NASA Capability Roadmaps Executive Summary

This document is the result of eight months of hard work and dedication from NASA, industry, other government agencies, and academic experts from across the nation. It provides a summary of the capabilities necessary to execute the Vision for Space Exploration and the key architecture decisions that drive the direction for those capabilities. This report is being provided to the Exploration Systems Architecture Study (ESAS) team for consideration in development of an architecture approach and investment strategy to support NASA future mission, programs and budget requests. In addition, it will be an excellent reference for NASA's strategic planning. A more detailed set of roadmaps at the technology and sub-capability levels are available on CD. These detailed products include key driving assumptions, capability maturation assessments, and technology and capability development roadmaps

Mutational activation of BRAF confers sensitivity to transforming growth factor beta inhibitors in human cancer cells

Recent data implicate elevated transforming growth factor-β (TGFβ) signalling in BRAF inhibitor drug-resistance mechanisms, but the potential for targeting TGFβ signalling in cases of advanced melanoma has not been investigated. We show that mutant BRAFV600E confers an intrinsic dependence on TGFβ/TGFβ receptor 1 (TGFBR1) signalling for clonogenicity of murine melanocytes. Pharmacological inhibition of the TGFBR1 blocked the clonogenicity of human mutant BRAF melanoma cells through SMAD4-independent inhibition of mitosis, and also inhibited metastasis in xenografted zebrafish. When investigating the therapeutic potential of combining inhibitors of mutant BRAF and TGFBR1, we noted that unexpectedly, low-dose PLX-4720 (a vemurafenib analogue) promoted proliferation of drug-naïve melanoma cells. Pharmacological or pharmacogenetic inhibition of TGFBR1 blocked growth promotion and phosphorylation of SRC, which is frequently associated with vemurafenib-resistance mechanisms. Importantly, vemurafenib-resistant patient derived cells retained sensitivity to TGFBR1 inhibition, suggesting that TGFBR1 could be targeted therapeutically to combat the development of vemurafenib drug-resistance

Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life

Progressive Scalp Thinning Over Mesh Cranioplasty and the Role of Lipotransfer

To evaluate the role of lipotransfer in progressive scalp thinning following titanium mesh cranioplasty. METHODS: Retrospective review of single surgeon, single tertiary referral experience of all patients who underwent mesh cranioplasty. Patient demographics, prior radiotherapy, frequency and timing of scalp thinning, and treatment course data were obtained. RESULTS: A total of 144 patients were included, 77 male and 67 female with mean ages 58.2 and 54.8, respectively. One hundred four patients (72%) developed mesh exposure or impending exposure requiring reconstruction. Fifty-six patients (54%) with scalp thinning were treated with lipotransfer, 40 of which were salvaged and the remainder of these patients definitively managed with cranioplasty and reconstruction. Prior radiotherapy was found to be associated with higher rates of mesh exposure (P = .0028), but not predictive of response to lipotransfer. CONCLUSION: Lipotransfer is a useful technique in managing moderate scalp thinning following mesh cranioplasty. Mesh exposure or severe thinning require definitive cranioplasty and reconstruction

Single-Point Fixation for Noncomminuted Zygomaticomaxillary Complex Fractures-A 20-Year Experience

PURPOSE: Zygomaticomaxillary complex (ZMC) fractures occur often. However, no clinical consensus has been reached regarding the number of fixation points required when performing open reduction and internal fixation (ORIF). The objective of the present study was to explore the utility of single-point fixation in the management of noncomminuted ZMC fractures. PATIENTS AND METHODS: We analyzed the data from a retrospective case series of 211 patients treated during a 20-year period. RESULTS: The mean length of follow-up was 3.4 months. Of the 211 patients, 162 with noncomminuted ZMC fractures had been treated with single-point fixation of the zygomaticomaxillary buttress. During the follow-up period, 1 patient experienced tooth loss because of a root present in the fracture line, 7 experienced intraoral plate exposure, with 2 subsequently undergoing plate exchange, and 8 developed a wound infection. No patients required orthognathic surgery or cheek implants for malar asymmetry. No patient developed hypoglobus or enophthalmos, and none required revision ORIF of their ZMC fracture. CONCLUSIONS: To the best of our knowledge, the present study represents the largest series in the literature reporting the surgical results and outcomes of patients with noncomminuted ZMC fractures treated with single-point fixation. In experienced hands, we believe this is a viable surgical option if appropriate surgical considerations are made