dataesr/scientific-paragraphs-categorization huggingface dataset:
As far as we know, our study is the first to have estimated genetic parameters for calf diarrhea and umbilical infections in beef calves, as well as the first to have generated estimates of maternal genetic and common environmental variances for diseases affecting both beef and dairy calves. This first report on maternal parameters should be considered as preliminary results because our dataset lacked multigenerational data that would have enabled an accurate separation of direct and maternal effects. To date, only a few studies have estimated direct genetic parameters for diseases in the calves of dairy or dual-purpose breeds, and most of these estimates focused on BRD. For example,  Henderson et al. (2011)  estimated the heritability of umbilical (14%) and respiratory (9%) diseases in Holstein heifers, and more recently,  Mahmoud et al.
49) with maternal genetic resistance to early diarrhea. By contrast, a strong negative correlation (tending towards -1) was estimated between maternal genetic resistance to Umb1 and Diar2. In addition, strongly unfavorable maternal genetic correlations were estimated between Umb2 and both Diar1 (-0. 68) and Diar2 (-0. 85). These results suggest that selection to improve maternal genetic resistance to late umbilical infection may adversely affect resistance to diarrhea, as well as maternal genetic resistance to early umbilical infection. Until these results can be corroborated or disputed using a larger dataset, we would not recommend the use of Umb2 as a selection criterion for the improvement of general calf health. Instead, our data suggest that selection on both maternal and direct genetic resistance to early umbilical infection (Umb1) could potentially improve resistance to early umbilical infection and early and late diarrhea.
Online Database Search Strategy In order to find the studies assessing the anesthesia-related death and complications, an online database search was performed. In the online search, the terms (ASA or American-Society-of-Anesthesiologists) and (anesthesia or anaesthesia) and (death or mortality or risk or morbidity or complication or outcome) and (veterinary or animal) were entered in Pubmed, Google Scholar, Scopus, and VetMed Resources on April 1st 2018. In VetMed Resource, the results were filtered by "journal article, " "English language, " "death rate, " "morbidity, " and "clinical aspects. " One paper was hand searched from the reference section of other papers and books. The outcome variables included anesthesia-related mortality and complications in any domestic animal species. The anesthesia-related mortality was defined as death where anesthesia could not be excluded as a potential cause.
A RR = 1. 0 indicated there was no difference in risk of anesthesiarelated morbidity or mortality for patients assigned either ASA PS <III or ASA PS ≥III. The random-effects statistical model, which allows for differences in the treatment effect from study to study, was used for this analysis  (42). The RR, the Cochran's Q, and the I 2 were calculated using MedCalc Statistical Software version 18. 2. 1 (MedCalc Software bvba, Ostend, Belgium).
Studies Included in the Analysis A total of 233 studies were retrieved using the online research database strategy (65 from Pubmed, 14 from Google Scholar, 5 from Scopus, and 148 from VetMed Resources) and by hand searching the literature (1 study). From these, 162 were excluded because, based on the abstract, they were not relevant to our study, 25 studies were excluded because of the inclusion of patients with only a specific ASA PS, 18 were excluded because of no full data provision to calculate the RR and incidence of mortality or complication, and 14 studies were excluded because of no assessment of the anestheticrelated mortality and complication according to the ASA PS (Figure  5 ). A total of 14 studies with 241,509 patients (131,024 dogs; 102,064 cats; 8,394 rabbits; and 27 pigs) from 236 clinics (1 from USA, 1 from France, 18 from Japan, 42 from Spain, and 174 from UK) assessed from 1984 to 2016 met the inclusion criteria (Table  1 ).
The validation of alternative tests is the process by which the reliability and relevance of a test are established for a particular purpose  (Balls et al. 1990 ). Over the last several decades, the European centre for validation of alternative methods (ECVAM), in co-operation with international experts, has set up guidelines for validation. Seven modules are proposed for the validity assessment of a test: test definition (scientific purpose and mechanistic basis), intra-laboratory variability, transferability, inter-laboratory variability, predictive capacity, applicability domain, and performance standard  (Hartung et al. 2004). In Europe, anyone may submit an application for validation of an alternative method to ECVAM. ECVAM then consults its network for the preliminary assessment of regulatory relevance (PARERE).
Note that for drugs, this is easily achieved, as human data are available. For other chemicals, there may only be animal data, which may be less relevant. As stated before, it should be considered that comparing the results of one organ with those of a whole organism is not a fair comparison. Developing a novel and ideal model requires effort, creativity, and innovation. Hence, collaboration between academia, regulators, and industry is necessary to develop such models for the mutual benefit of all. A collaborative approach to novel model development could lead to an open access database of protocols and methodologies for developing such models, which could also serve as reference for validation and standardisation of the created models  (Alépée et al. 2014).
Results Clinical, animal, and environmental isolates genotyping using CGF40, MLST and whole genome sequencing (WGS). C. jejuni clinical isolates from 2009 appeared to be highly diverse with 85 CGF40 clusters based on 100% of similarity between isolates, and 62 STs  29. Clinical isolates from 2015 were also highly diverse with 229 CGF40 genotypes found. In addition, MLST performed on a subset of these clinical isolates (n = 79) using WGS, revealed 54 different STs, and 79% of the clinical isolates belonged to the 12 most common clonal complexes found (ST-21, ST-206, ST-257, ST-353, ST-48, ST-464, ST-22, ST-283, ST-42, ST-45, ST-52 and ST-658 complexes). A total of 1,618 animal and environmental C. jejuni isolates from putative sources of human infection (i. e. chicken, ruminant, environment, and pets) constituted the comparison data set of CGF40 genotypes, while the comparison data sets of MLST and host-segregating markers profiles comprised respectively 857 and 740 isolates characterized in previous studies (Supplementary Table  S1 ).
Accuracy of the several genotypes data in source attribution through self-attribution tests. The accuracy of the different genotyping methods in source attribution was assessed with isolates of a known origin. Self-attributions were performed on randomly selected subsets of isolates from each of the 4 putative contamination sources and the rates of correct self-attributions are shown in the Fig. 1. The probabilities of assignment of these isolates to the others sources are presented in the Table  1 , as well as their confidence interval at 95%. The probabilities of correct self-attribution using CGF40 markers for source attribution were estimated to 49% in chicken (CI95% = 0. 418, 0. 553), 40% in ruminant (CI95% = 0. 330, 0. 469), 76% in environment (CI95% = 0. 701, 0. 828), and 0% (CI95% = 0.
Based on large datasets of C. jejuni isolates from several putative sources of human contamination, the most likely origins of French campylobacteriosis from 2009 and 2015 were determined. In contrast to the majority of source attribution studies performed on MLST genes and using STRUCTURE software  20, 22, 37  , ruminants were the most common putative source of campylobacteriosis from 2009 in France (55%), and were equal to chicken in clinical cases from 2015 (38% for ruminant, 41-43% for chicken) based on MLST assignments. Nevertheless, this result is consistent with other source attribution studies  33, 38  , and may support a greater role for the ruminant reservoir in campylobacteriosis  39. However, when host-segregating-based assignments were considered, as they showed a better accuracy in self-attribution than MLST, ruminant and chicken were equally important in France in 2009, but there were more attributions to chicken in 2015, comparable to other studies  [19] [20] [21] 31, 34, 40.
Comparative Genomic Fingerprinting (CGF40). CGF40 fingerprints were generated from 8 Multiplex PCRs according to primer sets previously published  25  as well as experimental conditions  29. The PCR results were converted into binary data corresponding to the absence (0) or the presence (1) of each of the 40 markers in the bacterial genomes and the CGF40 fingerprints of these 40 genes (CGF40) were stored into BioNumerics ® soft- ware (v 7. 6, Applied Maths, Belgium). Each binary CGF40 fingerprint was then used in the source attribution model to assign an origin to clinical C. jejuni isolates from 2009 and 2015. To perform this, all clinical, animal and environmental isolates were previously genotyped using CGF40  10, 29, 77, 79.
MultiLocus Sequence Typing (MLST). Alleles of the seven housekeeping MLST genes (aspA, glnA, gltA, glyA, pgm, tkt and uncA) were determined as previously described  29. Alleles, sequence types (ST) and clonal complexes (CC) of isolates from cattle, pets, environment and clinical cases from 2015 were determined from whole genome sequence (WGS) data and by comparison of the sequences to the PubMLST database (http://pubmlst. org/campylobacter) on BIGSdb  82. MLST characterization through WGS was performed using a subset of isolates from cattle, pets, environment and clinical cases from 2015, keeping the same proportion as for CGF40 genotypes. The global experimental design is presented in Fig. 4.
Whole Genome Sequencing (WGS). Genomes were sequenced using the Ion Torrent technology on an Ion Torrent Proton machine (Life Technologies) according to previously published conditions  24. Assemblies were produced by either MIRA version 4. 0rc1 83 or SPAdes 3. 1. 1  84. Among 156 C. jejuni genomes newly sequenced, an average of 150 contigs was obtained with a median value of 62 contigs. The average of the total assembled sequence length is 1,715,087 bp (Supplementary Table  S2 ). French genomes sequenced in this study or previously  24  were augmented with 491 genomes of C. jejuni isolated from chicken, ruminant, environmental water and wild birds from different countries and published in previous studies (Fig. 4 )  [85] [86] [87] [88]. This gave a total of 859 C. jejuni genomes to constitute our study dataset (Supplementary Table  S1 ) in which allelic variations among 15 host segregating markers  24  was assessed for the source attribution study.
These host-segregating markers were preferred to whole genome to perform source attribution, as their potential in source attribution has been demonstrated  24  , while the whole genome was shown to not improve assignment compared with MLST  23. Accuracy of the several genotypes data in source attribution through self-attribution tests. To assess the accuracy of attribution probabilities obtained with each genotyping method, self-attribution tests were performed within the different host populations, as described in previous studies using MLST or the host-segregating markers  20, 24. Random subsets of twenty isolates from each hosts population were assigned to a dataset from unknown origin and 10 independent self-attribution tests were performed to assign these isolates to a source. Accuracy of genotyping methods were considered as significantly different when no overlap of their 95% confidence interval were observed.
Clinical isolates were distinguished from host populations isolates using POPFLAG. Host datasets used as a reference to probabilistically attribute a source to clinical isolates included isolates from 3 putative sources of contamination (chicken, cattle and environment) (Supplementary Table  S1 ). Pets were added as a source of infection in a second analysis since their role in campylobacteriosis as reservoir or vector is not fully elucidated  32, 90, 91.
Acknowledgements This publication made use of the Campylobacter Multi Locus Sequence Typing website (https://pubmlst. org/campylobacter/) at the  University of Oxford (Jolley & Maiden 2010, BMC Bioinformatics ,  11:595 ). The authors thank  Michèle Gourmelon  from  IFREMER  and  Francis Mégraud  and  Philippe Lehours  from the  National Reference Centre for Campylobacter and Helicobacter  for kindly providing the environmental and clinical isolates of C. jejuni. This work was supported by the  General Council of Côtes d' Armor (Conseil Départemental des Côtes d' Armor)  and the  General Directorate for Army (Direction Générale de l' Armement ).
Other options, such as supporting data acquisition from the home environment or providing evening or weekend disease awareness events, can offer convenience benefits for pet owners. Another important part of preparing for COAST is defining key focus areas. In order to avoid the under-diagnosis of OA in 'at risk' populations, a suggested key focus area is the assessment of preclinical dogs with OA risk factors, to facilitate discussions with pet owners, establish baseline COAST scores, define the interval to reevaluation and to ultimately improve the accuracy of disease monitoring over time. Opportunities within general practice for identifying such dogs are listed in Table  1. Particular attention should be focused on the education of owners of young, genetically predisposed breeds, or owners of dogs that have recently experienced joint injury or surgery.
Conflict of interest statement BDX Lascelles has received honoraria for Elanco-sponsored speaking engagements, and is a paid consultant of Elanco and for Eli Lilly. JF Innes is a member of the executive of CVS (UK) Ltd. He is the developer of the 'Liverpool Osteoarthritis in Dogs' (LOAD) CMI which is licensed to Elanco by University of Liverpool. In the last 2 years, he has received honoraria from Elanco and Norbrook Laboratories. He is also a director of Veterinary Tissue Bank Ltd. All other authors of COAST are paid consultants of Elanco and have received honoraria from Elanco within the last 2 years. None of the authors has any other financial or personal relationships that could inappropriately influence or bias the content of the paper. Appendix: Supplementary material Supplementary data associated with this article can be found, in the online version, at https://doi.
DNA Manipulations Genomic sequences were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database 1. Searches for DNA and protein homologies were carried out using the National Center for Biotechnology Information (NCBI 2 ) and the European Molecular Biology Laboratory (EMBL) -European Bioinformatics Institute server 3. Primers were synthesized by Sigma-Genosys (Haverhill, United Kingdom). DNA sequencing was performed by the "Servicio de Secuenciación del Centro de Investigación Médica Aplicada" (Pamplona, Spain). Restriction-modification enzymes were used under the conditions recommended by the manufacturer. Plasmid and chromosomal DNA were extracted with Qiaprep Spin Miniprep (Qiagen) and Ultraclean Microbial DNA Isolation Kits (Mo Bio Laboratories), respectively. When needed, DNA was purified from agarose gels using the Qiack Gel Extraction Kit (Qiagen).
Serial 10-fold dilutions of each homogenate were performed and each dilution was plated by triplicate. Plates were incubated at 37 • C for 5 days. At several points during the infection process, the identity of the spleen isolates was confirmed by PCR. The individual data were normalized by logarithmic transformation, and the mean log CFU/spleen values and the standard deviations (n = 5) were calculated.
Flow Cytometry To assess activation and maturation, BMDC were analyzed for surface expression of classical maturation markers at 24 h post-treatment with the different Brucella strains and derived mutants. Cells were labeled with fluorochrome-conjugated antibodies specific for mouse CD11c:APC-Cy7 (clone N418), IA-IE:PE (MHC class II clone M5/114. 15. 2) (PE), CD86:FITC (Clone GL-1), CD40:APC (clone 3/23), and CD80:PE-Cy5 (clone 16-10A1), all from BioLegend. Labeled cells were then subjected to multi-color cytometry using a LSR II UV (Becton Dickinson) and the data analyzed using FlowJo Software by first gating on the CD11c + population (100,000 events) prior to quantifying expression of receptors. Cells were stimulated with E. coli LPS (055:B5) as a positive control.
RESULTS The Brucella lptA Orthologs Encode a Lipid A Phosphate-Ethanolamine Transferase A genomic search in the KEGG database revealed that all Brucella spp. carry an ORF (BMEI0118 in B. melitensis) homologous to Neisseria meningitidis lptA, a pEtN transferase that modifies lipid A  (Cox et al. , 2003). Strikingly, in B. abortus but not in other Brucella spp. , all genomic sequences available at KEGG show a deletion of a thymine in position 774 that should result in a truncated protein lacking the amino acids related to the enzymatic activity  (Naessan et al. , 2008 ; Figure  1  and Supplementary Figure  S1  and Supplementary Table  S2 ). In addition to LptA, two other pEtN transferases have been identified in N. meningitidis: Lpt-3 and Lpt-6, which, respectively, modify the LPS core at the third and sixth position of heptose II  (Mackinnon et al.
FUNDING This research was supported by the  Institute for Tropical Health funders  ( Obra Social la CAIXA, Fundaciones Caja Navarra and Roviralta, PROFAND, Ubesol, ACUNSA, and Artai ) and grants  MINECO  ( AGL2014-58795-C4-1-R, Bru-Epidia 291815-FP7/ERANET/ANIHWA ),  Aragón Government  (Consolidated Group  A14 ), and  Marie Curie Career Integration Grant U-KARE  ( PCIG13-GA-2013-618162 ). TLB is the recipient of a Ph. D. Fellowship funded by the  Department for Employment and Learning (Northern Ireland ,  United Kingdom ).
| Data collection for laryngoplasty procedures Technical implantation differences were noted for each surgeon. All sutures were left in place and labeled, and the entire larynx with the overlying segment of the esophagus and its entry was excised by 1 observer masked to the surgeon who had performed the implantations. The cricopharyngeus and thyropharyngeus muscles that cover the vestibulum esophagi dorsally were separated and removed to have a complete view of the vestibulum esophagi. The distances from the insertion of the CAD on the caudal apex of the muscular process to the adventitia (D-AV) and lumen (D-LUM) of the vestibulum esophagi on the rostral spine of the arytenoid cartilage were measured. The distances between the insertion of the CAD on the caudal apex of the muscular process and the medial entry point and lateral exit point of the sutures for N1, N2, J1, and J2 and the sagittal exit point on the arcuate crest for NS were measured, and their average was calculated (hereafter called suture distance; Table  1 , Figure  2 ).
ACKNOWLEDGMENT The authors thank the students, interns, residents, and staff of the  Large Animal Clinic of Ghent University  for their time and help during the laryngoplasty procedures;  Thomas Van Bergen PhD , DVM,  Diplomate ECVS  ( Ghent University ) for the convincing advice to publish this anatomical finding;  Laurence Brandenberger MSoc , research assistant ( University of Berne ); and  Yu-Mei Chang Phd ,  CStat  ( Royal Veterinary College ) for providing statistical support.
). In each case, at least two observers recorded the modes from video footage. One was naïve (trained in ethology, but who had never observed horses before), while the other was accustomed to observing horses. Only the measures that present good reliability between the observers were selected and reused in the present experiment. Moreover, to check the inter-observer reliability, 20% of the data of the present experiment were reanalysed by a second observer (OBS 2), also blind to the treatment (a sample of 100 images: 4 images per horses randomly chosen during the session, on 25 horses). The level of observers' agreement on the facial expressions was high (Cohen's Kappa and percentage agreement for Height of neck: 1 and 100%; Opening of eye: 0. 97 and 99%; Lip tension: 0. 88 and 93%; Position of ears: 0.
Oxytocin and cortisol assays were performed and replicated in the INRA laboratory, Nouzilly, France. The experimenter was totally blind to the treatment. For oxytocin an ELISA (kit ADI-901-153, Enzo Life Sciences) was performed after molecular extraction using Sep-Pak C18 cartridges (Waters). Cortisol was assayed using radio immunology (RIA) after steroid extraction with a solvent (ethyl acetate/cyclohexane). Replicate measurements were performed. The intra-assay coefficients of variation were 17% at 20 ng/ml for cortisol, and 1. 5% at 100 pg/ml for oxytocin. The assay sensitivities were 0. 5 ng/ml and 7. 8 pg/ml for cortisol and oxytocin respectively. Data presenting intra-assay coefficients of variation higher than 20% were excluded from the analyses. Parameters recorded: Heart rate and heart rate variability.
The mean heart rate and heart rate variability (RR interval, RMSSD, SDNN) were recorded at S11 during the 10-min grooming session (Supplementary Figure  S1 ). The heart monitor system (Polar Equine RS800CX Science, Polar Oy, Finland) consisted of a flexible belt with two integrated electrodes, a transmitter, a separate storage device, and the corresponding software (Polar Pro Trainer, Version 5). The electrodes were placed behind the left humerus and across the sternum, and electrical conductivity was enhanced using ultrasound gel. The storage device was fixed to the belt within range of the transmitter. Animals were habituated to the device three times during the week preceding the beginning of the experiment.
These analyses were performed using Xlstat software (Addinsoft, Paris, France) with significance accepted at P ≤ 0. 05. We present the original P values because in cases of low sample size, the usefulness of using corrections for multiple comparisons is highly debated and results in a loss of power  [66] [67] [68]. Oxytocin and cortisol were analysed with linear mixed-effects models (lmm) in R (version 3. 3. 2, R Development Core Team, 2016) using the lmer function from the lme4 package. Models were fitted with restricted maximum likelihood estimation (REML) and p-values were derived using the Satterthwaite approximations (anova function from the lmerTest package). These models included oxytocin or cortisol as a response variable, the session number (S1 or S11), the factor "before or after session" and the treatment group (G or S) as fixed factors, as well as all possible interactions between them.
The individual identity of the horses was included as a random factor. Non-significant interactions were removed from the final models (for oxytocin, this was the case of the interactions between groups x before/after, and session number x before/after; for cortisol, no factors or interactions were significant). Residuals were checked graphically for normal distribution and homoscedasticity. Post hoc analyses were conducted using a Tukey's test. The angle between the neck and withers was measured on the image using a protractor (130° was the lowest angle observed while 237° was the highest). b See Supplementary Figure  S2  for pictures of the lips. The datasets generated and analysed during the current study are available from Zenodo (https://doi. org/10. 5281/zenodo. 1321000).
Acknowledgements We would like to thank  Fabrice Reigner ,  Jean-Marie-Yvon ,  Louise Quatre-Sous ,  Flore Lenglet  for their assistance during the experiment and  Sue Edrich  from the translation agency Interconnect for correcting the English manuscript. IFCE ( French Horse and Riding Institute ) funded this experiment. This funding source had no role in study design, data collection or analysis, or preparation or submission of the manuscript.