dataesr/scientific-paragraphs-categorization huggingface dataset:
, 2008). It has been shown that low temperatures (<30 • C) promote the expression of genes associated with biofilm development, including genes involved in curli (csgA and mlrA) or cellulose (yaiC) production  (Olsen et al. , 1989; Arnqvist et al. , 1992; White-Ziegler et al. , 2008). Interestingly, although O26:H11 strains formed weaker biofilms than other strains, they formed significantly stronger biofilms at 18 • C than at 30 • C. Also, all but one O26:H11 strains were negative for pgaA, a gene coding for the export of poly-N-acetyl-D-glucosamine (PGA) that promotes biofilm formation  (Itoh et al. , 2008; data not shown). In addition, pgaA sequence is also absent in the sequenced genomes of STEC O26 strains available in GenBank. In conclusion, the ability of strains to form a biofilm might contribute to their persistence in coastal environments.
ACKNOWLEDGMENTS This work was funded by the  European Regional Development Fund Interreg IVA Programme , as part of the collaborative project  RiskManche. The thesis of CB was supported by a grant from  Ifremer  and the  Agence de l'Eau Loire-Bretagne. We thank  Clémence Balière  from the  University of Caen and Céline Courroux from Hôpital Robert-Debré , for their participation in the sampling and technical assistance and  Dominique Hervio-Heath  (Ifremer) and  Huw Taylor  ( University of Brighton, UK ) for their critical review of the manuscript. Work in the  LREC-USC-laboratory  was financed by the grant  CN2012/303  from  Consellería de Cultura, Educación e Ordenación Universitaria  ( Xunta de Galicia ) and The  European Regional Development Fund, ERDF).
Objective. Previous reports of the RAPID-axSpA trial (NCT01087762) described the efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with axial spondyloarthritis (SpA), including ankylosing spondylitis (AS) and nonradiographic axial SpA. We report efficacy and safety data up to week 96 of the study. Methods. The RAPID-axSpA trial is double-blind and placebo-controlled to week 24, dose-blind to week.
48, and open-label to week 204. Outcome variables included Assessment of SpondyloArthritis international Society criteria for 20% and 40% improvement in disease activity (ASAS20/40), ASAS partial remission responses (analyzed by nonresponder imputation), AS Disease Activity Score (ASDAS), ASDAS inactive disease, ASDAS major improvement, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Bath AS Metrology Index (BASMI) linear ClinicalTrials.
Address correspondence to J. Sieper, MD, ChariteUniversitätsmedizin Berlin, Medizinische Klinik I, Rheumatologie, Hindenburgdamm 30, 12203 Berlin, Germany. E-mail: joachim. sieper@ charite. de. Submitted for publication  March 26, 2014 ; accepted in revised form  November 20, 2014. score (analyzed by the last observation carried forward method). Safety data were collected for patients treated with >1 dose of CZP. Results. Of the 325 patients who were randomized, 218 received CZP from week 0. Of these, 93% completed week 24, 88% completed week 48, and 80% completed week 96. Improvements in ASAS responses were maintained to week 96 (for ASAS20, 67. 4%, 72. 0%, and 62. 8% at weeks 24, 48, and 96, respectively), as well as improvements in ASDAS, BASDAI (mean score 3. 3, 3. 1, and 3. 0 at weeks 24, 48, and 96, respectively), BASFI, and BASMI linear score.
PATIENTS AND METHODS Patients. Detailed inclusion and exclusion criteria for the RAPID-axSpA trial have been reported previously  (12). Eligible patients had active disease (Bath AS Disease Activity Index [BASDAI]  [14]  Ն4 and spinal pain Ն4), had an inadequate response to Ն1 NSAID, and fulfilled the ASAS criteria for adult-onset axial SpA  (2). The study included patients with AS (Ͼ50% of patients) and patients with nonradiographic axial SpA (no definitive sacroiliitis on radiography), as defined by the modified New York criteria  (1). Further exclusion criteria have been described previously  (12). Trial design. Treatment procedures. The RAPID-axSpA trial (ClinicalTrials. gov identifier: NCT01087762) is a phase III, multicenter trial of treatment of axial SpA, which is double-blind and placebo-controlled to week 24, dose-blind to week 48, and an open-label extension to week 204.
All cases of PPD Ն5 mm or suspected tuberculosis were reviewed post hoc by independent experts. Active tuberculosis was confirmed according to the World Health Organization criteria for tuberculosis. Statistical analysis. The majority of efficacy outcomes are presented for all patients randomized to receive either CZP 200 mg every 2 weeks or CZP 400 mg every 4 weeks at baseline (randomized set), although selected data are also shown for patients who were rerandomized from placebo to either of the CZP dose regimens at week 16 or 24. Response rates (%) were calculated using nonresponder imputation (NRI), and quantitative assessments are shown as arithmetic means and use last observation carried forward imputation. Observed data are also shown for patients completing week 96. Analyses are presented in the overall axial SpA population and for the AS and nonradiographic axial SpA subpopulations.
Any remaining diet was withdrawn early on the following day. All animal interventions were performed in accordance with the European Directive number 86/609, and the rules of the "Guide for the Care and Use of Laboratory Animals", 7th edition, 1996, Institute for Laboratory Animal Research (ILAR), Washington, DC. 2. 2. 1. 1. Telemetry monitored evaluations in Cynomolgus primates. The effects of etamicastat (15, 45 and 90 mg/kg) on arterial blood pressure, heart rate and the main parameters of the electrocardiogram were evaluated following oral (p. o. capsule) administration in the conscious male Cynomolgus primate monitored by telemetry. The doses of etamicastat were based on the results from a maximum tolerated dose (MTD) study in Cynomolgus monkeys in which the MTD was established as 120 mg/kg/day (BIAL data on file).
There was 1 treatment group of 4 primates following a 4 × 4 Latin-square design. There was a washout period of 1 week between each treatment. Animals were dosed at approximately the same time each day. Venous blood samples (approximately 1 ml) for determination of etamicastat in plasma were taken prior to dosing and at 2 and 4 h after the start of dose administration, or as close as was reasonably practicable to these time points. Four male Cynomolgus primates were surgically implanted with telemetry transducers, type TL11M2-D70-PCT (Data Sciences International), for the measurement of arterial blood pressure and lead II electrocardiogram (ECG). Briefly, using sterile techniques and with the animals anaesthetized with isofluorane, the implant body was placed intraperitoneally in the lower quarters of the abdominal cavity and the blood pressure catheter introduced into the femoral artery with the tip estimated to be in the terminal abdominal aorta.
2. 2. 2. 1. Cardiac evaluation after single ascending administration in young healthy humans. This was a single-center, entry-into-man, phase 1, double-blind, randomized, placebo-controlled study (trial registration EudraCT No. 2007-001181-33) in 10 sequential groups of 8 healthy male subjects each. In compliance with a randomization list generated by using computerized techniques, within each group 2 subjects were randomized to receive placebo and the remaining 6 to receive etamicastat. Etamicastat was administered as single oral doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 or 1200 mg. Eligible volunteers were admitted to the unit 2 days prior (Day -2) to receiving the study medication (Day 1) and remained in the unit under clinical supervision for at least 72 h after dosing (Day 4). During admission, SBP and DBP and HR were recorded in supine position (after resting for at least 10 min) using a Dinamap® (GE Healthcare) monitor at the following times: Day -1 (the day prior to dosing)time 0 (24 h before dosing) and 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16 h after; Day 1 (dosing day)pre-dose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, and 72 h post-dose.
Cardiac evaluation after repeated oral administration in young and elderly healthy volunteers. This was an open-label, single-center, parallel-group study (trial registration EudraCT No. 2008-002127-82) in a group of 12 healthy young male subjects and a group of 12 healthy elderly male subjects. Participants were drawn from the study center's pool of volunteers. Volunteers eligible for participation were healthy male volunteers between 18 and 45 years (young group) or 65 years or more (elderly group), non-smokers or smokers of less than 10 cigarettes per day. Subjects were considered ineligible for participation if they: had been administered any investigational drug within 90 days, prescription drug within 30 days or over-the-counter drugs within 7 days before admission; showed to be prone to orthostatic hypotension, defined by a difference between supine SBP and standing SBP ≥ 20 mm Hg or a difference between supine DBP and standing DBP ≥ 10 mm Hg; or presented a ECG QTc interval reading ≥ 450 ms (young subjects) or ≥470 ms (elderly subjects).
Cardiac evaluation after repeated oral administration in hypertensive patients. This was a Phase IIa, double-blind, randomized, placebocontrolled study (trial registration EudraCT No. 2008-002789-69) investigating three dosage regimens of etamicastat (50, 100 or 200 mg, oncedaily, for 10 days) in 3 groups of 8 hypertensive male patients aged between 18 and 45 years. Within each group, it was planned to randomize 2 subjects to receive placebo and the remaining 6 subjects to receive etamicastat. Randomization was performed by means of computerized techniques. Doses of 50, 100 and 200 mg of etamicastat were investigated in ascending order. The decision to proceed to the next dose depended on the tolerability assessment of the previous dose level. Each patient participated in the study for approximately 8 weeks.
Statistical analysis Reported values are expressed as means ± standard error of the mean (SEM) or means with confidence intervals (CI). Statistical analysis was performed using the Dynamic Microsystem software GB-Stat version 6. 5. For in vitro (hERG) study, multisample analysis (ANOVA followed by Dunnett's test) was performed to test statistical significance of all concentrations tested. For in vivo (telemetry) studies, intra-group comparison was performed using an one-way analysis of variance (time) with repeated measures at each time, followed by Dunnett's t test in case of significant time effect, to compare each time value with the T0 values (i. e. basal value before each treatment). Inter-group statistical analysis was also performed using a two-way analysis of variance (group, time) with repeated measures at each time, followed by a one-way analysis of variance (group) at each time in case of significant group × time interaction.
Binding of [ 14 C]etamicastat to the human plasma proteins was moderate with a mean of 73. 9% (Bial data on file). As such, the ratio between the 44. 0 μg/ml IC 50 for hERG and the 0. 035 μg/ml unbound ETPC (44. 0/0. 044 = 1000) is 33 times higher the 30-fold safety margin. The no-effect concentration of 1. 0 μg/ml is 23-fold higher than the unbound clinical C max (0. 044 μg/ml). As such, the observed in vitro effect in the hERG assay is highly unlikely to have any clinical impact and this is supported by the review of Redfern et al. [30] , which concluded that a greater than 30-fold margin between hERG IC 50 and unbound clinical C max was sufficiently reassuring. In conclusion, the blockade of hERG current amplitude by etamicastat together with the QTc interval prolongation observed in conscious telemetered Cynomolgus monkeys can be considered as modest with respect to the plasma concentrations found for these effects and to those expected for beneficial cardiovascular activity in humans.
2  In particular, the smallness of the amplitude of the latter leads to a better constraint on α. The BaBar and Belle experiments reported evidence for the B 0 → ρ 0 ρ 0 decay  [8, 9]  with an average branching fraction of B(B 0 → ρ 0 ρ 0 ) = (0. 97 ± 0. 24) × 10 -6  [8, 9]. Despite small observed signal yields, each experiment measured the fraction f L of decays yielding a longitudinally polarised final state through an angular analysis. The Belle collaboration did not find evidence for polarisation, f L = 0. 21 +0. 22  -0. 26  [9] , while the BaBar experiment measured a mostly longitudinally polarised decay, f L = 0. 75 +0. 12  -0. 15 [8]. These results differ at the level of 2. 0 standard deviations. The large LHCb data set may shed light on this discrepancy. In addition, LHCb may confirm the hint of B 0 → ρ 0 f 0 (980) decays reported by Belle  [9].
Data sets and selection requirements The analysed data correspond to an integrated luminosity of 1. 0 fb -1 and 2. 0 fb -1 from pp collisions recorded at a centre-of-mass energy of 7 TeV, collected in 2011, and 8 TeV, collected in 2012, by the LHCb experiment at CERN. The LHCb detector  [10, 11]  is a single-arm forward spectrometer covering the pseudorapidity range 2 < η < 5, designed for the study of particles containing b or c quarks. It includes a high-precision tracking system consisting of a silicon-strip vertex detector surrounding the pp interaction region  [12] , a large-area silicon-strip detector located upstream of a dipole magnet with a bending power of about 4 Tm, and three stations of silicon-strip detectors and straw drift tubes  [13]  placed downstream of the magnet. The tracking system provides a measurement of momentum, p, of charged particles with a relative uncertainty that varies from 0.
The model parameters are determined from a simultaneous fit of simulated signal events that fulfill the trigger, reconstruction and selection chain, for each data taking period. The values of the tail parameters are identical for the B 0 and B 0 s mesons. Their mass difference is constrained to the value from Ref. [21]. The mean and width of the modified Crystal Ball function are free parameters of the fit to the data. - π + π )( - π + π ( → 0 B ) - π + π )( - π + π ( → s 0 B Combinatorial Partially reconstructed ) - π + π )( - π + (K → 0 B LHCb ] 2 ) [MeV/c - π + )(K - K + M (K 5100 5200 5300 5400 5500 - π + )(K - K + (K → 0 B ) + π - )(K - K + (K → s 0 B Combinatorial Partially reconstructed LHCb Figure 1: Reconstructed invariant mass spectrum of (left)(π + π -)(π + π -) and (right)(K + K -)(K + π -).
The limited size of the simulated events samples that meet all selection criteria result in a systematic uncertainty of 1. 7% (2. 6%) on the measurement of the relative branching fraction for the 2011 (2012) data-taking period. The impact of the discrepancies between experimental and simulated data related to the B 0 meson kinematical properties is 0. 6% (1. 2%). The efficiencies of the particle-identification requirements are determined from control samples of data with a systematic uncertainty of 0. 5%, mostly originating from the limited size of the calibration samples. An additional 1% systematic uncertainty on the tracking efficiency is added accounting for different interaction lenghts between π and K. The relative branching fraction is measured to be B(B 0 → ρ 0 ρ 0 ) B(B 0 → φK * (892) 0 ) = 0.
An additional strap was placed over the metatarsophalangeal joints to maintain and standardize forefoot position. Testing in the locked-unit occurred by fastening the boot of the dynamometer to the platform by a block that was placed vertically at the base of the boot (Fig  1A ). The open-unit configuration was created by removing the block to unlock the boot from the platform and by placing the heel of the boot onto a ball-bearing housing. This allowed movement of the lower limb horizontally but kept the knee and ankle joints in the established positions within the orthosis (Fig  1B ). Torque was sampled at 2 kHz using a custom built Matlab program (Matlab 7. 12, The MathWorks Inc. , MA, USA) and a 16-bit A/D board (National Instruments, Texas, USA) interfaced to a personal computer.
Data analysis The torque was calculated as described in Toumi et al. [25]. The force-torque signal was filtered by a 10 Hz low-pass filter (2 nd order Butterworth filter, zero lag) and was corrected for gravity by subtracting the baseline. The MVC and electrostimulation trials resulting in the highest generated torque in each condition were used for further analysis. The maximal torque corresponded to the maximal mean torque reached during the contraction over a 0. 5-s period. For the locked-and open-unit configurations, the bilateral index was calculated for both voluntary and electrically-induced contractions using the maximal torques from unilateral left, unilateral right and bilateral contractions. The Bilateral Index (%) = (bilateral torque / (unilateral left torque + unilateral right torque)) Ã 100 was also determined and a score lower than 100% was indicative of a bilateral strength deficit whereas a bilateral index higher than 100% suggested a bilateral facilitation  [30].
EMG was quantified as root mean square amplitude over the 0. 5-s period that corresponded to the maximal plateau of torque. To evaluate the level of coactivation, the EMG activity recorded from the tibialis anterior during PF was divided by the maximal EMG of the tibialis anterior recorded during dorsiflexion, and expressed as a percentage of MVC. All data processing was performed off-line using a custom built Matlab program (Matlab 7. 12, The MathWorks Inc. , Natick, MA, USA).
Statistics Data are reported as mean ± standard deviation (SD). The unilateral and bilateral left and right PF torques were used to compute the Bilateral Index (%) for the locked-and open-unit configuration in voluntary and electrically stimulated contractions. These indexes for voluntary and electrostimulation were independently evaluated with a test of means against the reference value of 100% to determine whether a deficit or facilitation was evident. Then, a paired t-test was also used to compare these indexes between the locked-and open-unit configurations. A task (unilateral, 'separated' bilateral) x setup configuration (locked-unit, open-unit) x side (left, right) 3-way repeated measures analysis of variance (ANOVA) was conducted for voluntary and electrically stimulated contractions.
Muscle activity from the torso directed towards maintaining the centre of balance but unrelated to the movement may have a neural influence on coactivation of the dorsiflexors and further enhance joint stability. In conclusion, the present data demonstrated that body adjustments contribute substantially to torque and that when these adjustments are contained within a measure of PF the bilateral strength deficit is recorded. However, when the measured torque is only due to the ankle joint muscles, bilateral and unilateral torques are similar. The vast majority of the literature on the bilateral strength deficit has clearly speculated and attempted to study a neural phenomenon. These data indicate that further exploration into a neural phenomenon underlying the bilateral strength deficit needs to account for body adjustments in the measurements of torque.
Data Collection Data were obtained from the European Group for Blood and Marrow Transplantation (EBMT) or Eurocord registries. The MDS subcommittee of the Chronic Malignancies Working Party and Eurocord both approved this study, which was performed according to the Declaration of Helsinki. All patients gave written consent for their data registration. Data were extracted by the EBMT office from PROMISE and Eurocord, and a questionnaire was sent to transplant centers to confirm HLA typing and request for the last follow-up status.
Study databases and population characteristics Almost all individuals resident in Scotland are registered with primary care, which provides a comprehensive array of healthcare services (free at the point of care), including prescriptions for medications. We used the Practice Team Information network, which covers a 5% representative sample of Scottish practices  [19]. Using the unique Community Health Index (CHI) number, specific patient-level data approved for use in this project were extracted and then linked to the Health Protection Scotland virology dataset, which consists of all laboratory-confirmed cases of influenza in Scotland. Once linkage had been completed, the analysis file was anonymised by replacing the unique CHI number with a study identifier. We established key population characteristics: sex, age (0-4, 5-14, 15-44, 45-64, 65-74, and ≥ 75 years), socioeconomic status (Scottish Index of Multiple Deprivation scores  [20]  expressed as quintiles: 1 = most deprived to 5 = most affluent), receipt of pneumococcal and influenza vaccination in the previous year, smoking status (current, ex, non, not recorded), urban/rural residence (1 = large urban to 6 = remote rural), whether a patient was in a clinical group at risk of serious illness from influenza (i.
3%) and those presenting symptoms less than 14 days after vaccination (n = 47; 1. 4%). The West of Scotland Specialist Virology Centre is a World Health Organization-accredited National Influenza Center, which participates in the Quality Assurance programme to maintain this status. To calculate VE, patient swab data were linked with the unique patient identifier CHI, allowing characteristics of patients such as vaccination status to be established from general practice and hospital admission data. In 2005/06 when influenza B (B/ Malaysia/2506/2004) was the predominant circulating virus type, tests were performed in sufficient numbers to estimate VE against influenza B in that season. The Privacy Advisory Committee of the Information Services Division, National Services Scotland, approved the linkage and analysis of the anonymised datasets for this project.
Acknowledgements The authors would like to thank staff at  PCCIU, Health Protection Scotland  and the  Information Services Division , the general practices and virus laboratories that contributed data to the study and members of the Independent Steering Committee overseeing this work. This study was funded by a grant from the  National Institute for Health Research Health Services & Delivery Research Programme  ( 09/2000/37 ) (Simpson CR et al. , http://dx. doi. org/10. 3310/hsdr01100). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HS&DR programme,  NIHR ,  NHS  or the  Department of Health. The authors also acknowledge the financial support of  ECDC  through their IMOVE seasonal influenza vaccination project led by  Epiconcept , which allowed virology data cleaning for the 2008/09 season.
Filipin staining of free cholesterol and fluorescence microscopy Differentiated cells on polylysine-coated slides were treated with SMs or vehicle for 24 h. Filipin staining was performed essentially as previously described  [31]. The adipocytes were viewed with a fluorescence microscope (Axioskop, Zeiss) using a UV filter set (365-nm excitation, 395-nm beam splitter and 420-nm long pass filter). The microscope was coupled with a camera (Hamamatsu Photonics C5310, Japan) and with SigmaScan Pro software (SPSS, Erkrath, Germany) to capture images.
Statistical analysis The effects of different SMs, GSH or PPMP were expressed relative to the controls, which were assigned an arbitrary value of 100 or 1. The results are presented as the means±SEM and have been analyzed for statistical significance using ANOVAS tests, followed by Student-Newman-Keuls tests (StatView software, SAS Institute, Cary, NC, USA). Univariate statistical analysis was performed by linear regression analysis to indicate correlations between the variables. The level of significance was set at P<0. 05.