dataesr/scientific-paragraphs-categorization huggingface dataset:
Confirming the target population and route of administration After the realization that anti-IL-5 therapy should be targeted specifically to patients with severe asthma with eosinophilic inflammation, and that an appropriate primary endpoint for the trials should be exacerbations rather than lung function, a larger study was carried out to establish optimal dosing and patient characteristics associated with response to mepolizumab. DREAM (NCT01000506) was a large Phase 2b/3, placebocontrolled, dose-ranging, randomized trial including patients with severe asthma with recurrent exacerbations and blood and/ or sputum evidence of eosinophilic inflammation (or alternatively high FeNO levels or history of asthma control deterioration after ICS/OCS reduction) who were receiving high-dose ICS, with or without maintenance OCS, plus additional controllers.
In MENSA (NCT01691521), patients with recurrent asthma exacerbations (!2 in the previous year) and evidence of eosinophilic inflammation (blood eosinophil count !150 cells/mL at screening or !300 cells/mL during the previous 12 months) despite high ICS doses and 3 months of treatment with at least 1 additional controller were included. Patients received mepolizumab 75 mg IV or mepolizumab 100 mg SC or placebo every 4 weeks for 32 weeks. 34 Reductions in the annualized rate of exacerbations were similar for both mepolizumab formulations, with reductions of 47% (95% confidence interval [CI]: 28, 60) and 53% (95% CI: 36, 65) with mepolizumab IV and SC, respectively, versus placebo (P <. 001; primary endpoint). Improvements in quality of life (as measured by the St George's Respiratory Questionnaire [SGRQ] total score; P <.
001), asthma control (as measured by the Asthma Control Questionnaire [ACQ]-5; P <. 001), and lung function (P <. 05) were also seen (Table  I ). Following the initial positive results from the Nair et al study,  29  the effect of mepolizumab on OCS use was assessed in the phase 3 SIRIUS (NCT01691508) trial. It was important to test this given that OCS represents a burdensome additional therapy associated with negative side effects,  35  with a substantial proportion of patients with severe eosinophilic asthma requiring chronic OCS use. In SIRIUS, which included patients with severe eosinophilic asthma who required daily OCS to maintain asthma control, mepolizumab 100 mg SC had a significant OCSsparing effect and despite this also reduced exacerbations and improved control of asthma symptoms compared with placebo over 20 weeks.
Long-term efficacy As anti-IL-5 treatments have become established for the treatment of severe eosinophilic asthma and their use within clinical practice has become more commonplace, attention has turned to the duration of their clinical effects. Long-term efficacy of mepolizumab beyond 1 year of treatment has been assessed in 2 open-label studies: COSMOS (NCT01842607) and the COSMOS extension, COSMEX (NCT02135692), which followed patients for up to 4. 8 years after starting treatment with mepolizumab. 58, 72 Both studies showed that long-term treatment with mepolizumab is associated with significant and durable improvements. In COSMEX, the on-treatment On-treatment 25 (  16 ) 20 (  13 ) 24 (  16 ) 19 (  12 ) 27 (  14 ) 14 (  7 ) 16 (  8 ) 12 (  18 ) 1 (  1 ) exacerbation rate remained low (0.
93 events/year) in those who had participated in COSMOS or MENSA, and improvements in FEV 1 and ACQ-5 scores were maintained across the extension period. 58 In those patients who had a gap in their treatment of greater than 3 months between COSMOS and COSMEX, patients experienced a decrease in FEV 1 and an increase in ACQ-5 score. These data were consistent with the long-term safety study COLUMBA (NCT01691859). 73 The long-term efficacy of benralizumab has also been investigated in an openlabel extension of the phase 3 studies. Improvements in exacerbation rates and lung function were maintained into the second year of treatment. 74 Similarly, initial improvements in lung function and asthma control seen during the phase 3 reslizumab studies were maintained for up to 2 years in an open-label extension study.
FUTURE DIRECTIONS As more data are collected on the different anti-IL-5 therapies, further questions will be answered regarding their long-term clinical effects and treatment choice. Although the effect of Route of administration did not affect the dose-response relationship; 100 mg SC was the dose needed to achieve 90% of the maximal inhibition of blood eosinophils Landmark Phase 3 studies proved the efficacy of mepolizumab versus placebo Early lung function results were disappointing in patients with mild-to-moderate asthma The severe eosinophilic asthma phenotype was defined Long-term follow up studies suggested mepolizumab remains efficacious and safe after several years Patients with a severe form of asthma benefit from mepolizumab, particularly in terms of exacerbations Eligible patients not optimally controlled on omalizumab could be effectively switched to mepolizumab to improve asthma control and quality of life.
Moderate mepolizumab in a relatively long-term timeframe (up to 4. 8 years) is known, particularly compared with the timeframe over which the efficacy of other recently approved asthma biologics is known, further data will be collected and analyzed to address outstanding queries. These include the question of whether anti-IL-5 therapy and biologic therapies in general are disease modifying in asthma. It was previously considered that anti-IL-5 therapies could be disease modifying through prevention of airway remodeling, given that treatment with mepolizumab resulted in reduced expression of extracellular matrix proteins in the airway reticular basement membrane. 77 This was supported by the determination that mepolizumab 750 mg IV monthly for 50 weeks reduced computerized tomographyeassessed airway wall area.
Additional studies, such as COMET (NCT02555371), which is designed to determine whether patients who halt treatment after at least 3 years of mepolizumab use continue to maintain clinical benefit, should help to clarify whether maintenance suppression of eosinophilic airway inflammation is required. Other observational trials will reveal more information on the long-term effect of anti-IL-5 in real-world settings. These include a prospective, long-term observational study of mepolizumab SC in 1000 patients with up to 2 years of follow-up after at least 52 weeks of treatment at the investigator's discretion (NCT03028480). In addition, the prospective, real-world REALITI-A study of mepolizumab in patients in routine clinical practice is also being carried out. Indeed, an initial 12-month analysis of patients in REALITI-A has indicated that the effectiveness of mepolizumab is similar in real-world and clinical trial settings.
Study design and sample We used data from the EboMH  [16, 17]. The study was conducted from March 11 to April 7, 2019, seven months after the declaration of the end of the ninth outbreak of EVD in the DRC. It was conducted in the 18 rural and urban areas that reported at least one case of EVD in the three health zones (Bikoro, Iboko and Wangata) affected by the 2018 outbreak in Equateur Province. Adults aged 18 and over were selected from a two-stage stratified sample: 1) the affected rural and urban areas, according to their demographic weight, with reference to estimates from the National Statistics Institute; and 2) the proportion of women in affected rural and urban areas. A door-to-door survey was conducted by 26 investigators (including 12 women) who were trained for a day and a half on how to complete the questionnaire and ethical issues.
Statistical analyses All the statistical analyses were performed using the Statistical Package for Social Sciences (SPSS), version 25 for windows. First, percentages were computed to assess the distribution (Yes; No; I don't know) of the knowledge of the participants for each item. Then, chisquare tests were performed to assess the difference of prevalence between men and women for each item. Next, the difference of proportions test (z-test) were used to evaluate the difference between Yes and No answers for each item. We also conducted t-test analyses to evaluate difference of scores between participants according to gender. Finally, one-way Analyses of Variance were conducted to assess differences of scores between participants according to education level, religion and age group. To investigate predictors of EVD knowledge, we conducted a two-step hierarchical linear regression analysis.
We collected data on the following outcomes: 1. Health literacy. Health literacy was evaluated using Chew's three-item measure which contained the following questions: (i) How confident are you filling out medical forms by yourself?; (ii) How often do you have someone (like a family member, friend, hospital/clinic worker, or caregiver) help you read hospital materials?; and (iii) How often do you have problems learning about your medical condition because of difficulty understanding written information? [35, 36]. Patients who circled 'extremely' on the Likert-type scale for the first question, and 'none of the time' for the last two questions were categorized as having high health literacy skills.
Data collection and analysis Data was collected until the sample size was attained. Survey responses were collected over a three-day period. To address aim 1, we conducted a binary logistic regression analysis to examine possible associations between our dependent variable (0 = low understanding, 1 = high understanding) and the following independent categorical variables: age, gender, race, educational attainment, income level, health literacy, proficiency (0 = low numeracy and graph literacy, 1 = high numeracy and graph literacy), format (0 = icon array, 1 = bar graph) and graphical display format preference (0 = icon array, 1 = bar graph). To address aim 2, we conducted a logistic regression using 'proficiency' (0 = low numeracy and graph literacy, 1 = high numeracy and graph literacy) as the dependent variable and the following independent categorical variables: age, gender, race, educational attainment, income level, health literacy, understanding (0 = low understanding, 1 = high understanding) and graphical display format preference (0 = icon array, 1 = bar graph).
This article contains the following accomplishments: Four previously published general luminescence models involving quantum tunneling phenomena are summarized, and their mathematical formalism is presented. Even though the models discussed here do not contain new modeling concepts, the purpose of this paper is to pool existing models on feldspar luminescence production transparently, and to develop open-source software which can be shared and further developed in the future by the luminescence dosimetry community. The chosen models in this paper are based on first order kinetics, and partial analytical solutions are available in the literature for three of them. We present a new partial analytical solution for the fourth model. By using these partial analytical solutions, we detail flexible short R scripts  [10] , which do not require numerical integration of the differential equations.
It is also noted that in some published models, the symbol p(r ) is used instead of g(r ). Eq. (  5 ) is usually referred to as the unfaded distribution of distances. Fig. 1  depicts the nearest neighbor distribution of distances g(r ) between electrons and acceptors in the cube discussed above. The R code used to produce Fig. 1  evaluates the nearest neighbor distribution of distances between electrons and acceptors in the cube. The R package plot3D  [14]  is used to plot the random locations of the electrons (triangles) and acceptors (circles). The R package FNN  [15]  is used to evaluate the nearest-neighbor distance between each pair of electron and positive charge, and the code produces a histogram of the distribution of nearest neighbor distances in the system. All models considered in this paper are described mathematically by the concentration n(r , t) of trapped electrons, which is a function of the distance r and of the elapsed time t.
(  12 ), and the numerical results from the two approaches agreed to better than 1%. The first FSF from Table  1  is AFfortimeT(), and a simulation of the anomalous fading effect is shown in Listing 1, with a typical output shown in Fig. 3. For simplicity and clarity, Listing 1 contains a minimal R script required to produce the results of Fig. 3 , and the actual script contains additional graphics commands not shown in Listing 1. The complete scripts which produce the figures in this paper can be found in the GitHub repository referenced through Zenodo, http://doi. org/10. 5281/zenodo. 4429270. Line 1 loads the R-code for the FSF using the source() command. Lines 2 and 3 in this short code define the values of s and ρ , while line 4 defines the fading times for the simulation as the parameter timesAF = 0, 10 2 , 10 4 , 10 6 a after the start of the tunneling process.
This simplifies and speeds up significantly the calculation of the total remaining charge n(t) in Eq. (  14 ). Finally matplot() is used in line 7 to plot the four distributions of r at the fading times times = 0, 10 2 , 10 4 , 10 6 a. # f a d i n g t i m e s 0=10ˆ6 a r p r i m e s <= seq ( from = 0 , t o = 2. 2 , by = 0. 0 0 2 ) # r ' = 0 =2. 2 d i s t r i b s <= sapply ( timesAF , AFfortimeT , r p r i m e s , rho , s ) matplot ( r p r i m e s , d i s t r i b s ) n <= 0. 0 0 2 * colSums ( d i s t r i b s ) plot ( timesAF / ( 3 6 0 0 * 2 4 ) , 100 * n ) LISTING 1 R code demonstrating the function AFfortimeT() in a simulation of the charge distributions n(r , t) within the GST model shown in Fig. 2a. Figure  3  shows an example of the distribution obtained using Eq. (  10 ) as a function of the dimensionless distance r , and at times t = 0, 10 2 , 10 4 , 10 6 a after the start of the tunneling process.
The overall structure of the code in Listing 2 is kept identical to the structure of Listing 1, so that the users can readily follow and modify the code for their purposes. Lines 2-6 define the parameters ρ , D 0 , Ḋ, r and s. Lines 7 and 8 evaluate the three different irradiation times in seconds, and line 9 is the unfaded nearest neighbor distribution from Eq. (  5 ). Lines 11-13 are similar to the corresponding lines in Listing 1. These lines define again the matrix distribs which contains four columns corresponding to the four geological times, and matplot() is used plot the distributions at the end of the irradiation times. The results of the code are shown in Fig. 6 , and they are identical to Fig. 5a  in the paper by Li and Li  [23]. As the irradiation time increases, Fig. 6  shows that the asymmetric distribution of distances r approaches the distribution for a field saturated sample (× symbols).
Discussion and conclusions In this paper, several compact R functions have been presented, which can be used to simulate the TL and CW-IRSL signals from feldspars. These signals are of a complex nature, however, it is possible to simulate sequences of irradiation and thermal/optical treatments of feldspars in the laboratory, as well as under different thermal conditions in nature. The key concept that allows this uniform description of luminescence signals from both freshly irradiated as well as pretreated samples, is the time evolution of the nearest neighbor distribution following various optical and thermal events. The FSF are simple to use and very fast, with running times of all scripts in this paper of the order of seconds. They are also very flexible, the users can immediately change the parameters in the code, and can simulate various behaviors, without the need to carry out numerical integrations, which may become numerically unstable.
National patient safety incidents reporting platform We built an online patient safety incident reporting platform, secured by Nantes University Hospital and based on the Royal College of General Practitioners Patient Safety Incident Reporting and Learning Guidance  [8]. The home page gave the definition of a patient safety incident, and the objectives of the study (Supplementary Figures  1 2 3 ). A second page collected the characteristics of the reporter (age, department of practice, contact details), and their agreement to participate. A third page gathered data on the incident, including:.
Methods: We used a published systematic map protocol to identify studies addressing the effects of herbivores on Arctic vegetation. We conducted searches for relevant literature in online databases, search engines and specialist websites. Literature was screened to identify eligible studies, defined as reporting primary data on herbivore impacts on Arctic plants and plant communities. We extracted information on variables that describe the ecological context of the studies, from the studies themselves and from geospatial data. We synthesized the findings narratively and created a Shiny App where the coded data are searchable and variables can be visually explored.
Search for articles We searched for relevant literature first from the global databases of Web of Science Core Collection (all years search within Topic) and Scopus (article title, abstract and keyword search with no further limitations applied). Thereafter, we searched literature that these databases might have missed, and grey literature, from Google Scholar (title search standardized to disregard search history, including only the first 300 search results) and local/ regional and specialist databases or sources (listed in Additional file 2). The search string for the systematic map was optimized during scoping exercises as described by Soininen et al. [28]  and comprised two substrings: one targeted at delimiting the study region and system, and the other targeted at the exposure component of our primary question (i.
The sensitivity of the search string was very high, with only one article out of a subset of 1000 articles deemed as potentially relevant  [28]. We conducted our search in English in global search sources, and English together with relevant local languages (Russian, French, Finnish, Swedish, Norwegian, Icelandic and Danish) in searches from local/regional sources. In some cases, the full search strings had to be simplified because some search engines did not allow Boolean operators or the use of "wildcards" (*) or could handle only a reduced number of terms. Full details on the search sources and strings used in each search engine and how they were implemented in other languages, as well as access information on institutional access to paywalled databases are provided in Additional file 2.
Screening process Screening of the articles for relevancy was structured in four stages: (i) title screening, (ii) abstract screening, (iii) locality screening, and (iv) screening during data coding from the full text. Each article was assessed by two reviewers at the title and abstract screening stages, except for those found through Google Scholar and local/regional databases that were assessed by one reviewer. Locality and full text screening were assessed by one reviewer, with additional reviewers in cases that were not clear. These numbers refer to reviewers per article; several reviewers were involved in each screening phase. During screening, we erred on the side of inclusion. Exclusion of an article at title and abstract screening stages occurred upon the agreement of two independent reviewers.
The ROSES diagram is based on  [97]  on abstract" or "included". In the case of reviewer disagreement about inclusion, the article was kept for further stages of screening. No reviewers assessed articles they had authored or co-authored. When one reviewer had scored an article to be excluded based on title and the other reviewer based on abstract, the article was assigned the score "exclude based on abstract". Additional articles that were found through Google Scholar or from local/ regional sources were screened for both title and abstract by one reviewer and were only included in our database if they passed this screening stage. Articles that passed the title and abstract screening stage were then assessed for their geographical locality by one reviewer. Locality screening was based on geographical coordinates that were given in the text, extracted from maps provided in the publication, or extracted from Google Maps based on study location names mentioned in the text.
Reviewers carefully checked the full text against the eligibility criteria and reasons for exclusion were recorded. When in doubt, the article was reviewed by an additional reviewer. The complete database of retrieved articles, with information on exclusion stage and reasons (for full text stage only) is provided in Additional file 3 (see also Fig. 1 ). Locality screening diverges from the description in the published protocol  [28] , where the CAFF vegetation zone map ("CAFF Map Nr. 10",  [31] ) was planned to be used to delimit the Arctic region. That map was however no longer available, leading us to use the approach described here. We assessed the repeatability of title and abstract screening by measuring the consistency among reviewers to either include or exclude an article. For this, we used percent agreement and Cohen's kappa (κ) statistic  [32].
Eligibility criteria Eligible studies were defined as those as reporting primary data on herbivore impacts on Arctic plants and plant communities. To be included, studies had to include an eligible population, exposure, comparator and outcome (as defined in the objective of the review above). In addition, studies had to fulfill some requirements regarding their study design as described in this section. Eligible population Studies had to target an eligible population, i. e. , studies were excluded if they did not study Arctic terrestrial vegetation. This filtering included additional locality information, such as describing the study sites as boreal forests or temperate grasslands and, in some cases, inspecting Google Earth images of the study location to assess the extent of canopy cover and proximity to open tundra.
Additional criteria We excluded studies for which we could not access electronic or paper copies of the full text, as this prevented assigning studies to an ecological context. Similarly, we excluded studies that were not in a suitable format (Fig. 1 ), such as corrections of published articles, maps and raw datasets (cf. "Unsuitable text types" in ref. [34] ). We further excluded studies that presented data already reported in another article. For chapters of academic theses that were published as separate studies, we only included the published peer-reviewed versions, and for annual reports that presented incremental data, we only included the longest time-series. For all other studies, we checked for potential redundancy based on the study site. We first edited the spelling of study sites to be consistent across studies and then cross-checked all studies conducted at a given study site.
We did not attempt to contact the authors of the studies to obtain missing information or confirm unclear Table  1  Ecological context variables extracted from the studies included in the systematic map database during data coding Values in column "source" describe where the data is extracted from: P for publication (i. e. , data explicitly available in the published document), D for digital spatial data layers (i. e. , data extracted from a data layer based on the spatial coordinates given in the publication), and C for classified by the reviewers based on information available in the publication. For variables denoted with P and D, we used the D-version in our analysis to reduce the heterogeneity in the accuracy reported across studies. See Additional file 4 for a full list of variables extracted from the studies a Variable added after publication of the protocol b Variable data source differs from the planned source (i.