Characterization of background reflectivity for MEDUSA

The DARPA MEDUSA program goal is to detect, locate, and identify electro-optical threats in the vicinity of a moving platform. Laser sensing will be employed to find these threats by looking for anomalous reflections from threat sensors. However, the reflectivity variability (clutter) in both natural and manmade backgrounds will inherently limit target detection levels. In parallel with advanced component development by several aerospace contractors, a study of this clutter limitation was initiated in the long-wave (LW) and midwave (MW) infrared spectral regions to properly drive system design parameters. The analysis of clutter and associated limits on detection has been a major component of LANL efforts in laser remote sensing for non-proliferation. LANL is now analyzing existing data and conducting additional selected measurements in both the LWIR (9 and 10.6 pm) and MWIR (4.6 pm) in support of the DARPA program to increase our understanding of these clutter limitations and, thereby aid in the design and development of the MEDUSA system. The status of the LANL effort will be discussed. A variety of different natural and manmade target types have been investigated. Target scenes range from relatively low clutter sites typical of a southwestern desert to higher clutter downtown urban sites. Images are created by conducting raster scans across a scene interest. These images are then analyzed using data clustering techniques (e g K-means) to identify regions within the scene that contain similar reflectivity profiles. Data will be presented illustrating the reflectivity variability among different samples of the same target type, Le. within the same cluster, and among different data clusters. In general, it is found that the variability of reflectivities among similar targets is well represented by a log-normal distribution. Furthermore, manmade target tend to have higher reflectivities and more variability than natural targets. The implications of this observation for MEDUSA systems designed to locate and identify threat sensors will be discussed. The implications for chemical sensing applications will also be addressed

NACHOS, a CubeSat-Based High-Resolution UV-Visible Hyperspectral Imager for Remote Sensing of Trace Gases: System Overview, Science Objectives, and Preliminary Results

The Nano-satellite Atmospheric Chemistry Hyperspectral Observation System (NACHOS) is a high-throughput (f/2.9), high spectral resolution (1.3 nm optical, 0.57 nm sampling) hyperspectral imager covering the 300-500 nm spectral region with 350 spectral bands. The combined 1.5U instrument payload and 1.5U spacecraft bus comprise a 3U CubeSat. Spectroscopically similar to NASA’s Ozone Monitoring Instrument (OMI), which provides wide-field coverage at ~20 km spatial resolution, NACHOS offers complementary targeted measurements at far higher spatial resolution of ~0.4 km/pixel from 500 km altitude over its 15 ̊ across-track field of view. NACHOS incorporates highly streamlined onboard gas-retrieval algorithms, alleviating the need to routinely downlink massive hyperspectral data cubes. This paper discusses the instrument design, requirements leading to it, preliminary results, and science goals, including monitoring NO2 as a proxy for anthropogenic greenhouse gases, low-level degassing of SO2 and halogen oxides at pre-eruptive volcanoes, and formaldehyde from wildfires. Aiming for an eventual many-satellite constellation providing both high spatial resolution and frequent target revisits, the current NACHOS project is launching two CubeSats, the first already launched to the International Space Station aboard the NG-17 Cygnus vehicle on February 19, 2022 and awaiting deployment to its final orbit in June, and the second launching June 29, 2022

A cluster randomised trial of educational messages to improve the primary care of diabetes

<p>Abstract</p> <p>Background</p> <p>Regular laboratory test monitoring of patient parameters offers a route for improving the quality of chronic disease care. We evaluated the effects of brief educational messages attached to laboratory test reports on diabetes care.</p> <p>Methods</p> <p>A programme of cluster randomised controlled trials was set in primary care practices in one primary care trust in England. Participants were the primary care practices' constituent healthcare professionals and patients with diabetes. Interventions comprised brief educational messages added to paper and electronic primary care practice laboratory test reports and introduced over two phases. Phase one messages, attached to Haemoglobin A1c (HbA1c) reports, targeted glycaemic and cholesterol control. Phase two messages, attached to albumin:creatinine ratio (ACR) reports, targeted blood pressure (BP) control, and foot inspection. Main outcome measures comprised practice mean HbA1c and cholesterol levels, diastolic and systolic BP, and proportions of patients having undergone foot inspections.</p> <p>Results</p> <p>Initially, 35 out of 37 eligible practices participated. Outcome data were available for a total of 8,690 patients with diabetes from 32 practices. The BP message produced a statistically significant reduction in diastolic BP (-0.62 mmHg; 95% confidence interval -0.82 to -0.42 mmHg) but not systolic BP (-0.06 mmHg, -0.42 to 0.30 mmHg) and increased the odds of achieving target BP control (odds ratio 1.05; 1.00, 1.10). The foot inspection message increased the likelihood of a recorded foot inspection (incidence rate ratio 1.26; 1.18 to 1.36). The glycaemic control message had no effect on mean HbA1c (increase 0.01%; -0.03 to 0.04) despite increasing the odds of a change in likelihood of HbA1c tests being ordered (OR 1.06; 1.01, 1.11). The cholesterol message had no effect (decrease 0.01 mmol/l, -0.04 to 0.05).</p> <p>Conclusions</p> <p>Three out of four interventions improved intermediate outcomes or process of diabetes care. The diastolic BP reduction approximates to relative reductions in mortality of 3% to 5% in stroke and 3% to 4% in ischaemic heart disease over 10 years. The lack of effect for other outcomes may, in part, be explained by difficulties in bringing about further improvements beyond certain thresholds of clinical performance.</p> <p>Trial Registration</p> <p>Current Controlled Trials, <a href="http://www.controlled-trials.com/ISRCTN2186314">ISRCTN2186314</a>.</p

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

EC-GLRT: Detecting Weak Plumes in Non-Gaussian Hyperspectral Clutter Using an Elliptically-Contoured Generalized Likelihood Ratio Test

We investigate the behavior of a detector for weak gaseous plumes in hyperspectral imagery that can be derived in terms of a generalized likelihood ratio test (GLRT) applied to an elliptically-contoured (EC) model for the distribution of back-ground clutter. Two limiting cases of this EC-GLRT detector are the adaptive matched filter (AMF) and the adaptive coher-ence estimator (ACE). While the general EC-GLRT detector does not share the specific optimality or invariance properties exhibited by these limiting cases, it provides an in-between model that can be competitive with both of them over a broad range of scenarios. Index Terms — hyperspectral imagery, chemical plume, matched filter, generalized likelihood ratio test, non-Gaussian distribution 1