dataesr/scientific-paragraphs-categorization huggingface dataset:
Statistical analysis Data are presented as means ± standard error of the mean. The areas under the curve (AUC) after ACTH injection were calculated with respect to ground by the trapezoidal approach  (Pruessner et al. , 2003). The area was limited to the 0 to 90 min period after ACTH injection because samples taken at 120 min were lost for one experimental group. Cortisol concentrations or AUC after ACTH injection were analyzed using linear mixed effects models (package 'nlme' of R) with the animal as a random factor to account for repeated measures and time of the day and season (basal cortisol concentrations), or ACTH dosage, season and age (AUC) as fixed factors. Statistical significance was set at P < 0. 05. Diurnal variations were also analyzed by cosinor with the R package 'season'  (Tong, 1976).
Acknowledgments The authors thank all the staff of the experimental station of  Beni-Abbes (W. Bechar). Special thanks to  Zahreddine Djazouli  ( University Saad Dahlab ,  W. Blida ) and  Yann Labrune  ( INRA, Castanet-Tolosan ) for help with statistical analyses, and  Nouria Boukenaoui  of the  Research Laboratory LRZA/USTHB  for technical support with cortisol immunoassays. The authors dedicate this work to the memory of their colleague  Yahia Lakhdari , LRZA/USTHB. Special thanks to  Prof. Byron C. Jones  ( UTHSC Memphis, TN, USA ) for editing the manuscript.
Ethics statement The research reported here does not involve data on human participants themselves, only on farm management practices they were using. All data were collected via questionnaires. All livestock owners were approached by their farm veterinarians, informed about the aim of the study and asked if they were willing to participate, thereby asking for their verbal consent. Questionnaires were only used with farmers who gave their verbal consent, which was noted on the questionnaire. Data being entered into the online database were anonymized by using the country code and the name of the veterinarian who provided the contact (in order to match the farms on veterinary practice). No names of farmers were recorded in the database. Livestock owners provided verbal consent for sampling their animals.
In the Netherlands, all blood samples and carcasses were sent to GD Animal Health in Deventer. In France, veterinarians involved in the on-farm data collection analysed the blood samples in their own laboratory if possible, or in a human diagnostic laboratory. Gross-pathological signs were recorded during the post-mortem examination by these veterinarians and bone-marrow samples stored in formaldehyde were sent to Oniris for histological analysis. In Belgium, blood samples from BNP suspected calves were examined in the laboratory of Ghent University, Department of Internal Diseases of Large Animals, and carcasses were sent to DGZ for necropsy. Post mortem reports were sent to the project office. A bone marrow sample was sent to the Department of Pathology at the Veterinary Faculty for final diagnosis of BNP.
Data collection The data for this study was collected by structured interviews using a questionnaire. Given the lack of knowledge of likely risk factors, apart from feeding of colostrum from PregSure vaccinated dams, the questionnaire covered a wide range of potential risk factors, including general management practices, colostrum and milk feeding practices, vaccine and medicine use, and BVD control measures (Table  1 ). Details of the clinical picture, such as of the number of calves affected by BNP in previous years, were requested. A copy of the questionnaire is provided in the supplementary material (S1 File). The questionnaire used in the case-control study consisted of two parts: The first part asked about herd-level management information (the focus of the current study) and the second part asked about the detailed history of affected calves and chosen control calves (the focus of the previously published study  [24].
Data used in the present study were not analysed for the previous publication  [24]. Because of the detailed information required from case farms on vaccinations and the management of the case and control calves, it was considered best for the veterinarian to complete the questionnaire with the farmer during a face-to-face interview in their local language. In France and Germany, the local veterinarian was sent a copy of the translated questionnaire and was asked to complete this with the farmer and return it to the project coordinators in their respective country. After the questionnaires were obtained by the coordinators, the answers were checked for plausibility and completeness and, if necessary, veterinarians were contacted for clarification. In the Netherlands and Belgium, one project veterinarian visited all case farms and completed the questionnaire together with the farmer.
Each case farm interview lasted 1. 5 to 2 hours. For control farms, less detailed information was required as there were no affected calves. Thus these farmers were contacted by telephone and a time for a telephone interview was arranged. Telephone interviews were carried out by the project coordinators in the respective countries. All data were entered into a centralised database via a web-based data-entry form developed at Ghent University, Department of Reproduction, Obstetrics and Herd Health, using the open source software LimeSurvey (http://www. limesurvey. org). Data were then exported first to a Microsoft Excel spreadsheet for preliminary cleaning and then into the SAS for Windows 9. 3 statistical software for coding, further cleaning and analysis.
Data analysis The database table consisted of 1462 records. If case farms had several BNP calves the farm was represented multiple times in the database table. Since for the present analysis only farm information was relevant, therefore duplicate records, representing information on different calves from the same farm, were deleted. If conflicting information had been entered for a farm, paper records were consulted for clarification. Records of case farms without a matched control farm and records with a high percentage of missing values were deleted from the analysis dataset. This resulted in a subset of data for analysis comprising 1250 observations. Categorical variables with small numbers of observations in some categories were aggregated into a smaller number of categories based on epidemiologically and biologically sensible criteria.
05 for entry and > 0. 1 for removal. To assess collinearity between variables, pair-wise associations were examined using polychoric correlations. If two variables were highly correlated (r > 0. 8) only one was offered to the modelling algorithm, chosen based on biological reasoning or a lower p-value. For the final model of the analysis across risk factor groups, first-order-interactions between the significant main effect variables were assessed for their statistical significance. Results are presented as odds ratios together with their 95% confidence intervals. All analyses were conducted using SAS for Windows version 9. 3 (SAS Institute, Cary, North Carolina, USA).
Descriptive results In total, 212 farm records had to be omitted from the analysis due to duplication, incomplete data or not being matched with a case or control farm. Thus, 1250 farm records remained in the final database, of which 363 were case farms and 887 were control farms. Belgium contributed 70 case and 160 control farms, France 116 cases and 297 controls, Germany 77 cases and 203 controls and The Netherlands 100 cases and 227 controls. In total, there were 812 dairy farms, 228 beef farms and 210 mixed farms. These were not evenly distributed between the countries (Table  2 ). The types of BVD vaccine used on case and control farms are shown in Table  3. More than half of the control farms had not used any BVD vaccine, compared with only 7% of the case farms. More than 85% of the case farms had used the BVD vaccine PregSure, compared with 22% of the control farms.
024, vitamin E/selenium, p = 0. 027 and pour-on insecticides, p = 0. 043; Table  4 ). Within the risk factor group 'BVDV related variables' several variables were correlated with each other. The variable 'reason for starting a BVD vaccination programme' was excluded from the multivariable analysis, as it would have limited the dataset to those farms that had a BVD vaccination programme in place. Only the variable 'BVD vaccination' was found to be significantly associated with the case-control status (Table  4 ). All variables retained in the individual risk factor group models were examined for correlations and then included in the combined multivariable analysis. A polychoric correlation coefficient of > 0. 8 was found between the variable 'BVD vaccination' (BVD vaccine used, PregSure used, other BVD vaccine used) from the risk factor group 'BVD related variables' and 'BVD vaccination used on farm' (yes/no) from the risk factor group 'Vaccinations'.
The current study was designed to fulfil that knowledge gap. It was not possible to recruit the target number of 100 case farms and up to 400 control farms for each country during the one-year study period due to limited case reporting in some countries. But the study still generated a database with 363 case and 887 control farms suitable for analysis, thereby providing sufficient statistical power to detect smaller effect sizes and representing a broader spectrum of cattle farming systems than any of the previous studies. The case definitions used in each of the countries before the beginning of the study differed slightly with regard to blood value thresholds or pathological findings. For the present study, we used the same criteria across the four study countries. A calf was only classified as a BNP case if it showed clinical signs and if panmyelophthisis was found in bone marrow histology and/or if thrombocytopenia (values below 150 x 109/litre) and leukocytopenia (values below <5 x 109/litre) were present.
Additionally, farm managers of case farms were interviewed within a period of 2-10 weeks of the case being diagnosed to further minimise recall bias. Data collection on control farms offered less potential for heterogeneity in information bias between countries, as all interviews were conducted by telephone in all four countries. It is possible that face-to-face interviews have resulted in better data quality than telephone interviews, thereby causing differential information bias between case and control farms. However, as the questions used for comparison between case and control farms were all about general herd and calf management, this bias was considered negligible. Further actions for reducing potential bias were taken at the analysis level. Data collected on BVDV related issues were cross-checked and combined into a reduced set of new variables, thus providing more reliable information and resulting in less multicollinearity between the variables.
Data collected for different age groups were analysed separately as well as aggregated at the whole herd level, as the answers were highly collinear between the age groups. In the final conditional logistic regression model, only three variables were significant: BVDV vaccination, feeding of colostrum from calf's own dam, and feeding of pooled colostrum. The variable 'BVD vaccination' incorporated vaccination information for all age groups and also the type of vaccine used (no BVD vaccination, PregSure used with or without other BVD vaccines, and other BVD vaccines used except PregSure). This variable had the largest effect size in the multivariable analysis. Of all the risk factors, the highest odds ratio was for using PregSure vaccine either alone or in combination with other BVDV vaccines.
Amplification and sequencing Gene rrs (1171 bp). Sequencing of the rrs gene (16SrRNA) was performed using the following primers: SQ1 (5 0 -AGAGTTTGATCMTGGCTCAG-3 0 ), SQ2 (5 0 -AAACTCAAA-GRATTGACGGG-3 0 ), SQ3 (5 0 -CCCGTCAATYCTTTGAG-TTT-3 0 ), SQ4 (5 0 -CGTGCCAGCAGCCGCG-3 0 ), SQ5 (5 0 -CGCGGCTGCTGGCACG-3 0 ) and SQ6 (5 0 -CGGTGTGTA-CAAGGCCC-3 0 ) (0. 2 μM) according to the Sanger method adapted by the DYE terminator sequencing kit (Amersham Biosciences, Uppsala, Sweden). The nucleotide sequences were determined with an automated sequencer ABI 377 (Applied Biosystems, Foster City, CA, USA) according to the manufacturer's instructions by the Biofidal (Vaux-en-Velin, France). According to the recommendations of Rodríguez-Nava et al. [7] ; the sequences were aligned using the Clustal X program  [13].
Materiales Y métodos Se utilizaron 41 cepas Tipo del género Nocardia de colecciones internacionales, a las cuales fueron secuenciados los genes rrs y hsp65 que no se encontraban en GenBank. Las secuencias de los genes secA1, rpoB y gyrB, fueron obtenidas completamente del GenBank. El gen sodA de todas las cepas fue secuenciado en nuestro laboratorio (Tabla 1).
TABLA 1. Números de acceso para 6 genes de las diferentes cepas tipo de Nocardia obtenidos del GenBank Números de Acceso Gen Especie Clave rrs hsp65 secA1 rpoB gyrB sodA 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 N. abscessus N. amamiensis N. anaemiae N. aobensis N. araoensis N. arthritidis N. asiatica N. asteroides N. beijingensis N. brasiliensis N. brevicatena N. carnea N. cerradoensis N. coubleae N. cyriacigeorgica N. exalbida N. farcinica N. flavorosea N. fluminea N. gamkensis N. higoensis N. ignorata N. inohanensis N. mexicana N. neocaledoniensis N. niigatensis N. nova N. otitidiscaviarum N. paucivorans N. pneumoniae N. pseudobrasiliensis N. puris N. seriolae N. shimofusensis N. sienata N. thailandica N. transvalensis N.
Stratification of the population Trading and movements of live cattle have been widely considered as the main pathway for brucellosis introduction into free cattle herds  [19] [20] [21] [22] [23] [24]. Given that the movements of quarantined cattle (following a suspicion in a herd) are restricted  [6] , the threat of brucellosis introduction is posed by the presence of brucellosis in the unrestricted population, i. e. infected herds which have not yet been detected  [24]. Therefore, we considered that the risk of disease introduction into a herd was related to the number of bovine purchases (from France or another country). The cattle herd population was divided into three risk groups: no-trade, lowtrade and high-trade groups. The proportion of herds in the no-trade group corresponded to the annual proportion of holdings which did not introduce any bovine during 2010-2014 (calculated using data from the national cattle register database).
Surveillance costs Overall, the current surveillance system (scenario 1) was estimated to cost at least 15 million €, which matches the data-based evaluation of 17 million € for 2013 (based on numbers of vets' visits, samples and laboratory analyses from the French national animal health information database)  [11]. The breakdown was as follow: 10. 2 million € for programmed surveillance, 2. 7 million € for introduction (purchase) controls, and 3. 7 million € for abortion investigations; other marginal expenses (not considered in the scenario tree analysis) included 0. 5 million € for surveillance derogations in fattening herds and about 0. 03 million € for investigations of suspect cases  [11]. Simplifying hypotheses considered in the scenario-tree model made that some costs were somewhat underestimated in comparison to the data-based study.
Acknowledgments The importance of the participants in this project cannot be overemphasised. The authors would like to thank all of the farmers and GDS representatives, the veterinarians and their GTV representatives, the veterinary services agent and laboratory technicians for their time and insight, which were essential to this project. The authors also thank all the experts contacted during this study for their suggestions and advice in setting up the interview guides, particularly  Jean-Yves Millemann  and  Sebastien Gardon  for the additional helpful sociological suggestions in preparing the manuscript. The authors gratefully acknowledge  Andrew Catley  for his help in reviewing the manuscript and in widening the scope of application.
We used conjugate gradient and incomplete LU as the coarse grid solver. The coarse grid solver was terminated after 25 iterations, or if the initial residual was reduced by a factor of 10 4. The non linear solver uses picard iterations with rtol 10 -2 or atol 10 -4. pTatin3D  (May et al. , 2014 (May et al. , , 2015) )  is an open source code copyrighted under GNU General Public License v. 3 and may be accessed 1 at https://bitbucket. org/jedbrown/ptatin3d. pTatin3D heavily leverages functionality from PETSc, which can be freely downloaded at http://www. mcs. anl. gov/petsc. Input files are available upon request from the corresponding author.
Acknowledgements Maps were realised with GMT, post processing with Paraview. The paper benefited of discussions with  C. Basile ,  D. Aslanian  and  P. De Clarens  through the  Action Marge Program. D. A. May  and  L. Le Pourhiet  acknowledge the  Swiss National Supercomputing Centre  ( CSCS ) for compute time on  Piz Dora , obtained under the production proposal grant  20131011-2135237.
Clinical data collection Efficacy parameters such as exercise capacity assessments (6-min walk distance, 6-MWD), plasma N-terminal probrain natriuretic peptide (NT pro-BNP), and the laboratory safety parameters leukocytes and bilirubin were chosen for PK/PD modeling to further explore the small changes found in the safety analysis. The effect of selexipag exposure on erythrocytes and hemoglobin was investigated since PAH patients frequently encounter anemia. 8 Vital signs (blood pressure, heart rate), occurrence of prostacyclin-related and hemorrhage AEs were investigated since prostacyclin analogs are known to have vasodilatory and platelet aggregation inhibitory effects. Efficacy and safety parameter assessments were performed at baseline, weeks 4 (except 6-MWD), 8, 16, 26, every 6 months thereafter, at the end of study, and also if there was a suspected primary endpoint event.
Covariate selection (PK). Physiologically meaningful relations between patient characteristics and model parameters were tested for statistical significance. To avoid analysis of small subgroups, only covariates present in more than 5% of the analyzed study population were formally tested. The covariates tested (defined prior to database closure) were body weight, sex, age, race/ethnicity, organ function parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and creatinine clearance (CLcr) as well as CYP3A4/2C8 inhibitors that could influence the exposure to selexipag or ACT-333679, frequently used comedications in PAH such as ERAs and PDE5 inhibitors as well as digoxin, and disease status (NYHA/WHO functional class (FC)). Categorical (grouped) covariates were modeled as differences to a reference group.
The reference group was female for sex, Asian for race/ethnicity, na€ ıve for PAHspecific comedication, class II for NYHA/WHO FC at baseline, no use of CYP inhibitors, and digoxin comedication. Covariates were modeled as a power relationship. For a continuous covariate, the parameter value for the i-th subject, for example, drug clearance (CL), was defined as: CL pop;i 5 CL pop Ã covariate= typical covariate value ð Þ ð Þ H For categorical covariates, the parameter estimate for a category was estimated as the product of the reference category and the category-specific difference b, e. g. , CL male 5 CL female Ã exp b male ð Þ The typical covariate values were derived from the data using a round value close to mean and median (40 years of age, 70 kg body weight, 100 mL/min/1. 73 m 2 CLcr, 20 U/ L AST, 20 U/L ALT, and 10 lmol/L total bilirubin).
Clinical response modeling Use of PK data. The model-estimated individual steadystate exposure at the IMD over one dosing interval (12 h) was defined as the combined AUC of selexipag and ACT-333679 with weights according to their potencies, ACT-333679 being 37-fold more potent than selexipag. 2 The individual steady-state combined exposure (AUC combined ) at the IMD over a 12-h dosing interval was derived as: AUC combined 5 1=38 Ã AUC selexipag 1 37=38 Ã AUC ACT-333679 Placebo subjects were assigned an IMD and AUC combined equal to 0. Use of PD data. Vital signs (systolic, diastolic, and mean arterial blood pressure, heart rate), laboratory values (hemoglobin, red blood cell count, NT pro-BNP, total bilirubin, white blood cell count), and exercise capacity (6-MWD) were averaged per subject over the steady-state period from week 8 to week 52 (based on observed data only, missing data were not imputed).
Acknowledgments. We thank  Jochen Zisowsky  ( Actelion)  for contributions in the development of the PK model for the healthy subjects,  Olaf Mackenroth  ( Swiss Bioquant ) for the bioanalytics,  Mikael Saulay  and  Olivier Hauswirth  (Aptiv, now  ICON ) for dataset programming and preparation,  Denis Boutin  ( Actelion ) for support with data management expertise,  Kaelig Chatel  (Lixoft) for technical expertise with Monolix modeling, and  Ralph Preiss  and  Rainer Zimmermann  ( Actelion ) for helpful discussions. All the above have provided the corresponding author with the permission to be named in the article. Clinical Trial Registration. https://www. Clinicaltrials. Gov/ct2/ show/NCT01106014, NCT 01106014.
Two-photon laser-scanning microscopy and image acquisition For 2P-LSM we built a custom-made microscope with four channels for simultaneous recording of different FPs. Three dichroic mirrors split the fluorescence signal between a Zeiss W Plan Apochromat objective (20x, NA 1. 0, water immersion; Carl Zeiss GmbH, Jena, Germany) and four Photo Multiplier Tubes (Hamamatsu, Japan). Modified ScanImage software  (Pologruto et al. 2003)  was used to drive the microscope. Photographic and epifluorescence overviews of the spinal cord were acquired using a 5x objective (NA 0. 15; Zeiss, Jena, Germany) and a CCD camera (Fig. 3b, c ). High resolution in vivo imaging was performed using the custom-made microscope equipped with a fs-pulsed titanium-sapphire laser (Chameleon Ultra II; Coherent, Glasgow, UK).
Methods Yola software was used to develop an online educational tool covering DFU history and examination, arterial assessment, microbiology, radiology and management of osteomyelitis. The tool contains links to NICE guidance and other relevant learning resources. A quiz using patient scenarios is included. Feedback from podiatrists was elicited by questionnaires and a focus group. Patients with non-infected or mildly infected DFUs were recruited from community podiatry clinics in 2 UK regions. Exclusion criteria included immunosuppression or receipt of antibiotics within the previous 2 weeks. Antibiotics were prescribed based on clinical judgement at the baseline assessment. Our gold standard defining DFU infection was the clinician's judgement one week later, while still blinded to test results, factoring in the response to antibiotic therapy, if prescribed.
Aim The aim of this study was to explore the effect of AFO and stance width on standing balance in people with DPN compared to a healthy control group. Methods 18 subjects per group were investigated (DPN vs Healthy). Participants stood in standardised footwear (Pullman, USA) with their eyes closed. The medial borders of their feet were either 4 or 16 cm apart. For each stance width people stood in 2 conditions; "AFO" or "No AFO". The order of the stance width and AFO use was randomised. After a random (1-3 seconds) period frontal plane movement of markers placed on the shoulders (acromion process) was recorded during a 1 second baseline period using 3D motion analysis (CodaMotion, UK). The centre point between shoulder markers was calculated in MatLab (Mathworks UK) for subsequent calculation of sway velocity.