Phase I study of dose escalation to dominant intraprostatic lesions using high-dose-rate brachytherapy.

PurposeRadiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy.Material and methodsEnrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA < 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity.ResultsThe median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years).ConclusionsDose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients' enrollment

Report of the committee on a commercially developed space facility

Major facilities that could support significant microgravity research and applications activity are discussed. The ground-based facilities include drop towers, aircraft flying parabolic trajectories, and sounding rockets. Facilities that are intrinsically tied to the Space Shuttle range from Get-Away-Special canisters to Spacelab long modules. There are also orbital facilities which include recoverable capsules launched on expendable launch vehicles, free-flying spacecraft, and space stations. Some of these existing, planned, and proposed facilities are non-U.S. in origin, but potentially available to U.S. investigators. In addition, some are governmentally developed and operated whereas others are planned to be privately developed and/or operated. Tables are provided to show the facility, developer, duration, estimated gravity level, crew interaction, flight frequency, year available, power to payload, payload volume, and maximum payload mass. The potential of direct and indirect benefits of manufacturing in space are presented

Magellan: Preliminary description of Venus surface geologic units

Observations from approximately one-half of the Magellan nominal eight-month mission to map Venus are summarized. Preliminary compilation of initial geologic observations of the planet reveals a surface dominated by plains that are characterized by extensive and intensive volcanism and tectonic deformation. Four broad categories of units have been identified: plains units, linear belts, surficial units, and terrain units

Sulfated glycans engage the Ang–Tie pathway to regulate vascular development

The angiopoietin (Ang)–Tie pathway is essential for the proper maturation and remodeling of the vasculature. Despite its importance in disease, the mechanisms that control signal transduction through this pathway are poorly understood. Here, we demonstrate that heparan sulfate glycosaminoglycans (HS GAGs) regulate Ang–Tie signaling through direct interactions with both Ang ligands and Tie1 receptors. HS GAGs formed ternary complexes with Ang1 or Ang4 and Tie2 receptors, resulting in potentiation of endothelial survival signaling. In addition, HS GAGs served as ligands for the orphan receptor Tie1. The HS–Tie1 interaction promoted Tie1–Tie2 heterodimerization and enhanced Tie1 stability within the mature vasculature. Loss of HS–Tie1 binding using CRISPR–Cas9-mediated mutagenesis in vivo led to decreased Tie protein levels, pathway suppression and aberrant retinal vascularization. Together, these results reveal that sulfated glycans use dual mechanisms to regulate Ang–Tie signaling and are important for the development and maintenance of the vasculature

Spontaneous Calcium Release in Cardiac Myocytes: Store Overload and Electrical Dynamics

Heart disease is the leading cause of mortality in the United States. One cause of heart arrhythmia is calcium (Ca2+) mishandling in cardiac muscle cells. We adapt Izu\u27s et al. mathematical reaction-diffusion model of calcium in cardiac muscle cells, or cardiomyocytes implemented by Gobbert, and analyzed in Coulibaly et al. to include calcium being released from the sarcoplasmic reticulum (SR), the effects of buffers in the SR, particularly calsequestrin, and the effects of Ca2+ influx due to voltage across the cell membrane. Based on simulations of the model implemented in parallel using MPI, our findings aligned with known biological models and principles, giving us a thorough understanding of several factors that influence Ca2+ dynamics in cardiac myocytes. Specifically, dynamic calcium store will cap previous calcium blow-up seen in the model. Calcium channels located in spatial opposition of calcium release units produce more predictable intracellular calcium propagation. And we used multi-parametric calcium dynamics tables, which act as a multidimensional bifurcation diagram, to visualize parameter boundaries between different biophysical dynamics

Evaluating the Effects of Dimensionality in Advanced Avionic Display Concepts for Synthetic Vision Systems

Synthetic vision systems provide an in-cockpit view of terrain and other hazards via a computer-generated display representation. Two experiments examined several display concepts for synthetic vision and evaluated how such displays modulate pilot performance. Experiment 1 (24 general aviation pilots) compared three navigational display (ND) concepts: 2D coplanar, 3D, and split-screen. Experiment 2 (12 commercial airline pilots) evaluated baseline 'blue sky/brown ground' or synthetic vision-enabled primary flight displays (PFDs) and three ND concepts: 2D coplanar with and without synthetic vision and a dynamic multi-mode rotatable exocentric format. In general, the results pointed to an overall advantage for a split-screen format, whether it be stand-alone (Experiment 1) or available via rotatable viewpoints (Experiment 2). Furthermore, Experiment 2 revealed benefits associated with utilizing synthetic vision in both the PFD and ND representations and the value of combined ego- and exocentric presentations

Development of a Thin-Film Solar Cell Interconnect for the Powersphere Concept

Dual junction amorphous silicon (a-Si) solar cells produced on polyimide substrate have been selected as the best candidate to produce a lightweight solar array for the PowerSphere program. The PowerSphere concept features a space-inflatable, geodetic solar array approximately 0.6 meters in diameter and capable of generating about 20W of electrical power. Trade studies of various wiring concepts and connection methods led to an interconnect design with a copper contact that wraps around the edge, to the back of the solar cell. Applying Plasma Vapor Deposited (PVD) copper film to both sides and the edge of the solar cell produces the wrap around contact. This procedure results in a contact pad on the back of the solar cell, which is then laser welded to a flex circuit material. The flex circuit is constructed of copper in a custom designed routing pattern, and then sandwiched in a Kapton insulation layer. The flex circuit then serves as the primary power distribution system between the solar cells and the spacecraft. Flex circuit material is the best candidate for the wiring harness because it allows for low force deployment of the solar cells by the inflatable hinges on the PowerSphere. An additional frame structure, fabricated and assembled by ILC Dover, will reinforce the wrap around contact-flex blanket connection, thus providing a mechanically robust solar cell interconnect for the PowerSphere multifunctional program. The PowerSphere team will use the wraparound contact design approach as the primary solution for solar cell integration and the flex blanket for power distribution

Hispanic/Latinx ethnic differences in the relationships between behavioral inhibition, anxiety, and substance use in youth from the ABCD cohort

IntroductionElevated levels of behavioral inhibition (BI) may connote risk for both anxiety and substance use disorders. BI has consistently been shown to be associated with increased levels of anxiety, while the association between BI and substance use has been mixed. It is possible that the relationship between BI and substance use varies by individual difference factors. Hispanic/Latinx (H/L) youth in particular may have stronger relationships between BI, anxiety, and substance use.MethodsThe present study therefore evaluated (1) the prospective relationships between BI [assessed via self-reported behavioral inhibition system (BIS) scale scores], anxiety, and substance use in youth (n = 11,876) across baseline, 1-, and 2-year follow-ups of the Adolescent Brain Cognitive Development (ABCD) Study (ages 9–12) and (2) whether these relationships differed by H/L ethnicity while covarying for average behavioral approach system scores, race, sex, age, highest parental income, highest parental education, and past-year substance use (for analyses involving substance use outcomes).ResultsBaseline levels of BIS scores predicted increased anxiety symptoms at both 1- and 2-year follow-ups and did not differ by H/L ethnicity. Baseline levels of BIS scores also prospectively predicted increased likelihood of substance use at 2-year follow-up, but only for H/L youth and not at 1-year follow-up.DiscussionHigh scores on the BIS scale contribute risk to anxiety across ethnicities and may uniquely contribute to risk for substance use in H/L youth

Risk-shifting Through Issuer Liability and Corporate Monitoring

This article explores how issuer liability re-allocates fraud risk and how risk allocation may reduce the incidence of fraud. In the US, the apparent absence of individual liability of officeholders and insufficient monitoring by insurers under-mine the potential deterrent effect of securities litigation. The underlying reasons why both mechanisms remain ineffective are collective action problems under the prevailing dispersed ownership structure, which eliminates the incentives to moni-tor set by issuer liability. This article suggests that issuer liability could potentially have a stronger deterrent effect when it shifts risk to individuals or entities holding a larger financial stake. Thus, it would enlist large shareholders in monitoring in much of Europe. The same risk-shifting effect also has implications for the debate about the relationship between securities litigation and creditor interests. Credi-tors’ claims should not be given precedence over claims of defrauded investors (e.g., because of the capital maintenance principle), since bearing some of the fraud risk will more strongly incentivise large creditors, such as banks, to monitor the firm in jurisdictions where corporate debt is relatively concentrated