Blasts in context:the impact of the immune environment on acute myeloid leukemia prognosis and treatment

Acute myeloid leukemia (AML) is a cancer that originates from the bone marrow (BM). Under physiological conditions, the bone marrow supports the homeostasis of immune cells and hosts memory lymphoid cells. In this review, we summarize our present understanding of the role of the immune microenvironment on healthy bone marrow and on the development of AML, with a focus on T cells and other lymphoid cells. The types and function of different immune cells involved in the AML microenvironment as well as their putative role in the onset of disease and response to treatment are presented. We also describe how the immune context predicts the response to immunotherapy in AML and how these therapies modulate the immune status of the bone marrow. Finally, we focus on allogeneic stem cell transplantation and summarize the current understanding of the immune environment in the post-transplant bone marrow, the factors associated with immune escape and relevant strategies to prevent and treat relapse.</p

Associatioin of Plasma Aβ Peptides with Blood Pressure in the Elderly

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) and the Australian, longitudinal AIBL study (n = 576). In the combined sample, the Aß1-42/ Aß1-40 ratio was significantly and inversely associated with SBP (p = 0.03) and a similar trend was observed for DBP (p = 0.06). Using the median age (69) as a cut-off, the Aß1-42/Aß1-40 ratio was strongly associated with both SBP and DBP in elderly individuals (p = 0.002 and p = 0.03, respectively). Consistently, a high Aß1-42/ Aß1-40 ratio was associated with a lower risk of hypertension in both the combined whole sample (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.56-0.90) and (to an even greater extent) in the elderly subjects (OR, 0.53; 95% CI, 0.37–0.75). Lastly, all these associations appeared to be primarily driven by the level of plasma Aß1-40. Conclusion The plasma Aß1-42/Aß1-40 ratio is inversely associated with SBP, DBP and the risk of hypertension in elderly subjects, suggesting that Aß peptides affect blood pressure in vivo. These results may be particularly relevant in Alzheimer\u27s disease, in which a high Aß1-42/Aß1-40 plasma ratio is reportedly associated with a decreased risk of incident disease

Level 1-to-2 Data Processor Version 3.0: A Major Upgrade of the GOME/ERS-2 Total Ozone Retrieval Algorithm,

Abstract The Global Ozone Monitoring Experiment (GOME) was launched in April 1995, and the GOME Data Processor (GDP) retrieval algorithm has processed operational total ozone amounts since July 1995. GDP Level 1-to-2 is based on the two-step Differential Optical Absorption Spectroscopy (DOAS) approach, involving slant column fitting followed by Air Mass Factor (AMF) conversions to vertical column amounts. We present a major upgrade of this algorithm to Version 3.0. GDP 3.0 was implemented in July 2002, and the 9-year GOME data record from July 1995 to December 2004 has been processed using this algorithm. The key component in GDP 3.0 is an iterative approach to AMF calculation, in which AMFs and corresponding vertical column densities are adjusted to reflect the true ozone distribution as represented by the fitted DOAS effective slant column. A neural networkensemble is used to optimize the fast and accurate parameterization of AMFs. We describe results of a recent validation exercise for the operational version of the total ozone algorithm; in particular, seasonal and meridian errors are reduced by a factor of two. On a global basis, GDP 3.0 ozone total column results lie between -2% and +4% of ground-based values for moderate solar zenith angles lower than 70°. A larger variability of about +5% and -8% is observed for higher solar zenith angles up to 90°. Copyright OCIS codes 01

TROPOMI/S5P total ozone column data: global ground-based validation and consistency with other satellite missions

In this work, the TROPOMI near real time (NRTI) and offline (OFFL) total ozone column (TOC) products are presented and compared to daily ground-based quality-assured Brewer and Dobson TOC measurements deposited in the World Ozone and Ultraviolet Radiation Data Centre (WOUDC). Additional comparisons to individual Brewer measurements from the Canadian Brewer Network and the European Brewer Network (Eubrewnet) are performed. Furthermore, twilight zenith-sky measurements obtained with ZSL-DOAS (Zenith Scattered Light Differential Optical Absorption Spectroscopy) instruments, which form part of the SAOZ network (Système d'Analyse par Observation Zénitale), are used for the validation. The quality of the TROPOMI TOC data is evaluated in terms of the influence of location, solar zenith angle, viewing angle, season, effective temperature, surface albedo and clouds. For this purpose, globally distributed ground-based measurements have been utilized as the background truth. The overall statistical analysis of the global comparison shows that the mean bias and the mean standard deviation of the percentage difference between TROPOMI and ground-based TOC is within 0 –1.5 % and 2.5 %–4.5 %, respectively. The mean bias that results from the comparisons is well within the S5P product requirements, while the mean standard deviation is very close to those limits, especially considering that the statistics shown here originate both from the satellite and the ground-based measurements.This research has been supported by the European Space Agency “Preparation and Operations of the Mission Performance Centre (MPC) for the Copernicus Sentinel-5 Precursor Satellite” (contract no. 4000117151/16/1-LG)

Association of Plasma Aß Peptides with Blood Pressure in the Elderly

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) and the Australian, longitudinal AIBL study (n = 576). In the combined sample, the Aß1-42/ Aß1-40 ratio was significantly and inversely associated with SBP (p = 0.03) and a similar trend was observed for DBP (p = 0.06). Using the median age (69) as a cut-off, the Aß1-42/Aß1-40 ratio was strongly associated with both SBP and DBP in elderly individuals (p = 0.002 and p = 0.03, respectively). Consistently, a high Aß1-42/ Aß1-40 ratio was associated with a lower risk of hypertension in both the combined whole sample (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.56-0.90) and (to an even greater extent) in the elderly subjects (OR, 0.53; 95% CI, 0.37–0.75). Lastly, all these associations appeared to be primarily driven by the level of plasma Aß1-40. Conclusion The plasma Aß1-42/Aß1-40 ratio is inversely associated with SBP, DBP and the risk of hypertension in elderly subjects, suggesting that Aß peptides affect blood pressure in vivo. These results may be particularly relevant in Alzheimer\u27s disease, in which a high Aß1-42/Aß1-40 plasma ratio is reportedly associated with a decreased risk of incident disease

FDR4ATMOS (Task A): Improving SCIAMACHY Level 1 and add calibrated lunar data

The project FDR4ATMOS (Fundamental Data Records in the domain of satellite Atmospheric Composition) has been initiated by the European Space Agency (ESA). Task A of the project covers the improvement of the SCIAMACHY Level 1b degradation correction, with the aim to remove ozone trends from the SCIAMACHY Level 2 data set that were introduced during the development of baseline version 9 (both data sets not released). We will also, for the first time, add calibrated lunar data to Level 1, covering the whole spectral range of SCIAMACHY and the full mission time. The SCIAMACHY processing chain for better Ozone total column data: After the full re-processing of the SCIAMACHY mission with the updated processor versions, the validation showed that the total Ozone column drifted downward by nearly 2% over the mission lifetime. This drift is likely caused by changes in the degradation correction in the Level 1 processor, that led to subtle changes in the spectral structures. These are misinterpreted as an atmospheric signature. We updated the Level 0-1 processor accordingly and a full mission re-processing was done. As a major improvement we additionally incorporated calibrated lunar data in the SCIAMACHY Level 1b product. In the new Level 1b product we will provide the individual scans of the moon as well as disk integrated and calibrated lunar irradiance and reflectance. The instrument performed regular lunar observations building up a unique 10 year data set of lunar spectra from the UV to the SWIR with moderately high spectral resolution. SCIAMACHY scanned the full lunar disk and over the ten year mission time made 1123 observations of the moon. Most satellites can only observe the moon under very specific geometries due to instrument-viewing and orbit restrictions. SCIAMACHY, however, with a two mirror pointing system was much less constrained and was able to observe the moon under an extreme large variation of geometries (especially during dedicated lunar observation campaigns), allowing it thus potentially to tie different satellites and geometry observations together. During the individual lunar observations, SCIAMACHY only saw a small slice of the Moon and scanned over the moon in order to obtain data for the full disk. We combined the individual calibrated scans, correcting for scan speed and the fact the Moon does not fill the entire slit length. The calculation of distance-normalized lunar reflectances did not require an external solar spectrum, but used solar measurements of SCIAMACHY itself. This version of Level 1 will also be the first one that replaces the ENVISAT byte stream format with the netCDF format that is aligned with the product format of other atmospheric sensors like the Sentinels The paper will present the improvements of the Level 1 product, the results of the quality control and validation

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Copernicus Cal/Val Solution - D3.6 - Copernicus Cal/Val Solution

This document presents the synthesis of activities performed in Task 3 of the CCVS project. It gathers the main identified gaps and recommendations regarding: • Instrumentation technologies • Development of Cal/Val methods • In-situ measurement networks and field campaigns • Data distribution services The recommendations are selected in order to form a consistent plan to improve cal/val activities for all Sentinel missions, trying to find an overall balance across the main domains (optical observations, radar imaging, altimetry and atmospheric composition missions). Finally, we provide some recommendations regarding coordination, organization and processes involving the different actors of the Copernicus programme. Programmatic and sustainability aspects are not addressed in this document (cf. Task 4 documents)

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Shared genetic contribution to ischemic stroke and Alzheimer's disease

Objective Increasing evidence suggests epidemiological and pathological links between Alzheimer's disease (AD) and ischemic stroke (IS). We investigated the evidence that shared genetic factors underpin the two diseases. Methods Using genome-wide association study (GWAS) data from METASTROKE + (15,916 IS cases and 68,826 controls) and the International Genomics of Alzheimer's Project (IGAP; 17,008 AD cases and 37,154 controls), we evaluated known associations with AD and IS. On the subset of data for which we could obtain compatible genotype-level data (4,610 IS cases, 1,281 AD cases, and 14,320 controls), we estimated the genome-wide genetic correlation (rG) between AD and IS, and the three subtypes (cardioembolic, small vessel, and large vessel), using genome-wide single-nucleotide polymorphism (SNP) data. We then performed a meta-analysis and pathway analysis in the combined AD and small vessel stroke data sets to identify the SNPs and molecular pathways through which disease risk may be conferred. Results We found evidence of a shared genetic contribution between AD and small vessel stroke (rG [standard error] = 0.37 [0.17]; p = 0.011). Conversely, there was no evidence to support shared genetic factors in AD and IS overall or with the other stroke subtypes. Of the known GWAS associations with IS or AD, none reached significance for association with the other trait (or stroke subtypes). A meta-analysis of AD IGAP and METASTROKE + small vessel stroke GWAS data highlighted a region (ATP5H/KCTD2/ICT1) associated with both diseases (p = 1.8 × 10-8). A pathway analysis identified four associated pathways involving cholesterol transport and immune response. Interpretation Our findings indicate shared genetic susceptibility to AD and small vessel stroke and highlight potential causal pathways and loci. Ann Neurol 2016;79:739-74