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Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis.
Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy
Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms’ tumor: a CIBMTR retrospective analysis
Despite the dramatic improvement in the overall survival for patients diagnosed with Wilms’ tumor (WT), the outcomes for those that experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR). The 5-year estimates for event free survival (EFS) and overall survival (OS) were 36% (95% CI; 29 – 43%) and 45% (95% CI; 38 – 51%) respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality (TRM) showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. Since attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus high-dose chemotherapy followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. Since disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy
State of the Art: Small Spacecraft Technology
This report provides an overview of the current state-of-the-art of small spacecraft technology, with particular emphasis placed on the state-of-the-art of CubeSat-related technology. It was first commissioned by NASAs Small Spacecraft Technology Program (SSTP) in mid-2013 in response to the rapid growth in interest in using small spacecraft for many types of missions in Earth orbit and beyond, and was revised in mid-2015 and 2018. This work was funded by the Space Technology Mission Directorate (STMD). For the sake of this assessment, small spacecraft are defined to be spacecraft with a mass less than 180 kg. This report provides a summary of the state-of-the-art for each of the following small spacecraft technology domains: Complete Spacecraft, Power, Propulsion, Guidance Navigation and Control, Structures, Materials and Mechanisms, Thermal Control, Command and Data Handling, Communications, Integration, Launch and Deployment, Ground Data Systems and Operations, and Passive Deorbit Devices
Inhibition of HIV replication by amino-sugar derivatives
AbstractThe plant alkaloids castanospermine, dihydroxymethyldihydroxypyrrolidine and deoxynojirimycin have recently been shown to have potential anti-HIV activity [(1987) Proc. Natl. Acad. Sci. USA 84, 8120–8124; (1987) Nature 330, 74–77; (1987) Lancet i, 1025–1026]. They are thought to act by inhibiting α-glucosidase I, an enzyme involved in the processing of N-linked oligosaccharides on glycoproteins. We report here the relative efficacy of a spectrum of amino-sugar derivatives as inhibition of HIV cytopathicity. Several α-glucosidase inhibitors and α-fucosidase inhibitors were found to be active at concentrations which were non-cytotoxic
BioSentinel: Monitoring DNA Damage Repair Beyond Low Earth Orbit on a 6U Nanosatellite
We are designing and developing a 6U nanosatellite as a secondary payload to fly aboard NASAs Space Launch System (SLS) Exploration Mission (EM) 1, scheduled for launch in late 2017. For the first time in over forty years, direct experimental data from biological studies beyond low Earth orbit (LEO) will be obtained during BioSentinels 12- to 18-month mission. BioSentinel will measure the damage and repair of DNA in a biological organism and allow us to compare that to information from onboard physical radiation sensors. This data will be available for validation of existing models and for extrapolation to humans.The BioSentinel experiment will use the organism Saccharomyces cerevisiae (yeast) to report DNA double-strand-break (DSB) events that result from space radiation. DSB repair exhibits striking conservation of repair proteins from yeast to humans. The flight strain will include engineered genetic defects that prevent growth and division until a radiation-induced DSB activates the yeasts DNA repair mechanisms. The triggered culture growth and metabolic activity directly indicate a DSB and its repair. The yeast will be carried in the dry state in independent microwells with support electronics. The measurement subsystem will sequentially activate and monitor wells, optically tracking cell growth and metabolism. BioSentinel will also include TimePix radiation sensors implemented by JSCs RadWorks group. Dose and Linear Energy Transfer (LET) data will be compared directly to the rate of DSB-and-repair events measured by the S. cerevisiae biosentinels. BioSentinel will mature nanosatellite technologies to include: deep space communications and navigation, autonomous attitude control and momentum management, and micropropulsion systems to provide an adaptable nanosatellite platform for deep space uses
Comparing Notes: Recording and Criticism
This chapter charts the ways in which recording has changed the nature of music criticism. It both provides an overview of the history of recording and music criticism, from the advent of Edison’s Phonograph to the present day, and examines the issues arising from this new technology and the consequent transformation of critical thought and practice
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Wider Still and Wider: British Music Criticism since the Second World War
This chapter provides the first historical examination of music criticism in Britain since the Second World War. In the process, it also challenges the simplistic prevailing view of this being a period of decline from a golden age in music criticism
Collapsible Space Telescope (CST) for Nanosatellite Imaging and Observation
Nanosatellites have gained broad use within the university and scientific communities for a variety of applications ranging from Space Weather, Space Biology and Astrobiology. There is great interest to develop high-quality nanosatellite imaging applications to support Earth Observations, Astrophysics and Heliophysics Missions. NASA Ames Research Center is developing a low cost, deployable telescope that, when coupled with the appropriate imager, will provide high-resolution imaging for Earth and Space Observations. The collapsible telescope design is a Strain Deployable Ritchey Chrétien Cassegrain telescope that can fit within the volume of 1U x 4U portion of a 6U nanosatellite platform. Additional telescope optical prescriptions compatible with the same deployable architecture are being explored. For example, a faster Ritchey-Chretien Cassegrain shortens the deployable volume and allows better matching to a slitor integral field unit spectrometer instrument where a modest-sized evenly illuminated field size is a driver. The revised packaging may enable room for field-flattener lenses for imaging applications. Our prototype instrument backend is a remote sensing compact spectropolarimeter with no moving parts, currently under development. The ability to integrate a deployable Cassegrain telescope into a nanosatellite platform matches desires outlined within the TA08 Remote Sensing Instruments/Sensors Technical Area Roadmap and represents game changing technologies in small satellite subsystems to include the potential for swarm missions with distributed apertures
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