ALBERT

Description: Alexander Russell , Anthony Yeates and Jonathan Eastwood review the state of the art and interesting future directions in this developing field, drawing on the RAS discussion meeting held on 12 December 2014.

Description: The Large-aperture Experiment to Detect the Dark Age (LEDA) was designed to detect the predicted O(100) mK sky-averaged absorption of the cosmic microwave background by hydrogen in the neutral pre- and intergalactic medium just after the cosmological Dark Age. The spectral signature would be associated with emergence of a diffuse Lyα background from starlight during ‘Cosmic Dawn’. Recently, Bowman et al. have reported detection of this predicted absorption feature, with an unexpectedly large amplitude of 530 mK, centred at 78 MHz. Verification of this result by an independent experiment, such as LEDA, is pressing. In this paper, we detail design and characterization of the LEDA radiometer systems, and a first-generation pipeline that instantiates a signal path model. Sited at the Owens Valley Radio Observatory Long Wavelength Array, LEDA systems include the station correlator, five well-separated redundant dual polarization radiometers and back-end electronics. The radiometers deliver a 30–85 MHz band (16 〈z 〈 34) and operate as part of the larger interferometric array, for purposes ultimately of in situ calibration. Here, we report on the LEDA system design, calibration approach, and progress in characterization as of 2016 January. The LEDA systems are currently being modified to improve performance near 78 MHz in order to verify the purported absorption feature.

Description: Background: In both the novel and pre-novel agents era, high dose therapy followed by autologous hematopoietic cell transplant (AHCT) has been shown to prolong survival in multiple myeloma (MM) in randomized trials, but prospective have only included younger patients (65 -70 years and younger). Given that the median age at diagnosis of MM is 66 years, it is important to know the outcomes of AHCT in older patients. Similarly, the definite outcomes of AHCT in very young patients (70 years; N=105) and young (≤50 years, N=86) and compared the outcomes. The primary objectives were to assess overall survival (OS), progression free survival, (PFS), and non-relapse mortality (NRM) in these two groups. Results: Eighty-sex patients were young (≤50 years), while 105 patients were old (〉70 years). Young patients had better performance status and lower co-morbidity index, while majority of older cohort received dose reduced high dose melphalan between 140-180 mg/m2. Median follow up of survivors in the younger cohort was 33 months (range, 2-164) compared to the 22.5 months (3-133) in the old group (p=0.02). The PFS at 1 year was 60% (95%CI 46-72) for young patients and 58 (95%CI, 45-69) for the old ones. The OS at 1 year was 92% (95% CI 84-96) for younger and 85% (95% CI 76-91) for the older cohorts. On multivariate analysis, age did not have any effect on survival (p =0.82), high-risk cytogenetics (HR 2.2, 95% CI 1.06-4.6, p=0.04) was associated with higher mortality. High-risk cytogenetics (HR 1.2, 95% CI 1.1-3.5, p=0.004) and non-responding or progressive disease at transplantation (HR, 5.0 95% CI 1.8-13.5, p=0.02) were significantly associated with inferior PFS. Conclusion: Age by itself should not be a limiting factor in considering the modality of AHCT. However consideration could be given to augmenting therapy for young patients with additional novel treatments post transplant given their similar outcomes with the old patients based on our study. Overall survival between the two age groups, 1: 〉70 years old and 2: ≤50 years old. Overall survival between the two age groups, 1: 〉70 years old and 2: ≤50 years old. Figure Figure. Disclosures Hamadani: Takeda: Research Funding. Hari:Merck: Research Funding; BMS: Honoraria.

Description: Key Points Blockade of IL-27 signaling mitigates the severity of GVHD by recalibrating the effector and regulatory arms of the immune system. Inhibition of IL-27 augments the reconstitution of CD4+ and CD8+ regulatory T cells and increases the stability of Foxp3 expression.

Description: Antibodies (abs) specific for heparin/platelet factor 4 (H/PF4) complexes are a hallmark of heparin-induced thrombocytopenia and thrombosis (HIT) and are thought to play a role in predisposing patients to thrombocytopenia and thrombosis. A solid phase assay that uses H/PF4 complexes as targets for ab detection (PF4 ELISA) is almost invariably positive in patients with HIT. This test can be performed quickly and a negative result makes HIT very unlikely; however, many patients testing positive in this assay do not develop HIT. A second test, the serotonin release assay (SRA), considered the "gold standard" for HIT diagnosis, selectively detects HIT abs that activate platelets and are presumptively pathogenic. A positive SRA test correlates well with clinical HIT but the SRA is technically demanding and is routinely performed only by a few reference laboratories, precluding its use for early patient diagnosis and management. This can have adverse consequences since both over- and under-diagnosis of HIT can have serious medical and economic impact. We recently showed that platelet-activating HIT abs preferentially recognize PF4 bound to platelet glycosaminoglycans in the absence of heparin (Blood 2015; 125(1): 155-61). Based on this finding we developed a technically simple assay (PF4-dependent p-selectin expression assay [PEA]) for detection of platelet-activating HIT abs. In the PEA, target platelets are first "primed" for activation by being incubated with PF4 and are then exposed to patient serum. P-selectin expression (percent of maximum) is measured as an indicator of platelet activation (Thromb Haemost. 2015; 114(5) epub). Specificity of a positive test result is confirmed by inhibition with high dose heparin (HDH). To compare diagnostic performance of the PEA and the SRA, 91 sera from patients referred for HIT testing who had been assigned clinical scores for HIT ("4T scores") ranging from 0 to 8 (low to high likelihood of HIT, respectively) were tested in both assays. Samples from patients with Intermediate or High 4T scores (4-8) and PF4 ELISA OD values 〉1.0 were considered "HIT-positive " given that neither criterion by itself has a high positive predictive value for HIT. Intermediate to High 4T-scored patients with PF4 ELISA ODs 24% p-selectin expression. For this analysis, a sample was considered PEA-positive if p-selectin expression was 〉24%, and inhibited 〉50% with HDH. Results are shown in Fig 1. The apparent superiority of the PEA over the SRA for identifying HIT-positive patients suggested that the PEA might be intrinsically more sensitive than the SRA for detecting platelet activating abs. This was confirmed by testing serial dilutions of 3 arbitrarily selected High-4T HIT abs against identical target platelets. A representative result is shown in Fig 2. The many attractive features of the PEA, especially its technical simplicity and its ability to identify patients judged to have a high likelihood of HIT suggest that its use can facilitate early diagnosis and improve management of this diagnostically challenging disorder. In Figures 1 and 2, the solid and dotted lines represent positive cut-offs of the SRA and PEA, respectively. Figure 1. Thirty patients judged to be HIT-positive were tested in the PEA and SRA. The PEA was positive in 27 and the SRA in 16. Fig 1B. The PEA was positive in 8 and the SRA in 3 among 61 HIT-negative patients. The two assays had similar specificity (87% [PEA] vs. 95% [SRA]; p=ns), however, the PEA had significantly higher diagnostic sensitivity than the SRA (90% [PEA] vs. 53% [SRA]; p

Description: Summary We present software to characterize and rank potential therapeutic (drug) targets with data from public databases and present it in a user-friendly format. By understanding potential obstacles to drug development through the gathering and understanding of this information, combined with robust approaches to target validation to generate therapeutic hypotheses, this approach may provide high quality targets, leading the process of drug development to become more efficient and cost-effective. Availability and implementation The information we gather on potential targets concerns small-molecule druggability (ligandability), suitability for large-molecule approaches (e.g. antibodies) or new modalities (e.g. antisense oligonucleotides, siRNA or PROTAC), feasibility (availability of resources such as assays and biological knowledge) and potential safety risks (adverse tissue-wise expression, deleterious phenotypes). This information can be termed ‘tractability’. We provide visualization tools to understand its components. TractaViewer is available from https://github.com/NeilPearson-Lilly/TractaViewer Supplementary information Supplementary data are available at Bioinformatics online.

Description: Fugitive emissions from waste disposal sites are important anthropogenic sources of the greenhouse gas methane (CH4). As a result of the growing world population and the recognition of the need to control greenhouse gas emissions, this anthropogenic source of CH4 has received much recent attention. However, the accurate assessment of the CH4 emissions from landfills by modeling and existing measurement techniques is challenging. This is because of inaccurate knowledge of the model parameters and the extent of and limited accessibility to landfill sites. This results in a large uncertainty in our knowledge of the emissions of CH4 from landfills and waste management. In this study, we present results derived from data collected during the research campaign COMEX (CO2 and MEthane eXperiment) in late summer 2014 in the Los Angeles (LA) Basin. One objective of COMEX, which comprised aircraft observations of methane by the remote sensing Methane Airborne MAPper (MAMAP) instrument and a Picarro greenhouse gas in situ analyzer, was the quantitative investigation of CH4 emissions. Enhanced CH4 concentrations or CH4 plumes were detected downwind of landfills by remote sensing aircraft surveys. Subsequent to each remote sensing survey, the detected plume was sampled within the atmospheric boundary layer by in situ measurements of atmospheric parameters such as wind information and dry gas mixing ratios of CH4 and carbon dioxide (CO2) from the same aircraft. This was undertaken to facilitate the independent estimation of the surface fluxes for the validation of the remote sensing estimates. During the COMEX campaign, four landfills in the LA Basin were surveyed. One landfill repeatedly showed a clear emission plume. This landfill, the Olinda Alpha Landfill, was investigated on 4 days during the last week of August and first days of September 2014. Emissions were estimated for all days using a mass balance approach. The derived emissions vary between 11.6 and 17.8 kt CH4 yr−1 with related uncertainties in the range of 14 to 45 %. The comparison of the remote sensing and in situ based CH4 emission rate estimates reveals good agreement within the error bars with an average of the absolute differences of around 2.4 kt CH4 yr−1 (±2. 8 kt CH4 yr−1). The US Environmental Protection Agency (EPA) reported inventory value is 11.5 kt CH4 yr−1 for 2014, on average 2.8 kt CH4 yr−1 (±1. 6 kt CH4 yr−1) lower than our estimates acquired in the afternoon in late summer 2014. This difference may in part be explained by a possible leak located on the southwestern slope of the landfill, which we identified in the observations of the Airborne Visible/Infrared Imaging Spectrometer – Next Generation (AVIRIS-NG) instrument, flown contemporaneously aboard a second aircraft on 1 day.

Description: Visible–shortwave infrared imaging spectroscopy provides valuable remote measurements of Earth's surface and atmospheric properties. These measurements generally rely on inversions of computationally intensive radiative transfer models (RTMs). RTMs' computational expense makes them difficult to use with high-volume imaging spectrometers, and forces approximations such as lookup table interpolation and surface–atmosphere decoupling. These compromises limit the accuracy and flexibility of the remote retrieval; dramatic speed improvements in radiative transfer models could significantly improve the utility and interpretability of remote spectroscopy for Earth science. This study demonstrates that nonparametric function approximation with neural networks can replicate radiative transfer calculations and generate accurate radiance spectra at multiple wavelengths over a diverse range of surface and atmosphere state parameters. We also demonstrate such models can act as surrogate forward models for atmospheric correction procedures. Incorporating physical knowledge into the network structure provides improved interpretability and model efficiency. We evaluate the approach in atmospheric correction of data from the PRISM airborne imaging spectrometer, and demonstrate accurate emulation of radiative transfer calculations, which run several orders of magnitude faster than first-principles models. These results are particularly amenable to iterative spectrum fitting approaches, providing analytical benefits including statistically rigorous treatment of uncertainty and the potential to recover information on spectrally broad signals.

Description: An Arctic and Antarctic sea ice area and extent dataset has been generated by EUMETSAT's Ocean and Sea Ice Satellite Application Facility (OSISAF) using the record of microwave radiometer data from NASA's Nimbus 7 Scanning Multichannel Microwave radiometer (SMMR) and the Defense Meteorological Satellite Program (DMSP) Special Sensor Microwave/Imager (SSM/I) and Special Sensor Microwave Imager and Sounder (SSMIS) satellite sensors. The dataset covers the period from October 1978 to April 2015 and updates and further developments are planned for the next phase of the project. The methodology for computing the sea ice concentration uses (1) numerical weather prediction (NWP) data input to a radiative transfer model for reduction of the impact of weather conditions on the measured brightness temperatures; (2) dynamical algorithm tie points to mitigate trends in residual atmospheric, sea ice, and water emission characteristics and inter-sensor differences/biases; and (3) a hybrid sea ice concentration algorithm using the Bristol algorithm over ice and the Bootstrap algorithm in frequency mode over open water. A new sea ice concentration uncertainty algorithm has been developed to estimate the spatial and temporal variability in sea ice concentration retrieval accuracy. A comparison to US National Ice Center sea ice charts from the Arctic and the Antarctic shows that ice concentrations are higher in the ice charts than estimated from the radiometer data at intermediate sea ice concentrations between open water and 100 % ice. The sea ice concentration climate data record is available for download at www.osi-saf.org, including documentation.

Description: The recent thinning and shrinking of the Arctic sea ice cover has increased the interest in seasonal sea ice forecasts. Typical tools for such forecasts are numerical models of the coupled ocean sea ice system such as the North Atlantic/Arctic Ocean Sea Ice Model (NAOSIM). The model uses as input the initial state of the system and the atmospheric boundary condition over the forecasting period. This study investigates the potential of remotely sensed ice thickness observations in constraining the initial model state. For this purpose it employs a variational assimilation system around NAOSIM and the Alfred Wegener Institute's CryoSat-2 ice thickness product in conjunction with the University of Bremen's snow depth product and the OSI SAF ice concentration and sea surface temperature products. We investigate the skill of predictions of the summer ice conditions starting in March for three different years. Straightforward assimilation of the above combination of data streams results in slight improvements over some regions (especially in the Beaufort Sea) but degrades the over-all fit to independent observations. A considerable enhancement of forecast skill is demonstrated for a bias correction scheme for the CryoSat-2 ice thickness product that uses a spatially varying scaling factor.