Greenland Ice Sheet surface melt amplified by snowline migration and bare ice exposure

Greenland Ice Sheet mass loss has recently increased because of enhanced surface melt and runoff. Since melt is critically modulated by surface albedo, understanding the processes and feedbacks that alter albedo is a prerequisite for accurately forecasting mass loss. Using satellite imagery, we demonstrate the importance of Greenland’s seasonally fluctuating snowline, which reduces ice sheet albedo and enhances melt by exposing dark bare ice. From 2001 to 2017, this process drove 53% of net shortwave radiation variability in the ablation zone and amplified ice sheet melt five times more than hydrological and biological processes that darken bare ice itself. In a warmer climate, snowline fluctuations will exert an even greater control on melt due to flatter ice sheet topography at higher elevations. Current climate models, however, inaccurately predict snowline elevations during high melt years, portending an unforeseen uncertainty in forecasts of Greenland’s runoff contribution to global sea level ris

Three steps to data quality

Background The quality of data in general practice clinical information systems varies enormously. This variability jeopardises the proposed national strategy for an integrated care records service and the capacity of primary care organisations to respond coherently to the demands of clinical governance and the proposed quality-based general practice contract. This is apparent in the difficulty in automating the audit process and in comparing aggregated data from different practices. In an attempt to provide data of adequate quality to support such operational needs, increasing emphasis is being placed on the standardisation of data recording. Objective To develop a conceptual framework to facilitate the recording of standardised data within primary care. Method A multiprofessional group of primary care members from the South Thames Research Network examined leading guidelines for best practice. Using the nominal group technique the group prioritised the information needs of primary care organisations for managing coronary heart disease according to current evidence. Results Information needs identified were prioritized and stratified into a functional framework. Conclusion It has been possible within the context of a primary care research network to produce a framework for standardising data collection. Motivation of front-line clinicians was achieved through the incorporation of their views into the synthesis of the dataset

Measuring functional activities of patients in a stroke unit: Comparison of a sensor based Real Time Location System with the Observational Behaviour Mapping Technique [Poster Abstract]

Introduction: To overcome the limitations of the current activity monitoring methods and to effectively investigate early stage functional activities post stroke, we are developing a new computerised Real Time Location System (RTLS).Having previously established excellent RTLS reliability (Intraclass Correlation Coefficients≥0.90), this study aims to determine its validity by comparing it to the Observational Behaviour Mapping Technique (OBMT). Methods: All rooms routinely accessed by patients are fitted with infra-red room locators which send their location codes to specialised Radio-Frequency Identification (RFID) tags. The RFID tags that have in-built motion sensors transmit their location and movement signals to a computer. All participating patients and staff members wear the tags and additional tags are attached to equipment like walking-aids and wheelchairs. Simultaneously, on various days, OBMT is being used to record patients’ location, interaction and activity every ten minutes. Descriptive statistics and Pearson’s Correlation Coefficients (PCCs) are being used for statistical analysis. Results: So far, we have analysed the results for the location category of three patients and have observed only small differences between the two systems for mean time spent in own room (diff=7min; OBMT=550, RTLS=557) and in therapy room (diff=4min; OBMT=90, RTLS=86). Further analysis will involve comparing the methods for time spent in categories like interacting with staff members, doing therapeutic and non therapeutic activities and using equipment. Conclusion: Based on results, we hope to determine that the RTLS is a valid system for continuous, unobtrusive patient activity measurement and can provide much needed quantifiable information about functional recovery post stroke

In crystallo-screening for discovery of human norovirus 3C-like protease inhibitors.

Outbreaks of human epidemic nonbacterial gastroenteritis are mainly caused by noroviruses. Viral replication requires a 3C-like cysteine protease (3CLpro) which processes the 200 kDa viral polyprotein into six functional proteins. The 3CLpro has attracted much interest due to its potential as a target for antiviral drugs. A system for growing high-quality crystals of native Southampton norovirus 3CLpro (SV3CP) has been established, allowing the ligand-free crystal structure to be determined to 1.3 Å in a tetrameric state. This also allowed crystal-based fragment screening to be performed with various compound libraries, ultimately to guide drug discovery for SV3CP. A total of 19 fragments were found to bind to the protease out of the 844 which were screened. Two of the hits were located at the active site of SV3CP and showed good inhibitory activity in kinetic assays. Another 5 were found at the enzyme's putative RNA-binding site and a further 11 were located in the symmetric central cavity of the tetramer

A new computerised system can continuously measure functional activities of patients in a stroke rehabilitation unit

Background: To be able to measure patient activity in a continuous and unobtrusive manner we are developing a new automated system based on Real Time Location Technology. This would also allow us to overcome limitations of the current activity monitoring methods. Having established excellent reliability of the system (Intraclass Correlation Coefficients≥0.90) we validated it against Observational Behaviour Mapping Techniques and obtained a high level of agreement between the two methods. The mean differences for time spent in own room and physiotherapy room were 1.1 and 1.5 minutes respectively. To date, the system has measured continuous activity of 43 patients from admission to discharge. Methods: Each participant wore a Radio Frequency identification tag with an in-built motion sensor. This tag, worn on the unaffected wrist receives infra-red location signals from room locators fitted in all rooms accessed by the patients. The tag transmits the location and movement signals to a computer. Bespoke software programmes were developed to collect and process data. Descriptive statistics and charts were used for analysis. Results: Here we report the individual activity profiles of 2 patients. Summary charts (emailed separately) illustrate some individual differences in the activity of these patients. Both patients spent the majority of their time in their own rooms (mean 88.6% and 77.5%) where patient 2 was less active. Patients were most active whilst in physiotherapy (mean 98% and 95%). Conclusion: With further development of the software we are aiming to build a comprehensive picture of functional recovery. Therefore, the analysis of other key aspects such as time spent sitting in the chair, lying in bed, transfers or walking in the corridor will be added. This may also give more insight into the kind of activity undertaken in their own rooms. Ultimately, the aim is to generate a better understanding of early rehabilitation post stroke

Derivation of High Spatial Resolution Albedo from UAV Digital Imagery:Application over the Greenland Ice Sheet

Measurements of albedo are a prerequisite for modeling surface melt across the Earth's cryosphere, yet available satellite products are limited in spatial and/or temporal resolution. Here, we present a practical methodology to obtain centimeter resolution albedo products with accuracies of ?5% using consumer-grade digital camera and unmanned aerial vehicle (UAV) technologies. Our method comprises a workflow for processing, correcting and calibrating raw digital images using a white reference target, and upward and downward shortwave radiation measurements from broadband silicon pyranometers. We demonstrate the method with a set of UAV sorties over the western, K-sector of the Greenland Ice Sheet. The resulting albedo product, UAV10A1, covers 280 km2, at a resolution of 20 cm per pixel and has a root-mean-square difference of 3.7% compared to MOD10A1 and 4.9% compared to ground-based broadband pyranometer measurements. By continuously measuring downward solar irradiance, the technique overcomes previous limitations due to variable illumination conditions during and between surveys over glaciated terrain. The current miniaturization of multispectral sensors and incorporation of upward facing radiation sensors on UAV packages means that this technique could become increasingly common in field studies and used for a wide range of applications. These include the mapping of debris, dust, cryoconite and bioalbedo, and directly constraining surface energy balance models.publishersversionPeer reviewe

Measuring continuous patient activity post-stroke using a novel sensor-based computerised system

Introduction To be able to measure patient activity in a continuous and unobtrusive manner we have developed a new system based on Real Time Location Technology. Having previously established excellent reliability and validity of the system, it has been effectively used to measure patients’ walking ability and activity levels in a rehabilitation unit and at home. Method Fifty-two participants wore a Radio Frequency Identification tag on their unaffected wrist. This tag has an in-built motion sensor and continuously transmits the location and movement signals to a computer with bespoke software programmes to collect and process data. Descriptive statistics and graphs depicting average duration of walking were used for analysis. Results To date, activity levels of 25 patients during hospitalisation and of 9 patients at home have been analysed. From admission to discharge relatively small changes in activity level were observed. For instance the overall activity in own room increased by only 7% (Admission=60%; Discharge=67%). However, post-discharge activity at home decreased considerably by 54% (Discharge =73%; Home=19%). Similarly relatively low average duration of walking were observed when measured for 22 hospitalised patients; 10 minutes per day (Minimum=1minute; Maximum=90 minutes).The graphs gave in-depth information about gait recovery patterns of individual patients. Discussion So far interesting aspects of early, functional recovery post-stroke were revealed. Ultimately, the aim is to develop a comprehensive system that can provide activity feedback to patients, carers and clinicians. This could function as a motivational strategy to further improve patient activity levels in a rehabilitation unit and at home

Anti-myeloma efficacy of CAR-iNKT is enhanced with a long-acting IL-7, rhIL-7-hyFc

Multiple myeloma (MM), a malignancy of mature plasma cells, remains incurable. B-cell maturation antigen (BCMA) is the lead protein target for chimeric antigen receptor (CAR) therapy because of its high expression in most MM, with limited expression in other cell types, resulting in favorable on-target, off tumor toxicity. The response rate to autologous BCMA CAR-T therapy is high; however, it is not curative and is associated with risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. Outcomes in patients treated with BCMA CAR-T cells (CAR-Ts) may improve with allogeneic CAR T-cell therapy, which offer higher cell fitness and reduced time to treatment. However, to prevent the risk of graft-versus-host disease (GVHD), allogenic BCMA CAR-Ts require genetic deletion of the T-cell receptor (TCR), which has potential for unexpected functional or phenotype changes. Invariant natural killer T cells (iNKTs) have an invariant TCR that does not cause GVHD and, as a result, can be used in an allogeneic setting without the need for TCR gene editing. We demonstrate significant anti-myeloma activity of BCMA CAR-iNKTs in a xenograft mouse model of myeloma. We found that a long-acting interleukin-7 (IL-7), rhIL-7-hyFc, significantly prolonged survival and reduced tumor burden in BCMA CAR-iNKT-treated mice in both primary and re-challenge settings. Furthermore, in CRS in vitro assays, CAR-iNKTs induced less IL-6 than CAR-Ts, suggesting a reduced likelihood of CAR-iNKT therapy to induce CRS in patients. These data suggest that BCMA CAR-iNKTs are potentially a safer, effective alternative to BCMA CAR-Ts and that BCMA CAR-iNKT efficacy is further potentiated with rhIL-7-hyFc