bluuebunny/crossref_metadata_2025_split huggingface dataset:
THUR 159 Radiological findings in two patients with autoimmune GFAP astrocytopathy
Authors: Daniel White , Markand Patel , Wasim Muhammad , Tom Hayton , Satheesh Ramalingam , Vijay Sawlani , Saiju Jacob 
Published: October 2018

BackgroundAutoimmune Glial Fibrillary Acidic Protein (GFAP) Astrocytopathy is a relatively new category of immune-mediated disease involving the central nervous system that demonstrates a widely variable spectrum of clinical presentations, ranging from the relatively mild or subacute onset of cognitive impairment, seizures, encephalopathy, meningeal symptoms to more complex forms of encephalomyelitis.Materials and MethodsWe present a radiological review of two cases which were recently diagnosed in our institution. They presented with fever, meningoencephalitis and bilateral papilloedema. CSF antibody analysis (GFAPα-IgG) from Mayo Clinic confirmed the diagnosis of GFAP in both cases.ResultsThe typical radiological findings in both of the cases were a radial pattern of enhancement in brain and longitudinally extensive myelitic lesions in the spinal cord. The first patient improved with immunosupression treatment. The second patient had a significantly more severe clinical presentation with drug-refractory progression, who later died.ConclusionPatients presenting with subacute onset of cognitive impairment, meningoencephalomyelitis and papilloedema should raise the suspicion of autoimmune GFAP astrocytopathy. Though it is a relatively new disease entity, the radial pattern of enhancement and long spinal cord lesions on imaging are striking and CSF and serum antibodies are highly specific.
WED 167 Socioeconomic status and progression of disability in ms
Authors: Harding Katharine , Kingwell Elaine , Wardle Mark , Zhu Feng , Robertson Neil , Tremlett Helen 
Published: October 2018

There is evidence that socioeconomic status (SES) is associated with multiple sclerosis (MS) incidence; however it is less clear whether there is also an association with long-term prognosis.3113 patients were selected from the MS registries of British Columbia, Canada (n=2069), and Cardiff, Wales (n=1044). SES, based on neighbourhood-level average income, was measured at onset of MS. Cox proportional hazards regression was used to analyse the association of SES with time to sustained and confirmed EDSS 6.0 and EDSS 4.0. The association between SES and EDSS scores was assessed longitudinally by a linear regression model fitted using generalised estimating equations (GEE) with an exchangeable working correlation structure. All models were adjusted for age at onset, sex, year of onset, initial course and DMT. The cohorts were analysed individually and results combined using meta-analysis.SES was associated with hazard of reaching EDSS 6.0 (adjusted hazard ratio [aHR]=0.90, 95% CI 0.89–0.91), and 4.0 (aHR=0.93, 0.88–0.98). GEE modelling confirmed association of SES with EDSS (β=−0.13, [−0.18- −0.08], p<0.001). We found evidence that lower SES is associated with poorer outcomes. Reasons for this are complex but may include lifestyle or comorbidity. Our findings are relevant for planning and development of MS services.
THUR 178 Infections during grade 3/4 lymphopenia with cladribine tablets
Authors: Cook Stuart , Leist Thomas , Comi Giancarlo , Montalban Xavier , Sylvester Elke , Hicking Christine , Dangond Fernando 
Published: October 2018

BackgroundIn CLARITY, cladribine tablets 3.5 mg/kg (CT3.5) demonstrated efficacy in relapsing MS patients. The most common AE was lymphopenia, reflecting cladribine’s mode of action. Integrated safety analysis showed infection incidence was not higher in patients receiving CT3.5 vs placebo, bar a small increase of herpes zoster (HZV).ObjectivePost-hoc analysis examined infectious AEs occurring concurrently with Grade 3/4 lymphopenia (G3/4) in CT3.5 treated patients.MethodsThe AE profile for CT3.5 during the periods of G3/4 was analysed. Adjusted-AE incidences per 100 patient years (Adj-AE/100PY) were calculated in a cohort of patients receiving CT3.5 monotherapy in clinical trials.ResultsData are presented as Adj-AE/100PY: G3/4 vs without G3/4. Adj-AE/100PY for any infections/infestations was 57.53 vs 24.50. Infections were similar between periods. ≥50% cases with G3/4 were easily-treatable upper- respiratory-tract infections (nasopharyngitis: 13.48 vs 5.24; upper-respiratory-tract infection: 9.67 vs 3.41; pharyngitis: 4.51 vs 0.73). HZV occurred in 4 patients with G3/4 (4.50 vs 0.73); cases were dermatomal and mild-to- moderate in severity. Single occurrences were reported for most infectious AEs. Opportunistic infections were single occurrences, not severe, serious or difficult-to-treat.ConclusionsG3/4 increased frequency of infections but did not affect the type of infectious AEs in CT3.5 treated patients. HZV profile was uncomplicated, consistent with findings of previous analyses.Disclaimerhttp://medpub-poster.merckgroup.com/ABN2018DISC_Grade34.pdf
WED 182 Cladribine tablets effects on lymphocytes in ms patients
Authors: Soelberg-Sorensen Per , Dangond Fernando , Hicking Christine , Giovannoni Gavin 
Published: October 2018

BackgroundLymphopenia is expected from the mechanism of action of cladribine tablets 3.5 mg/kg (CT3.5)ObjectiveInvestigate absolute lymphocyte counts (ALC; 312 weeks) and subsets (240 weeks) in RRMS patients receiving 2 annual courses of CT3.5.MethodsPooled data from patients randomised to CT3.5 over 2 years in CLARITY/CLARITY-Extension inclusive of the PREMIERE registry (n=685).ResultsBaseline: median ALC=1.86 × 109/L. Year-1: ALC reached nadir at 9 weeks post-treatment with CT3.5 (1.00 × 109/L). Year-2: ALC reached nadir at Week-55 (0.81 × 109/L), then recovered to the normal range (≥1.00 × 109/L; Week-96). ALC was in normal range in 75% of patients by Week-144. Baseline median CD4+ were 851 cells/µL. Nadirs occurred at Week-16 (385 cells/µL) in Year-1 and at Week-60 (292 cells/µL) in Year-2; values increased after nadirs and regained threshold (350 cells/µL, ~Week-120). Baseline median CD8+ were 378 cells/µL. Nadirs occurred at Week-16 (239 cells/µL; Year 1) and Week-72 (232 cells/µL; Year 2). CD8+ recovered quickly after treatment and remained above 200 cells/µL at all times. Baseline median CD19+ were 205 cells/µL. Nadirs occurred at Week-9 (18 cells/µL; Year-1) and Week-52 (31 cells/µL; Year-2). CD19+ then reached threshold of 100 cells/µL by the end of Year-2.ConclusionLymphocyte recovery begins soon after CT3.5. ALC, CD19+ B and CD4+ T cells; reached threshold by 7.5, 12 and 18 months. CD8+ cells remained above threshold.Disclaimerhttp://medpub-poster.merckgroup.com/ABN2018DISC_LongLymph.pdf
WED 014 Oct minimises unnecessary investigation for suspected papilloedema
Authors: Thomas Coysh , David Whiteside , Sarah Williamson , Louwai Muhammed , Vinod Metta , Fatemeh Geranmayeh , Barry Seemungal , Carolyn Gabriel , Joanna Ball , Richard Nicholas 
Published: October 2018

BackgroundOptical coherence tomography (OCT) is a rapid and painless way to provide a record of the optic disc structure. Though not specific, it can identify swollen optic discs. We determined the impact of OCT prior to referral on the pathway for managing suspected papilloedema.MethodsAudit of adults referred from the Western Eye Hospital to St Mary’s Hospital with suspected papilloedema was performed between 1/1/17 and 16/5/17. A follow-up re-audit was performed from 1/6/17 to 31/8/17 following implementation of OCT prior to referral.ResultsThe initial audit identified 50 patients over 136 days and the re-audit 26 patients over 92 days. In the initial audit 6/50 had OCT and 17/50 (34%) were admitted. 6/50 patients were subsequently found not to have papilloedema on fundoscopy, none of whom had OCT. 4/6 underwent unnecessary neuroimaging and lumbar puncture. 3 were admitted, equating to 18% of all admissions, for an average of 2.3 days. In the re-audit all had OCT, 6/26 (23%) were admitted and none were subsequently found not to have papilloedema.ConclusionUse of OCT prior to referral for suspected papilloedema helps to reduce unnecessary investigations.
THUR 196 Pregnancy outcomes in alemtuzumab-treated rrms patients
Authors: David Rog , Jiwon Oh , Christina Chambers , Kerstin Hellwig , Pamela McCombe , Luke Chung , Nadia Daizadeh , S Compston D Alastair 
Published: October 2018

Murine studies show no alemtuzumab-related teratogenicity, but no controlled human clinical studies of alemtuzumab in pregnancy exist. In phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies, patients received 2 annual alemtuzumab courses. Two extension studies provided longer-term evaluation (NCT00930553; TOPAZ [NCT02255656]). Pregnant/lactating patients were ineligible for further treatment but were followed up for safety. As of 1 April 2017, 248 pregnancies occurred in 156/972 alemtuzumab-treated female patients (mean [SD] age at conception, 32.5 [4.4] years; mean [SD] time from last alemtuzumab dose to conception, 33.5 [22.6] months; 16 within 4 months of dosing), with 218 completed, 14 ongoing, and 16 with unknown outcomes. Of completed pregnancies with known outcomes, 147 (67%) were live births with no congenital abnormalities or birth defects. There were 48 (22%) spontaneous abortions, 22 (10%) elective abortions, and 1 (0.5%) stillbirth. To date, there has been no signal for teratogenicity. Incidence of spontaneous abortions was comparable with treatment-naive MS patients (5%–21%) and the general population (17%–22%). Real-world data are currently collected by the International Lemtrada Pregnancy Exposure Registry, a prospective, non-interventional, observational safety study enrolling patients in ≥19 countries who become pregnant within 4 months of alemtuzumab exposure.Study Support: Sanofi.
Comparing short versions of the Alcohol Use Disorders Identification Test (AUDIT) in a military cohort
Authors: Watterson Jason , Gabbe B , Dietze P , Bowring A , Rosenfeld J V 
Published: October 2018

BackgroundThe Alcohol Use Disorders Identification Test (AUDIT) is widely used for monitoring harmful alcohol consumption among high-risk populations. A number of short versions of AUDIT have been developed for use in time-constrained settings. In military populations, a range of AUDIT variations have been used, but the optimal combination of AUDIT items has not been determined.MethodsA total of 952 participants (80% male), recruited as part of a wider study, completed the AUDIT-10. We systematically assessed all possible combinations of three or four AUDIT items and established AUDIT variations using the following statistics: Cronbach’s alpha (internal consistency), variance explained (R2) and Pearson’s correlation coefficient (concurrent validity).ResultsMedian AUDIT-10 score was 7 for males and 6 for females, and 380 (40%) participants were classified as having a score indicative of harmful or hazardous alcohol use (≥8) according to WHO classifications.A novel four-item AUDIT variation (3, 4, 8 and 9) performed consistently higher than established variations across statistical measures; it explained 85% of variance in AUDIT-10, had a Pearson’s correlation of 0.92 and Cronbach’s alpha was 0.63. The FAST, an established shortened AUDIT variant, together with several other four-item novel variants of AUDIT-10 performed similarly. The AUDIT-C performed consistently low on all measures, but with a satisfactory level of internal consistency (75%).ConclusionShortened AUDIT variations may be suitable alternatives to the full AUDIT for screening hazardous alcohol consumption in military populations. Four-item AUDIT variations focused on short-term risky drinking and its consequences performed better than three item versions.Trial registration numberACTRN12614001332617.
Innate Myeloid Cell Subset-Specific Gene Expression Patterns in the Human Colon are Altered in Crohn’s Disease Patients
Authors: Sekido Yuki , Yasumizu Yoshiaki , Nishimura Junichi , Kayama Hisako , Matsuno Hiroshi , Ogino Takayuki , Miyoshi Norikatsu , Takahashi Hidekazu , Haraguchi Naotsugu , Hata Taishi , Matsuda Chu , Doki Yuichiro , Mori Masaki , Takeda Kiyoshi , Ohkura Naganari , Sakaguchi Shimon , Mizushima Tsunekazu 
Published: October 2018

<b><i>Background/Aims:</i></b> There is a heterogeneous subset innate myeloid cells, such as macrophages and dendritic cells, in the human intestinal lamina propria. Several studies have demonstrated that these cells contribute to the maintenance of gut homeostasis through the induction of inflammatory responses and tolerance via cell type-specific mechanisms; whereas, disrupted innate immune responses are implicated in the pathogenesis of Crohn’s disease (CD). However, the detailed mechanisms by which each innate myeloid subset regulates gut homeostasis and inflammation largely remain unknown. We aimed to clarify the comprehensive gene expression profiles of innate myeloid cell ­subsets in the lamina propria from normal human colons (NC) and the inflamed colon sites from patients with Crohn’s disease (CDi). <b><i>Methods:</i></b> We performed RNA-sequencing analysis and precise bioinformatics analysis on 3 innate myeloid cell subsets, CD14<sup>–</sup>CD11c<sup>–</sup>, CD14<sup>–</sup>CD11c<sup>+</sup>, and CD14<sup>+</sup>CD11c<sup>+</sup>CD163<sup>low</sup> cells from NC and CDi. <b><i>Results:</i></b> Transcriptional analysis of the 3 subsets from the NC showed distinct gene expression patterns and gene ontology (GO) enrichment analysis revealed the associated innate myeloid subset-specific biological process (BP) terms. In addition, changes in gene expression patterns were observed in innate myeloid subsets from CDi. Furthermore, the core GO-BP terms for the genes upregulated in the innate myeloid cells from CDi were distinct from those found in NC. <b><i>Conclusion:</i></b> Our data identified the innate myeloid cell subset-specific transcriptomes and the associated enriched GO-BP terms in the NC and found these patterns were altered in CDi.
The Making of the Good British Muslim
Authors: Püttmann Friedrich 
Published: October 2018

Abstract
This article investigates the meaning and political implications of the poppy hijab, a headscarf sporting British World War Remembrance poppies and intended to give British Muslims a new way of showing their social integration in public. Based on fieldwork with Muslims in London, I argue, however, that instead of furthering Muslims’ equitable inclusion in British society, the poppy hijab rather represents a Foucauldian “technology of the self” for them to prove that they are “good British Muslims”. As such, it reflects the unequal relations of power in society and may foster rather than lower general suspicion towards Muslims in Britain.
Hadrian’s Wall in Context: A Multi-Proxy Palaeoenvironmental Perspective from Lakes
Authors: Dark Petra 
Published: October 2018

AbstractThe Hadrian’s Wall area has more pollen sequences spanning Late Antiquity than any other part of the British Isles, but most are from peat bogs, posing problems of distinguishing between changes in the local wetland vegetation and events in the wider landscape. Here, an alternative perspective is offered by multi-proxy analyses of sediments from two lakes—Crag Lough and Grindon Lough—adjacent to the central sector of Hadrian’s Wall and the Stanegate, respectively. These demonstrate that at least the central sector of the Hadrianic frontier was constructed in a landscape already shaped by two millennia of woodland clearance, burning, farming and soil erosion. Roman military presence led to changes in agricultural and settlement patterns, but the overall impact, from an environmental perspective, was minor compared to that of prehistoric peoples. Roman withdrawal led to a relaxation in land use intensity, resulting in woodland regeneration on areas least favourable to agriculture, probably encouraged by climatic deterioration. The landscape, overall, remained predominantly open and agricultural, however, resembling that of the Late Iron Age. A multi-proxy multi-site approach offers the greatest prospect of understanding environmental and landscape changes connected with Roman military presence and withdrawal, and the varied spatial and temporal scales on which they occurred.
Environment, Climate and Society in Roman and Byzantine Butrint
Authors: Morellón Mario , Sinopoli Gaia , Izdebski Adam , Sadori Laura , Anselmetti Flavio , Hodges Richard , Regattieri Eleonora , Wagner Bernd , Brushulli Brunhilda , Ariztegui Daniel 
Published: October 2018

AbstractA multiproxy analysis (sedimentology, geochemistry and pollen) of sediments recovered in the Butrint lagoon (Albania) allows us to reconstruct the environmental changes that occurred in the area during the 1st millenniumAD. In this paper, we compare these analytical results with the evidence provided by archaeological investigations carried out at the site of the Roman city of Butrint (surrounded by these lagoon waters) and in the city’s hinterlands. From this, we can say that different periods of farming and siltation (AD400–600 and 700–900) were accompanied by increased run-off and wetter conditions in the region. This coincided with the territorial and economic expansion of the Byzantine empire, suggesting the key role of trade in the profound land use changes experienced in Butrint.
Climate Impacts from Afforestation and Deforestation in Europe
Authors: Strandberg G. , Kjellström E. 
Published: October 2018

Abstract
Changes in vegetation are known to have an impact on climate via biogeophysical effects such as changes in albedo and heat fluxes. Here, the effects of maximum afforestation and deforestation are studied over Europe. This is done by comparing three regional climate model simulations—one with present-day vegetation, one with maximum afforestation, and one with maximum deforestation. In general, afforestation leads to more evapotranspiration (ET), which leads to decreased near-surface temperature, whereas deforestation leads to less ET, which leads to increased temperature. There are exceptions, mainly in regions with little water available for ET. In such regions, changes in albedo are relatively more important for temperature. The simulated biogeophysical effect on seasonal mean temperature varies between 0.5° and 3°C across Europe. The effect on minimum and maximum temperature is larger than that on mean temperature. Increased (decreased) mean temperature is associated with an even larger increase (decrease) in maximum summer (minimum winter) temperature. The effect on precipitation is found to be small. Two additional simulations in which vegetation is changed in only one-half of the domain were also performed. These simulations show that the climatic effects from changed vegetation in Europe are local. The results imply that vegetation changes have had, and will have, a significant impact on local climate in Europe; the climatic response is comparable to climate change under RCP2.6. Therefore, effects from vegetation change should be taken into account when simulating past, present, and future climate for this region. The results also imply that vegetation changes could be used to mitigate local climate change.
Fidelity of the Observational/Reanalysis Datasets and Global Climate Models in Representation of Extreme Precipitation in East China
Authors: He Sicheng , Yang Jing , Bao Qing , Wang Lei , Wang Bin 
Published: October 2018

AbstractRealistic reproduction of historical extreme precipitation has been challenging for both reanalysis and global climate model (GCM) simulations. This work assessed the fidelities of the combined gridded observational datasets, reanalysis datasets, and GCMs [CMIP5 and the Chinese Academy of Sciences Flexible Global Ocean–Atmospheric Land System Model–Finite-Volume Atmospheric Model, version 2 (FGOALS-f2)] in representing extreme precipitation over East China. The assessment used 552 stations’ rain gauge data as ground truth and focused on the probability distribution function of daily precipitation and spatial structure of extreme precipitation days. The TRMM observation displays similar rainfall intensity–frequency distributions as the stations. However, three combined gridded observational datasets, four reanalysis datasets, and most of the CMIP5 models cannot capture extreme precipitation exceeding 150 mm day−1, and all underestimate extreme precipitation frequency. The observed spatial distribution of extreme precipitation exhibits two maximum centers, located over the lower-middle reach of Yangtze River basin and the deep South China region, respectively. Combined gridded observations and JRA-55 capture these two centers, but ERA-Interim, MERRA, and CFSR and almost all CMIP5 models fail to capture them. The percentage of extreme rainfall in the total rainfall amount is generally underestimated by 25%–75% in all CMIP5 models. Higher-resolution models tend to have better performance, and physical parameterization may be crucial for simulating correct extreme precipitation. The performances are significantly improved in the newly released FGOALS-f2 as a result of increased resolution and a more realistic simulation of moisture and heating profiles. This work pinpoints the common biases in the combined gridded observational datasets and reanalysis datasets and helps to improve models’ simulation of extreme precipitation, which is critically important for reliable projection of future changes in extreme precipitation.
Antipsychotic drug use and pneumonia: Systematic review and meta-analysis
Authors: Dzahini O , Singh N , Taylor D , Haddad PM 
Published: October 2018

Objectives: The purpose of this study was to investigate the association of antipsychotic exposure to the incidence and mortality of pneumonia. Methods: The design of this study involved meta-analysis of observational studies identified from electronic databases. Results: In total, 19 studies were included in the systematic review and 14 in the meta-analysis. Risk of pneumonia was increased by first-generation antipsychotics (risk ratio 1.69, 95% confidence interval 1.34–2.15; five studies), second-generation antipsychotics (risk ratio 1.93, 95% confidence interval 1.55–2.41; six studies) and all antipsychotics (risk ratio 1.83, 95% confidence interval 1.60–2.10; seven studies) compared with no antipsychotic use. Pneumonia risk did not differ in seven studies comparing first-generation antipsychotics with second-generation antipsychotics (risk ratio 1.07, 95% confidence interval 0.85–1.35). Case fatality rate was not different in pneumonia cases associated with antipsychotic exposure versus cases without exposure (risk ratio 1.50; 95% confidence interval 0.76–2.96; two studies). All antipsychotics with data from ⩾2 studies allowing meta-analysis, were associated with a significantly increased pneumonia risk (i.e. haloperidol, olanzapine, clozapine, risperidone, quetiapine, zotepine). Conclusion: Exposure to both first-generation antipsychotics and second-generation antipsychotics is associated with an increased pneumonia risk. Clinicians need to be vigilant for the occurrence of pneumonia in patients commencing antipsychotics, especially those with other risk factors for pneumonia including older age, chronic respiratory disease, cerebrovascular disease, dysphagia and smoking.