bluuebunny/crossref_metadata_2025 huggingface dataset:
Phonetic divergence in bilingual speakers is modulated by language attitude
Authors: Law Wai Ling , Francis Alexander L.
Published: October 2015

Bilingual speakers’ speech varies phonetically according to many factors such as age of arrival and of acquisition of the second language (L2) (e.g., Flege et al., 1999). However, such temporal factors may not be as relevant to populations with more uniform language experience, as in pervasively multilingual societies. In such diglossic situations, speakers’ attitudes toward each of their languages may have a stronger influence on everyday pronunciation, as they do for language learning (Moyer, 2007) and phonetic accommodation to interlocutors (Dmitrieva et al., 2015). This study was designed to determine whether bilingual speakers’ attitude toward their language(s) and associated culture(s) modulates phonetic properties of their speech. Native Cantonese-English bilinguals living in Hong Kong (N = 20) produced near homophones in both languages under conditions emphasizing each language on different days. The degree of diphthongization of Cantonese /o/ and English /oʊ/, and Cantonese /aɪ/ and English /ɑɪ/ were quantified acoustically and compared to attitude scores elicited in a questionnaire. Participants with a more positive attitude toward Cantonese showed larger cross-language differences in diphthongization of these pairs, demonstrating an effect of language attitude on phonetic properties of speech and highlighting the contribution of sociolinguistic factors to phonetic variability in diglossic contexts.
Wireless underwater acoustic beamforming using chip-scale atomic clock timers
Authors: Freeman Simon E. , Emokpae Lloyd , Edelmann Geoffrey F.
Published: October 2015

Obtaining the directionality of the sound field is typically performed using a cabled array of hydrophones, connected to a central data collection device. The cable introduces vulnerability wherein an electrical break in the line or dragging by currents or anchors may render the array inoperable. An underwater wireless beamforming system, which transmits time and recorded low-frequency sounds using directional high-frequency acoustic communications between elements, is presented here. Each element is contained in a standalone housing that contains batteries, amplifiers, signal conditioning hardware and a field-programmable gate array (FPGA)-based signal processing computer. Low-frequency sounds are recorded at a sampling rate of 2 kHz, then transmitted using binary phase-shift-key (BPSK) encoding at a center frequency of 750 kHz. Inter-element spacing estimates are facilitated by the time-stamped high-frequency signals. System timing is controlled by a Symmetricom® SA.45s chip-scale atomic clock (CSAC) embedded in each unit, connected to the FPGA. In addition, a CSAC output waveform is divided and modified to form the high-frequency multiplier waveform for the BPSK signal. The elements were deployed in shallow water offshore of Panama City, FL, in August 2015. [This work was supported by the Office of Naval Research.]
Equations describing finite-amplitude effects in acoustic fish abundance estimation
Authors: Lunde Per
Published: October 2015

Species identification of fish and abundance estimation of zooplankton employ frequencies typically in the range of 20–400 kHz. Estimates are based on measurement of (a) the single-target backscattering cross section, σbs, used in echo sounder calibration and fish target strength measurements; and (b) the volume backscattering coefficient, sv, used in oceanic surveying. The power budget equations used today for σbs and sv pre-assume small-amplitude signals (i.e., linear sound propagation). For operating frequencies about 100 kHz and higher, finite-amplitude (nonlinear) sound propagation effects in seawater may cause measurements errors at accessible echo sounder transmit power levels. In the present work, power budget equations are derived for σbs and sv that account for finite-amplitude sound propagation effects. The expressions derived can be used to establish upper limits for echo sounder transmit power levels, in order to reduce finite-amplitude errors in calibration and surveying. They can alternatively be used to develop correction factors for calibration and/or survey data already subjected to finite-amplitude errors. The expressions derived are fully consistent with the small-signal expressions used in fisheries acoustics today.
A cavitation threshold for transient signals applied to laboratory-scale sparker-induced pulses
Authors: Esplin J. James , Kim Benjamin , Culver R. Lee
Published: October 2015

The phenomenon known as cavitation can occur when a volume of liquid is subjected to a pressure that falls below a “cavitation threshold”. Following this cavitation inception, a rupturing of the fluid or rapid growth of microbubbles occurs. The cavitation threshold is typically thought to be equal to the vapor pressure of the fluid; however, laboratory experiments involving underwater high-amplitude sparker-induced pulses have demonstrated that this is not necessarily the case. This presentation introduces a generalized threshold for transient acoustic pulses based on previous work of a threshold for constant-frequency transient signals. The output of this transient cavitation threshold will be compared against simulation and experiment.
Nonlinear acoustic pulse propagation in ocean waveguides containing an elastic seabed
Authors: Maestas Joseph T. , Collis Jon M.
Published: October 2015

High intensity underwater sources, such as explosions, generate nonlinear finite-amplitude pulses that behave differently than linear acoustic pulses within shallow water waveguides. The nonlinearity is known to decrease the critical angle for total internal reflection from that of the linear case when the seafloor is approximated as a fluid. However, this result has not been extensively studied for elastic seafloors where shear waves are present. In this work, a time-domain model is developed assuming an isotropic linear elastic bottom, inviscid water column, and allowing for nonlinear advective acceleration and a nonlinear equation of state. The model is numerically implemented using a high-order Godunov scheme and then benchmarked against tank experiment data for the linear case. The nonlinear model is used to study the critical grazing angle for ocean bottoms of varying shear speeds to determine the combined effect of nonlinearity and elasticity on bottom penetration.
Acoustical Society of America Distinguished Service Citation: Allan D. Pierce
Authors: Lynch James F.
Published: October 2015

The Distinguished Service Citation is awarded to a present or former member of the Society in recognition of outstanding service to the Society.
Acoustical Society of America Silver Medal in Engineering Acoustics: John L. Butler
Authors: Lindberg Jan , Moffett Mark
Published: October 2015

The Silver Medal is presented to individuals, without age limitation, for contributions to the advancement of science, engineering, or human welfare through the application of acoustic principles, or through research accomplishment in acoustics.
Acoustical Society of America Silver Medal in Psychological and Physiological Acoustics: Roy D. Patterson
Authors: Yost William A. , Leek Marjorie R. , Meddis Raymond
Published: October 2015

The Silver Medal is presented to individuals, without age limitation, for contributions to the advancement of science, engineering, or human welfare through the application of acoustic principles, or through research accomplishment in acoustics.
Acoustical Society of America Silver Medal in Speech Communication: John J. Ohala
Authors: Maddieson Ian , Beddor Patrice Speeter
Published: October 2015

The Silver Medal is presented to individuals, without age limitation, for contributions to the advancement of science, engineering, or human welfare through the application of acoustic principles, or through research accomplishment in acoustics.
Athlete and Coach Development in the Sevilla Club de Fútbol Youth Academy: A Values-Based Proposition
Authors: Solana-Sánchez Antonio , Lara-Bercial Sergio , Solana-Sánchez David
Published: October 2015

Professional youth football (soccer) academies face a number of challenges related to the contrasting and at times competing nature of their goals. Marrying long-term development of players with success in youth competitions and combining the development of young people as athletes with their growth as human beings are some examples. Professional football clubs and those tasked with leading their academies have to make key decisions as to how these challenges will be addressed. In this paper we argue that those decisions must be made based on a clearly shared philosophy and accompanying set of values. We present some of the key principles governing the work of the Sevilla Club de Fútbol Youth Academy and the rationale behind them. These principles span from developmental, methodological and pedagogical choices to the building of an internal long-term approach to coach development.
The Golgi apparatus is a functionally distinct Ca
2+
store regulated by the PKA and Epac branches of the β
1
-adrenergic signaling pathway
Authors: Yang Zhaokang , Kirton Hannah M. , MacDougall David A. , Boyle John P. , Deuchars James , Frater Brenda , Ponnambalam Sreenivasan , Hardy Matthew E. , White Edward , Calaghan Sarah C. , Peers Chris , Steele Derek S.
Published: October 2015

Calcium released from the Golgi apparatus may promote receptor trafficking to the surface of cardiomyocytes.
Frontrunners of T cell activation: Initial, localized Ca
2+
signals mediated by NAADP and the type 1 ryanodine receptor
Authors: Wolf Insa M. A. , Diercks Björn-Philipp , Gattkowski Ellen , Czarniak Frederik , Kempski Jan , Werner René , Schetelig Daniel , Mittrücker Hans-Willi , Schumacher Valéa , von Osten Manuel , Lodygin Dimitri , Flügel Alexander , Fliegert Ralf , Guse Andreas H.
Published: October 2015

High-resolution imaging of live T cells characterizes the early Ca
2+
signals required for T cell activation.
Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells
Authors: Rusin Scott F. , Schlosser Kate A. , Adamo Mark E. , Kettenbach Arminja N.
Published: October 2015

Proteomics and bioinformatics reveal a role for the phosphatase PP6 in opposing phosphorylation by casein kinase 2.
Cancer as a case of uncontrolled traffic
Authors: Kiberstis Paula A.
Published: October 2015

Mutations that disrupt protein trafficking can contribute to cancer development.
Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer’s disease mouse models
Authors: Huang Yunhong , Skwarek-Maruszewska Aneta , Horré Katrien , Vandewyer Elke , Wolfs Leen , Snellinx An , Saito Takashi , Radaelli Enrico , Corthout Nikky , Colombelli Julien , Lo Adrian C. , Van Aerschot Leen , Callaerts-Vegh Zsuzsanna , Trabzuni Daniah , Bossers Koen , Verhaagen Joost , Ryten Mina , Munck Sebastian , D’Hooge Rudi , Swaab Dick F. , Hardy John , Saido Takaomi C. , De Strooper Bart , Thathiah Amantha
Published: October 2015

Loss of GPR3 reduced amyloid plaque burden and improved cognition in four mouse models of Alzheimer’s disease, suggesting that GPR3 may be a potential therapeutic target.
The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease
Authors: Sidman Richard L. , Li Jianxue , Lawrence Matthew , Hu Wenzheng , Musso Gary F. , Giordano Ricardo J. , Cardó-Vila Marina , Pasqualini Renata , Arap Wadih
Published: October 2015

A stable small peptide that binds to two retinal VEGF receptors blocks angiogenesis in murine and nonhuman primate models of human blinding retinal diseases.
Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague
Authors: Stasulli Nikolas M. , Eichelberger Kara R. , Price Paul A. , Pechous Roger D. , Montgomery Stephanie A. , Parker Joel S. , Goldman William E.
Published: October 2015

During pneumonic plague, the bacterium
Yersinia pestis
elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (RNA-seq) analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are downregulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both
in vitro
and
in vivo
that
Y. pestis
increases neutrophil survival in a manner that is dependent on the type III secretion system effector YopM. This research explores the complexity of spatially distinct host-microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand
Y. pestis
virulence.

IMPORTANCE
Yersinia pestis
is a high-priority pathogen and continues to cause outbreaks worldwide. The ability of
Y. pestis
to be transmitted via respiratory droplets and its history of weaponization has led to its classification as a select agent most likely to be used as a biological weapon. Unrestricted bacterial growth during the initial preinflammatory phase primes patients to be infectious once disease symptoms begin in the proinflammatory phase, and the rapid disease progression can lead to death before
Y. pestis
infection can be diagnosed and treated. Using
in vivo
analyses and focusing on relevant cell types during pneumonic plague infection, we can identify host pathways that may be manipulated to extend the treatment window for pneumonic plague patients.
Hypertriglyceridaemia unresponsive to multiple treatments
Authors: Backes James M , Dayspring Thomas D , Hoefner Daniel M , Moriarty Patrick M
Published: October 2015

A 52-year-old man with a longstanding history of hypertriglyceridaemia (approximately 7 mmol/L (600 mg/dL)), unresponsive to treatment, presented to a lipid-specialty clinic. Additional triglyceride-lowering therapies were added with no effect. It was then noted that despite the apparent hypertriglyceridaemia, his serum sample was clear. A ‘glycerol blank’ was then requested from an advanced lipid laboratory, which reported a triglyceride value of 0.7 mmol/L (62 mg/dL). These findings suggest isolated asymptomatic glycerol kinase deficiency (GKD) or ‘pseudohypertriglyceridaemia’. The falsely elevated triglyceride values in such individuals are a result of excess serum glycerol and clinical laboratories measuring glycerol to report triglyceride concentrations. After discontinuation or modification of the patient's primary triglyceride-lowering agents, the lipid panels and triglyceride values remained comparable to previous readings. Recognition of asymptomatic GKD is important to prevent unnecessary treatment and overestimated cardiovascular risk.
Predictors of the antibody response to influenza vaccination in older adults with type 2 diabetes
Authors: McElhaney Janet E , Garneau Hugo , Camous Xavier , Dupuis Gilles , Pawelec Graham , Baehl Sarra , Tessier Daniel , Frost Eric H , Frasca Daniela , Larbi Anis , Fulop Tamas
Published: October 2015

Objective

Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic inflammatory diseases of the elderly. Its development is related to the alteration of the immune system with aging characterized by immunosenescence and inflamm-aging. In turn, T2DM also alters the immune response. As a consequence, older people with T2DM are more susceptible to influenza and to its complications as compared with healthy controls. Vaccination against influenza has shown poor efficacy in the older population and even less efficacy in patients with diabetes. We studied here the antibody response to vaccination in healthy and diabetic elderly participants.

Research design and methods

In 2 groups of elderly participants (healthy N=119 and T2DM N=102), we measured the immunogenicity of influenza vaccine by hemagglutination inhibition assays. We assessed several blood and functional parameters as potential predictors of the vaccine efficacy.

Results

We found no difference between antibody responses in diabetic elderly compared with healthy elderly. Among the biological and functional determinants, the cytomegalovirus (CMV) serostatus played a more prominent role in determining the magnitude of response. We concluded that in addition to age and diabetic status, immunological history such as CMV status should be taken into account. None of the other biological or functional parameters studied could be reliably linked to the vaccine antibody response in older adults who are not frail including those with well-controlled diabetes.

Conclusions

Our data strongly suggest that influenza vaccine should be administered to elderly patients with T2DM; however, the immune determinants of the antibody response to influenza vaccination should be further investigated.
Association between alcohol consumption and Korean young women's bone health: a cross sectional study from the 2008 to 2011 Korea National Health and Nutrition Examination Survey
Authors: Seo Seonwha , Chun Sungsoo , Newell Maxine Andrea , Yun Mieun
Published: October 2015

Objectives

To assess the association between alcohol consumption and healthy Korean young women bone by Alcohol Use Disorders Identification Test (AUDIT) scores and drinking consumption; frequency and amount.

Design

Cross-sectional study composed of three parts: health interview, health examination, nutrition survey.

Setting

2008–2011 Korea National Health and Nutrition Examination Survey.

Participants

Of the 21 303 participants whose bone mineral density (BMD) was assessed, 1176 healthy women aged 19–30 years were selected.

Primary and secondary outcome measures

Mean BMD T-scores of the total femur (TF), femur neck (FN) and lumbar spine (LB) by drinking consumption and AUDIT scores, and the odds of having a low BMD (T-score <−1) at the sites by AUDIT scores.

Results

After adjustment, lower BMD was found at three sites in those who drank more and had higher AUDIT scores. These associations were significant by AUDIT scores at TF (p=0.002) and FN (p=0.004) and by drinking frequency and amount at FN (p=0.029 and 0.039, respectively). The adjusted OR of having low BMD increased significantly, particularly at FN, in those who had higher AUDIT scores such as 16–17 harmful drinking (OR 4.31; 95% CI 1.16 to 16.06) and 20–40 alcohol dependence (OR 5.99; 95% CI 1.69 to 21.21), compared with young women who scored 0–7 low-risk drinking or abstinence. No beneficial effect of moderate drinking was observed at any of the sites and the association between alcohol consumption and bone health was most evident at FN.

Conclusions

It is crucial to promote the awareness of alcohol harm on Korean young women's bone health. At the same time, since alcohol's effect on the bone is complex with cumulative effects of various factors over the years and there is an absence of studies with young women in their twenties, more studies, in particular for FN, are needed with more precise and appropriate design to confirm our findings.
THE PROFILE OF MULTIPLE SCLEROSIS IN GENERAL PRACTICE
Authors: Binks Sophie , Green Liz
Published: October 2015

Introduction

Multiple sclerosis (MS) is a long-term neurological condition requiring a multi-disciplinary team approach. Recently, NICE highlighted the role of primary care professionals in MS management through an updated clinical guideline. This quality improvement project investigated aspects of MS patient care in a large Brighton GP practice.

Method

Electronic GP records were searched to identify all currently registered patients with a diagnosis of MS. Details of initial presentation, epidemiology and care received over a one-year period were examined.

Results

There were 19 patients, representing a prevalence of 186 per 100,000. Most patients first presented in GP with sensory disturbance, optic neuritis or motor symptoms. The mean number of primary care contacts per patient per year was 4.3, compared to 0.4 contacts per person per year with a neurologist and 0.5 with the MS nurse. 46% of GP consultations were wholly or partially related to the patient's MS. Around half of patients took up proactive interventions such as flu vaccination (47%) and Vitamin D monitoring (50%).

Conclusions

Primary care professionals are significant contributors to the care of people with MS with frequent patient contact. During this project, patients were reminded of preventive care opportunities and this will be re-audited in 2015.
ALEMTUZUMAB IMPROVES 3-YEAR QUALITY OF LIFE IN CARE-MS II
Authors: Coles Alasdair , Giovannoni Gavin , Moreau Thibault , Havrdova Eva , Margolin David , Kasten Linda , Singer Barry
Published: October 2015

In the 2-year, phase 3 CARE–MS II study (NCT00548405) of relapsing-remitting multiple sclerosis (RRMS) patients with inadequate efficacy response to prior therapy, alemtuzumab demonstrated superior efficacy and quality-of-life (QoL) improvements versus subcutaneous interferon beta-1a, with manageable safety. Here, QoL outcomes are examined in alemtuzumab-treated patients at Year 3 in an ongoing extension study (NCT00930553). 393 of 435 alemtuzumab 12 mg-treated patients entered the extension study; 80 received as-needed alemtuzumab retreatment during Year 3. Mean Functional Assessment of multiple sclerosis total score (scale 0–176) improved from baseline to year 3 (119.1 vs 124.8; P<0.0001), with 5 of 6 subscales significantly improved. Mean Short-Form 36–Item survey physical and mental component summary scores (scale 1–100) rose from baseline to Year 3 (42.7 vs 44.7; P<0.0001, and 44.9 vs 46.5; P=0.042, respectively), with 6 of 8 subscales improved, and 82% and 73% of patients, respectively, having a stable or improved score at Year 3. EuroQol 5–dimensional visual analogue scale score improved from baseline to Year 3 (70.1 vs 73.0; P=0.0045). Overall sustained improvement in physical, mental, and emotional aspects of QoL were observed through 3 years in this population of alemtuzumab-treated RRMS patients, even though most patients received only 2 alemtuzumab treatment courses.
MANAGEMENT OF ADVERSE REACTIONS TO ALEMTUZUMAB INFUSION
Authors: Sharrack Basil , Mayer Lori , Coles Alasdair , Hartung Hans-Peter , Havrdova Eva , Selmaj Krzysztof , Margolin David , Compston Alastair
Published: October 2015

In the 2-year, phase 3 CARE-MS studies of alemtuzumab in patients with relapsing-remitting multiple sclerosis, infusion-associated reactions (IARs) were the most common adverse events. Here we report on IARs during 4-year follow-up. Patients who were treatment-naive (CARE-MS I; NCT00530348) or with inadequate efficacy response to prior therapy (CARE-MS II; NCT00548405) received 2 annual courses of alemtuzumab 12 mg, and as-needed retreatment in an extension study (NCT00930553). Patients received methylprednisolone on the first 3 days of each course. IARs were any adverse event occurring between start of infusion and within 24 hours after end of infusion. 742/811 alemtuzumab-treated patients entered extension. Over 4 years, 70.4% received only 2 initial treatment courses; 22.6% and 6.1% received 3 and 4 courses, respectively. IARs were most frequent in Course 1 (84.7%) versus Courses 2 (68.5%), 3 (65.7%), and 4 (71.1%); frequency decreased on infusion Days 2 and 3 versus Day 1. IARs were predominantly mild to moderate; none led to study withdrawal or death. Serious IAR incidence was 3.1%. Most common IARs were skin disorders (predominantly rash), headache, pyrexia, and nausea. One confirmed anaphylaxis and one non-anaphylactoid hypotension event resolved with treatment. Effective IAR management included premedication, infusion monitoring, symptomatic treatment, and infusion interruption/adjustment.
SUSAC'S SYNDROME: A CASE SERIES FROM A REGIONAL NEUROSCIENCES UNIT
Authors: King Dominic , Appleton Jason Philip , Jacob Saiju
Published: October 2015

The clinical triad of branch retinal artery occlusions, hearing loss and encephalopathy constitutes Susac's Syndrome. This rare, immune mediated, microangiopathic disorder shows a variable course with a preponderance of 3 to 1 for women, mainly in their 2nd to 4th decade. The condition relies on diagnosis and early aggressive immunosuppressive therapy to avoid severe sequale. Unfortunately, due to the paucity of experience, and a variable disease course, often lacking all elements of the triad concurrently, diagnosis continues to be delayed.

We present five cases (Age 34–45, M:F–1:4) seen at our regional neurosciences centre, which highlight the diagnostic differences and challenges and the variety of management techniques adopted. Three patients had a monophasic illness and two had a relapsing remitting course. In addition, we provide an up-to-date literature review on the pathophysiology, diagnosis and management of this rare and fascinating condition.

Susac's disease, otherwise described as retinocochleocerebral vasculopathy, RED-M (retinopathy, encephalopathy, deafness associated microangiopathy) and SICRET (small infarcts of cochlear, retinal and encephalic tissues), is a syndromic pathology requiring the recognition of a triad of deficits to make a diagnosis. The relevance of this and the difficulty in diagnosis is exemplified in the cases presented here.
EXPERT OPINIONS ON THE DIAGNOSIS AND TREATMENT OF PATIENTS WITH AQP4-NEGATIVE NMO/MS OVERLAPPING SYNDROMES
Authors: Juryńczyk Maciej , Weinshenker Brian , Wingerchuk Dean , Akman-Demir Gulsen , Asgari Nasrin , Barnes David , Boggild Mike , Chaudhuri Abhijit , Leite Isabel
Published: October 2015

Distinguishing aquaporin-4-antibody(AQP4-Ab)-negative neuromyelitis optica spectrum disorders (NMOSD) from optico-spinal predominant MS is a clinical challenge with important treatment implications. 12 AQP4-Ab-negative patients presenting to an NMO clinic were selected for having overlapping features of NMO and MS. 27 NMO and MS experts reviewed their case vignettes, including relevant findings. Opinions were categorized for diagnosis (NMO, MS, indeterminate, other) and treatment (MS drugs, immunosuppression, none). The mean proportion of agreement for diagnosis was low (0.51). The majority opinion was divided between NMO versus MS (9 cases), monophasic longitudinally extensive transverse myelitis (LETM) versus NMOSD (1), acute disseminated encephalomyelitis versus NMO (1), and recurrent isolated optic neuritis (ON) versus NMOSD (1). LETM and/or ON with limited recovery even if accompanied by typical MS features (short TM, mild ON, oligoclonal bands), were associated with a low rate of MS diagnoses. TM with short lesions or mild ON did not preclude a diagnosis of NMO. Agreement on treatment was higher (0.64) with immunosuppression being the most common choice not only in patients with NMO but also in those indeterminate between NMO and MS. Experts frequently disagree on the diagnosis of NMO/MS overlapping syndromes. Prospective long-term studies on ultimate diagnosis in this group of patients are needed.
AN AUDIT OF HOSPITALISATION IN MYASTHENIA GRAVIS PATIENTS
Authors: Maddison Paul , Ghosh Rukmini
Published: October 2015

Myasthenia gravis (MG) may cause acute, profound neurological illness, not infrequently requiring hospital admission, associated with significant morbidity and rarely mortality, despite effective immunosuppressive treatments. The reasons why patients with MG require hospital admission are not clear, although an audit of MG admissions conducted in Manchester identified early bulbar symptoms as predictive of increased risk of hospital admission. We aimed to replicate the Manchester audit in Nottingham, UK, to identify the factors responsible for admission that may be common to different UK centres. There were 124 admissions in 94 MG patients (2002–2012). Commonest reason for admission was first diagnostic presentation in 34 patients (34/124 admissions, 27%), with MG exacerbation resulting in admission in a further 32 patients (45/124 admissions, 36%). Triggers for exacerbation of MG were mostly unknown (50%), with 41% thought to be due to infection, and 6% due to reduction in steroid dose. In common with the previous UK audit, steroid doses in the 4 weeks prior to admission for MG relapse were only increased in 4/15, and unchanged in 7/15, despite all suffering bulbar symptoms. In accordance with other data, we have found that worsening bulbar symptoms, especially in the elderly population, are a risk for admission.
RARE PARANEOPLASTIC POLYNEUROPATHY SECONDARY TO SKIN MELANOMA
Authors: Kioulachidis Konstantinos , Ailenei Elena , Afshari Fardad , Mockova Martina
Published: October 2015

Paraneoplastic diseases of peripheral and central nervous systems are rare manifestations of malignancies. Here we report a rare case of 51 year old male who presented with symmetrical progressive sensory and motor deficit over the course of one year. His past medical history included a malignant melanoma excised 5 years ago from the skin of interscapular region.

His nerve conduction studies showed evidence of severe, symmetrical, predominantly sensory, axonal peripheral neuropathy. He under-went CT chest-abdomen-pelvis which showed large right axillary lymph nodes. Axillary Lymph node biopsy contained metastatic melanoma cells positive with MelanA and HMB 45. Analysis of the BRAF gene from biopsy sample cells revealed the presence of a mutation within codon 600 of the BRAF gene. All further investigations did not show evidence of any other type of tumour.

Paraneoplastic syndromes can affect the motor, sensory and autonomic nervous systems and are associated with lung cancer, especially small-cell lung cancer, lymphoma and gynecological tumors. To our knowledge our case is the first report of paraneoplastic polyneuropathy secondary to malignant melanoma.

The presence of paraneoplastic neuropathy should be considered in all patients with malignancy and can happen at any point in the disease prior or after induction of any treatment. We report rare case of malignant melanoma presenting with paraneoplastic polyneuropathy.
BING-NEEL SYNDROME: A RARE CAUSE OF PROGRESSIVE GAIT DISTURBANCE AND DEMENTIA
Authors: Doshi Anisha , Haque Anis , Chowdhury Muhammad , Boyd Kevin
Published: October 2015

A 69 year old retired lady presented with a 3 year history of progressive gait disturbance with unsteadiness and falls. Over the preceding year she had become recluse, failing to attend social gatherings and becoming anxious. She complained of lethargy and poor appetite and had lost weight. A witnessed generalised seizure led to admission. Examination revealed mixed pyramidal and extrapyramidal signs in the limbs with global hyperreflexia and upgoing plantars. There was upper limb ataxia with bilateral intention tremor and myoclonus. She was only obeying one stage commands.

Investigations revealed elevated ESR and monoclonal IgM kappa band with paraprotein concentration 9.4 g/L. MRI whole axis revealed periventricular diffuse T2 and FLAIR signal change and prominence of the leptomeninges along the distal spinal cord, conus medullaris and cauda equina. Bone scan showed prominent uptake within both humeri. Bone marrow trephine biopsy indicated a low-grade B-cell lymphoproliferative disorder; lymphoplasmacytic lymphoma. Serial CSF analysis revealed lymphocytic pleocytosis with elevated protein of 4.47–6.25 g/L. CSF protein electrophoresis demonstrated the presence of an IgM paraprotein with monoclonal IgM kappa band on immunonofixation. CSF immunophenotyping confirmed the presence of clonal B–cells.

We therefore present a rare case of Bing-Neel Syndrome, CNS manifestation of Wäldenstroms Macroglobulinaemia.
CO-MORBIDITY BURDEN IN PARKINSON'S DISEASE AND MATCHED CONTROLS
Authors: Goddard Hannah , Macleod Angus , Counsell Carl
Published: October 2015

Background

Idiopathic Parkinson's disease (PD) is a common, disabling, neurodegenerative disorder. The overall co-morbidity burden associated with PD is unclear, but may be important to adjust for when predicting prognosis or comparing cases and controls.

Aims

▸ To determine how best to assess overall co-morbidity in PD

▸ To compare PD co-morbidity burden to that of age- and sex-matched controls

Methods

Data from an incident, community-based cohort of 205 patients with PD and 148 age-, sex- and GP-matched controls (the PINE study) were used. The intra- and inter-rater reliability and mortality predictive ability of three co-morbidity scales (the Charlson Co-Morbidity Index, the Cumulative Illness Rating Scale and a disease count) were evaluated. The co-morbidity burden of cases and controls was compared at baseline and over 5 years of follow-up.

Results and conclusions

The Charlson Co-Morbidity Index was more reliable for use in PD and was the only scale that was independently predictive of mortality (hazard ratio=1.20, [95% CI 1.07–1.34]). There was no significant difference between cases and controls at baseline (p=0.20). Charlson Co-Morbidity Index scores increased over time. This increase was greater in patients with PD than controls and greater in patients and controls who died earlier.
SLEEP AND CIRCADIAN RHYTHM REGULATION IN EARLY PARKINSON'S DISEASE
Authors: Breen David , Vuono Romina , Nawarathna Upekshani , Fisher Kate , Shneerson John , Reddy Akhilesh , Barker Roger
Published: October 2015

Aim

Sleep disturbances are recognised as a common non-motor complaint in Parkinson's disease but their aetiology is poorly understood. We set out to define the sleep and circadian phenotype of early-stage Parkinson's disease patients.

Methods

We began by assessing the sleep characteristics of a large population-representative incident Parkinson's disease cohort (n=239) at the University of Cambridge. We went on to carry out more comprehensive case-control sleep assessments in a subgroup of these patients (n=30) and matched controls (n=15). Outcome measures were sleep diagnoses and sleep architecture based on polysomnography studies; actigraphy assessment; and 24-hour analyses of serum cortisol, melatonin and peripheral clock gene expression (Bmal1, Per2, and Rev-Erbα).

Results

Subjective sleep complaints were present in almost half of newly-diagnosed patients and correlated significantly with poorer quality of life. Parkinson's disease patients exhibited increased sleep latency, reduced sleep efficiency and reduced REM sleep. In addition, there was a sustained elevation of serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1 expression in Parkinson's disease patients compared to controls.

Conclusions

The sleep dysfunction seen in early Parkinson's disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms.
ELEVATED SALIVARY DJ-1 IN PARKINSON'S DISEASE IS ASSOCIATED WITH ALTERED SALIVARY SECRETION
Authors: Masters Joseph , Noyce Alaistair , Giovannoni Gavin , Warner Tom , Proctor Gordon
Published: October 2015

Aim

To investigate the composition of saliva in patients with Parkinson's disease (PD).

Methods

Saliva was collected from 16 patients with PD and 22 age-matched controls. Salivary DJ-1 concentrations were measured with quantitative immunoblotting; total protein concentration with a BCA assay; amylase with an amylase activity assay; and mucin concentrations with periodic-acid Schiff stained SDS gels.

Results

Salivary flow rate was not significantly different between patients and controls. Patient saliva showed increases in DJ-1 concentration (0.84 vs 0.42 µg/ml, p=0.001) and total protein concentration (8.4 vs 5.0 mg/ml, p=0.001). In patients, adjusted DJ-1 levels correlated with disease severity measured with the Unified Parkinson's Disease Rating Scale (p=0.019). Concentrations of amylase, but not mucins, were elevated in the saliva of patients (0.127 vs 0.061 units/ml, p<0.001) and correlated positively with both total protein (p<0.001) and DJ-1 concentration (p<0.013).

Conclusions

This preliminary study suggests that the saliva of patients with PD is different in composition to that of controls, which supports the notion that saliva may be a good candidate for biomarker discovery in PD. Altered protein secretion may be a manifestation of autonomic dysfunction in PD.
BED PARTNER ‘GAS-LIGHTING’ AS A CAUSE OF FICTITIOUS SLEEP-TALKING
Authors: Bashford James , Leschziner Guy
Published: October 2015

We report a rare and striking, but under-recognised, cause of reported sleep-talking to a specialist sleep clinic. A 67 year-old right-handed bus driver was referred with one year's history of sleep-talking reported by his bed-partner of eighteen months. The somniloquy occurred on most nights, beginning within ten minutes of sleep and lasting several minutes to hours. The speech was elaborate relating to ex-girlfriends, often describing explicit sexual activities.

Nocturnal polysomnography demonstrated clinically significant obstructive sleep apnoea and the working diagnosis was that obstructive events were triggering a non-REM parasomnia.

On review two months later his partner reported on-going nocturnal speech. However, the patient's mounting curiosity had led to the implementation of surreptitious night-time electronic recordings. It soon became apparent that his partner's account was fictitious. Full psychiatric evaluation of his partner excluded morbid jealousy and psychotic illness.

We highlight the psychological phenomenon of gas-lighting, coined from the 1938 play Gas Light, in which a husband systematically torments his unsuspecting wife in order to provoke admission to a mental health unit. This phenomenon should be considered amongst the differential diagnoses of unusual presentations to sleep clinic, especially pertinent in this setting as the clinical assessment relies heavily on the bed-partner account.
ANALYSIS OF CONVULSIVE SEIZURES AT A DGH EMERGENCY DEPARTMENT
Authors: Edwards Amy , Percival Kevin , Zouita Louisa , Arevalo Jan , O'Dwyer John Philip
Published: October 2015

Introduction

Seizures represent 3% of all emergency department attendances.

Methods

A list of all possible seizure mimics was generated from ED computerized triage systems from 1/1/12 to 31/12/13. Data was extracted manually from review of ED notes and analyzed.

Results

905 seizure attendances by 636 patients were examined over 2 years. 340 men and 296 women accounted for them, with average age 33±28 years. 245 patients had a history of epilepsy and were taking at least one AED. >2 AEDs were used by 32 patients. 22 had known Non-Epileptic Attacks (NEAD). Convulsive seizures occurred in 429 and Status Epilepticus in 13. The mode for the number of convulsive events in ED was 2 for NEAD patients and 1 for others. Lactate and neutrophils in NEAD were 1.3±0.3 mM and 4.4±1.2×10^9/L respectively. In other patients with convulsive seizures, they were 3.2 ±3.2 mM (median 2.1) and 6.6±3.1×10^9/L (median 6.1). 73 had neuroimaging acutely. Few patients with NEAD were admitted. 1/3 of convulsive seizures were admitted.

Conclusion

This retrospective service audit indicates the burden of epilepsy attendance in a busy hospital. There is a potential role for more acute neurology input to prevent unnecessary admissions, and a pathway for non-epileptic attack sufferers.
WHY NEUROLOGY? THE CAREER CHOICES OF CURRENT UK NEUROLOGY TRAINEES
Authors: Thomas Rhys , Devine Helen , Donnelly Ann , Foulkes Alexander , Galtrey Clare , Khaleeli Zhaleh , Lawrence Joanne , Novak Marianne , Redgrave Jessica , Tallantyre Emma
Published: October 2015

Introduction

It is important that we attract high-calibre medics to neurology. There are few studies of what motivated neurologists to choose their speciality, when they chose, or what else they might have become.

Methods

All UK neurology trainees were invited to complete an online survey.

Results

160 trainees responded (53% female; 17% less-than-fulltime). 54% decided on neurology before graduating (6% before medical school), whilst 29% decided after foundation training. Common reasons to choose neurology included: academically interesting (72%); clinical exposure as a student or junior (67%); personality fit (53%); influential role-model (37%). Less common motivations included lifestyle, family friendliness, prestige, and family members with neurological conditions. Two trainees chose neurology because they personally have a neurological condition. When asked what their second choice of medical career would have been the answers were diverse and 31 different specialties were named, but only one might have been a neurosurgeon.

Conclusions

Careers advice should begin early in medical school and continue through medical training with direct exposure to clinical neurology. Traditional neurology values such as the intellectual challenge should be emphasised. Neurologists have a broad interest in medical and psychiatric specialties underlining the importance of core medical training to developing neurologists of the future.
IMPACT OF A CLINICAL PATHWAY ON THE MANAGEMENT OF FIRST SEIZURES AT A DISTRICT GENERAL HOSPITAL
Authors: Georgieva Zoya , Altemimi Harith
Published: October 2015

Diagnostic confidence and management of first seizures can be challenging, particularly for junior doctors. This audit evaluates the impact of a clinical pathway based on recommendations by the College of Emergency Medicine, which intended to improve the management of such patients at a UK DGH.

A systematic search identified cases spanning 3 months either side of the date of introduction of the pathway. 23 pre- and 25 post-pathway cases presenting to A&E or as inpatients were randomly selected, excluding cases with a known seizure-related diagnosis.

The pathway was only utilised in 16% of cases. Referral to neurology clinic increased from 30% to 52%, but attending within the recommended 2 weeks of ictus remained infrequent (8%). Clinical assessment worsened in several categories, including documenting a drug history, obtaining an ECG, and blood glucose measurement. Documenting discussions about driving decreased from 43% to 36%.

Findings confirm suboptimal investigation and follow-up of first seizures, with a surprising deterioration after introduction of a local clinical guideline. This audit demonstrates the importance of cultural change in addition to the availability of a structured guideline. We propose this can be achieved by dedicated junior doctor training sessions and development of a patient information leaflet.
SERIAL NERVE CONDUCTION STUDIES IN A GUILLAIN-BARRÉ SYNDROME VARIANT: THE EVOLUTION OF DEMYELINATING CHANGES
Authors: Morgan Catherine , Wakerley Benjamin , Fuller Geraint
Published: October 2015

Guillain Barré syndrome (GBS) varies both in terms of clinical phenotype and underlying pathology. Serial assessments allow greater understanding of the pathophysiology. The evolution of neurophysiological changes is particularly helpful in distinguishing between demyelination and reversible axonal conduction failure.

Bilateral facial weakness with distal paraesthesias is a rare subtype of GBS. In the largest case series 64% had abnormalities in motor and 27% in sensory conduction on single neurophysiological assessments; this was interpreted as a demyelinating neuropathy.

We report an 18-year-old male with bilateral lower motor neurone facial weakness preceded by distal paraesthesias following a ‘flu-like illness. Examination of power and sensation was normal. Deep tendon reflexes were present. Cerebrospinal fluid showed albuminocytologic dissociation. By 6 weeks his facial weakness had almost completely resolved without treatment.

Serial nerve conduction studies were performed. The first study (day 4) found prolonged distal motor latency and delayed F waves in posterior tibial and common peroneal nerves; normal sensory studies. Second study (day 18) found distal motor latencies and F waves had increased in upper and lower limb nerves. Third study (day 60) found improvement but abnormalities remained with changes similar to the first study.

The neurophysiological changes became more marked while he improved clinically. These serial studies confirmed the primary pathological process of this GBS variant to be demyelination.
A CLINICAL AUDIT OF ACUTE MANAGEMENT OF STROKE-LIKE EPISODES FROM A NATIONAL MITOCHONDRIAL DISEASE CENTRE
Authors: Shaw Sarah , Ng Yi Shiau , Whittaker Roger , McFarland Robert , Turnbull Doug , Gorman Grainne , Schaefer Andrew
Published: October 2015

Background

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is an acute and severe neurological presentation most commonly associated with a point mutation in the mitochondrial tRNA Leu (UUR)gene, m.3243A>G. The onset of stroke-like episodes (SLE) is often subtle and the diagnosis is not considered until progressive encephalopathy and refractory focal seizures ensue.

Objective

To review the acute management of SLE in patients with m.3243A>G related MELAS syndrome and implement revision of current centre guidelines.

Method

The medical records of adult patients (over 16 years) with m.3243A>G-related MELAS syndrome were reviewed over a 20 year period (1995 to 2014). Clinical presentation, brain imaging, EEG findings and seizure management were evaluated.

Results

We identified 47 SLEs occurring in 22 m.3243A>G MELAS patients (mean age 33 years). Seizures of occipital origin were most common. Time to hospital admission and investigation was highly variable. Recognition and treatment of seizure activity was often delayed.

Conclusion

This audit is the first to highlight the need for early recognition and prompt management of SLE in MELAS and the role of seizure control to improve clinical outcome.
CLINICAL MANIFESTATIONS OF DNMT1 MUTATIONS
Authors: Fox Robin , Gosal David , Ealing John , Murphy Helen
Published: October 2015

DNMT1 gene mutations have been previously associated with neurological syndromes in small numbers of patients. We present seven cases – a patient with a previously unreported DNMT1 mutation and a family with six members affected by a more classical DNMT1 syndrome.

A 20-year-old patient with a history of common variable immune deficiency presented with sensory loss. He developed a syndrome of hereditary sensory and autonomic neuropathy (HSAN1E), cataplexy, cerebellar atrophy, deafness, and cutaneous manifestations of a scleroderma spectrum disorder. There was no family history. Genetic testing revealed the patient was heterozygous for a previously unreported in-frame deletion mutation, c.1635_1637delCAA p.(Asn545del) in the DNMT1 gene exon 20. Parental DNA analysis suggested a de novo occurrence.

A 53-year-old female patient presented with unsteadiness and falls. On assessment she was found to have cerebellar ataxia, bilateral ptosis, deafness and narcolepsy. Questioning revealed five further affected members of her family with the same clinical syndrome, in an autosomal dominant inheritance pattern. Genetic testing revealed a missense mutation in the exon 21 region of the DNMT1 gene – p.Ala570Val.

DNMT1 mutations, whilst rare, are associated with a specific constellation of neurological features and increased recognition will lead to an increased understanding of this condition.