A Study of the 20 Day Superorbital Modulation in the High-Mass X-ray Binary IGR J16493-4348

We report on Nuclear Spectroscopic Telescope Array (NuSTAR), Neil Gehrels Swift Observatory (Swift) X-ray Telescope (XRT) and Swift Burst Alert Telescope (BAT) observations of IGR J16493-4348, a wind-fed Supergiant X-ray Binary (SGXB) showing significant superorbital variability. From a discrete Fourier transform of the BAT light curve, we refine its superorbital period to be 20.058 $\pm$ 0.007 days. The BAT dynamic power spectrum and a fractional root mean square analysis both show strong variations in the amplitude of the superorbital modulation, but no observed changes in the period were found. The superorbital modulation is significantly weaker between MJD 55,700 and MJD 56,300. The joint NuSTAR and XRT observations, which were performed near the minimum and maximum of one cycle of the 20 day superorbital modulation, show that the flux increases by more than a factor of two between superorbital minimum and maximum. We find no significant changes in the 3-50 keV pulse profiles between superorbital minimum and maximum, which suggests a similar accretion regime. Modeling the pulse-phase averaged spectra we find a possible Fe K$\alpha$ emission line at 6.4 keV at superorbital maximum. The feature is not significant at superorbital minimum. While we do not observe any significant differences between the pulse-phase averaged spectral continua apart from the overall flux change, we find that the hardness ratio near the broad main peak of the pulse profile increases from superorbital minimum to maximum. This suggests the spectral shape hardens with increasing luminosity. We discuss different mechanisms that might drive the observed superorbital modulation.Comment: 17 pages, 14 figures, 3 tables, accepted for publication in The Astrophysical Journal on 2019 May 1

Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency.

Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency. Methods: In this cross-sectional study, ELISA was used to measure six markers of innate immunity (sCD163, CCL18, LBP, sCD14, IL-18, and CRP) in plasma from 30 GRN mutation carriers (17 asymptomatic, 13 symptomatic) and 29 controls. Voxel based morphometry was used to model associations between marker levels and brain atrophy in mutation carriers relative to controls. Linear regression was used to model relationships between plasma marker levels with mean frontal white matter integrity [fractional anisotropy (FA)] and the FTLD modified Clinical Dementia Rating Scale sum of boxes score (FTLD-CDR SB). Results: Plasma sCD163 was higher in symptomatic GRN carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); p < 0.05]. Plasma CCL18 was higher in symptomatic GRN carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); p < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus (p FWE corrected <0.05) in all mutation carriers relative to controls. Plasma LBP levels inversely correlated with bilateral frontal white matter FA (R2 = 0.59, p = 0.009) in mutation carriers. Elevation in plasma was positively correlated with CDR-FTLD SB (b = 2.27 CDR units/μg LBP/ml plasma, R2 = 0.76, p = 0.003) in symptomatic carriers. Conclusion: FTLD-GRN is associated with elevations in peripheral biomarkers of macrophage-mediated innate immunity, including sCD163 and CCL18. Clinical disease severity and white matter integrity are correlated with blood LBP, suggesting a role for peripheral immune activation in FTLD-GRN

Landsat 9 Thermal Infrared Sensor 2 Architecture and Design

The Thermal Infrared Sensor 2 (TIRS-2) will fly aboard the Landsat 9 spacecraft and leverages the Thermal Infrared Sensor (TIRS) design currently flying on Landsat 8. TIRS-2 will provide similar science data as TIRS, but is not a buildto-print rebuild due to changes in requirements and improvements in absolute accuracy. The heritage TIRS design has been modified to reduce the influence of stray light and to add redundancy for higher reliability over a longer mission life. The TIRS-2 development context differs from the TIRS scenario, adding to the changes. The TIRS-2 team has also learned some lessons along the way

Randomized Controlled Trial of Fish Oil and Montelukast and Their Combination on Airway Inflammation and Hyperpnea-Induced Bronchoconstriction

Both fish oil and montelukast have been shown to reduce the severity of exercise-induced bronchoconstriction (EIB). The purpose of this study was to compare the effects of fish oil and montelukast, alone and in combination, on airway inflammation and bronchoconstriction induced by eucapnic voluntary hyperpnea (EVH) in asthmatics. In this model of EIB, twenty asthmatic subjects with documented hyperpnea-induced bronchoconstriction (HIB) entered a randomized double-blind trial. All subjects entered on their usual diet (pre-treatment, n = 20) and then were randomly assigned to receive either one active 10 mg montelukast tablet and 10 placebo fish oil capsules (n = 10) or one placebo montelukast tablet and 10 active fish oil capsules totaling 3.2 g EPA and 2.0 g DHA (n = 10) taken daily for 3-wk. Thereafter, all subjects (combination treatment; n = 20) underwent another 3-wk treatment period consisting of a 10 mg active montelukast tablet or 10 active fish oil capsules taken daily. While HIB was significantly inhibited (p0.017) between treatment groups; percent fall in forced expiratory volume in 1-sec was −18.4±2.1%, −9.3±2.8%, −11.6±2.8% and −10.8±1.7% on usual diet (pre-treatment), fish oil, montelukast and combination treatment respectively. All three treatments were associated with a significant reduction (p0.017) in these biomarkers between treatments. While fish oil and montelukast are both effective in attenuating airway inflammation and HIB, combining fish oil with montelukast did not confer a greater protective effect than either intervention alone. Fish oil supplementation should be considered as an alternative treatment for EIB

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice

Landsat 9 TIRS-2 Architecture and Design

No abstract availabl

Landsat 9 TIRS-2 Architecture and Design

TIRS-2 will fly on the LandSat 9. Like TIRS on Landsat 8, TIRS-2 will produce radiometrically calibrated, geo-located thermal image data. USGS is responsible for operational code. TIRS-2 image data will have the same performance characteristics as that of TIRS on Landsat 8 except better in some cases

Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration

Objective: We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease progression. Methods: Baseline plasma NfL concentrations were measured with single-molecule array in original (n = 277) and validation (n = 297) cohorts. C9orf72, GRN, and MAPT mutation carriers and noncarriers from the same families were classified by disease severity (asymptomatic, prodromal, and full phenotype) using the CDR Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR+NACC-FTLD). Linear mixed-effect models related NfL to clinical variables. Results: In both cohorts, baseline NfL was higher in asymptomatic mutation carriers who showed phenoconversion or disease progression compared to nonprogressors (original: 11.4 ± 7 pg/mL vs 6.7 ± 5 pg/mL, p = 0.002; validation: 14.1 ± 12 pg/mL vs 8.7 ± 6 pg/mL, p = 0.035). Plasma NfL discriminated symptomatic from asymptomatic mutation carriers or those with prodromal disease (original cutoff: 13.6 pg/mL, 87.5% sensitivity, 82.7% specificity; validation cutoff: 19.8 pg/mL, 87.4% sensitivity, 84.3% specificity). Higher baseline NfL correlated with worse longitudinal CDR+NACC-FTLD sum of boxes scores, neuropsychological function, and atrophy, regardless of genotype or disease severity, including asymptomatic mutation carriers. Conclusions: Plasma NfL identifies asymptomatic carriers of FTLD-causing mutations at short-term risk of disease progression and is a potential tool to select participants for prevention clinical trials. Trial registration information: ClinicalTrials.gov Identifier: NCT02372773 and NCT02365922. Classification of evidence: This study provides Class I evidence that in carriers of FTLD-causing mutations, elevation of plasma NfL predicts short-term risk of clinical progression

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development