Diffusion MR Characteristics Following Concurrent Radiochemotherapy Predicts Progression-Free and Overall Survival in Newly Diagnosed Glioblastoma.

The standard of care for newly diagnosed glioblastoma (GBM) is surgery, then radiotherapy (RT) with concurrent temozolomide (TMZ), followed by adjuvant TMZ. We hypothesized patients with low diffusivity measured using apparent diffusion coefficient (ADC) histogram analysis evaluated after RT+TMZ, prior to adjuvant TMZ, would have a significantly shorter progression-free (PFS) and overall survival (OS). To test this hypothesis we evaluated 120 patients with newly diagnosed GBM receiving RT+TMZ followed by adjuvant TMZ. MRI was performed after completion of RT+TMZ, prior to initiation of adjuvant TMZ. A double Gaussian mixed model was used to describe the ADC histograms within the enhancing tumor, where ADCL and ADCH were defined as the mean ADC value of the lower and higher Gaussian distribution, respectively. An ADCL value of 1.0 um2/ms and ADCH value of 1.6 um2/ms were used to stratify patients into high and low risk categories. Results suggest patients with low ADCL had significantly shorter PFS (Cox Hazard Ratio = 0.12, P = 0.0006). OS was significantly shorter with low ADCL tumors, showing a median OS of 407 vs. 644 days (Cox Hazard Ratio = 0.31, P = 0.047). ADCH was not predictive of PFS or OS when accounting for age and ADCL. In summary, newly diagnosed glioblastoma patients with low ADCL after completion of RT+TMZ are likely to progress and die earlier than patients with higher ADCL. Results suggest ADC histogram analysis may be useful for patient risk stratification following completion of RT+TMZ

The development, implementation and early learnings of a training program to advance interest in behavioral research careers among undergraduate BIPOC students majoring in psychology.

OBJECTIVES: Black, indigenous and people of color (BIPOC) remain underrepresented in research occupations. This report discusses a collaboration to train undergraduate BIPOC students in clinical research between a public health institute, two medical schools, and a historically Black College or University (HBCU). This nine-month program trained BIPOC undergraduates in research methodology, psychology, and addiction science, and immersed trainees in real-world research. The program included didactic seminars, experiential activities, and a mentored research project culminating in a poster and oral presentation. METHODS: Key learnings, program satisfaction survey results, and preliminary outcomes from the first three program cohorts (N = 6 students) are presented. This program addressed several barriers hypothesized to contribute to the limited number of BIPOC students pursuing research careers, including mentorship from BIPOC faculty and financial concerns. RESULTS: Students reported moderate to high satisfaction with the program and endorsed gaining new research skills. Limitations and future directions are discussed. CONCLUSION: The expansion of the BIPOC health and research workforce is an urgent priority given the importance of BIPOC professionals to the health of our nation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04650386

Landsat Imagery from a CubeSat: Results and Operational Lessons from the R3 Satellite\u27s First 18 Months in Space

R3 is a 3-U CubeSat launched on a RocketLab Electron into a 500 km circular orbit at 85° inclination on December 16th, 2018. The spacecraft flies a multispectral sensor that takes data in the six Landsat visible and near infrared bands. The R3 sensor mates a custom refractive telescope with a Materion Precision Optics Landsat filter, and an ON Semiconductor fast-framing high-sensitivity Si CMOS array, to produce 50-km wide, 44-m resolution Landsat-like image strips. Data are taken in push-broom mode and are downlinked via a 100Mbps compact lasercom system. Frames are then co-added on the ground in time-delay-integration (TDI) fashion to increase signal-to-noise ratio and create multi-spectral Earth images from the compact sensor. The system is an engineering concept demonstration of a compact multispectral sensor in CubeSat form. We describe our ConOps, flight operations, sensor focus and alignment, initial imaging check out, and initial comparisons of R3 data to Landsat-8 imagery of the same Earth locations. RGB, color infrared, and normalized differential vegetation index (NDVI) products are compared between CUMULOS and Landsat-8. Results show good multispectral image quality from the CubeSat sensor, and illustrate the ability of R3 to detect vegetation and other features in a manner similar to Landsat, as well as the challenge in perfectly exposing all 6 VIS/NIR Landsat bands using our commercial 10-bit CMOS array. We also highlight the performance of the compact laser communications system which enabled the successful performance of this mission

JWST mirror and actuator performance at cryo-vacuum

The James Webb Space Telescope (JWST) telescope’s Secondary Mirror Assembly (SMA) and eighteen Primary Mirror Segment Assemblies (PMSAs) are each actively controlled in rigid body position via six hexapod actuators. Each of the PMSAs additionally has a radius of curvature actuator. The mirrors are stowed to the mirror support structure to survive the launch environment and then must be deployed 12.5 mm to reach the nominally deployed position before the Wavefront Sensing & Control (WFSC) alignment and phasing process begins. JWST requires testing of the full optical system in a Cryogenic Vacuum (CV) environment before launch. The cryo vacuum test campaign was executed in Chamber A at the Johnson Space Center (JSC) in Houston Texas. The test campaign consisted of an ambient vacuum test, a cooldown test, a cryo stable test at 65 Kelvin, a warmup test, and finally a second ambient vacuum test. Part of that test campaign was the functional and performance testing of the hexapod actuators on the flight mirrors. This paper will describe the testing that was performed on all 132 hexapod and radius of curvature actuators. The test campaign first tests actuators individually then tested how the actuators perform in the hexapod system. Telemetry from flight sensors on the actuators and measurements from external metrology devices such as interferometers, photogrammetry systems and image analysis was used to demonstrate the performance of the JWST actuators. The mirror move commanding process was exercised extensively during the JSC CV test and many examples of accurately commanded moves occurred. The PMSA and SMA actuators performed extremely well during the JSC CV test, and we have demonstrated that the actuators are fully functional both at ambient and cryo temperatures and that the mirrors will go to their commanded positions with the accuracy needed to phase and align the telescope

Spitzer observations of the thermal emission from WASP-43b

WASP-43b is one of the closest-orbiting hot Jupiters, with a semimajor axis of a = 0.01526 +/- 0.00018 AU and a period of only 0.81 days. However, it orbits one of the coolest stars with a hot Jupiter (Tstar = 4520 +/- 120 K), giving the planet a modest equilibrium temperature of Teq = 1440 +/- 40 K, assuming zero Bond albedo and uniform planetary energy redistribution. The eclipse depths and brightness temperatures from our jointly fit model are 0.347% +/- 0.013% and 1670 +/- 23 K at 3.6 {\mu}m and 0.382% +/- 0.015% and 1514 +/- 25 K at 4.5 {\mu}m. The eclipse timings improved the estimate of the orbital period, P, by a factor of three (P = 0.81347436 +/- 1.4*10-7 days) and put an upper limit on the eccentricity (e = 0.010+0.010 -0.007). We use our Spitzer eclipse depths along with four previously reported ground-based photometric observations in the near-infrared to constrain the atmospheric properties of WASP-43b. The data rule out a strong thermal inversion in the dayside atmosphere of WASP-43b. Model atmospheres with no thermal inversions and fiducial oxygen-rich compositions are able to explain all the available data. However, a wide range of metallicities and C/O ratios can explain the data. The data suggest low day-night energy redistribution in the planet, consistent with previous studies, with a nominal upper limit of about 35% for the fraction of energy incident on the dayside that is redistributed to the nightside.Comment: 11 pages, 9 figure

Thermal Emission of WASP-14b Revealed with Three Spitzer Eclipses

Exoplanet WASP-14b is a highly irradiated, transiting hot Jupiter. Joshi et al. calculate an equilibrium temperature Teq of 1866 K for zero albedo and reemission from the entire planet, a mass of 7.3 +/- 0.5 Jupiter masses and a radius of 1.28 +/- 0.08 Jupiter radii. Its mean density of 4.6 g/cm3 is one of the highest known for planets with periods less than 3 days. We obtained three secondary eclipse light curves with the Spitzer Space Telescope. The eclipse depths from the best jointly fit model are $0.224\%$ +/- $0.018\%$ at 4.5 {\mu}m and $0.181\%$ +/- $0.022\%$ at 8.0 {\mu}m. The corresponding brightness temperatures are 2212 +/- 94 K and 1590 +/- 116 K. A slight ambiguity between systematic models suggests a conservative 3.6 {\mu}m eclipse depth of $0.19\%$ +/- $0.01\%$ and brightness temperature of 2242 +/- 55 K. Although extremely irradiated, WASP-14b does not show any distinct evidence of a thermal inversion. In addition, the present data nominally favor models with day night energy redistribution less than $~30\%$. The current data are generally consistent with oxygen-rich as well as carbon-rich compositions, although an oxygen-rich composition provides a marginally better fit. We confirm a significant eccentricity of e = 0.087 +/- 0.002 and refine other orbital parameters.Comment: 16 pages, 16 figure

Possible thermochemical disequilibrium in the atmosphere of the exoplanet GJ 436b

The nearby extrasolar planet GJ 436b--which has been labelled as a 'hot Neptune'--reveals itself by the dimming of light as it crosses in front of and behind its parent star as seen from Earth. Respectively known as the primary transit and secondary eclipse, the former constrains the planet's radius and mass, and the latter constrains the planet's temperature and, with measurements at multiple wavelengths, its atmospheric composition. Previous work using transmission spectroscopy failed to detect the 1.4-\mu m water vapour band, leaving the planet's atmospheric composition poorly constrained. Here we report the detection of planetary thermal emission from the dayside of GJ 436b at multiple infrared wavelengths during the secondary eclipse. The best-fit compositional models contain a high CO abundance and a substantial methane (CH4) deficiency relative to thermochemical equilibrium models for the predicted hydrogen-dominated atmosphere. Moreover, we report the presence of some H2O and traces of CO2. Because CH4 is expected to be the dominant carbon-bearing species, disequilibrium processes such as vertical mixing and polymerization of methane into substances such as ethylene may be required to explain the hot Neptune's small CH4-to-CO ratio, which is at least 10^5 times smaller than predicted

Influence of coding variability in APP-Aß metabolism genes in sporadic Alzheimer's disease

The cerebral deposition of Aß42, a neurotoxic proteolitic derivate of amyloid precursor protein (APP), is a central event in Alzheimer’s disease (AD)(Amyloid hypothesis). Given the key role of APP-Aß metabolism in AD pathogenesis, we selected 29 genes involved in APP processing, Aß degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 435 sporadic and mainly late-onset AD cases and 801 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, which were nominally significant, were found to be very rare coding variants (MAF 0.3%-0.8%) that map to genes involved in APP processing (MEP1B), trafficking and recycling (SORL1), Aß extracellular degradation (ACE) and clearance (LRP1). Moreover, four genes (ECE1, LYZ, TTR and MME) have been found as nominally associated to AD using c-alpha and SKAT tests. We suggest that Aβ degradation and clearance, rather than Aβ production, may play a crucial role in the etiology of sporadic AD

Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells

In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B stage. A subsequent functional light chain (LC) rearrangement then results in the surface expression of IgM at the immature B cell stage. Here we show that interruption of basal IgM signaling in immature B cells, either by the inducible deletion of surface Ig via Cre-mediated excision or by incubating cells with the tyrosine kinase inhibitor herbimycin A or the phosphatidylinositol 3-kinase inhibitor wortmannin, led to a striking “back-differentiation” of cells to an earlier stage in B cell development, characterized by the expression of pro-B cell genes. Cells undergoing this reversal in development also showed evidence of new LC gene rearrangements, suggesting an important role for basal Ig signaling in the maintenance of LC allelic exclusion. These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms

Influence of coding variability in APP-Aß metabolism genes in sporadic Alzheimer's disease

The cerebral deposition of Aß42, a neurotoxic proteolitic derivate of amyloid precursor protein (APP), is a central event in Alzheimer’s disease (AD)(Amyloid hypothesis). Given the key role of APP-Aß metabolism in AD pathogenesis, we selected 29 genes involved in APP processing, Aß degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 435 sporadic and mainly late-onset AD cases and 801 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, which were nominally significant, were found to be very rare coding variants (MAF 0.3%-0.8%) that map to genes involved in APP processing (MEP1B), trafficking and recycling (SORL1), Aß extracellular degradation (ACE) and clearance (LRP1). Moreover, four genes (ECE1, LYZ, TTR and MME) have been found as nominally associated to AD using c-alpha and SKAT tests. We suggest that Aβ degradation and clearance, rather than Aβ production, may play a crucial role in the etiology of sporadic AD