dataesr/scientific-paragraphs-categorization huggingface dataset:
Background: Most randomised clinical trials typically exclude a significant proportion of asthma patients, including those at higher risk of adverse events, with comorbidities, obesity, poor inhaler technique and adherence, or smokers. However, these patients might differentially benefit from extrafine-particle inhaled corticosteroids (ICS). This matched cohort, database study, compared the effectiveness of extrafine-particle with fine-particle ICS in a reallife population initiating ICS therapy in the Netherlands. Methods: Data were from the Pharmo Database Network, comprising pharmacy and hospital discharge records, representative of 20 % of the Dutch population. The study population included patients aged 12 -60, with a General Practice-recorded diagnosis for asthma (International Classification of Primary Care code R96), when available, ≥2 prescriptions for asthma therapy at any time in their recorded history, and receiving first prescription of ICS therapy as either extrafine-particle (ciclesonide or hydrofluoroalkane beclomethasone dipropionate [BDP]) or fine-particle ICS (fluticasone propionate or non-extrafine-particle-BDP).
Background Traditional randomized controlled trials (RCT) aim to establish a clear cause-and-effect relationship between an intervention and an outcome. Although asthma RCTs have high internal validity, a problem is that they typically represent fewer than 5 % of patients with a current diagnosis of asthma  [1, 2]. Patients at high risk of adverse events, with comorbid conditions such as obesity, rhinitis or smoking, or those with poor inhaler technique and adherence, are typically excluded. Real-life research can help balance the limitations of a RCT design  [1]. Using real-life medical information recorded in primary care databases allows assessment of long-term outcomes in broader asthma populations cared for under usual conditions. These populations also include patients with unstable asthma often excluded from RCTs, but routinely seen by clinicians in primary care settings  [3].
Traditional inhaler devices for controlling asthma symptoms produce fine particles with a mass median aerodynamic diameter (MMAD) of 2-4 μm; however, some newer pressurized metered dose inhalers (pMDI) using hydrofluoroalkane propellant generate an aerosol of smaller, extrafine-particles with an MMAD <2 μm  [4, 5]. RCTs 8-12 weeks in duration have reported that extrafine-particle ICS is equally effective as fine-particle ICS in controlling asthma symptoms  [6, 7]. Some patients typically excluded in these studies (see above) might differentially benefit from extrafine-particle ICS  [4]. For these reasons, real-life database comparative effectiveness studies may usefully complement traditional RCTs to evaluate whether different properties of extrafine-particle and fine-particle ICS result in different effects in broader clinical populations.
Relevant real-life database studies in the UK and US show matched asthma patients prescribed extrafineparticle hydrofluoroalkane beclomethasone dipropionate (EF-HFA-BDP) for the first time had equivalent or better odds of achieving asthma control over 1 year than patients initiating fluticasone, despite being prescribed lower doses  [8] [9] [10]. In contrast to findings from some RCTs  [6, 7] , these studies suggest that extrafine-particle ICS offers further clinical benefits in asthma control compared with fine-particle ICS therapy in real-life populations. To determine whether this finding can be generalized in other settings with different healthcare systems and possibly different prescribing habits, this real-life database study compared the effectiveness of initiating ICS therapy in patients with asthma in the Netherlands prescribed extrafine-particle ciclesonide or EF-HFA-BDP (Qvar®) versus fine-particle ICS fluticasone propionate or non-extrafine-particle-beclomethasone dipropionate (Non-EF-BDP).
Study design and data source This was a matched cohort, database study, consisting of a baseline and outcome period. The baseline period served for patient characterization and confounder definition and was 1 year before the initiation date of ICS therapy. The outcome period was 1 year following the initiation date for evaluating the effectiveness of ICS therapy. The initiation date was the date when patients received their first prescription of extrafine-particle ICS (either ciclesonide or EF-HFA-BDP), or fine-particle ICS (either fluticasone or Non-EF-BDP). The study period was from January 1998 to December 2012. An independent steering committee was involved in a priori development of study design, review of analyses and interpretation of results  [11]. The study was registered with the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP, study no.
8391), and conducted in accordance with the ENCePP Code of Conduct. The study design is summarized in Additional file 1: Figure  S1. Anonymous data to inform the study objectives were obtained from the Pharmo Database Network provided by the Pharmo Institute for Drugs Outcome Research (Utrecht, the Netherlands). The Pharmo Database Network comprises, among other databases, linked Outpatient Pharmacy, General Practice (GP), Hospitalization and Clinical Laboratory Register databases, and accounts for almost 3 million patients' , representative of 20 % of the Dutch population. The Outpatient Pharmacy database includes the dispensing records of more than 200 community pharmacies and is linked to hospital discharge records. Data from the Pharmo Institute were provided in accordance with Dutch privacy laws.
Outcomes The rate of severe asthma exacerbations in the year following ICS therapy initiation, one of three co-primary outcomes, was defined based on the American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force definition to include asthma-related hospital admissions or prescription for acute courses of oral corticosteroids. Asthma-related admissions were defined as any hospital entry for asthma or any lower respiratory reason (including lower respiratory tract infections). Acute oral corticosteroid use associated with asthma exacerbation treatment was defined as all courses that were not maintenance therapy, and/or all courses where dosing instructions suggested exacerbation treatment. Emergency department data were not included in the exacerbation definition as these data were not available in the database.
Statistical analysis The database extraction and statistical analysis plan were written before any analyses were conducted  [12]. All analysis was carried out using IBM SPSS Statistics version 22, Microsoft Office EXCEL 2007, and SAS version 9. 3. Complete details on statistical analysis methods are in the Additional file 1: Figure  S1. Patients were exact-matched (1:1) based on key baseline demographic and clinical characteristics to ensure comparison of similar patients and to reduce potential confounders  [13]. Matching criteria were informed from baseline differences between treatment cohorts as evidenced by exploratory analysis (t-test/chi square test, p < 0. 05), from expert clinical advice, and from previous research experience, and included the following: sex, age, exact year of ICS therapy initiation, severe exacerbations, LABA and LTRA prescriptions, and SABA daily dose.
This seems to suggest that the present findings can be extrapolated to healthcare systems and prescribing patterns in different countries. Collectively, these studies provide balance to findings reported in some RCTs that extrafine-particle ICS is only equally effective as fineparticle ICS in achieving asthma control  [3, 4]. However, as with all real-life comparative database studies, this study has its limitations as well. Limitations could derive from using the Pharmo Database Network, including disease misclassification biases from the almost exclusive use of "asthma prescriptions" to individuate patients with asthma, and the impossibility to adjust for all potential confounders, such as potential confounding by severity for factors indiscernible from patient records or patient-reported outcomes.
Asthma diagnosis data, defined as a General Practice recorded diagnosis for asthma (ICPC code R96), were available in the General Practice database for only 12. 2 % of the study population. In addition, the results of this study only apply to healthier patients who survive at least 1 year following prescription date. Therefore, this study cannot exclude potential survivor bias  [11, 13, 17]. Although specific to respiratory disease, this study could not accurately assess lung function, or symptom control. However, short-acting β2 agonist prescriptions were included in the study as a substitute for asthma symptoms in the 'overall asthma control' measure, because short-acting β2 agonist use reflects symptom control  [18]. The control cutoff point of a mean shortacting β2 agonist use of ≥2 puffs per day corresponds to the level 2 category (2 of 4, with 1 being the best controlled) of the validated approach of Schatz et al.
[18]  for short-acting β2 agonist canister dispensing to assess asthma symptom control. During the study period, 1399/2981 (47 %) eligible patients initiating extrafineparticle ICS therapy were matched, and 1399/8200 (17 %) of those initiating fine-particle ICS were matched, possibly indicating that patients in neither cohort were representative of those who initiate extrafine-particle or fine-particle ICS therapy in the Netherlands. Finally,  b Fine-particle ICS: non-extrafine-particle beclomethasone dipropionate (Non-EF-BDP); fluticasone propionate (FP) c Fluticasone-equivalent dose for fine-particle ICS (FP and Non-EF-BDP) delivered via a pressurized metered dose inhaler d EF-HFA-BDP/ciclesonide equivalent dose for extrafine-particle ICS delivered via a pressurized-metered dose inhaler although smoking status was not reported in the study due to poor availability within the Pharmo Database Network, possible COPD patients were included (e.
Conclusions This study in a real-life population shows that extrafineparticle ICS are associated with better asthma control and better odds of therapy stability than fine-particle ICS, at significantly lower prescribed doses, despite patients having otherwise similar baseline characteristics after exact matching. These results for a Dutch population confirm relevant real-life asthma studies conducted in the UK and US, and seem generalizable to countries with different healthcare systems and prescribing habits. The findings also provide balance to findings reported in some randomized asthma RCTs. The study applied reliable prescribing and medical information recorded in a well-maintained database for a diverse clinical population, a population including those at high risk of exacerbations, with comorbid rhinitis, smokers and nonsmokers.
Funding Funds to acquire the dataset from the  Pharmo Institute for Drug Outcomes Research (Utrecht , the Netherlands) were provided by  RiRL. The study received institutional support from  Teva Pharmaceuticals Europe B. V. Gokul Gopalan , a Senior Global Medical Director (Respiratory), at  Teva Pharmaceuticals, Frazer, PA, US , at the time of this study, assisted with study design, but neither  Teva Pharmaceuticals Europe B. V. nor Teva Pharmaceuticals , Frazer, PA, US, contributed, either in part or in whole, to the collection, analysis, or interpretation of study data, manuscript writing, or the decision to submit the manuscript for publication.
Part of the cell population was transplanted into mice. Detailed histopathological and molecular investigations were performed looking for pre-malignant lesions and signs of malignancy. Epidemiology: The results from the track structure modelling and stem cell experiments were combined to generate a relative risk model. Dose reconstruction and data analysis tools were developed for a multi-centre prospective epidemiological study using data from paediatric proton therapy treatments, which will test the relative risk model. The project has made initial plans for the study as a collaboration between centres in Europe and the USA.
Overall, we thus cautiously endorse the long intellectual tradition that associates mercantilism with state-building, or with an emerging practice of governmentality, rather than with capture, oppression and sterility. This conclusion applies however to the period under review only, and it does not imply any judgment, positive or negative, regarding the actual impact of this policy on the development of the French economy under the Ancien Régime. The rest of this article is developed as follows. We first briefly review the literature on mercantilism and show where exactly the present contribution fits in (Section 2). The next section discusses the institutional context of the time and how the Bureau du Commerce fitted in (Section 3). We then move to the investigation and decision-making process that underpinned the distribution of rents and franchises to firms and we describe the archives from which we built our dataset (Section 4).
Collected data In order to analyse systematically how privileges to private entrepreneurs were granted in practice, we built a database that includes all 267 submissions made to the Bureau between 1724 and 1744. We thus systematically collected and coded the main characteristics of each submission as of the whole deliberation and decision-making process. 11 We rely primarily on the Avis des Députés, the contributions of the provincial Intendants, and the minutes of the deliberations of the Bureau. In most cases, these sources allow us to identify the content of the initial application; the position and arguments brought forward by the other voices involved in the investigation; the conclusions reached at the plenary meeting of the Bureau; the final decision with the list of privileges that were actually granted, and the official justification that backed them up.
11 Our database has been built entirely on the archives of the Bureau du Commerce which kept at the Archives Nationales (Fond F 12 ); see  Bonnassieux (1900)  for a most useful inventory. We relied on three types of documents: i) the minutes of the Bureau (F 12 51 to 91), with at least three entries for each case (deliberation and recommendation, decision by the Minister, draft of the official decree); ii) The files and the personal notes left over by the Secrétaire of the Bureau or its members (F 12 662-670 and 685 to 704); iii) The Avis des Députés (F 12 693 to 724) that provide a precise description of each project, and add a cross-regional or sectoral perspective, and references to similar cases submitted earlier to the Bureau. transportation, warehousing), among which almost two-thirds are new ventures; the remaining third are submissions for a renewal or an extension of an already granted privilege.
Rubber-stamping: Can we trust the data? Before we move forwards and analyse how this industrial policy was conducted, we have to consider however the possibility that the description on individual projects might have been endogenous to the final decision of the Bureau. Indeed, we cannot directly observe the intrinsic characteristics of projects, neither can we rely on the descriptions provided by the entrepreneurs themselves: they typically envisaged a grand and glorious future for their firm while also harbouring preconceptions about what the Bureau wanted to read and support. Last but not least, the Bureau itself could have been only a façade behind which rents would have been handed out "as usual", following external factors like court politics or local clientelistic deals. For the following three reasons, we think however that our database is not strongly biased, hence that there is no endogeneity flowing backwards from the final decisions to the project descriptions.
No Easy Access to Privilèges The first evidence that emerges from our dataset is that success was in no way guaranteed: a significant proportion of submissions were rejected (28. 5%) and an equivalent share (29. 2%) received less than initially requested. The balance (42. 3%) corresponds to fully successful submissions. Figure  1  also shows that entrepreneurs who submitted demands to the Bureau had little chance of obtaining benefits in all four blocks of possible privileges. There was a clear pattern of only granting two "components": a status and either a territorial exclusivity or a tax cut on income and/or custom duties. Only 4. 8% of the claimants were able to obtain privileges pertaining to all four categories. This observation is also reflected in the table of correlation (see Table  A1  in Appendix) showing that there is only a weak correlation among the four categories of advantages granted: ranging from 0.
Analysis Collected between March 2011 and April 2012, the dataset of XENON100 represent 224. 6 live days with 34 kg fiducial mass and include some improvements : a longer exposure, a significantly lower intrinsic 85 Kr contamination, an improved electronic noise con-dition and a lower trigger threshold. Regularl calibrations were done with various radioactive sources. 232 Th and 60 Co sources was used to determine the electronic recoil (ER) background. The nuclear recoil (NR) response of the detector was determined from a neutron source ( 241 AmBe). The electron lifetime in liquid xenon was estimate from a 137 Cs source. A profile likellihood (PL) approach is used to test the background-only and signal hypothesis. The systematic uncertainties in the energy scale and in the background expectation was profiled out and represented in the limit.
Thus, considering putative environmental preferences and the observed variation in adult abundances of the two species  (Bouchemousse, Lévêque, et al. , 2016) , the timing and intensity of settlement may differ between the two species during a year. The existence of a phenological shift may ultimately lead to an increase in competition between the two species, giving the advantage to the species settling first. To test for differential postsettlement patterns, we gathered data monthly on the settlement dynamics of the two Ciona species in four marinas over 2 years (over 4 years in one of them) on settlement panels. Species-diagnostic molecular markers were used to reliably identify species at the juvenile stage.
| Statistical analyses We analyzed the number of juveniles settled per dm 2 (i. e. , juvenile density). We first investigated the annual settlement dynamics of Ciona spp. in each marina (i. e. , from March of year y to March of year y + 1). Assuming that each major settlement event follows a Gaussian distribution, the number and characteristics (e. g. , time of settlement) of discrete settlement events of juveniles were estimated using a modal decomposition analysis carried out with the R package MIXDIST  (Green & Macdonald, 1985; R Development Core Team, 2014). This package contains maximum-likelihood-based methods to find the best fit between the observed data and a mixture of Gaussian distributions  (Green & Macdonald, 1985). The density data were smoothed using a weighted moving average at the third order to rule out irregularities  (Frontier & Pichod-Viale, 1991).
Prior to the modal decomposition analysis, the normality of each dataset modified by the weighted moving average was tested using a Shapiro test in R (the shapiro. test function). A significant deviation from normality is a prerequisite before attempting to find the best mixture of Gaussian curves explaining the data. To compare the settlement rate among marinas and settlement periods, we used a two-way analysis of variance (ANOVA) on the average density value computed across the month showing the highest density of juveniles (m) and the preceding and following months (m -1 and m + 1). For months characterized by an overlap between two settlements events within a calendar year, density values were divided by two. "Marinas" (n = 4) and "settlement periods" (n = 4) were considered as random factors.
| Does competition with its native congener limit the invasiveness of C. robusta? Despite its advantage during the warmer season, we documented a consistently low recruitment success in C. robusta than in C. intestinalis. For example, the maximum value observed over the whole dataset was in Château in October 2014, with a density value of 361. 6 juv/dm 2 , a value more than two times lower than for C. intestinalis (898. 7 juv/dm 2 ) at the same place and date. The same result was observed for the adult stage in all sampling periods (Figure  5 ). Inhibition of settlement and subsequent growth by a superior competitor can strongly influence the abundance of species, as shown in numerous cases for marine invertebrates  (Davis, Butler, & Vanaltena, 1991; Grosberg, 1981) , including in ascidians  (Rius et al.
tory for treatment each month between March 2013 and March 2015 (i. e. , a 25-month dataset). In Moulin Blanc, the experimental design started much earlier, with the first panel series set up in November 2010 (and retrieved in December 2010) and the last one retrieved in F I G U R E 1 (a) Location of the study sites. Map was downloaded from http://d-maps. com/carte. php?num_car=2,765&lang=fr. (b) Settlement panels employed for the experiment. Juveniles of Ciona spp. were counted and sampled on the horizontal panel (indicated by the white arrow). The dotted arrow indicates a temperature data logger (TidbiT ® v2). Photograph credit: Laurent Lévêque. (c) Counts were carried out on a grid of 11 × 11 cells. Hatched cells along the border of the panel were not considered to avoid edge effects.
I G U R E 4 Graphical outcomes of the modal decomposition analysis for determining the number and properties of each major settlement events of Ciona robusta and Ciona intestinalis in 2013 and 2014 in the three marinas where the two species were found living in syntopy (i. e. , Moulin Blanc, Château, and Trébeurden). The blue line (histogram) corresponds to the observed dataset (i. e. , distribution of the density of juveniles for each month). The values were averaged per panels (n = 3 replicates) and smoothed using a running average over three classes (i. e. , 3 months). Result of Shapiro-Wilk tests (W: value of the statistic, p, probability) on the deviation of the observed data from a normal distribution are provided: All distributions are significantly different from a normal distribution.
ACKNOWLEDGMENTS The authors are very grateful to  G. Dubois , the divers of the  Marine Operations department (Service Mer & Observation) at the Roscoff Biological Station , and all of the people that accompanied us in the field to retrieve the panels monthly over the 4 years of the study. We are thankful to  A. Yunnie  for her help on the experimental work and for collecting part of the 2011 juvenile dataset and to  A. Courteille  for assistance with DNA extraction and determination of juveniles sampled in 2013. We also thank the marina operators for their permission to conduct the experiment. The authors are grateful to  Xavier Turon  for his suggestions to improve the manuscript. This work was supported by funding from the  ANR  project  HYSEA  (no. ANR-12-BSV7-0011 ) and the  Interreg IVa Marinexus  project.
F I G U R E 4 Graphical outcomes of the modal decomposition analysis for determining the number and properties of each major settlement events of Ciona robusta and Ciona intestinalis in 2013 and 2014 in the three marinas where the two species were found living in syntopy (i. e. , Moulin Blanc, Château, and Trébeurden). The blue line (histogram) corresponds to the observed dataset (i. e. , distribution of the density of juveniles for each month). The values were averaged per panels (n = 3 replicates) and smoothed using a running average over three classes (i. e. , 3 months). Result of Shapiro-Wilk tests (W: value of the statistic, p, probability) on the deviation of the observed data from a normal distribution are provided: All distributions are significantly different from a normal distribution.