Establishing and Prioritising Research Questions for the Treatment of Alopecia Areata: The Alopecia Areata Priority Setting Partnership

BACKGROUND: Alopecia areata is a common hair loss disorder that results in patchy to complete hair loss. Many uncertainties exist around the most effective treatments for this condition. OBJECTIVES: To identify uncertainties in alopecia areata management and treatment that are important to both service users (people with hair loss, carers and relatives) and healthcare professionals. METHODS: An alopecia areata priority setting partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in alopecia areata. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total 2747 treatment uncertainties were submitted by 912 participants, of which 1012 uncertainties relating to alopecia areata (and variants) were analyzed. Questions were combined into "indicative uncertainties" following a structured format. A series of ranking exercises further reduced this list to a top 25 that were taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for alopecia areata to guide researchers and funding bodies to support studies important to both patients and clinicians. This article is protected by copyright. All rights reserved

Slow dynamics and aging of a confined granular flow

We present experimental results on slow flow properties of a granular assembly confined in a vertical column and driven upwards at a constant velocity V. For monodisperse assemblies this study evidences at low velocities ($1<V<100 \mu m/s$) a stiffening behaviour i.e. the stress necessary to obtain a steady sate velocity increases roughly logarithmically with velocity. On the other hand, at very low driving velocity ($V<1 \mu m/s$), we evidence a discontinuous and hysteretic transition to a stick-slip regime characterized by a strong divergence of the maximal blockage force when the velocity goes to zero. We show that all this phenomenology is strongly influenced by surrounding humidity. We also present a tentative to establish a link between the granular rheology and the solid friction forces between the wall and the grains. We base our discussions on a simple theoretical model and independent grain/wall tribology measurements. We also use finite elements numerical simulations to confront experimental results to isotropic elasticity. A second system made of polydisperse assemblies of glass beads is investigated. We emphasize the onset of a new dynamical behavior, i.e. the large distribution of blockage forces evidenced in the stick-slip regime

CryoSat Ice Baseline-D validation and evolutions

The ESA Earth Explorer CryoSat-2 was launched on 8 April 2010 to monitor the precise changes in the thickness of terrestrial ice sheets and marine floating ice. To do that, CryoSat orbits the planet at an altitude of around 720 km with a retrograde orbit inclination of 92∘ and a quasi repeat cycle of 369 d (30 d subcycle). To reach the mission goals, the CryoSat products have to meet the highest quality standards to date, achieved through continual improvements of the operational processing chains. The new CryoSat Ice Baseline-D, in operation since 27 May 2019, represents a major processor upgrade with respect to the previous Ice Baseline-C. Over land ice the new Baseline-D provides better results with respect to the previous baseline when comparing the data to a reference elevation model over the Austfonna ice cap region, improving the ascending and descending crossover statistics from 1.9 to 0.1 m. The improved processing of the star tracker measurements implemented in Baseline-D has led to a reduction in the standard deviation of the point-to-point comparison with the previous star tracker processing method implemented in Baseline-C from 3.8 to 3.7 m. Over sea ice, Baseline-D improves the quality of the retrieved heights inside and at the boundaries of the synthetic aperture radar interferometric (SARIn or SIN) acquisition mask, removing the negative freeboard pattern which is beneficial not only for freeboard retrieval but also for any application that exploits the phase information from SARIn Level 1B (L1B) products. In addition, scatter comparisons with the Beaufort Gyre Exploration Project (BGEP; https://www.whoi.edu/beaufortgyre, last access: October 2019) and Operation IceBridge (OIB; Kurtz et al., 2013) in situ measurements confirm the improvements in the Baseline-D freeboard product quality. Relative to OIB, the Baseline-D freeboard mean bias is reduced by about 8 cm, which roughly corresponds to a 60 % decrease with respect to Baseline-C. The BGEP data indicate a similar tendency with a mean draft bias lowered from 0.85 to −0.14 m. For the two in situ datasets, the root mean square deviation (RMSD) is also well reduced from 14 to 11 cm for OIB and by a factor of 2 for the BGEP. Observations over inland waters show a slight increase in the percentage of good observations in Baseline-D, generally around 5 %–10 % for most lakes. This paper provides an overview of the new Level 1 and Level 2 (L2) CryoSat Ice Baseline-D evolutions and related data quality assessment, based on results obtained from analyzing the 6-month Baseline-D test dataset released to CryoSat expert users prior to the final transfer to operations

CryoSat instrument performance and ice product quality status

Over the past 20 years, satellite radar altimetry has shown its ability to revolutionise our understanding of the ocean and climate. Previously, these advances were largely limited to ice-free regions, neglecting large portions of the Polar Regions. Launched in 2010, the European Space Agency’s (ESA) polar-orbiting CryoSat satellite was specifically designed to measure changes in the thickness of polar sea ice and the elevation of the ice sheets and mountain glaciers. To reach this goal, the CryoSat products have to meet the highest performance standards, achieved through continual improvements of the associated Instrument Processing Facilities. Since April 2015, the CryoSat ice products are generated with Baseline-C, which represented a major processor upgrade. Several improvements were implemented in this new Baseline, most notably the release of freeboard data within the Level 2 products. The Baseline-C upgrade has brought significant improvements to the quality of Level-1B and Level-2 products relative to the previous Baseline-B products, which in turn is expected to have a positive impact on the scientific exploitation of CryoSat measurements over land ice and sea ice. This paper provides an overview of the CryoSat ice data quality assessment and evolutions, covering all quality control and calibration activities performed by ESA and its partners. Also discussed are the forthcoming evolutions of the processing chains and improvements anticipated in the next processing Baseline

The Roles of the S3MPC: Monitoring, Validation and Evolution of Sentinel-3 Altimetry Observations

The Sentinel-3 Mission Performance Centre (S3MPC) is tasked by the European Space Agency (ESA) to monitor the health of the Copernicus Sentinel-3 satellites and ensure a high data quality to the users. This paper deals exclusively with the effort devoted to the altimeter and microwave radiometer, both components of the Surface Topography Mission (STM). The altimeters on Sentinel-3A and -3B are the first to operate in delay-Doppler or SAR mode over all Earth surfaces, which enables better spatial resolution of the signal in the along-track direction and improved noise reduction through multi-looking, whilst the radiometer is a two-channel nadir-viewing system. There are regular routine assessments of the instruments through investigation of telemetered housekeeping data, calibrations over selected sites and comparisons of geophysical retrievals with models, in situ data and other satellite systems. These are performed both to monitor the daily production, assessing the uncertainties and errors on the estimates, and also to characterize the long-term performance for climate science applications. This is critical because an undetected drift in performance could be misconstrued as a climate variation. As the data are used by the Copernicus Services (e.g., CMEMS, Global Land Monitoring Services) and by the research community over open ocean, coastal waters, sea ice, land ice, rivers and lakes, the validation activities encompass all these domains, with regular reports openly available. The S3MPC is also in charge of preparing improvements to the processing, and of the development and tuning of algorithms to improve their accuracy. This paper is thus the first refereed publication to bring together the analysis of SAR altimetry across all these different domains to highlight the benefits and existing challenges

SAS6-like protein in Plasmodium indicates that conoid-associated apical complex proteins persist in invasive stages within the mosquito vector

The SAS6-like (SAS6L) protein, a truncated paralogue of the ubiquitous basal body/centriole protein SAS6, has been characterised recently as a flagellum protein in trypanosomatids, but associated with the conoid in apicomplexan Toxoplasma. The conoid has been suggested to derive from flagella parts, but is thought to have been lost from some apicomplexans including the malaria-causing genus Plasmodium. Presence of SAS6L in Plasmodium, therefore, suggested a possible role in flagella assembly in male gametes, the only flagellated stage. Here, we have studied the expression and role of SAS6L throughout the Plasmodium life cycle using the rodent malaria model P. berghei. Contrary to a hypothesised role in flagella, SAS6L was absent during gamete flagellum formation. Instead, SAS6L was restricted to the apical complex in ookinetes and sporozoites, the extracellular invasive stages that develop within the mosquito vector. In these stages SAS6L forms an apical ring, as we show is also the case in Toxoplasma tachyzoites. The SAS6L ring was not apparent in blood-stage invasive merozoites, indicating that the apical complex is differentiated between the different invasive forms. Overall this study indicates that a conoid-associated apical complex protein and ring structure is persistent in Plasmodium in a stage-specific manner

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research