Analysis and compensation for errors in electrical impedance tomography images and ventilation-­related measures due to serial data collection

Electrical impedance tomography (EIT) is increasingly being used as a bedside tool for monitoring regional lung ventilation. However, most clinical systems use serial data collection which, if uncorrected, results in image distortion, particularly at high breathing rates. The objective of this study was to determine the extent to which this affects derived parameters. Raw EIT data were acquired with the GOE­MF II EIT device (CareFusion, Höchberg, Germany) at a scan rate of 13 images/s during both spontaneous breathing and mechanical ventilation. Boundary data for periods of undisturbed tidal breathing were corrected for serial data collection errors using a Fourier based algorithm. Images were reconstructed for both the corrected and original data using the GREIT algorithm, and parameters describing the filling characteristics of the right and left lung derived on a breath by breath basis. Values from the original and corrected data were compared using paired t­ tests. Of the 33 data sets, 23 showed significant differences in filling index for at least one region, 11 had significant differences in calculated tidal impedance change and 12 had significantly different filling fractions (p = 0.05). We conclude that serial collection errors should be corrected before image reconstruction to avoid clinically misleading results

Constraining Martian Regolith and Vortex Parameters From Combined Seismic and Meteorological Measurements

The InSight mission landed on Mars in November 2018 and has since observed multiple convective vortices with both the high performance barometer and the low-noise seismometer SEIS that has unprecedented sensitivity. Here, we present a new method that uses the simultaneous pressure and seismic measurements of convective vortices to place constraints on the elastic properties of the Martian subsurface and the Martian vortex properties, while also allowing a reconstruction of the convective vortex trajectories. From data filtered in the (0.02–0.3 Hz) frequency band, we estimate that the mean value of η (η = E/[1 − ν2], where E is the Young's modulus and ν is the Poisson's ratio) of the Martian ground in the region around SEIS is 239 ± 140 MPa. In addition, we suggest that the previously reported paucity of vortex seismic observations to the west of InSight may be due to the fact that the ground is harder to the west than to the east, consistent with geomorphological surface interpretations

Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue

Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias is inherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mm biopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB but low clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action

The interior of Mars as seen by InSight (Invited)

InSight is the first planetary mission dedicated to exploring the whole interior of a planet using geophysical methods, specifically seismology and geodesy. To this end, we observed seismic waves of distant marsquakes and inverted for interior models using differential travel times of phases reflected at the surface (PP, SS...) or the core mantle-boundary (ScS), as well as those converted at crustal interfaces. Compared to previous orbital observations1-3, the seismic data added decisive new insights with consequences for the formation of Mars: The global average crustal thickness of 24-75 km is at the low end of pre-mission estimates5. Together with the the thick lithosphere of 450-600 km5, this requires an enrichment of heat-producing elements in the crust by a factor of 13-20, compared to the primitive mantle. The iron-rich liquid core is 1790-1870 km in radius6, which rules out the existence of an insulating bridgmanite-dominated lower mantle on Mars. The large, and therefore low-density core needs a high amount of light elements. Given the geochemical boundary conditions, Sulfur alone cannot explain the estimated density of ~6 g/cm3 and volatile elements, such as oxygen, carbon or hydrogen are needed in significant amounts. This observation is difficult to reconcile with classical models of late formation from the same material as Earth. We also give an overview of open questions after three years of InSight operation on the surface of Mars, such as the potential existence of an inner core or compositional layers above the CM

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma.

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action

The mechanical properties of the Martian soil at the InSight landing site

The InSight mission is a NASA geophysical mission aimed at better understanding the structure of Mars and of the other rocky plan-ets of the solar system. To do so, various instruments are used, including a very sensitive seismometer (SEIS) and a dynamic self-penetrating heat probe (HP3) that have been placed on the Mars surface by the Instrument Deployment Arm (IDA). Besides geophys-ical data (which have definitely enriched and completed existing knowledge on the structure of Mars), the InSight instruments, togeth-er with orbiter observations and tests carried out on the soil with the IDA, have significantly increased the knowledge of the geologi-cal and geotechnical characteristics of the surface material at the InSight site, which is made up of a basaltic sand. In-situ data were also successfully compared with terrestrial previous estimates from terrestrial lab tests, carried out on various soil simulants. Small strain (elastic) parameters at small strains were derived from wave velocity measurements between the self-penetrating probe and the seismometer. Strength data were derived from both IDA operations and penetration data. The soil includes some pebbles within a somewhat cohesive sandy matrix, limiting the heat probe penetration to only 40 cm length. Thermal data were also obtained, allowing for some thermo-elastic modelling of the effect of the Phobos (one of the “Moons” of Mars) eclipses. Elastic data were also derived from the effects of wind on the ground, detected by SEIS

Constraints on the shallow elastic and anelastic structure of Mars from InSight seismic data

Mars’s seismic activity and noise have been monitored since January 2019 by the seismometer of the InSight (Interior Exploration using Seismic Investigations, Geodesy and Heat Transport) lander. At night, Mars is extremely quiet; seismic noise is about 500 times lower than Earth’s microseismic noise at periods between 4 s and 30 s. The recorded seismic noise increases during the day due to ground deformations induced by convective atmospheric vortices and ground-transferred wind-generated lander noise. Here we constrain properties of the crust beneath InSight, using signals from atmospheric vortices and from the hammering of InSight’s Heat Flow and Physical Properties (HP3) instrument, as well as the three largest Marsquakes detected as of September 2019. From receiver function analysis, we infer that the uppermost 8–11 km of the crust is highly altered and/ or fractured. We measure the crustal diffusivity and intrinsic attenuation using multiscattering analysis and find that seismic attenuation is about three times larger than on the Moon, which suggests that the crust contains small amounts of volatiles