dataesr/scientific-paragraphs-categorization huggingface dataset:
Study outcomes The primary endpoint for outcome assessment will be the attainment of antifungal exposures associated with optimal efficacy. These target exposures are described in Table  2  and where available are based on PK/PD data from clinical studies, are used as therapeutic drug monitoring targets,  6  or alternatively are from animal or in vitro studies upon which product information dosing is based. Patients will also be followed for up to 30 days after enrolment into the study to evaluate 30-day mortality.
Statistical analysis Descriptive statistics on demographic, clinical, and PK-/PDrelated data will be performed using the statistical package SPSS version 28. 0. 1. 0 (IBM Corp. , Armonk, NY, USA) and presented as the number (%), mean ± standard deviation, or median (interquartile range), as appropriate. The achievement of the PK/PD targets will be performed by visual inspection of the results and comparison with the specified target exposures.
Statistical considerations A targeted minimum of 12 patients for each drug is based on data from previous non-interventional pharmacokinetic studies in critically ill patients. 15e19 A higher number of patients will increase certainty about the currently unknown exposure variability between different ICUs and countries. The data generated in the study will be summarised using descriptive statistics and subject to descriptive pharmacokinetic analysis. For this purpose, a noncompartmental analysis will be performed to describe the overall drug exposure using Phoenix® WinNonlin® software (Certara, St Louis, MO, USA). The noncompartmental PK results will underpin the primary outcome analyses. For drugs where >10% of patients are identified to have non-therapeutic antifungal exposures, a nonlinear mixedeffects modelling approach, using NONMEM® (ICON plc, Dublin, Ireland), will be utilised for population PK analysis and dosing simulations.
They were all shod, clinically healthy and, according to Swiss animal welfare legislation, their vibrissae were not trimmed. All stallions included in this study were approved breeding stallions. However, none of them was mating at the time of data collection. The last mating occurred at least 7 months (first group observed) or, respectively, 2 months (second group observed) before the start of the study. Prior to data collection, the stallions might have been housed on several occasions in adjacent box stalls and/or hitched next to each other when driven in front of the carriage. Thus, they might have "known" each other but never had the possibility of unrestricted physical contact.
Behavioural Data Collection Each stallion was filmed over a 24 h period on days 19 and 20 in each CB and SB, using a surveillance camera (Panasonic WV SW316 LE, HD resolution of 1280 × 960 at 30 fps, integrated infrared spotlight) mounted high on the walls in each box stall in order to gain an adequate visual field. A total of 768 h of videos were recorded. The behaviour of each stallion in both CB and SB stabling was encoded from the videos by a trained ethologist using The Observer XT v. 11. 5 software (Noldus Information Technology, Wageningen, The Netherlands). Videos were analysed in a randomised order.
Behavioural Data Collection Each stallion was filmed over a 24 h period on days 19 and 20 using a surveillance camera (Panasonic WV SW316 LE, HD resolutio fps, integrated infrared spotlight) mounted high on the walls in each gain an adequate visual field. A total of 768 h of videos were recorde each stallion in both CB and SB stabling was encoded from the video ogist using The Observer XT v. 11. 5 software (Noldus Informatio geningen, The Netherlands). Videos were analysed in a randomised.
Activity Budget All the videos were analysed a second time to create an activity budget for both SB and CB stabling using the scan sampling method, with a recording interval of 5 min over 24 h per horse. The following activities were recorded: feeding (including exploratory behaviours related to feed intake), standing (including resting), sternal recumbency, lateral recumbency, moving (excluding single steps during feeding), maintenance (e. g. , drink, defecate, masturbate, roll, self-grooming) and social interaction. Data were collected only when the horse was in the stable, free to move, without being handled by a human.
Injuries Data Collection Pre-existing injuries were recorded as soon as the stallions were housed in the experimental stable (day 0) as a baseline. Each additional injury was recorded by a veterinarian on the same data collection sheet on days 2, 4, 11 and 18 of the stay in a CB and an SB. All injuries were recorded, including those that were obviously not attributable to social interactions (e. g. , related to itching or caused by poorly fitted riding or carriage driving equipment). An injury scale was developed to categorise the severity of every injury (Table  2 ). The injury's location on the horse's body was noted on a sketch with defined body areas (Figure  4 ). The size (categorised as follows: S: <2. 5 × 2. 5 cm; M: <5 × 5 cm; L: <10 × 10 cm; XL: <15 × 15 cm) and an indication of whether treatment of the wound was required were also noted.
Data Analysis 2. 5. 1. Social Interactions Statistical analyses were performed using the R software (version 4. 1. 1, R Core Team, 2020). The significance level was set at p < 0. 05. Linear mixed-effects models (LMM, the lmer function from the lme4 package) were carried out to test the effect of SB vs. CB stabling on social interactions. The models included the total duration of interactions (in minutes), the mean duration per interaction (in seconds) and the occurrence (in number) as a response variable. The fixed effect variables were the valence (positive, negative, unknown), the stabling (SB, CB), the order of data collection (SB first, CB first), the group (namely the season in which the data collection took part: February-April, October-December) and the interaction between these factors.
Category SB CB 1 32% (37) 40% (10) 2 50% (58) 44% (11) 3 17% (20) 16% (4) 4-6 0% (0) 0% (0) In SB, the largest proportions of injuries were those recorded on the head (40%) and around the zygomatic arch above the eyes (33%). These two body areas accounted for the largest proportions of injuries in Categories 2 and 3 (Table  7 ). In CB, injuries were also mainly located on the head (32%), followed by the legs (28%) (Table  8 ). No injuries were recorded on the neck in CB compared to 9 injuries in SB. Out of the entire data set, four injuries required treatment. Three of these, recorded in the SB, were located near the eye, and were therefore treated with anti-inflammatory eye drops. The fourth injury was a self-injury of the bulb recorded in the CB and treated with disinfectant healing cream.
Behavioural Data In the SB, with all valences combined, the total duration of social interactions increased by a factor of 10 to an average duration of 51 min over 24 h compared to 5 min in the CB. In the present study, only active social interactions, often involving tactile contact, were recorded. Passive interactions such as spatial proximity-which often have a long duration-were not considered. Regarding the activity budget, social interactions represented 3. 8% of the recorded scans in the SB compared to 0. 4% in the CB. With an average daily occurrence of 113 social interaction sequences compared to 24 occurrences in the CB, the SB encouraged the stallions to initiate a social interaction sequence more often. The possibility of socially interacting can be considered a substantial environmental enrichment  [38]  for individually housed stallions.
In the present study, play sequences were assigned a positive valence because they are composed of several distinct affiliative behaviours that are not intended to injure the conspecific. Play in adult stallions could also be considered an important possibility to redirect frustration to a behaviour with rewarding character. It may represent a way for adults to relieve stress  [41]. The total duration of social interactions with a negative valence represented 13-14% of the interactions in both SB and CB stabling. Under natural conditions, the frequency of assessed agonistic behaviours in bachelor bands is highly variable, depending on the populations studied and the related parameters (number of horses, pen size, data collection method, etc. ). Several authors have reported that the rate of aggression is low and agonistic interactions rarely result in actual fights that might cause serious injury  [2, 6, 43].
Acknowledgments: We would like to thank  Miriam Sprick  and  Petra Igel  for injury data collection and the staff members of the  Swiss National Stud Farm  who supported this project. We are grateful to  Anne-Laure Maigrot ,  Marie Roig-Pons ,  Annik Gmel  and  Sabrina Briefer-Freymond  for their support for the statistical analysis and their valuable comments on an earlier version of this manuscript. Many thanks to  Marianne Cockburn  for the English proofreading and for the deliberation on equine housing system terminology. Special thank you to  Maia Bachmann  for creating the horse body sketch we used to record the location of the injuries.
Quintuplicate ECGs were averaged from 24-h continuous ECG Holter recordings taken for cohorts 7-14 on up to 3 separate days. Triplicate ECGs were recorded in cohorts 9 and 12-14 on three separate days and five follow-up visits. Safety and plasma pharmacokinetic (PK) data from Day 15 post-dose were reviewed in a blinded fashion by the SRC prior to administration of the next dose. Blood samples for plasma PK analysis were collected over a followup period of 6 months after the end-of-study, or until the plasma concentration of acoziborole was below the level of quantification (BLQ). Parts II (food effect) and III (multiple dose escalation) were cancelled following the first dose in part one due to the long half-life of acoziborole in healthy volunteers. Part IV was an intermediate open-label pharmacokinetic study to assess the effect of activated charcoal on the plasma concentration of acoziborole, following the results of the bile-duct cannulation in dogs.
Two cohorts of three participants received charcoal 24 h after administration of a single oral dose of 20 mg acoziborole in capsule form. Cohort 1 received 60 g activated charcoal 10 minutes before breakfast for seven days. Cohort 2 received 20 g activated charcoal three times daily 10 minutes before each meal for 7 days. Blood samples were collected up to 192 h post-dose for PK analysis. Participants were monitored as in part I. Data were reviewed by the SRC to determine an adapted treatment schedule of acoziborole with charcoal to allow resumption of part I. Part VI was a complementary open-label study in two cohorts of six participants to evaluate the bioavailability of acoziborole in tablet compared with capsule form (part I). Each cohort received a single dose of either 40 or 160 mg acoziborole in tablet form.
Pharmacokinetic Analysis Levels of SCYX-7158 and its metabolite SCYX-3109 were determined in plasma and analysed on a Kinetex C18, 2. 6 µm, 50 × 3. 0 mm I. D. column using a validated liquid chromatography-tandem mass spectrometry (LCMS/MS) method. In lithium heparinised plasma, the quantification limit of SCYX-7158 and SCYX-3109 was 0. 25 ng/mL and 10 ng/mL, respectively. Pharmacokinetic parameters for acoziborole and its metabolite SCYX-3109 were estimated using non-compartmental methods (Phoenix WinNonlin ® software, version 6. 3, Pharsight Corporation, Mountain View, CA, USA). The plasma pharmacokinetic parameters studied were: maximum plasma concentration (C max ); time to reach C max (t max ); time to the start of absorption (t lag ); elimination rate constant (k e ), determined by log-linear regression using at least three time points on the terminal phase including the last time point and excluding C max ; terminal elimination half-life (t 1/2 ), determined by linear regression using at least three time points; area under the plasma concentration-time curve (AUC) from time zero to 96 h post-dose (AUC 0-96 ) before the administration of activated charcoal, AUC from time zero to the last measurable concentration (AUC 0-t ), and AUC and from time zero to infinity (AUC 0-∞ ), all determined by a linear trapezoidal method.
Acknowledgements The clinical studies were performed by the  SGS Aster Clinical Unit (Paris, France ) and  Eurofins Optimed (Gières, France). Pharmacokinetic and statistical analysis, and preparation of the clinical study report was performed by  PhinC Development (Evry, France). The manuscript was prepared by  Paul Glossop  ( Sandexis Medicinal Chemistry Ltd, Sandwich, UK ) and  Eliane Tarral MD  ( Seven Office, Chambery France ). This study was funded by the  Norwegian Agency for Development and Cooperation (Norad) ,  Norwegian Ministry of Foreign Affairs , as part of  Norway 's in-kind contribution to EDCTP2 (Norway); the  Federal Ministry of Education and Research (BMBF)  through  KfW (Germany) ; the  Dutch Ministry of Foreign Affairs  ( DGIS, the Netherlands ); the  Swiss Agency for Development and Cooperation (SDC) (Switzerland) ;  UK aid (UK) ; the  Bill & Melinda Gates Foundation  (Grant #  INV 002384 ); and  Médecins Sans Frontières (MSF).
Study population and collected information We used advertisements on social media to recruit 52 volunteers and their leisure horse(s) for participation in the study. The condition to participate was that the horse had received enough training to walk safely on a leash in a familiar environment. The horses were located in 26 different places (private homes or private stables) in Southern Finland. A total of 72 horses participated in the study, of which 57 individuals passed a training phase (see below) and could be tested (29 females and 28 males-27 geldings, 1 stallion). Data from these 57 individuals were used for the analyses. The horses ranged in age from 2 to 26 years (mean ± SD = 12. 21 ± 5. 56) and were of mixed breeds (see  Liehrmann et al. 2022  in the section Availability of data and materials for details).
Of the 57 horses which performed the test, 56 completed all 10 trials, with one mare completing only 9 because she got distracted during the last trial and did not focus on the task after becoming distracted. All tests were video recorded for later analysis of the success using the Behavioural Observation Research Interactive Software (BORIS)  (Friard and Gamba 2016). Two observers coded the videos to test the inter-observer reliability but considering the horses' choices were unambiguous, observers had 100% inter-observer reliability.
Statistical analysis Statistical analyses were performed using the statistical software R, version 3. 6. 3 (R Core Team 2022) and figures were created using the ggplot2 package  (Wickham 2016 ). We checked for potential collinearity between our variables of interest (relationship length, social environment, physical environment, age and sex) using Spearman and χ 2 correlation tests. There was a significant moderate correlation between the relationship length and the age of the horse (Spearman, r s = 0. 49, P < 0. 0001, N = 57), but this was below a collinearity level of r s < 0. 7 generally considered as problematic for modelling both parameters simultaneously, and both were therefore kept in the same model  (Zuur et al. 2010). There is also a strong association between the social and physical environments (χ 2 = 45.
77 ± 0. 35, z = -2. 24, p = 0. 025). There were no significant differences between horses alternating between paddocks and fields (64%) and horses spending all year in bigger fields (M2: Estimate ± SE = -0. 58 ± 0. 35, Fig. 2  a Effect of the social environment of the horses on their success in the pointing task. b Effect of the horses' physical environments on their success in the pointing task. The error bars represent the 95% confidence intervals. '*' indicates significant differences with a p-value < 0. 05. '**' Indicates significant differences with a p-value < 0. 01. The means and their associated 95% confidence intervals were extracted from the models M1 and M2 using the function emmeans from the "emmeans" package z = -1. 64, p = 0. 106). There were no significant differences between the horses living in paddocks most of the year and horses alternating between paddocks and fields (M2: Estimate ± SE = 0.
Lambing data collection Ewes were first checked at 6:30 a. m. followed by multiple times, at least hourly, during the day, with the last check at 5:30 p. m. If a ewe was observed to be in active labour, experienced animal carers would check on her every 30 min until birth. According to the approved animal research protocol, ewes were provided assistance if no progression was made after 2 h from observations of protruding fetal membranes or fetal body parts; however, in the present study, none of the recorded ewes required assistance. For the first 2 h after a lamb was born, ewe and offspring were left undisturbed to allow bonding to take place. At 2 h after lambing for lambs born during the day, or on the following morning for lambs born during the night, lambs were weighed using hand-held scales (Tru Test, QLD, Australia).
The sex was determined by visual inspection and the lamb was tagged by visual and RFID tags in both ears (Shearwell, VIC, Australia). Of each lamb born in the supervised lambing enclosure, the time of birth was identified from the stored video data and recorded. Of the collected lambing data, lambing date and time of day were recorded for the use in the presented study. Lamb breed and sex were recorded and reported but not statistically analysed as the study design did not support this. Other lambing data was collected as part of regular husbandry practices and not included in further analyses.
Behaviour data The supervised lambing paddock was set up with 10 day and night video surveillance cameras (Hikvision Digital Technology Co, Hangzhou, China) positioned around the paddock to cover the entire area. The cameras were connected to digital video recorders and footage captured using IVMS4200 software (Hikvision Digital Technology Co). Intensity of labour was classified subjectively post hoc using stored video records by a single observer familiar with lambing ewes, taking into account the duration of the birth. Birth events were classified as normal/eutocic or difficult/dystocic based on the duration from the first observation of abdominal contractions to expulsion of the lamb. A birth that exceeded 120 min from the first abdominal contractions was classed as a dystocic event. Quality and completeness of the video record was noted for the time period of 2 h following birth.
Ewes with video records with poor visibility, for example due to poor lighting or angling away from the cameras, were excluded from the study. Of the videos collected during this study, nine difficult/dystocic events were selected for detailed analysis which were characterised by extended duration of the overall parturition process from first observation of abdominal contraction to the completed expulsion of a live, viable lamb. Of the recorded normal labour events, nine events were chosen for detailed annotation which were comparable to the date and time of day to the difficult events. Behavioural Observation Research Interactive Software (BORIS  [18] ) was used to continuously annotate a period of 2 h after full expulsion of the lamb. An ethogram was developed by observing normal and postlambing-specific behaviours, then grouping like behaviours and eliminating rare or singular behaviours.
Data processing and analysis Behaviour transitions (BT), recorded as the number of behaviour changes observed in the 2 h after lambing, were recorded for each ewe. Behaviour transitions include all transitions between every recorded behaviour, divided by the total observed time. The metric BT was a calculation output provided by the behaviour annotation software package BORIS  [18]. Data were entered into MS Excel (Microsoft, Redmont, WA, USA), where data were organised and descriptive statistics were performed (e. g. mean, range, standard deviation). The range of behaviours performed by each ewe were recorded and tabled as total number of occurrences and total duration for the observation period and expressed as percentage of the time budget within the observation period. Comparisons between the two birth types were made for each individual behaviour and for each behaviour category.
Statistical analyses were performed using R (R Foundation for Statistical Computing, Vienna, Austria; Team, 2013). When analysing count data (eg. BT), type III Wald chi square tests were used. When comparing values between eutocic and dystocic labours (eg. time spent grooming) Student's t-tests were used. Where individual behaviours were of insufficient frequency to support statistical analysis, observations for the behavioural category were combined and reanalysed. For all tests, significance was considered achieved when P 0. 05.
Dystocic events lead to lower maternal behaviour expression Merinos are highly gregarious, and in an attempt to return to the flock quickly, may move from the birth site before the lamb is able to follow  [2]  or abandon mute or low-vigour lambs  [24]. Dystocia can affect the expression of correct postnatal behaviour in the ewe and the lamb, leading to poorer outcomes compared to eutocia. In this study, we examined the effect of duration of lambing on the postpartum behaviour of Merino ewes. Sire breeds used in the study included both Merino and Border Leicester rams, but it was outside the scope of this study to investigate the effect of the lamb genotype on the behavioural expression of the ewe, as the available video data for dystocic ewes included mainly ewes carrying cross-bred lambs.
Data Analysis Efficacy and safety were assessed in all randomized animals that received at least one dose of either deslorelin or the sodium chloride. Efficacy analyses were based on the intention-to-treat (ITT) population using the last-observation-carried-forward method for handling missing data. The ITT population matched the safety population. Results are presented as mean ± standard error (SE). All analyses were performed using SAS version 9. 4 software. A two-sided 5% significance level was used. Efficacy criteria were compared between groups at each time point between D45 and D372 using the Cochran-Mantel-Haenszel test stratified by center with the RIDIT transformation and the general association statistic for binary endpoints and row mean score for continuous endpoints (FREQ procedure from SAS).
Moreover, a return to normal reproductive function has also been demonstrated by the use of questionnaires. One questionnaire was sent to French cat breeders to evaluate the duration of effect, fertility after use, changes in behavior, etc. The survey presented data from 57 tom cats and 15 different breeds, treated 1-3 times. A total of 24 tom cats, after a full inhibition period, were subsequently presented to females, and all 24 (100%) mated successfully at a mean of 15. 5 ± 3. 5 months after implantation, leading to litters of 2-7 kittens  [16]. Another questionnaire conducted as an online survey to cat owners from 28 countries who had used deslorelin implants in their tom cats with single or repeated administrations evaluated a total of 486 answers and 31 different breeds. In this survey, all the efficacy parameters were described to have reverted after the end of the implant period; 70.