dataesr/scientific-paragraphs-categorization huggingface dataset:
2. Non-systematic, Efforts to coordinate Shared municipal Coordinated: Suitability Coordinated: The Test if 20% of each partially coordinated MPA planning and waters across alliances: for MPAs was based on decision tree used the habitat was MPA establishment management were Local governments in the characteristics of suitability layer and protected in shared undertaken by local undertaken by alliances an alliance might have areas where MPAs were spatial context to municipal waters government alliances of local governments, an agreement to jointly established when determine the location within each each with one to five manage their municipal coordination was of potential MPAs. The alliance. municipalities in a waters as initiated and facilitated MPA sizes from the shared bay, gulf, or recommended by the by CI-Philippines from database (from 2008- coastal stretch.
Cardiovascular risk stratification The 10-year risks for cardiovascular mortality (ESC), coronary heart disease (ATP-III) and ASCVD (ACC/AHA) were calculated for each individual on the basis of the three equation scores using online calculators [14-16]. A coefficient of 1. 5 was applied when a patient presented two of the following three characteristics: disease progression for over 10 years, rheumatoid factor or anti-CCP positivity and extra-articular signs and symptoms  [9]. The recommended thresholds were used for the application of the European (ESC), ATP-III and ACC/AHA statin treatment guidelines. Based on each guideline, the patients were classified into 3 categories: "no treatment", "treatment considered", "recommended treatment". eTables 1-3 in the Supplementary data presents the details of these 3 treatment categories by each guideline.
Statistical analyses Statistical analysis was performed using Stata 13 software (StataCorp LP, College Station, TX, US). Baseline characteristics were presented as mean (±standard-deviation) or median (interquartile range) for continuous data (assumption of normality assessed using the Shapiro-Wilk test) and as the number of patients and associated percentages for categorical parameters. Comparisons of the three equation scores were made using the Stuart-Maxwell test for categorical parameters. The tests were two-sided, with a Type I error set at α = 0. 05. Since the SCORE equation was validated for the population aged 40-65 years, an additional sub-group analysis was performed by age.
Study population There were 970 patients enrolled in the COMEDRA study. Among this initial population, patients were excluded because they were receiving a statin (n = 168), were under the age of 40 (N = 49) or because there were missing data (n = 76). The 677 analyzed patients were mainly women (N = 547, 80. 8%) with a mean RA disease duration of 11. 4 (6. 5-19. 8) years (Table  1 ). The RA characteristics and the cardiovascular risks are presented in Table  1  for all patients and in Tables  2  and 3  for patients aged 40-65 and those over the age of 65. The EULAR coefficient needed to be applied in 59. 9% of the patients.
Acknowledgments This work was performed under the financial support of the  COPOMOL  project #  ANR-13-IS04-0004  from  Agence Nationale de la Recherche. We also acknowledge financial support from Projet Attractivité 2014 from  Université Paris-Sud. We thank  Maxence Lepers ,  Maykel L. González-Martínez ,  Olivier Dulieu  and  John L. Bohn  for discussions.
The data sets were divided randomly into five parts of equal size and equal number of samples from each class. One part was set aside as the test set, whereas the training set consisted of the four remaining parts. The training set was used in the inner fivefold cross-validation to select the best number of probes N A {8, 16, 32, 64}, that is, the number of probes maximising the average accuracy of the predictors. False discovery rates, a confidence measure that accounts for multiple testing, o0. 05 were considered significant for differential expression and o0. 25 for gene set analysis, as recommended by  Subramanian et al (2005). This microarray data set is available from the Gene Expression Omnibus  (Edgar et al, 2002)  under accession number GSE60542.
RESULTS No strong global transcriptional difference between N0 primary tumours, N þ primary tumours and nodal metastases. We profiled the transcriptomes of 11 primary PTCs with no detectable nodal invasion, 17 primary PTCs with nodal invasion and 17 patient-matched nodal metastases. We also profiled a number of control samples. These included 24 patient-matched non-cancerous thyroid tissues (11 from N0, 13 from N þ patients), and 4 normal lymph nodes, and technical and biological replicates including additional nodal metastasis for 3 patients, adjacent blocks for 5 primary tumours, 4 non-cancerous thyroid tissues and 1 nodal metastasis. The non-cancerous thyroid tissues were taken from the thyroid tissues adjacent to the tumor, and in the contralateral thyroid lobe whenever possible. To compare the global molecular phenotypes of these samples, we projected them on the two first principal components, representing together 46% of the total variance of the data set (Figure  1 ).
We performed a supervised search for genes differentially expressed between N þ primary tumours and their matched metastases (details in Material and Methods) -an approach widely used in previous studies  (Huang et al, 2003; Kikuchi et al, 2003; Nagata et al, 2003; Tamoto et al, 2004; Croner et al, 2005  We detected 1074 probes more expressed in metastases than in primary tumours (Supplementary Table  S3 ). To gain functional insight, we ran a gene set enrichment analysis (GSEA)  (Subramanian et al, 2005)  using a gene set database composed of the Gene Ontology biological processes based on categories, signatures of primary tumour vs nodal metastasis from previous studies  (Nagata et al, 2003; Hao et al, 2004; Hoang et al, 2005; Roepman et al, 2005; Xi et al, 2005; Bidus et al, 2006; Finak et al, 2006; Wang et al, 2006b; Feng et al, 2007; Inamura et al, 2007; Nguyen et al, 2007; Suzuki and Tarin, 2007; Casey et al, 2009; Ellsworth et al, 2009; Edfeldt et al, 2011)  and a signature of normal thyroid differentiation (Tomas et al, 2012).
To further investigate why the same signatures had an opposite regulation in PTC metastases, we estimated their expression in primary tumour RNA-seq data from The Cancer Genome Atlas (TCGA). All three signatures had a significantly higher median expression in breast than thyroid tumours (Supplementary Figure  S2 ). Thus, the referential defining of 'up-' and 'nodal up-' and 'downregulation' is different in these two types of cancer. An equal expression of stroma-related genes in nodal metastases could lead to opposite senses of differential expression when comparing with related primary tumours. We noted, however, that this tentative explanation could not apply to gastric cancer because it had the lowest stroma-related expression among all TCGA cancers. Differential expression between N0 and N þ tumours is reproducible in patient-matched non-cancerous tissues, but not in independent PTC data sets.
In other words, there was high similarity in transcriptional signals associated with nodal status in the non-cancerous and tumour tissues. This is a straightforward consequence of the established fact (Figure  2 ) that transcriptomes of a tumour and its matched non-cancerous tissues were correlated on a global scale. To validate these results, we considered the 129 and 11 genes sets as signatures and evaluated their expression in three published PTC data sets with nodal status information. These signatures were not consistently regulated. To assess comprehensively the discrepancies between data sets, we selected the 200 top genes ordered by their fold change of expression and associated with nodal status in each one of the three data sets and in our data set. We then tested all these signatures in all data sets (Figure  5C ).
Figure3. Gene expression differences between nodal metastases and patient-matched primary tumours. (A) A gene set enrichment analysis (Subramanian et al, 2005)  for the nodal metastases vs patient-matched primary tumours comparison with gene sets from the Gene Ontology Biological Processes database (black) and curated gene sets from previous studies investigating nodal metastasis or stromal gene expression (Hoang et al, 2005; Wang et al, 2005; Feng et al, 2007; Suzuki and Tarin, 2007; Casey et al, 2009; Ellsworth et al, 2009 ; blue, only significant gene sets are shown (see Supplementary TableS2for the full list of investigated gene sets) and a signature of thyroid differentiation (Tomas et al, 2012; green). Red bars denote increased expression in metastases compared with primary tumours and green bars denote decreased expression.
ACKNOWLEDGEMENTS We thank  Franc¸oise Lallemand ,  Sandy Haussy ,  Samira Majjaj  for their contribution,  Chantal Degraef  for her technical assistance,  Andrea Karambelas  for final proofreading and  Jacques E Dumont  for his advice. VD was funded by  FNRS  Grants  14657170  and  19556102. MT and MS were supported by  FRIA/FNRS  grant. Other supports include Welbio,  Fondation Contre le Cancer, Fonds de la Recherche Scientifique Medicale (FRSM) ,  Fonds National de la Recherche Scientifique (FNRS) ,  Plan Cancer  (action 29),  Televie, Les Amis de l'Institut Bordet and Fondation Van Buuren. www. bjcancer. com| DOI:10. 1038/bjc. 2014. 665 This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 4.
His electrocardiogram (ECG) showed a sinus bradycardia at 40 bpm with a firstdegree atrio-ventricular block. Evolution was favorable after progressive verapamil discontinuation. Analysis performed on the French Pharmacovigilance Database between July 1, 2000 and December 1, 2014 found four other cases of cardiac adverse events related to high-dose verapamil used in CH prevention (two cases of syncope with complete atrio-ventricular block with verapamil 1200 and 240 mg daily, respectively, one syncope related to sick sinus syndrome with verapamil 360 mg daily, and one case of sinus bradycardia with verapamil 720 mg daily). Although available studies seem to demonstrate an apparent good tolerance, this off-label practice should not be considered as standard of care and requires strict cardiac monitoring, as suggested by the Agence Nationale de Securitedu Medicament (ANSM) in a recent re-evaluation of the benefit/risk ratio of high-dose verapamil used in CH prevention.
This case was notified to the Centre Regional de Pharmacovigilance de Basse Normandie and then registered in the French Pharmacovigilance Database. The intrinsic causality assessment retained for verapamil in our case was 'very likely' (C3S3 or I6) and the extrinsic causality assessment (bibliographic causality assessment) retained was 'expected effect' (B4) according to the French method for causality assessment  [3].
Review of the French Pharmacovigilance Database Analysis performed on the French Pharmacovigilance Database between July 1, 2000 and December 1, 2014 found four other cases of cardiac adverse events related to the use of high-dose verapamil in CH prevention. The assessment of causality was performed according to the French method for causality assessment  [18]. Terms used for this analysis included verapamil, cephalalgia, atrioventricular block, bradycardia, syncope, cardiac disorders and cardiac arrests. For the verapamil causality assessment, only the cases with a 'probable' imputability were maintained. Two of them were cases of syncope with complete atrio-ventricular block (verapamil 1200 mg daily in a 54-year-old man and 240 mg daily in a 53-year-old man, respectively), one was a syncope related to sick sinus syndrome (verapamil 360 mg daily associated with a lithium intoxication in a 42-year-old man) and the last was a case of sinus bradycardia (verapamil 720 mg daily in a 24-year-old man).
It could also seem reasonable to perform at least one trans-thoracic echocardiography before verapamil initiation (particularly for high doses) in order to assess the left ventricular ejection fraction. In the setting of 'cardiologic' verapamil use, the European Society of Cardiology guidelines  [26]  recommend an echography before verapamil initiation. In fact, verapamil is a potent negative inotropic agent that could induce cardiogenic shock in case of systolic heart failure  [26]  or in case of voluntary poisoning  [27]. These recommendations seem all the more important to observe if the patient is old or has significant cardiovascular comorbidities. Indeed, given literature data  [10, 25]  and the French Pharmacovigilance Database, patients presenting with serious cardiac adverse events seem to be the oldest.
However, in this case, the use of high-dose verapamil is an especially high-risk practice as it exposes patients to serious cardiac side effects (ECG abnormalities) and to the risk of major drug-drug interactions. Finally, it is unfortunate that no blood drug confirmatory assay was achieved in clinical studies and in cases reported in the French Pharmacovigilance Database. Therapeutic plasma levels of verapamil are 0. 20-0. 35 lg/mL, with toxic concentration at values exceeding 9 lg/mL  [17]. A confirmatory assay would allow the link between high-dose verapamil and serious cardiac adverse events occurrence to be tested, it could help clinicians to avoid 'toxic' doses and it could also inform the verapamil dosage escalation without reaching the toxicity threshold. Our recommendations are consistent with those published recently by the Agence Nationale de Securitedu Medicament (ANSM), which recently re-evaluated the benefit/risk ratio of high posology verapamil used in CH prevention  [39].
Conclusions Safety issues remain rightfully prominent with high-dose verapamil in CH  [22]. Serious cardiac adverse events, although a very infrequent direct event from high-dose verapamil, nevertheless remain a risk as significant ECG abnormalities can develop with time even on a stable dose  [22]. However, the benefits of using verapamil in CH (if necessary at doses exceeding those used by cardiologists in hypertension) for pain management and prevention in selected and appropriate patients seem be favorable  [3, 4]. The above-described case report and the French Pharmacovigilance Database review show that care must be taken when administering off-label high-dose verapamil in CH. This work is consistent with a recent report published by ANSM  [39]  and the French Headache Society guidelines  [6]  granting a temporary recommended use for verapamil administered orally in the prophylactic treatment of CH.
This work deals with the applicability of the linear estimation technique (LE) to invert spectral measurements of aerosol optical depth (AOD) provided by AERONET CIMEL sun photometers. The inversion of particle properties using only direct-sun AODs allows the evaluation of parameters such as effective radius (r eff ) and columnar volume aerosol content (V ) with significantly better temporal resolution than the operational AERONET algorithm which requires both direct sun and sky radiance measurements. Sensitivity studies performed demonstrate that the constraints on the range of the inversion are very important to minimize the uncertainties, and therefore estimates of r eff can be obtained with uncertainties less than 30 % and of V with uncertainties below 40 %. The LE technique is applied to data acquired at five AERONET sites influenced by different aerosol types and the retrievals are compared with the results of the operational AERONET code.
Good agreement between the two techniques is obtained when the fine mode predominates, while for coarse mode cases the LE results systematically underestimate both r eff and V. The highest differences are found for cases where no mode predominates. To minimize these biases, correction functions are developed using the multi-year database of observations at selected sites, where the AERONET retrieval is used as the reference. The derived corrections are tested using data from 18 other AERONET stations offering a range of aerosol types. After correction, the LE retrievals provide better agreement with AERONET for all the sites considered. Finally, the LE approach developed here is applied to AERONET and star-photometry measurements in the city of Granada (Spain) to obtain dayto-night time evolution of columnar aerosol microphysical properties.
Constraints used in the inversion The sun-photometer CIMEL is the standard instrument of the AERONET network. It is able to measure sun direct irradiance and separate it spectrally by using interference filters centered at 340, 380, 440, 500, 670, 870 and 1020 nm. The instruments are calibrated by AERONET and the final errors in AOD(λ) are approximately ± 0. 02 for λ < 400 nm and of ± 0. 01 for λ > 400 nm  (Holben et al. , 1998). All of the AERONET data used in this study were Level 2. 0 (cloudscreened and quality-assured). More details can be found in  Holben et al. (1998)  and  Smirnov et al. (2000). From the AOD(λ) measurements, the spectral deconvolution algorithm (SDA)  (O'Neill et al. , 2001a (O'Neill et al. , , b, 2003) )  provides also the fraction of the total optical depth that is due to the fine mode only (η) at the reference wavelength of 500 nm.
Retrieval of aerosol microphysical properties with improved temporal resolution The ability to obtain higher temporal resolution aerosol microphysical property retrievals by inversion of AODs (as compared with the AERONET operational retrieval) is illustrated in Fig. 5. This Figure uses data obtained at GSFC on 2 June 2000. Mean AOD at 440 nm (AOD(440)) for this day is about 0. 77 and the Ångström exponent α(440-870) is about 1. 88, implying by reference to Fig. 1  that aerosol particles are rather small. The backward-trajectory analysis obtained from the HYSPLIT model  (Draxler and Rolph, 2003)  revealed that the high values of α(440-870) and high aerosol loading are due to air masses with origins in the industrial areas of the east coast of the US. For this particular day, only four Level 2.
9. Again, linear fits V = Aη + B were done, where the parameters for these fits are reported in Table  1  as well. Moreover, we performed simulations in the same manner as for the effective radius shown in Fig. 10. The results of these simulations are in Fig. 11c. Again the pattern obtained by LE and regularization are generally similar. But we observe significant differences compared to the corrections functions of Fig. 11b , both for coarse and fine mode dominant cases. We also note that retrievals of columnar volume aerosol content by inverting AODs possess larger uncertainties than retrievals based on the full AERONET data set due to the more limited information. While further studies of these differences would be desirable (NASA SMD Workshop Atmospheric Composition Outstanding Questions (https:// espo.
nasa. gov/home/content/NASA_SMD_Workshop), such studies are beyond the scope of the present work. To evaluate the proposed correction functions, 18 AERONET stations, different from those used to generate the correction, were selected. These sites, listed in Table  2 , present different aerosol types: anthropogenic pollution (P), biomass-burning (BB) and dust (D). The sites are located in urban (U), remote areas (R) or in coastal area (C). Table  2  also provides mean values of AOD(440) and α(440-870) at each site. We use all AERONET Level 2. 0 data through 2013 at each site and create a data set of more than 75 000 comparisons between the operational AERONET and LE algorithms. Table  3  presents mean relative differences r eff and V and standard deviations averaged over all 75 000 observations before and after correction for the four ranges of η used.
Also it is include if they are remote (R), urban (U) or coastal (C). The mean aerosol optical at 440 nm (AOD mean ) and Ångström parameter between 440-870 nm (α mean ) are included. Also, the mean and standard deviations of the differences between linear estimation and the operational AERONET code, before and after applying corrections, are included both for effective radius (r eff ) and columnar volume aerosol content (V ). All Data ----0. 25 ± 0. 31 1. 2 ± 0. 5 -5. 9 39. 4 3. 9 32. 6 -45. 3 24. 1 -1. 5 32. 3 r LE eff -r AERONET eff r AERONET eff V LE -V AERONET V AERONET Place Latitude Table  3. Means and standard deviations of the relative differences between linear estimation (LE) and operational AERONET retrievals. For each interval of η is given values before and after applying corrections as well as the total number of intercomparisons.
1020 nm. More instrument specifications can be found in  (Pérez-Ramírez et al. , 2008a , b, 2012b). Errors of AODs are approximately 0. 02 for λ < 800 nm and 0. 01 for λ > 800 nm  (Pérez-Ramírez et al. , 2011). The data are cloud-screened following the procedure described in  (Pérez-Ramírez et al. , 2012c) , providing AODs every 30 min. The day-time values plotted for the Granada station are from LE retrievals using AODs from AERONET Level 2. 0 data. The spectral range of the inversion by LE is 380-1020 nm for both instruments. Figure  13  shows a day-tonight time evolution of AOD(440) (AOD at 436 nm for nighttime), α(440-870) (α(440-880) for night-time), η, r eff and V for the period from 20 to 30 July 2010. Table  4  shows the mean values of these parameters during each day and night, as well as the origin of 5-day backward trajectories.
, 2013). and those obtained by AERONET (V AERONET ). We used the database of ∼ 75 000 intercomparisons combining all the sites of Table  2. Black lines correspond to data with no-correction while red lines are for data after applying correction functions. Table  4. For the period 20-30 July using sun and star photometry measurement at Granada (Spain), mean values of day-and night-time aerosol optical depth (AOD) at 440 nm (436 for night-time), Angström exponent α computed between 440-870 nm (436-870 for nighttime), fine mode fraction to aerosol optical depth (η), effective radius (r eff ) and columnar volume aerosol content (V ). Also the air masses that reached the study area every day and night are presented. Backward trajectories of air masses were computed by HYSPLIT model at 1500 m a.
As an example of this, we presented LE retrievals using star photometry measurements in the city of Granada (southeast of Spain) demonstrating the feasibility of the aerosol particle parameter estimation during the night-time. Continuity in day-to-night aerosol microphysical properties was observed for the different air masses reaching this area by coupling these nighttime retrievals with the daytime ones based on AERONET data. However, more variability of the star-photometer data inversion is associated with the higher uncertainties in the AODs provided by star photometer. Therefore, further improvements in star photometry are needed by limiting the effects of atmospheric turbulence in such measurements. The proposed LE inversion approach provides bulk parameters of the total size distribution while separate retrievals of these parameters for the fine and the coarse mode separately would be desirable.
Acknowledgements. This work was supported by the  NASA   Atmospheric Composition Program  and by the  NASA Aerosols, Clouds, Ecosystems mission. Support has also been provided by the  Spanish Ministry of Science and Technology  through projects  CGL2010-18782  and  CSD2007-00067 , by the  Andalusian Regional Government  through projects  P10-RNM-6299  and  P08-RNM-3568 , by the  EU  through  ACTRIS  project ( EU INFRA-2010-1. 1. 16-262254 ),and by the  Postdoctoral Program of the University of Granada. The authors would like to express their gratitude to the  NOAA Air Resources Laboratory and Naval Research Laboratory  for the HYSPLIT model. We also thank the  AERONET network  and especially the principal investigators of the various stations used for their efforts in establishing and maintaining the AERONET sites.