dataesr/scientific-paragraphs-categorization huggingface dataset:
2015)  includes the assessment of the environmental impact of a broad range of technologies at the 'whole-of-system' levelurban water system. Therefore, the change in the preference of the assessment methodologies would be better explained if the assessment scale is also known. In case that the assessment scale coincides with the application scale of the technologies, then the reason behind this change in preferences is clear. Moreover, on-ground projects at macro scale are more focused on the economic aspect of their technologies, as 40% of these projects use CBA. Some useful ICT tools were used and reported in these projects too. They can be grouped as (i) data or databases (including GIS for 3D visualization, weather gridded, energy carbon footprint, data mining sensors, cloud-based geo-referenced system for storing & communicating the acquired water quality information, or websites containing data for mapping of pilot areas), (ii) models (for temporary housing, climate adaptation, water management strategies or for gamming in some apps), (iii) monitoring and control systems (for online greenhouse gases emission in wastewater treatment plants based on wireless sensor networks, for ecosystem services adapted to urban areas, for real-time flood mitigation, for waterloops or for automation and process control in general), (iv) decision suport sytems to selectamong alternatives or to identify potential pollutant sources & predict the effectiveness of mitigation measures.
The time-frequency distribution of a signal provides information about how the spectral content of a signal evolves with time, thus providing an ideal tool to dissect, analyze, and interpret nonstationary signals  [10]. Contrary to classical methods, the need of a timefrequency representation (TFR) is stemmed from the inadequacy of either time domain or frequency domain analysis to fully describe the nature of nonstationary signals  [10]. In literature, there are numerous methods to obtain energy density as a function of time and frequency simultaneously as the short-time Fourier transform (STFT), Hilbert-Huang transform (HHT), and wavelet transform (WT)  [10] [11] [12]. In this study, the scaling properties of PM10 data are firstly analyzed, and then the TFR is investigated. In order to highlight the performance of the Hilbert space, an analysis of PM10 data was also performed in the Fourier space.
Experimental data Guadeloupe archipelago is a French West Indies island located in the middle of the Caribbean basin, i. e. , 16. 25°N latitude and 61. 58°W longitude, which experiences a tropical and humid climate  [13, 14]. The time series analyzed here belong to Guadeloupe air quality network which is managed by the Gwad'Air agency (http:// www. gwadair. fr/). PM10 concentrations are measured at Pointe-à-Pitre (16. 2422°N 61. 5414°W) using the Thermo Scientific tapered element oscillating microbalance (TEOM) models 1400ab and 1400-FDMS. Hourly PM10 concentrations were sampled during the period from 1 January 2005 to 31 December 2010. We processed these data into daily average concentrations. In total, there are 2150 daily averaged data points available continuously for 6 years. Figure  1  displays PM10 daily signal illustrating huge fluctuations and thus indicating a strong variability.
Conclusion In this paper, we investigated scaling and time-frequency properties of PM10 data in Hilbert frame. The performances obtained in the Hilbert space are compared with those achieved in the Fourier space. Firstly, with the Hilbert spectral analysis (HSA), a power law behavior is clearly observed on the frequency range 2:09 Â 10 À7 ⩽f ⩽4:57 Â10 À5 Hz which corresponds to time scales 6:1hours⩽T⩽55:4 days with an estimated spectral exponent β h =1. 02AE 0. 10. As HSA methodology has a very local ability in both physical and spectral spaces, the influence of intermittent dust events with huge fluctuations is included in the amplitude-frequency space which is not the case in Fourier spectrum. Thereafter, PM10 data are illustrated in time-frequency representations with the Hilbert spectrum and spectrogram.
The results provide the evidence that HS-based TFR performs better than SPEC. The higher resolution in TFR offers better fluctuations of PM10 energy for f < 1μ Hz. This is due to the fact that it is impossible to increase the TF resolution at the desired levelinSPEC. ThemajorassetofHSisthatthe time resolution can be as precise as the sampling period and the frequency resolution depends on the choice up to the Nyquist limit. In addition, contrary to SPEC which introduces a noticeable amount of cross-spectral energy terms during the use of window function with overlapping, HS is fully adaptive to datasets due to the decomposition of the signals. These first results suggest a substantial possibility to perform a profound dynamical analysis of PM10 concentrations for the Caribbean area in order to quantify the origin and the threshold pollution.
In a retrospective database review of patients who experienced an asymptomatic LVEF decline to <50%, there was no significant difference in LVEF at follow-up between patients who continued versus those who interrupted trastuzumab therapy. 40  Furthermore, the prospective SAFE-HEaRt study demonstrated that interruption of HER2 therapies may not be necessary in patients with cardiac dysfunction (i. e. , LVEF 40-49% and no HF symptoms). 41  Patients were closely monitored and received HF therapies, and 90% were able to complete the planned course of therapy without a cardiac event or worsening of LVEF. When considering interruption of trastuzumab, the risk-benefit assessment of prognosis from cancer versus HF should be discussed with the multidisciplinary team. 23.
g. , oncologists, cardiologists, and geriatricians), primary care physicians, industry, governments, and the general population. The need for increased awareness and education also extends to the patients themselves, since many cancer survivors do not know they are at increased risk of CV morbidity and mortality as a result of their treatment. Advocacy Registries, such as the EURObservational Registry Programme (EORP) also play an important role in identifying long-term CV outcomes, especially those that are uncommon. The EORP is a registry for CV and rare diseases. It uses an international protocol and data sharing with the medical community, regulatory bodies, and healthcare stakeholders. This allows for comparison of data on the management of major CV diseases globally, which can help improve patient care.
Acknowledgements This article was generated from discussions during a Cardiovascular Round Table (CRT) workshop organised in January 2020 by the  European Society of Cardiology (ESC). The ESC CRT is a strategic forum for high-level dialogue between 20 industry companies (pharmaceutical, devices and diagnostics) and the ESC leadership to identify and discuss key strategic issues for the future of cardiovascular health in Europe. The authors would like to thank  Pauline Lavigne  and  Steven Portelance  (unaffiliated, supported by the ESC) for contributions to writing, and editing the manuscript. PF was supported by the  National Research, Development and Innovation Office of Hungary  ( National Heart Program   NVKP 16-1-2016-0017 ) and by the  Higher Education Institutional Excellence Program   of the Ministry of Human Capacities in Hungary , within the framework of the  Therapeutic Development thematic program  of the  Semmelweis University.
Acknowledgements The authors thank  M. Burghammer  ( ID13 beamline, ESRF ) for experimental support,  D. Gebauer  and  M. Vogt  ( University of Siegen ) for sample holders and for wire bonding,  U. Scherf  ( Bergische Universität Wuppertal ) for providing polymer materials and  O. Thomas  ( IM2NP, University of Aix-Marseille ) for fruitful discussion. This work was supported by the  Bundesministerium für Bildung und Forschung , project no. :  05K13PS4  and the  Volkswagen Foundation , project no. :  96 697.
Observational data To compare the mixed layer depth (MLD) from the models to observations, the typical variable used to represent ocean convection depth, we use data from ARGO-profiles  (Holte et al. 2017 ) provided on a 1° grid. In the ARGO-data, the de Boyer  Montégut et al. (2004)  variable density threshold is used to calculate the mixed layer depth. Two different ARGO data sets of the mixed layer depth are used in this study: first, the climatological mean MLD in each grid point in March in the years 2000-2015; second, the maximum (mean over the two largest observed values in the period 2000-2015) MLD in each grid-point. Note that in many grid-points only a few ARGO-profiles exist and in some no profiles at all. Further, ARGOfloats generally sample to a depth of 2000m, thus MLD extending below 2000m are not captured.
In addition, the observational time period is short given the long time scales of variability in deep water formation. Thus, the ARGOobservations do only provide an estimate of the observed MLD. We use turbulent latent and sensible heat fluxes from the global ocean-surface heat flux products  developed by the Objectively Analyzed air-sea Heat Fluxes project at the Woods Hole Oceanographic Institution (WHOI-OAFlux) to evaluate the surface heat fluxes in our models. We use monthly means of the WHOI-OAFlux data on a 1° grid from 1958 onwards.
Although intermittent deep convection can occur in the Irminger Sea as well, we focus here only on the two regions with deepest convection. We use monthly mean values of the March MLD of the model simulations to calculate the DMV. Note, that short convection episodes that exceed z crit might thus be missed. We also calculate the DMV from the ARGO data as comparison to the model results. We infilled grid-points with missing data in the ARGO-data by interpolating the nearest neighbours. This and the short time series of the ARGO-data lead to uncertainties in the calculations of the DMV from ARGO and therefore it only provides a rough estimate for the real world. As an additional comparison, we also calculate the DMV based on critical depths of 0m, thus considering the full mixed layer. For correlations, we calculate the Pearson correlation coefficient (r).
org/10. 5194/os-2020-41 Preprint. Discussion started: 13 May 2020 c Author(s) 2020. CC BY 4. 0 License. over 1950-2014 with ARGO-data from 2000-2015. As we will discuss later more in detail, some of the models show a weakening of the convection with time. Thus comparing the same time period in models and ARGO would slightly reduce the overestimation of MLD compared to ARGO in these models. The MLD deepens with increasing ocean resolution in all models, except for AWI-CM-1-0. However, the models showing deepening MLDs are not fully independent, because they share NEMO as the ocean component, whereas AWI-CM-1-0 has FESOM as ocean component. On the other hand, even the global models with NEMO3. 6 as ocean component (compare HadGEM3-GC31, CNRM-CM6. 1, CMCC-CM2 and EC-Earth3P) differ considerably.
Acknowledgements This work has been funded by  PRIMAVERA  project, which is funded by the  European Union 's  Horizon 2020 programme , Grant Agreement no. 641727PRIMAVERA. The global ocean heat flux and evaporation products were provided by the  WHOI OAFlux  project (http://oaflux. whoi. edu)funded by the  NOAA   Climate Observations and Monitoring (COM) program.
Analysis of the TPMT gene sequence, performed in populations of various ethnic origins, has confirmed the genetic origin of the TPMT activity polymorphism and elucidated its molecular mechanisms  [55] , and identified more than forty allelic variants of the TPMT gene  [56]. The wild type TPMT * 1/TPMT * 1 genotype is consistent with the normal TPMT enzymatic activity. Standard doses of thiopurine drugs are less likely to be toxic in individuals with this genotype. It is retained that the heterozygotes with 1 wild-type allele and 1 variant (such as the TPMT * 1/* 2, TPMT * 1/TPMT * 1/* 3A, TPMT * 1/* 3B, TPMT * 1/* 3C, TPMT genotypes * 1/* 8 and TPMT * 1/* 16) have an intermediate TPMT activity, have an increased risk of haematological toxicity, and may require a lower dosage (Figure  2 ). The star alleles described are referenced in the TPMT nomenclature committee database (https://liu.
se/en/research/tpmt-nomenclature-committee) which lists the TPMT variants. The Pharmacogenic Variation Consortium (PharmVar) continues to update new alleles to provide the clinical and research communities of a repository and standardized nomenclature of pharmacogene variation. genotype. It is retained that the heterozygotes with 1 wild-type allele and 1 variant (such as the TPMT * 1 / * 2, TPMT * 1 / TPMT * 1 / * 3A, TPMT * 1 / * 3B, TPMT * 1 / * 3C, TPMT genotypes * 1 / * 8 and TPMT * 1 / * 16) have an intermediate TPMT activity, have an increased risk of haematological toxicity, and may require a lower dosage (Figure  2 ). The star alleles described are referenced in the TPMT nomenclature committee database (https://liu. se/en/research/tpmt-nomenclature-committee) which lists the TPMT variants.
Measuring the enzyme activity remains a standard but this test is unfortunately unavailable in many centers. If necessary, low doses of azathioprine can be administered, which can be increased if the drug is tolerated. However, it should be noted that profound myelosuppression in TPMT-deficient patients is not always avoidable and the majority of cases of myelosuppression associated with thiopurines appear in individuals who fall into the normal range of TPMT activity. Genotyping can provide a useful adjunct in these situations. Here, we have reported a new clinically important TPMT * 16 mutation in a young patient who received the thiopurine treatment. This molecular alteration has never been described to our knowledge and is not referenced in genetic databases such as ClinVar, Alamut, or Ensembl.
Acknowledgement The authors wish to thank  Maxim Barkov  and  Valentí Bosch-Ramon  for stimulating discussions, and the organizers for a wonderful conference. M. Z. gratefully acknowledges funding by the  German Ministry for Education and Research (BMBF)  through grant  05A17PC3. The work of M. B. is supported through the  South African Research Chair Initiative (SARChI)  of the  South African Department of Science and Technology (DST)  and  National Research Foundation. 4 F. J. and S. J. W. acknowledge support by the  German Ministry for Education and Research (BMBF)  through  Verbundforschung Astroteilchenphysik  grant  05A11VH2. J. -P. L. gratefully acknowledges  CC-IN2P3  (cc. in2p3. fr)for providing a significant amount of the computing resources and services needed for this work. A. W.
Future Perspectives for Advanced/Metastatic PanNETs Future perspectives for advanced/metastatic panNETs are summarized in Table  1. Strategy issues are raised with clinical trials comparing TEMCAP versus streptozotocin + 5-fluorouracil (NCT03351296) and TEMCAP versus capecitabine + dacarbazine (NCT03279601). The strategy of using the targeted therapy everolimus after treating with alkylating agents, versus before alkylating agents, is currently being evaluated (NCT02246127). Other targeted therapies such as cabozantinib (NCT03375320) or lenvatinib (NCT03950609) are also being evaluated. We can also note the place of trials on immunotherapy alone or in combination with certain targeted therapies.
Currently, there is no evidence to support the use of a triplet chemotherapy: a phase II trial tested the addition of paclitaxel to cisplatin-etoposide in 78 patients, with a high ORR (53%) but no benefit on OS compared with the standard cisplatin-etoposide regimen and with a greater toxicity  [66]. After progression under first-line treatment, little data is available on second and third-line therapies. Small retrospective series have shown the feasibility of treatment with CAPOX or FOLFOX, with an ORR between 23% and 29% and a mOS of 10 months  [29, 67, 68]. FOLFIRI regimen was evaluated in a retrospective study on 19 patients who progressed on etoposide-platinum  [69]. The ORR was 31%, mPFS was four months and mOS was 18 months, compared to 6. 8 months without treatment. Temozolomide, alone or in combination with capecitabine and bevacizumab was evaluated in 25 patients with poorly differentiated NECs, with 33% ORR and an OS of 22 months [70].
Future Perspectives in PanNECs Table  2  summarizes selected ongoing clinical trials on medical treatments in advanced/metastatic pNECs. The doublet cisplatin + etoposide is being challenged by TEMCAP (NCT02595424) and by other associations such as cisplatin + everolimus (NCT02695459) or cisplatin + irinotecan (NCT03963193). In a second-line setting, FOLFIRI is being challenged by the association TEMCAP (NCT03387592) and by the association FOLFIRI + bevacizumab (NCT02820857). Some targeted therapies such as everolimus are also being tested in second line (NCT02113800) or as a maintenance treatment (NCT02687958). Immunotherapy is also being evaluated, as monotherapy or in combination with chemotherapy or targeted therapy.
Statistical considerations AEs reported after administration of the study treatment were classified by system organ classes and preferred terms using the MedDRA dictionary. The number and proportion (%) of patients experiencing each AE was tabulated. The AEs were graded by severity and causality. PK parameters were analysed after logarithm transformation, and 95% confidence interval for the geometric mean were calculated. Descriptive statistics for continuous variables were as follows: number of observations (N), mean (MEAN), standard deviation (SD), minimum (MIN), median, and maximum (MAX). In PK variables also geometric mean (GMEAN) and coefficient of variation (CV) was calculated. In log-normal distribution, the formula CV = 100 Â square root (exp [variance of logtransformed data] À 1) was used: CV ¼ 100 Â ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi exp varianceoflogÀtransformeddata À 1 q 3.
Patient characteristics and study drug exposure In total, 23 patients with CRPC were enrolled into the study between 17 February 2015 and 22 June 2016, at four centres: three into the 50 mg twice daily, three into the 100 mg twice daily, six into the 200 mg twice daily, seven into the 300 mg twice daily, and four into the 500 mg twice daily dose level groups. The cut-off date for the data included in this report was 21 December 2017. Baseline demographics and disease characteristics are shown in Table  1. Median time on treatment was 12. 1 wk (0. 3-71. 7 wk). Nine (39%) patients continued treatment for more than 12 wk, and four (17%) were still receiving treatment at the time of data cut-off.
METHODS The clinical practice principles in this Perspective are based on field experience of providing direct care for people with RR/MDR-TB, engaging with TB programs, and listening to the views of TB-affected communities and civil society. Collectively, the authors have more than five decades experience working on RR/MDR-TB, and have worked extensively in the field since newer drugs and shorter regimens became available, supporting more than 30 countries during this time period. In addition to our robust, direct field experience, several of us have provided evidence for and served as observers and voting members at the 2016, 2018, and 2019 WHO Guideline Development Group Meetings. To ensure our coverage was comprehensive, we carried out a literature review using OVID, MedLINE and PubMED databases from January 1, 2016 to February 1, 2020 using the terms: 'rifampicin-resistant tuberculosis' or 'drug-resistant tuberculosis' with 'bedaquiline', 'delamanid', 'shorter', 'World Health Organization' or 'operational research'.
Its limitations include the continued use of PZA, EMB, and INH which have unclear efficacy in the context of treatment for RR/MDR-TB, increase the pill burden and are associated with adverse events. The combined use of INH and LZD-both of which can cause peripheral neuropathy-is especially problematic, most notably in other populations with risk factors for neuropathy, including people living with diabetes, people who use alcohol, and people living with HIV, although this risk could be mitigated by using LZD for a shorter duration (i. e. , 8 weeks or less). 2) One of the 'endTB' regimens. The endTB project is funded by Unitaid and carried out by the humanitarian organizations Interactive Research & Development, Médecins Sans Frontières, and Partners In Health. It has an observational study component  22  and two randomized clinical trials: endTB (NCT02754765) and endTB-Q (NCT03896685).
Monitoring for adverse events is essential when BDQ and/or DLM are given for longer than 24 weeks to continue to build the database on the safety and efficacy of this practice. Some countries may consider using the BPaL regimen under operational research conditions (see section on principles for operational research) for certain patients with FQ-resistant RR/MDR-TB and among those for whom designing an effective regimen based on existing WHO recommendations is not possible. As noted above, the BPaL regimen consisting of 6-9 months of BDQ, higher-dose LZD (1200 mg daily) and the novel nitroimidazole PTM was recently approved under the 'Limited Population Pathway for Antibacterial and Antifungal Agents' by the FDA. 31  This is a new regulatory approval pathway that is intended for treatment of diseases associated with high mortality and for which limited therapeutic options exist.
In other instances, LZD was completely discontinued (usually after 2 months) and the remainder of the regimen completed with just two drugs-BDQ and PTM. If either BDQ or PTM needs to be discontinued, however, the patient should be transitioned to a 'salvage' or 'rescue' regimen in some instances. The ongoing 'Ze-Nix' trial (NCT03086486) will assess different doses of LZD to see if lower rates of adverse drug reactions can be achieved. 37 Results of this study are expected in 2020. It is the opinion of the authors that countries may also consider using DLM as the nitroimidazole of choice in a BDQ and LZD-containing regimen (as is being done in the endTB study, the endTB-Q study, the BEAT TB study in South Africa, NCT04062201 and the SMART KIDS IMPAACT 2020 study); however, there have been no head-to-head comparisons of DLM and PTM to assess the comparative efficacy and safety of these two nitroimidazoles, including in the context of the BPaL regimen.
R E ´S U M E Ĺes diagnostics rapides, les nouveaux médicaments, les médicaments recyclés et les protocoles plus courts ont radicalement altéré le paysage du traitement des formes de TB résistantes à la rifampicine et multirésistantes (RR/MDR-TB). Il y a de nombreux essais cliniques en cours visant à créer une solide base de données pour guider le traitement de la RR/MDR-TB ; les études d'observation ainsi que les données des programmes ont contribu é à faire progresser le domaine du traitement. En décembre 2019, l'OMS a publié son deuxi ème « Rapid Communication » relatif à la prise en charge de la RR-TB ; l'OMS a r éit ér é sa recommandation ant érieure-que la majorit é des personnes atteintes de RR/MDR-TB re çoive des protocoles de traitement uniquement oraux-et autorise maintenant les protocoles spécifiques de plus courte dur ée pour être utilis és également par les programmes.