dataesr/scientific-paragraphs-categorization huggingface dataset:
Due to stronger modulation of insolation at high latitudes compared with low latitudes, the orbital forcing weakened the meridional temperature gradient during the early-to mid-Holocene. This phenomenon may, via different pathways, have weakened the AMOC  (Fischer and Jungclaus, 2010) , in turn related to North Atlantic modes of variability  (Brahim et al. , 2019). Nevertheless, such a response remains model dependent, as other processes, such as the reduction of sea ice export from the Arctic towards the North Atlantic, can lead to salinification of the convection sites and an increase in the AMOC  (Born et al. , 2010). When analysing the PMIP3 database for 6-ka BP,  Găinuşă-Bogdan et al. (2020)  found that the ensemble mean of models does show an intensification of the AMOC for that period compared to preindustrial simulations.
, 2018) , with the latter result observed in multiple models as being connected to sea-ice loss. Nevertheless, the whole PMIP3 database exhibits a very model-dependent result  (Găinuşă-Bogdan et al. , 2020) , highlighting very poor agreement on this topic within models. Additionally, a recent review paper examining Holocene variability in the ENSO concluded that a range of proxy-based records and model simulations all point to a weaker mid-Holocene ENSO variability  (Lu et al. , 2018a)  (see section 3. 1). Although the reason for the weaker ENSO is thought to originate from orbital forcing, the exact governing mechanisms remain unclear. The enhanced mid-Holocene NH summer insolation also increased the low-latitude land-ocean temperature contrast driving the summer monsoons  (Sjolte et al. , 2014).
, 2015; Toohey and Sigl, 2017). Nevertheless, a recent simulation of the relatively modest 1970 volcanic eruption that occurred in the Deception Volcano Island (Antarctica Peninsula) showed that ashes might have a larger distribution than previously thought  (Geyer et al. , 2017). Over the last millennium, volcanic eruptions have been reconstructed using the deposition of sulphate aerosols within the ice cores from Greenland and Antarctica (Fig. 9c ). The impacts of these eruptions are believed to have a major influence on the variability of the last millennium  (Schurer et al. , 2013). The cumulative effects of all the volcanic eruptions can explain the negative trend observed in the recent reconstructions from the PAGES2K database (PAGES2k  Consortium et al. , 2017). Volcanic eruptions can activate dynamic feedbacks within the climate system, making their impact last longer or differing only due to their radiative forcing.
The associated decrease in northward heat transport may then help to explain the onset and long-term duration of the LIA  (Miller et al. , 2012). Volcanic activity could also have played a substantial role in climatic variability during the Holocene  (Kobashi et al. , 2017) , but very little is known about this topic as well-dated and robust reconstructions of volcanic activity are scarce. Based on the GISP2 sulphate dataset, it has been suggested that there have been periods of more frequent explosive eruptions in the past (e. g. 9. 5-11. 5 ka cal BP;  Zielinski et al. , 1994) , and based on ice core reconstruction from Antarctica, the last 2 ka may have been exceptional over the Holocene in terms of volcanic activity. Nevertheless, developments in volcanic activity reconstructions are starting to provide interesting benchmarks (e.
6. -Summary and future perspectives Global instrumental records now extend over a century into the past and provide some coverage in parts of the 19th century  (Folland et al. , 2002). Improvement of these datasets is on-going as data recovery efforts uncover new and forgotten sources of direct climate observations and integrate them into existing datasets to improve global reanalyses  (Compo et al. , 2011; Slivinski et al. , 2019). These efforts are crucial for our understanding of climate variability and for testing dynamical climate predictions against observations. Indeed, recent progress indicates that large fluctuations in ENSO  (Luo et al. , 2008) , the NAO  (Smith et al. , 2019)  and the AMV  (Hermanson et al. , 2014)  can now be skilfully predicted at multiyear timescales. However, questions persist regarding the robustness of these results, especially given that our direct observational data and climate prediction tests are limited to the century timescale at best  (O'Reilly et al.
g. ,  Dee et al. , 2015; Steiger et al. , 2017)  and the development of free software (e. g. , ClimoRec by  Michel et al. , 2020)  using well dated and verified proxy databases, or of palaeoclimate data reanalysis techniques could yield such datasets  (Amrhein et al. , 2018; Tardif et al. , 2019). Hence, the presence of only a few cycles of low-frequency variability in our instrumental climate records, the importance of low-frequency variability for regional climate and the need for validation of climate models make modes of variability a high-priority topic for climate science. These points alone motivate the study of past variations in modes of climate variability using long climate-proxy records, and the extension of quantitative proxy-based records beyond the last millennium and their combination into improved reconstructions is needed to provide sufficiently long records with enough accuracy to understand low-frequency climate dynamics and draw robust conclusions from comparisons with climate models.
Acknowledgements A. H. is supported by a  Beatriu de Pinós -Marie Curie Cofund programme fellowship  ( 2016 BP 00023 ) and  HOLMODRIVE -North Atlantic Atmospheric Patterns influence on Western Iberia Climate: From the Lateglacial  to the Present ( PTDC/CTA-GEO/29029/2017 ) project funded by the  Fundação para a Ciência e a Tecnologia, Portugal (FCT). A. H. , S. G. , and S. P-R. thank the Spanish research project  PaleoModes  ( CGL2016-75281-C2-1-R ) which provided some of their financial support. E. M. -C. contribution was funded by the project  PARAMOUR (30454083)  from the  EOS  program by the F. R. SFNRS. CM-P is supported by the  Royal Society  (ref:  DH150185 ). P. O. contribution has been supported by the Ramon y Cajal senior tenure programme from the  Spanish Ministry of Economy and Competitiveness.
The  Spanish PTI PolarCSIC  (https://www. polarcsic. es) is also acknowledged for providing partial financial support to S. G. A. P. 's work was supported by a  Science Foundation   Ireland Career Development Award  ( 17/CDA/4695 ), a research centre award ( 12/RC/2289_P2 ), an  investigator award  ( 16/IA/4520 ), and a  Marine Research Programme  funded by the  Irish Government , cofinanced by the  European Regional Development Fund  ( Grant-Aid  Agreement No. PBA/CC/18/01 ). J. S. is supported by the strategic research program of ModEling the Regional and Global Earth system (MERGE) hosted by the  Faculty of Science at Lund University. D. S. is supported by  Blue-Action (European Union 's  Horizon 2020 research and innovation program , Grant Number:  727852 ) and  EUCP (European Union 's  Horizon 2020 research and innovation programme  under grant agreement no 776613) projects as well as by the  French national program LEFE/INSU  with  VADEMECUM  project.
14, 15 lthough both strategies are effective as GvHD prophylaxis, there is a paucity of comparative data on ATG versus PTCy in haploidentical transplantation. Ruggeri et  al. conducted a retrospective study using data from the European Society for Blood and Marrow Transplantation (EBMT) registry on 308 patients with acute myeloid leukemia, and compared outcomes between those given ATG (n=115) or PTCy (n=193) as a GvHD prevention strategy. On multivariate analysis, compared to ATG, PTCy use was associated with significantly better leukemia-free survival (P=0. 03) and GvHD-free/relapsefree survival (GRFS) (P=0. 03). To our knowledge, no studies have reported comparative data between ATG and PTCy platforms in ALL patients undergoing haploidentical transplantation. 16 We used the EBMT database to conduct a comparative analysis between ATG and PTCy strategies in ALL patients undergoing haploidentical HCT using bone marrow or peripheral blood as the source of hematopoietic cells for the graft.
Data source and patients This is a retrospective multicenter analysis using the dataset of the Acute Leukemia Working Party of the EBMT group registry. The EBMT is a voluntary working group of more than 600 transplant centers that are required to report, annually, all consecutive hematopoietic cell transplants and follow-ups. Audits are performed routinely to determine the accuracy of the data. The study was planned and approved by the Acute Leukemia Working Party of the EBMT. In addition, the study protocol was approved by the institutional review board at each site and complied with countryspecific regulatory requirements. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The subjects included in this analysis were adults (≥18 years) with ALL who underwent their first haploidentical HCT between 2007 and 2017, were reported to the ''Promise'' database of the EBMT and received either ATG or PTCy as a GvHD prevention strategy.
NK-UTWind Code Model First, the full-scale FOWT was numerically modeled and analyzed using NK-UTWind code (an in-house code developed by The University of Tokyo for coupled analysis of FOWT). In the analysis code, the rotor and floating body were modeled as beam elements; the mooring system was modeled using the quasi-static catenary mooring method; however, the lumped mass method was also an alternative. For calculating the aerodynamic load acting on the rotor, the wind turbine analysis code, FAST  [17] , based on the blade element momentum theory developed by NREL (National Renewable Energy Laboratory), was used. A complete description of the method implemented in NK-UTWind can be found in  [18]. See an example of the mesh in Figure  7. estimate the wave velocity field, and the instantaneous wave load is evaluated considering the submergence of each structural element; see details in  [19].
WAMIT Code Model Besides the analysis performed with NK-UTWind code, the behavior of the FOWT was also evaluated using the WAMIT code, a commercial Boundary Element Method (BEM) code for analyzing wave interactions with offshore structures. The code evaluates the hydrodynamic loads through the radiation/diffraction problem in the frequency domain. Since WAMIT code calculations applied a different method than those employed in NK-UTWind, comparing the motion of the response amplitude operators (RAOs) obtained with both software indicates how conditions each methodology is better at reproducing the experiments. The WAMIT simulation was performed on the full scale with a low-order mesh composed of 4654 flat quadrilateral and triangular panels with a mean edge length of approximately 1. 3 m in full scale, as illustrated in Figure  8.
Since WAMIT is based on the potential flow and mooring lines are not directly modeled in the code, it is necessary to include an external linear stiffness matrix to partially model mooring effects. The mooring line characteristics were included in the software Edtools ® that calculated the full As most FOWTs are comprised of slender structural elements such as cylinders, NK-UTWind employs the Morison equation for the evaluation of the hydrodynamic loads, as represented by the following equations: dF x dF y = ρA       (1 + C ax ). u x 1 + C ay. u y       -ρA C ax. v x C ay. v y + 1 2 ρD|u -v|       C dx (u x -v x ) C dy u y -v y       ( 1 ) where ρ is the fluid density, A is the cross-sectional area, u x and u y are water particle velocities in x and y-direction. v x and v y are velocities of the structural element in x and y-direction in the global coordinate system.
ve interactions with offshore structures. The code evaluates the hydrody adiation/diffraction problem in the frequency domain. Since WAMIT code fferent method than those employed in NK-UTWind, comparing the m plitude operators (RAOs) obtained with both software indicates how con is better at reproducing the experiments. MIT simulation was performed on the full scale with a low-order mesh c rilateral and triangular panels with a mean edge length of approximately trated in Figure  8. AMIT is based on the potential flow and mooring lines are not directly mo essary to include an external linear stiffness matrix to partially model moo line characteristics were included in the software Edtools ® that calcula ix using the formulation presented in  [21] , the non-diagonal terms due to oupling was also considered.
The sketch of the mooring lines setup is il characteristics of the mooring lines were the same as those presented p Since WAMIT is based on the potential flow and mooring lines are not directly modeled in the code, it is necessary to include an external linear stiffness matrix to partially model mooring effects. The mooring line characteristics were included in the software Edtools ® that calculated the full stiffness matrix using the formulation presented in  [21] , the non-diagonal terms due to the degree-of-freedom coupling was also considered. The sketch of the mooring lines setup is illustrated in Figure  9. The characteristics of the mooring lines were the same as those presented previously in Table  4. The full external matrix calculated as the described procedure and considered in the WAMIT code analysis is shown in Table  8.
In general, the experimental results from regular and irregular wave tests were similar for all degrees of freedom. Figure  10  presents the RAO surge results. The experimental and numerical results agreed very well for short-period waves,  < 15 s. Moreover, even for long-period waves, the comparison was good and showed the same qualitative behavior. Small differences could be observed around 22 s that represent the period of the pitch motion. The system presented a strong surge and pitch coupling due to the turret characteristic of the mooring lines. Numerical calculations using NK-UTWind code could observe the peak in the surge due to the pitch natural period, and the numerical results agreed well with the experiments. However, external damping in the cross-terms of the damping matrix should be added due to the coupling between the degrees of freedom in the WAMIT code calculations.
Some differences between NK-UTWind and WAMIT codes could probably be due to the difference in mooring settings for the numerical calculation. A single material quasistatic mooring was applied for NK-UTWind code with non-linear behavior; however, a linear matrix of stiffness was used for the WAMIT code. For NK-UTWind code calculations, the agreement was very good for short-wave periods, T < 15 s. A cancelation point was observed around 16 s, and two peaks located in the natural periods of heave and pitch. The range between 16 and 25 s was susceptible to damping levels (cancelation and resonance region); therefore, the limitation of the Rayleigh damping matrix applied to tune the motions individually in each degree of freedom was not successful. For WAMIT code calculation, the external damping should be input as an external damping matrix.
It was possible to observe that the crossed terms due to the coupling between heave and pitch  In general, the experimental results from regular and irregular wave tests were similar for all degrees of freedom. Figure  10  presents the RAO surge results. The experimental and numerical results agreed very well for short-period waves, T < 15 s. Moreover, even for long-period waves, the comparison was good and showed the same qualitative behavior. Small differences could be observed around 22 s that represent the period of the pitch motion. The system presented a strong surge and pitch coupling due to the turret characteristic of the mooring lines. Numerical calculations using NK-UTWind code could observe the peak in the surge due to the pitch natural period, and the numerical results agreed well with the experiments.
Some differences between NK-UTWind and WAMIT codes could probably be due to the difference in mooring settings for the numerical calculation. A single material quasi-static mooring was applied for NK-UTWind code with non-linear behavior; however, a linear matrix of stiffness was used for the WAMIT code. For NK-UTWind code calculations, the agreement was very good for short-wave periods, T < 15 s. A cancelation point was observed around 16 s, and two peaks located in the natural periods of heave and pitch. The range between 16 and 25 s was susceptible to damping levels (cancelation and resonance region); therefore, the limitation of the Rayleigh damping matrix applied to tune the motions individually each of freedom was not successful. For WAMIT code calculation, the external damping should be input as an external damping matrix.
Influence of the tower and pontoon rigidities on the RAO tension result at the front guy wire (T1), and its comparison between the experiment and numerical calculation. In general, the force measurements comparison between experimental and numerical results from the NK-UTWind code showed a good qualitative agreement. Two peaks could be observed in all results. For the wave periods between 7 and 8 s, the wavelength was equal to the distance between columns projected in the wave direction; thus, the sagging moment took maximum value when the wave crest came to the fore column and side column, and the wave trough was located around the central column. The highest peak observed around the wave periods between 22 and 27 s occurred due to the large pitch motion response in this range of wave period.
Influence of the Platform Structural Rigidity on the Tension and Bending Moment Responses The influence of the rigidity of the tower column and pontoons were studied numerically using the NK-UTWind code. Three levels of rigidity were analyzed, as presented in Table  10. The changes of rigidity were done at the pontoon and/or tower column values. In general, the force measurements comparison between experimental and numerical results from the NK-UTWind code showed a good qualitative agreement. Two peaks could be observed in all results. For the wave periods between 7 and 8 s, the wavelength was equal to the distance between columns projected in the wave direction; thus, the sagging moment took maximum value when the wave crest came to the fore column and side column, and the wave trough was located around the central column.
Acknowledgments: This research is based on the results obtained from a project,  JPNP14022 , commissioned by the  New Energy and Industrial Technology Development Organization (NEDO). The authors would like to thank  NEDO  for allowing the publication of the paper. The authors would like to thank the student Marques, M. A. from the  Federal University of Pernambuco (UFPE), Brazil , for his help during the image developments;  Ms. Matsui ,  R. , and  Eng. Nimura , T. from the  National Maritime Research Institute (NMRI), Japan , and  Hashimoto , K. from  Osaka Prefecture University (OPU), Japan , for their assistance in carrying out experiments; and,  Eng. Sakamoto ,  H. from  Fractaly Co. Ltd. , Japan , for model manufacturing and assembly. Prof. Gonçalves , R. T. thanks to the  Japan Society for the Promotion of Science (JSPS)  for the grant as  JSPS International Research Fellow  ( P18355 ,  Graduate School of Engineering, The University of Tokyo ).
Data collection Background clinical information was collected about previous history of motion sickness, history of sickness associated with general anaesthesia, smoking history, and any other issues with nausea or vomiting. Participants were asked to complete a pain score by using the descriptive visual analogue scale (VAS). This is a validated tool and one of the most frequently used methods in rating pain scales. It is easy to use, requires no verbal or reading skills, and can be used in a variety of settings. The pain scores from 24 hours before admission up to three days postoperatively were collected daily. The use of any analgesia or anti-emetics in the 24 hours prior to admission was recorded. The amount of oral fluid consumed was recorded from 18. 00 hours the day before surgery. Subsequently from day 0 to three, daily information of pain scores, nausea and vomiting, analgesia and antiemetics requirements, and information on passing first flatus and bowel motion were obtained directly by asking the patients and confirmed from the nursing staff and the clinical notes.
Our study showed that the mean (±SD) for operative POSSUM score in the CHO group was 16. 97 (±5. 76) versus 14. 49 (±2. 64) in the placebo group (p=0. 019). To determine the association between the operative POSSUM score and type of surgery (IDS, PDS), we carried out a post-hoc analysis to compare operative POSSUM score between IDS and PDS regardless the type of the study drink (CHO, placebo). We found that the IDS group had lower operative POSSUM scores with mean (±SD) score of 15. 67 (±5. 21) versus 15. 84 (±3. 80) in PDS. This was not statistically significant, but suggested a trend that IDS group do better postoperatively. In addition, we looked at further historic data retrospectively (2006-2016). These data were obtained from St James's University Hospital Gynaecological Oncology department in Leeds.
PATENT PLUS (NCT01179334) was a phase II, randomised, double-blind, placebo-controlled study to assess the safety and efficacy of riociguat in combination with sildenafil in patients with PAH (Table  1 ). 46 Eighteen patients with PAH receiving sildenafil 20 mg 3 times daily (tid) were randomised 2:1 to receive riociguat or placebo, with a primary endpoint of change in systolic BP at 12 weeks. No significant effect on BP was observed, and there were no signs of favourable effects on pulmonary haemodynamics or exercise capacity. One patient withdrew due to blurry vision that was considered drug related. The other 17 patients were entered into an LTE study and followed for an average of 305 days. In the LTE, 9 (53%) patients reported serious AEs (SAEs) and 3 patients (18%) died due to SAEs (subdural haematoma following a fall, cardiac arrest and right heart failure), which were considered by the investigator not to be drug related.
| PATENT-1 PATENT-1 was a phase III, 12-week, double-blind, randomised, placebo-controlled study (NCT00810693; Table  1 ). 40 A total of 443 patients with symptomatic PAH entered the study and were randomised to receive placebo (n = 126), riociguat individually adjusted to a maximum of 2. 5 mg tid (n = 254) or a maximum of 1. 5 mg tid (n = 63; exploratory dose). In PATENT-1, of the 254 patients in the riociguat 2. 5 mg tid group, 48% were treatment-naïve and 52% were pretreated with an ERA (44%) or nonintravenous prostanoid (7%). Fifty-two percent of patients in the placebo group were treatment-naïve and 48% were pretreated with an ERA (43%) or nonintravenous prostanoid (5%). Pulmonary Hypertension (LPH) questionnaire. 62 In a post hoc analysis of PATENT-1, riociguat improved the proportion of patients achieving a number of clinically relevant responder thresholds.
| PATENT-2 Of the 405 patients who completed PATENT-1, 396 (98%) enrolled in the LTE PATENT-2 (NCT00863681) in which all patients received open-label riociguat up to a maximum of 2. 5 mg tid. 41, 42 Of the 396 patients entering PATENT-2, 199 (50%) patients were also receiving an ERA or a prostanoid, or both. More than 80% of patients achieved the 2. 5 mg tid maximum dose by Week 8, and 86% remained on this dose at 1 year. The median treatment duration was 139 weeks. At the final data cut-off, 275 patients (69%) remained in the study. Overall, 340 patients (86%) received ≥2 years of riociguat treatment. The study was terminated during the LTE due to increased SAEs and mortality and an unfavourable risk:benefit ratio.