dataesr/scientific-paragraphs-categorization huggingface dataset:
Baseline characteristics of patients with COPD at initiation of triple therapy From the THIN France database, a total of 3134 patients initiated a triple therapy regimen for COPD and met the inclusion and exclusion criteria in the study period. Of these, 485 patients (15. 5%) initiated SITT (table  1 ). In 2019, the first full calendar year in the study period after the introduction of SITT in France, the proportion of patients initiating SITT was 28. 2% (table 1). Overall, the mean age at initiation of triple therapy was 67. 3 years and 44. 2% of the patients were female (table 1). These demographics were similar between MITT and SITT. The most common comorbidity was history of asthma (prevalence of 45. 6% of all patients) and approximately a quarter of patients had a record of asthma in the preceding 12 months.
DISCUSSION This is the first large real-world study on patients with COPD in France who initiated triple therapy since the availability of SITT in 2018. The patients included in this study were similar to other studies conducted in France prior to 2018, in terms of age, sex and certain comorbidities which supports the robustness of this study's findings. 34 35 The patient characteristics were also in line with a study carried out using the UK primary care database, the Clinical Practice Research Datalink. 36 6] [27]  Moreover, the sensitivity analyses provided no evidence that chronic bronchitis or asthma affected the finding that SITT was observed to have a greater persistence than MITT. The results of this study highlight the high disease burden of patients with COPD who require triple therapy, with frequent comorbidities comprising hypertension, depression, diabetes and asthma.
44 This difference was due to the definition of the time denominator in the PDC estimate. Indeed, in Zucchelli study, the time denominator includes the time after the treatment discontinuation, therefore, COPD medication prescribed by a specialist was not captured by the HSD primary care database giving rise to apparent treatment gaps. Another study from Germany (2010-2012), however, provided the estimate of patients with a medical possession ratio "MPR" >80% among persistent users. 45 The observed rate of MPR>80% was 70% and thus more in line with the current study, however, only monotherapy or dual therapy were assessed. The use of either time denominator to define PDC is appropriate although care must be taken when interpreting 'good adherence' and comparing studies. 33 pecifically, our study demonstrated that persistent users of triple therapy tend to obtain dispensation refills at regular intervals and gaps, and that it is relatively rare for patients who initiate triple therapy to spend over 20% of days without treatment.
However, while the PDC has been advocated by the Pharmacy Quality Alliance to quantify adherence in chronic diseases, the PDC remains a relatively crude statistic based on the pattern of dates of refill only and thus cannot account for whether patients Open access use the appropriate inhaler technique to deliver the correct dose. 46 he strength of this study is the use of real-world data from THIN database that is reflective of French clinical practice. 47 Furthermore, prescriptions from differing specialists are obtained via the linkage with pharmacy data which is important given that triple therapy may be expected to be initiated by a specialist. However, certain limitations should be considered when interpreting the results. First, the study relies on the accuracy of recording the diagnosis of COPD with case identification based solely on the use of diagnostic codes as recorded by healthcare professionals.
To better analyse real-world prescription of triple therapy in COPD, we also considered patients recorded with chronic bronchitis, and did not exclude patients with comorbidities including asthma and bronchiectasis. Our sensitivity analyses demonstrated that comorbid asthma and inclusion of chronic bronchitis in the case definition did not impact the observed difference in persistence between SITT and MITT. Another important limitation is that we do not have access to spirometry data such as forced expiratory volume in 1 s (FEV 1 ), FEV 1 /forced vital capacity and postbronchodilator reversibility, a fundamental diagnostic feature for COPD. 6 Thus, there is potential for misclassification of diagnosis. Furthermore, due to low collection in the database, it was not feasible to include eosinophil test results and smoking history which again are important in the history of patients with COPD.
Acknowledgements Additional clinical review was provided by  Dr Henri Leleu  ( Public Health Expertise, France ) and review and editing assistance was provided by  Dr Lucy Tran ,  Dr Victoria Parsons  and  Salman Ramjaun  (EpiFocus, UK). Contributors AC and AM performed data management and statistical analyses and provided the initial draft version under the guidance of NP, CVF, GD and TP. All authors were involved in the interpretation of data. All authors reviewed the manuscript, provided input and have approved the final version. AC is responsible for the overall content as the guarantor. Funding This study was supported by  AstraZeneca, France.
Materials and Methods This study was conducted through a specialized search in the PUBMED database using descriptors and Boolean operators. We included systematic reviews, studies involving experimental animal or human models, review articles, and case reports, provided they were freely available in full text in the English language. The search for articles was conducted using the following descriptors: "endocannabinoid system", "endocannabinoid and inflammation", "endocannabinoid and immune system", "endocannabinoid and receptors", "Palmitoylethanolamide", "Palmitoylethanolamide and Inflammation", "Palmitoylethanolamide and immunomodulator", "Palmitoylethanolamide and receptors", without considering the publication year. The literature search was conducted between 2022 (October-November) and 2023 (April-May), resulting in a total of 216 studies.
Requirements for FRMs for S3 Topography Products This work explores the opportunities to provide FRM datasets for the calibration and validation of surface topography thematic data products for inland waters, land ice, and sea ice. First, in this section, we consider what is required for an in situ or airborne dataset to be considered FRM and present the concept of FRM approaches for different surfaces. We also present how such datasets can be made available to a broad user community through a central data hub.
Furthermore, FRMs themselves should be validated through comparisons between them, or between different instruments at an FRM site. Note that the term 'FRM' can be used both for the measurements (data points) themselves, and for the infrastructure established (i. e. , the instruments and processing chain). It can also be used both for measurements that support the 'fundamental data record' from the satellite (level 1 or early level 2 data) and measurements that support 'thematic data products. ' In this paper, we consider Sentinel-3 STM thematic data products, as described in Section 2. 3. 2.
Monte Carlo methods can cope with more sophisticated measurement functions; however, they are computationally expensive and may not be possible for very large datasets. Finally, in the fifth step, the uncertainty information should be stored for long-term data preservation purposes, so that future scientists can understand the detail of what has occurred and disseminate it, usually in summary form, for today's users. Traditionally, comparisons have been used for approach (a), i. e. , to monitor whether satellite and reference measurements agree within the stated satellite 'absolute accuracy' requirements, a term that is intended to specify an acceptable bias to agreed references. Approach (b) relies on the (usually unjustified) assumption that non-satellite measurements have negligible uncertainty compared to satellite observations and that any transfer or representation uncertainty in converting from the non-satellite measurand to the satellite measurand is also negligible.
Satellite Thematic Data Product (TDP) A metrological approach starts with defining the measurand and, because it is the purpose of an FRM to provide validation of the satellite data product, a metrological approach to an FRM must start by understanding the satellite's measurand. Satellite datasets are processed through several stages to obtain a series of different measurands, usually moving from a raw measured signal up to a geophysical product of interest. There can be benefits of providing an FRM comparison for the different satellite measurands at different stages of this processing. The most basic product provided by the European Space Agency (ESA) (as with other space agencies) is the level 1 dataset  [12] , known by the ESA as the 'fundamental data record' (FDR) if it follows QA4EO principles itself  [13].
This approach has significant limits, especially where there are multi-peak echoes, and physical-based retracking models are under development. These physical-based models consider the specular nature  [17]  of the returned signal over small inland water bodies, and/or the penetration in the media (over land ice). Whatever retracker is used, it is also important to note that the satellite track varies from orbit to orbit. Over a large lake, this is dealt with by defining a virtual station as a larger area over which the lake surface is considered an equipotential surface and therefore different tracks can be combined. Over rivers, a choice can be made between creating a similar virtual station and correcting individual tracks to a particular position using a model of the height variation in the river between the tracks and the virtual station, or by providing the specific track position as part of the satellite dataset.
g. ,  [41, 42] ) or to monitor changes in surface elevation over time (e. g. ,  [43, 44] ). For DSM applications, a widespread coverage of data is needed over a period short enough that the snow/ice surface will not have changed significantly. For surface elevation changes, it is important to monitor the same locations repeatedly over long time periods. Radar altimetry data over land ice can be hard to interpret when there are complex surface variations within the signal footprint. Over such surfaces, the returned waveforms can have a complex set of peaks and be affected by penetration in the medium. Independent reference measurements can be collected in airborne or snow vehicle campaigns or from semi-permanent stations on the ice. Such stations can be sensitive to drifting snow and other temporary changes, and need to be precisely georeferenced, accounting for topography.
Over lakes, the FRM comparison is performed against a satellite product measurand that is the average water height within the virtual station. Campaign measurements (from a UAV or a raft behind a boat) can be used to determine an FRM value for the average height within the virtual station at the time of the campaign. Data from a fixed station can be used to provide a time series of this value, where the fixed station is either within the virtual station or close by. Over a river, the FRM needs to be translated to the location of the satellite overpass or a defined virtual station. This spatial transfer must compensate for the river slope, which has been previously determined through a UAV or boat campaign measurement along the relevant stretch of river. Such campaigns must be performed for different river conditions at different times of year.
St3TART Project Approach The first phase of the St3TART project had the aim of preparing a roadmap for operational provision of FRMs for the inland water, sea ice, and land ice products from Sentinel-3. This involved reviewing existing independent (non-satellite) measurements and measurement campaigns through a literature review, installing instruments, and/or performing prototype measurement campaigns, which included considering the processing of data from an FRM and what transformations are required to convert the FRM measurement into the measurand of the Sentinel-3 satellite, and performing the initial stages of an uncertainty budget, including identifying key sources of uncertainty and showing the metrological traceability of the observations. The results of the literature reviews and prototype measurements were used in each case to categorise different FRM options.
Because each surface had different scientific and practical challenges, the different teams emphasised these different aspects in different ways. The inland water team focused on establishing a small number of prototype 'supersites' on European rivers (see Section 4. 1) with instruments and field campaigns to correct for river topography in comparison with the satellite observations. The sea ice team focused on field campaigns to demonstrate the ability of drone-borne lidar instruments in the harsh Arctic environment. The land ice team collated data from existing instrumentation and previous field campaigns to make a prototype quantitative uncertainty assessment. All of these efforts should be seen as the first step towards operational FRM provision and considerable additional work is needed.
Disseminating FRM to Users It is important to ensure that FRM measurements, and their associated documentation, providing traceability and uncertainty analysis, are available to the Cal/Val community in a free and accessible manner. To enable this to happen, a website has been established, with a user-friendly interface, permitting sharing FRM measurements with the community: the FRM Data Hub, which is accessible to the public at the following URL: https://frmdatahub. noveltis. fr/ (accessed on 3 rd October 2023). All users can see available data, but to download data, registration is needed. To facilitate the integration of new datasets in the database, a format specification document has been produced, describing the filename convention and the metadata of the datasets. The chosen format is NetCDF, as NetCDF files are ubiquitous in Earth sciences and therefore fully supported by a wide array of software solutions (QGIS, Panoply, ncview, nco, cdo, etc.
) and libraries in most common languages (Fortran, C/C++, Python, Java, etc. ). In addition, the format specification document lists the global attributes and the variable attributes that are needed or optional for the FRM Data Hub. Through the website, a user can browse data, filter data by surface type, time period, geographic area, type of sensor, or provider, and then select measurements and visualise the associated metadata, before downloading any dataset of interest. The format specification document also specifies the way to distribute uncertainty variables: there shall be at least one uncertainty variable per variable, with an uncertainty value per observation point. Ideally, the different sources of uncertainties shall be distinguished. To take this into account, 3 uncertainty variables can be defined: • variable_standard_name_uncertainty_systematic: to cover uncertainties associated with effects that lead to errors that are common from observation to observation.
• variable_standard_name_uncertainty_structural: to cover uncertainties associated with errors that vary in ways between 'systematic' and 'random'. The variable attributes of the uncertainty variables shall give a link towards a document describing how uncertainties have been calculated. It is also important to ensure the "operational aspect" of data provision. The Sentinel-3 Land STM Mission Performance Cluster (MPC) has requirements on the timeliness of measurements, e. g. , validation data shall be available within 2 days after the measurement for hydrology Short Time Critical (STC) products. This means that some processes must be defined to operationalise the production and distribution of FRMs. The FRM Data Hub shall then offer interfaces such as FTP or API, to enable providers to push their FRM data automatically to users as soon as they are produced.
The airborne team overflew two Sentinel-3A satellite tracks and one Sentinel-3B satellite track, where the Sentinel-3B track was the same track under which the Ice-T buoy was deployed. The campaigns have demonstrated the capability to use a lidar-and camera-equipped drone system in Arctic conditions with temperatures as low as -13 • C on both land and ship  [59]. The total freeboard at the interface between sea ice and water was computed for the data collected by the lidar altimeter, together with surface classification using the camera to take pictures of the observed surface. The campaigns further demonstrated the use of miniature radars to estimate snow depth with an accuracy of the order of a couple of cm from an autonomous drifting Ice-T buoy. Finally, the campaigns used a variety of sensors and platforms for the validation of Sentinel-3 over sea ice, i.
Towards Metrological Uncertainty for Land Ice Products An initial uncertainty assessment was performed, identifying and quantifying the key sources of uncertainty in the measurements. This assessment considered the error correlation structures (i. e. , systematic and random effects) between different observation stations in the same region and temporarily between measurements at different times. Uncertainties in FRM data from fixed stations will relate to the GNSS, the sonic or laser rangers, and the spatial transfer performed with the DSM. The Cal/Val approach will also need to assess uncertainty in the POCA location and in the interpretation of the waveform, e. g. , using electromagnetic models  [79]. The PPP method for GNSS measurements avoids the need for a base station and the first-order ionospheric delay is removed through the combination of dual-frequency GNSS measurements.
Due to the remoteness and resource-intensive logistics, potential airborne FRM campaigns in Antarctica should be coordinated with other air-based projects as an add-on or side activity, for example, through the SCAR initiative RINGS  [85]. In summary, we have the following recommendations for in situ campaigns: a. Annual or biannual campaigns of 1-2 weeks in the Arctic (Greenland and/or Arctic ice caps) and Antarctica (coastal region) in conjunction with FRM station servicing or established in situ monitoring programmes. b. Snow vehicle surveys with kinematic GNSS along targeted Sentinel-3 tracks within periods of one month time separation. c. Auxiliary data should be collected on snow properties (stratigraphy/layers, grain size, density, and temperature) from GPR, probing, snow pits, or shallow cores.
Satellite Data 2. 3. 1. 231 Purpose and Types of ComparisonsThe purpose of the FRM is to support the calibration and validation of the satellite altimeter observational datasets by providing non-satellite (in situ and ground-based aircraft and shipborne remote sensing techniques) references for comparisons. From a conceptual perspective, the results of such comparisons could be interpreted in three different ways: (a) To validate that observation values are within an expected tolerance; (b) To evaluate the uncertainty associated with the satellite observation; (c) To validate independently determined uncertainties.
Methods COREVIH IDF Est is a group of 27 clinical centers located in the Paris area, with approximately 11,000 HIV-infected patients on follow-up in 2014. All centers use the computerized Nadis ® database as an electronic health record (EHR) for patient follow-up and care. Demographic data, clinical outcomes, ART history and laboratory tests (CD4 T cell count and HIV-1 RNA) are collected at each patient's visit by the clinician, the rate of completion is monitored and is > 90%. In the EHR, the reason for any ART change has to be reported to be able to print the patient's prescription, so the reason for the switch is accurately reported.
Patients We conducted a retrospective multicenter observational cohort study within the COREVIH IDF Est clinical centers enrolling ART-experienced patients. Eligible patients were adult patients (≥ 18 years old) with controlled HIV-1 infection on any stable ART regimen (no limit on the previous number of regimens) who switched to E/C/F/TDF between February 2014 (date of approval of E/C/F/TDF in France) and August 2015. Controlled HIV-1 infection was defined by plasma HIV-1 RNA < 50 copies/mL without ART modification in the previous 12 months. Before enrollment in the Nadis ® database, it is required that patients sign an informed consent form which was approved by the Paris Saint-Louis ethics committee and Commission Nationale Informatique et Libertés (CNIL) allowing the use of patients' data for non-interventional studies without the need for further consent in accordance with French regulations (CNIL, number 1,171,457).
Study procedures Our primary objective was to assess the efficacy and tolerance of the switch to E/C/F/TDF measured by determination at W48 of the proportion of patients still on E/C/F/TDF and with plasma HIV-1 RNA < 50 copies/mL. At baseline (date of the switch), the following data were extracted: date of HIV infection, date of first ART, number of previous ART and type of regimen, nadir CD4 T cell count or CD4 T cell count at ART initiation, CD4 T cell count (within 6 months before the switch), the reason for switching to E/C/F/TDF, creatinine levels and estimated Glomerular filtration rate (eGFR) using MDRD, history of prior virologic failure and previous genotypes. If the genotypes were not available in the database for patients who failed (at baseline and at virological failure), we went back to the paper chart or contacted the virology laboratory to collect the information.
Statistical analysis The primary analysis was an intent-to-treat (ITT) analysis using the FDA snapshot algorithm at W48. Patients were classified in the following categories: (i) virological success defined as plasma viral load < 50 copies/ml at W48 (time window W36-W72) while on E/C/F/TDF; (ii) virologic failure: plasma viral load ≥ 50 copies/ml at any visit after the switch; (iii) no data: missing data or lost to follow-up and discontinuation of E/C/F/TDF for reasons other than virologic failure at a prior visit. Data are presented as median with IQR for continuous variables and frequencies with percentages for qualitative variables. Categorical variables were compared using Fisher's exact tests while quantitative variables were compared using Wilcoxon signed-rank tests. Comparisons between patients with virological failure and virological success were performed to assess if the following baseline risks factors were associated with virological failure: age, gender, mode of HIV infection acquisition, use of INSTI or PI/r before switch, time since HIV infection diagnosis, duration of ART, duration of viral suppression before the switch, nadir and baseline CD4 T cell counts, creatinine plasma level, previous resistance-associated mutations (RAM) to at least one drug of the regimen.
Safety results (data not shown) There was a significant change in creatinine levels between the switch and W48 but not clinically meaningful: the median creatinine level was 79 µmol/L (IQR 70-89) at baseline and 85 (IQR 75-96) at W48  (p < 0. 001); data not shown; among the 382 patients, 38 and 57 creatinine values were missing at baseline and W48 respectively. All patients who discontinued E/C/F/TDF between the switch and W48 were analyzed to describe reasons for treatment discontinuation and identify clinically significant adverse events leading to treatment discontinuation. Among the 43 treatment discontinuations, 23/43 (54. 0%) were related to mild adverse events: 10 gastro-intestinal, three renal adverse events and two mild transaminase elevation; other various adverse events were seen in eight patients (nightmares in two, fatigue or muscular pain in two, tachycardia in one and reason was not specified for three patients).