dataesr/scientific-paragraphs-categorization huggingface dataset:
a b s t r a c t Background: About 70-80% of patients with colorectal liver metastases appear as ineligible for a curative treatment approach. Transarterial chemoembolisation (TACE) using irinotecan-eluting beads has emerged as a promising treatment option in cases with irresectable liver metastases. Despite being in clinical practice for years, little is known about the treatment characteristics and outcomes when used as per routine hospital practice. Methods: Patients with hepatic metastases from colorectal cancer origin, admitted to contributing centres to receive TACE with drug-eluting LifePearl® Microspheres loaded with irinotecan, as part of their standard care, will be consecutively added to the registry. Data will be collected until the end of study, loss to follow-up or death. Primary endpoint is the characterisation of the treatment usage at the selected sites in Europe.
Eligible patients All patients with CRLM decided to be treated with LP-IRI by the centre's multidisciplinary tumour board and therefore treated with LP-IRI are eligible. Eligible centres were selected by CIRSE and meet the selection criteria below: • Having performed a total of 40 treatments of any liver metastases with drug-eluting beads to date or a total of at least 10 treatments of any liver metastases with drug-eluting beads in the last 12 months • Having performed at least 1 treatment with LP-IRI • Are willing to comply with the observational study requirements, including presenting the possibility to participate in the observational study to all subjects that are eligible This study (clinicaltrials. gov NCT03086096) is performed in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines and was approved by local Ethics Committees of participating centres.
At each timepoint, all patients that have data available for determination of an endpoint in the time interval will be included in the summary statistics for that time point. In addition, for the final analysis, a presentation including only patients that have data available at all or a subset of the timepoints will also be given. The time points to include will be based on the available data in order to maximise the number of patients to be included. Health-related quality of life data will be analysed using version 3 of the EORTC QLQ-C30 Scoring Manual (2001). Data will be presented for the global health status/QoL score, functional and symptom dimensions and for individual items. Since a deterioration of quality of life is expected as the natural course of disease progresses in patients treated with LP-IRI, a bilateral paired sample Student's t -test at the 5% level will be used to determine any statistical difference in quality of life from baseline.
Furthermore, particular care must be given to addressing potential selection bias in the study. Patient selection bias is addressed by contractually agreeing with all participating centres that the possibility to participate in the observational study must be presented to all patients that are eligible. In order to assess possible centre selection bias, countries and centres will be compared as far as possible with respect to background characteristics. At the time of manuscript submission, 23 centres from 12 countries have enroled 110 patients in CIREL ( Table  3  ). The first patient was enroled in February 2018. While data collection was originally foreseen to terminate on 31 January 2022 with up to 500 patients enroled, the CIREL Steering Committee decided to end patient enrolment after 30 months instead of 36 months due to low patient enrolment.
Acknowledgments We would like to thank  Terumo Europe NV  for providing an unrestricted educational grant that funded the study,  Dr. Carole Déan  for support with navigating the regulatory environment in France,  Prof. Patrick Chevallier ,  Dr. Raul Garcia ,  Dr. Hassan Malik  and  Dr. Simon Pernot  for their contribution to CIREL, as well as all participating centres and personnel involved in CIREL.
g. , Braque, Cezanne, Matisse) and friends and acquaintances of  Keynes (e. g. , Duncan Grant, Vanessa Bell). The collection has remained intact to the present day, with the pictures being hung at the College and at the Fitzwilliam Museum in Cambridge. Importantly, Keynes was interested in art as an investment. He carefully and extensively documented his transactions and these records, held at the archives of King's College, are the main data sources employed in this study. The records contain a detailed list of all the pictures acquired by Keynes. For most of the works, we locate purchase prices and dates from original invoices and correspondence together with a few prices from alternative art historical sources. The archival records also contain multiple valuations and auction estimates postdating Keynes' death.
We also procure expert appraisals of market value for the important works in the collection at the end of 2013 and in early 2019. 2 e use our hand-collected data to compute the total expenditures by Keynes on his collection over the period  1917-1945, and to estimate overall valuations for the years 1946, 1959, 1981, 1988, 2000, 2013, and 2019. The collection appreciated strongly over time: while Keynes' total expenditures amounted to less than 13,000 British pounds, the collection had an estimated market value of more than 76 million pounds in early 2019. This translates into a nominal internal rate of return (IRR) of 10. 4% (6. 1% in real terms). The year 2019 value of the art collection is only 16% lower than what it would have been if Keynes had instead invested his outlays in U. K. equities, reinvesting dividends (costlessly) back into the portfolio; the annualized underperformance relative to the equity market is just 0.
Extreme idiosyncratic positive returns-or the absence thereof-will matter a whole lot for the total return of any art portfolio. Fourth, a conspicuous feature of the Keynes collection is its high concentration: the ten most expensive purchases represent 80% of his aggregate expenditure on art. Using unique data on other collections, we provide evidence that the concentration of the Keynes art collection is a characteristic shared with other art portfolios. Portfolio concentration amplifies the importance of idiosyncratic return components. Yet some investors may find concentrated investment portfolios attractive, especially in an asset market where individual returns are positively skewed. At the same time, our results yield insights on the limitations of art price indexes as both a guide to asset allocation and a performance benchmarking tool.
The Keynes collection The departure point for our data collection is the 1959 memorandum on the Keynes collection prepared by Richard Kahn, who succeeded Keynes as the bursar of King's College in 1946. This document provides information on the artist, title, and size for all 135 pieces in the collection. The memorandum groups together artworks according to their year 1959 location. It includes 26 pictures held at King's College, 23 works on loan to the Fitzwilliam Museum, 85 in the Fitzwilliam picture reserve, and a portrait of Keynes by Duncan Grant on loan to Milo Keynes. Table  1  summarizes the distribution of artworks by artist. In keeping with Keynes' career as a collector described in the previous section, it is not surprising that the collection contains many works by Bloomsbury artists and friends, such as Grant, Bell, and Roberts, and items by Impressionist and Postimpressionist artists, such as Braque, Cezanne, Degas, and Picasso.
7% at the end of the data set. The valuation of the collection, especially from inception to final valuation, is therefore robust to alternative methods for dealing with missing values. Table  4  documents the relative performance of the collection over time with respect to three benchmarks. We estimate the total portfolio value that would have accumulated if, instead of buying his artworks, Keynes had invested in U. K. equities. Following  Kaplan and Schoar (2005) , we compute for each year the public market equivalent (PME) ratio of the value of Keynes' art investments to the value of the equivalent investment in the equity market index of  Dimson, Marsh, and Staunton (2002, 2019). We assume the investment in the equity index mimics the timing and magnitude of Keynes' actual art expenditures.
If Keynes had put his funds into common stocks, the value of his investments by the beginning of 2019 would have been £90. 2 million instead of £76. 2 million from artworks, which implies a PME of 0. 84. By how much has the Keynes collection underperformed on an annual basis? The alpha -sometimes called the "excess IRR"-is the constant to be added to the benchmark return to make the PME equal to one  (Phalippou and Gottschalg 2009). 6 At the foot of the third column, we see that the annualized alpha of the Keynes collection, measured relative to the equity index, is -0. 2% per year. The next two columns of Table  4  compare the investment returns from the Keynes collection with another alternative strategy that was investable, namely, U. K. government bonds, again using data from  Dimson, Marsh, and Staunton (2019).
thank the  Centre for Endowment Asset Management (CEAM) at Cambridge University  and its supporters, Invesco and Newton (to D. C. and E. D. ); the J. M. Keynes Fellowship at Cambridge University (to D. C. ); and  ANR/Investissements d'Avenir  [grant  ANR-11-IDEX-0003/Labex Ecodec/ANR-11-LABX-0047 ] (to C. S. ).
The data set that we construct in this paper is almost unique. The only other research on returns realized from an actual art portfolio is Landes' (2000)  study of the collection of Victor and Sally Ganz. The Ganz collection was selected with hindsight for research because of its extraordinary financial value at the time of resale (Vogel 1997). In contrast, the Keynes collection is less exposed to the criticism of ex post selection, because Keynes' claim to fame is unrelated to his activities as an art collector. A different perspective on the historical profitability of art investments is offered by David, Huemer, and Oosterlinck (2019) , who study the transactions of a major dealer.
The results of our methods are validated using a 3D model constructed using real underwater data and comparing them to the results which would have been obtained using an image-scaling method supporting an arbitrary tilt of the surface  (Davis and Tusting, 1991). The effects of noise, camera perspective angle and camera-scene distance on our process and final estimates of scale are further analyzed. Finally, the results of using our method to scale a model reconstructed from data acquired during the SUBSAINTES 2017 cruise (doi:10. 17600/ 17001000)  (Escartín et al. , 2017)  are presented.
Pose estimation The scale estimation process requires the knowledge of the camera pose = P R R t SE [ ] (3) T T defined as the projection from the world to the camera frame at the moment the image was taken. As these images contain laser spots, they do not reflect the real appearance of the environment and are, as such, considered undesirable in the 3D reconstruction process, specially in the densification and texture mapping steps. To estimate the poses, images can potentially still be included in the SfM step (and excluded from rest) or, alternatively, the pose can be computed through a separate feature-based image localization method presented here. Salient 2D features extracted from the image, are matched with a full set of features associated with the model's sparse set of 3D points. Feature detection and matching procedures can be adjusted for each specific dataset, and do not influence the scale estimation process, as long as it is possible to produce successful pairs of 3D-2D observations ( = X x { , } k j ).
To avoid any potentially erroneous 3D points affecting the final calibration, a robust estimation method such as RANSAC can be utilized. Finally, the origin of the laser is determined by computing the intersection between the now estimated direction of the laser beam and plane. It is important to note that, in underwater scenarios, significant refraction can occur at the air-acrylic-water interface of the laser housing. This effect has to be considered in the calibration procedure, either mathematically or by performing the data acquisition underwater. Alternatively, the partially constrained method requires the knowledge of the distance between the parallel pair of lasers and that the camera center is equidistant to the laser origins (without the need for the knowledge of its value). For most cases, commercially available laser scalers have laser beams that are adequately parallel.
Results To assess the applicability and theoretical accuracy of the two proposed approaches (PCM and FUM), tests were performed on both real and simulated scenario datasets. To validate the performance using different laser configurations and acquisition conditions, we have used a real 3D model built using underwater imagery, as depicted in Fig. 8. Various laser measurements were generated as they would have been captured during an ROV survey. As the absolute scale of the model is not precisely known, for the purpose of this evaluation, it was assumed that the model and its scale are correct. Therefore, the performance can be evaluated by comparing the deviations of the estimated scales with the assumed (imposed) correct value of the scale of the model ( = s 1). This allowed us to confirm the correctness of our approaches, as well as analyze the effects of various types and levels of noise have on the estimation.
Data The generation of image and laser data as they would have been recorded in real scenarios enabled us to simulate different perspective angles and camera-scene distances, and analyze their effects on the resulting estimations of scales. The measuring system consisted of an ideal pinhole camera and laser scalers. Both the intrinsic parameters of the camera and the refraction of the lasers occurring at the air-housingwater interface were correctly modelled in the calibration. A real 3D model depicted in Fig. 8  was used in this simulation. The 3D chimney was reconstructed from 908 images of an underwater vent field at the deep-sea Lucky Strike area, collected during the MOMARSAT 2015 cruise (doi:10. 17600/15000200). The model covers an area of approximately 200 m 2 with a height range of ~13 m.
Real scenario The fully unconstrained method was used on a real dataset collected during the SUBSAINTES cruise (doi: 10. 17600/ 17001000). Throughout the cruise, extensive seafloor imagery was collected using the ROV VICTOR 6000 (IFREMER)  (Michel et al. , 2003)  with a mounted monocular camera (Sony FCB-H11 with corrective optics and dome port), and a laser scaler with four laser beams positioned around the camera (Fig. 16 ). The intrinsic parameters of the camera were determined using a standard calibration procedure  (Bouguet, 2008)  assuming a pinhole model together with the 3rd degree radial distortion model. Once calibrated, the camera parameters were kept constant through the entire acquisition process. One of the main goals of this cruise is to identify, map, and measure indicators of displacement at the seafloor associated with a recent submarine earthquake  (Escartín et al.
Conclusions This paper introduced two novel methods for automatic scaling of SfM-based 3D reconstructions using laser scalers, methods that are applicable for routine underwater surveys with ROVs or AUVs. Both methods were validated using a series of generated datasets based on an 3D model derived from submarine field imagery, and showed its applicability in real scenarios using a dataset collected during a recent cruise (SUBSAINTES 2017). The two approaches presented here, namely the fully and partially constrained methods, overcome a multitude of restrictions imposed by prior laser photogrammetry methods (e. g. , laser alignment with the optical axis of the camera, perpendicularity of laser beams with the scene). These methods, within the step of pose estimation, also remove the need for manual identification of identical points on the image and 3D model, an extremely time-consuming and error-prone processing step.
Acknowledgement This study is based on results from the MOMARSAT 2015 and SUBSAINTES 2017 cruises, that deployed the ROV VICTOR 6000 ( IFREMER, France ) for image acquisition used here. These cruises (ship and ROV time) were funded by the  French Ministry of Research. We commend the work of the crew, officers, and engineers that participated on these cruises and made possible this data acquisition. Partial funding was provided by the  European Union 's  Horizon 2020 project ROBUST  (grant agreement  690416-H2020-CS5-2015-onestage ) (to K. Istenič), project  Eurofleets Plus  (grant agreement  824077 ), the  Spanish Ministry of Education, Culture and Sport  under project  UDRONE CTM2017-83075-R  (to  R. Garcia  and  N. Gracias) , the  ANR   SERSURF   Project  ( ANR-17-CE31-0020 , France) (to  J.
Background. The European Renal Association -European Dialysis and Transplant Association (ERA-EDTA) Registry collects data on kidney replacement therapy (KRT) via national and regional renal registries in Europe and countries bordering the Mediterranean Sea. This article summarizes the 2018 ERA-EDTA Registry Annual Report, and describes the epidemiology of KRT for kidney failure in 34 countries. Methods. Individual patient data on patients undergoing KRT in 2018 were provided by 34 national or regional renal registries and aggregated data by 17 registries. The incidence and prevalence of KRT, the kidney transplantation activity and the survival probabilities of these patients were calculated. Results. In 2018, the ERA-EDTA Registry covered a general population of 636 million people. Overall, the incidence of KRT for kidney failure was 129 per million population (p.
INTRODUCTION This article summarizes the European Renal Association -European Dialysis and Transplant Association (ERA-EDTA) Registry's 2018 Annual Report, providing the most recent data on the epidemiology of kidney replacement therapy (KRT) for kidney failure in Europe, and countries bordering the Mediterranean Sea  [1]. In total, 51 national or regional renal registries from 34 countries provided data to the ERA-EDTA Registry, of which 34 renal registries from 18 countries provided individual patient data, and another 17 renal registries provided aggregated data from 17 countries (Supplementary Appendix S1). In total, these registries cover a general population of 636 million people, which is lower than the 694 million people covered in the 2017 Annual Report  [2] , as this year Croatia, Georgia, Poland and Sfax region (Tunisia) could not be included.
Acknowledgements This work was supported by the  Wellcome Trust  (Grants  104924/14/Z/14  and  203285/C/16/Z ); the  ERC  (Advanced Grant  320969 ); the  EPSRC (CDT in Synthesis for Biology and Medicine ,  EP/L015838/1 ),  MRC/EPSRC/BBSRC Next-generation Microscopy  ( MR/K01577X/1 );  MRC/EPSRC  ( EP/L016052/1 );  UKRI BBSRC  ( BB/P026354/1 );  Wolfson Foundation ;  MRC  ( MC_UU_12010/unit  programmes  G0902418  and  MC_UU_12025 );  John Fell Fund; EPA Cephalosporin Fund ; and the  Deutsche Forschungsgemeinscha  (Research unit  1905 ,  Jena Excellence Cluster  " Balance of the Microverse ", project number  316213987 -SFB 1278  (project  C05 )). ATF thanks  Christ Church ,  Oxford, for a Junior Research Fellowship. VW thanks the  DFG  for a Research Fellowship. YX and KGL were supported by the  EPSRC CDT in Synthesis for Biology and Medicine  ( EP/ L015838/1 ).
Next, we examined the effects of various targeted drugs on the survival of MPN cells. In these experiments, we found that the JAK2 and STAT5 blockers examined induce apoptosis in HEL cells and SET-2 cells (Figure  A4 ). In a separate set of experiments, we applied ruxolitinib and AC-4-130 in combination in HEL and SET-2 cells. However, no clear additive or synergistic effects of this drug combination was observed (Data not shown  [54] ). We also examined the effects of the JAK2 and STAT5 inhibitors on proliferation of two pSTAT5-low/negative solid cancer cell lines, A2780 and A375. As shown in Table  A3 , these cells were in general less sensitive to these drugs compared to HEL cells or SET2 cells. [H]-thymidine was added for 16 h and its incorporation was analyzed using a beta counter. The diagrams show the mean ± standard deviation (SD) of at least three independent experiments performed in triplicate.
A well-known example in DNA processing is the selective amplification induced by primer selection and PCR or the large number of unknown reads when metagenomes are analyzed  [152, 157, 158]. A primer-free rRNA gene sequencing approach developed by Karst et al. [126]  facilitated the discovery of unknown microbial diversity. The authors suggest to combine poly(A)-tailing and reverse transcription of SSU rRNA molecules with synthetic long-read sequencing. Using this approach, they were able to generate high-quality, full-length SSU rRNA sequences, without primer bias, at high throughput and observed a large proportion of so far undescribed diversity in their study  [126]. Bioinformatics analysis of obtained sequence data is neither standardized nor biases that are clearly expressed. For performing the data evaluations of 16S rRNA gene sequences, free software solutions and wellworking forums like Qiime2  [159]  and Mothur  [160]  are available.
Operational taxonomic units (OTUs) are used for long time to analyze high-throughput barcoding, e. g. , using marker-genes like 16S rRNA and or the ITS region for high throughput sequencing data. In addition, amplicon sequence variants (ASVs) can be used that based on exactly resolved, down to the level of single-nucleotide differences over the sequenced gene region. Benefits of finer resolution are immediately apparent, and the status of ASVs as consistent labels with intrinsic biological meaning identified independently from a reference database  [154]. The improvements in reusability, reproducibility, and comprehensiveness are sufficiently great so that ASVs could replace OTUs as the standard unit of marker-gene analysis and reporting  [161]. Several studies and joint projects have been performed to compare different tools and pipelines, showing significant differences in outcome depending on the tool or pipeline and the settings used  [162] [163] [164] [165].
It is obvious that besides sufficient sequencing depth, the choice of database for annotation of reads has a strong influence on the outcome. Moreover, the choice of parameters such as cutoff values, filtering of chimeras, and other, which is often done automatically, has a strong influence on the outcome. For example, as a result of data evaluation methods allowing investigation of taxa with a representation of more than 1% only, rare taxa are often neglected  [166]. Such rare taxa, however, constitute up to 28% of all microbes, can represent key players in some habitats, and may be of importance for structuring communities  [167]. They can have an over-proportional role in biogeochemical cycles and may be a hidden driver of microbiome function  [168] [169] [170]. Moreover, microorganisms carrying antibiotic resistance genes often belong to the rare taxa in native microbiomes; under stress conditions, they provide the insurance for health and survival and ensure the plasticity of the ecosystem  [171].