dataesr/scientific-paragraphs-categorization huggingface dataset:
2015). Second, the mode of administration should also be considered. PRO measures have traditionally been administered by paper and pencil, but new technologies offer the potential to use electronic measures. Electronic measures administered before or during a clinic visit allow results to be available at the time of consultation and may facilitate symptom monitoring to guide supportive treatment. One example is the PROMIS instrument, which is available using computer adaptive testing or through REDCap software. Computer adaptive testing selects questions based on the previous responses that patients have provided to approximate the construct being measured in the fewest number of questions. The implementation of routine assessment of patients' QoL on clinical care and clinical trials has the potential to improve patients' well-being.
Fertility Preservation Techniques in Females Gonadotropin-Releasing Hormone Agonists (GnRHa) Despite success in animal models, the value of GnRHa to preserve ovarian function during chemotherapy in human subjects is uncertain. A Cochrane database review (2011) concluded that the use of GnRH agonists should be considered for ovarian protection in women of reproductive age who are receiving chemotherapy  (Chen et al. 2011).
Introduction Umbilical cord blood transplantation (UCBT) from unrelated donors is a suitable option of HSCT for patients in whom it is indicated, and a suitable related or unrelated BM or PB donor is not available in due time. Since the 1990s, the majority of UCBT have been performed in children, but the number in adults was growing steadily. In fact, since 2004 the number of UCBT in adults registered in Eurocord was higher than in children. However, a certain decline in the UCBT activity has been observed over the last few years, which is mainly due to an increasing activity of partially matched related (haploidentical) HSCT. It should be noted that, although both options compete in the same niche, their comparative data are very limited and randomized studies are not yet available. As far as we know, two phase III randomized studies are currently ongoing to compare UCBT and haplo-HSCT in the RIC and MAC setting (NCT0159778 and NCT02386332, respectively).
2015)  along with updated guidelines for clinical practice  (Snowden et al. 2012 ) and immune monitoring and biobanking  (Alexander et al. 2015). With the increase in evidence, the guidelines have become more disease specific. A successful collaboration involving significant non-European collaborating partners resulted in the EBMT guidelines for auto-HSCT in systemic sclerosis  (Farge et al. 2017). A further collaborative review with the European Crohn's and Colitis Organisation (ECCO), which has recently been published, includes recommendations for patient selection, transplant technique and follow-up of HSCT in patients with Crohn's disease  (Snowden et al. 2018). Guidelines for MS and neurological diseases are in preparation. The current state of the EBMT database in relation to various ADs is summarised in Tables 91.
1 and 91. 2. At the time of writing, over 2500 patients receiving HSCT for an AD have been reported to the EBMT, the largest international database, with activity reported to other registries adding substantially to the worldwide numbers. The most recent EBMT activity survey identified autoimmune diseases as the fastest growing indication group for HSCT  (Passweg et al. 2018). Based on this reported activity, this chapter will cover the main neurological, rheumatological and gastroenterological indications for auto-HSCT, along with reference to the rare AD indications and alloge-neic HSCT. More detailed literature can be sourced from recently published reviews  (Snowden et al. 2017 (Snowden et al. , 2018;; Burt and Farge 2018; Alexander and Hiepe 2017).
e. either the specific 'BEAM + ATG' regimen or the more generic regimen of CY 200 mg/kg combined with ATG, led to their recommended use in the current EBMT ADWP guidelines  (Snowden et al. 2012). More recent data suggests that 'high-intensity' regimens, incorporating BU, have higher rates of PFS but potentially greater toxicity, including TRM  (Atkins et al. 2016). Retrospective registry data suggest that graft purging has no added benefit to the transplant outcome  (Snowden et al. 2012). Currently, auto-HSCT is considered to be most effective in patients with relapsing MS, who are not older than 45 years, have had the illness for less than 10 years, are not very disabled (EDSS ≤6) and have very active disease with evidence of enhancement on their MRI  (Muraro et al. 2017 ). An international randomised controlled phase III trial is currently being conducted to compare auto-HSCT with currently available MDTs (MIST Study, ClinicalTrials.
Although PFS in this study was only 29% at 5 years, TRM had gradually improved. In addition, this study indicated that CD34-selection was associated with a significantly reduced relapse incidence. More recently, reports from two independent Chinese groups, both with 10-year follow-up, demonstrated remarkable clinical responses with PFS of 86% and 68%, respectively, while TRM across both studies was only 2%. Current recommendations suggest HSCT in patients with sustained or relapsed active disease (BILAG category A) remaining steroid dependent after at least 6 months of the best standard therapy (including MMF and CY with or without anti-CD20), with documented evidence of visceral involvement  (Snowden et al. 2012). The only controlled study conducted to compare auto-HSCT with cur-rently available MDTs in SLE is currently ongoing in a phase II multicentre trial in Germany (ClinicalTrials.
Patients with neuroblastoma ≤18 months at diagnosis need biological profiling and are only eligible with high-risk biological features, in particular MYCN amplification  (Canete et al. 2009). Double HSCT approaches. The EBMT data on repetitive HDT/HSCT approaches shows no advantage over single HDT/HSCT. However, the elective selection of particular poorprognosis patients in phase II settings is a likely bias. Recent data from a randomized trial in neuroblastoma emerged with superiority for the tandem strategy for high-risk neuroblastoma front-line patients  (Park et al. 2016 ). Busulfan-melphalan. This HDT combination is the only one in the EBMT database resulting in significantly improved survival rates in neuroblastoma and Ewing tumours. Allo-HSCT. No advantage for allo-HSCT can be detected in the EBMT data for any paediatric solid tumour indication.
EBMT Data (See Tables The median age for 2818 evaluable brain tumour patients (2809 autologous, 9 allogeneic) is 6 years with 2039 receiving HDT during primary treatments and 442 after relapse (disease status not specified in 337). Medulloblastoma is the leading indication with 69% followed by astrocytoma (7%), glioblastoma (7%), ependymoma (6%) and other nonspecified CNS tumours (11%). Medulloblastoma patients' outcome is better when submitted to HDT/SCT in first remission and if younger <3 years. A more detailed analysis by various brain tumours histologies and distinct risk factors is not possible in the current dataset.
IT System At the time of writing the EBMT Registry is using ProMISe software designed by Ronald Brand, who worked as a Professor of Biostatistics at LUMC in the Netherlands prior to his retirement in 2017. The data is stored in an SQL server database based in the same location. During 2018, the EBMT Registry is continuing with an upgrade project and intends to switch to an electronic data capture system named MACRO, part C. R. de Elvira (*) • S. Hewerdine EBMT, London, UK e-mail: carmen. ruiz@ebmt. org of the company Elsevier. Again, this will be a hosted environment and the server will abide by all standards in safety and security, and any other data protection standards required by the EU GDPR, that has become law in May 2018.
Data Protection The EBMT Registry follows EU directives regarding data protection. It is the responsibility of the EBMT to ensure that centres and donor registries are aware of this. The EBMT requests that all centres outside the EU sign an EU Regulations Statement declaring they will follow EU regulations regarding data safety. The most up-to-date information on EBMT data protection can be found on the Data Management pages of the EBMT website, in particular the full Registry Function document. As the Registry Office is located in London, the database has been registered with the Information Commissioner's Office in the United Kingdom. All EBMT centres must obtain informed consent from their patients and/or donors before the data can be submitted to the EBMT. Data is semianonymised: we store date of birth and usually the patient initials; never full names.
Registry Function The main function of the Registry is to collect pertinent and good quality clinical data. The main use of these data is clinical research, but it will also be used to support the mission of the EBMT in aspects such as the inspection, auditing and accreditation of transplant centres. EBMT led studies is the single most important use of the Registry data. The EBMT registry can use all the data submitted to them. It is understood that data submitted to the EBMT can be used for research and published by the EBMT WP as long as the existing Guidelines for the Conduct of Registry Studies using the EBMT Registry Database and the Authorship guidelines for EBMT publications are followed. Both documents are mandatory reading for any WP investigator wishing to perform a registry study.
National Registries for HSCT National registries operating in some countries, usually under the umbrella of a medical association, have become part of the EBMT data flow by mutual consent and are using the same central database. These national registries use their data for their own purposes, which may encompass national requirements for registration of transplants, research, demographics, etc. Where these registries exist, the responsibility of the EBMT Registry for data management may be partially devolved to them. That said, EBMT centres belonging to a National Registry have as much access to the EBMT Registry staff and services as any other centre member. We enjoy a close collaboration with a number of national societies and a list of partners can be found on the EBMT website.
Access to the Registry All individuals must submit an Access request for internet access to the data. Accepted signatories are: • Principal investigator of a transplant centre (centre's data only) or donor registry (donor registry's data only) • Working Party chair (for access to data within the remit of that WP) • The President of the EBMT (for data within the remit of an EBMT Committee) • Director of an institution or study group with which we have a partnership. In this case, the partner must also submit a signed form from every centre involved granting access of their data to that institution or study group. • Registry head for EBMT Registry staff Individuals who by the nature of their work have direct access to the EBMT Registry databases (IT system/server managers) have no access rights to the data and would be in breach of contract if they manipulate it.
Types of Access Users of the Registry system can access their own data in which case they can request permission to do any of the following: • Data entry* • Lists of patient data* • Data download* • Tables with aggregated data (frequencies and cross tabulations) The types of access marked with (*) are restricted since they may include identification of the patients. This type of access can only be requested by an accepted signatory for a set of nominated individuals. The access provided is personal and cannot be transferred to other individuals, not even within the same centre. The Central Registry Office reserves the right to cancel access without warning if it is felt that patient confidentiality might be at risk. The unrestricted access, tables with aggregated data, is available to all members and sponsors.
Data Flow For MED A or B for HSCT, the first registration must be submitted on the day of transplant (day 0) or within a week of day 0. An update should be submitted when 100 days have elapsed from the date of transplant, or when the patient dies, whichever comes first. Regular annual follow-up data must be submitted for all patients from then onwards. For MED A for cell therapy (without HSCT), the first registration must be submitted on the day of infusion (day 0) or within a week of day 0. An update should be submitted every 6 months. For more detailed and up-to-date information, see document Submitting data to the EBMT The data can reach the Registry through two channels: (a) Direct data entry by a centre. This is the preferred and most common method. (b) Direct data entry by a small number of national registries on behalf of specific centres that submit paper forms to them.
Centres can enter the data directly (option a), or fill in the MED A or MED B paper forms and send it to their national registry if available (option b). When the data is entered directly by the centre into the EBMT database, this ensures immediate access by the EBMT and authorised users to the centre's data. This is the preferred method. Centres who use this system may be approached by the national registry, if they belong to one, or by the EBMT registry with requests for data corrections or clarifications. All centres can request to view their data, even if it has been entered by a National Registry on their behalf.
Acknowledgements The authors are grateful to  Ms. Ann O'Leary ,  Ms. Nicola Alderson ,  Dr. Neema Mayor  and  Mrs. Pauline Dodi  at  Anthony Nolan  for providing information and advising on the content of this chapter. Acknowledgements We thank  Myriam Labopin ,  Richard Szydlo  and  Hein Putter  for their contributions to this chapter. 57 P. Bader  (*)  Division for Stem Cell Transplantation and Immunology, University Hospital for Children  and  Adolescents Goethe University Frankfurt am Main Frankfurt Germany  e-mail: peter. bader@kgu. de H. Kreyenberg Division   of Stem Cell Transplantation and Immunology, Center for Children and Adolescents University Hospital Frankfurt Frankfurt Germany G. Ossenkoppele Department of Hematology Universitaire Medische Centra, VU University Medical Center Amsterdam The Netherlands A.
DA. Cost-effectiveness of pediatric central venous catheters in the UK: a secondary publication from the CATCH clinical trial. Front Pharmacol. 2017;8:644. Ullman AJ, Cooke ML, Mitchell M, et al. , Dressings and securement devices for central venous catheters (CVC). Cochrane Database Syst Rev. 2015;(9):CD010367. Vacca M, Perseghin P, Accorsi P, et al. Central venous catheter insertion in peripheral blood hematopoietic stem cell sibling donors: the SIdEM (Italian Society of Hemapheresis and Cell Manipulation) point of view. Transfus Apher Sci. 2014;50:200-6. Wildgruber M, Lueg C, Borgmeyer S, et al. Polyurethane versus silicone catheters for central venous port devices implanted at the forearm. Eur J Cancer. 2016;59:113-24. Open Access This chapter is licensed under the terms of the Creative Commons Attribution 4.
Protective environment for hematopoietic cell transplant (HSCT) recipients: the Infectious Diseases Working Party EBMT analysis of global recommendations on healthcare facilities. Bone Marrow Transplant. 2018;53:1131. https://doi. org/10. 1038/s41409-018-0141-5. Tacconelli E, Cataldo MA, Dancer SJ, et al. ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant Gram-negative bacteria in hospitalized patients. Clin Microbiol Infect. 2014;20(Suppl 1):1-55. sodes of neutropenia. Cochrane Database Syst Rev. 2016;4:CD006247. Yokoe D, Casper C, Dubberke E, et al. Infection prevention and control in health-care facilities in which hematopoietic cell transplant recipients are treated. Bone Marrow Transplant. 2009;44:495-7.
HSCT from MUD trial on behalf of the SAA working party of the 2016), use of BM vs PB, and CMV status EBMT (RACE trial; ClinicalTrials. gov number, 10/10 or 8/8 feasible in 2-3 months and (Bacigalupo et al. 2015). NCT02099747). age < 20 years • For patients older than 30 years, monotherapy with eltrombopag, an oral thrombopoietin- 77. 3 receptor agonist, produced in prospective studies in refractory patients an overall response of 40% with trilineage responses in some cases (Olnes et al. 2012; Desmond et al. Refractory/relapse 2014). A retrospective French study found similar results on patients with relapsed/ refractory SAA. The overall rates of red blood 10/10 (8/8 matched UD) Young (<30 years) cell and platelet transfusion independence First year were 7%, 33%, 46%, and 46 at 1, 3, and 6, months and last follow-up, respectively.
3. 2 Up-Front Matched Unrelated Donor Transplantation first-line therapy after conditioning with FCC. Results were excellent, with OS and EFS of 96% and 92%, respectively, low GVHD rates, and only one death (from idiopathic pneumonia) (Dufour et al. 2015b). This cohort was then com- pared with historical matched controls who had received (1) first-line MRD HSCT, (2) first-line IST with horse ATG + CSA, and (3) MUD HSCT post-IST failure as second-line therapy. Outcomes for the up-front unrelated cohort were similar to MRD HSCT and superior to IST and UD HSCT post-IST failure. Similar results were observed in another pediatric study (Choi et al. 2017). Currently a North American study aims to compare outcomes of children with SAA treated de novo with IST vs MUD HSCT (ClinicalTrials. gov number NCT02845596).
, 2018) , means that identifying the single most important bias is nearly impossible. Soon, however, results from the CMIP6 experiments will be released  (Eyring et al. , 2016) , and the many dedicated forced MIPs should at least allow for the identification of the model component that is most crucial to get right. Finally, as models are tuned and evaluated with respect to observational datasets, we have to bear in mind that these are few and limited in time. The datasets used in this study contain fewer than 25 years of continuous observations, which is too short to capture any long term variability. Furthermore, the majority of sub-surface velocity observations are based on mooring measurements with limited horizontal and vertical resolution. Maintaining these continuous time series are maintained, and further complementing them with higher resolution observations from, for example, sea gliders  (Høydalsvik et al.
Acknowledgements We acknowledge the  World Climate Research Programme 's Working Group on Coupled Modelling, which is responsible for CMIP, and we thank the climate modelling groups (whose models are listed in Table 1 of this paper) for producing and making available their model output. We thank the two anonymous reviewers whose suggestions significantly increased the readability of this study. The authors thank  L. H. Smedsrud  for the constructive discussion at EGU2017 that strongly inspired this paper.
Funding information C. H. is funded by a  VINNOVA Marie Curie Cofund fellowship  (Dnr. 2015-01487 ) and the  Research Council of Sweden  project  WAOW (Dnr. 2018-03859 ). M. Å is funded by the  Research Council of Norway  project  PATHWAY  (grant  263223 ), and the  Blue-Action  project (European Union's  Horizon 2020 research and innovation program , grant number:  727852 ).
Data Accessibility Statement All CMIP5 outputs can be freely downloaded from any Earth System Grid Federation partner website; those used in this study were retrieved from that of DKRZ (https:// cera-www. dkrz. de/). The SODA reanalysis data sets are available through www. soda. umd. edu, whereas GECCO2 and OraS4 are available through the CliSAP-Integrated Climate Data Center (http://icdc. cen. uni-hamburg. de/). The scripts for computing the heat transport and tracking the source of the inflows are available on C. H. personal website: http://cheuze. com/scripts-data.
Lack of reliable peak detection impedes automated analysis of large-scale gas chromatography-mass spectrometry (GC-MS) metabolomics datasets. Performance and outcome of individual peak-picking algorithms can differ widely depending on both algorithmic approach and parameters, as well as data acquisition method. Therefore, comparing and contrasting between algorithms is difficult. Here we present a workflow for improved peak picking (WiPP), a parameter optimising, multi-algorithm peak detection for GC-MS metabolomics. WiPP evaluates the quality of detected peaks using a machine learning-based classification scheme based on seven peak classes. The quality information returned by the classifier for each individual peak is merged with results from different peak detection algorithms to create one final high-quality peak set for immediate down-stream analysis.
Attempting this by hand is a laborious process unsuited for epidemiological size datasets and also impedes reproducibility of this important data analysis step. Instead, this is commonly achieved by using one of many software options on the market, e. g. , XCMS  [4] , metaMS  [5] , MetAlign  [6] , mzMine  [7] , ADAP-GC  [8, 9] , PyMS  [10] , and eRah  [11]. It is commonly understood that there are still certain conditions in which these automated methods are sub-optimal, and the user-defined settings, as well as some of the hard coded features of each software will have a large impact on the results  [12]. However, each tends to have its strengths and weaknesses and will result in a slightly different result  [8, 12]. In this study, we sought to combine the strengths of different algorithms while minimizing the weaknesses.
Supervised learning uses an existing classified dataset(s) to train the model. This has the advantage that the resulting model is easy to optimise and validate  [13]. We present a novel approach to automate peak picking in GC-MS data in order to optimise the reproducibility, accuracy, and quality of the process by combining the strengths of multiple existing or new peak picking algorithms. We apply a visualization strategy combined with a support vector machine (SVM)-based supervised machine learning approach to assess and learn peak quality. The learned model enables us to perform automatic optimisation of parameters for different peak picking algorithms. This is achieved by scoring the algorithm results on a representative data set. The learned model is also used to evaluate and integrate peaks suggested by two or more embedded (pre-existing) peak picking algorithms.
The workflow result is a single high quality, high confidence peak set, which is suitable for immediate further downstream analysis. Once workflow for improved peak picking (WiPP) has been trained for a particular setting (resolution and sample type), it can quickly process large data sets automatically without further user involvement. The WiPP output format is designed to be easily searched by mass spectral library software, such as NIST, and can be subsequently analysed using standard statistical tools. It consists of a. csv and a. msp file, detailing the individual peaks as chromatographic retention time or retention index-mass spectral fragment groups and their associated individual absolute mass spectral peak intensities.
Results To demonstrate and evaluate the performance of the WiPP method, we determined the recovery of compounds from a known mix at different concentrations (Section 2. 1). To quantify the added value, we also compared WiPP results with those obtained from the individual algorithms used within WiPP. Furthermore, we performed a case study using a complex biological data set: We compared results obtained using WiPP to a published independent analysis by a third party (Section 2. 2). Readers less familiar with peak detection, algorithm benchmarking, and machine learning approaches might benefit from first reading Section 4. 1 of Material and Methods, which explains important concepts and defines relevant terms and necessary technical jargon.