, and early change in EDSS score may have prognostic value, over many years, in RRMS.
OCULAR MG IN 101 CASES: TOWARDS A RISK OF GENERALISATION (‘ROG’) SCORE
Authors: Wong Sui , Petrie Aviva , Plant Gordon
Published: October 2015

Background

There is no prognostic test to predict generalized myasthenia gravis (GMG) risk in patients with ocular disease. We aimed to create a predictive risk score.

Method

Multi-centre retrospective cohort study: OMG for minimum 3 months, untreated with immunosuppression for minimum 2 years or until GMG onset.

Results

101 (57F) patients included. Median follow-up 8.4 y(2–42) from onset. 31 developed GMG at median 1.31 y (3.5 mo–20.2 y); 19 within 2 y.

3 significant predictors from univariable logistic regression analysis (p<0.10); adjusted ORs in multivariable model (Chi-square p=0.001): seropositivity 5.63 (1.42,22.33); presence of ≥1 comorbidity including autoimmune disorders 5.56 (0.66,46.62); thymic hyperplasia 6.66 (0.45,98.01).

Prognostic score derived from the coefficients of the logistic model: sum of the points(one point for presence of each of the above predictive factors); classified ‘low risk’ if ≤1, ‘high risk’ if ≥2. Predicted probabilities: 0.07 (SD 0.03) for ‘low risk’, 0.39(SD 0.09) for ‘high risk’. Negative predictive value 91%(79,98), positive predictive value 38% (23,54), area under ROC curve 0.74 (0.64,0.85).

Conclusions

We present one of the few natural history studies on OMG and create the first predictive score to prognosticate the risk of GMG. This approach of risk stratification moves us towards addressing the question of modifying GMG risk in high-risk patients.
PARAMYOTONIA CONGENITA & SODIUM CHANNEL MYOTONIA: ARE THEY DISTINCT DISEASES?
Authors: Rayan Dipa Raja , Horga Alejandro , Matthews Emma , Sud Richa , McCall Samuel , Hanna Michael
Published: October 2015

Paramyotonia congenita (PMC) and sodium channel myotonia (SCM) have been considered as phenotypically distinct diseases since the potassium aggravated myotonias were first described. They are marked by the presence and absence of weakness and thought to have distinctive neurophysiology patterns. However there is little phenotypic data published comparing large groups of these patients. We investigated a large cohort of 137 patients with mutations in the sodium channel, SCN4A, to identify phenotypic differences between these groups. We found that, whilst there were distinct differences between those patients with Hyperkalaemic periodic paralysis and PMC/SCM, there were no significant phenotypic differences between PMC and SCM patients. This was both when comparing patients with and without episodes of weakness and comparing those with distinct neurophysiology patterns. We therefore propose that PMC and SCM, whilst being separate from Hyperkalaemic periodic paralysis, are part of a spectrum of the same disease and that patients are more likely to lie at a particular point on that spectrum depending on their specific genotype.
SINGLE CENTRE RANDOMISED PILOT STUDY OF TWO REGIMENS (30 MINS DAILY OR 30 MINS WEEKLY FOR 12 WEEKS) OF TRANSCUTANEOUS TIBIAL NERVE STIMULATION USING A NOVEL DEVICE FOR TREATING MULTIPLE SCLEROSIS-RELATED OVERACTIVE BLADDER SYMPTOMS
Authors: Seth Jai , Haslam Collette , Gonzales Gwen , Pakzad Mahreen , Vashisht Arvind , Elneil Sohier , Sahai Arun , Knowles Charles , Tucker Art , Panicker Jalesh
Published: October 2015

Introduction

Percutaneous tibial nerve stimulation (PTNS) is effective for managing multiple sclerosis (MS)-related overactive bladder (OAB) symptoms. However the need for weekly clinic visits restricts its use. The purpose of this study was to evaluate safety and efficacy of a novel, self-applying device for managing OAB symptoms.

Study design, materials and methods

48 patients reporting OAB (MS n=24, idiopathic n=24), were randomized (1:1) to either daily or weekly treatments for 12 weeks with geko™, a novel device stimulating the tibial nerve transcutaneously. Efficacy was assessed using validated questionnaires (ICIQ-OAB, ICIQLUTS-QoL) and bladder diaries filled at weeks 4, 8, and 12. Urinary neurotrophins (Nerve growth factor (NGF) and Brain derived neurotrophic factor) were measured.

Results

34 patients (MS n=19) completed the study. 18 patients responded to treatment (53%); 72% of responders belonged to the MS cohort. Multilevel regression analysis suggested significant improvements in questionnaire scores (ICIQ-OAB –10.2 (–13.5 to –6.9; p=0.001), ICIQLUTS-QOL –40.8 (–57.4 to –24.3; p=0.000)), without differences between weekly and daily-treated arms. No significant adverse effects were reported and patients rated the treatment as easy to use and comfortable. NGF levels at baseline were significantly greater in non-responders (p=0.05).

Concluding message

In this pilot study, a patch device suitable for self-application at home appears to be an effective, safe and convenient alternative for managing MS-related OAB symptoms.
ANTI-JCV TITRES INCREASE OVER TIME WITH NATALIZUMAB TREATMENT
Authors: Raffel Joel , Gafson Arie , Nicholas Richard
Published: October 2015

Objectives

This study sought to evaluate rates of anti-JCV antibody seroconversion and prospective change in antibody titre in a cohort of people with MS receiving natalizumab.

Methods

Anti-JCV antibody results (n=1154) from the second-generation STRATIFY JCV™ DxSelect™ test were analysed from an observational cohort of MS patients on natalizumab (n=485; n= 340 with repeat testing).

Results

At baseline, 59% (287/485) of patients were JCV seropositive; 33% (162/485) had a high anti-JCV antibody index (> 1.5). Baseline titres and rates of seropositivity increased slightly with baseline patient age. With multiple tests repeated over time, 22.3% of seronegative patients converted to seropositive. When comparing pairs of prospective tests, seroconversion rate was greater than seroreversion rate (40/373 (10.7%) vs 18/296 (6.1%); p<0.05). Moreover, anti-JCV antibody titres increased across prospective paired tests (mA-B 0.095; paired t(668)=4.6; p<0.0001) – an effect that was independent of baseline sample titre. This magnitude of antibody level increase far exceeds that expected due to age alone.

Conclusions

Our data suggest that natalizumab therapy itself causes anti-JCV antibody titres to increase over time. Future work should investigate the underlying mechanisms, and clinical relevance to risk stratification of this phenomenon.
ANALYSIS OF THE TOPIC STUDY USING 2010 MCDONALD CRITERIA
Authors: Rog David , Wolinsky Jerry , Truffinet Philippe , Thangavelu Karthinathan , Miller Aaron
Published: October 2015

Introduction

TOPIC (NCT00622700) was designed to evaluate teriflunomide in patients with a first clinical episode suggestive of multiple sclerosis (MS). Teriflunomide 14 mg reduced risk of relapse determining conversion to clinically definite MS by 42.6%, and of new relapse or magnetic resonance imaging lesion by 34.9% vs placebo. After study initiation, the 2005 McDonald criteria were revised, potentially allowing earlier MS diagnosis.

Methods

The 2010 McDonald criteria were applied retrospectively. Patients who received teriflunomide 14 mg or placebo for ≤108 weeks were grouped according to fulfilment of 2010 criteria at baseline. Time to MS was analysed for those not fulfilling the 2010 criteria at baseline. Additional post hoc analyses will evaluate differences in outcomes based on baseline radiological characteristics of reclassified patients.

Results

Patients receiving teriflunomide 14mg (n=214) or placebo (n=197) were analysed. For those not meeting the 2010 criteria (n=163), probability of conversion to MS was 54.1% (14 mg) and 74.4% (placebo). Teriflunomide 14mg reduced the probability of conversion to MS by 39.1% vs placebo. Data regarding time to MS based upon baseline radiological characteristics will be presented.

Conclusions

Teriflunomide demonstrates a consistent treatment effect in patients with MS diagnosed according to differing diagnostic criteria. (Study supported by Genzyme, a Sanofi company).
PSYCHOLOGICAL ATTRIBUTES AND WORK INSTABILITY IN MS
Authors: Wicks C R , Ward Karl , Stroud Amanda , Tennant Alan , Ford Helen
Published: October 2015

For people with MS (PWMS) the relationship between job retention and psychological factors is unclear. This may lead to psychological interventions to aid job retention. This study aims to investigate relationships between psychological factors, work instability and MS in a longitudinal prospective study of PWMS in paid employment.

Participants completed two time point questionnaire packs of validated scales with repeat testing planned. 221 employed PWMS were recruited. Mean age was 40.6; 75.1% were female. 91% had relapsing-remitting MS (RRMS). 213 (96.4%) completed the baseline questionnaire, 199 completed month 8. Disease progression was mostly stable with just 3% transitioning from RRMS. 57.2% were at medium/high risk of job loss, with only marginal changes in work instability at 8 months. 14% reported high physical and psychological impact of MS at baseline which remained unchanged. There was a strong association between risk of job loss and both physical and psychological variables. Some psychological variables fluctuated, e.g. depression fell from 24.6% to 14.5%. No changes were reported in levels of fatigue or pain over this period.

Psychological attributes in MS appear to fluctuate but contribute to work instability. Further investigation will clarify this relationship and inform possible intervention strategies.
PATIENT-REPORTED OUTCOMES AND DISABILITY IN MULTIPLE SCLEROSIS
Authors: Scolding Neil , Wang Hongwei , Liu Yan , Steinman Lawrence
Published: October 2015

In the 2-year, phase 3 CARE-MS II study (NCT00548405), alemtuzumab demonstrated superior clinical and patient-reported outcomes (PROs) over subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis patients who had inadequate efficacy response to prior therapy. To further evaluate the relationship between PROs and disability, Short-Form 36-Item (SF-36) survey physical component summary (PCS) and mental component summary (MCS), and Functional Assessment of Multiple Sclerosis (FAMS) scores were analysed against Expanded Disability Status Scale (EDSS) outcomes, adjusted for baseline characteristics and randomisation arm. A 1.0-point difference in baseline EDSS score was associated with 2.0-point PCS, 0.8-point MCS, and 4.0-point FAMS worsening over 12 months (all P<0.001). A 1.0-point annualised EDSS score worsening corresponded to a 2.2-point PCS, 1.6-point MCS, and 6.0-point FAMS worsening (all P<0.001). For baseline EDSS score <4.0, 1.0-point annualised worsening was associated with 7.2-point FAMS and 2.0-point MCS worsening (both P<0.001). For baseline EDSS score ≥4.0, 1.0-point worsening corresponded to worsening on FAMS (2.4 points; P=0.04), but not MCS (P=0.82). Given that a half-point EDSS change is considered the minimum reliably measurable clinical difference, a 1.0-point change in SF-36 PCS and MCS or 3.0-point change in FAMS may represent a minimum important difference in PRO for multiple sclerosis patients.
HEAD JOLTING NYSTAGMUS: HEAD-SHAKING-INDUCED OCCLUSION OF THE HORIZONTAL SEMICIRCULAR CANAL
Authors: Kaski Diego , Bronstein Adolfo , Cutfield Nick , Buckwell David , Banga Rupan , Ray Jaydip , Chavda Swarupsinh , Irving Richard
Published: October 2015

Background and aims

We report a new syndrome (head jolting nystagmus, HJN) that expands the differential diagnosis of head-movement induced paroxysmal vertigo.

Methods and results

Two male patients (65 and 58 yrs) described rotational vertigo after violent and brief (1–2 s) oscillations of the head (head jolting) that triggered intense horizontal nystagmus lasting 45s. Accelerations of the head required to induce these episodes could only be achieved by the patients themselves. In Patient 1 the episodes gradually disappeared over a 6–year period. In Patient 2, 3–Tesla MRI suggested a filling defect in the left horizontal semicircular canal. He underwent surgical canal plugging that resolved the symptoms.

Conclusion and relevance

We attribute HJN to dislodged material within the horizontal semicircular canal, and provide a mechanistic model to explain its origin.
SPINAL STENOSIS IN FAMILIAL TRANSTHYRETIN AMYLOIDOSIS
Authors: Carr Aisling , Evans Matthew , Pelayo-Negro Ana , Shah Sachit , Choi David , Blake Julian , Phadke Rahul , Gilmore JD , Hawkins PN , Reilly Mary
Published: October 2015

Background

Transthyretin-associated amyloidosis (ATTR) is the commonest cause of hereditary amyloidosis. Age at onset is 50–60 years with average life-expectancy of 7–14 years. Lumbar spinal stenosis also presents in late middle-age; related to disc degeneration, spondylolisthesis and age-related degenerative processes, such as WT-TTR amyloid deposition. Mutant-TTR has not been described in this scenario. Recent therapeutic developments in ATTR, with disease modifying potential, make histological evaluation clinically relevant.

Case

Family history prompted screening in an asymptomatic female carrier (heterozygous I84S) at age 42. At age 47 she developed sensory disturbance and pain in the left leg, brought on by exercise and relieved by rest. One year on, exercise tolerance <100 meters and she had sphincter disturbance. Examination revealed decreased pinprick sensation in the L5 dermatome and asymmetry of ankle and knee jerks, pulses were present. A disc bulge at L2/3 with superimposed narrowing of the lumbar canal due to ligamentum flavum hypertrophy was seen on MRI. Immunohistochemistry labelled ATTR deposits in the excised connective tissue. There was neurological improvement post-operatively but amyloid-symptoms qualified her for inclusion in ATTR treatment trials.

Discussion

We recommend histological examination for amyloid on tissue from spinal decompression and TTR gene analysis if this is positive.
A PROSPECTIVE CLINICAL AND IMMUNOLOGICAL STUDY OF LATE ONSET MYASTHENIA GRAVIS
Authors: Sadalage Girija , Jacob Saiju , Buckley Camilla , Hilton-Jones David , Vincent Angela , Maddison Paul
Published: October 2015

There is an increasing incidence and prevalence of MG in older patients (>50 years) – defined as Late Onset Myasthenia Gravis (LOMG). This study aims to define the demographics, clinical features, response to treatment and immunological features which may distinguish LOMG from the early onset patients (who will also be recruited as controls).

Who to refer?

▸ All patients should be over the age of 18 years, able to provide informed consent.

▸ The study aims to recruit patients who are willing to travel to one of the myasthenia clinics in Birmingham, Nottingham or Oxford

▸ All patients with a new diagnosis of MG (or diagnosed in the last 12 months) prior to immunosuppression.

▸ Diagnosis of MG based on typical clinical features and the presence of AChR or MuSK Abs, or evidence of neuromuscular transmission defect on single fibre EMG.

What it involves for patients

▸ Management will be as per usual practice

▸ Annual serum samples at follow up with QoL and MG composite scores

▸ Follow up for 5 years (3 years by the clinical research fellow and 2 years optionally by the local participating neurologists).
5 YEARS EXPERIENCE OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL): A RETROSPECTIVE PILOT AUDIT
Authors: Datta Sayan , Lee Rebecca , Webb Tom , Ismail Azzam , Jung Agam
Published: October 2015

Introduction

Primary Central Nervous System lymphoma (PCNSL) is responsible for 5% of all primary brain tumours within the UK. Barriers to diagnosis include steroid-responsiveness/false-negative biopsy and poor CSF sensitivity. We performed a pilot audit reflecting 5 years experience of PCNSL diagnosis based on criteria derived from 2011 British Neuro-Oncology guidelines.

Methods

Retrospective case note and electronic patient record review for patients between 2008 to 2013 with biopsy-proven label of PCNSL. Imaging and staging results were reviewed to exclude secondary/metastatic disease.

Results

20 patients were identified; median age of 58 and 60% were male. Top three clinical presentations were cognitive, paresis and ataxia. Median duration of symptoms was 21 days (range 3 to 180) and median time to biopsy was 14 days.

Pre-biopsy

5 patients had negative CSF, 20% had steroids with documented clinical reason, 5% had record of HIV status checked and 88% had CT staging.

Conclusion

Despite limitations, this audit identified that the majority of these patients received steroids pre-biopsy, but in some cases, this may have reasonably been withheld. There is scope for a diagnostic algorithm to highlight safe withholding of steroids, early HIV testing and appropriate staging investigations, downplaying the importance of CSF sampling.