dataesr/scientific-paragraphs-categorization huggingface dataset:
Together, the ten Solar Orbiter instruments will enable correlative studies to provide a complete description of the plasma making up the solar wind -its origin, transport processes, and elemental composition. Solar Orbiter data are expected to vastly improve on those of the Helios spacecraft  (Porsche 1977; Schwenn & Marsch 1990 , 1991 ), launched in 1974 and 1976 , and the Ulysses mission  (Wenzel et al. 1992). Solar Orbiter's six remote-sensing instruments will provide novel imaging and spectroscopic observations of the Sun, its corona, and the inner heliosphere, and address key problems in heliophysics by measurement of the Sun's magnetic field, in particular at the solar poles, and of the plasma state of the corona. Solar Orbiter's out-of-ecliptic observations of the Sun from short distance will be unique, and will be further augmented by measurements of NASA's Parker Solar Probe mission  (Fox et al.
g. Helios 1 and 2 carried only a single, limited remote-sensing instrument, the Zodiacal Light Experiment;  Leinert et al. (1975) ). Near perihelion, Solar Orbiter provides time series of ultraviolet (UV) and extreme ultraviolet (EUV) images of the Sun's corona at unprecedented spatial resolution, which allow us to study coronal heating processes at small scales and better understand the dynamic forcing of the heliosphere by the Sun's corona. So far, data of this kind have only been obtained for short time intervals during suborbital rocket flights (e. g. by Hi-C,  Kobayashi et al. 2014; Rachmeler et al. 2019). Williams et al. (2020)  analysed data from the Hi-C 2. 1 rocket flight in 2018 and find that Hi-C 2. 1 can resolve individual 'strands' of coronal loops as small as ∼ 200 km. This is significantly smaller than the spatial resolution of SDO/AIA (down to ≈ 1.
2019). The same study also suggests that there is an impulsive mechanism associated with solar-wind energisation, and that micro-instabilities also contribute to the solar wind heating. In addition to the above, the heliosphere is also frequently experiencing transient events, such as CMEs, on a wide range of scales. In the following sections, we discuss the four overarching science questions of Solar Orbiter in detail and specify how its data will contribute to answering them.
Imaging spectrometers have a small field of view due to the time it takes to build up an image (see Fig. 3  for the case of Hinode/EIS). However, solar wind can emanate from multiple regions, so a large field of view significantly increases the likelihood that one of them is mag-netically connected to the spacecraft's location. One way to explore this is to perform full-Sun rasters, which are time consuming but provide spectroscopic information across the whole Sun. This takes a couple of days and is now carried out by both Hinode/EIS and the Interface Region Imaging Spectrometer (IRIS) on a regular basis. Brooks et al. (2015)  describe the analysis of such a dataset, from which they determined the Doppler velocity and the elemental composition, and combined these with global magnetic field models.
2020 ), but it is still unclear how frequent this is close to the Sun, where the solar wind is seen to be more dynamic with the recently observed switchbacks  (Kasper et al. 2019). There is also evidence for folds in the magnetic field  (Tenerani et al. 2020) , from cross-helicity  (Balogh et al. 1999 ) and proton-alpha streaming data  (Yamauchi et al. 2004 ), but their origin is also unknown. Are they related to photospheric reconnection (e. g. Rouppe van der  Voort et al. 2016; Ortiz et al. 2020) , chromospheric reconnection features such as jets (e. g. Shibata et al. 2007; Robustini et al. 2018)  or velocity shears  (Landi & Bettarini 2012) ? How Solar Orbiter will address these questions. Detailed measurements of the solar wind plasma and its magnetic field, simultaneously acquired with remote-sensing measurements of the photosphere and corona, are key to deciphering the source regions of the solar wind and the heliospheric magnetic field.
How Solar Orbiter will address the question. Solar Orbiter will provide the missing seed particle data for models of SEP acceleration associated with shocks by systematically mapping the suprathermal ion pool in the inner heliosphere with spectroscopic and in-situ data. The extended mission phase will add the out-of-ecliptic dimension to this, making it possible to further probe the solar and interplanetary origins of the seed particle populations. For SEPs accelerated along coronal loops or in reconnection regions, the Solar Orbiter's perihelia will be advantageous because particle properties will be accurately measured, also with much more precise information on the coronal location. This will allow us to distinguish between low coronal sources that result in stripping of escaping particles and higher sources.
2003 ) cannot be mapped well from locations near the ecliptic plane. In particular, the meridional flow, a key aspect of flux transport dynamo models, is not fully characterised (e. g. Böning et al. 2017; Lin & Chou 2018; Mandal et al. 2018). 2008 ) demonstrated that even with only a single day of observations, complex velocity fields can be derived. Uniquely, Solar Orbiter's provision of magnetograms away from the Sun-Earth line will for the first time enable stereoscopic helioseismology by combining data with ground-or space-based helioseismic observations from 1 AU. For global helioseismology, this will help by significantly reducing mode leakage in Fourier space. In addition, deeper layers of the convection zone can be probed by considering additional acoustic ray paths. This will require observations beyond the baselined ten-day remotesensing windows, and the mission's science operations teams have started assessing whether or not and in what ways this can be accomplished.
(1989) ;  Sheeley (1991) ;  Makarov et al. (2003) ). In addition, SO/PHI will probe the cancellation processes that take place when flux elements of opposite polarity meet as part of the polarity reversal process. These interactions are expected to occur on comparatively short timescales, as they are driven by granular and supergranular flows once the features are sufficiently close together. The large overlap between Solar Orbiter's EUI Full-Sun Imager and the Metis coronagraph will allow us to trace structures from the far off-disc corona down to the limb and critically confront models of the extended coronal connectivity extrapolated from magnetograms provided by SO/PHI. The combination of Solar Orbiter's high-latitude observations with data acquired by spacecraft in the ecliptic plane will enable investigations of the three-dimensional structure of the inner heliosphere, such as for example the heliospheric current sheet, whose inclination is commonly used as a proxy for the tilt of the solar magnetic dipole.
The black inner circle indicates the minimal perihelion distance of 0. 28 AU that Solar Orbiter will reach during its nominal mission phase. November 2021 will inject the spacecraft into a heliocentric science orbit with perihelion at 0. 32 AU. This will mark the beginning of the NMP. Venus will be encountered inbound for the third Venus GAM (V3) in September 2022, starting a sequence of resonance orbits of 5:4, 4:3, 3:2, 3:2, and 3:2 with respect to Venus' orbit. These ratios determine the different orbital periods of Solar Orbiter during the mission's lifetime, which are 180, 169, and 150 days, respectively. Figure  28  displays heliocentric latitude and distance as a function of time. This sequence has been selected primarily for its excellent data downlink properties, which had to be traded off against reaching high solar inclinations more quickly.
Acknowledgements. Solar Orbiter is a space mission of international collaboration between  ESA  and  NASA. The spacecraft has been developed by Airbus and is being operated by  ESA  from the  European Space Operations Centre (ESOC) in Darmstadt, Germany. Science operations are carried out at  ESA 's  European Space Astronomy Centre (ESAC) in Villafranca del Castillo ,  Spain. Conceiving , designing and building  Solar Orbiter  has been an international team effort of many people. In particular, the authors would like to thank  ESA's Mission Operations Centre (MOC)  and  Science Operations Centre (SOC)  teams,  Yves Langevin  and  Jose-Manuel Sánchez Pérez  for their skillful optimisation of mission trajectories, the  ESA  and  NASA  Project offices, Airbus, IABG,  NASA-LSP, ULA , and all national funding agencies that have enabled Solar Orbiter.
The German contribution to SO/PHI is funded by the  Bundesministerium für Wirtschaft und Technologie through Deutsches Zentrum für Luftund Raumfahrt e. V. (DLR) , Grants No. 50 OT 1001/1201/1901  as well as  50 OT 0801/1003/1203/1703 , and by the  President of the Max Planck Society (MPG). The Spanish contribution has been partially funded by  Ministerio de Ciencia, Innovaci/'on y Universidades  through projects  ESP2014-56169-C6  and  ESP2016-77548-C5. IAA-CSIC acknowledges financial support from the  Spanish Research Agency (AEI/MCIU)  through the  "Center of Excellence Severo Ochoa" award  for the  Instituto de Astrofísica de Andalucía  ( SEV-2017-0709 ). The French contribution is funded by the  Centre National d'Etudes Spatiales. Further detailed acknowledgements regarding each instrument can be found in the individual instrument papers of this special issue.
R. A. H. is supported by the  NASA Solar Orbiter Collaboration Office , under contract  NNG09EK11I. The Spanish contribution to  SO/PHI  has been funded by the  Spanish Ministry of Science and Innovation through several projects , the last one of which being  RTI2018-096886-B-C5 , and by  "Centro de Excelencia Severo Ochoa" Programme  under grant  SEV-2017-0709. The authors would like to highlight Rainer Schwenn's (1941Schwenn's ( -2017) ) important and enthusiastic contribution to the Solar Orbiter mission in its early phase. Portions of the text have been reproduced with permission from Müller et al. (2013) copyright by Springer. The authors would like to thank  John Leibacher  and  Bernhard Fleck  for their support, and the referee for providing helpful suggestions.
Insights from the expert elicitation and their limits Expert assessment is critical for informing decisions that require judgements that go beyond established knowledge and model simulations  94. For this reason, expert opinion is often used in environmental assessments, either as a means to assess confidence levels or rank potential outputs  7  or as data points that offer estimates that could not be provided otherwise  95, 96. This expert assessment also highlights key knowledge gaps and uncertainties, for example in the impact of permafrost aggradation and degradation on the future peatland C balance (see Supplementary Information and Extended Data Fig. 1 ). Our dataset reflects two main schools of thought that are anchored in conflicting evidence from the literature: rapid C loss from deep peats and slow recovery of the peatlands following permafrost thaw  59, 60  , and net C gain from rapidly recovering plant production owing to warm and moist conditions following thaw  1, 28.
Acknowledgements This work developed from the  PAGES (Past Global Changes) C-PEAT  ( Carbon in Peat on EArth through Time ) working group; we acknowledge support from  PAGES  funding by the  American and Swiss National Science Foundations. We also thank the  International Union for Quaternary Research (INQUA)  and the  Department of Geography at Texas A&M University  for workshop support. We thank  P. Campbell  for creating the peatland infographic, as well as  D. McGuire  for his comments on a previous version of the manuscript. We also acknowledge research support from  Universidad Javeriana  (J. C. B. ); the  National Science Foundation of the United States  under grant nos. 1802838  ( J. Loisel ), 1019523 (J. L. B. ) and 1802825 (C. T. and S. F. ); the  National Environment Research Council of the United Kingdom  under grant nos.
NE/1012915  and  NE/S001166/1  (A. V. G. -S. and D. J. C. ); the  Attraction and Insertion of Advanced Human Capital Program of the National Commission for Scientific and Technological Research of Chile  and the  NEXER-UMAG  project under grant no. 7718002  (C. A. M. ); the  Geological Survey Land Resources Research and Development program  of the United States (M. C. J. ); the  Natural Sciences and Engineering Research Council of Canada  ( M. Garneau , S. F. ,  T. Lacourse  and J. W. ); the  National Science Centre of Poland  under grant no. 2015/17/B/ST10/01656  (M. L. ); the  Academy of Finland  projects  286731  and  319262  ( T. Larmola ); the  Belgian National Fund for Scientific Research  under grant no. 1167019N  (W. S. ); the  Office of International Affairs and Global Network at Chulalongkorn University  (S.
Background: Atypical hemolytic uremic syndrome (aHUS) triggered by pregnancy is a rare disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor obtained through selective modifications to eculizumab, is efficacious in inhibiting complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. In this analysis, we report outcomes in a subgroup of patients from the 311 study who developed TMA postpartum. Methods: This was a phase 3, multicenter trial evaluating efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete TMA response (simultaneous platelet count normalization [≥150 × 10 9 /L], lactate dehydrogenase normalization [≤246 U/L] and 25% improvement in serum creatinine) through the 183-day initial evaluation period.
Trial oversight and study design The 311 clinical trial (NCT02949128) is a phase 3, single arm, multicenter study designed to evaluate the efficacy and safety of ravulizumab administered by intravenous (IV) infusion to adults with aHUS naïve to complement inhibitor treatment. Patients from the trial included in this analysis were ≥18 years of age and weighed ≥40 kg with active TMA (thrombocytopenia, evidence of hemolysis and kidney dysfunction) at postpartum. All patients included in this analysis had evidence of TMA lasting for ≥3 days. Patients could meet the platelet and lactate dehydrogenase (LDH) criteria (<150 × 10 9 and ≥1. 5 x upper limit of normal, respectively) based on results from local laboratories, but the serum creatinine criteria (≥ upper limit of normal) must have been confirmed by the central laboratory at baseline.
5 and 37. 5%, respectively). The current subgroup did not show a preponderance of any type of safety signal. In the full 311 cohort the most common AEs were headache, diarrhea, and vomiting  [24] , while headache and pyrexia were the most common in this subgroup. No patients died or contracted a meningococcal infection. This study has limitations that must be noted. aHUS is an ultra-rare disease with an estimated prevalence of 4. 9 per million and annual incidence rate between 0. 23-1. 9 per million  [27]. As postpartum patients account for only around 4% of diagnosed cases of aHUS  [3] , there is not a large enough pool of complement inhibitor-naïve patients presenting postpartum to conduct a placebocontrolled trial. Currently this sub-analysis is the largest postpartum dataset utilized in a prospective study of patients with aHUS; no comparator or control group was utilized for the full 311 cohort, meaning that conclusions drawn from this subanalysis must be interpreted with caution.
Conclusion CDK4 and CDK6 inhibitors represent one of the most exciting recent developments for women with HR+/HER2-metastatic breast cancer, potentially providing a new standard of care for these patients. Abemaciclib offers a new, effective treatment option, both in the first-line advanced setting and following cancer progression on previous endocrine therapy. Although no direct comparison studies have been undertaken, patients treated with abemaciclib experience a higher rate of diarrhoea than other CDK4 and CDK6 inhibitors, but also lower rates of haematological side effects that enables continuous dosing and simplified blood monitoring (NICE 2019a). The efficacy of abemaciclib in early stage breast cancer is being evaluated and results in this patient population are awaited (ClinicalTrials.
Compliance with Ethics Guidelines The clinical study (ClinicalTrials. gov identifier: NCT02700815) was conducted in compliance with the clinical trial protocol, the principles laid down in the Declaration of Helsinki, in accordance with ICH-GCP, and was based on the Guideline on Clinical Development of Fixed Combination Medicinal Products of the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) current at trial initiation  [33]. The study was done to support the registration of a new product so the respective guidelines had to be followed in addition to the specific requests from the German Federal Institute for Drugs and Medical Devices. The study protocol (EudraCT number 2015-000404-25), protocol amendment and associated documents were reviewed by the Independent Ethics Committees and/or Institutional Review Boards (IECs/IRBs) of the participating centers; the master ethics committee is Ethik-Kommission der Bayrischen Landesa ¨rztekammer, Mu ¨nchen, Germany (Ethic Committee 16004) and further details of local committees can be found in Supplementary Table  S1.
[5]  showed that a 1. 16% diclofenac gel significantly reduced POM by 75% versus 23% compared with placebo at 48 h after application, and this change represented clinically relevant pain relief. In addition, all POM scores were significantly reduced versus placebo from 1 h after application  [5]. In this study, however, diclofenac was formulated as ethanolamine salt, and therefore may have exposed different skin absorption properties compared with the formulation used in our study (diclofenac sodium) which could have contributed to the apparent lack of efficacy of diclofenac alone. In a phase 1 study comparing the bioavailability of diclofenac in a diclofenac ? capsaicin combination gel to a reference product of diclofenac gel (Voltarol Ò 2. 32% gel) in healthy volunteers, the diclofenac exposure following application of the topical gel combination product was less than half from the reference product (NCT03074162)  [28, 29].
As other topical diclofenac formulations have been proven to be effective for the treatment of lower back pain/neck pain, the principle of enhancing the effectiveness of the single ingredients by a combined topical formulation containing capsaicin and diclofenac may still be proven by further research. Funding. This study was sponsored by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. The development of this manuscript was supported by the current marketing authorisation holder Sanofi-Aventis Group. The Rapid Service Fee was also funded by Sanofi-Aventis group. Medical Writing Assistance. The authors would like to acknowledge Bernward Fladung, a freelancer working for Sanofi-Aventis and Claire Lydon of iMed Comms, an Ashfield Company, part of UDG Healthcare plc for medical writing support that was funded by Sanofi-Aventis in accordance with Good Publications Practice (GPP3) guidelines (https://www.
RL reviewed and approved the trial protocol, had the medical oversight during trial conduct, evaluated the trial results and reviewed and approved the trial report. Disclosures. Caty Ebel-Bitoun, Thomas W. Weiser and Robert Lange are employees of Sanofi-Aventis. Barbara Peil is an employee of Boehringer Ingelheim, who sponsored the study. Hans-Georg Predel has received study grants, honoraria for speaking at congresses and consultancy fees from Boehringer Ingelheim and Sanofi-Aventis. Compliance with Ethics Guidelines. The clinical study (ClinicalTrials. gov identifier: NCT02700815) was conducted in compliance with the clinical trial protocol, the principles laid down in the Declaration of Helsinki, in accordance with ICH-GCP, and was based on the Guideline on Clinical Development of Fixed Combination Medicinal Products of the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) current at trial initiation  [33].
The study was done to support the registration of a new product so the respective guidelines had to be followed in addition to the specific requests from the German Federal Institute for Drugs and Medical Devices. The study protocol (EudraCT number 2015-000404-25), protocol amendment and associated documents were reviewed by the Independent Ethics Committees and/or Institutional Review Boards (IECs/IRBs) of the participating centers; the master ethics committee is Ethik-Kommission der Bayrischen Landesa ¨rztekammer, Mu ¨nchen, Germany (Ethic Committee 16004) and further details of local committees can be found in Supplementary Table  S1. Informed consent was obtained from each patient in writing before randomization and the rights of patients were protected. Data Availability. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications.
The radiative forcing of the aerosol-radiation interaction can be decomposed into clear-sky and cloudysky portions. Two sets of multi-model simulations within Aerosol Comparisons between Observations and Models (AeroCom), combined with observational methods, and the time evolution of aerosol emissions over the industrial era show that the contribution from cloudy-sky regions is likely weak. A mean of the simulations considered is 0. 01 ± 0. 1 W m -2. Multivariate data analysis of results from Aero-Com Phase II shows that many factors influence the strength of the cloudy-sky contribution to the forcing of the aerosolradiation interaction. Overall, single-scattering albedo of anthropogenic aerosols and the interaction of aerosols with the short-wave cloud radiative effects are found to be important factors.
Multivariate data analysis Multivariate data analysis in this study is based on results from a subset of the models participating in AeroCom Phase II (CAM5, GOCART, HadGEM2, IMPACT, INCA, ECHAM-HAM, OsloCTM2 and SPRINTARS). These eight models participated in the AeroCom Phase II experiment  (Myhre et al. , 2013a)  with no constrain on aerosol processes, and in addition they participated in the host model AeroCom exercise with fixed aerosol optical properties  (Stier et al. , 2013). From the latter, FIX2scat and FIX3abs experiments can be used to retrieve the contributions from cloudy-sky to RFari in two highly idealized aerosol radiative properties experiments. FIX2scat is a purely scattering aerosol case, and FIX3abs is an absorbing aerosol case. The origin of the different variables derived from AeroCom Phase II model simulations  (Myhre et al.
Variables that point in the opposite direction of each other are negatively correlated. Variables that are perpendicular to each other are not correlated with each other. The missing data (see Table  1 ) for two of the models (LMDZ-INCA and ECHAM-HAM) are filled-in using regularized iterative PCA. This technique estimates the missing values, based on the correlation between the variables and the principal components  (Josse and Husson, 2012). RFari cloud (second term in Eq. 1) is added as a supplementary variable in PCA. This is to ensure that this dependent variable, the cloudy-sky contribution, does not influence the projected correlations the independent variables have on each other. The same approach is applied to FIX2scat and FIX3abs, as these variables are not independent, as they are composed of the many of the variables used in the analysis.