Recent Advances in the Molecular Characterization of Circulating Tumor Cells

Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch((R)) system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs hold for oncology lies at the level of molecular characterization. Clinical treatment decisions may be more effective if they are based on molecular characteristics of metastatic cells rather than on those of the primary tumor alone. Molecular characterization of CTCs (which can be repeatedly isolated in a minimally invasive fashion) provides the opportunity for a. real-time liquid biopsy that allows assessment of genetic drift, investigation of molecular disease evolution, and identification of actionable genomic characteristics. This review focuses on recent advances in this area, including approaches involving immunophenotyping, fluorescence in situ hybridization (FISH), multiplex RT-PCR, microarray, and genomic sequencing

Infrared aircraft measurements of stratospheric composition over Antarctica during September 1987

The JPL Mark IV interferometer recorded high resolution, infared solar spectra from the NASA DC-8 aircraft during flights over Antarctica in September 1987. The atmospheric absorption features in these spectra were analyzed to determine the overburdens of O3, NO, NO2, HNO3, ClONO2, HCl, HF, CH4, N2O, CO, H2O and CFC-12. The spectra were obtained at latitudes which ranged between 64 degrees S and 86 degrees S, allowing the composition in the interior of the polar vortex to be compared with that at the edge. The latitude dependence observed for NO, HO2, HNO3, ClONO2, HCl and HF are summerized. The values at 30 deg S were observed on the ferry flight from New Zealand to Hawaii. The dashed lines connecting the two were interpolated across the region for which there are no measurements. The chemically perturbed region is seen to consist of a collar of high HNO3 and ClONO2 surrounding a core in which the overburdens of these and of HCl and NO2 are very low. Clear increases in the overburdens of HF and HNO3 were observed during the course of September in the vortex core. HCl and NO2 exhibited smaller, less significant increases. The overburdens of the tropospheric source gases, N2O, CH4, CF2Cl2, and H2O were observed to much smaller over Antarctica than at mid-latitudes. This, together with the fact that HF over Antarctica was more that double its mid-latitude value, suggests that downwelling has occurred

Robotic Exploration of Moon and Mars: Thematic Education Approach

Safe, sustained, affordable human and robotic exploration of the Moon, Mars, and beyond is a major NASA goal. Robotic exploration of the Moon and Mars will help pave the way for an expanded human presence in our solar system. To help share the robotic exploration role in the Vision for Space Exploration with classrooms, informal education groups, and the public, our team researched and consolidated the thematic story components and associated education activities into a useful education materials set for educators. We developed the set of materials for a workshop combining NASA Science Mission Directorate and Exploration Systems Mission Directorate engineering, science, and technology to train informal educators on education activities that support the robotic exploration themes. A major focus is on the use of robotic spacecraft and instruments to explore and prepare for the human exploration of the Moon and Mars

Spherical harmonic representation of the main geomagnetic field for world charting and investigations of some fundamental problems of physics and geophysics

Quiet-day data from MAGSAT were examined for effects which might test the validity of Maxwell's equations. Both external and toroidal fields which might represent a violation of the equations appear to exist, well within the associated errors. The external field might be associated with the ring current, and varies of a time-scale of one day or less. Its orientation is parallel to the geomagnetic dipole. The toriodal field can be confused with an orientation in error (in yaw). It the toroidal field really exists, its can be related to either ionospheric currents, or to toroidal fields in the Earth's core in accordance with Einstein's unified field theory, or to both

Spherical harmonic representation of the main geomagnetic field for world charting and investigations of some fundamental problems of physics and geophysics

The data processing of MAGSAT investigator B test tapes and data tapes, and tapes of selected data on 15 magnetically quiet days is reported. The 1980 World Chart spherical model was compared with the MAGSAT (3/80) and MAGSAT vector data were used in the models. An article on modelling the geomagnetic field using satellite data is included

Association between recipient’s preexisting antibodies and allograft vasculopathy and mortality in heart transplant patients

Objectives: To evaluate the role of preexisting Angiotensin II receptor type I antibodies (AT1RAb) and anti-HLA antibodies in predicting mortality and cardiac allograft vasculopathy (CAV) among heart transplant patients. Methods: In this retrospective cohort study, we included 114 adults who received heart transplant from January 1st, 2007 to December 31, 2014 and were followed up at Nebraska Medicine. 48 hours pre-transplant sera sample were used to detect antibodies. A cutoff of 10UL/ml was used for AT1RAb positive and mean fluorescence intensity of 3,000 and 1,500 were used for anti HLA class I and class II, respectively. Patients were positive for composite antibodies if they were positive for anti-HLA, or AT1R antibodies. Survival analysis was conducted to compare the risk for mortality or CAV between antibody positive and negative groups. Result: Participants who had positive composite antibodies had higher probability of having CAV (p=0.05). Participants who were negative for AT1RAb trended toward a lower risk of mortality or developing CAV compared to AT1RAb positive counterparts. Conclusion: Positive status for any of anti-HLA or AT1RAb increased the risk of CAV. AT1RAb positivity is possibly linked with higher risk of death or developing CAV. Future study can focus on verifying these trends and the potential interaction effect between anti-HLA and AT1R antibodies

Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis

The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. This review will discuss the use of circulating tumor cell (CTC) analysis as an effective means of tracking and characterizing metastatic disease progression in preclinical mouse models of breast and prostate cancer and the resulting lessons learned about CTC and metastasis biology. We will also discuss how the use of clinically-relevant CTC technologies such as the CellSearch((R)) and Parsortix platforms for preclinical CTC studies can serve to enhance the study of cancer biology, new biomarkers, and novel therapies from the bench to the bedside

Adaptation of Semiautomated Circulating Tumor Cell (CTC) Assays for Clinical and Preclinical Research Applications

The majority of cancer-related deaths occur subsequent to the development of metastatic disease. This highly lethal disease stage is associated with the presence of circulating tumor cells (CTCs). These rare cells have been demonstrated to be of clinical significance in metastatic breast, prostate, and colorectal cancers. The current gold standard in clinical CTC detection and enumeration is the FDA-cleared CellSearch system (CSS). This manuscript outlines the standard protocol utilized by this platform as well as two additional adapted protocols that describe the detailed process of user-defined marker optimization for protein characterization of patient CTCs and a comparable protocol for CTC capture in very low volumes of blood, using standard CSS reagents, for studying in vivo preclinical mouse models of metastasis. In addition, differences in CTC quality between healthy donor blood spiked with cells from tissue culture versus patient blood samples are highlighted. Finally, several commonly discrepant items that can lead to CTC misclassification errors are outlined. Taken together, these protocols will provide a useful resource for users of this platform interested in preclinical and clinical research pertaining to metastasis and CTCs

Seismic Performance of Slender C-Shaped Walls Subjected to UniI- and Bi-Directional Loading

Reinforced concrete structural walls are common as the primary lateral load resisting system in modern mid- and high-rise buildings constructed in seismic regions, yet few research programs have investigated the seismic performance of modern, slender walls with nonplanar cross-sectional geometries. Three large-scale, C-shaped wall specimens, designed per ACI 318-08, were tested under uni- and bi-directional loading at the University of Illinois at Urbana-Champaign (UIUC). This paper presents experimental results including the cyclic load-deformation response and measured versus nominal flexural/shear strengths as well as a description of damage sequence. Final failure occurs due to a flexure-tension failure of boundary elements where multiple previously buckled bars fracture. From these tests, it is possible to conclude that with respect to uni- versus bi-directionally loading C-shaped walls have similar strong-axis load-deformation response until 0.75% drift as well as effective flexure/shear stiffness; however, there is a notable reduction in strong-axis ductility due to bi-directional loading. When comparing C-shaped walls to planar walls, the C-shaped specimens exhibit a more ductile flexural-tension controlled response where wall flanges contribute significantly to carrying compressive loads. Additionally, wall flanges and boundary elements are noted to be critical to resisting shear demands after the lightly-reinforced wall web has deteriorated

Family preferences for home or hospital care at diagnosis for children with diabetes in the DECIDE study.

This is the final version of the article. Available from Wiley via the DOI in this record.AIMS: A diagnosis of Type 1 diabetes in childhood can be a difficult life event for children and families. For children who are not severely ill, initial home rather than hospital-based care at diagnosis is an option although there is little research on which is preferable. Practice varies widely, with long hospital stays in some countries and predominantly home-based care in others. This article reports on the comparative acceptability and experience of children with Type 1 diabetes and their parents taking part in the DECIDE study evaluating outcomes of home or hospital-based treatment from diagnosis in the UK. METHODS: Semi-structured interviews with 11 (pairs of) parents and seven children were conducted between 15 and 20 months post diagnosis. Interviewees were asked about adaptation to, management and impact of the diabetes diagnosis, and their experience of initial post-diagnosis treatment. RESULTS: There were no differences between trial arms in adaptation to, management of or impact of diabetes. Most interviewees wanted to be randomized to the 'home' arm initially but expressed a retrospective preference for whichever trial arm they had been in, and cited benefits relating to learning about diabetes management. CONCLUSIONS: The setting for early treatment did not appear to have a differential impact on families in the long term. However, the data presented here describe different experiences of early treatment settings from the perspective of children and their families, and factors that influenced how families felt initially about treatment setting. Further research could investigate the short-term benefits of both settings.National Institute for Social Care and Health Research Clinical Research Centr