dataesr/scientific-paragraphs-categorization huggingface dataset:
7 The SEA-ICEMR staff has been actively involved in the development, maintenance, and improvement of this system. The eMIS allows local malaria centers to send individual malaria data directly to the centralized database  8  while the data visualization platform assists prompt decision-making for national-level policymakers and local control practitioners. For example, the eMIS allowed easy extraction and visualization of villagelevel malaria incidences in previous years and selection of high vivax incidence villages in Yala and Narathiwas Provinces to implement a pilot project of primaquine (PQ) MDA in 2019. We also used the eMIS to browse 10-year malaria incidence data to identify the hotspot malaria villages on the Thailand-Myanmar border to study how population movement influences malaria transmission using a mobile tracking application.
To better monitor the progress in malaria control, the SEA-ICEMR program has installed an integrated malaria surveillance system, incorporating cross-sectional surveys, active case detection, and passive case detection (PCD), to actively follow the malaria epidemiology in multiple sentinel sites along the international borders. ] [11]  In contrast to the aggregated data usually collected by the national malaria databases, data collected from the ICEMR projects are based at the individual level. Case reports on the personal level have been used to identify high-risk populations and hotspot areas. Data generated from the program have been regularly shared with the local malaria control centers to identify urgent problems such as outbreaks and fine-tune their targeted control strategy. At the China-Myanmar border, our surveillance data have guided the local health bureaus to implement intensified vector control to suppress vivax malaria outbreaks.
Acknowledgments: We would like to thank the staff at our malaria research stations along the international borders of Thailand, China, and  Myanmar  for technical support. We also thank the patients and their guardians for participating in clinical studies. Financial support: The  Southeast Asian International Center of Excellence for Malaria Research  was supported by the  National Institute of Allergy and Infectious Diseases (NIAID) ,  NIH, USA  ( U19AI089672 ).
METHODS The present study conforms to the principles of the Declaration of Helsinki, and all authors guarantee the integrity of data from their respective institutions. Approval from a local ethics committee or internal review board was obtained at each participating center. Clinical HF was considered on the basis of current guidelines, at a stage at which clinical symptoms are apparent and may be accompanied by signs. 15 A C C : C A R D I O O N C O L O G Y , V O L. 4 , N O. 4 , 2 0 2 2 Gonzalez-Lopez et al N O V E M B E R 2 0 2 2 : 4 4 2 -4 5 4 ATTR-CM Without Clinical HF was the cutoff value required for inclusion of symptomatic patients in the tafamidis clinical trial. 13 In all cases, genetic testing confirmed the absence or presence of mutations in the TTR gene. Overall survival in 118 patients with transthyretin amyloid cardiomyopathy without heart failure symptoms at initial evaluation was 96.
COHORT COMPOSITION. This was a multicenter, longitudinal cohort study comprising consecutive patients with ATTR-CM without HF symptoms evaluated at 4 European (Hospital Universitario Puerta de Hierro Majadahonda, Spain; Fondazione IRCCS Policlinico S. Matteo, Italy; University of Bologna and S. Orsola-Malpighi Hospital, Italy; and University Hospital Henri Mondor, France) and 2 U. S. (Columbia University Irving Medical Center, New York, New York; variant transthyretin amyloidosis (ATTR-v) or wild-type transthyretin amyloidosis (ATTR-wt) with ATTR-CM and without HF symptoms or histories of HF symptoms at initial evaluation were retrospectively identified from existing databases.
acoramidis) are currently being tested in randomized controlled trials for ATTR-CM (NCT03997383, NCT04153149, NCT04136171, and NCT03860935). Although early diagnosis of a progressive fatal disease could potentially offer a number of therapeutic opportunities, the tafamidis ATTR-CM trial and all the ongoing ATTR-CM trials included only patients with ATTR-CM with HF symptoms. To complicate things further, ATTR-CM commonly affects elderly individuals, who could be affected by many other diseases, which might influence decisions about the initiation of long-term and expensive treatments, despite the fact that the Food and Drug Administration and European Medicines Agency have authorized tafamidis for the treatment of ATTR-CMwithout restricting it to patients with overt HF. 20  Given the substantial number of events found during follow-up among patients with ATTR-CM without HF symptoms in our study and the underlying pathophysiological mechanism of the disease, early modification of its natural history by specific TTR therapies could be meaningful.
( acoramidis) are currently being tested in randomized controlled trials for ATTR-CM (NCT03997383, NCT04153149, NCT04136171, and NCT03860935). Although early diagnosis of a progressive fatal disease could potentially offer a number of therapeutic opportunities, the tafamidis ATTR-CM trial and all the ongoing ATTR-CM trials included only patients with ATTR-CM with HF symptoms. To complicate things further, ATTR-CM commonly affects elderly individuals, who could be affected by many other diseases, which might influence decisions about the initiation of long-term and expensive treatments, despite the fact that the Food and Drug Administration and European Medicines Agency have authorized tafamidis for the treatment of ATTR-CMwithout restricting it to patients with overt HF. 20  Given the substantial number of events found during follow-up among patients with ATTR-CM without HF symptoms in our study and the underlying pathophysiological mechanism of the disease, early modification of its natural history by specific TTR therapies could be meaningful.
] [44] [45]  Retrospective trial analyses have shown that there is the potential to integrate risk scores into pulmonary arterial hypertension clinical trials to identify and screen for a particular risk population and enable time, sample size, and cost savings. 46 The ZENITH trial (NCT04896008) restricts enrolment to high-risk individuals defined as WHO/New York Heart Association class III or IV and who have a REVEAL Lite 2 risk score greater than or equal to 10 in the eligibility criteria. Because high-risk patients with pulmonary arterial hypertension have higher baseline rates of clinical worsening events as compared with lowrisk or intermediate-risk patients, the targeted trial sample size in ZENITH will be 166 patients, which is substantially smaller than other pulmonary arterial hypertension trials with clinical worsening primary endpoints.
52 Seamless designs combine two separate phase 2 and phase 3 trials that are operationally seamless. Adaptive seamless phase 2/3 trials therefore use data from phase 2 to inform the phase 3 study (appendix p 5). The goals of using adaptive seamless phase 2/3 trials are to reduce cost and duration of separate phase 2 and 3 trials, which is particularly important in a rare disease such as pulmonary arterial hypertension, with few patients available for trial participation. Other potential advantages of using adaptive designs include reducing the number of patients needed in the phase 3 study, improved selection of target doses and participants for the phase 3 trial, and identification of covariates between short-term endpoints in phase 2 and long-term clinical outcomes in phase 3. A seamless phase 2/3 trial (NCT04732221) is evaluating an inhaled soluble guanylate cyclase stimulator (MK-5475), using a phase 2 study to select the best safety profile and efficacy for reducing pulmonary vascular resistance, progressing to a phase 3 confirmatory cohort evaluating the effect on 6MWD.
Similarly, the IMPAHCT study (NCT05036135) is a randomised, double-blind study with a phase 2b, an intermediate phase, and a phase 3. Continuous recruitment is used, and an operationally seamless adaptive design allows for optimal dose selection. In phase 2b, a low, medium, and high dose of inhaled imatinib will be compared with placebo and the dose with the optimal efficacy and safety properties for the phase 2b outcomes will be selected for phase 3. Adaptive trials might use traditional frequentist statistical approaches or Bayesian approaches using data from patients enrolled before and after adaptation. Philosophically, Bayesian approaches differ from the frequentist statistical approach in trials, which must reject a null hypothesis that two treatments are equivalent, to establish efficacy or safety, or both.
Pragmatic trial designs are currently being used in the SPHERe trial  70  and in a study comparing monotherapy and dual therapy in paediatric pulmonary arterial hypertension (NCT04039464). Pragmatic trials face several challenges, including the monitoring and reporting of safety events, which could, in turn, alter usual care. Because pragmatic trials are usually not blinded, reporting of adverse events and the reasons for discontinuation might be biased. Other challenges include obtaining detailed informed consent in clinical practice settings, the absence of incentives or support to centres for enrolment or data collection, and the time and effort required on the part of patients, clinicians, and investigators in participating in trials. Pulmonary arterial hypertension treatment availability, reimbursement, and clinical practice patterns might vary considerably between countries, which could influence enrolment and generalisability of pragmatic trials in pulmonary arterial hypertension.
Solutions for these issues include creating organised research centres to support and execute pragmatic trials across several clinics, and use of existing data infrastructure to data collection. For example, linkage to electronic health records could overcome certain problems in pragmatic trials with adverse event reporting and could accurately identify serious adverse events, as shown in the West of Scotland Coronary Prevention Study. 71, 72 However, electronic health record systems might not be available in some low-income and middle-income countries or in non-academic centres in other settings. A pragmatic pulmonary arterial hypertension trial could also be embedded within an existing disease registry for data collection, like the Pulmonary Hypertension Association Registry in the USA, which already uses electronic case report forms and includes patient-reported measures such as quality of life.
The CardioMEMS system is a small, wireless monitoring sensor implanted in the pulmonary artery to monitor pulmonary arterial pressure and heart rate. A study published in 2011 showed that patients with left heart failure monitored and managed by CardioMEMS had significantly fewer hospitalisations due to heart failure as compared with the control group. 90 CardioMEMS is reported to be safe and reliable in patients with left heart failure. 91, 92 The use of CardioMEMS has been tested in a small cohort of 26 patients with severe pulmonary arterial hypertension,  93  and is being used in two other studies to titrate treatment to goal mean pulmonary artery pressure (ARTISIAN[NCT05203510] and CS1-003 [NCT05224531]). The main limitation of using the present CardioMEMS system as a trial endpoint is that it evaluates only pulmonary artery pressure, which does not reflect the severity of pulmonary arterial hypertension, and misses important prognostic factors such as cardiac output and stroke volume index.
Which drugs are currently in phase 2 and 3 clinical trials? Several medications with novel mechanisms of action or unique delivery routes are transitioning into phase 3 investigation (figure  3 ; table). 133 Specifically, through efforts to optimise drug delivery, dry powder inhalation has emerged as an appealing route of administration that continues to be investigated in phase 3 trials (ie, treprostinil, PDE5is, and soluble guanylate cyclase stimulators), primarily with the goal of improving patient convenience. 134, 135 Investigational approaches on existing pathways include ralinepag, a novel prostacyclin receptor agonist currently in phase 3 trials,  136  inhaled vardenafil, a PDE5i in a phase 2 trial (NCT04266197), and MK-4575, an inhaled soluble guanylate cyclase stimulator in a phase 2/3 trial (NCT04732221).
121,120Future pulmonary arterial hypertension clinical trials might mandate pulmonary arterial hyper tension patient representa tives on steering committees and carefully consider patient perspectives in trial design, conduct, and how results will be communicated to patients after the trial is completed. The 6th World Symposium on Pulmonary Hypertension also recommended including patient partners as con sultants in the trial design process to ensure the importance of overall wellbeing as a central component. 121A patient reported outcome is any report of Phase Estimated size Key eligibility criteria Primary outcome Ralinepag, prostacyclin receptor agonist ADVANCE (NCT03626688) 3 700 WHO/NYHA Class II-IV Time to first clinical worsening event ADVANCE CAPACITY 3 193 WHO/NYHA Class II or III, V E /VCO 2 ≥38, Change in peak VO 2 at week 28 (NCT04084678) VO 2 ≥10 to <18 mL/kg per min Vardenafil DPI (RT234), inhaled phosphodiesterase type-5 inhibitor VIPAH-PRN (NCT04266197) 2 86 WHO/NYHA Class II-IV Treatment-emergent adverse events, change in blood pressure, change in peak VO 2 MK-5475, inhaled soluble guanylate cyclase stimulator INSIGNIA-PAH (NCT04732221) 2/3 450 WHO/NYHA Class II-IV Phase 2, change in PVR at week 12; phase 3, change in 6MWD at week 12 Sotatercept, TGFβ superfamily modulator STELLAR (NCT04576988) 3 324 WHO/NYHA Class II or III, PVR ≥5 WU Change in 6MWD at week 24 HYPERION (NCT04811092) 3 662 Newly diagnosed, intermediate and high Time to clinical worsening, defined as the first risk confirmed morbidity event or death ZENITH (NCT04896008) 3 200 WHO/NYHA Class III and IV at high risk Time to first confirmed morbidity or mortality event, defined as all-cause death, lung transplantation, or pulmonary arterial hypertension-worsening-related hospitalisation of ≥24 h Seralutinib, inhaled PDGF-R, CSF1R, and c-KIT inhibitor TORREY (NCT04456998) 2 86 WHO/NYHA Class II or III, PAWP or LVEDP Change in PVR at week 24 ≤12 if PVR ≥5 and <6•25 WU, or PAWP or LVEDP ≤15 if PVR ≥6•25 WU Imatinib DPI (AV-101), inhaled tyrosine kinase inhibitor IMPAHCT (NCT05036135) 2b/3 462 WHO/NYHA Class II-IV Phase 2b, change in PVR at week 24; phase 3, change in 6MWD at week 24 Rodatristat ethyl, tryptophan hydroxylase inhibitor ELEVATE-2 (NCT04712669) 2 90 WHO/NYHA Class II or III, PAWP or LVEDP Change in PVR at week 24 ≤12 if PVR ≥4•4 and <6•25 WU, or PAWP or LVEDP ≤15 if PVR ≥6•25 WU Apabetalone, BRD4 inhibitor APPROACH-2 (NCT04915300) 2 72 WHO/NYHA Class II or III, Change in PVR at week 24 mPAP >20 mm Hg, PVR >5 WU 6MWD=6-minute walking distance.
A basic means to establish and understand variations in climate and ocean water properties is through sediment mass accumulation rates (MARs), which are quantified measurements of solid material flux to the seabed (mass Abstract Sediment mass accumulation rate (MAR) is a proxy for paleoceanographic conditions, especially if biological productivity generated most of the sediment. We determine MAR records from pelagic calcareous sediments in Tasman Sea based on analysis of 11 boreholes and >3 million seismic reflection horizon picks. Seismic data from regions of 10,000-30,000 km 2 around each borehole were analyzed using data from International Ocean Discovery Program Expedition 371 and other boreholes. Local MAR was affected by deepwater currents that winnowed, eroded, or deposited seafloor sediment.
MAR Calculation We calculate total MAR, because it is robust, but note that the concentration of carbonate varies across the region and through time (Figure  6 ). This correction is discussed later, but not included in our quantitative estimates, because we have insufficient compositional data to build a model of carbonate concentration with space and time. For the late Neogene period of most interest, the carbonate content is consistently ∼90% (Figure  6 ). We consider the sediment pile as a series of layers and, based on many measurements of samples, assume constant grain density of 2,700 kg m -3. All depths and two-way travel times for seismic reflections are measured downwards and relative to a zero datum at the seabed. MAR𝐴𝐴 = 𝜌𝜌𝑔𝑔𝑔𝑔𝑔𝑔𝑔𝑔𝑔𝑔 ∫ 𝑧𝑧 𝑙𝑙+1 𝑧𝑧 𝑙𝑙 (1 -𝜙𝜙)𝑑𝑑𝑧𝑧 𝐴𝐴 𝑏𝑏𝑔𝑔𝑏𝑏𝑏𝑏 𝑙𝑙 -𝐴𝐴 𝑡𝑡𝑡𝑡𝑡𝑡 𝑙𝑙 (2) The porosity   is fit empirically to data as a function of depth (Figure  6  and Equation  3 ).
Northern New Caledonia Trough (NCTN) Northern New Caledonia Trough was mapped over 15,000 km 2 using high-quality seismic reflection data (Figures S11-S13 in Supporting Information S1). Age and sediment information is derived from Site U1507, which is located on the basin floor adjacent to Norfolk Ridge. The seabed gently slopes toward the axis of the trough, and swath bathymetry images reveal subtle relief associated with basin floor fans that are derived from incised canyons on the lower part of nearby Norfolk Ridge slope (Figure  S11  in Supporting Information S1). Seismic reflection interpretation reveals a series of debris flows derived from the flank of Norfolk Ridge, and sediment cores from Site U1507 contain abundant evidence for sediment gravity flows derived from the ridge. Therefore, MAR values derived from around Site U1507 broadly reflect MAR from the flank of Norfolk Ridge but are higher than local pelagic sedimentation rates, because we have mapped a local depocenter that accumulates sediment from a broader region through concentration by sediment gravity flows to the basin floor.
Conclusions and Future Climate Change We present an analysis of Tasman Sea MARs based on a revised biostratigraphic and compaction analysis of 11 boreholes and >3 million seismic reflection horizon picks tied to those boreholes. We depth converted seismic reflection interpretations and accounted for compaction using physical properties data from IODP Expedition 371. We analyzed a region of 10,000-30,000 km 2 around each borehole, but the total size of northern Zealandia is ∼3 × 10 6 km 2. Our study shows that regional variability in MAR is significant, due to the action of deepwater currents that have winnowed, created hiatuses, or eroded sediment at the seabed (1,000-3,000 m depth) in some places and deposited bedforms (drifts, contourites, dunes, fans, etc. ) in others. Therefore, it is necessary to average MARs over larger areas to obtain estimates that can be used to infer past ocean productivity.
Data Availability Statement Digital files of seismic horizon picks, age models, and code (that could be reused for analysis of other regions) are available at https://github. com/RupertSutherland/sedBasin (https://doi. org/10. 5281/zenodo. 5502246). Seismic reflection data were compiled, described, and made available by  Sutherland et al. (2012)  and are most easily obtained from GNS Science (https://data. gns. cri. nz/pbe) or New Zealand Petroleum & Minerals (https://data. nzpam. govt. nz). TECTA 2015 data (NCTN region) are available from https://doi. org/10. 17600/15001300 and by typing in "TECTA" in the search bar at IFREMER: https://donnees-campagnes. flotteoceanographique. fr/search (embargo until 2022). TAN1409 data can be obtained from https://data. gns. cri. nz/pbe. ETOPO data set: https:// www.
Therefore, household-based resources may have become more important in predicting family and child well-being. While some family resources were unlikely to change during the period, such as parental education or housing conditions, others might have been affected by the lockdown and COVID itself, such as parent physical and mental health, or by the economic crisis; some families experienced a drop in income and a deterioration in their employment situation. We assess the role of family resources and their variation in predicting change in family well-being during the lockdown. We make use of data from the Elfe Sapris survey, a web survey administered during the first French lockdown in April and May 2020 to about 5,000 families participating to the Etude longitudinale française depuis l'enfance (Elfe), France's generalist nationally representative birth cohort study.
A specific COVID survey from a national child birth cohort The Elfe-SAPRIS 1 data was collected through a web survey conducted as part of the Elfe (French longitudinal study since childhood) study, a population-based cohort following children born in continental France from the time of their birth in 2011 onwards  (Charles et al. 2020 ). 2 The Elfe-SAPRIS survey was administered to the 13,696 Elfe parents with a valid e-mail address between 16th April and 3 rd May 2020, during the first lockdown (see Figure  A1  in the Appendix). A second questionnaire was administered between 2 nd May and June 21 st. The children in the sample were 9. 5 years old on average at the time of the Sapris survey. The survey questions covered coronavirus-related health, household socioeconomic characteristics, children's activities, family relationships, and child wellbeing (as assessed by parents).
A total of 4,877 questionnaires were completed. The response rate of 38% is relatively low, and was lower among younger parents, those living in urban areas -especially the Paris metropolitan area-and in apartments, those with a 1 This survey is part of a larger project, SAPRIS (Health, perception, practices, relations, and social inequalities during the COVID-19 crisis), a series of coordinated add-on surveys administered to the participants of existing cohorts of adults (e. g. , E3N-E4N and Nutrinet) and children (Elfe and Epipage2, a cohort of children born prematurely)  (Bajos et al. 2021 ). 2 Children were born at a random sample of 341 maternity units throughout continental France and were sampled at four intervals with initial data collection occurring in April, June/July, September/October, and November/December 2011.
Interviews were carried out in the maternity unit shortly after a child's birth, by telephone roughly two months post-birth, and again when the child was approximately 1, 2, 3. 5 and 5. 5 years of age. Data were collected on diverse topics, including socioeconomic background, parenting, child development, and living conditions. lower levels of education, immigrants and non-working mothers. While the response rate is lower than comparable web surveys that have been performed previously on the Elfe cohort 3 , the population structure of respondents is very similar to a previous web survey conducted when the child was 7 and half. In this article, we focus on the 4,485 households who completed the Elfe-SAPRIS survey either during the first round, and otherwise during the second round, provided responses for the four outcomes considered, and responded in the pre-lockdown waves.
SDQ is scored such that higher scores indicate more difficulties. The SDQ is not directly comparable to our other outcomes, as we are able to observe it at two data points: once before and again during the lockdown; we therefore calculate change in child well-being by comparing these two scores. On the other hand, our others outcomes are only collected during the lockdown survey and question the parent directly about the change in family well-being, by questioning whether relationships improved or deteriorated. Therefore, in order to construct a child well-being outcome that is comparable with our other outcomes, we first build a continuous indicator of the variation in SDQ scores at the two time points available (Figure  1  bottom right panel shows the distribution). We then class children according to whether their well-being appears to have improved (children whose SDQ score is lower during lockdown than at age 5.