Core-power and decay-time limits for disabled automatic-actuation of LOFT ECCS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, G.H.

1978-06-05

The Emergency Core Cooling System (ECCS) for the LOFT reactor may need to be disabled for modifications or repairs of hardware or instrumentation or for component testing during periods when the reactor system is hot and pressurized, or it may be desirable to enable the ECCS to be disabled without the necessity of cooling down and depressurizing the reactor. LTR 113-47 has shown that the LOFT ECCS can be safely bypassed or disabled when the total core power does not exceed 25 kW. A modified policy involves disabling the automatic actuation of the LOFT ECCS, but still retaining the manualmore » activation capability. Disabling of the automatic actuation can be safely utilized, without subjecting the fuel cladding to unacceptable temperatures, when the LOFT power decays to 70 kW; this power level permits a maximum delay of 20 minutes following a LOCA for the manual actuation of ECCS.« less

LOFT, TAN650. Camera facing southeast. From left to right: stack ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT, TAN-650. Camera facing southeast. From left to right: stack in distance, pre-amp wing, dome, north side of loft "service building." Note poured concrete wall of pre-amp wing on lower section; pumice block above. Date: May 2004. INEEL negative no. HD-39-19-3 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

What makes a good LOFT scenario? Issues in advancing current knowledge of scenario design. [Line Oriented Flight Training

NASA Technical Reports Server (NTRS)

Gregorich, Steven E.

1991-01-01

An effort is made to ascertain which combinations of technical demands and crew coordination should be incorporated in training scenarios in order to maximize the effectiveness of training for crew members. Such high-fidelity simulation, which has come to be known as 'line-oriented flight training' or LOFT, involves the practice of both technical and crew coordination skills in a realistic setting, in conjunction with periodic reviews of performance via videotaped feedback. Attention is given to the integration of appropriate information, the measurement of objective task demands, the character of information from LOFT students, and the leeway allowed LOFT instructors.

Be/X-Ray Pulsar Binary Science with LOFT

NASA Technical Reports Server (NTRS)

Wilson-Hodge, Colleen A.

2011-01-01

Accretion disks are ubiquitous in astronomical sources. Accretion powered pulsars are a good test bed for accretion disk physics, because unlike for other objects, the spin of the neutron star is directly observable allowing us to see the effects of angular momentum transfer onto the pulsar. The combination of a sensitive wide-field monitor and the large area detector on LOFT will enable new detailed studies of accretion powered pulsars which I will review. RXTE observations have shown an unusually high number of Be/X-ray pulsar binaries in the SMC. Unlike binaries in the Milky Way, these systems are all at the same distance, allowing detailed population studies using the sensitive LOFT WFM, potentially providing connections to star formation episodes. For Galactic accreting pulsar systems, LOFT will allow measurement of spectral variations within individual pulses, mapping the accretion column in detail for the first time. LOFT will also provide better constraints on magnetic fields in accreting pulsars, allowing measurements of cyclotron features, observations of transitions into the centrifugal inhibition regime, and monitoring of spin-up rate vs flux correlations. Coordinated multi-wavelength observations are crucial to extracting the best science from LOFT from these and numerous other objects.

LOFT. Containment and service building (TAN650) ground floor plan. Penetrations ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Containment and service building (TAN-650) ground floor plan. Penetrations in dome wall. Shielded personnel maze at airlock door. Reactor chamber floor hatches and holddowns. Rails in concrete floor. Kaiser engineers 6413-11-STEP/LOFT-650-A-2. Date: October 1964. INEEL index code no. 036-650-00-486-122214 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

LOFT. Containment and service building (TAN650). Room number and function ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Containment and service building (TAN-650). Room number and function of each room. Identifies type of floor, paint, walls, ceiling, doors. This is sheet 1 of a 2-page drawing. Kaiser engineers 6413-11-STEP/LOFT-650-XX. Date: October 1965. INEEL index code no. 036-650-00-486-122228 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

CALIBRATION OF INSTRUMENTS FOR RADIATION MEASUREMENTS FROM LOFTED VEHICLES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banks, W.O.

1962-05-01

The designs and developments accomplished by the Air Proving Ground Certer in support of Project TRUMP are considered. Project TRUMP pertains to the design and developmert of methods for measuring radiation from lofted vehicles. Several methods of simulating the space environment, for purposes of ground calibration of instruments to be lofted, are proposed. A mathematical approach, similar to that used by early Smithsonian solar constant seekers, is presented. (auth)

The Large Observatory For X-ray Timing (LOFT): The ESA Mission and Proposed US Contributions

NASA Astrophysics Data System (ADS)

Ray, Paul S.; Feroci, M.; den Herder, J.; Bozzo, E.; Chakrabarty, D.; Wilson, C.; Consortium, LOFT; US-LOFT Collaboration

2013-04-01

High-time-resolution X-ray observations of compact objects provide direct access to strong-field gravity, to the equation of state of ultradense matter and to black hole masses and spins. A 10 m2-class instrument in combination with good spectral resolution is required to exploit the relevant diagnostics and answer fundamental questions about matter under extreme conditions. The Large Observatory For X-ray Timing (LOFT), selected by ESA as one of the four Cosmic Vision M3 candidate missions to undergo an assessment phase, will revolutionize the study of collapsed objects in our Galaxy and of the brightest supermassive black holes in active galactic nuclei. Thanks to an innovative design and the development of large-area monolithic silicon drift detectors, the Large Area Detector (LAD) on board LOFT will achieve an effective area of over 10 m2 (more than an order of magnitude larger than any spaceborne predecessor) in the 2-30 keV range (up to 50 keV in expanded mode), yet still fits in a conventional platform and medium-class launcher. With this large area and a spectral resolution of <260 eV, LOFT will yield unprecedented information on strongly curved spacetimes and matter under extreme conditions of pressure and magnetic field strength. A second instrument onboard LOFT, the Wide Field Monitor (WFM), will discover and localize X-ray transients and impulsive events and monitor spectral state changes with unprecedented sensitivity and coverage. Through the LOFT Burst Alert System (LBAS), locations and times of impulsive events discovered by the WFM will be relayed to the ground within about 30 seconds. In this talk, we will present an overview of the design and status of the LOFT mission and describe the proposed US contributions currently under evaluation by NASA. NRL participation in LOFT is funded by NASA.

LOFT complex, camera facing west. Mobile entry (TAN624) is position ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT complex, camera facing west. Mobile entry (TAN-624) is position next to containment building (TAN-650). Shielded roadway entrance in view just below and to right of stack. Borated water tank has been covered with weather shelter and is no longer visible. ANP hangar (TAN-629) in view beyond LOFT. Date: 1974. INEEL negative no. 74-4191 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

LOFT. Containment and service building (TAN650). Section through north/south axis. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Containment and service building (TAN-650). Section through north/south axis. Shows basement and four additional levels of pre-amp tower, shielded roadway, chambers below reactor floor, railroad door, sumps, shielding. Section C shows basement sumps and chambers below reactor floor. Kaiser engineers 6413-11-STEP/LOFT-650-A-5. Date: October 1964. INEEL index code no. 036-650-00-486-122217 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

LOFT. Containment and service building (TAN650). South elevation, details, section. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Containment and service building (TAN-650). South elevation, details, section. Shows part of duct enclosure, railroad door opening, roof ventilators, shielded personnel entrance, and change room. Section F shows view from west looking toward shielding around airlock door on main floor. Kaiser engineers 6413-11-STEP/LOFT-650-A-9. Date: October 1964. INEEL index code no. 036-650-00-486-122221 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Ares I First Stage Propulsion System Status

NASA Technical Reports Server (NTRS)

Priskos, Alex S.

2010-01-01

With the retirement of the Space Shuttle inevitable, the US is faced with the need to loft a reliable cost-effective, technologically viable solution to bring the nation s fleet of spacecraft back up to industry standard. It must not only support the International Space Station (ISS), it must also be capable of supporting human exploration beyond low Earth orbit (LEO). NASA created the Constellation Program to develop a new fleet including the launch vehicles, the spacecraft, and the mission architecture to meet those objectives. The Ares First Stage Team is tasked with developing a propulsion system capable of safely, dependably and repeatedly lofting that new fleet. To minimize technical risks and development costs, the Solid Rocket Boosters (SRBs) of Shuttle were used as a starting point in the design and production of a new first stage element. While the first stage will provide the foundation, the structural backbone, power, and control for launch, the new propulsive element will also provide a greater total impulse to loft a safer, more powerful, fleet of space flight vehicles. Substantial design and system upgrades were required to meet the mass and trajectory requisites of the new fleet. Noteworthy innovations and design features include new forward structures, new propellant grain geometry, a new internal insulation system, and a state-of-the art avionics system. Additional advances were in materials and composite structures development, case bond liners, and thermal protection systems. Significant progress has been made in the design, development and testing of the propulsion and avionics systems for the new first stage element. Challenges, such as those anticipated with thrust oscillation, have been better characterized, and are being effectively mitigated. The test firing of the first development motor (DM-1) was a success that validated much of the engineering development to date. Substantive data has been collected and analyzed, allowing the Ares First Stage team to move forward, fine-tune the design, and advance to production of the second development motor (DM-2), which is now in fabrication. This paper will provide an overview of the design, development, challenges, and progress on the production of the new Ares First Stage propulsion system

Modelling and Characterisation of Detection Models in WAMI for Handling Negative Information

DTIC Science & Technology

2014-02-01

behaviour of the multi-stage detectors used in LoFT. This model is then used in a Probabilistic Hypothesis Density Filter (PHD). Unlike most multitarget...Therefore, we decided to use machine learning techniques which could model — and pre- dict — the behaviour of the detectors in LoFT. Because we are using...on feature detectors [8], motion models [13] and descriptor and template adaptation [9]. 2.3.2 State Model The state space of LoFT is defined in 2D

LOFT. Mobile test building (TAN624) is recycled from ANP program ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Mobile test building (TAN-624) is recycled from ANP program for placement before LOFT containment building door. It has not yet been connected to containment building. Note borated water tank at right of dome. Narrow, vertical structure at right of door is shroud is shroud for air exhaust duct. Filter vaults lie between duct shroud and stack. Camera facing westerly. Date: 1974. INEEL negative no. 74-1072 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

LOFT. Containment and service building (TAN650). Section through east/west axis ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Containment and service building (TAN-650). Section through east/west axis of building as viewed from the north. Shows steel ladder to top of dome, gable roof of borated water tank enclosure, pumice block siding of pre-amp tower, metal siding of duct enclosure. Kaiser engineers 6413-11-STEP/LOFT-650-A-6. Date: October 1964. INEEL index code no. 036-650-00-486-122218 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

LOFT. Containment and service building (TAN650). Section through east/west axis ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Containment and service building (TAN-650). Section through east/west axis of building as viewed from the south. Shows basement and grade levels of containment building, connection to control room on west side, air filter vaults, and duct enclosure for air exhaust system. Kaiser engineers 6413-11-STEP/LOFT-650-A-4. Date: October 1964. INEEL index code no. 036-650-00-486-122216 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Spatial patterns in the condition index of the wild Pacific oyster Crassostrea gigas in a macrotidal coastal ecosystem: Influence of tidal processes and beyond

NASA Astrophysics Data System (ADS)

Gasmi, Sonia; Bernard, Ismaël; Pouvreau, Stéphane; Maurer, Danièle; Schaal, Gauthier; Ganthy, Florian; Cominassi, Louise; Allain, Gwenhael; Sautour, Benoit; David, Valérie

2017-01-01

In macrotidal coastal ecosystems, spatial heterogeneity of the water column properties is induced by both oceanic and continental influences. Hydrodynamic processes generate a land-sea gradient of environmental conditions, affecting the biological performances of sedentary organisms. The aim of the present study is to establish an extensive spatial assessment in the reproductive investment of the wild Pacific oyster Crassostrea gigas in Arcachon Bay. This is done by looking for a relationship between the Lawrence and Scott condition index (LSCI) and two tidal processes: the immersion level (IL) and the local oceanic flushing time (LoFt). The LSCI of C. gigas was assessed, just before gamete release, at 68 sampling stations in Arcachon Bay. Oyster performance was overall low and spatially variable. Significant differences in the LSCI were detected between the outer and inner bay. Oyster reefs located toward the mouth of the bay exhibited high LSCI (between 9 and 11), while oyster reefs located in inner bay, especially in south-eastern part around the Eyre River, had low LSCI (below 6). Linear modelling allowed to highlight significant effects of both tidal processes IL and LoFt on the obtained LSCI gradient. IL, LoFt explained 33% of the spatial variability observed on LSCI (IL = 3%; LoFt = 17%; LoFt + IL: 13%), 6% were attributed to the intra-station variation (ISv). Thus, high IL and rapid LoFt favor a better development of somatic-gonadal volume, probably because of longer feeding time and higher supply of food from the ocean by tide flows. Disentangling the effects of IL and LoFt on LSCI allowed to describe the spatial pattern in 61% of variability not explained by both tidal factors. A residual gradient directed southeast-northwest highlighted that others factors, independent from IL and LoFt seems to hamper inner bay oyster reproductive performance. Consequently, investigating on the ecological functioning (Eyre influences), trophic potential and anthropogenic pressures of this zone seem crucial on the understanding of C. gigas reproductive pattern in Arcachon Bay.

View northeast of mould loft and plating cutting shop in ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View northeast of mould loft and plating cutting shop in structural assembly shop (building no. 541) - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structural Assembly Shop, League Island, Philadelphia, Philadelphia County, PA

12. Interior view from sanctuary showing choir loft, vestibule, and ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. Interior view from sanctuary showing choir loft, vestibule, and chapel entrance, facing south - Mountain Home Air Force Base, Base Chapel, 350 Willow Street, Cantonment Area, Mountain Home, Elmore County, ID

14. FACILITY IDENTIFICATION STENCILED ON ROOF BEAM, 'RIGGING LOFT' PORTION ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. FACILITY IDENTIFICATION STENCILED ON ROOF BEAM, 'RIGGING LOFT' PORTION OF BUILDING 4. - Chollas Heights Naval Radio Transmitting Facility, Public Works Shop, 6410 Zero Road, San Diego, San Diego County, CA

United Airlines LOFT training

NASA Technical Reports Server (NTRS)

Cavanagh, D.; Traub, B.

1981-01-01

Line oriented training is used in a broader, more generic sense that as a specific program under FAR 12.1409 and AC 120-35. A company policy was adopted more than twenty years ago requiring that all pilot checks and recurrent training be conducted with a full crew occupying the seats they occupy on the line. Permission was obtained to reschedule the hours for recurrent proficiency training to include one and one-half hours of LOFT flight. The number of emergencies and abnormal procedures which could be undertaken were considered and the introduction of an a occasional incapacitation revealed which person is the most difficult to replace on the widebodies. By using the LOFT concept, every training period can be structured like a typical line flight. The use of LOFT in simulator syllabus development and problems that need to be refined are discussed.

32. SAR1, VIEW FROM STABLE LOFT. SCE negative no. 10319, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

32. SAR-1, VIEW FROM STABLE LOFT. SCE negative no. 10319, November 1, 1923. Photograph by G. Haven Bishop. - Santa Ana River Hydroelectric System, SAR-1 Powerhouse, Redlands, San Bernardino County, CA

Lessons from cross-fleet/cross-airline observations - Evaluating the impact of CRM/LOFT training

NASA Technical Reports Server (NTRS)

Butler, Roy E.

1991-01-01

A review is presented of the crew resource management/line oriented flight training (CRM/LOFT) program to help determine the level of standardization across fleets and airlines in the critical area of evaluating crew behavior and performance. One of the goals of the project is to verify that check airmen and LOFT instructors within organizations are evaluating CRM issues consistently and that differences observed between fleets are not a function of idiosyncracies on the part of observers. Attention is given to the research tools for crew evaluation.

35. CHARGING DOOR OF CUPOLA FORM LOFT, WITH FORKS FOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

35. CHARGING DOOR OF CUPOLA FORM LOFT, WITH FORKS FOR FEEDING COKE, FOUNDRY BELOW-LOOKING NORTH. - W. A. Young & Sons Foundry & Machine Shop, On Water Street along Monongahela River, Rices Landing, Greene County, PA

17. Truss suspended column, industrial loft building, looking at southeast ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. Truss suspended column, industrial loft building, looking at southeast corner. Note open floor plan as a result of the floor beams being suspended from above. - Dry Dock Engine Works, 1801 Atwater Street, Detroit, MI

16. Exterior of assembly building (mold loft #2) used for ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

16. Exterior of assembly building (mold loft #2) used for runabout production, constructed CA. 1932. Most of the production run boats were assembled here. - Barbour Boat Works, Tryon Palace Drive, New Bern, Craven County, NC

12. Interior view of main cabin showing stairs to loft ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. Interior view of main cabin showing stairs to loft area, note construction of balcony and roof - Dean E. Call Property, Big Springs Summer Home Area, Lot 5, Block D, Island Park, Fremont County, ID

44. TANK LOFT: PLANS, ELEVATIONS AND DETAILS, Y&D No. 107722 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

44. TANK LOFT: PLANS, ELEVATIONS AND DETAILS, Y&D No. 107722 Scales as indicated; July 2, 1929 - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

17. Detail view of the southern half of the loft ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. Detail view of the southern half of the loft in the west side of the barn, looking toward the barrels and center post - Chellberg Farm, Barn, 900 North Mineral Springs Road, Porter, Porter County, IN

Core power and decay time limits for a disabled LOFT ECCS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atkinson, S.A.

1978-01-09

An analysis was done to determine at what LOFT total core power (nuclear plus decay power) the ECCS could be inoperable. The criteria used for the analysis was that the maximum fuel clad temperature should not exceed 1650/sup 0/F given a loss of coolant. Calculations for natural convection cooling of the fuel by air with an inlet temperature of 580/sup 0/F determined that the limiting core power is 25 kW (discounted by 15 percent to 20 percent for potential uncertainties). Shutdown times are listed for when the LOFT ECCS can be safely bypassed or disabled.

45. STEEL FRAMING FOR LOFT, Y&D No. 107723 Scales 1/2' ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

45. STEEL FRAMING FOR LOFT, Y&D No. 107723 Scales 1/2' and 1-1/2' = 1'; July 2, 1929 - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

MEASUREMENT OF MOTION CORRECTED WIND VELOCITY USING AN AEROSTAT LOFTED SONIC ANEMOMETER

EPA Science Inventory

An aerostat-lofted, sonic anemometer was used to determine instantaneous 3 dimensional wind velocities at altitudes relevant to fire plume dispersion modeling. An integrated GPS, inertial measurement unit, and attitude heading and reference system corrected the wind data for th...

51. LOFT. HEATING. PLANS, ELEVATIONS 7 DETAILS, Y&D No. 107729 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

51. LOFT. HEATING. PLANS, ELEVATIONS 7 DETAILS, Y&D No. 107729 Scales 3/16', 1/4', 1/2', and 1'; July 2, 1929 - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

20. Interior of assembly building (mold loft #2) used for ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. Interior of assembly building (mold loft #2) used for runabout production-woodworking shop. Note counter-weighted vertical sliding doors along wall to left to move materials and boats to other room. - Barbour Boat Works, Tryon Palace Drive, New Bern, Craven County, NC

Proposed US Contributions to LOFT

NASA Technical Reports Server (NTRS)

Wilson-Hodge, Colleen

2013-01-01

Proposed US Enhancements include:Tantalum X -ray collimator, Additional ground station, Large Observatory for X-Ray Timing (LOFT) instrument team participation, US science support center & data archive, and Science enabled by US hardware. High-Z material with excellent stopping power. Fabricated using a combination of laser micromachining and chemical etching. Known technology capable of producing high-aspect ratio holes and large open fractions. Reduces LOFT LAD background by a factor of 3. Telemetry formats for LOFT based upon RXTE/EDS experience. Ground system software and strategies for WFM based upon RXTE/ASM automated pipeline software. MSFC engineering trade studies supporting the Ta collimator. Burst alert triggers based upon Fermi/GBM and HETE-2. Science Enhancements Enabled by US Hardware include: Tantalum collimator: Reduces background by factor of 3. Improves sensitivity to faint sources such as AGN. Eliminates contamination by bright/variable sources. outside the LAD field of view. US Ground Station: Enables continuous telemetry of all events from the WFM. Allows LAD to observe very bright >500 mCrab sources with full event resolution.

Prepartum and postpartum open-field behavior and maternal responsiveness in mice bidirectionally selected for open-field thigmotaxis.

PubMed

Leppänen, Pia K; Ravaja, Niklas; Ewalds-Kvist, S Béatrice M

2008-01-01

The authors examined pre- and postpartum open-field (OF) behavior and maternal responsiveness in mice that they bidirectionally selected for OF thigmotaxis. The authors tested 40 female mice under 3 conditions: prepartum OF, postpartum OF, and a pup retrieval test. In both OF conditions, the high OF thigmotaxis (HOFT) mice were more thigmotactic but explored and reared less than the low OF thigmotaxis (LOFT) mice, indicating that the HOFT mice were more emotional. In the postpartum condition, the HOFT mothers also defecated more and ambulated less than the LOFT mothers. The increase in grooming after parturition was more conspicuous among the LOFT mothers than among the HOFT mothers. The LOFT mothers were also more attracted to their pups in the OF, but the retrieval test did not show any substantial line differences. The results suggested that the line difference in emotionality was more pronounced during lactation than during pregnancy, although parturition exerted no effect on thigmotaxis.

Large Observatory for x-ray Timing (LOFT-P): a Probe-class mission concept study

NASA Astrophysics Data System (ADS)

Wilson-Hodge, Colleen A.; Ray, Paul S.; Chakrabarty, Deepto; Feroci, Marco; Alvarez, Laura; Baysinger, Michael; Becker, Chris; Bozzo, Enrico; Brandt, Soren; Carson, Billy; Chapman, Jack; Dominguez, Alexandra; Fabisinski, Leo; Gangl, Bert; Garcia, Jay; Griffith, Christopher; Hernanz, Margarita; Hickman, Robert; Hopkins, Randall; Hui, Michelle; Ingram, Luster; Jenke, Peter; Korpela, Seppo; Maccarone, Tom; Michalska, Malgorzata; Pohl, Martin; Santangelo, Andrea; Schanne, Stephane; Schnell, Andrew; Stella, Luigi; van der Klis, Michiel; Watts, Anna; Winter, Berend; Zane, Silvia

2016-07-01

LOFT-P is a mission concept for a NASA Astrophysics Probe-Class (<$1B) X-ray timing mission, based on the LOFT M-class concept originally proposed to ESAs M3 and M4 calls. LOFT-P requires very large collecting area, high time resolution, good spectral resolution, broad-band spectral coverage (2-30 keV), highly flexible scheduling, and an ability to detect and respond promptly to time-critical targets of opportunity. It addresses science questions such as: What is the equation of state of ultra dense matter? What are the effects of strong gravity on matter spiraling into black holes? It would be optimized for sub-millisecond timing of bright Galactic X-ray sources including X-ray bursters, black hole binaries, and magnetars to study phenomena at the natural timescales of neutron star surfaces and black hole event horizons and to measure mass and spin of black holes. These measurements are synergistic to imaging and high-resolution spectroscopy instruments, addressing much smaller distance scales than are possible without very long baseline X-ray interferometry, and using complementary techniques to address the geometry and dynamics of emission regions. LOFT-P would have an effective area of >6 m2, > 10x that of the highly successful Rossi X-ray Timing Explorer (RXTE). A sky monitor (2-50 keV) acts as a trigger for pointed observations, providing high duty cycle, high time resolution monitoring of the X-ray sky with 20 times the sensitivity of the RXTE All-Sky Monitor, enabling multi-wavelength and multimessenger studies. A probe-class mission concept would employ lightweight collimator technology and large-area solid-state detectors, segmented into pixels or strips, technologies which have been recently greatly advanced during the ESA M3 Phase A study of LOFT. Given the large community interested in LOFT (>800 supporters*, the scientific productivity of this mission is expected to be very high, similar to or greater than RXTE ( 2000 refereed publications). We describe the results of a study, recently completed by the MSFC Advanced Concepts Office, that demonstrates that such a mission is feasible within a NASA probe-class mission budget.

Antibacterial flame retardant cotton high loft nonwovens

USDA-ARS?s Scientific Manuscript database

Renewable resources for raw materials and biodegradability of the product at the end of the useful life is entailing a shift from petroleum-based synthetics to agro based natural fibers such as cotton, especially for producing high specific volume high loft nonwovens. Cotton is highly flammable and ...

Core-power and decay-time limits for disabled automatic-actuation of LOFT ECCS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, G.H.

1978-11-22

The Emergency Core Cooling System (ECCS) for the LOFT reactor may need to be disabled for modifications or repairs of hardware or instrumentation or for component testing during periods when the reactor system is hot and pressurized, or it may be desirable to enable the ECCS to be disabled without the necessity of cooling down and depressurizing the reactor. A policy involves disabling the automatic-actuation of the LOFT ECCS, but still retaining the manual actuation capability. Disabling of the automatic actuation can be safely utilized, without subjecting the fuel cladding to unacceptable temperatures, when the LOFT power decays to 33more » kW; this power level permits a maximum delay of 20 minutes following a LOCA for the manual actuation of ECCS. For the operating power of the L2-2 Experiment, the required decay-periods (with operating periods of 40 and 2000 hours) are about 21 and 389 hours, respectively. With operating periods of 40 and 2000 hours at Core-I full power, the required decay-periods are about 42 and 973 hours, respectively. After these decay periods the automatic actuation of the LOFT ECCS can be disabled assuming a maximum delay of 20 minutes following a LOCA for the manual actuation of ECCS. The automatic and manual lineup of the ECCS may be waived if decay power is less than 11 kW.« less

Photocopy of drawing located at National Archives, San Bruno, California ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing located at National Archives, San Bruno, California (Navy # 106-A-17). NAVFAC relocated sail loft building 106 1st floor plan; sail loft area, August 1, 1977. - Mare Island Naval Shipyard, Boat Shop, California Avenue, west side between Ninth & Tenth Streets, Vallejo, Solano County, CA

LOFT. Interior view of entry (TAN624) rollup door. Camera is ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Interior view of entry (TAN-624) rollup door. Camera is inside entry building facing south. Rollup door was a modification of the original ANP door arrangement. Date: March 2004. INEEL negative no. HD-39-5-2 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Aerostat-lofted instrument and sampling method for determination of emissions from open area sources

EPA Science Inventory

An aerostat-borne instrument and sampling method was developed to characterize air samples from area sources, such as emissions from open burning. The 10 kg battery-powered instrument system, termed "the Flyer," is lofted with a helium-filled aerostat of 4 m nominal diameter and ...

Baloon-lofted pollutant sampling of open burning and open detonation: abstract

EPA Science Inventory

The U.S. EPA has developed a balloon-lofted, ~10 kg instrument pack for sampling open burning (OB) and open detonation (OD) events for pollutants. The instrument pack, termed the “Flyer,” and its accompanying maneuverable balloon system, are intended to sample OB/OD plumes to de...

Monitoring the Crab Nebula with LOFT

NASA Technical Reports Server (NTRS)

Wilson-Hodge, Colleen A.

2012-01-01

From 2008-2010, the Crab Nebula was found to decline by 7% in the 15-50 keV band, consistently in Fermi GBM, INTEGRAL IBIS, SPI, and JEMX, RXTE PCA, and Swift BAT. From 2001-2010, the 15-50 keV flux from the Crab Nebula typically varied by about 3.5% per year. Analysis of RXTE PCA data suggests possible spectral variations correlated with the flux variations. I will present estimates of the LOFT sensitivity to these variations. Prior to 2001 and since 2010, the observed flux variations have been much smaller. Monitoring the Crab with the LOFT WFM and LAD will provide precise measurements of flux variations in the Crab Nebula if it undergoes a similarly active episode.

Facilitation techniques as predictors of crew participation in LOFT debriefings

NASA Technical Reports Server (NTRS)

McDonnell, L. K.

1996-01-01

Based on theories of adult learning and airline industry guidelines for Crew Resource Management (CRM), the stated objective during Line Oriented Flight Training (LOFT) debriefings is for instructor pilots (IP's) to facilitate crew self-analysis of performance. This study reviews 19 LOFT debriefings from two major U.S. airlines to examine the relationship between IP efforts at facilitation and associated characteristics of crew participation. A subjective rating scale called the Debriefing Assessment Battery was developed and utilized to evaluate the effectiveness of IP facilitation and the quality of crew participation. The results indicate that IP content, encouragement, and questioning techniques are highly and significantly correlated with, and can therefore predict, the degree and depth of crew participation.

LOFT. Interior, control room in control building (TAN630). Camera facing ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Interior, control room in control building (TAN-630). Camera facing north. Sign says "This control console is partially active. Do not operate any switch handle without authorization." Date: May 2004. INEEL negative no. HD-39-14-3 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

LOFT. Reactor arrives at containment building (TAN650), now being pushed ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Reactor arrives at containment building (TAN-650), now being pushed by locomotive. Camera facing northerly. Note "Hello Dolly" and "PWR MTA No. 1" (pressurized water reactor mobile test assembly) signs. Date: 1973. INEEL negative no. 73-3710 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

LOFT. Reactor apparatus leaves A&M building (TAN607). Shielded locomotive has ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Reactor apparatus leaves A&M building (TAN-607). Shielded locomotive has aerojet logo, which replaced old general electric logo, pulls reactor from assembly shop on dolly. Camera facing easterly. Date: 1973. INEEL negative no. 73-3700 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Preliminary posttest analysis of LOFT loss-of-coolant experiment L2-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, J.R.; Grush, W.H.; Keeler, C.D.

A preliminary posttest analysis of Loss-of-Coolant Experiment (LOCE) L2-2, which was conducted in the Loss-of-Fluid Test (LOFT) facility, was performed to gain an understanding of the cause of the disparity between predicted and measured fuel rod cladding temperature responses in the LOFT core. LOCE L2-2 is the first experiment in the LOFT Power Ascension Series L2 (first series of LOFT nuclear experiments), which was designed to investigate the response of the LOFT nuclear core to the blowdown, refill, and reflood transients during LOCEs conducted at gradually increasing power levels. LOCE L2-2 was conducted at 50% power (25 MW, 26.38 kW/m).more » Results show that a core-wide rewet occurred early in the transient (during blowdown starting at about 7 s after rupture) which was not calculated in the pretest prediction analysis. This early core-wide rewet resulted in the peak fuel rod cladding temperatures being lower (by a mean value of 166/sup 0/K for 24 thermocouples) than had been calculated. This preliminary posttest analysis was concerned solely with determining why the early core-wide rewet was not predicted by the RELAP4/MOD6 pretest analysis and be no means is it a complete posttest analysis of LOCE L2-2 results. However, during this analysis, several errors made in the prettest analysis were found, and their impact on the predicted results is assessed. Three factors were postulated to have caused the disparity between predicted and measured fuel rod cladding temperatures for LOCE L2-2: (a) the initial fuel rod stored energy, (b) the heat transfer surface, and (c) the hydraulics calculation. These factors were examined and are discussed in this report. It was determined that core hydraulics, as influenced by the calculation of broken loop cold leg break flow, was the major factor causing the disparity.« less

LOFT. Containment building entry, an adapted use of TAN624, which ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Containment building entry, an adapted use of TAN-624, which originated as the mobile test building for the ANP program. Camera facing north. Note four-rail track entered building stack at right of view. Date: March 2004. INEEL negative no. HD-39-4-1 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Group 4: Instructor training and qualifications

NASA Technical Reports Server (NTRS)

Sessa, R.

1981-01-01

Each professional instructor or check airman used in LOFT training course should complete an FAA approved training course in the appropriate aircraft type. Instructors used in such courses need not be type-rated. If an instructor or check airman who is presently not line-qualified is used as a LOFT instructor, he or she should remain current in line-operational procedures by observing operating procedures from the jump seat on three typical line segments pr 90 days on the appropriate aircraft type. ("Line qualification" means completion as a flight crew member of at least three typical line segments per 90 days on the appropriate aircraft type.) The training should include the requirement of four hours of LOFT training, in lieu of actual aircraft training or line operating experience.

Atmospheric propagation modeling indicates homing pigeons use loft-specific infrasonic 'map' cues.

PubMed

Hagstrum, Jonathan T

2013-02-15

Results from an acoustic ray-tracing program using daily meteorological profiles are presented to explain 'release-site biases' for homing pigeons at three experimental sites in upstate New York where W. T. Keeton and his co-workers at Cornell University conducted extensive releases between 1968 and 1987 in their investigations of the avian navigational 'map'. The sites are the Jersey Hill and Castor Hill fire towers, and another near Weedsport, where control pigeons from the Cornell loft vanished in random directions, in directions consistently >50 deg clockwise and in directions ∼15 deg clockwise from the homeward bearing, respectively. Because Cornell pigeons were disoriented at Jersey Hill whereas birds from other lofts were not, it is inferred that Jersey Hill lies within an acoustic 'shadow' zone relative to infrasonic signals originating from the Cornell loft's vicinity. Such signals could arise from ground-to-air coupling of near-continuous microseisms, or from scattering of direct microbaroms off terrain features, both of which are initially generated by wave-wave interactions in the deep ocean. HARPA runs show that little or no infrasound from the loft area arrived at Jersey Hill on days when Cornell pigeons were disoriented there, and that homeward infrasonic signals could have arrived at all three sites from directions consistent with pigeon departure bearings, especially on days when these bearings were unusual. The general stability of release-site biases might be due to influences of terrain on transmission of the homeward signals under prevailing weather patterns, whereas short-term changes in biases might be caused by rapid shifts in atmospheric conditions.

LOFT. Containment building (TAN650) detail. Camera facing east. Service building ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Containment building (TAN-650) detail. Camera facing east. Service building corner is at left of view above personnel access. Round feature at left of dome is tank that will contain borated water. Metal stack at right of view. Date: 1973. INEEL negative no. 73-1085 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Baseline design of the filters for the LAD detector on board LOFT

NASA Astrophysics Data System (ADS)

Barbera, M.; Winter, B.; Coker, J.; Feroci, M.; Kennedy, T.; Walton, D.; Zane, S.

2014-07-01

The Large Observatory for X-ray Timing (LOFT) was one of the M3 missions selected for the phase A study in the ESA's Cosmic Vision program. LOFT is designed to perform high-time-resolution X-ray observations of black holes and neutron stars. The main instrument on the LOFT payload is the Large Area Detector (LAD), a collimated experiment with a nominal effective area of ~10 m2 @ 8 keV, and a spectral resolution of ~240 eV in the energy band 2-30 keV. These performances are achieved covering a large collecting area with more than 2000 large-area Silicon Drift Detectors (SDDs) each one coupled to a collimator based on lead-glass micro-channel plates. In order to reduce the thermal load onto the detectors, which are open to Sky, and to protect them from out of band radiation, optical-thermal filter will be mounted in front of the SDDs. Different options have been considered for the LAD filters for best compromise between high quantum efficiency and high mechanical robustness. We present the baseline design of the optical-thermal filters, show the nominal performances, and present preliminary test results performed during the phase A study.

Evaluating the effectiveness of cockpit resource management training

NASA Technical Reports Server (NTRS)

Helmreich, Robert L.

1989-01-01

The concept of providing flight crews with intensive training in crew coordination and interpersonal skills (cockpit resource management training - CRM) is outlined with emphasis on full mission simulator training (line-oriented flight training - LOFT). Findings from several airlines that have instituted CRM and LOFT are summarized. Four types of criteria used for evaluating CRM programs: observer ratings of crew behavior, measures of attitudes regarding cockpit management, self-reports by participants on the value of the training, and case studies of CRM-related incidents and accidents are covered. Attention is focused on ratings of the performance of crews during line flights and during simulator sessions conducted as a part of LOFT. A boomerang effect - the emergence of a subgroup that has changed the attitudes in the opposite direction from that desired is emphasized.

LOFT. Interior view of entry to reactor building, TAN650. Camera ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Interior view of entry to reactor building, TAN-650. Camera is inside entry (TAN-624) and facing north. At far end of domed chamber are penetrations in wall for electrical and other connections. Reactor and other equipment has been removed. Date: March 2004. INEEL negative no. HD-39-5-1 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

LOFT complex in 1975 awaits renewed mission. Aerial view. Camera ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT complex in 1975 awaits renewed mission. Aerial view. Camera facing southwesterly. Left to right: stack, entry building (TAN-624), door shroud, duct shroud and filter hatches, dome (painted white), pre-amp building, equipment and piping building, shielded control room (TAN-630), airplane hangar (TAN-629). Date: 1975. INEEL negative no. 75-3690 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Group 2: Real time LOFT operations

NASA Technical Reports Server (NTRS)

Cavanagh, D.

1981-01-01

All LOFT scenarios should be constructed so as to provide the highest degree of realism that is economically, technically, and operationally feasible. The more realistic the situation, the faster the crew will adjust their thinking and provide reactions which would be typical of a line-flight orientation. The goal is to produce crew performance which would be typical of a crew on an actual line flight, given the same set of circumstances that were developed during the scenario. The briefing which is provided to the crew before entering the simulator for LOFT, the trip papers, the communications throughout the flight, the role played by the instructor, and so on, are important factors, crucial to the establishment and maintenance of a high degree of realism. Crews should have all manuals and other required equipment for a normal line-flight.

Posttest analysis of LOFT LOCE L2-3 using the ESA RELAP4 blowdown model. [PWR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perryman, J.L.; Samuels, T.K.; Cooper, C.H.

A posttest analysis of the blowdown portion of Loss-of-Coolant Experiment (LOCE) L2-3, which was conducted in the Loss-of-Fluid Test (LOFT) facility, was performed using the experiment safety analysis (ESA) RELAP4/MOD5 computer model. Measured experimental parameters were compared with the calculations in order to assess the conservatisms in the ESA RELAP4/MOD5 model.

LOFT. Construction view of tunnel during 1957 to compare with ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Construction view of tunnel during 1957 to compare with HAER photo ID-33-E-358 above. Tunnel sections were pre-cast, then joined together. Photographer described this as :Personnel and service tunnel running east-west in test building of the FET." Date: December 19, 1957. Photographer: Jack L. Anderson. INEEL negative no. 57-6206 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

LOFT complex, aerial view taken on same on same day ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT complex, aerial view taken on same on same day as HAER photo ID-33-E-376. Camera facing south. Note curve of rail track toward hot shop (TAN-607). Earth shielding on control building (TAN-630) is partly removed, showing edge of concrete structure. Great southern butte on horizon. Date: 1975. INEEL negative no. 75-3693 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Posttest RELAP4 analysis of LOFT experiment L1-4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grush, W.H.; Holmstrom, H.L.O.

Results of posttest analysis of LOFT loss-of-coolant experiment L1-4 with the RELAP4 code are presented. The results are compared with the pretest prediction and the test data. Differences between the RELAP4 model used for this analysis and that used for the pretest prediction are in the areas of initial conditions, nodalization, emergency core cooling system, broken loop hot leg, and steam generator secondary. In general, these changes made only minor improvement in the comparison of the analytical results to the data. Also presented are the results of a limited study of LOFT downcomer modeling which compared the performance of themore » conventional single downcomer model with that of the new split downcomer model. A RELAP4 sensitivity calculation with artificially elevated emergency core coolant temperature was performed to highlight the need for an ECC mixing model in RELAP4.« less

Burst Oscillation Probes of Neutron Stars and Nuclear Burning with LOFT

NASA Technical Reports Server (NTRS)

Strohmayer, Tod

2012-01-01

X-ray brightness oscillations during thermonuclear X-ray bursts--burst oscillations--have provided a new probe of neutron star spins as well as of the dependent nuclear burning processes. The frequency drift and amplitude evolution of the oscillations observed during bursts can in principle place constraints on the physics of thermonuclear flame spreading and the dynamics of the burning atmosphere. I use simulations appropriate to LOFT to explore the precision with which the time dependence of the oscillation frequency can be inferred. This can test, for example, different models for the frequency drift, such as up-lift versus geostrophic drift. I also explore the precision with which asymptotic frequencies can be constrained in order to estimate the capability for LOFT to detect the Doppler shifts induced by orbital motion of the neutron star from a sample of bursts at different orbital phases.

Neutron Star Spin Measurements and Dense Matter with LOFT

NASA Technical Reports Server (NTRS)

Strohmayer, Tod

2011-01-01

Observations over the last decade with RXTE have begun to reveal the X-ray binary progenitors of the fastest spinning neutron stars presently known. Detection and study of the spin rates of binary neutron stars has important implications for constraining the nature of dense matter present in neutron star interiors, as both the maximum spin rate and mass for neutron stars is set by the equation of state. Precision pulse timing of accreting neutron star binaries can enable mass constraints. Particularly promIsing is the combination of the pulse and eclipse timing, as for example, in systems like Swift 11749.4-2807. With its greater sensitivity, LOFT will enable deeper searches for the spin periods of the neutron stars, both during persistent outburst intervals and thermonuclear X-ray bursts, and enable more precise modeling of detected pulsations. I will explore the anticipated impact of LOFT on spin measurements and its potential for constraining dense matter in neutron stars

LOFT data acquisition and visual display system (DAVDS) presentation program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bullock, M.G.; Miyasaki, F.S.

1976-03-01

The Data Acquisition and Visual Display System (DAVDS) at the Loss-of-Fluid Test Facility (LOFT) has 742 data channel recording capability of which 576 are recorded digitally. The purpose of this computer program is to graphically present the data acquired and/or processed by the LOFT DAVDS. This program takes specially created plot data buffers of up to 1024 words and generates time history plots on the system electrostatic printer-plotter. The data can be extracted from two system input devices: Magnetic disk or digital magnetic tape. Versatility has been designed in the program by providing the user three methods of scaling plots:more » Automatic, control record, and manual. Time required to produce a plot on the system electrostatic printer-plotter varies from 30 to 90 seconds depending on the options selected. The basic computer and program details are described.« less

KSC-2011-3095

NASA Image and Video Library

2011-04-26

CAPE CANAVERAL, Fla. -- NASA's Gravity Recovery and Interior Laboratory, or GRAIL, mission logo on the side of the United Launch Alliance Delta II rocket that will loft the spacecraft into lunar orbit. The GRAIL mission is a part of NASA's Discovery Program. GRAIL will fly twin spacecraft in tandem orbits around the moon for several months to measure its gravity field. The mission also will answer longstanding questions about Earth's moon and provide scientists a better understanding of how Earth and other rocky planets in the solar system formed. GRAIL is scheduled to launch September 8, 2011. For more information visit: http://science.nasa.gov/missions/grail/. Photo credit: NASA/Jim Grossmann

Texas International Airlines LOFT program

NASA Technical Reports Server (NTRS)

Sommerville, J.

1981-01-01

A line-oriented flight training program which allows the crew to work as a team to solve all problems, abnormal or emergency, within the crew concept. A line-oriented check ride takes place every six months for the pilot as a proficiency check. There are advantages and disadvantages to this program. One disadvantage is that since it is designed as a check-ride, the scenarios must be structured so that the average pilot will complete the check-ride without complication. This system is different from a proficiency check which can be stopped at a problem area so training to proficiency can take place before proceeding with the check.

LOFT. Reactor support apparatus inside containment building (TAN650). Camera is ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Reactor support apparatus inside containment building (TAN-650). Camera is on crane rail level and facing northerly. View shows top two banks of round conduit openings on wall for electrical and other connections to control room. Ladders and platforms provide access to reactor instrumentation. Note hatch in floor and drain at edge of floor near wall. Date: 1974. INEEL negative no. 74-219 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Eastern Airlines LOFT program

NASA Technical Reports Server (NTRS)

Beach, B. E.

1981-01-01

Beginning with scenario design and development issues, Eastern Airlines committed itself to the full four-hour LOFT training format without the additional time for specific maneuvers. Abnormals and emergency conditions, pacing, and quiet periods are included in the scenarios which are written for the instructor to follow verbatim. Simulator capabilities, performance assessment; training vs. checking; crew composition and scheduling; satisfactory completion; the use of video performance printouts; the number of instructors; instructor training and standardization; and initial, transition, and upgrade training are discussed.

Homing Pigeons Respond to Time-Compensated Solar Cues Even in Sight of the Loft

PubMed Central

Armstrong, Chris; Wilkinson, Helen; Meade, Jessica; Biro, Dora; Freeman, Robin; Guilford, Tim

2013-01-01

The sun has long been thought to guide bird navigation as the second step in a two-stage process, in which determining position using a map is followed by course setting using a compass, both over unfamiliar and familiar terrain. The animal’s endogenous clock time-compensates the solar compass for the sun’s apparent movement throughout the day, and this allows predictable deflections in orientation to test for the compass’ influence using clock-shift manipulations. To examine the influence of the solar compass during a highly familiar navigational task, 24 clock-shifted homing pigeons were precision-tracked from a release site close to and in sight of their final goal, the colony loft. The resulting trajectories displayed significant partial deflection from the loft direction as predicted by either fast or slow clock-shift treatments. The partial deflection was also found to be stable along the entire trajectory indicating regular updating of orientation via input from the solar compass throughout the final approach flight to the loft. Our results demonstrate that time-compensated solar cues are deeply embedded in the way birds orient during homing flight, are accessed throughout the journey and on a remarkably fine-grained scale, and may be combined effectively simultaneously with direct guidance from familiar landmarks, even when birds are flying towards a directly visible goal. PMID:23717401

LADEE UVS (UltraViolet Visible Spectrometer) and the Search for Lunar Exospheric Dust: A Detailed Spectral Analysis

NASA Technical Reports Server (NTRS)

Wooden, Diane H.; Cook, Amanda; Colaprete, Anthony; Shirley, Mark; Vargo, Kara; Elphic, Richard C.; Hermalyn, Brendan; Stubbs, Timothy John; Glenar, David A.

2014-01-01

The Lunar Atmosphere and Dust Environment Explorer (LADEE) executed science observations in lunar orbit spanning 2013-Oct-16- 2014-04-18 UT. LADEE's Ultraviolet/Visible Spectrometer (UVS) studies the composition and temporal variations of the tenuous lunar exosphere and dust environment, utilizing two sets of optics: a limb-viewing telescope, and a solar-viewer. The limb-viewing telescope observes illuminated dust and emitting gas species while the Sun is just behind the lunar limb. The solar viewer, with its diffuser, allows UVS to also stare directly at the solar disk as it approaches the limb, sampling progressively lower exosphere altitudes. Solar viewer "Occultation" activities occur at the lunar sunrise limb, as the LADEE spacecraft passes into the lunar night side, facing the Sun (the spacecraft orbit is near-equatorial retrograde). A loss of transmission of sunlight occurs by the occultation of dust grains along the line-of-sight. So-called "Inertial Limb" activities have the limb-viewing telescope pointed at the lit exosphere just after the Sun has set. Inertial Limb activities follow a similar progression of diminishing sampling altitudes but hold the solar elongation angle constant so the zodiacal light contribution remains constant while seeking to observe the weak lunar horizon glow. On the dark side of the moon, "Sodium Tail" activities pointed the limb-viewing telescope in the direction of the Moon's sodium tail (similar to anti-sunward), during different lunar phases. Of the UVS data sets, these show the largest excess of scattered blue light, indicative of the presence of small (approximately 100 nm) dust grains in the tail. Correlations are sought between dust in the sodium tail and meteor streams and magnetotail crossings to investigate impact- versus electrostatic-lofting. Once lofted, nanoparticles can become charged and picked up by the solar wind. The LADEE UVS Occultation, Inertial Limb, and Sodium Tail spectral datasets provide evidence of a lunar dust exosphere.

Developing A SPOT CRM Debriefing Tool

NASA Technical Reports Server (NTRS)

Martin, Lynne; Villeda, Eric; Orasanu, Judith; Connors, Mary M. (Technical Monitor)

1998-01-01

In a study of CRM LOFT briefings published in 1997, Dismukes, McDonnell & Jobe reported that briefings were not being utilized as fully as they could be and that crews may not be getting the full benefit from LOFT that is possible. On the basis of their findings, they suggested a set of general guidelines for briefings for the industry. Our work builds on this study to try to provide a specific debriefing tool which provides a focus for the strategies that Dismukes et al suggest.

LOFT. Containment building (TAN650) with fourrail tracks in place. Stack ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT. Containment building (TAN-650) with four-rail tracks in place. Stack has been erected. Curved shroud over doorway and to the right is weather protection for railroad door seen in HAER photo ID-33-E-367. Motor-operated door rolls on wheels to open and close. Service portions of containment building can be seen at rear of dome on left and right. Camera facing north. Date: 1973. INEEL negative no. 73-1600 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Loft: An Automated Mesh Generator for Stiffened Shell Aerospace Vehicles

NASA Technical Reports Server (NTRS)

Eldred, Lloyd B.

2011-01-01

Loft is an automated mesh generation code that is designed for aerospace vehicle structures. From user input, Loft generates meshes for wings, noses, tanks, fuselage sections, thrust structures, and so on. As a mesh is generated, each element is assigned properties to mark the part of the vehicle with which it is associated. This property assignment is an extremely powerful feature that enables detailed analysis tasks, such as load application and structural sizing. This report is presented in two parts. The first part is an overview of the code and its applications. The modeling approach that was used to create the finite element meshes is described. Several applications of the code are demonstrated, including a Next Generation Launch Technology (NGLT) wing-sizing study, a lunar lander stage study, a launch vehicle shroud shape study, and a two-stage-to-orbit (TSTO) orbiter. Part two of the report is the program user manual. The manual includes in-depth tutorials and a complete command reference.

Mice selectively bred for open-field thigmotaxis: life span and stability of the selection trait.

PubMed

Leppänen, Pia K; Ewalds-Kvist, S Béatrice M; Selander, Ritva-Kajsa

2005-04-01

In 2 experiments, the authors examined 69 mice selectively bred for high or low levels of open-field (OF) thigmotactic behavior (high open-field thigmotaxis [HOFT] and low open-field thigmotaxis [LOFT], respectively). They found that the strains differed in defecation during the 60-min exposure to the OF. Furthermore, the strains differed with regard to their life spans: The more thigmotactic HOFT mice lived longer than the LOFT mice. The strains were not differentiated by food intake or excretion. The strain difference in thigmotaxis was not age dependent, and it persisted in the home-cage condition as well. Neither the location (center or wall) of the starting point nor the shape (circular or square) of the OF arena affected the difference in wall-seeking behavior between the two strains. The authors concluded that the difference in thigmotaxis (or emotionality) between the HOFT and LOFT mice is a stable and robust feature of these animals.

Transport of ice into the stratosphere and the humidification of the stratosphere over the 21st century.

PubMed

Dessler, A E; Ye, H; Wang, T; Schoeberl, M R; Oman, L D; Douglass, A R; Butler, A H; Rosenlof, K H; Davis, S M; Portmann, R W

2016-03-16

Climate models predict that tropical lower-stratospheric humidity will increase as the climate warms. We examine this trend in two state-of-the-art chemistry-climate models. Under high greenhouse gas emissions scenarios, the stratospheric entry value of water vapor increases by ~1 part per million by volume (ppmv) over this century in both models. We show with trajectory runs driven by model meteorological fields that the warming tropical tropopause layer (TTL) explains 50-80% of this increase. The remainder is a consequence of trends in evaporation of ice convectively lofted into the TTL and lower stratosphere. Our results further show that, within the models we examined, ice lofting is primarily important on long time scales - on interannual time scales, TTL temperature variations explain most of the variations in lower stratospheric humidity. Assessing the ability of models to realistically represent ice-lofting processes should be a high priority in the modeling community.

Transport of ice into the stratosphere and the humidification of the stratosphere over the 21st century

PubMed Central

Dessler, A.E.; Ye, H.; Wang, T.; Schoeberl, M.R.; Oman, L.D.; Douglass, A.R.; Butler, A.H.; Rosenlof, K.H.; Davis, S.M.; Portmann, R.W.

2018-01-01

Climate models predict that tropical lower-stratospheric humidity will increase as the climate warms. We examine this trend in two state-of-the-art chemistry-climate models. Under high greenhouse gas emissions scenarios, the stratospheric entry value of water vapor increases by ~1 part per million by volume (ppmv) over this century in both models. We show with trajectory runs driven by model meteorological fields that the warming tropical tropopause layer (TTL) explains 50–80% of this increase. The remainder is a consequence of trends in evaporation of ice convectively lofted into the TTL and lower stratosphere. Our results further show that, within the models we examined, ice lofting is primarily important on long time scales — on interannual time scales, TTL temperature variations explain most of the variations in lower stratospheric humidity. Assessing the ability of models to realistically represent ice-lofting processes should be a high priority in the modeling community. PMID:29551841

Transport of Ice into the Stratosphere and the Humidification of the Stratosphere over the 21st Century

NASA Technical Reports Server (NTRS)

Dessler, A. E.; Ye, H.; Wang, T.; Schoeberl, M. R.; Oman, L. D.; Douglass, A. R.; Butler, A. H.; Rosenlof, K. H.; Davis, S. M.; Portmann, R. W.

2016-01-01

Climate models predict that tropical lower-stratospheric humidity will increase as the climate warms. We examine this trend in two state-of-the-art chemistry-climate models. Under high greenhouse gas emissions scenarios, the stratospheric entry value of water vapor increases by approx. 1 part per million by volume (ppmv) over this century in both models. We show with trajectory runs driven by model meteorological fields that the warming tropical tropopause layer (TTL) explains 50-80% of this increase. The remainder is a consequence of trends in evaporation of ice convectively lofted into the TTL and lower stratosphere. Our results further show that, within the models we examined, ice lofting is primarily important on long time scales - on interannual time scales, TTL temperature variations explain most of the variations in lower stratospheric humidity. Assessing the ability of models to realistically represent ice-lofting processes should be a high priority in the modeling community.

LOFT/FET complex. Construction view of abutment footings for arches of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LOFT/FET complex. Construction view of abutment footings for arches of hangar (TAN-629). Tunnels between basement of hangar and control building (TAN-630) had to fit between arches. (Note concrete work taking place at hole at lower edge of view. This photo may document unexpected bubble in underlying lava rock. It was dumped full of concrete and a footing made. Source: Interview with John DeClue). Date: December 19, 1957. Photographer: Jack L. Anderson. INEEL negative no. 57-6203 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Modeling the Impact Ejected Dust Contribution to the Lunar Exosphere: Results from Experiments and Ground Truth from LADEE

NASA Astrophysics Data System (ADS)

Hermalyn, B.; Colaprete, A.

2013-12-01

A considerable body of evidence indicates the presence of lofted regolith dust above the lunar surface. These observations range from multiple in-situ and orbital horizon glow detections to direct measurement of dust motion on the surface, as by the Apollo 17 Lunar Ejecta and Meteorites (LEAM) experiment. Despite this evidence, the specific mechanisms responsible for the lofting of regolith are still actively debated. These include impact ejection, electrostatic lofting, effects of high energy radiation, UV/X- rays, and interplay with solar wind plasma. These processes are highly relevant to one of the two main scientific objectives of the Lunar Atmosphere and Dust Environment Explorer (LADEE) mission (due to launch September, 2013): to directly measure the lunar exospheric dust environment and its spatial and temporal variability towards the goal of better understanding the dust flux. Of all the proposed mechanisms taking place on the lunar surface, the only unequivocal ongoing process is impact cratering. Hypervelocity impact events, which mobilize and redistribute regolith across planetary surfaces, are arguably the most pervasive geologic process on rocky bodies. While many studies of dust lofting state that the impact flux rate is orders of magnitude too low to account for the lunar horizon glow phenomenon and discount its contribution, it is imperative to re-examine these assumptions in light of new data on impact ejecta, particularly from the contributions from mesoscale (impactor size on the order of grain size) and macroscale (impactor > grain size) cratering. This is in large part due to a previous lack of data, for while past studies have established a canonical ejecta model for main-stage ejection of sand targets from vertical impacts, only recent studies have been able to begin quantitatively probing the intricacies of the ejection process outside this main-stage, vertical regime. In particular, it is the high-speed early-time ejecta that will reach significant altitude above the surface and remain aloft ballistically for hours. In addition, ejecta dynamics in the transition regime between microcratering and macro scale events is not yet well understood. As such, there is no currently accepted encompassing model of impact ejecta delivery to the lunar exosphere. It is important to note that the work described here is not to duplicate or exclude other lofting mechanisms -- in reality, the lofting of dust is almost definitely a complex combination of processes -- but instead to provide essential constraints on the impact contribution. This study attempts to constrain the expected contributions from cratering to the lunar exosphere by assessing the ejecta 'background' signal lofted above the surface and the effects of transient focused events (meteor showers) which can produce significant increases in ejecta. In particular, this work couples scaling of previous ejecta studies with Monte-Carlo and ballistics models and will present LADEE data analysis (particularly from the UVS and LDEX instruments) and interpretation in context of constraining the ejected mass distribution. These results are relevant to both our understanding of exospheric dust and for constraint of hazards for future human habitation.

Atmospheric propagation modeling indicates homing pigeons use loft-specific infrasonic ‘map’ cues

USGS Publications Warehouse

Hagstrum, Jonathan T.

2013-01-01

Results from an acoustic ray-tracing program using daily meteorological profiles are presented to explain ‘release-site biases’ for homing pigeons at three experimental sites in upstate New York where W. T. Keeton and his co-workers at Cornell University conducted extensive releases between 1968 and 1987 in their investigations of the avian navigational ‘map’. The sites are the Jersey Hill and Castor Hill fire towers, and another near Weedsport, where control pigeons from the Cornell loft vanished in random directions, in directions consistently >50 deg clockwise and in directions ∼15 deg clockwise from the homeward bearing, respectively. Because Cornell pigeons were disoriented at Jersey Hill whereas birds from other lofts were not, it is inferred that Jersey Hill lies within an acoustic ‘shadow’ zone relative to infrasonic signals originating from the Cornell loft’s vicinity. Such signals could arise from ground-to-air coupling of near-continuous microseisms, or from scattering of direct microbaroms off terrain features, both of which are initially generated by wave–wave interactions in the deep ocean. HARPA runs show that little or no infrasound from the loft area arrived at Jersey Hill on days when Cornell pigeons were disoriented there, and that homeward infrasonic signals could have arrived at all three sites from directions consistent with pigeon departure bearings, especially on days when these bearings were unusual. The general stability of release-site biases might be due to influences of terrain on transmission of the homeward signals under prevailing weather patterns, whereas short-term changes in biases might be caused by rapid shifts in atmospheric conditions.

Status of the assessment phase of the ESA M3 mission candidate LOFT

NASA Astrophysics Data System (ADS)

Corral van Damme, Carlos; Ayre, Mark; Lumb, David; Short, Alexander D.; Rando, Nicola

2012-09-01

LOFT (Large Observatory For x-ray Timing) is one of four candidates for the M3 slot (launch in 2024, with the option of a launch in 2022) of ESAs Cosmic Vision 2015 - 2025 Plan, and as such it is currently undergoing an initial assessment phase lasting one year. The objective of the assessment phase is to provide the information required to enable the down selection process, in particular: the space segment definition for meeting the assigned science objectives; consideration of and initial definition of the implementation schedule; an estimate of the mission Cost at Completion (CaC); an evaluation of the technology readiness evaluation and risk assessment. The assessment phase is divided into two interleaved components: (i) A payload assessment study, performed by teams funded by member states, which is primarily intended for design, definition and programmatic/cost evaluation of the payload, and (ii) A system industrial study, which has essentially the same objectives for the space segment of the mission. This paper provides an overview of the status of the LOFT assessment phase, both for payload and platform. The initial focus is on the payload design status, providing the reader with an understanding of the main features of the design. Then the space segment assessment study status is presented, with an overview of the principal challenges presented by the LOFT payload and mission requirements, and a presentation of the expected solutions. Overall the mission is expected to enable cutting-edge science, is technically feasible, and should remain within the required CaC for an M3 candidate.

Orbital Observations of Dust Lofted by Daytime Convective Turbulence

NASA Astrophysics Data System (ADS)

Fenton, Lori; Reiss, Dennis; Lemmon, Mark; Marticorena, Béatrice; Lewis, Stephen; Cantor, Bruce

2016-11-01

Over the past several decades, orbital observations of lofted dust have revealed the importance of mineral aerosols as a climate forcing mechanism on both Earth and Mars. Increasingly detailed and diverse data sets have provided an ever-improving understanding of dust sources, transport pathways, and sinks on both planets, but the role of dust in modulating atmospheric processes is complex and not always well understood. We present a review of orbital observations of entrained dust on Earth and Mars, particularly that produced by the dust-laden structures produced by daytime convective turbulence called "dust devils". On Earth, dust devils are thought to contribute only a small fraction of the atmospheric dust budget; accordingly, there are not yet any published accounts of their occurrence from orbit. In contrast, dust devils on Mars are thought to account for several tens of percent of the planet's atmospheric dust budget; the literature regarding martian dust devils is quite rich. Because terrestrial dust devils may temporarily contribute significantly to local dust loading and lowered air quality, we suggest that martian dust devil studies may inform future studies of convectively-lofted dust on Earth.

Pigeon Navigation: Different Routes Lead to Frankfurt

PubMed Central

Schiffner, Ingo; Wiltschko, Roswitha

2014-01-01

Background Tracks of pigeons homing to the Frankfurt loft revealed an odd phenomenon: whereas birds returning from the North approach their loft more or less directly in a broad front, pigeons returning from the South choose, from 25 km from home onward, either of two corridors, a direct one and one with a considerable detour to the West. This implies differences in the navigational process. Methodology/Principle Findings Pigeons released at sites at the beginning of the westerly corridor and in this corridor behave just like pigeons returning from farther south, deviating to the west before turning towards their loft. Birds released at sites within the straight corridors, in contrast, take more or less straight routes. The analysis of the short-term correlation dimension, a quantity reflecting the complexity of the system and with it, the number of factors involved in the navigational process, reveals that it is significantly larger in pigeons choosing the westerly corridor than in the birds flying straight - 3.03 vs. 2.85. The difference is small, however, suggesting a different interpretation of the same factors, with some birds apparently preferring particular factors over others. Conclusions The specific regional distribution of the factors which pigeons use to determine their home course seems to provide ambiguous information in the area 25 km south of the loft, resulting in the two corridors. Pigeons appear to navigate by deriving their routes directly from the locally available navigational factors which they interpret in an individual way. The fractal nature of the correlation dimensions indicates that the navigation process of pigeons is chaotic-deterministic; published tracks of migratory birds suggest that this may apply to avian navigation in general. PMID:25391144

Design of combinatorial libraries for the exploration of virtual hits from fragment space searches with LoFT.

PubMed

Lessel, Uta; Wellenzohn, Bernd; Fischer, J Robert; Rarey, Matthias

2012-02-27

A case study is presented illustrating the design of a focused CDK2 library. The scaffold of the library was detected by a feature trees search in a fragment space based on reactions from combinatorial chemistry. For the design the software LoFT (Library optimizer using Feature Trees) was used. The special feature called FTMatch was applied to restrict the parts of the queries where the reagents are permitted to match. This way a 3D scoring function could be simulated. Results were compared with alternative designs by GOLD docking and ROCS 3D alignments.

Group 1: Scenario design and development issues

NASA Technical Reports Server (NTRS)

Sherwin, P.

1981-01-01

All LOFT scenarios and flight segments should be designed on the basis of a detailed statement of specific objectives. These objectives must state what kind of situation is to be addressed and why. The origin, routing, and destination of a particular scenario should be dictated by the specific objectives for that scenario or leg. Other factors to be considered are the desired weather, climate, etc. Simulator visual system, as well as other capabilities and limitations must be considered at a very early stage of scenario design. The simulator navigation area must be apropriate and must coincide with current Jeppeson charts. Much of the realism of LOFT is destroyed if the crew is unable to use current manuals and other materials.

The LOFT Mission Concept - A Status Update

NASA Technical Reports Server (NTRS)

Feroci, M.; Bozzo, E.; Brandt, S.; Hernanz, M.; van Der Klis, M.; Liu , L. -P.; Orleanski, P.; Pohl, M.; Santangelo, A.; Schanne, S.;

Do release-site biases reflect response to the Earth's magnetic field during position determination by homing pigeons?

PubMed

Mora, Cordula V; Walker, Michael M

2009-09-22

How homing pigeons (Columba livia) return to their loft from distant, unfamiliar sites has long been a mystery. At many release sites, untreated birds consistently vanish from view in a direction different from the home direction, a phenomenon called the release-site bias. These deviations in flight direction have been implicated in the position determination (or map) step of navigation because they may reflect local distortions in information about location that the birds obtain from the geophysical environment at the release site. Here, we performed a post hoc analysis of the relationship between vanishing bearings and local variations in magnetic intensity using previously published datasets for pigeons homing to lofts in Germany. Vanishing bearings of both experienced and naïve birds were strongly associated with magnetic intensity variations at release sites, with 90 per cent of bearings lying within +/-29 degrees of the magnetic intensity slope or contour direction. Our results (i) demonstrate that pigeons respond in an orderly manner to the local structure of the magnetic field at release sites, (ii) provide a mechanism for the occurrence of release-site biases and (iii) suggest that pigeons may derive spatial information from the magnetic field at the release site that could be used to estimate their current position relative to their loft.

The WFM Instrument of the LOFT mission

NASA Astrophysics Data System (ADS)

Gálvez, J. L.; Hernanz, M.; Álvarez, L.; LOFT/WFM Team

2013-05-01

LOFT, the Large Observatory For X-ray Timing, was selected by ESA in 2011 as one of the four M3 (medium class) missions concepts of the Cosmic Vision programme that will compete for a launch opportunity at the start of the 2020s. LOFT includes two instruments: the Large Area Detector (LAD), a ˜10 m^2 collimated X-ray detector in the 2-50 keV range (up to 80 keV in extended mode), and the Wide Field Monitor (WFM), a coded-mask wide field X-ray monitor based on silicon radiation detectors. We, the Institute of Space Sciences (CSIC-IEEC) in Barcelona, are deeply involved in the LOFT mission, sharing the leadership of the WFM instrument with DTU Space in Denmark. We are responsible of the mechanics of the WFM, including the structural and thermal design. The WFM baseline is a set of 4 units (each unit corresponds to 2 co-aligned cameras) arranged in arch, covering a field of view at zero response of 180°× 90°, and one more unit pointing to the anti-sun direction. The structure of each camera lies on its own coded mask of Tungsten, 150 μm thick, a collimator and the detector plane (20 cm below the mask) providing a fine (arc minutes) angular resolution. The camera detector plane (182 cm^2) will operate at -20°C in order to achieve an energy resolution FWHM of less than 500 eV in the 2-50 keV energy range. The WFM has the main scope of catching good triggering sources to be pointed with the LAD. Its large field of view will permit to observe in the same energy range of the LAD about 50% of the sky at once. The WFM is designed also to catch transient/bursting events down to a few mCrab fluxes and will provide for them data with fine spectral and timing resolution (up to 10 μsec).

29 CFR 1926.56 - Illumination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... and waste areas, accessways, active storage areas, loading platforms, refueling, and field maintenance..., mechanical and electrical equipment rooms, carpenter shops, rigging lofts and active storerooms, barracks or...

Reference Models for Structural Technology Assessment and Weight Estimation

NASA Technical Reports Server (NTRS)

Cerro, Jeff; Martinovic, Zoran; Eldred, Lloyd

2005-01-01

Previously the Exploration Concepts Branch of NASA Langley Research Center has developed techniques for automating the preliminary design level of launch vehicle airframe structural analysis for purposes of enhancing historical regression based mass estimating relationships. This past work was useful and greatly reduced design time, however its application area was very narrow in terms of being able to handle a large variety in structural and vehicle general arrangement alternatives. Implementation of the analysis approach presented herein also incorporates some newly developed computer programs. Loft is a program developed to create analysis meshes and simultaneously define structural element design regions. A simple component defining ASCII file is read by Loft to begin the design process. HSLoad is a Visual Basic implementation of the HyperSizer Application Programming Interface, which automates the structural element design process. Details of these two programs and their use are explained in this paper. A feature which falls naturally out of the above analysis paradigm is the concept of "reference models". The flexibility of the FEA based JAVA processing procedures and associated process control classes coupled with the general utility of Loft and HSLoad make it possible to create generic program template files for analysis of components ranging from something as simple as a stiffened flat panel, to curved panels, fuselage and cryogenic tank components, flight control surfaces, wings, through full air and space vehicle general arrangements.

Experimental & Numerical Modeling of Non-combusting Model Firebrands' Transport

NASA Astrophysics Data System (ADS)

Tohidi, Ali; Kaye, Nigel

2016-11-01

Fire spotting is one of the major mechanisms of wildfire spread. Three phases of this phenomenon are firebrand formation and break-off from burning vegetation, lofting and downwind transport of firebrands through the velocity field of the wildfire, and spot fire ignition upon landing. The lofting and downwind transport phase is modeled by conducting large-scale wind tunnel experiments. Non-combusting rod-like model firebrands with different aspect ratios are released within the velocity field of a jet in a boundary layer cross-flow that approximates the wildfire velocity field. Characteristics of the firebrand dispersion are quantified by capturing the full trajectory of the model firebrands using the developed image processing algorithm. The results show that the lofting height has a direct impact on the maximum travel distance of the model firebrands. Also, the experimental results are utilized for validation of a highly scalable coupled stochastic & parametric firebrand flight model that, couples the LES-resolved velocity field of a jet-in-nonuniform-cross-flow (JINCF) with a 3D fully deterministic 6-degrees-of-freedom debris transport model. The validation results show that the developed numerical model is capable of estimating average statistics of the firebrands' flight. Authors would like to thank support of the National Science Foundation under Grant No. 1200560. Also, the presenter (Ali Tohid) would like to thank Dr. Michael Gollner from the University of Maryland College Park for the conference participation support.

34. HILLMAN BARGE AND CONSTRUCTION COMPANY EMPLOYEES EXAMINING BARGE RAKE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

34. HILLMAN BARGE AND CONSTRUCTION COMPANY EMPLOYEES EXAMINING BARGE RAKE PART PATTERN, NORTHWEST MOLD LOFT - Hillman Barge & Construction Company, Paul Thomas Boulevard, Brownsville, Fayette County, PA

Subsonic Aircraft Soot: A Tracer Documenting Stratospheric Vertical Mixing and Barriers to Inter-Hemispheric Exchanges

NASA Technical Reports Server (NTRS)

Pueschel, Rudolf F.; Gore, Warren J. (Technical Monitor)

1996-01-01

Pole-to-pole variability of soot aerosol from subsonic aircraft is evidence of two important aspects of stratospheric transport. Vertical transport to 20 km pressure altitude from flight levels near 10-12 km cannot be explained by isentropic mixing. Instead, lofting in the tropics is a possibility. A strong meridional gradient implies that stratospheric soot aerosol residence time is shorter than are mixing times between the hemispheres. Therefore, little if any of exhaust constituents (with residence times similar to that of aircraft soot aerosol), emitted in heavily traveled flight corridors in northern mid-latitudes by a future supersonic fleet, would be transported to the southern hemisphere. However, a significant fraction of NOx could be lofted to altitudes above flight levels where it would dominate ozone depletion.

The SIRIUS mixed analog-digital ASIC developed for the LOFT LAD and WFM instruments

NASA Astrophysics Data System (ADS)

Cros, A.; Rambaud, D.; Moutaye, E.; Ravera, L.; Barret, D.; Caïs, P.; Clédassou, R.; Bodin, P.; Seyler, J. Y.; Bonzo, A.; Feroci, M.; Labanti, C.; Evangelista, Y.; Favre, Y.

2014-07-01

We report on the development and characterization of the low-noise, low power, mixed analog-digital SIRIUS ASICs for both the LAD and WFM X-ray instruments of LOFT. The ASICs we developed are reading out large area silicon drift detectors (SDD). Stringent requirements in terms of noise (ENC of 17 e- to achieve an energy resolution on the LAD of 200 eV FWHM at 6 keV) and power consumption (650 μW per channel) were basis for the ASICs design. These SIRIUS ASICs are developed to match SDD detectors characteristics: 16 channels ASICs adapted for the LAD (970 microns pitch) and 64 channels for the WFM (145 microns pitch) will be fabricated. The ASICs were developed with the 180nm mixed technology of TSMC.

Historic American Buildings Survey Marc Blair Photographer, summer 1966 WEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Historic American Buildings Survey Marc Blair Photographer, summer 1966 WEST (entry) END with CHOIR LOFT - Grace Protestant Episcopal Church, 1041 Wisconsin Avenue Northwest, Washington, District of Columbia, DC

Regional Simulations of Stratospheric Lofting of Smoke Plumes

NASA Astrophysics Data System (ADS)

Stenchikov, G. L.; Fromm, M.; Robock, A.

2006-12-01

The lifetime and spatial distribution of sooty aerosols from multiple fires that would cause major climate impact were debated in studies of climatic and environmental consequences of a nuclear war in the 1980s. The Kuwait oil fires in 1991 did not show a cumulative effect of multiple smoke plumes on large-scale circulation systems and smoke was mainly dispersed in the middle troposphere. However, recent observations show that smoke from large forest fires can be directly injected into the lower stratosphere by strong pyro-convective storms. Smoke plumes in the upper troposphere can be partially mixed into the lower stratosphere because of the same heating and lofting effect that was simulated in large-scale nuclear winter simulations with interactive aerosols. However nuclear winter simulations were conducted using climate models with grid spacing of more than 100 km, which do not account for the fine-scale dynamic processes. Therefore in this study we conduct fine-scale regional simulations of the aerosol plume using the Regional Atmospheric Modeling System (RAMS) mesoscale model which was modified to account for radiatively interactive tracers. To resolve fine-scale dynamic processes we use horizontal grid spacing of 25 km and 60 vertical layers, and initiate simulations with the NCEP reanalysis fields. We find that dense aerosol layers could be lofted from 1 to a few km per day, but this critically depends on the optical depth of aerosol layer, single scatter albedo, and how fast the plume is being diluted. Kuwaiti plumes from different small-area fires reached only 5-6 km altitude and were probably diffused and diluted in the lower and middle troposphere. A plume of 100 km spatial scale initially developed in the upper troposphere tends to penetrate into the stratosphere. Short-term cloud resolving simulations of such a plume show that aerosol heating intensifies small-scale motions that tend to mix smoke polluted air into the lower stratosphere. Regional simulations allow us to more accurately estimate the rate of lifting and spreading of aerosol clouds. But they do not reveal any dynamic processes that could prevent heating and lofting of absorbing aerosols.

Extracting lunar dust parameters from image charge signals produced by the Lunar Dust Experiment

NASA Astrophysics Data System (ADS)

Stanley, J.; Kempf, S.; Horanyi, M.; Szalay, J.

2015-12-01

The Lunar Dust Experiment (LDEX) onboard the Lunar Atmosphere and Dust Environment Explorer (LADEE) is an impact ionization dust detector used to characterize the lunar dust exosphere generated by the impacts of large interplanetary particles and meteor streams (Horanyi et al., 2015). In addition to the mass and speed of these lofted particles, LDEX is sensitive to their charge. The resulting signatures of impact events therefore provide valuable information about not only the ambient plasma environment, but also the speed vectors of these dust grains. Here, impact events produced from LDEX's calibration at the Dust Accelerator Laboratory are analyzed using an image charge model derived from the electrostatic simulation program, Coulomb. We show that parameters such as dust grain speed, size, charge, and position of entry into LDEX can be recovered and applied to data collected during LADEE's seven-month mission.

2010 JPC Abstract: Ares I First Stage Propulsion System Status

NASA Technical Reports Server (NTRS)

Priskos, Alex S.

2010-01-01

In November 2005, NASA created the Constellation Program to develop an entirely new fleet of spacecraft to include the Ares I Crew Launch Vehicle and Ares V Cargo Launch vehicles. This mission architecture included the Orion capsule (which would be used to transport astronauts to low-Earth orbit and beyond), the Altair lunar lander, and an Earth departure stage. The Ares First Stage Team has made significant progress on the design of a propulsion system to meet the objectives of the Constellation Program. Work on a first stage element propulsion system capable of lofting a new fleet of spacecraft is well underway. To minimize technical risks and development costs, the Solid Rocket Boosters (SRBs) of Shuttle served as a starting point in the design of a new motor that would meet the requirements of those new vehicles. This new propulsive element will provide greater total impulse utilizing a fifth segment to loft a safer, more powerful fleet of space flight vehicles. Performance requirements, basic architecture, and obsolescence issues were all factors in determining the new first stage element design and configuration. Early efforts focused on creating designs that would be capable of supporting the requisite loads and environments. While the motor casings are Shuttle legacy, because of Ares I s unique in-line configuration, the first stage will require entirely new forward structures (forward skirt, forward skirt extension, aeroshell, and frustum) and a modified systems tunnel. The use of composites facilitated a change in the geometry, which in turn afforded the ability to focus strength where it was needed without additional mass. The Ares First Stage rocket motor casting tooling was designed and built to achieve a propellant grain geometry that produces the specific required ballistic profile. The new propellant formulation is a polybutadiene acrylonitrile (PBAN) copolymer, which has been modified to attain the desired burn rate and retain adequate tailoring capability.

Posttest REALP4 analysis of LOFT experiment L1-3A

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, J.R.; Holmstrom, H.L.O.

This report presents selected results of posttest RELAP4 modeling of LOFT loss-of-coolant experiment L1-3A, a double-ended isothermal cold leg break with lower plenum emergency core coolant injection. Comparisons are presented between the pretest prediction, the posttest analysis, and the experimental data. It is concluded that pressurizer modeling is important for accurately predicting system behavior during the initial portion of saturated blowdown. Using measured initial conditions rather than nominal specified initial conditions did not influence the system model results significantly. Using finer nodalization in the reactor vessel improved the prediction of the system pressure history by minimizing steam condensation effects. Unequalmore » steam condensation between the downcomer and core volumes appear to cause the manometer oscillations observed in both the pretest and posttest RELAP4 analysis.« less

152. Historic American Buildings Survey, Donald W. Dickensheets, Photographer. March ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

152. Historic American Buildings Survey, Donald W. Dickensheets, Photographer. March 28, 1940. PENDENTIVE MURAL - CHOIR LOFT - ST. MARK WITH LION. (NORTHEAST ELEVATION) - San Xavier del Bac Mission, Mission Road, Tucson, Pima County, AZ

5. Historic American Buildings Survey, Bill Engdahl for HedrichBlessing, Photographers, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. Historic American Buildings Survey, Bill Engdahl for Hedrich-Blessing, Photographers, February, 1979 ENTRANCE AND CHOIR-LOFT WINDOW. - Sacred Heart Roman Catholic Church, East Sixth & East Elizabeth Streets, Brownsville, Cameron County, TX

A Summing Up. Allen Memorial Art Museum Addition, Oberlin, Ohio

ERIC Educational Resources Information Center

Progressive Architecture, 1977

1977-01-01

Venturi and Rauch's addition to the Allen Art Museum at Oberlin College is in two separate parts: a loft that houses new facilities for the art department and a gallery for contemporary art. (Author/MLF)

Facilitating LOS Debriefings: A Training Manual

DOT National Transportation Integrated Search

1997-03-01

This manual is a practical guide to help airline instructors effectively : facilitate debriefings of Line Oriented Simulations (LOS). It is based on a : recently completed study of Line Oriented Flight Training (LOFT) debriefings at : several U.S. ai...

133. Historic American Buildings Survey, Donald W. Dickensheets, Photographer. March ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

133. Historic American Buildings Survey, Donald W. Dickensheets, Photographer. March 28, 1940. EAST SIDE CLEAR STORY MAIN CHURCH FROM CHOIR LOFT. (WEST ELEVATION). - San Xavier del Bac Mission, Mission Road, Tucson, Pima County, AZ

Concentration and Transport of Carbon Monoxide from the California Wildfires

NASA Image and Video Library

2009-09-04

Carbon monoxide in the smoke from the Station fire was lofted high into the atmosphere, where it was observed by JPL Atmospheric Infrared Sounder instrument onboard NASA Aqua satellite. Animation available at the Photojournal.

LOFT Debriefings: An Analysis of Instructor Techniques and Crew Participation

NASA Technical Reports Server (NTRS)

Dismukes, R. Key; Jobe, Kimberly K.; McDonnell, Lori K.

1997-01-01

This study analyzes techniques instructors use to facilitate crew analysis and evaluation of their Line-Oriented Flight Training (LOFT) performance. A rating instrument called the Debriefing Assessment Battery (DAB) was developed which enables raters to reliably assess instructor facilitation techniques and characterize crew participation. Thirty-six debriefing sessions conducted at five U.S. airlines were analyzed to determine the nature of instructor facilitation and crew participation. Ratings obtained using the DAB corresponded closely with descriptive measures of instructor and crew performance. The data provide empirical evidence that facilitation can be an effective tool for increasing the depth of crew participation and self-analysis of CRM performance. Instructor facilitation skill varied dramatically, suggesting a need for more concrete hands-on training in facilitation techniques. Crews were responsive but fell short of actively leading their own debriefings. Ways to improve debriefing effectiveness are suggested.

Gravity anomalies without geomagnetic disturbances interfere with pigeon homing--a GPS tracking study.

PubMed

Blaser, Nicole; Guskov, Sergei I; Entin, Vladimir A; Wolfer, David P; Kanevskyi, Valeryi A; Lipp, Hans-Peter

2014-11-15

The gravity vector theory postulates that birds determine their position to set a home course by comparing the memorized gravity vector at the home loft with the local gravity vector at the release site, and that they should adjust their flight course to the gravity anomalies encountered. As gravity anomalies are often intermingled with geomagnetic anomalies, we released experienced pigeons from the center of a strong circular gravity anomaly (25 km diameter) not associated with magnetic anomalies and from a geophysical control site, equidistant from the home loft (91 km). After crossing the border zone of the anomaly--expected to be most critical for pigeon navigation--they dispersed significantly more than control birds, except for those having met a gravity anomaly en route. These data increase the credibility of the gravity vector hypothesis. © 2014. Published by The Company of Biologists Ltd.

Modern Day Re-analysis of Pinatubo SO2 Injection, Cloud dispersion and Stratospheric Aerosols

NASA Astrophysics Data System (ADS)

Bhartia, P. K.; Krotkov, N. A.; Aquila, V.; Hughes, E. J.; Li, C.; Fisher, B. L.

2016-12-01

Cataclysmic June 15 1991 eruption of Mt. Pinatubo injected largest amount of SO2 in the lower stratosphere during the satellite era. The resulting volcanic clouds were tracked by the NASA's Nimbus 7 TOMS sensor that provided first estimates of total emissions of SO2 gas ( 15+/-3 Mt). Over time SO2 converted to long-lasting sulfate aerosols affecting radiation balance and composition of the stratosphere. Large numbers of articles and papers published in the past 25 years make this the most well-studied volcanic eruption. Still, several unresolved scientific issues remain: SO2 injection height, subsequent lofting of SO2 and aerosols in the stratosphere, how much sulfate aerosols were produced in the eruption (i.e., initial sulfate to SO2 ratio), and impact on stratospheric ozone. To answer these questions we have re-analyzed past satellite measurements using modern day tools, such as re-analyzed wind data from Goddard Modeling and Assimilation Office (GMAO), improved trajectory analysis tools, better radiative transfer model to process backscatter UV data from N7/TOMS and two NOAA SBUV/2s sensors, which provided measurements at shorter UV wavelengths that are sensitive to aerosols and SO2 in the mid stratosphere ( 25 km). We have also re-analyzed aerosol data from SAGE, AVHRR, and several instruments on the UARS satellite. These data provide strong support for recent assessment by modelers that the bulk of SO2 mass injected by the volcano was well below the 25 km altitude, contrary to earlier estimates. We also find convincing evidence that there was significant amount of sulfate aerosols embedded even in the day-old SO2 cloud. These results strongly support the hypothesis that SO2 gas self-lofted to 25 km as seeen by UARS MLS several weeks after the eruption and aerosols to 35 km, as seen by the SAGE sensor several months later.

Prevalence of wheezing and atopic diseases in Austrian schoolchildren in conjunction with urban, rural or farm residence.

PubMed

Horak, Elisabeth; Morass, Bernhard; Ulmer, Hanno; Genuneit, Jon; Braun-Fahrländer, Charlotte; von Mutius, Erika

2014-09-01

A large number of studies have consistently shown that children growing up on a farm have a reduced prevalence of allergic disorders. The GABRIEL Advanced Study was conducted in five rural areas of southern Germany, Switzerland, Austria and Poland to shed light on the protective 'farm effect' on asthma and atopic disease. Whereas, the GABRIEL Advanced Study focussed on rural children only, the present study incorporates data from Innsbruck town children also. A screening questionnaire was developed to identify children with and without atopic disease within their living environment. Children were stratified into farm children, rural children and Innsbruck-town children. Within the farming environment, regular exposure to the following key factors of interest was predefined: the animal shed, the hay loft and farm milk. Wheezing in the past 12 months (W12), doctor-diagnosed (dd)-asthma, dd-allergic rhinitis and dd-atopic dermatitis were evaluated by using standardized questions from the International Study of Asthma and Allergies in Childhood (ISAAC) RESULTS: Farm children with regular exposure showed a lower risk for W12 (odds ratios (OR) = 0.3; 95%; confidence interval (CI) 0.2-0.5), dd-asthma (OR = 0.4; 95% CI 0.2-0.9) and dd-hay fever (OR 0.2; 95% CI 0.1-0.4). The protective effect of regular exposure extended to rural children but included W12 and dd-hay fever only. Multivariate logistic regression analysis for children being regularly exposed revealed protective attributes for the animal shed, the hay loft and farm milk. These data show that regular exposure to a farming environment protects against wheezing, asthma and hay fever. Regarding wheezing and hay fever, this effect was not restricted to children living on a farm but also notable in rural children with regular farm contact.

29 CFR 1926.56 - Illumination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Illumination. (a) General. Construction areas, ramps, runways, corridors, offices, shops, and storage areas... tunnel heading.) 10 General construction plant and shops (e.g., batch plants, screening plants, mechanical and electrical equipment rooms, carpenter shops, rigging lofts and active storerooms, barracks or...

29 CFR 1926.56 - Illumination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Illumination. (a) General. Construction areas, ramps, runways, corridors, offices, shops, and storage areas... tunnel heading.) 10 General construction plant and shops (e.g., batch plants, screening plants, mechanical and electrical equipment rooms, carpenter shops, rigging lofts and active storerooms, barracks or...

3. EAST SIDE SHOWING RECREATION PATIO ADDITION AT SOUTHERN END. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. EAST SIDE SHOWING RECREATION PATIO ADDITION AT SOUTHERN END. TWO-STORY PORTION AT SOUTHERN END CONTAINS 'RIGGING LOFT.' - Chollas Heights Naval Radio Transmitting Facility, Public Works Shop, 6410 Zero Road, San Diego, San Diego County, CA

Application of Nanofiber Technology to Nonwoven Thermal Insulation

DTIC Science & Technology

2006-11-01

polyester high-loft insulations, meltblown pitch carbon fiber, electrospun polyacrylonitrile, and silica aerogel -impregnated flexible fibrous insulation...supported flexible aerogels have polymer or carbon fibers dispersed in an aerogel matrix. Silica aerogels are transparent to thermal radiation, and do

"Dust Devils": Gardening Agents on the Surface of Mars, and Hidden Hazards to Human Exploration?

NASA Technical Reports Server (NTRS)

Marshall, J.; Smith, P.; White, B.; Farrell, W.

1999-01-01

Dust devils are familiar sites in the and regions of the world: they can produce quite spectacular displays of dust lofting when the vortices scavenge very loose dust from a dry lake bed or from recently disturbed agricultural fields. If one were to arrive at the center of an arid region, take one photograph, or even a series of photographs over a period of several days, then return the images for laboratory analysis, it would be most likely concluded that the region was inactive from an aeolian perspective. No images of general dust movement were obtained, nor were any dust devils "caught on camera" owing to their ephemeral and unpredictable appearance, and the fact that there was deceptively little residue of their actions. If, however, a camera were to take a 360 degree continuous recording over a period of a year, and the film were then to be shown at high speed over a period a several minutes, the impression might be that of a region ravaged by air vorticity and dust movement. Extrapolate this over geological time, and it is possible to visualize dust devils as prime aeolian agents, rather than insignificant vagaries of nature, On Mars, the thin atmosphere permits the surface of the planet to be heated but it does not itself retain heat with the capacity of the earth's atmosphere. This gives rise to greater thermal instability near the surface of Mars as "warm" air pockets diapiritically inject themselves into higher atmospheric layers. Resulting boundary-layer vorticity on Mars might therefore be expected to produce dust devils in abundance, if only seasonally. The spectacular images of dust devils obtained by Pathfinder within its brief functional period on the planet testify to the probability of highly frequent surface vorticity in light of the above reasoning about observational probability. Notably, the Pathfinder devils appeared to be at least a kilometer in height. There are several consequences for the geology of Mars, and for human exploration, if dust devils are to be expected in reasonable abundance. First, from a geological perspective, the vortices will act as "gardening" agents for the top few centimeters of entrainable material. Over time (hundreds of millions, or billions of years being available), they will cover the surface with scouring paths, and the grain sizes that can be lofted by a vortex probably extends over the whole sand to dust range. The depositional paths are, of course, much larger, so that vortex-induced deposition is more widespread than vortex-induced erosion, and will without doubt, affect the whole region in which the dust devils occur (this might explain why rocks at the Viking site seemed oddly capped with dust in a region apparently subject to general aeolian scouring). On Mars, the lift forces in dust devils might be less than on earth owing to the much thinner atmosphere, but this may be counterbalanced by lower gravity and greater vortex velocities. Certainly, when active, other aeolian phenomena on Mars --sand motion and dust storms, seem no less energetic and no less capable of lofting sediments than equivalent terrestrial aeolian phenomena. Every several years, within the current climatic regime, the surface of Mars is subject to light dust fall from global dust storms. Over time, this should develop a very uniform surface layer, with commensurate uniformity in grain size, mineralogy, albedo, color, and general spectroscopic properties. Dust devils will disturb this situation by continually mixing the surface dust with underlying layers, perhaps composed of silt and sand. This size mixing will also involve compositional mixing. After some years, the thin layer of dust that may be difficult to entrain alone, becomes progressively mixed with coarser materials that could reduce the general aeolian threshold of the soil. Certainly the continual disturbance by vorticity will prevent surface stabilization that may bind or indurate grains (caused by slow cementation or ice welding at grain boundaries). If dust devils continually loft dust to kilometer heights, and the dust is sprayed into many cubic kilometers of atmosphere each time, could the devils produce a continual background of atmospheric dust that might be mistaken for the fallout of a distant large-scale dust storm? From a human exploration perspective, dust devils are unlikely to pose any, life- threatening situation for an astronaut unfortunate enough to encounter a momentary swirling cloud of loose soil. However, it is noted that pervasive dust is probably one of the greatest long-term hazards for a human encampment. The fineness and penetration capabilities of the dust, its electrostatic adhesive properties, and its complete ubiquity, render the material a persistent nuisance at best, but at worst, over a period of many months it is possible that space suits, machinery, habitat interiors, air filters, and so forth, could become jeopardized. Owing to dust penetration, the space suits used in the Apollo landings were rendered unusable after a few EVA activities. There will be a definite attempt to situate a human colony on Mars in an area that is far removed from the regions of the planet known for being the centers of major dust storms. At the heart of these storm systems, the dust lofting mechanics are unknown, but they are energetic and perhaps potentially life-threatening for an astronaut. Locating a colony in a region that appears from space to be meteorologically benign may lead to colony placement in a region prone to dust devils, but dust devils are not (or have not been) detectable from orbital observations: the region surveyed for placement will appear like the apparently inactive and area referred to earlier. The region may be spared from highly energetic weather systems, but it may not be necessarily immune from continual dust disturbance. Additional information is contained in the original.

"Dust Devils": Gardening Agents on the Surface of Mars, and Hidden Hazards to Human Exploration?

NASA Astrophysics Data System (ADS)

Marshall, J.; Smith, P.; White, B.; Farrell, W.

1999-09-01

Dust devils are familiar sites in the and regions of the world: they can produce quite spectacular displays of dust lofting when the vortices scavenge very loose dust from a dry lake bed or from recently disturbed agricultural fields. If one were to arrive at the center of an arid region, take one photograph, or even a series of photographs over a period of several days, then return the images for laboratory analysis, it would be most likely concluded that the region was inactive from an aeolian perspective. No images of general dust movement were obtained, nor were any dust devils "caught on camera" owing to their ephemeral and unpredictable appearance, and the fact that there was deceptively little residue of their actions. If, however, a camera were to take a 360 degree continuous recording over a period of a year, and the film were then to be shown at high speed over a period a several minutes, the impression might be that of a region ravaged by air vorticity and dust movement. Extrapolate this over geological time, and it is possible to visualize dust devils as prime aeolian agents, rather than insignificant vagaries of nature, On Mars, the thin atmosphere permits the surface of the planet to be heated but it does not itself retain heat with the capacity of the earth's atmosphere. This gives rise to greater thermal instability near the surface of Mars as "warm" air pockets diapiritically inject themselves into higher atmospheric layers. Resulting boundary-layer vorticity on Mars might therefore be expected to produce dust devils in abundance, if only seasonally. The spectacular images of dust devils obtained by Pathfinder within its brief functional period on the planet testify to the probability of highly frequent surface vorticity in light of the above reasoning about observational probability. Notably, the Pathfinder devils appeared to be at least a kilometer in height. There are several consequences for the geology of Mars, and for human exploration, if dust devils are to be expected in reasonable abundance. First, from a geological perspective, the vortices will act as "gardening" agents for the top few centimeters of entrainable material. Over time (hundreds of millions, or billions of years being available), they will cover the surface with scouring paths, and the grain sizes that can be lofted by a vortex probably extends over the whole sand to dust range. The depositional paths are, of course, much larger, so that vortex-induced deposition is more widespread than vortex-induced erosion, and will without doubt, affect the whole region in which the dust devils occur (this might explain why rocks at the Viking site seemed oddly capped with dust in a region apparently subject to general aeolian scouring). On Mars, the lift forces in dust devils might be less than on earth owing to the much thinner atmosphere, but this may be counterbalanced by lower gravity and greater vortex velocities. Certainly, when active, other aeolian phenomena on Mars --sand motion and dust storms, seem no less energetic and no less capable of lofting sediments than equivalent terrestrial aeolian phenomena. Every several years, within the current climatic regime, the surface of Mars is subject to light dust fall from global dust storms. Over time, this should develop a very uniform surface layer, with commensurate uniformity in grain size, mineralogy, albedo, color, and general spectroscopic properties. Dust devils will disturb this situation by continually mixing the surface dust with underlying layers, perhaps composed of silt and sand. This size mixing will also involve compositional mixing. After some years, the thin layer of dust that may be difficult to entrain alone, becomes progressively mixed with coarser materials that could reduce the general aeolian threshold of the soil. Certainly the continual disturbance by vorticity will prevent surface stabilization that may bind or indurate grains (caused by slow cementation or ice welding at grain boundaries). If dust devils continually loft dust to kilometer heights, and the dust is sprayed into many cubic kilometers of atmosphere each time, could the devils produce a continual background of atmospheric dust that might be mistaken for the fallout of a distant large-scale dust storm? From a human exploration perspective, dust devils are unlikely to pose any, life- threatening situation for an astronaut unfortunate enough to encounter a momentary swirling cloud of loose soil. However, it is noted that pervasive dust is probably one of the greatest long-term hazards for a human encampment. The fineness and penetration capabilities of the dust, its electrostatic adhesive properties, and its complete ubiquity, render the material a persistent nuisance at best, but at worst, over a period of many months it is possible that space suits, machinery, habitat interiors, air filters, and so forth, could become jeopardized. Owing to dust penetration, the space suits used in the Apollo landings were rendered unusable after a few EVA activities. There will be a definite attempt to situate a human colony on Mars in an area that is far removed from the regions of the planet known for being the centers of major dust storms. At the heart of these storm systems, the dust lofting mechanics are unknown, but they are energetic and perhaps potentially life-threatening for an astronaut. Locating a colony in a region that appears from space to be meteorologically benign may lead to colony placement in a region prone to dust devils, but dust devils are not (or have not been) detectable from orbital observations: the region surveyed for placement will appear like the apparently inactive and area referred to earlier. The region may be spared from highly energetic weather systems, but it may not be necessarily immune from continual dust disturbance. Additional information is contained in the original.

Particulate capture efficiency of a vegetative environmental buffer surrounding an animal feeding operation

USDA-ARS?s Scientific Manuscript database

Particulate matter emitted from tunnel-ventilated animal feeding operations (AFOs) is known to transport malodorous compounds. As a mitigation strategy, vegetative environmental buffers (VEBs) are often installed surrounding AFOs to capture particulates and induce lofting and dispersion. Currently, ...

DISTANT GOAL ORIENTATION IN BIRDS.

DTIC Science & Technology

homing to a Bowling Green , Ohio loft. Pigeons with one eye surgically removed were able to home. Helicopter tracking is suitable and efficient for...the observation of pigeon navigation behavior. The homeward path varies considerably from the straight line path, sudden attitude changes occur, very

Emissions from prescribed burning of timber slash piles in Oregon.

EPA Science Inventory

Emissions from burning piles of post-harvest timber slash (Douglas fir) in Grande Ronde, Oregon were sampled using an instrument platform lofted into the plume using a tether-controlled aerostat or balloon. Emissions of carbon monoxide, carbon dioxide, methane, particulate matte...

Comprehensive Examination of Bottom Ash, Soil Dust, and Direct Emissions and Aging of Laboratory Biomass Burning as Potential Sources of Ice Nucleating Particles

NASA Astrophysics Data System (ADS)

Polen, M.; Jahl, L.; Jahn, L.; Somers, J.; Sullivan, R. C.

2017-12-01

Recent laboratory and field studies have found that biomass burning can produce ice nucleating particles (INP) with varying efficiencies depending on fuel and burn conditions. Few studies have examined the ice nucleating potential of bottom ash, which has the potential to be lofted during intense burning events. To date, no publications have examined the impact of atmospheric aging or lofted soil particles on INP emitted from biomass burning. This study investigated each of these aspects through laboratory biomass fuel combustion studies. We burned a number of grasses from different locations, and collected filter samples of fresh and photochemically aged biomass burning aerosol, as well as bottom ash collected after the burn. Some burns included soil that the grasses grew in to test for the importance of soil dust to INP emissions lofting during intense fires. The composition and mixing state of the aerosol was determined using a suite of online and offline single-particle techniques. Our findings suggest that bottom ash is a relatively weak INP, but all samples froze consistently at -20 °C < T < -25 °C. We also found that oxidation of the biomass burning aerosol typically enhances ice nucleating activity over fresh, unaged particles, increasing the ice active site surface density by up to a factor of 3 at T = -25 °C. Lastly, the presence of soil dust can greatly enhance INP concentrations for biomass burning events with an increase in the freezing temperature spectrum by > 3 °C. Detailed analysis of these samples aims to provide a clearer understanding of what components of biomass burning increase the ambient concentrations of ice nucleation active particles, and how their ice nucleation properties evolve during atmospheric aging.

Injection of mineral dust into the free troposphere during fire events observed with polarization lidar at Limassol, Cyprus

NASA Astrophysics Data System (ADS)

Nisantzi, A.; Mamouri, R. E.; Ansmann, A.; Hadjimitsis, D.

2014-06-01

Four-year observations (2010-2014) with EARLINET polarization lidar and AERONET sun/sky photometer at Limassol (34.7° N, 33° E), Cyprus, were used to study the soil dust content in lofted fire smoke plumes advected from Turkey. This first systematic attempt to characterize less than 3 days old smoke plumes in terms of particle depolarization contributes to the more general effort to properly describe the life cycle of free-tropospheric smoke-dust mixtures from the emission event to phases of long-range transport (>4 days after emission). We found significant differences in the particle depolarization ratio (PDR) with values from 9-18% in lofted aerosol layers when Turkish fires contributed to the aerosol burden and of 3-13% when Turkish fires were absent. High Ångström exponents of 1.4-2.2 during all these events with lofted smoke layers, occuring between 1 and 3 km height, suggest the absence of a pronounced particle coarse mode. When plotted vs. the travel time (spatial distance between Limassol and last fire area), PDR decreased strongly from initial values around 16-18% (one day travel) to 4-8% after 4 days of travel caused by deposition processes. This behavior was found to be in close agreement with the literature. Computation of particle extinction coefficient and mass concentrations, separately for fine-mode dust, coarse-mode dust, and non-dust aerosol components show extinction-related dust fractions of the order of 10% (for PDR = 4%, travel times >4 days) and 50% (PDR = 15%, one day travel time) and mass-related dust fractions of 25% (PDR = 4%) to 80% (PDR = 15%). Biomass burning should be considered as another source of free tropospheric soil dust.

Prevalence of Chlamydia psittaci in the feral pigeon population of Basel, Switzerland.

PubMed

Geigenfeind, Ila; Vanrompay, Daisy; Haag-Wackernagel, Daniel

2012-02-01

Feral pigeons (Columba livia) are commonly infected with Chlamydia psittaci, the agent of psittacosis in humans. To assess the risk of zoonosis posed by feral pigeons in the urban environment, we determined the prevalence of Chlamydia psittaci by detection of the outer-membrane protein A (ompA) gene of this pathogen in pharyngeal and cloacal samples of 202 feral pigeons present in a loft in Basel, Switzerland. Additionally, we examined 620 fresh faecal droppings of feral pigeons at six public sites in Basel. The ompA gene of C. psittaci could be detected in only 17 (8.4 %) of the 202 feral pigeons in the loft. C. psittaci DNA was present in nine (2.0 %) of 447 of the pharyngeal swabs and 11 (3.2 %) of the 348 cloacal swabs. Genotyping of the ompA gene revealed genotype B in seven of the birds. In one bird, a mixed infection was detected with the genotypes A, B and E/B, which, to our knowledge is the first time such an infection has been reported. Some of these birds immigrated into the loft as adults. To our knowledge, this is the first study to document how the interconnectedness between feral pigeon subpopulations favours the spread of C. psittaci. C. psittaci DNA was not detected in any of the faecal droppings collected at the six public areas. In spite of the low levels of C. psittaci shedding by feral pigeons in Basel, close contact to feral pigeons bears the risk of zoonotic transmission of C. psittaci. Feral pigeon management programmes and public education should be implemented to reduce the risk of a pigeon-to-human transmission of such pathogenic agents.

Pigeons and their droppings as reservoirs of Candida and other zoonotic yeasts.

PubMed

Rosario Medina, Inmaculada; Román Fuentes, Lorena; Batista Arteaga, Miguel; Real Valcárcel, Fernando; Acosta Arbelo, Félix; Padilla Del Castillo, Daniel; Déniz Suárez, Soraya; Ferrer Quintana, Otilia; Vega Gutiérrez, Belinda; Silva Sergent, Freddy; Acosta-Hernández, Begoña

The importance of pigeons as reservoirs and carriers of Cryptococcus neoformans and other species of this genus is well-known; however, less is known about their role as reservoirs and carriers of other yeasts that impact public health. The present study was performed on Gran Canaria Island to define yeasts other than Cryptococcus spp. that have been reported to impact public health and which could be carried by pigeons. Samples were obtained from 83 pigeon lofts (Columba livia); moreover, 331 crop samples, 331 cloacal samples and 174 dropping samples were collected. In addition, 17 dropping samples were taken from a total of 17 public squares. Samples were inoculated on Sabouraud dextrose agar with chloramphenicol. Different yeast species, i.e. Candida guilliermondii (24.36%), Candida kefyr (1.21%), Saccharomyces cerevisiae (2.43%), and Trichosporon asahii (1.21%) were isolated for the first time from the cloaca. The most frequently isolated yeast from the crop, cloaca and dropping samples from lofts was C. guilliermondii (30.46%, 24.36% and 49.37%, respectively). In addition, for the first time, C. kefyr (3.65%), Candida pelliculosa (2.43%), Candida rugosa (1.21%), T. asahii (3.65%), Trichosporon mucoides (3.65%) and Prototheca wickerhamii (1.21%) were obtained from crop samples; Candida pelliculosa (1.20%), T. asahii (9.63%) and T. mucoides (7.22%) were isolated from dropping samples in the lofts. Candida albicans was the most frequently isolated yeast in dropping samples collected in public squares. It can be assumed that pigeons and their droppings act as carriers and reservoirs of Candida spp. and other zoonotic yeasts. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Twenty-three generations of mice bidirectionally selected for open-field thigmotaxis: selection response and repeated exposure to the open field.

PubMed

Leppänen, Pia K; Ravaja, N; Ewalds-Kvist, S B M

2006-03-01

We examined: (a) the response to bidirectional selection for open-field (OF) thigmotaxis in mice for 23 generations and (b) the effects of repeated exposure (during 5 days) on different OF behaviors in the selectively bred high OF thigmotaxis (HOFT) and low OF thigmotaxis (LOFT) mice. A total of 2049 mice were used in the study. Prior to the testing in the selection experiment, the mice were exposed to the OF apparatus for approximately 2 min on each of 4 consecutive days. Thus, the selection was based on the scores registered on the 5th day after the four habituation periods. The HOFT mice were more thigmotactic than the LOFT mice in almost each generation. The HOFT mice also tended to rear less than the LOFT mice, which was explained by the inverse relationship between emotionality and exploratory tendencies. The lines did not generally differ in ambulation. Sex differences were found in thigmotaxis, ambulation, and rearing. In the repeated exposure experiment, the development of nine different OF behaviors across the 5 days of testing was addressed. Both lines ambulated, explored, and reared most on the 1st, 4th, and 5th days. Grooming and radial latency decreased and thigmotaxis increased linearly across the testing days. Line differences were found in ambulation, exploration, grooming, and rearing, while sex differences were manifested in ambulation and exploration. The line difference in thigmotaxis was evident only on the 5th day. Temporal changes were partially at variance with the general assumptions. OF thigmotaxis was found to be a powerful characteristic for producing two diverging lines of mice.

STUDIES OF THE ORIGIN OF HIGH-FREQUENCY QUASI-PERIODIC OSCILLATIONS OF MASS-ACCRETING BLACK HOLES IN X-RAY BINARIES WITH NEXT-GENERATION X-RAY TELESCOPES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beheshtipour, Banafsheh; Hoormann, Janie K.; Krawczynski, Henric, E-mail: b.beheshtipour@wustl.edu

Observations with RXTE ( Rossi X-ray Timing Explorer ) revealed the presence of high-frequency quasi-periodic oscillations (HFQPOs) of the X-ray flux from several accreting stellar-mass black holes. HFQPOs (and their counterparts at lower frequencies) may allow us to study general relativity in the regime of strong gravity. However, the observational evidence today does not yet allow us to distinguish between different HFQPO models. In this paper we use a general-relativistic ray-tracing code to investigate X-ray timing spectroscopy and polarization properties of HFQPOs in the orbiting Hotspot model. We study observational signatures for the particular case of the 166 Hz quasi-periodicmore » oscillation (QPO) in the galactic binary GRS 1915+105. We conclude with a discussion of the observability of spectral signatures with a timing-spectroscopy experiment such as the LOFT ( Large Observatory for X-ray Timing ) and polarization signatures with space-borne X-ray polarimeters such as IXPE ( Imaging X-ray Polarimetry Explorer ), PolSTAR ( Polarization Spectroscopic Telescope Array ), PRAXyS ( Polarimetry of Relativistic X-ray Sources ), or XIPE ( X-ray Imaging Polarimetry Explorer ). A mission with high count rate such as LOFT would make it possible to get a QPO phase for each photon, enabling the study of the QPO-phase-resolved spectral shape and the correlation between this and the flux level. Owing to the short periods of the HFQPOs, first-generation X-ray polarimeters would not be able to assign a QPO phase to each photon. The study of QPO-phase-resolved polarization energy spectra would thus require simultaneous observations with a first-generation X-ray polarimeter and a LOFT -type mission.« less

Age-forming aluminum panels

NASA Technical Reports Server (NTRS)

Baxter, G. I.

1976-01-01

Contoured-stiffened 63 by 337 inch 2124 aluminum alloy panels are machined in-the-flat to make integral, tapered T-capped stringers, parallel with longitudinal centerline. Aging fixture, which includes net contour formers made from lofted contour templates, has eggcrate-like structure for use in forming and checking panels.

Aerial sampling of emissions from biomass pile burns in Oregon

EPA Science Inventory

Emissions from burning piles of post-harvest timber slash in Grande Ronde, Oregon were sampled using an instrument platform lofted into the plume using a tether-controlled aerostat or balloon. Emissions of carbon monoxide, carbon dioxide, methane, particulate matter (PM2.5 µm), ...

Florida Journal of Communication Disorders, 1995.

ERIC Educational Resources Information Center

Langhans, Joseph J., Ed.

1995-01-01

This annual volume is a compilation of articles addressing evaluation, management, professional affairs, practice parameters, and clinical application of speech and language services. Featured articles include: (1) "Comparison of Pressure, Flow, and Resistance for Modal and Loft Register Productions" (Joseph L. Langhans and Peter J.…

Multiscale Modeling of Multi-decadal Trends in Ozone across the Northern Hemisphere & United States

EPA Science Inventory

Both observational and modeling studies have demonstrated that pollutants near the Earth’s surface can be convectively lofted to higher altitudes where strong winds can efficiently transport them from one continent to another, thereby impacting air quality on intercontinent...

Aerial Sampling of Emissions from Biomass Pile Burns in Oregon

EPA Science Inventory

Emissions from burning piles of post-harvest timber slash in Grande Ronde, Oregon were sampled using an instrument platform lofted into the plume using a tether-controlled aerostat or balloon. Emissions of carbon monoxide, carbon dioxide, methane, particulate matter (PM2.5 µm), ...

A small, lightweight multipollutant sensor system for ground-mobile and aerial emission sampling from open area sources

EPA Science Inventory

Characterizing highly dynamic, transient, and vertically lofted emissions from open area sources poses unique measurement challenges. This study developed and applied a multipollutant sensor and integrated sampler system for use on mobile applications including tethered balloons ...

EXPERIMENTS ON BUOYANT PLUME DISPERSION IN A LABORATORY CONVENTION TANK

EPA Science Inventory

Buoyant plume dispersion in the convective boundary layer (CBL) is investigated experimentally in a laboratory convection tank. The focus is on highly-buoyant plumes that loft near the CBL capping inversion and resist downward mixing. Highly- buoyant plumes are those with dimen...

The impact of cockpit automation on crew coordination and communication. Volume 1: Overview, LOFT evaluations, error severity, and questionnaire data

NASA Technical Reports Server (NTRS)

Wiener, Earl L.; Chidester, Thomas R.; Kanki, Barbara G.; Palmer, Everett A.; Curry, Renwick E.; Gregorich, Steven E.

1991-01-01

The purpose was to examine, jointly, cockpit automation and social processes. Automation was varied by the choice of two radically different versions of the DC-9 series aircraft, the traditional DC-9-30, and the glass cockpit derivative, the MD-88. Airline pilot volunteers flew a mission in the simulator for these aircraft. Results show that the performance differences between the crews of the two aircraft were generally small, but where there were differences, they favored the DC-9. There were no criteria on which the MD-88 crews performed better than the DC-9 crews. Furthermore, DC-9 crews rated their own workload as lower than did the MD-88 pilots. There were no significant differences between the two aircraft types with respect to the severity of errors committed during the Line-Oriented Flight Training (LOFT) flight. The attitude questionnaires provided some interesting insights, but failed to distinguish between DC-9 and MD-88 crews.

Expert systems for fault diagnosis in nuclear reactor control

NASA Astrophysics Data System (ADS)

Jalel, N. A.; Nicholson, H.

1990-11-01

An expert system for accident analysis and fault diagnosis for the Loss Of Fluid Test (LOFT) reactor, a small scale pressurized water reactor, was developed for a personal computer. The knowledge of the system is presented using a production rule approach with a backward chaining inference engine. The data base of the system includes simulated dependent state variables of the LOFT reactor model. Another system is designed to assist the operator in choosing the appropriate cooling mode and to diagnose the fault in the selected cooling system. The response tree, which is used to provide the link between a list of very specific accident sequences and a set of generic emergency procedures which help the operator in monitoring system status, and to differentiate between different accident sequences and select the correct procedures, is used to build the system knowledge base. Both systems are written in TURBO PROLOG language and can be run on an IBM PC compatible with 640k RAM, 40 Mbyte hard disk and color graphics.

Sensitivity of OMI SO2 measurements to variable eruptive behaviour at Soufrière Hills Volcano, Montserrat

NASA Astrophysics Data System (ADS)

Hayer, C. S.; Wadge, G.; Edmonds, M.; Christopher, T.

2016-02-01

Since 2004, the satellite-borne Ozone Mapping Instrument (OMI) has observed sulphur dioxide (SO2) plumes during both quiescence and effusive eruptive activity at Soufrière Hills Volcano, Montserrat. On average, OMI detected a SO2 plume 4-6 times more frequently during effusive periods than during quiescence in the 2008-2010 period. The increased ability of OMI to detect SO2 during eruptive periods is mainly due to an increase in plume altitude rather than a higher SO2 emission rate. Three styles of eruptive activity cause thermal lofting of gases (Vulcanian explosions; pyroclastic flows; a hot lava dome) and the resultant plume altitudes are estimated from observations and models. Most lofting plumes from Soufrière Hills are derived from hot domes and pyroclastic flows. Although Vulcanian explosions produced the largest plumes, some produced only negligible SO2 signals detected by OMI. OMI is most valuable for monitoring purposes at this volcano during periods of lava dome growth and during explosive activity.

Aerostat-Lofted Instrument Platform and Sampling Method for Determination of Emissions from Open Area Sources

EPA Science Inventory

Sampling emissions from open area sources, particularly sources of open burning, is difficult due to fast dilution of emissions and safety concerns for personnel. Representative emission samples can be difficult to obtain with flaming and explosive sources since personnel safety ...

NEW DEVELOPMENT IN DISPERSION EXPERIMENTS AND MODELS FOR THE CONVECTIVE BOUNDARY LAYER

EPA Science Inventory

We present recent experiments and modeling studies of dispersion in the convective boundary layer (CBL) with focus on highly-buoyant plumes that "loft" near the CBL top and resist downward mixing. Such plumes have been a significant problem in earlier dispersion models; they a...

Characterization of Air Emissions from Open Burning and Open Detonation of Gun Propellants and Ammunition

EPA Science Inventory

Emissions from open burning (OB) and open detonation (OD) of military ordnance and static fires (SF) of rocket motors were sampled in fall, 2013 at the Dundurn Depot (Saskatchewan, Canada). Emission sampling was conducted with an aerostat-lofted instrument package termed the “Fl...

The Female Rescuer in Newbery Books: Who Is She?

ERIC Educational Resources Information Center

Roberts, Sherron Killingsworth

A study used three Newbery books--"The Voyages of Dr. Doolittle (Lofting, 1922), "Charlotte's Web" (White, 1952), and "Maniac Magee" (Spinelli, 1990)--to examine three female characters identified in these books in the role of rescuer, accentuating their commonalities and differences within Jungian and feminist theory in…

Earth Science

NASA Image and Video Library

1994-04-12

The Atlas-1 (AC-77) that will loft the Geostationary Operational Environmental Satellite-J (GOES-J) next-generation advanced technology weather satellite into space sits poised for takeoff during final countdown operations at Cape Canaveral Air Station, Kennedy Space Center (KSC). GOES-J is atop the expendable launch vehicle inside the rocket's payload fairing.

Comparative study of through-air bonded and thermal calendered nonwovens

USDA-ARS?s Scientific Manuscript database

Over the years there has been increasing interest in developing flame retardant (FR) cotton-based nonwovens. Whereas majority of the work has been done with high loft nonwovens, since this has been of interest to bedding and home furnishing industry, the effect of web density on flame retardancy is ...

Photocopy of drawing located at National Archives, San Bruno, California ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing located at National Archives, San Bruno, California (Navy # 106-A-18). NAVFAC, relocate sail, loft, building 106 1st floor plan, boat shop. August 2, 1977. - Mare Island Naval Shipyard, Boat Shop, California Avenue, west side between Ninth & Tenth Streets, Vallejo, Solano County, CA

Aerostat-Based Sampling of Emissions from Open Burning and Open Detonation of Military Ordnance

EPA Science Inventory

Emissions from open detonation (OD), open burning (OB), and static firing (SF) of obsolete military munitions were collected using an aerostat-lofted sampling instrument maneuvered into the plumes with remotely controlled tether winches. PM2.5, PM10, metals, volatile organic comp...

Early Cerebral Blood Volume Changes Predict Progression After Convection-Enhanced Delivery of Topotecan for Recurrent Malignant Glioma.

PubMed

Surapaneni, Krishna; Kennedy, Benjamin C; Yanagihara, Ted K; DeLaPaz, Robert; Bruce, Jeffrey N

2015-07-01

To assess whether early changes in enhancing tumor volume (eTV) and relative cerebral blood volume (rCBV) 1 month after convection-enhanced delivery of topotecan in patients with recurrent malignant glioma correlated with 6-month disease progression status. Sixteen patients were enrolled in a Phase Ib trial of convection-enhanced delivery of topotecan for recurrent malignant glioma. Each patient was evaluated with serial follow-up magnetic resonance imaging at baseline and at 4- to 8-week intervals. Changes at 1 month compared with baseline in eTV and rCBV were evaluated as potential predictors of 6-month progression status, classified as either progressive disease or nonprogressive disease. Relationships between percent changes in eTV and rCBV at 1 month with the probability of progressive disease at 6 months were estimated by the use of logistic regression analysis. Receiver operating characteristic curves for varying percent change thresholds in eTV and rCBV were evaluated by the use of 6-month progressive disease as the reference. There was a significant difference in the percent change in rCBV at 1 month in patients with progressive disease compared with those with nonprogressive disease at 6 months (+12% vs. -29%, P = 0.02). Logistic regression analysis demonstrated on average that a 10% increase in rCBV at 1 month after convection-enhanced delivery of topotecan was associated with 1.7 times the odds of developing progressive disease at 6 months (95% confidence interval [CI] 1.0-2.9 P = 0.05). Receiver operating characteristic analysis for determining progressive disease at 6 months showed a greater area under the curve with rCBV (0.867; 95% CI 0.66-1.00) than with change in enhancing tumor volume (0.767; 95% CI 0.51-1.00). In this selected population of patients with recurrent malignant glioma treated with convection-enhanced delivery of topotecan, early changes in rCBV at 4 weeks after therapy may help predict progression status at 6 months. Copyright © 2015 Elsevier Inc. All rights reserved.

Epoch Analysis of On-Treatment Disability Progression Events over Time in the Tysabri Observational Program (TOP)

PubMed Central

Wiendl, Heinz; Butzkueven, Helmut; Kappos, Ludwig; Trojano, Maria; Pellegrini, Fabio; Paes, Dominic; Zhang, Annie; Belachew, Shibeshih

2016-01-01

Objective To evaluate the effect of natalizumab on disability progression beyond 2 years of treatment in clinical practice. Methods Analyses included the 496 relapsing-remitting multiple sclerosis (RRMS) patients among 5122 patients in the Tysabri Observational Program (TOP) who had completed 4 continuous years of natalizumab treatment and had baseline (study enrollment) and postbaseline Expanded Disability Status Scale (EDSS) assessments. Proportions of patients with 6-month or 12-month confirmed ≥1.0-point EDSS progression relative to baseline were compared in treatment months 1–24 and 25–48. Sensitivity analyses compared progression rates in months 13–24 and 25–36. Results Baseline characteristics appeared similar between the overall TOP population (N = 5122), patients who had completed 4 years of natalizumab treatment (n = 469), and patients eligible to complete 4 years in TOP who had discontinued natalizumab after 2 years of treatment (n = 514). Among 4-year completers, the proportion of patients with 6-month and 12-month confirmed EDSS progression decreased between months 1–24 and 25–48 of natalizumab treatment by 42% (from 10.9% to 6.3%; p < 0.01) and 52% (from 9.5% to 4.6%; p < 0.01), respectively. Few patients had 6-month or 12-month confirmed EDSS progression in both epochs (0.6% and 0.2%, respectively). Between months 13–24 and 25–36 of treatment, the proportion of patients with 6-month and 12-month confirmed EDSS progression decreased by 60% (from 7.5% to 3.0%; p < 0.01) and 58% (from 6.7% to 2.8%; p < 0.01), respectively. Significant reductions in disability progression events between months 13–24 and 25–36 were also observed in relapse-free patients. Conclusion In this observational study, the disability progression rate decreased further beyond 2 years of natalizumab treatment. Patients who responded well and remained on continuous natalizumab therapy for over 4 years had sustained and potentially enhanced reductions in EDSS progression over time. PMID:26771747

14 CFR 121.427 - Recurrent training.

Code of Federal Regulations, 2011 CFR

2011-01-01

... required by §§ 121.421(b) and 121.422(b), respectively. (4) Approved recurrent CRM training. For flight... operational flight training (LOFT) session. The recurrent CRM training requirement does not apply until a person has completed the applicable initial CRM training required by §§ 121.419, 121.421, or 121.422. (c...

Firebrands and spotting ignition in large-scale fires

Treesearch

Eunmo Koo; Patrick J. Pagni; David R. Weise; John P. Woycheese

2010-01-01

Spotting ignition by lofted firebrands is a significant mechanism of fire spread, as observed in many largescale fires. The role of firebrands in fire propagation and the important parameters involved in spot fire development are studied. Historical large-scale fires, including wind-driven urban and wildland conflagrations and post-earthquake fires are given as...

14 CFR 121.427 - Recurrent training.

Code of Federal Regulations, 2010 CFR

2010-01-01

... required by §§ 121.421(b) and 121.422(b), respectively. (4) Approved recurrent CRM training. For flight... operational flight training (LOFT) session. The recurrent CRM training requirement does not apply until a person has completed the applicable initial CRM training required by §§ 121.419, 121.421, or 121.422. (c...

Improved Grade Outcomes with an E-Mailed "Grade Nudge"

ERIC Educational Resources Information Center

Smith, Ben O.; White, Dustin R.; Kuzyk, Patricia C.; Tierney, James E.

2018-01-01

Information provided at the moment a person makes a decision can influence behavior in predictable ways. The United Kingdom's Behavioural Insights Team have used this idea to help improve the insulation of lofts, collect taxes, and even reduce litter. The authors of this article developed software that appends a personalized message to each…

PANORAMIC VIEW OF SHIPYARD NO. 3, LOOKING SOUTH. FROM LEFT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PANORAMIC VIEW OF SHIPYARD NO. 3, LOOKING SOUTH. FROM LEFT TO CENTER ARE THE FORGE SHOP, MACHINE SHOP, GENERAL WAREHOUSE, AND RIGGERS LOFT/PAINT SHOP/SHEET METAL SHOP. FROM CENTER TO RIGHT ARE THE FIVE BASINS - Rosie the Riveter National Historical Park, Richmond Shipyard No. 3, Point Potrero, Richmond, Contra Costa County, CA

CROCKETT BARN’S UPPER LEVEL, LOOKING NORTHEAST. This image shows the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CROCKETT BARN’S UPPER LEVEL, LOOKING NORTHEAST. This image shows the construction of the three interior bents, the south end of the loft and stairs, the ladder leading to the cupola, and the dance floor added in 2006. - Crockett Farm, Barn, 1056 Fort Casey Road, Coupeville, Island County, WA

15. Interior view, greenhouse, from the northwest. The greenhouse interior ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

15. Interior view, greenhouse, from the northwest. The greenhouse interior was quite modest, the space between the floor of the lower level and the joists carrying the loft floor is only five-and-one-half feet. - John Bartram House & Garden, Greenhouse, 54th Street & LIndbergh Boulevard, Philadelphia, Philadelphia County, PA

The development and implementation of cockpit resource management in UAL recurrent training

NASA Technical Reports Server (NTRS)

Shroyer, David H.

1987-01-01

Line Oriented Flight Training (LOFT) for United Airlines started in 1976. At that time it was basically no more than a line-simulated training function conducted in a full-mission simulator with no attention or stress on its human factor content. Very soon after the implementation of the LOFT program concerns were voiced about certain crew behavioral situations they were observing in the flight crew's execution of cockpit duties. These duties involved emergency procedures as well as irregular and normal procedures and situations. It was evident that new information was surfacing concerning crew interaction, or its lack thereof, in the cockpit and its effect on satisfactory performance. These observations naturally raised the question of how this information translated into the safety of aircraft operations. A training system had to be repetitive, the crew interactive, and the training had to be conducted under the crew concept. The foundation had to have two other factors: (1) it was necessary to have adequate human factor content, and (2) an advanced state-of-the-art simulator and appropriate electronic devices were required. These concepts are further discussed.

The Enigma of Lunar Dust Transport

NASA Technical Reports Server (NTRS)

Farrell, W. M.; Stubbs, T. J.; Vondrak, R. R.; Delory, G. T.; Halekas, J. S.

2011-01-01

We will review the highly contrasting points of view regarding the ability of fine dust grains to become transported in the near-space lunar environment. While Surveyor and Apollo camera images suggest the presence of a horizon glow that has been provocatively interpreted as levitated and/or lofted dust, there is contrasting geological evidence to indicate that surface regolith has not been moved in a substantial way. While electric forces have been suggested as a driver for grain dynamics, recent detailed modeling of near-surface non-monotonic potentials would suggest grains could not get to large heights. While lofting models require submicron grains to hold/contain 100's of elementary charges, it can be shown analytical1y that a grain residing on a flat surface would have an extremely low probability of having even a single electron on its surface, Can these diametrically opposing viewpoints be reconciled? We will review the pros and cons on both sides. and suggest that the UVS and LDEX instrument on LADEE will provide key new insights on dust transport at the Moon.

The LOFT perspective on neutron star thermonuclear bursts: White paper in support of the mission concept of the large observatory for X-ray timing

DOE Office of Scientific and Technical Information (OSTI.GOV)

in't Zand, J. J.M.; Malone, Christopher M.; Altamirano, D.

2015-01-14

The Large Area Detector (LAD) on the Large Observatory For X-ray Timing ( LOFT ), with a 8.5 m 2 photon- collecting area in the 2–30 keV bandpass at CCD-class spectral resolving power (λ/Δλ = 10 – 100), is designed for optimum performance on bright X-ray sources. Thus, it is well-suited to study thermonuclear X-ray bursts from Galactic neutron stars. These bursts will typically yield 2 x 10 5 photon detections per second in the LAD, which is at least 15 times more than with any other instrument past, current or anticipated. The Wide Field Monitor (WFM) foreseen for LOFTmore » uniquely combines 2–50 keV imaging with large (30%) prompt sky coverage. This will enable the detection of tens of thousands of thermonuclear X-ray bursts during a 3-yr mission, including tens of superbursts. Both numbers are similar or more than the current database gathered in 50 years of X-ray astronomy.« less

Methane mole fraction and δ13C above and below the trade wind inversion at Ascension Island in air sampled by aerial robotics

NASA Astrophysics Data System (ADS)

Brownlow, R.; Lowry, D.; Thomas, R. M.; Fisher, R. E.; France, J. L.; Cain, M.; Richardson, T. S.; Greatwood, C.; Freer, J.; Pyle, J. A.; MacKenzie, A. R.; Nisbet, E. G.

2016-11-01

Ascension Island is a remote South Atlantic equatorial site, ideal for monitoring tropical background CH4. In September 2014 and July 2015, octocopters were used to collect air samples in Tedlar bags from different heights above and below the well-defined Trade Wind Inversion (TWI), sampling a maximum altitude of 2700 m above mean sea level. Sampling captured both remote air in the marine boundary layer below the TWI and also air masses above the TWI that had been lofted by convective systems in the African tropics. Air above the TWI was characterized by higher CH4, but no distinct shift in δ13C was observed compared to the air below. Back trajectories indicate that lofted CH4 emissions from Southern Hemisphere Africa have bulk δ13CCH4 signatures similar to background, suggesting mixed emissions from wetlands, agriculture, and biomass burning. The campaigns illustrate the usefulness of unmanned aerial system sampling and Ascension's value for atmospheric measurement in an understudied region.

The OCO-2 Version 8 XCO2 Data Product Fall 2017 Release: Description and Preliminary Validation

NASA Astrophysics Data System (ADS)

O'Dell, C.; Eldering, A.; Crisp, D.; Fisher, B.; Gunson, M. R.; Kiel, M.; Mandrake, L.; Taylor, T. L.; Wennberg, P. O.

2017-12-01

Since beginning its science mission in September 2014, the Orbiting Carbon Observatory-2 (OCO-2) has provided 1-2 million estimates of the column average carbon dioxide (CO2) dry air mole fraction, XCO2, each month. While the Version-7 (V7) OCO-2 data product is generally of high quality, it includes some notable biases, including low and high biases in the tropical and extratropical oceans, respectively, and biases associated with unscreened clouds and variable topography. Because even small (<< 1 ppm) systematic biases can compromise the accuracy of CO2 flux inversion systems, reducing the bias in OCO-2 XCO2 estimates is critical to progress in understanding regional scale sources and sinks of CO2 via top-down inversion approaches. We present significant changes introduced in the new Version 8 (V8) XCO2 data product. These changes reflect improvements in instrument calibration, cloud filtering, the retrieval algorithm itself, and post-filtering methods. The most noteworthy change involved the inclusion of an optically-thin, upper-tropospheric/lower stratospheric aerosol type which simulates small aerosol particles high in the atmosphere, such as the Junge Layer and aerosols due to volcanic eruptions. It also mitigates the impact of zero level offsets due to a thin layer of ice that accumulates on the OCO-2 detectors, which actually mimics a small, lofted aerosol particle in the retrieval forward model. We show comparisons of the new XCO2 product to both TCCON and models. Improvements in the V8 screening also provides additional data over tropical oceans, which may enhance coverage in these regions. These data are currently being evaluated. Similarly, the new version 8 data may enable improved coverage at higher latitudes via a renewed focus on the challenging retrievals at higher solar zenith angles and over snow and ice covered surfaces.

Injection of mineral dust into the free troposphere during fire events observed with polarization lidar at Limassol, Cyprus

NASA Astrophysics Data System (ADS)

Nisantzi, A.; Mamouri, R. E.; Ansmann, A.; Hadjimitsis, D.

2014-11-01

Four-year observations (2010-2014) with EARLINET polarization lidar and AERONET sun/sky photometer at Limassol (34.7° N, 33° E), Cyprus, were used to study the soil dust content in lofted fire smoke plumes advected from Turkey. This first systematic attempt to characterize less than 3-day-old smoke plumes in terms of particle linear depolarization ratio (PDR), measured with lidar, contributes to the more general effort to properly describe the life cycle of free-tropospheric smoke-dust mixtures from the emission event to phases of long-range transport (> 4 days after emission). We found significant PDR differences with values from 9 to 18% in lofted aerosol layers when Turkish fires contributed to the aerosol burden and of 3-13 % when Turkish fires were absent. High Ångström exponents of 1.4-2.2 during all these events with lofted smoke layers, occurring between 1 and 3 km height, suggest the absence of a pronounced particle coarse mode. When plotted vs. travel time (spatial distance between Limassol and last fire area), PDR decreased strongly from initial values around 16-18% (1 day travel) to 4-8% after 4 days of travel caused by deposition processes. This behavior was found to be in close agreement with findings described in the literature. Computation of particle extinction coefficient and mass concentrations, derived from the lidar observations, separately for fine-mode dust, coarse-mode dust, and non-dust aerosol components show extinction-related dust fractions on the order of 10% (for PDR =4%, travel times > 4 days) and 50% (PDR =15%, 1 day travel time) and respective mass-related dust fractions of 25% (PDR =4%) to 80% (PDR =15%). Biomass burning should therefore be considered as another source of free tropospheric soil dust.

Liftoff of the 18 May 1980 surge of Mount St. Helens (USA) and the deposits left behind

NASA Astrophysics Data System (ADS)

Gardner, James E.; Andrews, Benjamin J.; Dennen, Robert

2017-01-01

The distance that ground-hugging pyroclastic density currents travel is limited partly by when they reverse buoyancy and liftoff into the atmosphere. It is not clear, however, what deposits are left behind by lofting flows. One current that was seen to liftoff was the surge erupted from Mount St. Helens on the morning of 18 May 1980. Before lofting, it had leveled a large area of thick forest (the blowdown zone). The outer edge of the devastated area—where trees were scorched but left standing (the scorched zone)—is where the surge is thought to have lifted off. Deposits in the outer parts of the blowdown and in the scorched zone were examined at 32 sites. The important finding is that the laterally moving surge traveled through the scorched zone, and hence, the change in tree damage does not mark the runout distance of the surge. Buoyancy reversal and liftoff are thus not preserved in the deposits where the surge lofted upwards. We propose, based on interpretation of eyewitness accounts and the impacts of the surge on trees and vehicles, that the surge consisted of a faster, dilute "overcurrent" and a slower "undercurrent," where most of the mass (and heat) was retained. Reasonable estimates for flow density and velocity show that dynamic pressure of the surge (i.e., its ability to topple trees) peaked near the base of the overcurrent. We propose that where the overcurrent began to liftoff, the height of peak dynamic pressure rose above the trees and stopped toppling them. The slower undercurrent continued forward, however, scorching trees, but lacked the dynamic pressure needed to topple them. Grain-size variations argue that it slowed from ˜30 m s-1 when it entered the scorched zone to ˜3 m s-1 at the far end.

Ejection and Lofting of Dust from Hypervelocity Impacts on the Moon

NASA Astrophysics Data System (ADS)

Hermalyn, B.; Schultz, P. H.

2011-12-01

Hypervelocity impact events mobilize and redistribute fine-grained regolith dust across the surfaces of planetary bodies. The ejecta mass-velocity distribution controls the location and emplacement of these materials. The current flux of material falling on the moon is dominated by small bolides and should cause frequent impacts that eject dust at high speeds. For example, approximately 25 LCROSS-sized (~20-30m diameter) craters are statistically expected to be formed naturally on the moon during any given earth year. When scaled to lunar conditions, the high-speed component of ejecta from hypervelocity impacts can be lofted for significant periods of time (as evidenced by the LCROSS mission results, c.f., Schultz, et al., 2010, Colaprete, et al., 2010). Even at laboratory scales, ejecta can approach orbital velocities; the higher impact speeds and larger projectiles bombarding the lunar surface may permit a significant portion of material to be launched closer to escape velocity. When these ejecta return to the surface (or encounter local topography), they impact at hundreds of meters per second or faster, thereby "scouring" the surface with low mass oblique impacts. While these high-speed ejecta represent only a small fraction of the total ejected mass, the lofting and subsequent ballistic return of this dust has the highest mobilization potential and will be directly applicable to the upcoming LADEE mission. A suite of hypervelocity impact experiments into granular materials was performed at the NASA Ames Vertical Gun Range (AVGR). This study incorporates both canonical sand targets and air-fall pumice dust to simulate the mechanical properties of lunar regolith. The implementation of a Particle Tracking Velocimetry (PTV) technique permits non-intrusive measurement of the ejecta velocity distribution within the ejecta curtain by following the path of individual ejecta particles. The PTV system developed at the AVGR uses a series of high-speed cameras (ranging from 11,000 to 500,000 frames per second) to allow measurement of particle velocity over the large dynamic range required for early-time, high-speed components of ejecta. Preliminary results for impacts into sand (Hermalyn and Schultz, 2010, 2011) reveal that early in the cratering process, ejection velocities are higher than assumed by dimensional scaling laws (Housen, et al., 1983). Moreover, the ejection angles of this early-time component are initially low (~30°) and gradually increase to reach nominal ejection angles (~45° for impacts into sand). In this study, we assess the expected ejecta velocities on the moon from the current impact flux and the possible effects of the secondary impacts of ejecta dust particles. By convolving these ejecta measurements with the lunar impact flux rate, an estimate can be derived for the amount and ballistic flight time of dust lofted above the surface of the moon over a given year.

Surface Disturbances at the Punggye-ri Nuclear Test Site: Another Indicator of Nuclear Testing?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pabian, Frank V.; Coblentz, David

A review of available very high-resolution commercial satellite imagery (bracketing the time of North Korea’s most recent underground nuclear test on 9 September 2016 at the Punggye-ri Underground Nuclear Test Site) has led to the detection and identification of several minor surface disturbances on the southern flank of Mt. Mantap. These surface disturbances occur in the form of small landslides, either alone or together with small zones of disturbed bare rock that appear to have been vertically lofted (“spalled”) as a result of the most recent underground explosion. Typically, spall can be uniquely attributed to underground nuclear testing and ismore » not a result of natural processes. However, given the time gap of up to three months between images (pre- and post-event), which was coincident with a period of heavy typhoon flooding in the area1, it is not possible to determine whether the small landslides were exclusively explosion induced, the consequence of heavy rainfall erosion, or some combination of the two.« less

Metals Fate And Transport Modelling In Streams And Watersheds: State Of The Science And USEPA Workshop Review

EPA Science Inventory

Metals pollution in surface waters from point and non-point sources (NPS) is a widespread problem in the United States and worldwide (Lofts et al., 2007; USEPA, 2007). In the western United States, metals associated with acid mine drainage (AMD) from hardrock mines in mou...

BEHAVE: fire behavior prediction and fuel modeling system - BURN subsystem, Part 2

Treesearch

Patricia L. Andrews; Carolyn H. Chase

1989-01-01

This is the third publication describing the BEHAVE system of computer programs for predicting behavior of wildland fires. This publication adds the following predictive capabilities: distance firebrands are lofted ahead of a wind-driven surface fire, probabilities of firebrands igniting spot fires, scorch height of trees, and percentage of tree mortality. The system...

Amarone: a modern wine coming from an ancient production technology.

PubMed

Paronetto, Lanfranco; Dellaglio, Franco

2011-01-01

Amarone wine is a renowned dry red wine produced in Valpolicella (Verona, Northern Italy). It is made from local grapes varieties (Corvina, Rondinella, and Molinara) that are slowly dried under natural conditions during the fall into winter. After the postharvest drying, carried out for several weeks in dedicated lofts called fruttaio, the grapes are vinified: crushed, given prefermentative cold maceration, undergo alcoholic fermentation on the skins, malolactic fermentation, and finally maturation. The partially dried grapes are traditionally crushed during the second half of January to February. Because cellar conditions are unfavorable for either alcohol or malolactic fermentation, selected microbial cultures (yeasts and malolactic bacteria) are often necessary to correctly manage fermentation. The progress of both fermentation processes needs constant surveillance. During maturation conducted in vessels or wooden containers (tonneau in durmast oak), clarification and stabilization lead to improvements in quality. Product specifications require that Amarone not be bottled before the wine has been aged for 2years (Anonymous (2010). Disciplinare di produzione dei vini a denominazione di Origine Controllata e Garantita "Amarone della Valpolicella". Gazzetta Ufficiale della Repubblica Italiana. Serie generale n. 84. April 12). Amarone achieved its DOCG (Controlled and Guaranteed Denomination) status in 2010. Copyright © 2011 Elsevier Inc. All rights reserved.

The Idea Generator: Lori Bell--Mid-Illinois Talking Book Center, East Peoria

ERIC Educational Resources Information Center

Library Journal, 2004

2004-01-01

Anyone who hires Loft Bell is getting two librarians: one who enthusiastically does the job, and another who develops new ideas, secures grants to fund them, and swiftly puts the ideas into action. There's nothing that makes a job more attractive to Bell than the freedom to try out new things. Jenny Levine, Internet development specialist at…

A&M. Jet engine test building (TAN609). Exterior. Equipment inside rollup ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

A&M. Jet engine test building (TAN-609). Exterior. Equipment inside roll-up door is blowdown test facility, part of loft-semiscale program. Note width of central section serving as blast protection for operator on left side. Photographer: Cahoon. Date: July 22, 1965. INEEL negative no. 65-3703 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

The Role of the Admissions Office in the Academic Intervention and Support Program.

ERIC Educational Resources Information Center

Stumhofer, Nancy C.

At the Schuykill Campus of Pennsylvania State University, an academic intervention and support system has been developed which identifies and monitors high-risk students until they are able to succeed on their own or decide to leave school. The campus's LOFT Learning Center has created a link with the Admission's Office that is central to the…

Accuracy of Mass and Radius Determination for Neutron Stars in X-ray Bursters from Simulated LOFT Spectra

NASA Astrophysics Data System (ADS)

Majczyna, A.; Madej, J.; Różańska, A.; Należyty, M.

2017-06-01

We present a simulation of an X-ray spectrum of a hot neutron star, as would be seen by the LAD detector on board of LOFT satellite. We also compute a grid of theoretical spectra corresponding to a range of effective temperatures Teff and surface gravities log g with values corresponding to compact stars in Type I X-ray bursters. A neutron star with the mass M=1.64 M⊙ and the radius R=11.95 km (which yields the surface gravity log g=14.30 [cgs] and the surface redshift z=0.30) is used in simulation. Accuracy of mass and radius determination by fitting theoretical spectra to the observed one is found to be M=1.64+0.16-0.02 M⊙ and R=11.95+1.57-0.40 km (2σ). The confidence contours for these two variables are narrow but elongated, and therefore the resulting constraints on the EOS cannot be strong. Note, that in this paper we aim to discuss error contours of NS mass and radius, whereas discussion of EOS is beyond the scope of this work.

Variable reluctance displacement transducer temperature compensated to 650$sup 0$F

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

In pressurized water reactor tests, compact instruments for accurate measurement of small displacements in a 650$sup 0$F environment are often required. In the case of blowdown tests such as the Loss of Fluid Test (LOFT) or Semiscale computer code development tests, not only is the initial environment water at 650$sup 0$F and 2200 psi but it undergoes a severe transient due to depressurization. Since the LOFT and Semiscale tests are run just for the purpose of obtaining data during the depressurization, instruments used to obtain the data must not give false outputs induced by the change in environment. A LOFTmore » rho v$sup 2$ probe and a Semiscale drag disk are described. Each utilizes a variable reluctance transducer (VRT) for indication of the drag-disk location and a torsion bar for drag-disk restoring force. The VRT, in addition to being thermally gain and null offset stable, is fabricated from materials known to be resistant to large nuclear radiation levels and has successfully passed a fast neutron radiation test of 2.7 x 10$sup 17$ nvt without failure. (auth)« less

Progress on Ares First Stage Propulsion

NASA Technical Reports Server (NTRS)

Priskos, Alex S.; Tiller, Bruce

2008-01-01

The mission of the National Aeronautics and Space Administration (NASA) is not simply to maintain its current position with the International Space Station and other space exploration endeavors, but to build a permanent outpost on the Moon and then travel on to explore ever more distant terrains. The Constellation Program will oversee the development of the crew capsule, launch vehicles, and other systems needed to achieve this mission. From this initiative will come two new launch vehicles: the Ares I and Ares V. The Ares I will be a human-rated vehicle, which will be used for crew transport; the Ares V, a cargo transport vehicle, will be the largest launch vehicle ever built. The Ares Projects team at Marshall Space Flight Center (MSFC) in Huntsville, Alabama is assigned with developing these two new vehicles. The Ares I vehicle will have an in-line, two-stage rocket configuration. The first stage will provide the thrust or propulsion component for the Ares rocket systems through the first two minutes of the mission. The First Stage Team is tasked with developing the propulsion system necessary to liftoff from the Earth and loft the entire Ares vehicle stack toward low-Earth orbit. Building on the legacy of the Space Shuttle and other NASA space exploration initiatives, the propulsion for the Ares I First Stage will be a Shuttle-derived reusable solid rocket motor. Progress to date by the First Stage Team has been robust and on schedule. This paper provides an update on the design and development of the Ares First Stage Propulsion system.

Of Lofts, Evidence and Mobile Times: The School Play as a Site of Memory

ERIC Educational Resources Information Center

Mackey, Sally

2012-01-01

How do we remember past arts events? What forms of tangible evidence exist to demonstrate such memories and what meanings can be taken from the archiving of artefacts in contemporary times? The research discussed in this article showed that a school production taking place 20 years ago is remembered as a significant event in the lives of its…

Day of Launch Profile Selection for Pad Abort Guidance

NASA Technical Reports Server (NTRS)

Whitley, Ryan J.

2010-01-01

A day of launch selection approach that involves choosing from an array of pitch profiles of varying loft was analyzed with the purpose of reducing the risk of a land landing failure during a pad abort. It was determined that selecting from three pitch profiles can reduce the number of waterline abort performance requirement failures approximately in half without compromising other performance metrics.

Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor

PubMed Central

Clatot, Florian; Perdrix, Anne; Augusto, Laetitia; Beaussire, Ludivine; Delacour, Julien; Calbrix, Céline; Sefrioui, David; Viailly, Pierre-Julien; Bubenheim, Michael; Moldovan, Cristian; Alexandru, Cristina; Tennevet, Isabelle; Rigal, Olivier; Guillemet, Cécile; Leheurteur, Marianne; Gouérant, Sophie; Petrau, Camille; Théry, Jean-Christophe; Picquenot, Jean-Michel; Veyret, Corinne; Frébourg, Thierry; Jardin, Fabrice

2016-01-01

Purpose To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment. Patients and methods ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas. Results Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome. Conclusion ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted. PMID:27801670

Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor.

PubMed

Clatot, Florian; Perdrix, Anne; Augusto, Laetitia; Beaussire, Ludivine; Delacour, Julien; Calbrix, Céline; Sefrioui, David; Viailly, Pierre-Julien; Bubenheim, Michael; Moldovan, Cristian; Alexandru, Cristina; Tennevet, Isabelle; Rigal, Olivier; Guillemet, Cécile; Leheurteur, Marianne; Gouérant, Sophie; Petrau, Camille; Théry, Jean-Christophe; Picquenot, Jean-Michel; Veyret, Corinne; Frébourg, Thierry; Jardin, Fabrice; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric

2016-11-15

To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment. ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas. Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome. ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted.

Language Assessment in a Snap: Monitoring Progress up to 36 Months

ERIC Educational Resources Information Center

Gilkerson, Jill; Richards, Jeffrey A.; Greenwood, Charles R.; Montgomery, Judy K.

2017-01-01

This article describes the development and validation of the Developmental Snapshot, a 52-item parent questionnaire on child language and vocal communication development that can be administered monthly and scored automatically. The Snapshot was created to provide an easily administered monthly progress monitoring tool that enables parents to…

Impact of Aerosols on Scene Collection and Scene Correction

DTIC Science & Technology

2009-03-01

the atmosphere on the way to the satellite. In order for a satellite- borne sensor to distinguish a target from its background, the difference between...the target and background top of the atmosphere radiance ( TLΔ ) must be greater than the sensor radiance sensitivity ( sLΔ ). The difference ...northwesterly, with prevailing surface visibilities between four and seven miles in dust, sand, or haze. Stronger flow over northern Saudi Arabia can loft

Dust Devils on Mars: Effects of Surface Roughness on Particle Threshold

NASA Technical Reports Server (NTRS)

Neakrase, Lynn D.; Greeley, Ronald; Iversen, James D.; Balme, Matthew L.; Foley, Daniel J.; Eddlemon, Eric E.

2005-01-01

Dust devils have been proposed as effective mechanisms for lofting large quantities of dust into the martian atmosphere. Previous work showed that vortices lift dust more easily than simple boundary layer winds. The aim of this study is to determine experimentally the effects of non-erodable roughness elements on vortex particle threshold through laboratory simulations of natural surfaces. Additional information is included in the original extended abstract.

An Overview of the National Shipbuilding Industrial Base,

DTIC Science & Technology

1982-04-01

increased use of modular construction. In the near future, laser welding and alignment, plasma cutting, air-cushion and water bearing materials handling...of computer graphics for design and lofting, laser alignment and welding , and robotization also will be adoptable by shipyards in the near future...introduced the "roll over" ship construction technique to maximize the use of down-hand welding with smooth production flow; modular construction

The interaction between design and occupier behaviour in the safety of new homes.

PubMed

McDermott, Hilary; Haslam, Roger; Gibb, Alistair

2007-03-01

The design of new homes includes many safety features intended to protect occupiers from injury or ill health within the home, however the effectiveness of these primary intervention measures is likely to be affected by user behaviour. This study examined the interaction between user activity and dwelling design and how this might affect health and safety. It aimed to identify how people use features within new homes and how this may limit the protection afforded by building design, codes and regulations. Forty, home-based, semi-structured, in-depth interviews and home inspections were conducted with individuals recently inhabiting a new home. A range of behaviours were reported in relation to building features including fire doors, pipes and cables, and loft access, which may lead to increased risk of injury or ill-health. For example, occupiers described interfering with the self-closing mechanisms on fire doors and drilling into walls without considering the location of services. They also reported knowingly engaging in unsafe behaviour when accessing the loft, increasing their risk of falls. The accounts suggest that designers and builders need to give greater consideration to how occupier behaviour interacts with building features so that improvements in both design and occupier education can lead to improved health and safety.

Continuation of epidermal growth factor receptor tyrosine kinase inhibitor treatment prolongs disease control in non-small-cell lung cancers with acquired resistance to EGFR tyrosine kinase inhibitors

PubMed Central

Chen, Qi; Quan, Qi; Ding, Lingyu; Hong, Xiangchan; Zhou, Ningning; Liang, Ying; Wu, Haiying

2015-01-01

Objectives Patients with non-small-cell lung cancer (NSCLC) develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) after tumor regression. No approved targeted therapies are currently available after initial EGFR TKI treatment. This study investigated the efficacy of continuing EGFR TKI therapy with local treatments for patients with NSCLC and local progression or minimal/slow progression on TKI therapy. Materials and Methods Fifty-five patients with NSCLC treated with EGFR TKIs and developed acquired resistance to the drug were included. Initial response to target therapy, median progression free survival (PFS1), progression pattern, and first progression site were assessed. Median progression free survival to physician assessment progression (PFS2) and difference between PFS1 and PFS2 (PFS difference) were also recorded. Results and Conclusion PFS1 was 11.2 months, PFS2 was 20.3 months, and PFS difference was 8.3 months. Nineteen patients (34.5%) who manifested progression received local therapy, and 16 (28.6%) underwent rebiopsy after progression with six positive EGFR T790M mutations detected. Cox proportional hazards regression model showed that only the first line of treatment was significantly correlated with PFS difference. NSCLC patients with acquired resistance to EGFR TKIs could benefit from the same TKI therapy through months to years of disease control. PMID:26172562

Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group.

PubMed

Janssens, Geert O; Gandola, Lorenza; Bolle, Stephanie; Mandeville, Henry; Ramos-Albiac, Monica; van Beek, Karen; Benghiat, Helen; Hoeben, Bianca; Morales La Madrid, Andres; Kortmann, Rolf-Dieter; Hargrave, Darren; Menten, Johan; Pecori, Emilia; Biassoni, Veronica; von Bueren, Andre O; van Vuurden, Dannis G; Massimino, Maura; Sturm, Dominik; Peters, Max; Kramm, Christof M

2017-03-01

Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression. At first progression, 31 children with DIPG, aged 2-16 years, underwent re-irradiation (dose 19.8-30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma. An interval of ≥3 months after upfront radiotherapy was required before re-irradiation. Thirty-nine patients fulfilling the same criteria receiving radiotherapy at diagnosis, followed by best supportive care (n = 20) or systemic therapy (n = 19) at progression but no re-irradiation, were eligible for a matched-cohort analysis. Median OS for patients undergoing re-irradiation was 13.7 months. For a similar median progression-free survival after upfront radiotherapy (8.2 versus 7.7 months; P = .58), a significant benefit in median OS (13.7 versus 10.3 months; P = .04) was observed in favour of patients undergoing re-irradiation. Survival benefit of re-irradiation increased with a longer interval between end-of-radiotherapy and first progression (3-6 months: 4.0 versus 2.7; P < .01; 6-12 months: 6.4 versus 3.3; P = .04). Clinical improvement with re-irradiation was observed in 24/31 (77%) patients. No grade 4-5 toxicity was recorded. On multivariable analysis, interval to progression (corrected hazard ratio = .27-.54; P < .01) and re-irradiation (corrected hazard ratio = .18-.22; P < .01) remained prognostic for survival. A risk score (RS), comprising 5 categories, was developed to predict survival from first progression (ROC: .79). Median survival ranges from 1.0 month (RS-1) to 6.7 months (RS-5). The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age or experience? The influence of age at implantation and social and linguistic environment on language development in children with cochlear implants.

PubMed

Szagun, Gisela; Stumper, Barbara

2012-12-01

The authors investigated the influence of social environmental variables and age at implantation on language development in children with cochlear implants. Participants were 25 children with cochlear implants and their parents. Age at implantation ranged from 6 months to 42 months ( M (age) = 20.4 months, SD = 22.0 months). Linguistic progress was assessed at 12, 18, 24, and 30 months after implantation. At each data point, language measures were based on parental questionnaire and 45-min spontaneous speech samples. Children's language and parents' child-directed language were analyzed. On all language measures, children displayed considerable vocabulary and grammatical growth over time. Although there was no overall effect of age at implantation, younger and older children had different growth patterns. Children implanted by age 24 months made the most marked progress earlier on, whereas children implanted thereafter did so later on. Higher levels of maternal education were associated with faster linguistic progress; age at implantation was not. Properties of maternal language input, mean length of utterance, and expansions were associated with children's linguistic progress independently of age at implantation. In children implanted within the sensitive period for language learning, children's home language environment contributes more crucially to their linguistic progress than does age at implantation.

Development and operations of the astrophysics data system

NASA Technical Reports Server (NTRS)

Murray, S. S.

1996-01-01

Monthly progress reports are given for the period April 1994 through September 1994. Each month's progress includes a general summary and overviews of Administrative functions, Systems Engineering, User Committee, User Support, Test and QA, System Integration, Development, Operations, and Suppliers of Data. These overviews include user and query statistics for the month.

Development and operations of the astrophysics data system

NASA Technical Reports Server (NTRS)

Murray, S. S.

1996-01-01

Monthly progress reports are given for the period October 1993 through March 1994. Each month's progress includes a general summary and overviews of Administrative functions, Systems Engineering, User Committee, User Support, Test and QA, System Integration, Development, Operations, and Suppliers of Data. These overviews include user and query statistics for the month.

Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.

PubMed

Antonia, Scott J; Villegas, Augusto; Daniel, Davey; Vicente, David; Murakami, Shuji; Hui, Rina; Yokoi, Takashi; Chiappori, Alberto; Lee, Ki H; de Wit, Maike; Cho, Byoung C; Bourhaba, Maryam; Quantin, Xavier; Tokito, Takaaki; Mekhail, Tarek; Planchard, David; Kim, Young-Chul; Karapetis, Christos S; Hiret, Sandrine; Ostoros, Gyula; Kubota, Kaoru; Gray, Jhanelle E; Paz-Ares, Luis; de Castro Carpeño, Javier; Wadsworth, Catherine; Melillo, Giovanni; Jiang, Haiyi; Huang, Yifan; Dennis, Phillip A; Özgüroğlu, Mustafa

2017-11-16

Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy. We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy. The coprimary end points were progression-free survival (as assessed by means of blinded independent central review) and overall survival (unplanned for the interim analysis). Secondary end points included 12-month and 18-month progression-free survival rates, the objective response rate, the duration of response, the time to death or distant metastasis, and safety. Of 713 patients who underwent randomization, 709 received consolidation therapy (473 received durvalumab and 236 received placebo). The median progression-free survival from randomization was 16.8 months (95% confidence interval [CI], 13.0 to 18.1) with durvalumab versus 5.6 months (95% CI, 4.6 to 7.8) with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42 to 0.65; P<0.001); the 12-month progression-free survival rate was 55.9% versus 35.3%, and the 18-month progression-free survival rate was 44.2% versus 27.0%. The response rate was higher with durvalumab than with placebo (28.4% vs. 16.0%; P<0.001), and the median duration of response was longer (72.8% vs. 46.8% of the patients had an ongoing response at 18 months). The median time to death or distant metastasis was longer with durvalumab than with placebo (23.2 months vs. 14.6 months; P<0.001). Grade 3 or 4 adverse events occurred in 29.9% of the patients who received durvalumab and 26.1% of those who received placebo; the most common adverse event of grade 3 or 4 was pneumonia (4.4% and 3.8%, respectively). A total of 15.4% of patients in the durvalumab group and 9.8% of those in the placebo group discontinued the study drug because of adverse events. Progression-free survival was significantly longer with durvalumab than with placebo. The secondary end points also favored durvalumab, and safety was similar between the groups. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).

Long-term outcomes for patients with chronic lymphocytic leukemia who discontinue ibrutinib.

PubMed

Jain, Preetesh; Thompson, Philip A; Keating, Michael; Estrov, Zeev; Ferrajoli, Alessandra; Jain, Nitin; Kantarjian, Hagop; Burger, Jan A; O'Brien, Susan; Wierda, William G

2017-06-15

Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported. Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively analyzed. Long-term outcomes among patients with CLL after they discontinued ibrutinib were analyzed. Ninety of 320 patients (28%) who were treated on ibrutinib-based regimens discontinued ibrutinib. Of these, 80 had relapsed/refractory disease, and 10 were treatment-naive. The median time to discontinuation was 15 months (range, 1.2-54 months). After a median follow-up of 38 months after starting ibrutinib, 40 patients (44%) remained alive. Major reasons for ibrutinib discontinuation were intolerance (n = 29; 32%), miscellaneous (n = 28; 31%), progression (n = 19; 21%), and Richter transformation (RT) (n = 9; 10%). The median survival according to the reason for discontinuation was 33 months for ibrutinib intolerance, 11 months for miscellaneous causes, 16 months for progressive CLL, and 2 months for RT. Among the 19 patients who had progressive CLL, 42% responded to subsequent therapy. Ibrutinib discontinuation was observed during therapy. Patients with CLL who had disease transformation had especially poor outcomes, whereas those who developed progressive disease during ibrutinib therapy had a median survival of <1.5 years. Survival was associated with the reason for discontinuation; patients who had progressive CLL had better survival compared with those who had disease transformation. Effective salvage strategies for patients with CLL who progress on ibrutinib therapy is of critical importance. Cancer 2017;123:2268-2273. © 2017 American Cancer Society. © 2017 American Cancer Society.

Operational Test and Evaluation Handbook for Aircrew Training Devices. Volume II. Operational Effectiveness Evaluation

DTIC Science & Technology

1982-02-01

should also convey an understanding of the differ- ences in learning behavior between initial learning activity and later skill maintenance and...refinement might then be, ATTACK MANEUVERS * Pop-up attack # Loft/ LADO type attack * Level/laydown attack Figure 5-4 showe diagrammatically the...sensitive to differ- ences in performance. Severai criteria should be used to guide the selection/development of performance measures, i.e., measure validity

Rolling Mill Hill, Nashville, TN

EPA Pesticide Factsheets

Rolling Mill Hill was the home to Nashville General Hospital from 1890 to the 1990s and encompassed several buildings and structures. These existing buildings of historical significance were re-used in the form of apartments. The original Trolley Barns on the site are now artists’ lofts and are home to several companies and non-profit offices. Nance Place, which entails additional buildings built on-site, is a Tax Credit Workforce Housing Development and is Platinum LEED certified.

Vemurafenib for BRAF V600 mutated advanced melanoma: results of treatment beyond progression.

PubMed

Scholtens, A; Geukes Foppen, M H; Blank, C U; van Thienen, J V; van Tinteren, H; Haanen, J B

2015-03-01

Selective BRAF inhibition (BRAFi) by vemurafenib or dabrafenib has become approved standard treatment in BRAF V600 mutated advanced stage melanoma. While the response rate is high, the response duration is limited with a progression-free survival (PFS) of 5-6months. Our observation of accelerated disease progression within some patients after stopping vemurafenib treatment has fostered the idea of treatment beyond progression (BRAFi TBP). In this retrospective study, we analysed 70 metastatic melanoma patients, treated at our institute, who experienced progression after prior objective response upon treatment with vemurafenib. Thirty-five patients that continued treatment beyond progression are compared with 35 patients who stopped BRAFi treatment at disease progression. Median overall survival beyond documented progression was found to be 5.2months versus 1.4months (95% confidence interval (CI): 3.8-7.4 versus 0.6-3.4; Log-Rank p=0.002) in favour of BRAFi TBP. In the multivariate survival analysis, stopping treatment at disease progression was significantly associated with shorter survival (hazard ratio: 1.92; 95% CI: 1.04-3.55; p=0.04). Our results suggest that continuing vemurafenib treatment beyond progression may be beneficial in advanced melanoma patients, who prior to progression responded to vemurafenib. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Radiographic Comparison of Progressive and Conventional Loading on Crestal Bone Loss and Density in Single Dental Implants: A Randomized Controlled Trial Study

PubMed Central

Ghoveizi, Rahab; Alikhasi, Marzieh; Siadat, Mohammad-Reza; Siadat, Hakimeh; Sorouri, Majid

2013-01-01

Objective: Crestal bone loss is a biological complication in implant dentistry. The aim of this study was to compare the effect of progressive and conventional loading on crestal bone height and bone density around single osseointegrated implants in the posterior maxilla by a longitudinal radiographic assessment technique. Materials and Methods: Twenty micro thread implants were placed in 10 patients (two implants per patient). One of the two implants in each patient was assigned to progressive and the other to conventional loading groups. Eight weeks after surgery, conventional implants were restored with a metal ceramic crown and the progressive group underwent a progressive loading protocol. The progressive loading group took different temporary acrylic crowns at 2, 4 and 6 months. After eight months, acrylic crowns were replaced with a metal ceramic crown. Computer radiography of both progressive and conventional implants was taken at 2, 4, 6, and 12 months. Image analysis was performed to measure the height of crestal bone loss and bone density. Results: The mean values of crestal bone loss at month 12 were 0.11 (0.19) mm for progressively and 0.36 (0.36) mm for conventionally loaded implants, with a statistically significant difference (P < 0.05) using Wilcoxon sign rank. Progressively loaded group showed a trend for higher bone density gain compared to the conventionally loaded group, but when tested with repeated measure ANOVA, the differences were not statistically significant (P > 0.05). Conclusion: The progressive group showed less crestal bone loss in single osseointegrated implant than the conventional group. Bone density around progressively loaded implants showed increase in crestal, middle and apical areas. PMID:23724215

Progressive central puberty in a toddler with partial androgen insensitivity.

PubMed

Dougan, Grace C; Uli, Naveen; Shulman, Dorothy I

2014-03-01

A male infant was diagnosed with partial androgen insensitivity caused by a novel mutation in the androgen receptor. At 3.5 months of age, he received 100 mg of testosterone intramuscularly over the course of 3 months to increase phallic size. He developed pubic hair after 5 months and signs of progressive central precocious puberty when re-examined at 17.5 months, which subsequently was suppressed with depot leuprolide. Copyright © 2014 Mosby, Inc. All rights reserved.

Economic impact of disease progression in follicular non-Hodgkin lymphoma

PubMed Central

Beveridge, Roy; Satram-Hoang, Sacha; Sail, Kavita; Darragh, Joseph; Chen, Clara; Forsyth, Michael; Reyes, Carolina

2011-01-01

Using a retrospective claims database, we estimated the economic costs of progression among patients with follicular non-Hodgkin lymphoma (f-NHL) treated in an outpatient community-based setting. Patients with f-NHL who received care between 1 July 2006 and 31 December 2009 were categorized into two cohorts based on whether they experienced progressive disease (PD) or not. Costs per patient per month (PPPM) were compared between patients with PD versus non-PD. Follow-up time was censored at the last entry for disease status or 6 months after the date of remission/stable disease or progression. Of the 1002 patients with f-NHL identified, 268 progressed and 734 did not. The mean overall costs PPPM over the 6-month follow-up period were significantly higher for patients with PD versus non-PD ($3527 vs. $860; difference = $2667; p < 0.001). This cost difference persisted within all resource categories evaluated. Results of this study indicate that therapies which delay progression for patients with f-NHL may result in potential cost savings. PMID:21745172

Eribulin mesylate (halichondrin B Analog E7389) in platinum-resistant and platinum-sensitive ovarian cancer: a two-cohort, phase II study

PubMed Central

Hensley, Martee L.; Kravetz, Sara; Jia, Xiaoyu; Iasonos, Alexia; Tew, William; Pereira, Lauren; Sabbatini, Paul; Whalen, Christin; Aghajanian, Carol A.; Zarwan, Corinne; Berlin, Suzanne

2011-01-01

Background Eribulin mesylate is a tubulin inhibitor with activity superior to paclitaxel in NIH:OVCAR-3 human epithelial ovarian cancer xenograft models. We sought to assess the efficacy of eribulin in platinum-resistant and platinum-sensitive recurrent ovarian cancer. Methods Patients with recurrent measurable epithelial ovarian cancer, ≤2 prior cytotoxic regimens, and adequate organ function were enrolled into two separate cohorts: 1) Platinum resistant (progression-free interval from last platinum-based therapy <6 months); and 2) Platinum sensitive (progression-free interval from last platinum-based therapy ≥6 months). Treatment: Eribulin 1.4 mg/m2 over 15 minutes by vein on days 1 and 8, every 21 days. Efficacy was determined by objective response by computed tomography. Results Platinum-resistant cohort: Thirty-seven patients enrolled. Thirty-six patients were evaluable for response and toxicity. Two patients achieved partial response (PR, 5.5%). Sixteen (44%) had a best response of stable disease. Median progression-free survival was 1.8 months (95% confidence interval, 1.4–2.8 months). Platinum-sensitive cohort: Thirty-seven patients enrolled, and all were evaluable for response. Seven patients achieved partial response (PR, 19%). Median progression-free survival was 4.1 months (95% confidence interval, 2.8–5.8 months). The major toxicity was grade 3 or 4 neutropenia (42% in platinum-resistant patients; 54% in platinum-sensitive patients). Conclusions Eribulin achieved objective response in 5.5% of women with platinum-resistant recurrent ovarian cancer and in 19% of women with platinum-sensitive disease. Median progression-free survival was 1.8 months in the platinum-resistant group and 4.1 months in the platinum-sensitive group. PMID:21935916

Review on comparative efficacy of bevacizumab, panitumumab and cetuximab antibody therapy with combination of FOLFOX-4 in KRAS-mutated colorectal cancer patients.

PubMed

Pathak, Surajit; S, Sushmitha; Banerjee, Antara; Marotta, Francesco; Gopinath, Madhumala; Murugesan, Ramachandran; Zhang, Hong; B, Bhavani; Girigoswami, Agnishwar; Sollano, Jose; Sun, Xiao-Feng

2018-01-26

Colorectal cancer, fourth leading form of cancer worldwide and is increasing in alarming rate in the developing countries. Treating colorectal cancer has become a big challenge worldwide and several antibody therapies such as bevacizumab, panitumumab and cetuximab are being used with limited success. Moreover, mutation in KRAS gene which is linked with the colorectal cancer initiation and progression further interferes with the antibody therapies. Considering median progression free survival and overall survival in account, this review focuses to identify the most efficient antibody therapy in combination with chemotherapy (FOLFOX-4) in KRAS mutated colorectal cancer patients. The bevacizumab plus FOLFOX-4 therapy shows about 9.3 months and 8.7 months of progression free survival for KRAS wild and mutant type, respectively. The overall survival is about 34.8 months for wild type whereas for the mutant it is inconclusive for the same therapy. In comparison, panitumumab results in better progression-free survival which is about (9.6 months) and overall survival is about (23.9 months) for the wild type KRAS and the overall survival is about 15.5 months for the mutant KRAS . Cetuximab plus FOLFOX-4 therapy shows about 7.7 months and 5.5 months of progression-free survival for wild type KRAS and mutant type, respectively. Thus, panitumumab shows significant improvement in overall survival rate for wild type KRAS , validating as a cost effective therapeutic for colorectal cancer therapy. This review depicts that panitumumab along with FOLFOX-4 has a higher response in colorectal cancer patients than the either of the two monoclonal antibodies plus FOLFOX-4.

Next Generation Attenuation Relationships for the Eastern United States (NGA-East)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahin, Stephen; Bozorgnia, Yousef

2016-04-11

This is a progress report to DOE for project Next Generation Attenuation for Central & Eastern US (NGA-East).This progress report consists of numerous monthly progress segments starting June 1, 2010 until December 31, 2015. Please note: the December 2015 progress report was issued in January 2016 due to the final university financial reporting at the end of this project. For each month, there is a technical progress list, and an update on the financial progress of the project. As you know, this project is jointly funded by the DOE, US Nuclear Regulatory Commission (NRC) and Electric Power Research Institute (EPRI).more » Thus, each segment includes financial progress for these three funding agencies.« less

Clinical efficacy and safety of bevacizumab monotherapy in patients with metastatic melanoma: predictive importance of induced early hypertension.

PubMed

Schuster, Cornelia; Eikesdal, Hans P; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E; Akslen, Lars A; Straume, Oddbjørn

2012-01-01

VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12-49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. ClinicalTrials.gov NCT00139360.

Venezuelan Equine Encephalitis Replicon Immunization Overcomes Intrinsic Tolerance and Elicits Effective Anti-Tumor Immunity to the ’Self’ Tumor-Associated Antigen, neu in a Rat Mammary Tumor Model

DTIC Science & Technology

2003-01-01

rat mammary tumor model Edward L. Nelson1, Darue Prieto2, Terri G. Alexander1, Peter Pushko3, Loreen A. Lofts3, Jonathan O. Rayner4, Kurt I. Kamrud4...7861–7867, 2001 28. Lachman LB, Rao XM, Kremer RH, Ozpolat B, Kiriakova G, Price JE: DNA vaccination against neu reduces breast can- cer incidence and

Combined vemurafenib and fotemustine in patients with BRAF V600 melanoma progressing on vemurafenib.

PubMed

Queirolo, Paola; Spagnolo, Francesco; Picasso, Virginia; Spano, Laura; Tanda, Enrica; Fontana, Valeria; Giorello, Laura; Merlo, Domenico Franco; Simeone, Ester; Grimaldi, Antonio Maria; Curvietto, Marcello; Del Vecchio, Michele; Bruzzi, Paolo; Ascierto, Paolo Antonio

2018-02-23

BRAF inhibitor vemurafenib achieves high response rate and an improvement in survival in patients with BRAF-mutated metastatic melanoma. However, median progression-free survival is only 6.9 months in the phase 3 study. Retrospective analyses suggest that treatment with BRAF inhibitors beyond initial progression might be associated with improved overall survival. We aimed to prospectively investigate the activity of prolonged treatment with vemurafenib and the addition of fotemustine in patients with systemic progression on prior single-agent BRAF inhibitor. In this two-centres, single-arm Phase 2 trial, we enrolled patients with systemic progressive disease during single-agent vemurafenib treatment. Participants received vemurafenib 960 mg twice daily or dose administered at time of disease progression with vemurafenib previous treatment and fotemustine 100 mg/m2 intravenously every three weeks. The primary endpoint was PFS. Thirty-one patients were enrolled in the study; 16 patients had brain metastases at baseline. Median PFS was 3.9 months and 19 patients (61.3%) achieved disease control (1 CR, 4 PR, 14 SD). For patients achieving disease control, median duration of treatment was 6 months. Median OS was 5.8 months from enrolment and 15.4 months from start of previous vemurafenib. Five patients (16.1%) had a G3-4 AE, the most common being thrombocytopenia, which occurred in 3 patients.This trial is registered with ClinicalTrials.gov number NCT01983124. The combination of vemurafenib plus fotemustine has clinical activity and an acceptable safety profile in BRAF-refractory patients.

Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma.

PubMed

Kaseb, Ahmed O; Morris, Jeffrey S; Iwasaki, Michiko; Al-Shamsi, Humaid O; Raghav, Kanwal Pratap Singh; Girard, Lauren; Cheung, Sheree; Nguyen, Van; Elsayes, Khaled M; Xiao, Lianchun; Abdel-Wahab, Reham; Shalaby, Ahmed S; Hassan, Manal; Hassabo, Hesham M; Wolff, Robert A; Yao, James C

2016-01-01

Clinicaltrials.gov #NCT01180959. Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib. For this single-arm, Phase II study, we recruited patients with Child-Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0-2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib). Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival. A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months - not defined). The 16-week progression-free survival rate was 43% (95% CI: 28%-59%), median time to progression was 3.9 months (95% CI: 2.0-8.3 months), and median overall survival duration was 9.9 months (95% CI: 8.3-15.5 months). Grade 3-4 adverse events included fatigue (13%), acne (11%), diarrhea (9%), anemia (7%), and upper gastrointestinal hemorrhage (7%). Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted.

Predictive Value of Early Tumor Shrinkage and Density Reduction of Lung Metastases in Patients With Metastatic Colorectal Cancer Treated With Regorafenib.

PubMed

Vanwynsberghe, Hannes; Verbeke, Xander; Coolen, Johan; Van Cutsem, Eric

2017-12-01

The benefit of regorafenib in colorectal cancer is not very pronounced. At present, there is lack of predictive biological or radiological markers. We studied if density reduction or small changes in size of lung metastases could be a predictive marker. We retrospectively measured density in size of lung metastases of all patients included in the CORRECT and CONSIGN trials at our center. Contrast-enhanced CT scan at baseline and at week 8 were compared. Data of progressive-free survival and overall survival were collected from the CORRECT and CONSIGN trials. A significant difference in progressive-free survival was seen in 3 groups: response or stable disease in size (5.36 vs. 3.96 months), response in density (6.03 vs. 2.72 months), and response in corrected density (6.14 vs. 3.08 months). No difference was seen for response in size versus stable disease or progressive disease in size. For overall survival, a difference was observed in the same 3 groups: response or stable disease in size (9.89 vs. 6.44 months), response in density (9.59 vs. 7.04 months), and response in corrected density (9.09 vs. 7.16 months). No difference was seen for response in size versus stable disease or progressive disease in size. Density reduction in lung metastases might be a good predictive parameter to predict outcome for regorafenib. Early tumor progression might be a negative predictive factor. If further validated, density reduction and early tumor progression might be useful to ameliorate the cost-benefit of regorafenib. Copyright © 2017 Elsevier Inc. All rights reserved.

Stereotactic Radiosurgery for the Treatment of Primary and Metastatic Spinal Sarcomas

PubMed Central

Balagamwala, Ehsan H.; Angelov, Lilyana; Suh, John H.; Djemil, Toufik; Magnelli, Anthony; Qi, Peng; Zhuang, Tingliang; Godley, Andrew

2016-01-01

Purpose: Despite advancements in local and systemic therapy, metastasis remains common in the natural history of sarcomas. Unfortunately, such metastases are the most significant source of morbidity and mortality in this heterogeneous disease. As a classically radioresistant histology, stereotactic radiosurgery has emerged to control spinal sarcomas and provide palliation. However, there is a lack of data regarding pain relief and relapse following stereotactic radiosurgery. Methods: We queried a retrospective institutional database of patients who underwent spine stereotactic radiosurgery for primary and metastatic sarcomas. The primary outcome was pain relief following stereotactic radiosurgery. Secondary outcomes included progression of pain, radiographic failure, and development of toxicities following treatment. Results: Forty treatment sites were eligible for inclusion; the median prescription dose was 16 Gy in a single fraction. Median time to radiographic failure was 14 months. At 6 and 12 months, radiographic control was 63% and 51%, respectively. Among patients presenting with pain, median time to pain relief was 1 month. Actuarial pain relief at 6 months was 82%. Median time to pain progression was 10 months; at 12 months, actuarial pain progression was 51%. Following multivariate analysis, presence of neurologic deficit at consult (hazard ratio: 2.48, P < .01) and presence of extraspinal bone metastases (hazard ratio: 2.83, P < .01) were associated with pain relief. Greater pain at consult (hazard ratio: 1.92, P < .01), prior radiotherapy (hazard ratio: 4.65, P = .02), and greater number of irradiated vertebral levels were associated with pain progression. Conclusions: Local treatment of spinal sarcomas has remained a challenge for decades, with poor rates of local control and limited pain relief following conventional radiotherapy. In this series, pain relief was achieved in 82% of treatments at 6 months, with half of patients experiencing pain progression by 12 months. Given minimal toxicity and suboptimal pain control at 12 months, dose escalation beyond 16 Gy is warranted. PMID:27074915

A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: a real-world experience

PubMed Central

Vici, Patrizia; Pizzuti, Laura; Michelotti, Andrea; Sperduti, Isabella; Natoli, Clara; Mentuccia, Lucia; Lauro, Luigi Di; Sergi, Domenico; Marchetti, Paolo; Santini, Daniele; Magnolfi, Emanuela; Iezzi, Laura; Moscetti, Luca; Fabbri, Agnese; Cassano, Alessandra; Grassadonia, Antonino; Omarini, Claudia; Piacentini, Federico; Botticelli, Andrea; Bertolini, Ilaria; Scinto, Angelo Fedele; Zampa, Germano; Mauri, Maria; D’Onofrio, Loretta; Sini, Valentina; Barba, Maddalena; Maugeri-Saccà, Marcello; Rossi, Ernesto; Landucci, Elisabetta; Tomao, Silverio; Alberti, Antonio Maria; Giotta, Francesco; Ficorella, Corrado; Adamo, Vincenzo; Russo, Antonio; Lorusso, Vito; Cannita, Katia; Barni, Sandro; Laudadio, Lucio; Greco, Filippo; Garrone, Ornella; Giulia, Marina Della; Marolla, Paolo; Sanguineti, Giuseppe; Cocco, Barbara Di; Ciliberto, Gennaro; Maria, Ruggero De; Gamucci, Teresa

2017-01-01

We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences emerged by pertuzumab pretreatment, with median progression-free and median overall survival of 4 and 17 months in pertuzumab-pretreated (p=0.13), and 6 and 22 months in pertuzumab-naïve patients (p=0.27). Patients who received second-line T-DM1 had median progression-free and median overall survival of 3 and 12 months (p=0.0001) if pertuzumab-pretreated, and 8 and 26 months if pertuzumab-naïve (p=0.06). In contrast, in third-line and beyond, median progression-free and median overall survival were 16 and 18 months in pertuzumab-pretreated (p=0.05) and 6 and 17 months in pertuzumab-naïve patients (p=0.30). In multivariate analysis, lower ECOG performance status was associated with progression-free survival benefit (p<0.0001), while overall survival was positively affected by lower ECOG PS (p<0.0001), absence of brain metastases (p 0.05), and clinical benefit (p<0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to confirm and interpret our data on apparently lower T-DM1 efficacy when given as second-line treatment after pertuzumab, and on the optimal sequence order. PMID:28915642

Sources and distribution of NO(x) in the upper troposphere at northern midlatitudes

NASA Technical Reports Server (NTRS)

Rohrer, Franz; Ehhalt, Dieter H.; Wahner, Andreas

1994-01-01

A simple quasi 2-D model is used to study the zonal distribution of NO(x). The model includes vertical transport in form of eddy diffusion and deep convection, zonal transport by a vertically uniform wind, and a simplified chemistry of NO, NO2 and HNO3. The NO(x) sources considered are surface emissions (mostly from the combustion of fossil fuel), lightning, aircraft emissions, and downward transport from the stratosphere. The model is applied to the latitude band of 40 deg N to 50 deg N during the month of June; the contributions to the zonal NO(x) distribution from the individual sources and transport processes are investigated. The model predicted NO(x) concentration in the upper troposphere is dominated by air lofted from the polluted planetary boundary layer over the large industrial areas of Eastern North America and Europe. Aircraft emissions are also important and contribute on average 30 percent. Stratospheric input is minor about 10 percent, less even than that by lightning. The model provides a clear indication of intercontinental transport of NO(x) and HNO3 in the upper troposphere. Comparison of the modelled NO profiles over the Western Atlantic with those measured during STRATOZ 3 in 1984 shows good agreement at all altitudes.

Continuous passive motion and its effects on knee flexion after total knee arthroplasty in patients with knee osteoarthritis.

PubMed

Liao, Chun-De; Huang, Yi-Ching; Lin, Li-Fong; Chiu, Yen-Shuo; Tsai, Jui-Chen; Chen, Chun-Lung; Liou, Tsan-Hon

2016-08-01

This study evaluated the effects of continuous passive motion (CPM) on accelerated flexion after total knee arthroplasty (TKA) and whether CPM application measures (i.e. initial angle and daily increment) are associated with functional outcomes. A retrospective investigation was conducted at the rehabilitation centre of a university-based teaching hospital. Patients who received CPM therapy immediately after TKA surgery were categorized into rapid-, normal-, and slow-progress groups according to their response to CPM during their acute inpatient stay. Knee pain, passive knee flexion, and knee function-measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-were assessed preoperatively at discharge and at 3- and 6-month outpatient follow-up visits. A total of 354 patients were followed for 6 months after inpatient-stay discharge. The patients in the rapid-progress group (n = 119) exhibited significantly greater knee flexions than those in the slow-progress group did (n = 103) at the 3-month follow-up [mean difference (MD) = 10.3°, 95 % confidence interval (CI) 4.3°-16.3°, p < 0.001] and 6-month follow-up (MD = 10.9°, 95 % CI 6.3°-15.6°, p < 0.001). Significant WOMAC score differences between the rapid- and slow-progress groups were observed at the 3-month follow-up (MD = 7.2, 95 % CI 5.4-9.1, p < 0.001) and 6-month follow-up (MD = 16.1, 95 % CI 13.4-18.7, p < 0.001). CPM initial angles and rapid progress significantly predicted short- and long-term outcomes in knee flexion and WOMAC scores (p < 0.001). When CPM is used, early application with initial high flexion and rapid progress benefits knee function up to 6 months after TKA. II.

Crevicular Fluid Biomarkers and Periodontal Disease Progression

PubMed Central

Oh, Min; Braun, Thomas M.; Ramseier, Christoph A.; Sugai, Jim V.; Giannobile, William V.

2014-01-01

Aim Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). Materials and Methods 100 individuals participated in a 12-month longitudinal investigation and categorized into 4 groups according to their periodontal status. GCF, clinical parameters, and saliva were collected bi-monthly. Sub-gingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6-months, patients received periodontal therapy and continued participation from 6-12 months. GCF samples were analyzed by ELISA for MMP-8, MMP-9, OPG, CRP and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p=0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. Results Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61,86). Conclusions Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745). PMID:24303954

Long-term profiling of mineral dust and pollution aerosol with multiwavelength polarization Raman lidar at the Central Asian site of Dushanbe, Tajikistan: case studies

NASA Astrophysics Data System (ADS)

Hofer, Julian; Althausen, Dietrich; Abdullaev, Sabur F.; Makhmudov, Abduvosit N.; Nazarov, Bakhron I.; Schettler, Georg; Engelmann, Ronny; Baars, Holger; Wadinga Fomba, K.; Müller, Konrad; Heinold, Bernd; Kandler, Konrad; Ansmann, Albert

2017-12-01

For the first time, continuous vertically resolved aerosol measurements were performed by lidar in Tajikistan, Central Asia. Observations with the multiwavelength polarization Raman lidar PollyXT were conducted during CADEX (Central Asian Dust EXperiment) in Dushanbe, Tajikistan, from March 2015 to August 2016. Co-located with the lidar, a sun photometer was also operated. The goal of CADEX is to provide an unprecedented data set on vertically resolved aerosol optical properties in Central Asia, an area highly affected by climate change but largely missing vertically resolved aerosol measurements. During the 18-month measurement campaign, mineral dust was detected frequently from ground to the cirrus level height. In this study, an overview of the measurement period is given and four typical but different example measurement cases are discussed in detail. Three of them are dust cases and one is a contrasting pollution aerosol case. Vertical profiles of the measured optical properties and the calculated dust and non-dust mass concentrations are presented. Dust source regions were identified by means of backward trajectory analyses. A lofted layer of Middle Eastern dust with an aerosol optical thickness (AOT) of 0.4 and an extinction-related Ångström exponent of 0.41 was measured. In comparison, two near-ground dust cases have Central Asian sources. One is an extreme dust event with an AOT of 1.5 and Ångström exponent of 0.12 and the other one is a most extreme dust event with an AOT of above 4 (measured by sun photometer) and an Ångström exponent of -0.08. The observed lidar ratios (and particle linear depolarization ratios) in the presented dust cases range from 40.3 to 46.9 sr (and 0.18-0.29) at 355 nm and from 35.7 to 42.9 sr (0.31-0.35) at 532 nm wavelength. The particle linear depolarization ratios indicate almost unpolluted dust in the case of a lofted dust layer and pure dust in the near-ground dust cases. The lidar ratio values are lower than typical lidar ratio values for Saharan dust (50-60 sr) and comparable to Middle Eastern or west-Asian dust lidar ratios (35-45 sr). In contrast, the presented case of pollution aerosol of local origin has an Ångström exponent of 2.07 and a lidar ratio (particle linear depolarization ratio) of 55.8 sr (0.03) at 355 nm and 32.8 sr (0.08) at 532 nm wavelength.

Mass Transportation in Massachusetts : demonstration project progress report no. 5 - tentative conclusions

DOT National Transportation Integrated Search

1963-11-22

This fifth progress report is submitted twelve months after the initiation of the first MTC-HHFA experiment, and ten months after the start of the large Boston and Maine Railroad. Because of the urgent need to present comprehensive analyses in some d...

Zoledronic acid in metastatic osteosarcoma: encouraging progression free survival in four consecutive patients.

PubMed

Conry, Robert M; Rodriguez, Michael G; Pressey, Joseph G

2016-01-01

Zoledronic acid (ZA) is a third-generation bisphosphonate in widespread clinical use to reduce pain and skeletal events in patients from a variety of malignancies with bone metastases. Pre-clinical studies indicate that ZA inhibits osteosarcoma through direct anti-proliferative effects, immune activation and anti-angiogenic activity. The purpose of this study was to evaluate the antitumor efficacy of ZA at standard dose until progression in patients with stage IV osteosarcoma lacking a standard of care treatment option proven to influence survival. Researchers retrospectively reviewed medical records of all patients at our institution with high-grade osteosarcoma presumed to be incurable due to metastases progressive after primary combination chemotherapy who received single agent ZA in an effort to delay progression. In our four-patient cohort following initiation of ZA, the median progression-free survival was 19 months, and median overall survival was 56+ months. Two of four patients have remained progression-free since starting ZA. The other two initially progressed after 18-20 months on ZA followed by metastasectomy of lung or dural metastases and further stability for over a year following resumption of ZA. After a 20-month progression-free interval on ZA alone, one patient had partial response following addition of pazopanib to ZA that likely contributed to long term disease control. The four patients experienced no significant toxicities despite protracted dosing of ZA for up to 5 years, and none have required chemotherapy since beginning ZA. Single agent ZA was associated with encouraging progression-free survival in four consecutive patients with metastatic osteosarcoma. Prospective trials of single agent ZA are warranted as protracted maintenance therapy in surgically incurable osteosarcoma relapsed or refractory to first line combination chemotherapy with radiographically measurable metastases.

Low-Dose Radiotherapy in Indolent Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rossier, Christine; Schick, Ulrike; Miralbell, Raymond

Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 monthsmore » (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.« less

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study

PubMed Central

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-01-01

Background Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. Patients and methods This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Results Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63–7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Conclusion Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects. PMID:29075129

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study.

PubMed

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-01-01

Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.

Clinical Efficacy and Safety of Bevacizumab Monotherapy in Patients with Metastatic Melanoma: Predictive Importance of Induced Early Hypertension

PubMed Central

Schuster, Cornelia; Eikesdal, Hans P.; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E.; Akslen, Lars A.; Straume, Oddbjørn

2012-01-01

Background VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Methods and Findings Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12–49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Conclusion Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. Trial Registration ClinicalTrials.gov NCT00139360. PMID:22719881

A Structured Reasoning Space for Design of Complex, Socio-Technical Systems

DTIC Science & Technology

2006-10-01

gather during midmorning at an identified location. The human intelligence sources indicate that the meeting will commence at 10 a.m. and finish ...refueling station. 21 Typ-s of .uppr-s1on capawility Soppe.oion lob. (.-a .h~po d" Coton ) Olotano.. O otk-lo n k brWg..t.. Tbo AabNity rl.o1 Loft...designer or analyst could use the reasoning space to consider whether current and alternative configurations can result in the plan being finished within

Next-Generation X-Ray Astronomy

NASA Technical Reports Server (NTRS)

White, Nicholas E.

2011-01-01

The future timing capabilities in X-ray astronomy will be reviewed. This will include reviewing the missions in implementation: Astro-H, GEMS, SRG, and ASTROSAT; those under study: currently ATHENA and LOFT; and new technologies that may enable future missions e.g. Lobster eye optics. These missions and technologies will bring exciting new capabilities across the entire time spectrum from micro-seconds to years that e.g. will allow us to probe close to the event horizon of black holes and constrain the equation of state of neutron stars.

4. OVERALL VIEW OF THE SOUTHEAST FACADE. THE BRICK MASONRY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. OVERALL VIEW OF THE SOUTHEAST FACADE. THE BRICK MASONRY WALLS ARE LAID IN COMMON BOND WITH A BRICK DETAIL SURROUNDING THE FLAT ARCHED WOODEN DOORS. THE SYMMETRICAL PLACEMENT OF DOORS HAS BEEN VISUALLY AFFECTED BY THE ADDITION OF A WOOD FIRE STAIR. A BEAM USED TO LOAD HAY INTO THE UPPER LOFT AREA PROTRUDES THROUGH THE MASONRY WALL JUST BELOW THE ROOF LINE. - Presidio of San Francisco, Cavalry Stables, Cowles Street, between Lincoln Boulevard & McDowell Street, San Francisco, San Francisco County, CA

Lidar Profiling In the lower Troposphere: experience from PECAN

NASA Astrophysics Data System (ADS)

Demoz, Belay B.; Delgado, Ruben; Caroll, Brian; Vermeesch, Kevin; Whiteman, David N.; Sakai, Ricardo; Tesfay, Sium; Cooper, Lorenza

2018-04-01

Results from the PECAN (Plains Elevated Convection at Night) campaign are discussed. In particular, the utility of simple backscatter lidars/ceilometers in quantifying atmospheric dynamics parameters and variables as well as evolution of the lower tropospheric dynamics are made. Cases of bore wave dynamics and the potential of these events in lofting of low level, moist, airmass and its consequence in thunderstorm initiation are made. A suite of thermodynamic profiling instruments are combined and compared to describe and visualize lower tropospheric dynamic evolution.

HOT CELL BUILDING, TRA632. EAST END OF BUILDING. CAMERA FACING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

HOT CELL BUILDING, TRA-632. EAST END OF BUILDING. CAMERA FACING WEST. TRUCK ENCLOSURE (1986) TO THE LEFT, SMALL ADDITION IN ITS SHADOW IS ENCLOSURE OVER METAL PORT INTO HOT CELL NO. 1 (THE OLDEST HOT CELL). NOTE PERSONNEL LADDER AND PLATFORM AT LOFT LEVEL USED WHEN SERVICING AIR FILTERS AND VENTS OF CELL NO. 1. INL NEGATIVE NO. HD46-32-4. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

Biomass burning aerosols characterization from ground based and profiling measurements

NASA Astrophysics Data System (ADS)

Marin, Cristina; Vasilescu, Jeni; Marmureanu, Luminita; Ene, Dragos; Preda, Liliana; Mihailescu, Mona

2018-04-01

The study goal is to assess the chemical and optical properties of aerosols present in the lofted layers and at the ground. The biomass burning aerosols were evaluated in low level layers from multi-wavelength lidar measurements, while chemical composition at ground was assessed using an Aerosol Chemical Speciation Monitor (ACSM) and an Aethalometer. Classification of aerosol type and specific organic markers were used to explore the potential to sense the particles from the same origin at ground base and on profiles.

Outcome prediction in plasmacytoma of bone: a risk model utilizing bone marrow flow cytometry and light-chain analysis.

PubMed

Hill, Quentin A; Rawstron, Andy C; de Tute, Ruth M; Owen, Roger G

2014-08-21

The purpose of this study was to use multiparameter flow cytometry to detect occult marrow disease (OMD) in patients with solitary plasmacytoma of bone and assess its value in predicting outcome. Aberrant phenotype plasma cells were demonstrable in 34 of 50 (68%) patients and comprised a median of 0.52% of bone marrow leukocytes. With a median follow-up of 3.7 years, 28 of 50 patients have progressed with a median time to progression (TTP) of 18 months. Progression was documented in 72% of patients with OMD vs 12.5% without (median TTP, 26 months vs not reached; P = .003). Monoclonal urinary light chains (ULC) were similarly predictive of outcome because progression was documented in 91% vs 44% without (median TTP, 16 vs 82 months; P < .001). By using both parameters, it was possible to define patients with an excellent outcome (lacking both OMD and ULC, 7.7% progression) and high-risk patients (OMD and/or ULC, 75% progression; P = .001). Trials of systemic therapy are warranted in high-risk patients. © 2014 by The American Society of Hematology.

Cyclophosphamide's addition in relapsed/refractory multiple myeloma patients with biochemical progression during lenalidomide-dexamethasone treatment.

PubMed

Cesini, Laura; Siniscalchi, Agostina; Grammatico, Sara; Andriani, Alessandro; Fiorini, Alessia; De Rosa, Luca; Za, Tommaso; Rago, Angela; Caravita, Tommaso; Petrucci, Maria Teresa

2018-05-02

The aim of this study was to evaluate the addition of cyclophosphamide in relapsed-refractory multiple myeloma patients (RRMM) who experienced biochemical relapse or progression without CRAB, during treatment with lenalidomide and dexamethasone (Rd), to slow down the progression in active relapse. This analysis included 31 patients with RRMM treated with Rd who received cyclophosphamide (CRd) at biochemical relapse. The CRd regimen was continued until disease progression. The median number of CRd cycles administered was 8 (range: 1-35). A response was observed in 9 (29%) patients. After a median observation time of 11 months, the median overall survival (OS) from the beginning of CRd was 17.7 months. The median progression-free survival (PFS) from the beginning of CRd was 13.1 months. The addition of cyclophosphamide delays the progression in patients who present a biochemical relapse during Rd treatment. The response rate and the duration of PFS obtained with minimal toxicities and low costs induced us to setting up a randomized clinical trial. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Predictors of Clinical Progression in HIV-1-Infected Adults Initiating Combination Antiretroviral Therapy with Advanced Disease in the Asia-Pacific Region: Results from the TREAT Asia HIV Observational Database

PubMed Central

Byakwaga, H.; Petoumenos, K.; Ananworanich, J.; Zhang, F.; Boyd, M. A.; Sirisanthana, T.; Li, P. C. K.; Lee, C.; Mean, C. V.; Saphonn, V.; Omar, S. F. S.; Pujari, S.; Phanuphak, P.; Lim, P. L.; Kumarasamy, N.; Chen, Y. M. A.; Merati, T. P.; Sungkanuparph, S.; Ditangco, R.; Oka, S.; Tau, G.; Zhou, J.; Law, M. G.; Emery, S.

2013-01-01

The majority of HIV-infected patients in developing countries commences combination antiretroviral therapy (cART) with advanced disease. We examined predictors of disease progression in patients initiating cART with CD4 count ≤200 cells/mm3 in the TREAT Asia HIV Observational Database. The main outcome measure was progression to either an AIDS-defining illness or death occurring 6 months after initiation of cART. We used survival analysis methods. A total of 1255 patients contributed 2696 person years of follow-up; 73 were diagnosed with AIDS and 9 died. The rate of progression to the combined end point was 3.0 per 100 person years. The factors significantly associated with a higher risk of disease progression were Indian ethnicity, infection through intravenous drug use, lower CD4 count, and hemoglobin ≤130 g/dL at 6 months. In conclusion, measurements of CD4 count and hemoglobin at month 6 may be useful for early identification of disease progression in resource-limited settings. PMID:23422741

Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study.

PubMed

von Minckwitz, Gunter; du Bois, Andreas; Schmidt, Marcus; Maass, Nicolai; Cufer, Tanja; de Jongh, Felix E; Maartense, Eduard; Zielinski, Christoph; Kaufmann, Manfred; Bauer, Wolfgang; Baumann, Klaus H; Clemens, Michael R; Duerr, Ralph; Uleer, Christoph; Andersson, Michael; Stein, Robert C; Nekljudova, Valentina; Loibl, Sibylle

2009-04-20

Trastuzumab shows clinical activity in human epidermal growth factor receptor 2 (HER-2)-positive early and advanced breast cancer. In the German Breast Group 26/Breast International Group 03-05 trial, we investigated if trastuzumab treatment should be continued beyond progression. Patients with HER-2-positive breast cancer that progresses during treatment with trastuzumab were randomly assigned to receive capecitabine (2,500 mg/m(2) body-surface area on days 1 through 14 [1,250 mg/m(2) semi-daily]) alone or with continuation of trastuzumab (6 mg/kg body weight) in 3-week cycles. The primary end point was time to progression. We randomly assigned 78 patients to capecitabine and 78 patients to capecitabine plus trastuzumab. Sixty-five events and 38 deaths in the capecitabine group and 62 events and 33 deaths in the capecitabine-plus-trastuzumab group occurred during 15.6 months of follow-up. Median times to progression were 5.6 months in the capecitabine group and 8.2 months in the capecitabine-plus-trastuzumab group with an unadjusted hazard ratio of 0.69 (95% CI, 0.48 to 0.97; two-sided log-rank P = .0338). Overall survival rates were 20.4 months (95% CI, 17.8 to 24.7) in the capecitabine group and 25.5 months (95% CI, 19.0 to 30.7) in the capecitabine-plus-trastuzumab group (P = .257). Overall response rates were 27.0% with capecitabine and 48.1% with capecitabine plus trastuzumab (odds ratio, 2.50; P = .0115). Continuation of trastuzumab beyond progression was not associated with increased toxicity. Continuation of trastuzumab plus capecitabine showed a significant improvement in overall response and time to progression compared with capecitabine alone in women with HER-2-positive breast cancer who experienced progression during trastuzumab treatment.

Recent Cycle Time Reduction at Langley Research Center

NASA Technical Reports Server (NTRS)

Kegelman, Jerome T.

2000-01-01

The NASA Langley Research Center (LaRC) has been engaged in an effort to reduce wind tunnel test cycle time in support of Agency goals and to satisfy the wind tunnel testing needs of the commercial and military aerospace communities. LaRC has established the Wind Tunnel Enterprise (WTE), with goals of reducing wind tunnel test cycle time by an order of magnitude by 2002, and by two orders of magnitude by 2010. The WTE also plans to meet customer expectations for schedule integrity, as well as data accuracy and quality assurance. The WTE has made progress towards these goals over the last year with a focused effort on technological developments balanced by attention to process improvements. This paper presents a summary of several of the WTE activities over the last year that are related to test cycle time reductions at the Center. Reducing wind tunnel test cycle time, defined here as the time between the freezing of loft lines and delivery of test data, requires that the relationship between high productivity and data quality assurance be considered. The efforts have focused on all of the drivers for test cycle time reduction, including process centered improvements, facility upgrades, technological improvements to enhance facility readiness and productivity, as well as advanced measurement techniques. The application of internet tools and computer modeling of facilities to allow a virtual presence of the customer team is also presented.

Progress Towards the Vindication of Panspermia

NASA Astrophysics Data System (ADS)

Wickramasinghe, N. C.; Wainwright, M.; Narlikar, J. V.; Rajaratnam, P.; Harris, M. J.; Lloyd, D.

Theories of panspermia are rapidly coming into vogue, with the possibility of the transfer of viable bacterial cells from one planetary abode to another being generally accepted as inevitable. The panspermia models of Hoyle and Wickramasinghe require the transfer of viable bacterial cells from interstellar dust to comets and back into interplanetary and interstellar space. In such a cycle a viable fraction of as little as 10-18 at the inception of a newly formed comet/planet system suffices for cometary panspermia to dominate over competing processes for the origin and transfer of life. The well-attested survival attributes of microbes under extreme conditions, which have recently been discovered, gives credence to the panspermia hypothesis. The prediction of the theory that comets bring microbes onto the Earth at the present time is testable if aseptic collections of stratospheric air above the tropopause can be obtained. We describe a recent collection of this kind and report microbiological analysis that shows the existence of viable cells at 41km, falling to Earth at the rate of a few tonnes per day over the entire globe. Some of these cells have been cultured in the laboratory and found to include microorganisms that are not too different from related species on the Earth. This is in fact what the Hoyle-Wickramasinghe theory predicts. The weight of evidence goes against the more conservative explanation that organisms are being lofted to the high atmosphere from the ground.

Quantification of Aerosol Derived Particulate Matter and Trace gases in the Coastal Belt of Kochi, Kerala, India

NASA Astrophysics Data System (ADS)

H, S. C.

2016-02-01

Aerosol chemistry is a window to unravel the various environmental health hazard problems. This open forum which deals with the study of formation, interaction, transformation of aerosol species, which could enable in the assessment of biogeochemical cycling of anthropogenic and toxic species. It also preserves the temperature balance and reservoir and sink for nutrients, trace metals and organic species. An inventory of air pollutants is a proactive and necessary first step towards the control of air pollution. Surveys and studies on the sources of pollution and their apportionment to different sources are a pre-requisite for alleviating environmental disorder. The Kochi City (The Queen of Arabian Sea), Kerala, India is a fast growing industrial region where mounting urbanization has been affecting the quality of the atmospheric environment. Cochin estuarine environment is progressively affected by marine pollution concomitant by industrial hazardous chemicals and municipal waste. Further, rapid urbanization and industrialization has lead to lofting and large scale advection of these omnipresent species in the atmosphere. Studies were conducted to assess the significance and potential impact occupied to these ubiquitous species. The major gaseous pollutants include gases like sulphur dioxide, nitrogen dioxide, ammonia and particulate matter (PM). An attempt was performed to unravel the inorganic species in the atmosphere and programmed by means of quantification of PM10 and trace gases. Their distribution pattern and outcomes are inferred.

48 CFR 2052.211-71 - Technical progress report.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Technical progress report... Technical progress report. As prescribed at 2011.104-70(b), the contracting officer shall insert the... solicitation. Technical Progress Report (JAN 1993) The contractor shall provide a monthly Technical Progress...

48 CFR 2052.211-71 - Technical progress report.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Technical progress report... Technical progress report. As prescribed at 2011.104-70(b), the contracting officer shall insert the... solicitation. Technical Progress Report (JAN 1993) The contractor shall provide a monthly Technical Progress...

48 CFR 2052.211-71 - Technical progress report.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Technical progress report... Technical progress report. As prescribed at 2011.104-70(b), the contracting officer shall insert the... solicitation. Technical Progress Report (JAN 1993) The contractor shall provide a monthly Technical Progress...

48 CFR 2052.211-71 - Technical progress report.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Technical progress report... Technical progress report. As prescribed at 2011.104-70(b), the contracting officer shall insert the... solicitation. Technical Progress Report (JAN 1993) The contractor shall provide a monthly Technical Progress...

Crevicular fluid biomarkers and periodontal disease progression.

PubMed

Kinney, Janet S; Morelli, Thiago; Oh, Min; Braun, Thomas M; Ramseier, Christoph A; Sugai, Jim V; Giannobile, William V

2014-02-01

Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). In this study, 100 individuals participated in a 12-month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi-monthly. Subgingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8, MMP-9, Osteoprotegerin, C-reactive Protein and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86). Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High doses of biotin in chronic progressive multiple sclerosis: a pilot study.

PubMed

Sedel, Frédéric; Papeix, Caroline; Bellanger, Agnès; Touitou, Valérie; Lebrun-Frenay, Christine; Galanaud, Damien; Gout, Olivier; Lyon-Caen, Olivier; Tourbah, Ayman

2015-03-01

No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. Uncontrolled, non-blinded proof of concept study 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Altered Orientation and Flight Paths of Pigeons Reared on Gravity Anomalies: A GPS Tracking Study

PubMed Central

Blaser, Nicole; Guskov, Sergei I.; Meskenaite, Virginia; Kanevskyi, Valerii A.; Lipp, Hans-Peter

2013-01-01

The mechanisms of pigeon homing are still not understood, in particular how they determine their position at unfamiliar locations. The “gravity vector” theory holds that pigeons memorize the gravity vector at their home loft and deduct home direction and distance from the angular difference between memorized and actual gravity vector. However, the gravity vector is tilted by different densities in the earth crust leading to gravity anomalies. We predicted that pigeons reared on different gravity anomalies would show different initial orientation and also show changes in their flight path when crossing a gravity anomaly. We reared one group of pigeons in a strong gravity anomaly with a north-to-south gravity gradient, and the other group of pigeons in a normal area but on a spot with a strong local anomaly with a west-to-east gravity gradient. After training over shorter distances, pigeons were released from a gravitationally and geomagnetically normal site 50 km north in the same direction for both home lofts. As expected by the theory, the two groups of pigeons showed divergent initial orientation. In addition, some of the GPS-tracked pigeons also showed changes in their flight paths when crossing gravity anomalies. We conclude that even small local gravity anomalies at the birth place of pigeons may have the potential to bias the map sense of pigeons, while reactivity to gravity gradients during flight was variable and appeared to depend on individual navigational strategies and frequency of position updates. PMID:24194860

Altered orientation and flight paths of pigeons reared on gravity anomalies: a GPS tracking study.

PubMed

Blaser, Nicole; Guskov, Sergei I; Meskenaite, Virginia; Kanevskyi, Valerii A; Lipp, Hans-Peter

2013-01-01

The mechanisms of pigeon homing are still not understood, in particular how they determine their position at unfamiliar locations. The "gravity vector" theory holds that pigeons memorize the gravity vector at their home loft and deduct home direction and distance from the angular difference between memorized and actual gravity vector. However, the gravity vector is tilted by different densities in the earth crust leading to gravity anomalies. We predicted that pigeons reared on different gravity anomalies would show different initial orientation and also show changes in their flight path when crossing a gravity anomaly. We reared one group of pigeons in a strong gravity anomaly with a north-to-south gravity gradient, and the other group of pigeons in a normal area but on a spot with a strong local anomaly with a west-to-east gravity gradient. After training over shorter distances, pigeons were released from a gravitationally and geomagnetically normal site 50 km north in the same direction for both home lofts. As expected by the theory, the two groups of pigeons showed divergent initial orientation. In addition, some of the GPS-tracked pigeons also showed changes in their flight paths when crossing gravity anomalies. We conclude that even small local gravity anomalies at the birth place of pigeons may have the potential to bias the map sense of pigeons, while reactivity to gravity gradients during flight was variable and appeared to depend on individual navigational strategies and frequency of position updates.

Evolution of the dust and water ice plume components as observed by the LCROSS visible camera and UV-visible spectrometer

NASA Astrophysics Data System (ADS)

Heldmann, Jennifer L.; Lamb, Justin; Asturias, Daniel; Colaprete, Anthony; Goldstein, David B.; Trafton, Laurence M.; Varghese, Philip L.

2015-07-01

The LCROSS (Lunar Crater Observation and Sensing Satellite) impacted the Cabeus crater near the lunar South Pole on 9 October 2009 and created an impact plume that was observed by the LCROSS Shepherding Spacecraft. Here we analyze data from the ultraviolet-visible spectrometer and visible context camera aboard the spacecraft. We use these data to constrain a numerical model to understand the physical evolution of the resultant plume. The UV-visible light curve peaks in brightness 18 s after impact and then decreases in radiance but never returns to the pre-impact radiance value for the ∼4 min of observation by the Shepherding Spacecraft. The blue:red spectral ratio increases in the first 10 s, decreases over the following 50 s, remains constant for approximately 150 s, and then begins to increase again ∼180 s after impact. Constraining the modeling results with spacecraft observations, we conclude that lofted dust grains remained suspended above the lunar surface for the entire 250 s of observation after impact. The impact plume was composed of both a high angle spike and low angle plume component. Numerical modeling is used to evaluate the relative effects of various plume parameters to further constrain the plume properties when compared with the observational data. Dust particle sizes lofted above the lunar surface were micron to sub-micron in size. Water ice particles were also contained within the ejecta cloud and simultaneously photo-dissociated and sublimated after reaching sunlight.

Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters

PubMed Central

2011-01-01

Background Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial. Methods Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients. Results Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm3, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively. Conclusions In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression. PMID:21831310

Salvage Stereotactic Body Radiotherapy for Isolated Lymph Node Recurrent Prostate Cancer: Single Institution Series of 94 Consecutive Patients and 124 Lymph Nodes.

PubMed

Jereczek-Fossa, Barbara Alicja; Fanetti, Giuseppe; Fodor, Cristiana; Ciardo, Delia; Santoro, Luigi; Francia, Claudia Maria; Muto, Matteo; Surgo, Alessia; Zerini, Dario; Marvaso, Giulia; Timon, Giorgia; Romanelli, Paola; Rondi, Elena; Comi, Stefania; Cattani, Federica; Golino, Federica; Mazza, Stefano; Matei, Deliu Victor; Ferro, Matteo; Musi, Gennaro; Nolè, Franco; de Cobelli, Ottavio; Ost, Piet; Orecchia, Roberto

2017-08-01

The purpose of the study was to evaluate the prostate serum antigen (PSA) response, local control, progression-free survival (PFS), and toxicity of stereotactic body radiotherapy (SBRT) for lymph node (LN) oligorecurrent prostate cancer. Between May 2012 and October 2015, 124 lesions were treated in 94 patients with a median dose of 24 Gy in 3 fractions. Seventy patients were treated for a single lesion and 25 for > 1 lesion. In 34 patients androgen deprivation (AD) was combined with SBRT. We evaluated biochemical response according to PSA level every 3 months after SBRT: a 3-month PSA decrease from pre-SBRT PSA of more than 10% identified responder patients. In case of PSA level increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6 to 9 months after SBRT. Median follow-up was 18.5 months. In 13 patients (14%) Grade 1 to 2 toxicity was reported without any Grade 3 to 4 toxicity. Biochemical response, stabilization, and progression were observed in 64 (68%), 10 (11%), and 20 (21%) of 94 evaluable patients. Clinical progression was observed in 31 patients (33%) after a median time of 8.1 months. In-field progression occurred in 12 lesions (9.7%). Two-year local control and PFS rates were 84% and 30%, respectively. Age older than 75 years correlated with better biochemical response rate. Age older than 75 years, concomitant AD administered up to 12 months, and pelvic LN involvement correlated with longer PFS. SBRT is safe and offers good in-field control. At 2 years after SBRT, 1 of 3 patients is progression-free. Further investigation is warranted to identify patients who benefit most from SBRT and to define the optimal combination with AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases.

PubMed

Robin, Tyler P; Breeze, Robert E; Smith, Derek E; Rusthoven, Chad G; Lewis, Karl D; Gonzalez, Rene; Brill, Amanda; Saiki, Robin; Stuhr, Kelly; Gaspar, Laurie E; Karam, Sana D; Raben, David; Kavanagh, Brian D; Nath, Sameer K; Liu, Arthur K

2018-06-16

Brain metastases are common in metastatic melanoma and radiosurgery is often utilized for local control. Immune checkpoint inhibitors (CPIs) play a central role in contemporary melanoma management; however, there is limited data exploring outcomes and potential toxicities for patients treated with CPIs and radiosurgery. We retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases (MBM) treated with Gamma Knife radiosurgery at a single institution between 2012 and 2017, and included only patients that initiated CPIs within 8 weeks before or after radiosurgery. Thirty-eight patients were included with a median follow-up of 31.6 months. Two-year local control was 92%. Median time to out-of-field CNS and extra-CNS progression were 8.4 and 7.9 months, respectively. Median progression-free survival (PFS) was 3.4 months and median overall survival (OS) was not reached (NR). Twenty-five patients (66%) received anti-CTLA4 and 13 patients (34%) received anti-PD-1+/-anti-CTLA4. Compared with anti-CTLA4, patients that received anti-PD-1+/-anti-CTLA4 had significant improvements in time to out-of-field CNS progression (p = 0.049), extra-CNS progression (p = 0.015), and PFS (p = 0.043), with median time to out-of-field CNS progression of NR vs. 3.1 months, median time to extra-CNS progression of NR vs. 4.4 months, and median PFS of 20.3 vs. 2.4 months. Six patients (16%) developed grade ≥ 2 CNS toxicities (grade 2: 3, grade 3: 3, grade 4/5: 0). Excellent outcomes were observed in patients that initiated CPIs within 8 weeks of undergoing radiosurgery for newly diagnosed MBM. There appears to be an advantage to anti-PD-1 or combination therapy compared to anti-CTLA4.

Sorafenib for the Treatment of Progressive Metastatic Medullary Thyroid Cancer: Efficacy and Safety Analysis.

PubMed

de Castroneves, Luciana Audi; Negrão, Marcelo Vailati; de Freitas, Ricardo Miguel Costa; Papadia, Carla; Lima, José Viana; Fukushima, Julia T; Simão, Eduardo Furquim; Kulcsar, Marco Aurélio Vamondes; Tavares, Marcos Roberto; Jorge, Alexander Augusto de Lima; de Castro, Gilberto; Hoff, Paulo Marcelo; Hoff, Ana Oliveira

2016-03-01

Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC. This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib. The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity. Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.

Exercise Improves Cognition in Parkinson’s Disease: the PRET-PD Randomized Clinical Trial

PubMed Central

David, Fabian J.; Robichaud, Julie A.; Leurgans, Sue E.; Poon, Cynthia; Kohrt, Wendy M.; Goldman, Jennifer G.; Comella, Cynthia L.; Vaillancourt, David E.; Corcos, Daniel M.

2015-01-01

Background This paper reports on the findings of the effect of two structured exercise interventions on secondary cognitive outcomes which were gathered as part of the Progressive Resistance Exercise Training in Parkinson’s disease randomized controlled trial. Methods This study was a prospective, parallel-group, single-center trial. Fifty-one non-demented patients with mild-to-moderate Parkinson’s disease were randomly assigned either to modified Fitness Counts or to Progressive Resistance Exercise, and were followed for 24 months. Cognitive outcomes were the Digit Span, Stroop, and Brief Test of Attention. Results Eighteen patients in modified Fitness Counts and 20 patients in Progressive Resistance Exercise completed the trial. At 12 and at 24 months no differences between groups were observed. At 12 months, relative to baseline, modified Fitness Counts improved on the Digit Span (estimated change, 0.3; Inter-Quartile Range, 0, 0.7; p=0.04) and Stroop (0.3; 0, 0.6; p=0.04), and Progressive Resistance Exercise improved only on the Digit Span (0.7; 0.3, 1; p<0.01). At 24 months, relative to baseline, modified Fitness Counts improved on the Digit Span (0.7; 0.3, 1.7; p<0.01) and Stroop (0.3; 0.1, 0.5; p=0.03), while Progressive Resistance Exercise improved on the Digit Span (0.5; 0.2, 0.8; p<0.01), Stroop (0.2; −0.1, 0.6; p=0.048), and Brief Test of Attention (0.3; 0, 0.8; p=0.048). No neurologic or cognitive adverse events were seen. Conclusions This study provides Class IV level of evidence that 24 months of Progressive Resistance Exercise or modified Fitness Counts may improve attention and working memory in non-demented patients with mild-to-moderate Parkinson’s disease. PMID:26148003

HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial.

PubMed

Ahmed, Nabil; Brawley, Vita; Hegde, Meenakshi; Bielamowicz, Kevin; Kalra, Mamta; Landi, Daniel; Robertson, Catherine; Gray, Tara L; Diouf, Oumar; Wakefield, Amanda; Ghazi, Alexia; Gerken, Claudia; Yi, Zhongzhen; Ashoori, Aidin; Wu, Meng-Fen; Liu, Hao; Rooney, Cliona; Dotti, Gianpietro; Gee, Adrian; Su, Jack; Kew, Yvonne; Baskin, David; Zhang, Yi Jonathan; New, Pamela; Grilley, Bambi; Stojakovic, Milica; Hicks, John; Powell, Suzanne Z; Brenner, Malcolm K; Heslop, Helen E; Grossman, Robert; Wels, Winfried S; Gottschalk, Stephen

2017-08-01

Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014. The duration of follow-up was 10 weeks to 29 months (median, 8 months). Monotherapy with autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus and genetically modified to express HER2-CARs with a CD28.ζ-signaling endodomain (HER2-CAR VSTs). Primary end points were feasibility and safety. The key secondary end points were T-cell persistence and their antiglioblastoma activity. A total of 17 patients (8 females and 9 males; 10 patients ≥18 years [median age, 60 years; range, 30-69 years] and 7 patients <18 years [median age, 14 years; range, 10-17 years]) with progressive HER2-positive glioblastoma received 1 or more infusions of autologous HER2-CAR VSTs (1 × 106/m2 to 1 × 108/m2) without prior lymphodepletion. Infusions were well tolerated, with no dose-limiting toxic effects. HER2-CAR VSTs were detected in the peripheral blood for up to 12 months after the infusion by quantitative real-time polymerase chain reaction. Of 16 evaluable patients (9 adults and 7 children), 1 had a partial response for more than 9 months, 7 had stable disease for 8 weeks to 29 months, and 8 progressed after T-cell infusion. Three patients with stable disease are alive without any evidence of progression during 24 to 29 months of follow-up. For the entire study cohort, median overall survival was 11.1 months (95% CI, 4.1-27.2 months) from the first T-cell infusion and 24.5 months (95% CI, 17.2-34.6 months) from diagnosis. Infusion of autologous HER2-CAR VSTs is safe and can be associated with clinical benefit for patients with progressive glioblastoma. Further evaluation of HER2-CAR VSTs in a phase 2b study is warranted as a single agent or in combination with other immunomodulatory approaches for glioblastoma.

Outcomes in patients with non-small-cell lung cancer and acquired Thr790Met mutation treated with osimertinib: a genomic study.

PubMed

Lin, Chia-Chi; Shih, Jin-Yuan; Yu, Chong-Jen; Ho, Chao-Chi; Liao, Wei-Yu; Lee, Jih-Hsing; Tsai, Tzu-Hsiu; Su, Kang-Yi; Hsieh, Min-Shu; Chang, Yih-Leong; Bai, Ya-Ying; Huang, Derek De-Rui; Thress, Kenneth S; Yang, James Chih-Hsin

2018-02-01

Osimertinib is approved for the treatment of non-small-cell lung cancer in patients who develop the EGFR Thr790Met mutation after treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). We assessed outcomes in patients with non-small-cell lung cancer and the EGFR Thr790Met mutation who were treated with osimertinib, a third-generation EGFR TKI, after previous treatment failure with one or more other EGFR TKIs. Eligible patients had been enrolled at one centre in the AURA study, had shown resistance to a previous EGFR TKI, and had EGFR-activating mutations and acquired Thr790Met mutation detectable in tumour tissue or plasma. Patients took 20-240 mg osimertinib per day until disease progression or development of intolerable side-effects. Plasma samples were collected every 6 weeks and tumour tissue biopsy was done at study entry and was optional after disease progression. We tested samples for resistance mechanisms, including EGFR-activating, Thr790Met, and Cys797Ser mutations, and assessed associations with overall survival, progression-free survival, and survival after disease progression. Of 71 patients enrolled in AURA, 53 were eligible for this analysis. Median progression-free survival was 11·1 months (95% CI 8·4-13·9) and overall survival was 16·9 months (11·7-29·1). 47 patients had disease progression. Median overall survival after osimertinib progression was 5·4 months (95% CI 4·1-10·0). Plasma samples were available for 40 patients after disease progression. 12 (30%) of these had the Thr790Met mutation (four of whom also had Cys797Ser mutations). Patients without detectable EGFR-activating mutations in plasma before treatment had the best overall and post-progression survival (22·4 months, 95% CI 15·6-not reached, and 10·8 months, 7·2-not reached, respectively). Loss of the Thr790Met mutation but presence of EGFR-activating mutations in plasma were associated with the shortest progression-free survival (median 2·6 months, 95% CI 1·3-not reached). In 22 post-progression tumour samples, we found one squamous cell and two small-cell transformations. We detected Thr790Met in nine (50%) of 18 samples, Cys797Ser in two (17%) of 12, cMET amplification in five (50%) of ten, BRAF mutation in one (8%) of 13, and KRAS mutation in one (8%) of 13. Heterogeneous resistance mechanisms developed in patients receiving osimertinib. Differences in resistance mechanisms might dictate future development strategies for osimertinib in clinical trials. AstraZeneca, Taiwan Ministry of Science and Technology. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Effects of 6 Months of Progressive High Effort Resistance Training Methods upon Strength, Body Composition, Function, and Wellbeing of Elderly Adults.

PubMed

Steele, James; Raubold, Kristin; Kemmler, Wolfgang; Fisher, James; Gentil, Paulo; Giessing, Jürgen

2017-01-01

The present study examined the progressive implementation of a high effort resistance training (RT) approach in older adults over 6 months and through a 6-month follow-up on strength, body composition, function, and wellbeing of older adults. Twenty-three older adults (aged 61 to 80 years) completed a 6-month supervised RT intervention applying progressive introduction of higher effort set end points. After completion of the intervention participants could choose to continue performing RT unsupervised until 6-month follow-up. Strength, body composition, function, and wellbeing all significantly improved over the intervention. Over the follow-up, body composition changes reverted to baseline values, strength was reduced though it remained significantly higher than baseline, and wellbeing outcomes were mostly maintained. Comparisons over the follow-up between those who did and those who did not continue with RT revealed no significant differences for changes in any outcome measure. Supervised RT employing progressive application of high effort set end points is well tolerated and effective in improving strength, body composition, function, and wellbeing in older adults. However, whether participants continued, or did not, with RT unsupervised at follow-up had no effect on outcomes perhaps due to reduced effort employed during unsupervised RT.

EVALUATION OF PATCHY ATROPHY SECONDARY TO HIGH MYOPIA BY SEMIAUTOMATED SOFTWARE FOR FUNDUS AUTOFLUORESCENCE ANALYSIS.

PubMed

Miere, Alexandra; Capuano, Vittorio; Serra, Rita; Jung, Camille; Souied, Eric; Querques, Giuseppe

2017-05-31

To evaluate the progression of patchy atrophy in high myopia using semiautomated software for fundus autofluorescence (FAF) analysis. The medical records and multimodal imaging of 21 consecutive highly myopic patients with macular chorioretinal patchy atrophy (PA) were retrospectively analyzed. All patients underwent repeated fundus autofluorescence and spectral domain optical coherence tomography over at least 12 months. Color fundus photography was also performed in a subset of patients. Total atrophy area was measured on FAF images using Region Finder semiautomated software embedded in Spectralis (Heidelberg Engineering, Heidelberg, Germany) at baseline and during follow-up visits. Region Finder was compared with manually measured PA on FAF images. Twenty-two eyes of 21 patients (14 women, 7 men; mean age 62.8 + 13.0 years, range 32-84 years) were included. Mean PA area using Region Finder was 2.77 ± 2.91 SD mm at baseline, 3.12 ± 2.68 mm at Month 6, 3.43 ± 2.68 mm at Month 12, and 3.73 ± 2.74 mm at Month 18 (overall P < 0.005); this accounts for PA progression rate of 0.821 mm/year. Atrophy progression was significantly greater among eyes with larger PA compared with smaller baseline PA at Months 6, 12, and 18. There was no statistically significant difference between semiautomated Region Finder PA area and manually measured PA area on FAF images. Fundus autofluorescence analysis by Region Finder semiautomated software provides accurate measurements of lesion area and allows us to quantify the progression of PA in high myopia. In our series, PA enlarged significantly over at least 12 months, and its progression seemed to be related to the lesion size at baseline.

Abiraterone and increased survival in metastatic prostate cancer.

PubMed

de Bono, Johann S; Logothetis, Christopher J; Molina, Arturo; Fizazi, Karim; North, Scott; Chu, Luis; Chi, Kim N; Jones, Robert J; Goodman, Oscar B; Saad, Fred; Staffurth, John N; Mainwaring, Paul; Harland, Stephen; Flaig, Thomas W; Hutson, Thomas E; Cheng, Tina; Patterson, Helen; Hainsworth, John D; Ryan, Charles J; Sternberg, Cora N; Ellard, Susan L; Fléchon, Aude; Saleh, Mansoor; Scholz, Mark; Efstathiou, Eleni; Zivi, Andrea; Bianchini, Diletta; Loriot, Yohann; Chieffo, Nicole; Kheoh, Thian; Haqq, Christopher M; Scher, Howard I

2011-05-26

Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy. We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate. After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate-prednisone group than in the placebo-prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate-prednisone group than in the placebo-prednisone group. The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 ClinicalTrials.gov number, NCT00638690.).

PSA response to cabazitaxel is associated with improved progression-free survival in metastatic castration-resistant prostate cancer: the non-interventional QoLiTime study.

PubMed

Hammerer, Peter; Al-Batran, Salah-Eddin; Windemuth-Kieselbach, Christine; Keller, Martin; Hofheinz, Ralf-Dieter

2018-03-01

To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. Men with mCRPC receiving cabazitaxel (25 mg/m 2 , every 3 weeks) plus oral prednis(ol)one (10 mg/day) were enrolled in the non-interventional, prospective QoLiTime study. Main outcome measures were progression-free survival and overall survival, in all patients and in those who showed a ≥ 50 or a ≥ 30% decrease in PSA relative to baseline after four cycles of cabazitaxel, as well as quality-of-life parameters. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P < 0.0001). Overall survival (50% cut-off) was 23.3 months in responders and 16.0 months in non-responders (P = 0.068); corresponding data at the 30% cut-off are 21.7 and 16.0 months (P = 0.057). Overall, 55.4% of men experienced ≥ 1 adverse event, 59.6% of whom had a serious adverse event. PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

Whole lung lavage: the salvage therapy for pulmonary alveolar proteinosis.

PubMed

Indira, K S Kumari; Rajesh, V; Darsana, V; Ranjit, U; John, Jiju; Vengadakrishnaraj, S P; Dharmadhikari, Shubhada Amol

2007-01-01

A 53-year-old school teacher presented with progressive exertional breathlessness and dry cough of three months duration. His diagnosis was confirmed as pulmonary alveolar proteinosis on open lung biopsy. In about three months, the disease progressed to life threatening respiratory failure. He was subjected to whole lung lavage (WLL) as a salvage therapy. The technical details of WLL performed on this patient are described. At six months follow up, he was clinically and functionally stable and leading a near normal life.

Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis.

PubMed

Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars; Dyrby, Tim B; Romme Christensen, Jeppe; Ammitzbøll, Cecilie; Madsen, Camilla Gøbel; Garde, Ellen; Lyksborg, Mark; Andersen, Birgit; Hyldstrup, Lars; Sørensen, Per Soelberg; Siebner, Hartwig R; Sellebjerg, Finn

2016-06-01

There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS. In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans. We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone. Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS. © The Author(s), 2015.

Eruptive history, petrology, and petrogenesis of the Joe Lott Tuff Member of the Mount Belknap Volcanics, Marysvale volcanic field, west-central Utah

USGS Publications Warehouse

Budding, Karin E.

1982-01-01

The Joe Lott Tuff Member of the Mount Belknap Volcanics is the largest rhyolitic ash-flow tuff sheet in the Marysvale volcanic field. It was erupted 19 m.y. ago, shortly after the changeover from intermediate-composition calc-alkalic volcanism to bimodal basalt-rhyolite volcanism. Eruption of the tuff resulted in the formation of the Mount Belknap Caldera whose pyroclastic intracaldera stratigraphy parallels that in the outflow facies. The Joe Loft Tuff Member is a composite ash-flow sheet that changes laterally from a simple cooling unit near the source to four distinct cooling units toward the distal end. The lowest of these units is the largest and most widespread; it is 64 m thick and contains a basal vitrophyre. Eruption of the lower unit led to the initial collapse of the caldera. The lower unit is followed upward by a 43 m middle unit, a 26 m pink-colored unit which is separated by a prominent air- fall layer, and a 31 m upper unit. The Joe Loft Tuff Member is an alkali rhyolite with 75.85-77.31 wt. % silica and 8.06-9.32 wt. % K2O+Na2O; the agpaitic index (Na2O+ K2O/Al2O3) is .77-.98. The tuff contains about I% phenocrysts of quartz, sanidine, oligoclase, augite, apatite, zircon, sphene, biotite, and oxidized Fe-Ti oxides. The basal vitrophyre contains accessory allanite, chevkinite, and magnesiohastingsite. The main cooling units are chemically and mineralogically zoned indicating that the magma chamber restratified prior to each major eruption. Within each of the two thickest cooling units, the mineralogy changes systematically upwards; the Or content and relative volume of sanidine decreases and An content of plagioclase increases. The basal vitrophyre of the lower unit has a bulk composition that lies in the thermal trough near the minima of Or-Ab-Q at 1 kb PH2O. Microprobe analyses of feldspar and chemical modeling on experimental systems indicate that pre-eruption temperatures were near 750?C and that the temperature increased during the eruption of the cooling units. The chemical gradients in the apatite and whole-rock data in the Joe Loft Tuff Member and the consistent mineral assemblages throughout the ash-flow cannot be explained by crystal settling. The fractionation of the Joe Lott Tuff Member appears to closer fit the model of convection-driven thermogravitational diffusion.

Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gan, Gregory N., E-mail: gregory.gan@ucdenver.edu; Weickhardt, Andrew J.; Scheier, Benjamin

Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progressionmore » meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.« less

Component Identification and Item Difficulty of Raven's Matrices Items.

ERIC Educational Resources Information Center

Green, Kathy E.; Kluever, Raymond C.

Item components that might contribute to the difficulty of items on the Raven Colored Progressive Matrices (CPM) and the Standard Progressive Matrices (SPM) were studied. Subjects providing responses to CPM items were 269 children aged 2 years 9 months to 11 years 8 months, most of whom were referred for testing as potentially gifted. A second…

In vivo measurements of tooth wear over 12 months.

PubMed

Rodriguez, J M; Austin, R S; Bartlett, D W

2012-01-01

The aim of this study was to measure the progression of tooth wear in a cohort of 63 patients, 43 males and 20 females with a mean age of 39.1 years. Recruitment followed referral from general practice to Guy's Hospital for advice/management of tooth wear. Addition silicone impressions were taken at 6-month intervals for a total of 12 months; impressions were subsequently poured in type IV gypsum. Casts were scanned using a non-contacting laser profilometer and then superimposed using Geomagic® Qualify 11. Wear was measured in μm by tooth per time interval. A questionnaire highlighting dietary, parafunctional and gastric risk factors was obtained from each participant. Clustered multiple regression analysis was used to determine the relationship between tooth wear progression and risk factors. Maximum follow-up times were 6 months for 63 participants and 12 months for 30 participants. The measurement error was 15 μm. At the tooth level, 72.2% of 1,078 teeth wore <15 μm over a 6-month period. At the subject level, 77.7% of 63 participants showed median wear <15 μm over a 6-month period. There was a statistical trend towards tooth wear progression being associated with gastric risk factors (p < 0.05). The lower molars and the upper anterior teeth were the most commonly affected teeth; the lower molars and the upper central incisors were the most severely affected teeth. Tooth wear progression was slow in this cohort, suggesting that tooth wear may be cyclical and inactive in the majority of participants. Copyright © 2011 S. Karger AG, Basel.

Progression-Free and Overall Survival of Patients With ALK Rearrangement-Positive Non-Small Cell Lung Cancer Treated Sequentially With Crizotinib and Alectinib.

PubMed

Watanabe, Satomi; Hayashi, Hidetoshi; Okamoto, Kunio; Fujiwara, Kimiko; Hasegawa, Yoshikazu; Kaneda, Hiroyasu; Tanaka, Kaoru; Takeda, Masayuki; Nakagawa, Kazuhiko

2016-11-01

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) show marked therapeutic efficacy in patients with non-small cell lung cancer (NSCLC) harboring the echinoderm microtubule-associated protein-like 4-ALK fusion gene. The effect on overall survival (OS) of sequential treatment with the first- and second-generation ALK-TKIs crizotinib and alectinib, respectively, has remained unknown. We have examined the clinical outcome of such sequential treatment in a retrospective analysis of patients with ALK-rearranged NSCLC. Eleven patients with ALK-rearranged NSCLC treated with crizotinib followed by alectinib were identified. The progression-free survival (PFS) and OS for these patients were determined from a retrospective review of their medical records. The median PFS on crizotinib or alectinib was 6.1 months (range, 1.0-15.4 months) and 15.2 months (range, 1.0-28.3 months), respectively. The median combined PFS for both crizotinib and alectinib was 18.2 months (range, 10.4-43.7 months). Crizotinib was continued beyond radiographic evidence of progressive disease in 6 of the 11 patients, with a median duration of postprogression crizotinib treatment of 9.4 months (range, 0-20.5 months). The OS period from the diagnosis of metastatic disease or the initiation of crizotinib treatment was 51.1 months (range, 20.9-69.5 months) and 48.6 months (range, 19.8-50.1 months), respectively. Our retrospective study has revealed durable survival for alectinib treatment after crizotinib failure in patients with ALK-rearranged NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

Everolimus for the Treatment of Advanced Pancreatic Neuroendocrine Tumors: Overall Survival and Circulating Biomarkers From the Randomized, Phase III RADIANT-3 Study.

PubMed

Yao, James C; Pavel, Marianne; Lombard-Bohas, Catherine; Van Cutsem, Eric; Voi, Maurizio; Brandt, Ulrike; He, Wei; Chen, David; Capdevila, Jaume; de Vries, Elisabeth G E; Tomassetti, Paola; Hobday, Timothy; Pommier, Rodney; Öberg, Kjell

2016-11-10

Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low- or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to open-label everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intent-to-treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85%) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95% CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95% CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95% CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of patients likely confounded the OS results.

Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study.

PubMed

Ou, Sai-Hong Ignatius; Ahn, Jin Seok; De Petris, Luigi; Govindan, Ramaswamy; Yang, James Chih-Hsin; Hughes, Brett; Lena, Hervé; Moro-Sibilot, Denis; Bearz, Alessandra; Ramirez, Santiago Viteri; Mekhail, Tarek; Spira, Alexander; Bordogna, Walter; Balas, Bogdana; Morcos, Peter N; Monnet, Annabelle; Zeaiter, Ali; Kim, Dong-Wan

2016-03-01

Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC. Alectinib 600 mg was administered orally twice daily. The primary end point was objective response rate (ORR) by central independent review committee (IRC). Of the 138 patients treated, 84 patients (61%) had CNS metastases at baseline, and 122 were response evaluable (RE) by IRC. ORR by IRC was 50% (95% CI, 41% to 59%), and the median duration of response (DOR) was 11.2 months (95% CI, 9.6 months to not reached). In 96 patients (79%) previously treated with chemotherapy, the ORR was 45% (95% CI, 35% to 55%). Median IRC-assessed progression-free survival for all 138 patients was 8.9 months (95% CI, 5.6 to 11.3 months). CNS disease control rate was 83% (95% CI, 74% to 91%), and the median CNS DOR was 10.3 months (95% CI, 7.6 to 11.2 months). CNS ORR in 35 patients with baseline measurable CNS lesions was 57% (95% CI, 39% to 74%). Of the 23 patients with baseline CNS metastases (measurable or nonmeasurable) and no prior radiation, 10 (43%) had a complete CNS response. At 12 months, the cumulative CNS progression rate (24.8%) was lower than the cumulative non-CNS progression rate (33.2%) for all patients. Common adverse events were constipation (33%), fatigue (26%), and peripheral edema (25%); most were grade 1 to 2. Alectinib is highly active and well tolerated in patients with advanced, crizotinib-refractory ALK-positive NSCLC, including those with CNS metastases. © 2015 by American Society of Clinical Oncology.

Advanced CRM training for instructors and evaluators

NASA Technical Reports Server (NTRS)

Taggart, William R.

1991-01-01

It is seen that if the maximum operational benefit of crew resource management (CRM) is to be achieved, the evaluator group is the principal key and specialized training that is ongoing is necessary for this group. The training must be customized to fit the needs of a particular organization, and the training must address key topical issues that influence organizational dynamics. Attention is given to the use of video and full length scripted NASA research LOFTS, behavioral markers and debriefing skills, the importance of policy and written CRM standards, and line oriented simulations debriefing performance indicators.

KSC-2011-6318

NASA Image and Video Library

2011-08-05

CAPE CANAVERAL, Fla. -- Reflected in water surrounding Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida, fire lights up a crystal-clear blue sky as a United Launch Alliance Atlas V rocket lofts NASA's Juno planetary probe into space. Liftoff was at 12:25 p.m. EDT Aug. 5. The solar-powered spacecraft will orbit Jupiter's poles 33 times to find out more about the gas giant's origins, structure, atmosphere and magnetosphere and investigate the existence of a solid planetary core. For more information, visit www.nasa.gov/juno. Photo credit: Courtesy Scott Andrews

KSC-2011-6313

NASA Image and Video Library

2011-08-05

CAPE CANAVERAL, Fla. -- Fire lights up a crystal-clear blue sky on Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida as a United Launch Alliance Atlas V rocket lofts NASA's Juno planetary probe into space. Liftoff was at 12:25 p.m. EDT Aug. 5. The solar-powered spacecraft will orbit Jupiter's poles 33 times to find out more about the gas giant's origins, structure, atmosphere and magnetosphere and investigate the existence of a solid planetary core. For more information, visit www.nasa.gov/juno. Photo credit: NASA/Tony Gray and Don Kight

KSC-2011-6311

NASA Image and Video Library

2011-08-05

CAPE CANAVERAL, Fla. -- Fire lights up a crystal-clear blue sky on Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida as a United Launch Alliance Atlas V rocket lofts NASA's Juno planetary probe into space. Liftoff was at 12:25 p.m. EDT Aug. 5. The solar-powered spacecraft will orbit Jupiter's poles 33 times to find out more about the gas giant's origins, structure, atmosphere and magnetosphere and investigate the existence of a solid planetary core. For more information, visit www.nasa.gov/juno. Photo credit: NASA/Tony Gray and Don Kight

KSC-2011-6317

NASA Image and Video Library

2011-08-05

CAPE CANAVERAL, Fla. -- Fire lights up a crystal-clear blue sky on Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida as a United Launch Alliance Atlas V rocket lofts NASA's Juno planetary probe into space. Liftoff was at 12:25 p.m. EDT Aug. 5. The solar-powered spacecraft will orbit Jupiter's poles 33 times to find out more about the gas giant's origins, structure, atmosphere and magnetosphere and investigate the existence of a solid planetary core. For more information, visit www.nasa.gov/juno. Photo credit: Courtesy Scott Andrews

KSC-2011-6312

NASA Image and Video Library

2011-08-05

CAPE CANAVERAL, Fla. -- Fire lights up a crystal-clear blue sky on Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida as a United Launch Alliance Atlas V rocket lofts NASA's Juno planetary probe into space. Liftoff was at 12:25 p.m. EDT Aug. 5. The solar-powered spacecraft will orbit Jupiter's poles 33 times to find out more about the gas giant's origins, structure, atmosphere and magnetosphere and investigate the existence of a solid planetary core. For more information, visit www.nasa.gov/juno. Photo credit: NASA/Tony Gray and Don Kight

The National Shipbuilding Research Program. Proceedings of the REAPS Technical Symposium (4th) held in New Orleans, Louisiana on 21-22 June, 1977

DTIC Science & Technology

1977-06-01

meeting. The Agenda in Appendix A lists topics and speakers, while Appendix B identifies Symposium attendees. TABLE OF CONTENTS Preface...225 253 271 I I T R E S E A R C H I N S T I T U T E 111 TABLE OF CONTENTS (Continued) Page USERS EXPERIENCE WITH REAPS SIMPLIFIED ALKON B.J. Breen...the development of computer graphics systems for ship design and lofting applications, software for marine transportation system economic analysis , and

Use and Design of an Active Data Dictionary for Local Validation of Input Data.

DTIC Science & Technology

1985-03-01

tl,--:selves ir tl~ce si tuations aire fro ~io-ntly lof~t to tlhcir ohfl Ipvices, an-. they aust 1.velo)p the ir own :r.tL i-,5 for v datinXL. inputs...progirams. Feijarltless off orijin, indocur.ite data aIre j’oi.;O.- in any -NTP ;-,,steni. Informa tion create.1 from inaccurite !Lta also tends to he...cLiect name, shcort name, syn%3nym or allases, source, narrative description, records/ filos that lise cr contain the lata object, data structure

Performance Tests of a Fast-Acting Valve for the Driver Tubes of a Large Blast/Thermal Simulator

DTIC Science & Technology

1992-05-01

ETVE. The lag time of the valve varied from 36 to 120 milliseconds from the time the fire signal was initiated to the time the first movement of the...ETVE Fire 2 ETVE Hall Effect 3 Pressure transducer in expansion tunnel at loft 4 Pressure transducer in expansion tunnel at 18ft 5 Pressure...be noted that the LED’s which were used during Phase I testing to indicate if the ETVE was ready to fire were disconnected by Eaton during Phase II

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL

PubMed Central

Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

2017-01-01

Background: Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Methods: Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Results: Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26–2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Conclusions: Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression. PMID:28117385

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

PubMed

Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

2017-06-01

Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.

Increasing Psychotherapists’ Adoption and Implementation of the Evidence-based Practice of Progress Monitoring

PubMed Central

Persons, Jacqueline B.; Koerner, Kelly; Eidelman, Polina; Thomas, Cannon; Liu, Howard

2015-01-01

Evidence-based practices (EBPs) reach consumers slowly because practitioners are slow to adopt and implement them. We hypothesized that giving psychotherapists a tool + training intervention that was designed to help the therapist integrate the EBP of progress monitoring into his or her usual way of working would be associated with adoption and sustained implementation of the particular progress monitoring tool we trained them to use (the Depression Anxiety Stress Scales on our Online Progress Tracking tool) and would generalize to all types of progress monitoring measures. To test these hypotheses, we developed an online progress monitoring tool and a course that trained psychotherapists to use it, and we assessed progress monitoring behavior in 26 psychotherapists before, during, immediately after, and 12 months after they received the tool and training. Immediately after receiving the tool + training intervention, participants showed statistically significant increases in use of the online tool and of all types of progress monitoring measures. Twelve months later, participants showed sustained use of any type of progress monitoring measure but not the online tool. PMID:26618237

Increasing psychotherapists' adoption and implementation of the evidence-based practice of progress monitoring.

PubMed

Persons, Jacqueline B; Koerner, Kelly; Eidelman, Polina; Thomas, Cannon; Liu, Howard

2016-01-01

Evidence-based practices (EBPs) reach consumers slowly because practitioners are slow to adopt and implement them. We hypothesized that giving psychotherapists a tool + training intervention that was designed to help the therapist integrate the EBP of progress monitoring into his or her usual way of working would be associated with adoption and sustained implementation of the particular progress monitoring tool we trained them to use (the Depression Anxiety Stress Scales on our Online Progress Tracking tool) and would generalize to all types of progress monitoring measures. To test these hypotheses, we developed an online progress monitoring tool and a course that trained psychotherapists to use it, and we assessed progress monitoring behavior in 26 psychotherapists before, during, immediately after, and 12 months after they received the tool and training. Immediately after receiving the tool + training intervention, participants showed statistically significant increases in use of the online tool and of all types of progress monitoring measures. Twelve months later, participants showed sustained use of any type of progress monitoring measure but not the online tool. Copyright © 2015 Elsevier Ltd. All rights reserved.

THE DEVELOPMENT OF PRE-VOCATIONAL EDUCATION LITERACY COURSES FOR USE WITH COMPUTER ASSISTED INSTRUCTION OF DISADVANTAGED YOUTH AND ADULTS. TECHNICAL PROGRESS REPORT.

ERIC Educational Resources Information Center

HANKIN, EDWARD K.; AND OTHERS

THIS TECHNICAL PROGRESS REPORT COVERS THE FIRST THREE MONTHS OF A PROJECT TO DEVELOP COMPUTER ASSISTED PREVOCATIONAL READING AND ARITHMETIC COURSES FOR DISADVANTAGED YOUTHS AND ADULTS. DURING THE FIRST MONTH OF OPERATION, PROJECT PERSONNEL CONCENTRATED ON SUCH ADMINISTRATIVE MATTERS AS TRAINING STAFF AND PREPARING FACILITIES. AN ARITHMETIC PROGRAM…

COSMIC monthly progress report

NASA Technical Reports Server (NTRS)

1994-01-01

Activities of the Computer Software Management and Information Center (COSMIC) are summarized for the month of January 1994. Tables showing the current inventory of programs available from COSMIC are presented and program processing and evaluation activities are discussed. Marketing and customer service activities in this period are presented as is the progress report of NASTRAN maintenance and support. Tables of disseminations and budget summary conclude the report.

miR-21 is associated with fibrosis and right ventricular failure

PubMed Central

Hu, Dong-Qing; Zhao, Mingming; Blay, Eddie; Sandeep, Nefthi; Ong, Sang-Ging; Jung, Gwanghyun; Kooiker, Kristina B.; Coronado, Michael; Fajardo, Giovanni; Bernstein, Daniel

2017-01-01

Combined pulmonary insufficiency (PI) and stenosis (PS) is a common long-term sequela after repair of many forms of congenital heart disease, causing progressive right ventricular (RV) dilation and failure. Little is known of the mechanisms underlying this combination of preload and afterload stressors. We developed a murine model of PI and PS (PI+PS) to identify clinically relevant pathways and biomarkers of disease progression. Diastolic dysfunction was induced (restrictive RV filling, elevated RV end-diastolic pressures) at 1 month after generation of PI+PS and progressed to systolic dysfunction (decreased RV shortening) by 3 months. RV fibrosis progressed from 1 month (4.4% ± 0.4%) to 3 months (9.2% ± 1%), along with TGF-β signaling and tissue expression of profibrotic miR-21. Although plasma miR-21 was upregulated with diastolic dysfunction, it was downregulated with the onset of systolic dysfunction), correlating with RV fibrosis. Plasma miR-21 in children with PI+PS followed a similar pattern. A model of combined RV volume and pressure overload recapitulates the evolution of RV failure unique to patients with prior RV outflow tract surgery. This progression was characterized by enhanced TGF-β and miR-21 signaling. miR-21 may serve as a plasma biomarker of RV failure, with decreased expression heralding the need for valve replacement. PMID:28469078

Progression-free survival/time to progression as a potential surrogate for overall survival in HR+, HER2- metastatic breast cancer.

PubMed

Forsythe, Anna; Chandiwana, David; Barth, Janina; Thabane, Marroon; Baeck, Johan; Tremblay, Gabriel

2018-01-01

Several recent randomized controlled trials (RCTs) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) have demonstrated significant improvements in progression-free survival (PFS); however, few have reported improvement in overall survival (OS). The surrogacy of PFS or time to progression (TTP) for OS has not been formally investigated in HR+, HER2- MBC. A systematic literature review of RCTs in HR+, HER2- MBC was conducted to identify studies that reported both median PFS/TTP and OS. The correlation between PFS/TTP and OS was evaluated using Pearson's product-moment correlation and Spearman's rank correlation. Subgroup analyses were performed to explore possible reasons for heterogeneity. Errors-in-variables weighted least squares regression (LSR) was used to model incremental OS months as a function of incremental PFS/TTP months. An exploratory analysis investigated the impact of three covariates (chemotherapy vs hormonal/targeted therapy, PFS vs TTP, and first-line therapy vs second-line therapy or greater) on OS prediction. The lower 95% prediction band was used to determine the minimum incremental PFS/TTP months required to predict OS benefit (surrogate threshold effect [STE]). Forty studies were identified. There was a statistically significant correlation between median PFS/TTP and OS (Pearson =0.741, P =0.000; Spearman =0.650, P =0.000). These results proved consistent for chemotherapy and hormonal/targeted therapy. Univariate LSR analysis yielded an R 2 of 0.354 with 1 incremental PFS/TTP month corresponding to 1.13 incremental OS months. Controlling the type of treatment (chemotherapy vs hormonal/targeted therapy), line of therapy (first vs subsequent), and progression measure (PFS vs TTP) led to an improved R 2 of 0.569 with 1 PFS/TTP month corresponding to 0.78 OS months. The STE for OS benefit was 5-6 months of incremental PFS/TTP. We demonstrated a significant association between PFS/TTP and OS, which may justify the use of PFS/TTP as a surrogate for OS benefit in HR+, HER2- MBC.

Clinicopathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax.

PubMed

Anderson, Mary Ann; Tam, Constantine; Lew, Thomas E; Juneja, Surender; Juneja, Manu; Westerman, David; Wall, Meaghan; Lade, Stephen; Gorelik, Alexandra; Huang, David C S; Seymour, John F; Roberts, Andrew W

2017-06-22

The BCL2 inhibitor venetoclax achieves responses in ∼79% of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (RR-CLL/SLL), irrespective of risk factors associated with poor response to chemoimmunotherapy. A limitation of this targeted therapy is progressive disease (PD) in some patients. To define the risk factors for progression, the clinicopathological features of PD, and the outcomes for patients after venetoclax failure, we analyzed 67 heavily pretreated patients on 3 early phase clinical trials. Investigations at progression included positron emission tomography scan and biopsy. Twenty-five (37%) patients manifested PD on therapy: 17 with Richter transformation (RT) and 8 with progressive CLL/SLL. RT occurred significantly earlier (median 7.9 months) than progressive CLL (median 23.4 months) ( P = .003). Among patients who received the recommended phase 2 dose of venetoclax or higher (≥400 mg/d), fludarabine refractoriness and complex karyotype were associated with progression (hazard ratio 7.01 [95% confidence interval 1.7-28.5]; P = .002 and 6.6 [1.5-29.8]; P = .005, respectively), whereas del(17p) and/or TP53 mutation were not ( P = .75). Median postprogression survival was 13 (<1-49.9) months. Bruton tyrosine kinase inhibitors were active in progressive CLL, but outcomes were mixed. Patients with disease that is fludarabine refractory or who have complex cytogenetics should have occult RT excluded before initiating venetoclax therapy. © 2017 by The American Society of Hematology.

Progress Towards Identifying and Quantifying the Organic Ice Nucleating Particles in Soils and Aerosols

NASA Astrophysics Data System (ADS)

Hill, T. C. J.; DeMott, P. J.; Fröhlich-Nowoisky, J.; Tobo, Y.; Suski, K. J.; Levin, E. J.; Kreidenweis, S. M.; Franc, G. D.

2014-12-01

Soil and plant surfaces emit ice nucleating particles (INP) to the atmosphere, especially when disturbed by wind, harvesting, rain or fire. Organic (biogenic) INP are abundant in most soils and dominate the population that nucleate >-15°C. For example, the sandy topsoil of sagebrush shrubland, a widespread ecotype prone to wind erosion after fire, contains ~106 organic INP g-1 at -6°C. The relevance of organic INP may also extend to colder temperatures than previously thought: Particles of soil organic matter (SOM) have been shown to be more important than mineral particles for the ice nucleating ability of agricultural soil dusts to -34°C. While the abundance of ice nucleation active (INA) bacteria on plants has been established, the identity of the organic INP in and emitted by soils remains a 40-year-old mystery. The need to understand their production and release is highlighted by recent findings that INA bacteria (measured with qPCR) account for few, if any, of the warm-temperature organic INP that predominate in boundary layer aerosols and snow; organic INP lofted with soil dusts seem a likely source. The complexity of SOM hinders its investigation. It contains decomposing plant materials, a diverse microbial and microfaunal community, humus, and inert organic matter. All are biochemically complex and all may contain ice nucleating constituents, either by design or by chance. Indeed the smoothness of the INP temperature spectra of soils is indicative of numerous, overlapping distributions of INP. We report recent progress in identifying and quantifying the organic INP in soils and boundary layer aerosols representative of West Central U.S. ecosystems, and how their characteristics may affect their dispersal. Chemical, enzymatic and DNA-based tests were used to assess contributions of INP from plant tissues, INA bacteria, INA fungi, organic crystals, monolayers of aliphatic alcohols, carbohydrates, and humic substances, while heat- and peroxide-based tests were used to estimate total organic INP abundance.

Knee Injuries Are Associated with Accelerated Knee Osteoarthritis Progression: Data from the Osteoarthritis Initiative

PubMed Central

Driban, Jeffrey B.; Eaton, Charles B.; Lo, Grace H.; Ward, Robert J.; Lu, Bing; McAlindon, Timothy E.

2014-01-01

Objective We aimed to evaluate if a recent knee injury was associated with accelerated knee osteoarthritis (KOA) progression. Methods In the Osteoarthritis Initiative (OAI) we studied participants free of KOA on their baseline radiographs (Kellgren-Lawrence [KL]<2). We compared three groups: 1) individuals with accelerated progression of KOA: defined as having at least one knee that progressed to end-stage KOA (KL Grade 3 or 4) within 48 months, 2) common KOA progression: at least one knee increased in radiographic scoring within 48 months (excluding those defined as accelerated KOA), and 3) no KOA: no change in KL grade in either knee. At baseline, participants were asked if their knees had ever been injured and at each annual visit they were asked about injuries during the prior 12 months. We used multinomial logistic regressions to determine if a new knee injury was associated with the outcome of accelerated KOA or common KOA progression after adjusting for age, sex, body mass index, static knee malalignment, and systolic blood pressure. Results A knee injury during the total observation period was associated with accelerated KOA progression (n=54, odds ratio [OR]=3.14) but not common KOA progression (n=187, OR=1.08). Furthermore, a more recent knee injury (within a year of the outcome) was associated with accelerated (OR=8.46) and common KOA progression (OR=3.12). Conclusion Recent knee injuries are associated with accelerated KOA. Most concerning is that certain injuries may be associated with a rapid cascade towards joint failure in less than one year. PMID:24782446

Letrozole in advanced breast cancer: the PO25 trial

PubMed Central

2007-01-01

Tamoxifen has been a standard first-line endocrine therapy for post-menopausal women with hormone-responsive advanced breast cancer, but more than half of patients fail to respond and time to progression is less than 12 months in responders. The third-generation aromatase inhibitors were developed to provide more effective alternatives to tamoxifen. In the Femara Study PO25, post-menopausal women with advanced breast cancer were randomized to receive letrozole 2.5 mg (n = 453) or tamoxifen 20 mg (n = 454) given orally daily until progressive disease occurred. Patients were permitted to cross over to the other treatment at progression. In the primary efficacy analysis, median time to progression (TTP) was significantly longer with letrozole than with tamoxifen (9.4 months vs. 6.0 months, respectively; P < 0.0001). The objective response rate (ORR) was significantly higher for letrozole than for tamoxifen (32% vs. 21%; P = 0.0002). Prospectively planned analyses of the intent-to-treat population showed that letrozole significantly improved overall survival (OS) compared with tamoxifen over the first 24 months of the trial. An exploratory analysis of patients, who did not cross over, indicated a median OS benefit of 14 months for letrozole compared with tamoxifen. Letrozole is the only third-generation aromatase inhibitor that has demonstrated significant improvements in ORR, TTP, and early OS. PMID:17333340

Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis.

PubMed

Pelzer, Uwe; Blanc, Jean-Frédéric; Melisi, Davide; Cubillo, Antonio; Von Hoff, Daniel D; Wang-Gillam, Andrea; Chen, Li-Tzong; Siveke, Jens T; Wan, Yin; Solem, Caitlyn T; Botteman, Marc F; Yang, Yoojung; de Jong, Floris A; Hubner, Richard A

2017-05-09

In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST). Mean Q-TWiST was calculated by weighting time spent by a utility of 1.0 for TWiST and 0.5 for TOX and REL. In threshold analyses, utility for TOX and REL were varied from 0.0 to 1.0. Patients in nal-IRI+5-FU/LV (n=117) vs 5-FU/LV (n=119) had significantly more mean time in TWiST (3.4 vs 2.4 months) and TOX (1.0 vs 0.3 months) but similar REL (2.5 vs 2.7 months). In the base case, nal-IRI+5-FU/LV patients had 1.3 months (95% CI, 0.4-2.1; 5.1 vs 3.9) greater Q-TWiST (threshold analyses range: 0.9-1.6 months). Within NAPOLI-1, nal-IRI+5-FU/LV resulted in statistically significant and clinically meaningful gains in quality-adjusted survival vs 5-FU/LV alone.

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy.

PubMed

Sehi, M; Bhardwaj, N; Chung, Y S; Greenfield, D S

2012-12-01

The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02-6.80, P=0.04), SLPECC inferior RNFLT (per -1 μm, HR=1.38, 95% CI: 1.02-2.2, P=0.02), and TDOCT inferior RNFLT (per -1 μm, HR=1.11, 95% CI: 1.04-1.2, P=0.001) had significant HRs for SAP progression. Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes.

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy

PubMed Central

Sehi, M; Bhardwaj, N; Chung, Y S; Greenfield, D S

2012-01-01

Purpose The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Methods Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Results Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02–6.80, P=0.04), SLPECC inferior RNFLT (per −1 μm, HR=1.38, 95% CI: 1.02–2.2, P=0.02), and TDOCT inferior RNFLT (per −1 μm, HR=1.11, 95% CI: 1.04–1.2, P=0.001) had significant HRs for SAP progression. Conclusion Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes. PMID:23060026

Progressive Occlusion of Small Saccular Aneurysms Incompletely Occluded After Stent-Assisted Coil Embolization : Analysis of Related Factors and Long-Term Outcomes.

PubMed

Lim, Jeong Wook; Lee, Jeongjun; Cho, Young Dae

2017-08-08

Incompletely occluded aneurysms after coil embolization are subject to recanalization but occasionally progress to a totally occluded state. Deployed stents may actually promote thrombosis of coiled aneurysms. We evaluated outcomes of small aneurysms (<10 mm) wherein saccular filling with contrast medium was evident after stent-assisted coiling, assessing factors implicated in subsequent progressive occlusion. Between September 2012 and June 2016, a total of 463 intracranial aneurysms were treated by stent-assisted coil embolization. Of these, 132 small saccular aneurysms displayed saccular filling with contrast medium in the immediate aftermath of coiling. Progressive thrombosis was defined as complete aneurysmal occlusion at the 6‑month follow-up point. Rates of progressive occlusion and factors predisposing to this were analyzed via binary logistic regression. In 101 (76.5%) of the 132 intracranial aneurysms, complete occlusion was observed in follow-up imaging studies at 6 months. Binary logistic regression analysis indicated that progressive occlusion was linked to smaller neck diameter (odds ratio [OR] = 1.533; p = 0.003), hyperlipidemia (OR = 3.329; p = 0.036) and stent type (p = 0.031). The LVIS stent is especially susceptible to progressive thrombosis, more so than Neuroform (OR = 0.098; p = 0.008) or Enterprise (OR = 0.317; p = 0.098) stents. In 57 instances of progressive thrombosis, followed for ≥12 months (mean 25.0 ± 10.7 months), 56 (98.2%) were stable, with minor recanalization noted once (1.8%) and no major recanalization. Aneurysms associated with smaller diameter necks, hyperlipidemic states and LVIS stent deployment may be inclined to possible thrombosis, if occlusion immediately after stent-assisted coil embolization is incomplete. In such instances, excellent long-term durability is anticipated.

Survival after failure of first-line chemotherapy in advanced gastric cancer patients: differences between Japan and the rest of the world.

PubMed

Takashima, Atsuo; Iizumi, Sakura; Boku, Narikazu

2017-07-01

In this review, we focus on post-progression survival after first-line chemotherapy of advanced gastric cancer, and particularly the differences between Japan and the rest of the world. We reviewed 15 recent phase III trials of which 4 were solely recruited from Japanese and 11 from rest of the world. The patient characteristics age, performance status, previous gastrectomy and the number of metastatic sites were similar in Japan and rest of the world. However, the diffuse histological type was more common in Japan. While overall survival was longer in Japan (10.5-14.1 vs. 7.9-12.2 months), progression-free survival tended to be shorter in Japan (3.6-6.0 vs. 3.1-7.4 months). Post-progression survival calculated as the difference between median overall survival and progression-free survival was clearly longer in Japan (6.9-8.6 vs. 2.4-6.2 months). The proportion of patients receiving second-line chemotherapy (%2nd-CX) was quite different in Japan and rest of the world (69-85% vs. 11-59%). Correlations between %2nd-CX and post-progression survival were strong (Spearman's rank correlation coefficient; ρ = 0.86, P < 0.001). Correlations between %2nd-CX and ratio of post-progression survival to total overall survival were also strong (ρ = 0.84, P < 0.001). Because a survival benefit of second-CX was documented in several phase III trials, it can be concluded that higher %2nd-CX partly contributed to extended post-progression survival. However, considering that second-CX increased survival only by ~1.5 months at median, other factors such as third-line chemotherapy may have some influences to prolonged post-progression survival. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Recurrent endometrial carcinoma: prognosis for patients with recurrence within 6 to 12 months is worse relative to those relapsing at 12 months or later.

PubMed

Miyake, Takahito; Ueda, Yutaka; Egawa-Takata, Tomomi; Matsuzaki, Shinya; Yokoyama, Takuhei; Miyoshi, Yukari; Kimura, Toshihiro; Yoshino, Kiyoshi; Fujita, Masami; Yamasaki, Masato; Enomoto, Takayuki; Kimura, Tadashi

2011-06-01

We evaluated association of prognosis of endometrial carcinoma patients and treatment-free intervals (TFIs). We compared the effectiveness of second-line chemotherapy performed for patients with TFIs of 6-12 months and 12 or more months following a first-line chemotherapy based on taxane (paclitaxel) and carboplatin, with or without the anthracycline (TC). Progression-free and overall survivals were significantly shorter in patients with TFIs of 6-12 months than those with TFIs of 12 or more months. Among the patients who received similar second-line chemotherapy, response rates of 15 patients with TFIs of 12 or more months and 7 patients with TFIs of 6-12 months were 67% and 43%, respectively. Progression-free survival was significantly worse in those with TFIs of 6-12 months (median, 7 months) than those with TFIs of 12 or more months (median, 12 months). Our small retrospective analysis suggests that recurrent endometrial carcinomas with TFIs of 6-12 months can be regarded as being partially sensitive to TC-based chemotherapy. Copyright © 2011 Mosby, Inc. All rights reserved.

78 FR 26215 - Jewish American Heritage Month, 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-03

... American Heritage Month, 2013 By the President of the United States of America A Proclamation In his second... American shores. We take this month to celebrate the progress that followed, and the bright future that... May 2013 as Jewish American Heritage Month. I call upon all Americans to visit www.JewishHeritageMonth...

Monitoring Indicators of Scholarly Language: A Progress-Monitoring Instrument for Measuring Narrative Discourse Skills

ERIC Educational Resources Information Center

Gillam, Sandra Laing; Gillam, Ronald B.; Fargo, Jamison D.; Olszewski, Abbie; Segura, Hugo

2017-01-01

The purpose of this study was to assess the basic psychometric properties of a progress-monitoring tool designed to measure narrative discourse skills in school-age children with language impairments (LI). A sample of 109 children with LI between the ages of 5 years 7 months and 9 years 9 months completed the "Test of Narrative Language"…

Progression of Structural Change in the Breast Cancer Genome

DTIC Science & Technology

2013-08-01

CNV !(months!143,!samples!have!already!been!approved!for!use)!.............................!6! 2b:!Develop!and!test!FISH!probes!to! detect !SMRT! CNV ...hormone+ therapy+resistance+–+likely+in+combination+with+some+of+the+other+mutations+identified+here.+ 2b:%Develop%and%test%FISH%probes%to% detect %SMRT% CNV ...4! Task!2:!Determine!impact!of!NCOR2/SMRT! CNV !on!breast!cancer!progression!(months!1424

Progress Monitoring in Reading: Comparison of Weekly, Bimonthly, and Monthly Assessments for Students at Risk for Reading Difficulties in Grades 2-4

ERIC Educational Resources Information Center

January, Stacy-Ann A.; Van Norman, Ethan R.; Christ, Theodore J.; Ardoin, Scott P.; Eckert, Tanya L.; White, Mary Jane

2018-01-01

The present study examined the utility of two progress monitoring assessment schedules (bimonthly and monthly) as alternatives to monitoring once weekly with curriculum-based measurement in reading (CBM-R). General education students (N = 93) in Grades 2-4 who were at risk for reading difficulties but not yet receiving special education services…

Comparative efficacy of disease-modifying therapies for patients with relapsing remitting multiple sclerosis: Systematic review and network meta-analysis.

PubMed

Fogarty, Emer; Schmitz, Susanne; Tubridy, Niall; Walsh, Cathal; Barry, Michael

2016-09-01

Randomised studies have demonstrated efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear how the magnitude of treatment efficacy varies across all currently available therapies. To perform a systematic review and network meta-analysis to evaluate the comparative efficacy of available therapies in reducing relapses and disability progression in RRMS. A systematic review identified 28 randomised, placebo-controlled and direct comparative trials. A network meta-analysis was conducted within a Bayesian framework to estimate comparative annualised relapse rates (ARR) and risks of disability progression (defined by both a 3-month, and 6-month confirmation interval). Potential sources of treatment-effect modification from study-level covariates and baseline risk were evaluated through meta-regression methods. The Surface Under the Cumulative RAnking curve (SUCRA) method was used to provide a ranking of treatments for each outcome. The magnitude of ARR reduction varied between 15-36% for all interferon-beta products, glatiramer acetate and teriflunomide, and from 50 to 69% for alemtuzumab, dimethyl fumarate, fingolimod and natalizumab. The risk of disability progression (3-month) was reduced by 19-28% with interferon-beta products, glatiramer acetate, fingolimod and teriflunomide, by 38-45% for pegylated interferon-beta, dimethyl fumarate and natalizumab and by 68% with alemtuzumab. Broadly similar estimates for the risk of disability progression (6-month), with the exception of interferon-beta-1b 250mcg which was much more efficacious based on this definition. Alemtuzumab and natalizumab had the highest SUCRA scores (97% and 95% respectively) for ARR, while ranking for disability progression varied depending on the definition of the outcome. Interferon-beta-1b 250mcg ranked among the most efficacious treatments for disability progression confirmed after six months (92%) and among the least efficacious when the outcome was confirmed after three months (30%). No significant modification of relative treatment effects was identified from study-level covariates or baseline risk. Compared with placebo, clear reductions in ARR with disease-modifying therapies were accompanied by more uncertain changes in disability progression. The magnitude of the reduction and the uncertainty associated with treatment effects varied between DMTs. While natalizumab and alemtuzumab demonstrated consistently high ranking across outcomes, with older interferon-beta and glatiramer acetate products ranking lowest, variation in disability progression definitions lead to variation in the relative ranking of treatments. Rigorously conducted comparative studies are required to fully evaluate the comparative treatment effects of disease modifying therapies for RRMS. Copyright © 2016 Elsevier B.V. All rights reserved.

Progressive Hearing Impairment in Children with Congenital Cytomegalovirus Infection.

ERIC Educational Resources Information Center

Dahle, Arthur J.; And Others

1979-01-01

Audiological assessment of 86 children (mean age 38 months at last evaluation time) with congenital cytomegalovirus infection revealed progressive hearing loss in four of 12 Ss with sensorineural hearing impairments. Case descriptions documented the progression of the hearing loss. (Author)

Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

PubMed

Desjardins, Annick; Quinn, Jennifer A; Vredenburgh, James J; Sathornsumetee, Sith; Friedman, Allan H; Herndon, James E; McLendon, Roger E; Provenzale, James M; Rich, Jeremy N; Sampson, John H; Gururangan, Sridharan; Dowell, Jeannette M; Salvado, August; Friedman, Henry S; Reardon, David A

2007-05-01

Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG). Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate. Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses. Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.

Saharan dust, convective lofting, aerosol enhancement zones, and potential impacts on ice nucleation in the tropical upper troposphere

NASA Astrophysics Data System (ADS)

Twohy, C. H.; Anderson, B. E.; Ferrare, R. A.; Sauter, K. E.; L'Ecuyer, T. S.; van den Heever, S. C.; Heymsfield, A. J.; Ismail, S.; Diskin, G. S.

2017-08-01

Dry aerosol size distributions and scattering coefficients were measured on 10 flights in 32 clear-air regions adjacent to tropical storm anvils over the eastern Atlantic Ocean. Aerosol properties in these regions were compared with those from background air in the upper troposphere at least 40 km from clouds. Median values for aerosol scattering coefficient and particle number concentration >0.3 μm diameter were higher at the anvil edges than in background air, showing that convective clouds loft particles from the lower troposphere to the upper troposphere. These differences are statistically significant. The aerosol enhancement zones extended 10-15 km horizontally and 0.25 km vertically below anvil cloud edges but were not due to hygroscopic growth since particles were measured under dry conditions. Number concentrations of particles >0.3 μm diameter were enhanced more for the cases where Saharan dust layers were identified below the clouds with airborne lidar. Median number concentrations in this size range increased from 100 l-1 in background air to 400 l-1 adjacent to cloud edges with dust below, with larger enhancements for stronger storm systems. Integration with satellite cloud frequency data indicates that this transfer of large particles from low to high altitudes by convection has little impact on dust concentrations within the Saharan Air Layer itself. However, it can lead to substantial enhancement in large dust particles and, therefore, heterogeneous ice nuclei in the upper troposphere over the Atlantic. This may induce a cloud/aerosol feedback effect that could impact cloud properties in the region and downwind.

Registers in Infant Phonation.

PubMed

Buder, Eugene H; McDaniel, Valerie F; Bene, Edina R; Ladmirault, Jennifer; Oller, D Kimbrough

2018-04-09

The primary vocal registers of modal, falsetto, and fry have been studied in adults but not per se in infancy. The vocal ligament is thought to play a critical role in the modal-falsetto contrast but is still developing during infancy (Tateya and Tateya, 2015). 41 Cover tissues are also implicated in the modal-fry contrast, but the low fundamental frequency (f o ) cutoff of 70 Hz, shared between genders, suggests a psychoacoustic basis for the contrast. Buder, Chorna, Oller, and Robinson (2008) 6 used the labels of "loft," "modal," and "pulse" for distinct vibratory regimes that appear to be identifiable based on spectrographic inspection of harmonic structure and auditory judgments in infants, but this work did not supply acoustic measurements to verify which of these nominally labeled regimes resembled adult registers. In this report, we identify clear transitions between registers within infant vocalizations and measure these registers and their transitions for f o and relative harmonic amplitudes (H1-H2). By selectively sampling first-year vocalizations, this manuscript quantifies acoustic patterns that correspond to vocal fold vibration types not previously cataloged in infancy. Results support a developmental basis for vocal registers, revealing that a well-developed ligament is not needed for loft-modal quality shifts as seen in harmonic amplitude measures. Results also reveal that a distinctively pulsatile register can occur in infants at a much higher f o than expected on psychoacoustic grounds. Overall results are consistent with cover tissues in infancy that are, for vibratory purposes, highly compliant and readily detached. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

PubMed Central

Herrick, Ariane L; Peytrignet, Sebastien; Lunt, Mark; Pan, Xiaoyan; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan J; Dinsdale, Graham; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon C; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jobanputra, Paresh; Jordan, Alison C; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja S; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susanna M; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

2018-01-01

Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. ‘Progressors’ were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). Results 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Conclusions Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. Trial registration number NCT02339441. PMID:29306872

Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms.

PubMed

Baum, Richard P; Kulkarni, Harshad R; Singh, Aviral; Kaemmerer, Daniel; Mueller, Dirk; Prasad, Vikas; Hommann, Merten; Robiller, Franz C; Niepsch, Karin; Franz, Holger; Jochems, Arthur; Lambin, Philippe; Hörsch, Dieter

2018-03-30

Peptide receptor radionuclide therapy (PRRT) of patients with somatostatin receptor expressing neuroendocrine neoplasms has shown promising results in clinical trials and a recently published phase III study. In our center, 2294 patients were screened between 2004 and 2014 by 68 Ga somatostatin receptor (SSTR) PET/CT. Intention to treat analysis included 1048 patients, who received at least one cycle of 90 Yttrium or 177 Lutetium-based PRRT. Progression free survival was determined by 68 Ga SSTR-PET/CT and EORTC response criteria. Adverse events were determined by CTCAE criteria. Overall survival (95% confidence interval) of all patients was 51 months (47.0-54.9) and differed significantly according to radionuclide, grading, previous therapies, primary site and functionality. Progression free survival (based on PET/CT) of all patients was 19 months (16.9-21), which was significantly influenced by radionuclide, grading, and origin of neuroendocrine neoplasm. Progression free survival after initial progression and first and second resumption of PRRT after therapy-free intervals of more than 6 months were 11 months (9.4-12.5) and 8 months (6.4-9.5), respectively. Myelodysplastic syndrome or leukemia developed in 22 patients (2.1%) and 5 patients required hemodialysis after treatment, other adverse events were rare. PRRT is effective and overall survival is favorable in patients with neuroendocrine neoplasms depending on the radionuclide used for therapy, grading and origin of the neuroendocrine neoplasm which is not exactly mirrored in progression free survival as determined by highly sensitive 68 Ga somatostatin receptor PET/CT using EORTC criteria for determining response to therapy.

Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms

PubMed Central

Baum, Richard P.; Kulkarni, Harshad R.; Singh, Aviral; Kaemmerer, Daniel; Mueller, Dirk; Prasad, Vikas; Hommann, Merten; Robiller, Franz C.; Niepsch, Karin; Franz, Holger; Jochems, Arthur; Lambin, Philippe; Hörsch, Dieter

2018-01-01

Introduction Peptide receptor radionuclide therapy (PRRT) of patients with somatostatin receptor expressing neuroendocrine neoplasms has shown promising results in clinical trials and a recently published phase III study. Methods In our center, 2294 patients were screened between 2004 and 2014 by 68Ga somatostatin receptor (SSTR) PET/CT. Intention to treat analysis included 1048 patients, who received at least one cycle of 90Yttrium or 177Lutetium-based PRRT. Progression free survival was determined by 68Ga SSTR-PET/CT and EORTC response criteria. Adverse events were determined by CTCAE criteria. Results Overall survival (95% confidence interval) of all patients was 51 months (47.0-54.9) and differed significantly according to radionuclide, grading, previous therapies, primary site and functionality. Progression free survival (based on PET/CT) of all patients was 19 months (16.9-21), which was significantly influenced by radionuclide, grading, and origin of neuroendocrine neoplasm. Progression free survival after initial progression and first and second resumption of PRRT after therapy-free intervals of more than 6 months were 11 months (9.4-12.5) and 8 months (6.4-9.5), respectively. Myelodysplastic syndrome or leukemia developed in 22 patients (2.1%) and 5 patients required hemodialysis after treatment, other adverse events were rare. Conclusion PRRT is effective and overall survival is favorable in patients with neuroendocrine neoplasms depending on the radionuclide used for therapy, grading and origin of the neuroendocrine neoplasm which is not exactly mirrored in progression free survival as determined by highly sensitive 68Ga somatostatin receptor PET/CT using EORTC criteria for determining response to therapy. PMID:29682195

A Southern California Perspective of the April, 1998 Trans-Pacific Asian Dust Event

NASA Technical Reports Server (NTRS)

Tratt, David M.; Frouin, Robert J.; Westphal, Douglas L.

1999-01-01

The Jet Propulsion Laboratory (JPL) coherent CO2 backscatter lidar has been in almost continuous operation since 1984 and has now accumulated a significant time-series database tracking the long-term and seasonal variability of backscatter from the atmospheric column above the Pasadena, Calif. locale. A particularly noteworthy episode observed by the lidar in 1998 was a particularly extreme instance of incursion by Asian-sourced dust during the closing days of April. Such events are not uncommon during the northern spring, when strong cold fronts and convection over the Asian interior deserts loft crustal material into the mid-troposphere whence it can be transported across the Pacific Ocean, occasionally reaching the continental US. However, the abnormal strength of the initiating storm in this case generated an atypically dense cloud of material which resulted in dramatically reduced visibility along the length of the Western Seaboard. These dust events are now recognized as a potentially significant, non-negligible radiative forcing influence. The progress of the April 1998 dust cloud eastward across the Pacific Ocean was initially observed in satellite imagery and transmitted to the broader atmospheric research community via electronic communications. The use of Internet technology in this way was effective in facilitating a rapid response correlative measurement exercise by numerous atmospheric observation stations throughout the western US and its success has resulted in the subsequent establishment of an ad hoc communications environment, data exchange medium, and mechanism for providing early-warning alert of other significant atmospheric phenomena in the future.

Proton Therapy for Reirradiation of Progressive or Recurrent Chordoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Mark W., E-mail: mmcdona2@iuhealth.org; Indiana University Health Proton Therapy Center, Bloomington, Indiana; Linton, Okechuckwu R.

2013-12-01

Purpose: To report the results in patients reirradiated with proton therapy for recurrent or progressive chordoma, with or without salvage surgery. Methods and Materials: A retrospective review of 16 consecutive patients treated from 2005 to 2012 was performed. All patients had received at least 1 prior course of radiation therapy to the same area, and all but 1 patient had at least 1 surgical resection for disease before receiving reirradiation. At the time of recurrence or progression, half of the patients underwent additional salvage surgery before receiving reirradiation. The median prior dose of radiation was 75.2 Gy (range, 40-79.2 Gy).more » Six patients had received prior proton therapy, and the remainder had received photon radiation. The median gross tumor volume at the time of reirradiation was 71 cm{sup 3} (range, 0-701 cm{sup 3}). Reirradiation occurred at a median interval of 37 months after prior radiation (range, 12-129 months), and the median dose of reirradiation was 75.6 Gy (relative biological effectiveness [RBE]) (range. 71.2-79.2 Gy [RBE]), given in standard daily fractionation (n=14) or hyperfractionation (n=2). Results: The median follow-up time was 23 months (range, 6-63 months); it was 26 months in patients alive at the last follow-up visit (range, 12-63 months). The 2-year estimate for local control was 85%, overall survival 80%, chordoma-specific survival 88%, and development of distant metastases 20%. Four patients have had local progression: 3 in-field and 1 marginal. Late toxicity included grade 3 bitemporal lobe radionecrosis in 1 patient that improved with hyperbaric oxygen, a grade 4 cerebrospinal fluid leak with meningitis in 1 patient, and a grade 4 ischemic brainstem stroke (out of radiation field) in 1 patient, with subsequent neurologic recovery. Conclusions: Full-dose proton reirradiation provided encouraging initial disease control and overall survival for patients with recurrent or progressive chordoma, although additional toxicities may develop with longer follow-up times.« less

A retrospective study of correlation of morphologic patterns, MIB1 proliferation index, and survival analysis in 134 cases of plasmacytoma.

PubMed

Ghodke, Kiran; Shet, Tanuja; Epari, Sridhar; Sengar, Manju; Menon, Hari; Gujral, Sumeet

2015-06-01

Plasmacytoma classified into solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) is characterized by infiltrate of plasma cells of diverse maturity and by their monoclonal immunoglobulin products. Both SPB and EMP represent different groups of neoplasm in terms of location, tumor progression, and overall survival rate. There is a need for features that indicate likelihood of myeloma in patients with plasmacytoma without other manifestations. This study was an attempt to study the morphologic patterns of plasmacytoma (SPB and EMP), MIB1 proliferation index, and correlation of these with clinicopathologic features and survival of the patients. The study group comprised of 134 cases of plasmacytoma (88 SPB and 46 EMP) over duration of 8 years and were graded as per Bartl's histologic grading system. Commonest site was vertebral body in SPB (36%) and upper aerodigestive tract in EMP (48%). On serum electrophoresis, overall M band was detected in 41% cases. Both SPB and EMP on histology revealed similar morphologic features. MIB1 proliferation index ranged from less than 1% to 80%. It was slightly higher in EMP in comparison with SPB (P value = .002). Seventy percent of cases, which progressed to multiple myeloma (MM) showed MIB1 labeling index more than 10%; however, it was not statistically significant in predicting the disease progression. With the median follow-up of 19 months (range, 1-99 months), 10 SPB had disease progression of which 7 converted to MM, and 3 developed EMP, with a median interval of 21 months (range, 8-75 months) for the development of MM and 3 months (range, 3-9 months) for the progression to EMP. Five-year survival for EMP varied by site, with poorest survival in brain/central nervous system EMP as compared with EMP at other sites. To conclude, grade and MIB1 proliferation index help in predicting aggressive course in plasmacytoma. Copyright © 2015 Elsevier Inc. All rights reserved.

Some dissociating factors in the analysis of structural and functional progressive damage in open-angle glaucoma.

PubMed

Hudson, C J W; Kim, L S; Hancock, S A; Cunliffe, I A; Wild, J M

2007-05-01

To identify the presence, and origin, of any "dissociating factors" inherent to the techniques for evaluating progression that mask the relationship between structural and functional progression in open-angle glaucoma (OAG). 23 patients (14 with OAG and 9 with ocular hypertension (OHT)) who had received serial Heidelberg Retina Tomograph (HRT II) and Humphrey Field Analyser (HFA) examinations for >or=5 years (mean 78.4 months (SD 9.5), range 60-101 months) were identified. Evidence of progressive disease was retrospectively evaluated in one eye of each patient using the Topographic Change Analysis (TCA) and Glaucoma Progression Analysis (GPA) for the HRT II and HFA, respectively. Six patients were stable by both techniques; four exhibited both structural and functional progression; seven exhibited structural progression, only, and six showed functional progression, only. Three types of dissociating factors were identified. TCA failed to identify progressive structural damage in the presence of advanced optic nerve head damage. GPA failed to identify progressive functional damage at stimulus locations, with sensitivities exhibiting test-retest variability beyond the maximum stimulus luminance of the perimeter, and where a perimetric learning effect was apparent. The three dissociating factors accounted for nine of the 13 patients who exhibited a lack of concordance between structural and functional progressive damage.

Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience.

PubMed

Leone, Francesco; Gatti, Marco; Massucco, Paolo; Colombi, Federica; Sperti, Elisa; Campanella, Delia; Regge, Daniele; Gabriele, Pietro; Capussotti, Lorenzo; Aglietta, Massimo

2013-01-15

Chemoradiotherapy (CRT) may render curative resection feasible in patients with locally advanced pancreatic carcinoma (LAPC). The authors previously demonstrated the achievement of significant disease control and a median survival of 14 months by CRT in patients with LAPC. In this study, they evaluated the use of induction chemotherapy followed by a CRT neoadjuvant protocol. Patients first received induction gemcitabine and oxaliplatin (GEMOX) (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)). Patients without disease progression then received gemcitabine twice weekly (50 mg/m(2) daily) concurrent with radiotherapy (50.4 grays) and were re-evaluated for resectability. Thirty-nine patients (15 with borderline resectable disease and 24 with unresectable disease) entered the study. The treatment was well tolerated. Disease control was obtained in 29 of 39 patients. Two patients progressed after GEMOX, and 7 progressed after CRT. After a median follow-up of 13 months, the median progression-free survival (PFS) was 10.2 months. The median PFS of patients with borderline resectable and unresectable disease was 16.6 and 9.1 months, respectively (P = .056). For the whole group, the median overall survival (OS) was 16.7 months (27.8 months for patients with borderline resectable disease, 13.3 for patients with unresectable disease; P = .045). Eleven patients (9 with borderline resectable disease and 2 with unresectable disease at diagnosis) underwent successful resection. Patients who underwent resection had a significantly longer median PFS compared with nonresected patients (19.7 months vs 7.6 months, respectively). The median OS among resected and nonresected patients was 31.5 months and 12.3 months, respectively (P < .001). The current results indicated that induction GEMOX followed by CRT is feasible in patients with LAPC. Both those with borderline resectable disease and those with unresectable disease received clinical benefit, a chance to obtain resectability, and improved survival. The authors concluded that this protocol warrants further evaluation. Copyright © 2012 American Cancer Society.

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

PubMed

Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

2016-11-01

Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

Vemurafenib beyond progression in a patient with metastatic melanoma: a case report.

PubMed

Grimaldi, Antonio M; Simeone, Ester; Palla, Marco; Festino, Lucia; Caracò, Corrado; Mozzillo, Nicola; Petrillo, Antonella; Muto, Paolo; Ascierto, Paolo A

2015-04-01

The prognosis of metastatic melanoma has changed markedly in recent years because of the advent of newer targeted therapies such as BRAF inhibitors. However, the response to BRAF inhibitor therapy is frequently nondurable in patients with advanced melanoma. Novel approaches are thus needed to overcome resistance to these agents and to improve the management of advanced melanoma patients after disease progression. Here, we present the case of a 44-year-old man diagnosed with advanced melanoma in July 2010, harboring a BRAF mutation. Melanoma progressed during first-line chemotherapy with dacarbazine, but showed significant benefit after the initiation of vemurafenib on August 2011. Six months later, the patient experienced disease progression in left-obturator lymphadenopathy; still, anti-BRAF treatment was continued together with stereotactic radiotherapy, and was interrupted only shortly for intestinal occlusion secondary to melanoma metastasis of the bowel. When his conditions were stable, after 1 month of vemurafenib treatment discontinuation, anti-BRAF therapy was reinitiated, with a positive outcome. Vemurafenib treatment was definitively discontinued for disease progression in the brain, peritoneum, lymph node, intestine, and skin in March 2013, after about 20 months from initiation, and the patient died a few weeks later. The clinical case presented here shows that treatment beyond progression with vemurafenib can yield a survival benefit in melanoma patients whose disease progresses in a few sites, which can be treated with locoregional therapies. This clinical strategy needs further validation in prospective clinical trials.

Behavioural characterisation of the alpha-mannosidosis guinea pig.

PubMed

Robinson, A J; Crawley, A C; Auclair, D; Weston, P F; Hirte, C; Hemsley, K M; Hopwood, J J

2008-01-25

alpha-Mannosidosis is a lysosomal storage disorder resulting from a functional deficiency of the lysosomal enzyme alpha-mannosidase. This deficiency results in the accumulation of various oligosaccharides in the lysosomes of affected individuals, causing somatic pathology and progressive neurological degeneration that results in cognitive deficits, ataxia, and other neurological symptoms. We have a naturally occurring guinea pig model of this disease which exhibits a deficiency of lysosomal alpha-mannosidase and has a similar clinical presentation to human alpha-mannosidosis. Various tests were developed in the present study to characterise and quantitate the loss of neurological function in alpha-mannosidosis guinea pigs and to follow closely the progression of the disease. General neurological examinations showed progressive differences in alpha-mannosidosis animals from approximately 1 month of age. Significant differences were observed in hind limb gait width from 2 months of age and significant cognitive (memory and learning) deficits were observed from 3 months of age. Evoked response tests showed an increase in somatosensory P1 peak latency in alpha-mannosidosis guinea pigs from approximately 2 months of age, as well as progressive hearing loss using auditory brainstem evoked responses. The alpha-mannosidosis guinea pig therefore appears to exhibit many of the characteristics of the human disease, and will be useful in evaluating therapies for treatment of central nervous system pathology.

Meniscal Extrusion Progresses Shortly after the Medial Meniscus Posterior Root Tear.

PubMed

Furumatsu, Takayuki; Kodama, Yuya; Kamatsuki, Yusuke; Hino, Tomohito; Okazaki, Yoshiki; Ozaki, Toshifumi

2017-12-01

Medial meniscus posterior root tears (MMPRT) induce medial meniscus extrusion (MME). However, the time-dependent extent of MME in patients suffering from the MMPRT remains unclear. This study evaluated the extent of MME after painful popping events that occurred at the onset of the MMPRT. Thirty-five patients who had an episode of posteromedial painful popping were investigated. All the patients were diagnosed as having an MMPRT by magnetic resonance imaging (MRI) within 12 months after painful popping. Medial meniscus body width (MMBW), absolute MME, and relative MME (100×absolute MME/MMBW) were assessed among three groups divided according to the time after painful popping events: early period (〈1 month), subacute period (1-3 months), and chronic period (4-12 months). In the early period, absolute and relative MMEs were 3.0 mm and 32.7%, respectively. Absolute MME increased up to 4.2 mm and 5.8 mm during the subacute and chronic periods, respectively. Relative MME also progressed to 49.2% and 60.3% in the subacute and chronic periods, respectively. This study demonstrated that absolute and relative MMEs increased progressively within the short period after the onset of symptomatic MMPRT. Our results suggest that early diagnosis of an MMPRT may be important to prevent progression of MME following the MMPRT.

Swollen joint count in psoriatic arthritis is associated with progressive radiological damage in hands and feet.

PubMed

Simon, P; Pfoehler, C; Bergner, R; Schreiber, M; Pfreundschuh, M; Assmann, G

2012-01-01

Psoriatic arthritis (PsA) may progress to joint damage. Determining clinical predictors of joint damage assessed by radiography is important. The aim of this study was to determine clinical factors as possible predictors for radiological damage in hands and feet of PsA patients with a 12-month follow-up. We conducted a retrospective study on 53 PsA patients who were taking disease-modifying anti-rheumatic drugs (DMARDs) and/or tumour necrosis factor (TNF)-alpha-blockers at a fixed dosage. The patients were observed in 118 follow-up visits (intervals of 12 months ± 3 months), according to a clinical and radiological protocol which included the documentation of the number of swollen and tender joints in hands and feet, the applied therapy, psoriasis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and global health assessment. Outcome was defined as radiographic damage of hands and feet (Ratingen score). For the statistical analysis the Chi-Square test for 2x2 crosstables (with Fisher's correction, as required) was used. Progressive radiological damage was more frequent among patients with an increasing swollen joint count (8 of 26 visits; 30.8%) than among those with a stable or decreased number of swollen joints (5 of 89 visits; 5.6%; p=0.001). The analysis of the patients stratified into the different treatment modalities resulted in a significant higher rate of radiological progress (20.8%) in patients on DMARD therapy compared with TNF-alpha blocking agents (0%) (p=0.009). During a 12-month follow-up of PsA patients, an increasing number of swollen joints heralds progression of radiological damage. TNF-alpha-blocker therapy appears to be superior to DMARDs in the protection from radiological progress.

Progression of diabetic retinopathy severity after treatment with dexamethasone implant: a 24-month cohort study the 'DR-Pro-DEX Study'.

PubMed

Iglicki, Matias; Zur, Dinah; Busch, Catharina; Okada, Mali; Loewenstein, Anat

2018-06-01

Intravitreal anti-vascular endothelial growth factor agents have been shown to reduce diabetic retinopathy (DR) progression; data on the effects of intravitreal corticosteroids on modifying disease severity are limited. This study evaluates the long-term effect of intravitreal dexamethasone implant (DEX) on the severity and progression of non-proliferative DR (NPDR). This was a retrospective cohort study. Sixty eyes from 60 consecutive patients with NPDR and diabetic macular edema (DME) treated with dexamethasone implant (DEX group) and 49 eyes from consecutive 49 patients without DME requiring observation only. Fundus angiography images from baseline and after 24 months were graded by two masked assessors into mild, moderate and severe NPDR and PDR, according to the ETDRS classification. Patients were followed up 1-3 and 4-6 months after each DEX implant. Re-treatment with DEX implant was on a pro re nata basis. Records were reviewed for performance of panretinal photocoagulation. Main outcome was as follows: change of DR ≥ 1 grade and progression to proliferative diabetic retinopathy (PDR). Three eyes (5%) in the DEX group and 43 (87.8%) eyes in the control group progressed to PDR (P < 0.0001). Twenty-five eyes (41.7%) in the DEX group but none in the control group demonstrated an improvement in DR severity (P < 0.0001). This study provides the first long-term evidence that DEX implant has the potential to not only delay progression of DR and PDR development, but may also improve DR severity over 24 months. Better understanding of the effects of corticosteroids will help guide its use in the treatment pathway of DR.

Durable brain response with pulse-dose crizotinib and ceritinib in ALK-positive non-small cell lung cancer compared with brain radiotherapy.

PubMed

Dudnik, Elizabeth; Siegal, Tali; Zach, Leor; Allen, Aaron M; Flex, Dov; Yust-Katz, Shlomit; Limon, Dror; Hirsch, Fred R; Peled, Nir

2016-04-01

Crizotinib achieves excellent systemic control in anaplastic lymphoma kinase-rearranged (ALK+) non-small cell lung cancer (NSCLC); however, central nervous system (CNS) metastases frequently occur as an early event. Whole brain irradiation, the standard treatment, results in neurocognitive impairment. We present a case series of three ALK+ NSCLC patients with progressing CNS metastases who were treated with pulse-dose crizotinib followed by ceritinib. Three ALK+ NSCLC patients treated between 2011 and 2014 (two males, two never smokers, age range 20-54years, all echinoderm microtubule-associated protein-like 4/ALK rearrangement), were diagnosed with progressing cerebral disease while receiving crizotinib. Clinico-pathological characteristics, treatments, and outcomes were analyzed. In two patients the progression was limited to the CNS, and radiological evidence of leptomeningeal spread was present in one patient. Sequential use of crizotinib 500mg administered once daily (pulse-dose) followed by ceritinib on progression achieved control of the disease in the CNS for over 18 months and over 7 months in Patient 1 and Patient 2, respectively. This strategy provided durable CNS control after whole-brain radiotherapy failure in Patient 1, and allowed the whole-brain radiotherapy to be deferred in Patient 2. Limited CNS progression was documented in Patient 3 while he was on standard-dose/pulse-dose crizotinib for 15months; durable (over 7 months) complete remission was achieved with stereotactic radiotherapy and ceritinib. Manipulating the crizotinib schedule in ALK+ NSCLC patients with CNS metastases and using a novel ALK-inhibitor at the time of further progression may provide durable CNS control and allow brain radiotherapy to be deferred. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of knee alignment in disease progression and functional decline in knee osteoarthritis.

PubMed

Sharma, L; Song, J; Felson, D T; Cahue, S; Shamiyeh, E; Dunlop, D D

2001-07-11

Knee osteoarthritis (OA) is a leading cause of disability in older persons. Few risk factors for disease progression or functional decline have been identified. Hip-knee-ankle alignment influences load distribution at the knee; varus and valgus alignment increase medial and lateral load, respectively. To test the hypotheses that (1) varus alignment increases risk of medial knee OA progression during the subsequent 18 months, (2) valgus alignment increases risk of subsequent lateral knee OA progression, (3) greater severity of malalignment is associated with greater subsequent loss of joint space, and (4) greater burden of malalignment is associated with greater subsequent decline in physical function. Prospective longitudinal cohort study conducted March 1997 to March 2000 at an academic medical center in Chicago, Ill. A total of 237 persons recruited from the community with primary knee OA, defined by presence of definite tibiofemoral osteophytes and at least some difficulty with knee-requiring activity; 230 (97%) completed the study. Progression of OA, defined as a 1-grade increase in severity of joint space narrowing on semiflexed, fluoroscopically confirmed knee radiographs; change in narrowest joint space width; and change in physical function between baseline and 18 months, compared by knee alignment at baseline. Varus alignment at baseline was associated with a 4-fold increase in the odds of medial progression, adjusting for age, sex, and body mass index (adjusted odds ratio [OR], 4.09; 95% confidence interval [CI], 2.20-7.62). Valgus alignment at baseline was associated with a nearly 5-fold increase in the odds of lateral progression (adjusted OR, 4.89; 95% CI, 2.13-11.20). Severity of varus correlated with greater medial joint space loss during the subsequent 18 months (R = 0.52; 95% CI, 0.40-0.62 in dominant knees), and severity of valgus correlated with greater subsequent lateral joint space loss (R = 0.35; 95% CI, 0.21-0.47 in dominant knees). Having alignment of more than 5 degrees (in either direction) in both knees at baseline was associated with significantly greater functional deterioration during the 18 months than having alignment of 5 degrees or less in both knees, after adjusting for age, sex, body mass index, and pain. This is, to our knowledge, the first demonstration that in primary knee OA varus alignment increases risk of medial OA progression, that valgus alignment increases risk of lateral OA progression, that burden of malalignment predicts decline in physical function, and that these effects can be detected after as little as 18 months of observation.

Realistic training for effective crew performance

NASA Technical Reports Server (NTRS)

Foushee, H. C.

1985-01-01

Evaluation of incident and accident statistics reveals that most problems occur not because of a lack of proficiency in pilot training, but because of the inability to coordinate skills into effective courses of action. Line-Oriented Flight Training (LOFT) and Cockpit Resource Management (CRM) programs provide training which will develop both individual crew member skills, as well as those associated with effective group function. A study conducted by NASA at the request of the U.S. Congress supports the argument for training that enhances crew performance in addition to providing individual technical skills, and is described in detail.

Pegasus - Winged workhorse

NASA Astrophysics Data System (ADS)

Furniss, Tim

1988-08-01

DARPA has initiated the development of a three-stage, solid-propellant air-launched booster for the lofting of small military satellites, or 'lightsats'. This vehicle, designated 'Pegasus', will because of its substantial endoatmospheric mission segment serve as a testbed for the validation of the CFD codes used by NASA as analytical tools in the design of the National Aerospace Plane. The three rocket stages are novel designs, incorporating such features as three-dimensionally woven carbon-carbon integral throat inserts and carbon-phenolic nozzles. The aircraft that will take Pegasus to launch altitude will be the B-52 previously used to launch the X-15.

A primer on clothing systems for cold-weather field work

USGS Publications Warehouse

Denner, J.C.

1993-01-01

Hypothermia in cold environments can be prevented by physiological adaptation and by the proper use of cold weather clothing. The human body adjusts to cold temperature by increasing the rates of basal metabolism, specific dynamic action, and physical exercise. Heat loss is reduced by vasoconstriction. Clothing systems for cold weather reduce loss by providing insulation and protection from the elements. Satisfactory cold- weather clothing is constructed of wool fabrics or the synthetic fibers polypropylene and polyester. Outerwear suitable for cold climates is insulated with down, high-loft polyester fiberfills, or the new synthetic thin insulators. (USGS)

CONTEXTUAL AERIAL VIEW OF "EXCLUSION" MTR AREA WITH IDAHO CHEMICAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONTEXTUAL AERIAL VIEW OF "EXCLUSION" MTR AREA WITH IDAHO CHEMICAL PROCESSING PLANT IN BACKGROUND AT CENTER TOP OF VIEW. CAMERA FACING EAST. EXCLUSION GATE HOUSE AT LEFT OF VIEW. BEYOND MTR BUILDING AND ITS WING, THE PROCESS WATER BUILDING AND WORKING RESERVOIR ARE LEFT-MOST. FAN HOUSE AND STACK ARE TO ITS RIGHT. PLUG STORAGE BUILDING IS RIGHT-MOST STRUCTURE. NOTE FAN LOFT ABOVE MTR BUILDING'S ONE-STORY WING. THIS WAS LATER CONVERTED FOR OFFICES. INL NEGATIVE NO. 3610. Unknown Photographer, 10/30/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma

PubMed Central

Iwamoto, F M.; Abrey, L E.; Beal, K; Gutin, P H.; Rosenblum, M K.; Reuter, V E.; DeAngelis, L M.; Lassman, A B.

2009-01-01

Background: Bevacizumab has recently been approved by the US Food and Drug Administration for recurrent glioblastoma (GBM). However, patterns of relapse, prognosis, and outcome of further therapy after bevacizumab failure have not been studied systematically. Methods: We identified patients at Memorial Sloan-Kettering Cancer Center with recurrent GBM who discontinued bevacizumab because of progressive disease. Results: There were 37 patients (26 men with a median age of 54 years). The most common therapies administered concurrently with bevacizumab were irinotecan (43%) and hypofractionated reirradiation (38%). The median overall survival (OS) after progressive disease on bevacizumab was 4.5 months; 34 patients died. At the time bevacizumab was discontinued for tumor progression, 17 patients (46%) had an increase in the size of enhancement at the initial site of disease (local recurrence), 6 (16%) had a new enhancing lesion outside of the initial site of disease (multifocal), and 13 (35%) had progression of predominantly nonenhancing tumor. Factors associated with shorter OS after discontinuing bevacizumab were lower performance status and nonenhancing pattern of recurrence. Additional salvage chemotherapy after bevacizumab failure was given to 19 patients. The median progression-free survival (PFS) among these 19 patients was 2 months, the median OS was 5.2 months, and the 6-month PFS rate was 0%. Conclusions: Contrast enhanced MRI does not adequately assess disease status during bevacizumab therapy for recurrent glioblastoma (GBM). A nonenhancing tumor pattern of progression is common after treatment with bevacizumab for GBM and is correlated with worse survival. Treatments after bevacizumab failure provide only transient tumor control. GLOSSARY CA9 = carbonic anhydrase 9; CI = confidence interval; FDG = [18F]fluorodeoxyglucose; FLAIR = fluid-attenuation inversion recovery; GBM = glioblastoma; HIF-1 α = hypoxia-inducible factor 1α; KPS = Karnofsky performance status; MR = magnetic resonance; OS = overall survival; PFS = progression-free survival; TMZ = temozolomide; VEGF = vascular endothelial growth factor; VEGFR = vascular endothelial growth factor receptor. PMID:19822869

Aberrant expression of copper associated genes after copper accumulation in COMMD1-deficient dogs.

PubMed

Favier, Robert P; Spee, Bart; Fieten, Hille; van den Ingh, Ted S G A M; Schotanus, Baukje A; Brinkhof, Bas; Rothuizen, Jan; Penning, Louis C

2015-01-01

COMMD1-deficient dogs progressively develop copper-induced chronic hepatitis. Since high copper leads to oxidative damage, we measured copper metabolism and oxidative stress related gene products during development of the disease. Five COMMD1-deficient dogs were studied from 6 months of age over a period of five years. Every 6 months blood was analysed and liver biopsies were taken for routine histological evaluation (grading of hepatitis), rubeanic acid copper staining and quantitative copper analysis. Expression of genes involved in copper metabolism (COX17, CCS, ATOX1, MT1A, CP, ATP7A, ATP7B, ) and oxidative stress (SOD1, catalase, GPX1 ) was measured by qPCR. Due to a sudden death of two animals, the remaining three dogs were treated with d-penicillamine from 43 months of age till the end of the study. Presented data for time points 48, 54, and 60 months was descriptive only. A progressive trend from slight to marked hepatitis was observed at histology, which was clearly preceded by an increase in semi-quantitative copper levels starting at 12 months until 42 months of age. During the progression of hepatitis most gene products measured were transiently increased. Most prominent was the rapid increase in the copper binding gene product MT1A mRNA levels. This was followed by a transient increase in ATP7A and ATP7B mRNA levels. In the sequence of events, copper accumulation induced progressive hepatitis followed by a transient increase in gene products associated with intracellular copper trafficking and temporal activation of anti-oxidative stress mechanisms. Copyright © 2014 Elsevier GmbH. All rights reserved.

ENGAGE: A Game Based Learning and Problem Solving Framework

DTIC Science & Technology

2012-07-13

Gamification Summit 2012  Mensa Colloquium 2012.2: Social and Video Games  Seattle Science Festival  TED Salon Vancouver : http...From - To) 6/1/2012 – 6/30/2012 4. TITLE AND SUBTITLE ENGAGE: A Game Based Learning and Problem Solving Framework 5a. CONTRACT NUMBER N/A 5b...Popović ENGAGE: A Game Based Learning and Problem Solving Framework (Task 1 Month 4) Progress, Status and Management Report Monthly Progress

76 FR 25519 - National Foster Care Month, 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-05

... Foster Care Month, 2011 By the President of the United States A Proclamation Progress in America can be... where they can feel secure and thrive. During National Foster Care Month, we renew our commitment to... possible for children when they cannot remain in their own homes. During National Foster Care Month, we...

Early MRI Detection and Closed Bone Graft Epiphysiodesis May Alter the Course of Avascular Necrosis Following Unstable Slipped Capital Femoral Epiphysis.

PubMed

Napora, Joshua K; Gilmore, Allison; Son-Hing, Jochen P; Grimberg, Dominic C; Thompson, George H; Liu, Raymond W

2018-04-01

Unstable slipped capital femoral epiphysis (SCFE) has an increased incidence of avascular necrosis (AVN). Early identification and surgical intervention for AVN may help preserve the femoral head. We retrospectively reviewed 48 patients (50 hips) with unstable SCFE managed between 2000 and 2014. AVN was diagnosed based on 2 different postoperative protocols. Seventeen patients (17 hips) had a scheduled magnetic resonance imaging (MRI) between 1 and 6 months from initial surgery, and the remaining 31 patients (33 hips) were evaluated by plain radiographs alone. If AVN was diagnosed, we offered core decompression and closed bone graft epiphysiodesis (CBGE) to mitigate its affects. At final follow-up, we assessed progression of AVN using the Steinberg classification. Overall 13 hips (26%) with unstable SCFEs developed AVN. MRI revealed AVN in 7 of 17 hips (41%) at a mean of 2.5 months postoperatively (range, 1.0 to 5.2 mo). Six hips diagnosed by MRI received surgical intervention (4 CBGE, 1 free vascularized fibula graft, and 1 repinning due to screw cutout) at a mean of 4.1 months (range, 1.3 to 7.2 mo) postoperatively. None of the 4 patients treated with CBGE within 2 months postoperatively progressed to stage IVC AVN. The 2 patients treated after 4 months postoperatively both progressed to stage VC AVN.Plain radiographs demonstrated AVN in 6 of 33 hips (18%) at a mean of 6.8 months postoperatively (range, 2.1 to 21.1 mo). One patient diagnosed with stage IVB AVN at 2.4 months had screw cutout and received CBGE at 2.5 months from initial pinning. The remaining 5 were not offered surgical intervention. Five of the 6 radiographically diagnosed AVN, including the 1 treated with CBGE, progressed to stage IVC AVN or greater. Although all patients with positive MRI scans developed radiographic AVN, none of the 4 patients treated with CBGE within 2 months after pinning developed grade IVC or greater AVN. Early MRI detection and CBGE may mitigate the effects of AVN after SCFE. Level III-retrospective comparative study.

NI-60RECURRENT PATTERNS OF BEVACIZUMAB MONOTHERAPY FOR RECURRENT PRIMARY GLIOBLASTOMA AND PERSPECTIVES ON BEVACIZUMAB-BASED THERAPIES

PubMed Central

Nagane, Motoo; Kobayashi, Keiichi; Saito, Kuniaki; Shiokawa, Yoshiaki

2014-01-01

BACKGROUND. Prognosis of patients with recurrent glioblastoma (GBM) remains dismal, their median overall survival (mOS) ranging from 7 to 10 months. Currently, bevacizumab (BEV), a monoclonal antibody against VEGF, has been widely used since it prolonged progression-free survival (PFS) accompanied with symptom relief in BEV trials. However, improvement of OS seems modest at most, and issues regarding short survival after BEV failure, invasive relapse, and difficulty in determining true progression remain unsolved. Here we examined the patterns of radiological BEV failure in relationship with survival of several post-treatment periods. METHODS. Twenty-five patients with primary GBM who were treated with BEV monotherapy at recurrence in Kyorin University hospital since August 2009 were included in this study. Mean age was 53 yo, 13 males/12 females, median KPS was 60 (30-100), and mOS from the initial surgery was 23.2 months. MRI patterns at BEV progression were determined using modified classification by Nowosielsky et al. (Neurology 2014) as follows: 1) T2-diffuse, 2) cT1-flare up, 3) Primary non-responders, 4) T2-circumscribed, and 5) Remote metastasis. RESULTS. mPFS and mOS of BEV monotherapy were 3.4 and 7.6 months, respectively, and post-BEV mOS was 4.7 months. Frequency and BEV-PFS/post-BEV OS were 1) 20%, 3.8/0.8 months; 2) 40%, 3.4/7.1 months, 3) 24%, 0.9/3.3 months, 4) 8%, 3.7/3.9 months, 5) 8%, 2.0/4.2 months. The cT1-flare up recurrent pattern was found most frequently with relatively better survivals, whereas the T2-diffuse recurrence included fatal brain stem invasion in two cases, resulting in poorer prognosis. CONCLUSIONS. BEV monotherapy showed limited survival benefit and the clinical course after BEV failure may differ by patterns of relapse. Although RANO criteria have been a standard method to determine progression, measurement of T2/FLAIR hyperintensity remains critically controversial. Efforts to improve BEV-based therapy for recurrent GBM including longitudinal and combined chemotherapy will be also discussed.

Vitamin D levels are associated with gross motor function in amyotrophic lateral sclerosis.

PubMed

Paganoni, Sabrina; Macklin, Eric A; Karam, Chafic; Yu, Hong; Gonterman, Fernando; Fetterman, K Ashley; Cudkowicz, Merit; Berry, James; Wills, Anne-Marie

2017-10-01

The objective of this study was to determine whether serum vitamin D [25(OH)D] levels are associated with disease progression in amyotrophic lateral sclerosis (ALS). 25(OH)D was measured in subjects enrolled in a multicenter study for validation of ALS biomarkers. Baseline 25(OH)D levels were correlated with baseline ALSFRS-R scores. Average 25(OH)D levels from baseline and month 6 visits (seasonally asynchronous) were used to predict subsequent rate of change in ALSFRS-R from month 6 to month 18. Most subjects had either insufficient or deficient 25(OH)D levels. Lower 25(OH)D was associated with lower ALSFRS-R gross motor scores, but not lower ALSFRS-R total scores at baseline. Levels of 25(OH)D were not predictive of disease progression over the next 12 months. 25(OH)D was associated with baseline gross motor ALSFRS-R scores but did not predict the rate of disease progression. Vitamin D levels may reflect poor mobility in patients with ALS. Muscle Nerve, 2017 Muscle Nerve 56: 726-731, 2017. © 2017 Wiley Periodicals, Inc.

Subacute ibuprofen treatment rescues the synaptic and cognitive deficits in advanced-aged mice

PubMed Central

Rogers, Justin T.; Liu, Chia-Chen; Zhao, Na; Wang, Jian; Putzke, Travis; Yang, Longyu; Shinohara, Mitsuru; Fryer, John D.; Kanekiyo, Takahisa; Bu, Guojun

2017-01-01

Aging is accompanied by increased neuroinflammation, synaptic dysfunction and cognitive deficits both in rodents and humans, yet the onset and progression of these deficits throughout the life span remain unknown. These aging-related deficits affect the quality of life and present challenges to our aging society. Here, we defined age-dependent and progressive impairments of synaptic and cognitive functions and showed that reducing astrocyte-related neuroinflammation through anti-inflammatory drug treatment in aged mice reverses these events. By comparing young (3 months), middle-aged (18 months), aged (24 months) and advanced-aged wild-type mice (30 months), we found that the levels of an astrocytic marker, GFAP, progressively increased after 18 months of age, which preceded the decreases of the synaptic marker PSD-95. Hippocampal long-term potentiation (LTP) was also suppressed in an age-dependent manner, where significant deficits were observed after 24 months of age. Fear conditioning tests demonstrated that associative memory in the context and cued conditions was decreased starting at the ages of 18 and 30 months, respectively. When the mice were tested on hidden platform water maze, spatial learning memory was significantly impaired after 24 months of age. Importantly, subacute treatment with the anti-inflammatory drug ibuprofen suppressed astrocyte activation, and restored synaptic plasticity and memory function in advanced-aged mice. These results support the critical contribution of aging-related inflammatory responses to hippocampal-dependent cognitive function and synaptic plasticity, in particular during advanced aging. Our findings provide strong evidence that suppression of neuroinflammation could be a promising treatment strategy to preserve cognition during aging. PMID:28254590

Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

PubMed Central

2012-01-01

Background Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. Methods We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment. Results Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively. Conclusions In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression. PMID:22943698

24 CFR 968.230 - Progress reports.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Progress reports. 968.230 Section 968.230 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... Fewer Than 250 Units) § 968.230 Progress reports. For each six-month period ending March 31 and...

40 CFR 35.1650-6 - Reports.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Reports. (a) States with Phase 1 projects shall submit semi-annual progress reports (original and one copy... in the next six months. (b) Phase 2. States with Phase 2 projects shall submit progress reports... Phase 2 project progress reports shall be determined by the size and complexity of the project, and...

40 CFR 35.1650-6 - Reports.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Reports. (a) States with Phase 1 projects shall submit semi-annual progress reports (original and one copy... in the next six months. (b) Phase 2. States with Phase 2 projects shall submit progress reports... Phase 2 project progress reports shall be determined by the size and complexity of the project, and...

Progression into Engineering. Building Bridges between Education, Training and Employment.

ERIC Educational Resources Information Center

Evans, Karen; And Others

This publication reports findings of a 12-month study of progression opportunities in engineering education and training, a study which explored ways of bridging the gap between skills and knowledge acquired through basic training and prevocational education and those required for progression to higher levels of occupational training and…

Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy.

PubMed

Krishnan, Sunil; Rana, Vishal; Janjan, Nora A; Varadhachary, Gauri R; Abbruzzese, James L; Das, Prajnan; Delclos, Marc E; Gould, Morris S; Evans, Douglas B; Wolff, Robert A; Crane, Christopher H

2007-07-01

The current study was conducted to determine whether there were differences in outcome for patients with unresectable locally advanced pancreatic cancer (LAPC) who received treatment with chemoradiation therapy (CR) versus induction chemotherapy followed by CR (CCR). Between December 1993 and July 2005, 323 consecutive patients with LAPC were treated at the authors' institution with radiotherapy and concurrent gemcitabine or fluoropyrimidine chemotherapy. Two hundred forty-seven patients received CR as initial treatment, and 76 patients received a median of 2.5 months of gemcitabine-based induction chemotherapy prior to CR. Most patients received a radiation dose of 30 grays in 10 fractions (85%) concurrently with infusional 5-fluorouracil (41%), gemcitabine (39%), or capecitabine (20%). The median follow-up was 5.5 months (range, 1-63 months). For all patients, the median overall survival (OS) and progression-free survival (PFS) were 9 months and 5 months, respectively, and the 2-year estimated OS and PFS rates were 9% and 5%, respectively. The median OS and PFS were 8.5 months and 4.2 months, respectively, in the CR group and 11.9 months and 6.4 months, respectively, in the CCR group (both P < .001). The median times to local and distant progression were 6.0 months and 5.6 months, respectively, in the CR group and 8.9 and 9.5 months, respectively, in the CCR group (P = .003 and P = .007, respectively). There was no significant difference in the patterns of failure with the use of induction chemotherapy. The results from this analysis indicated that, by excluding patients with rapid distant progression, induction chemotherapy may select patients with LAPC for optimal benefit from consolidative CR. The authors believe that this strategy of enriching the population of patients who receive a locoregional treatment modality merits prospective randomized evaluation. Copyright (c) 2007 American Cancer Society.

The impact of pre-intervention rate of kidney function change on the assessment of CKD progression.

PubMed

Fassett, Robert G; Geraghty, Dominic P; Coombes, Jeff S

2014-10-01

Without a run-in phase, chronic kidney disease (CKD) patients enrolled in clinical trials may not be identified as having progressive disease. The aim of this analysis was to quantify the effects of a run-in phase on kidney function outcome in CKD patients enrolled in the Lipid Lowering and Onset of Renal Disease (LORD) trial. The LORD trial assessed the effects of atorvastatin on the rate of change in the estimated glomerular filtration rate (eGFR) and included patients with serum creatinine 120 μmol/l. In this post hoc analysis, we assessed eGFR change during the 12-month period prior to enrolment, the 3-month run-in phase and the first 12-month period of the trial. Eighty of the original 132 patients (where retrospective data were available) were included. The rate of eGFR change during each period was compared. Overall kidney function decreased during the 12 months prior to enrolment by (mean, SD) 0.39 ± 0.98 ml/min/1.73 m(2)/month, improved during the 3-month run-in phase by 0.48 ± 2.90 ml/min/1.73 m(2)/month and decreased during the first 12 months of the trial by 0.15 ± 0.57 ml/min/1.73 m(2)/month. However, only 39 % of patients had declining eGFR during the 12 months prior, 19 % in the 3-month run-in and 42 % during the first 12-month study phase. Most patients (>60 %) entering this clinical trial had stable or improving kidney function. Enrolment was associated with further improved kidney function, which may have been due to 'regression to the mean' or to the Hawthorne effect. Investigators should include a run-in period to establish the presence of eGFR decline to use as an inclusion criterion in clinical trials assessing this measure of CKD progression.

Plasma D-dimer as a predictor of the progression of abdominal aortic aneurysm.

PubMed

Vele, E; Kurtcehajic, A; Zerem, E; Maskovic, J; Alibegovic, E; Hujdurovic, A

2016-11-01

Essentials D-dimer could provide important information about abdominal aortic aneurysm (AAA) progression. The greatest diameter of the infrarenal aorta and the value of plasma D-dimer were determined. AAA progression is correlated with increasing plasma D-dimer levels. The increasing value of plasma D-dimer could be a predictor of aneurysm progression. Background The natural course of abdominal aortic aneurysm (AAA) is mostly asymptomatic and unpredictable. D-dimer could provide potentially important information about subsequent AAA progression. Objectives The aims of this study were to establish the relationship between the progression of an abdominal aortic aneurysm (AAA) and plasma D-dimer concentration over a 12-month period and determine the value of plasma D-dimer in patients with sub-aneurysmal aortic dilatation. Patients/Methods This was a prospective observational study that involved 33 patients with an AAA, 30 patients with sub-aneurysmal aortic dilatation and 30 control subjects. The greatest diameter of the infrarenal aorta, which was assessed by ultrasound, and the value of plasma D-dimer were determined for all subjects at baseline assessment, as well as after 12 months for those with an AAA. Results A positive correlation was found between the diameter of an AAA and plasma D-dimer concentration at the baseline and the control measurement stages. There was a strong positive correlation between AAA progression and increasing plasma D-dimer concentration over a 12-month period. Among patients with sub-aneurysmal aortic dilatation (n = 30), the value of plasma D-dimer was higher compared with matched controls (n = 30). Conclusions There is a strongly positive correlation between AAA progression and increasing plasma D-dimer concentration. The value of plasma D-dimer is higher in patients with sub-aneurysmal aortic dilatation than in control subjects. © 2016 International Society on Thrombosis and Haemostasis.

Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein.

PubMed

Fleming, Sheila M; Salcedo, Jonathan; Fernagut, Pierre-Olivier; Rockenstein, Edward; Masliah, Eliezer; Levine, Michael S; Chesselet, Marie-Françoise

2004-10-20

Accumulation of alpha-synuclein in brain is a hallmark of synucleinopathies, neurodegenerative diseases that include Parkinson's disease. Mice overexpressing alpha-synuclein under the Thy-1 promoter (ASO) show abnormal accumulation of alpha-synuclein in cortical and subcortical regions of the brain, including the substantia nigra. We examined the motor deficits in ASO mice with a battery of sensorimotor tests that are sensitive to alterations in the nigrostriatal dopaminergic system. Male wild-type and ASO mice were tested every 2 months for 8 months for motor performance and coordination on a challenging beam, inverted grid, and pole, sensorimotor deficits in an adhesive removal test, spontaneous activity in a cylinder, and gait. Fine motor skills were assessed by the ability to grasp cotton from a bin. ASO mice displayed significant impairments in motor performance and coordination and a reduction in spontaneous activity as early as 2 months of age. Motor performance and coordination impairments became progressively worse with age and sensorimotor deficits appeared at 6 months. Fine motor skills were altered at 4 months and worsened at 8 months. These data indicate that overexpression of alpha-synuclein induced an early and progressive behavioral phenotype that can be detected in multiple tests of sensorimotor function. These behavioral deficits provide a useful way to assess novel drug therapy in genetic models of synucleinopathies.

Carbon ion radiotherapy performed as re-irradiation using active beam delivery in patients with tumors of the brain, skull base and sacral region.

PubMed

Combs, Stephanie E; Kalbe, Adriana; Nikoghosyan, Anna; Ackermann, Benjamin; Jäkel, Oliver; Haberer, Thomas; Debus, Jürgen

2011-01-01

To asses carbon ion radiation therapy (RT) performed as re-irradiation in 28 patients with recurrent tumors. Twenty-eight patients were treated with carbon ion RT as re-irradiation for recurrent chordoma and chondrosarcoma of the skull base (n=16 and n=2), one chordoma and one chondrosarcoma of the os sacrum, high-risk meningioma (n=3), adenoid-cystic carcinoma (n=4) as well as one SCCHN. All patients were treated using active raster scanning, and treatment planning was performed on CT- and MRI-basis. All patients were followed prospectively during follow-up. In all patients re-irradiation could be applied safely without interruptions. For skull base tumors, local tumor control after re-irradiation was 92% at 24 months and 64% at 36 months. Survival after re-irradiation was 86% at 24 months, and 43% at 60 months. In all three meningiomas treated with C12 for re-irradiation, the tumor recurrence was located within the former RT-field. Two patients developed tumor progression at 6 months, and in one patient the tumor remained stable for 67 months. In patients with head-and-neck tumors, three patients developed local tumor progression at 12, 24 and 29 months after re-irradiation. Median local progression-free survival was 24 months. For sacral tumors, re-irradiation offered palliation with tumor control for 24 and 36 months. Due to the physical characteristics particle therapy offers a new treatment modality in cases with tumor recurrences. With carbon ions, the additional biological benefits may be exploited for long-term tumor control. Further evaluation in a larger patients' cohort will be performed in the future. Copyright © 2010. Published by Elsevier Ireland Ltd.

{sup 18}F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohri, Nitin, E-mail: ohri.nitin@gmail.com; Bodner, William R.; Halmos, Balazs

Background: We previously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models. Methods: We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging {sup 18}F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapymore » dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size. Results: Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7 months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5 months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25 cc compared with 4% for lesions below 25 cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion. Conclusion: Pretreatment FDG-PET identifies lesions at risk for progression after CRT for locally advanced NSCLC. Strategies to improve local control should be tested on high-risk lesions, and treatment deintensification for low-risk lesions should be explored.« less

Pathological characteristics of spine metastases treated with high-dose single-fraction stereotactic radiosurgery.

PubMed

Katsoulakis, Evangelia; Laufer, Ilya; Bilsky, Mark; Agaram, Narasimhan P; Lovelock, Michael; Yamada, Yoshiya

2017-01-01

OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator-based single-fraction (18-24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36-80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6-50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7-86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2-70 months). CONCLUSIONS High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered.

Pathological characteristics of spine metastases treated with high-dose single-fraction stereotactic radiosurgery

PubMed Central

Katsoulakis, Evangelia; Laufer, Ilya; Bilsky, Mark; Agaram, Narasimhan P.; Lovelock, Michael; Yamada, Yoshiya

2017-01-01

OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may make it difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator–based single-fraction (18–24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36–80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6–50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7–86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2–70 months). CONCLUSIONS High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered. PMID:28041326

Reliability of chronic allograft nephropathy diagnosis in sequential protocol biopsies.

PubMed

Serón, Daniel; Moreso, Francesc; Fulladosa, Xavier; Hueso, Miguel; Carrera, Marta; Grinyó, Josep M

2002-02-01

Chronic allograft nephropathy (CAN) progresses rapidly during the first few months and slowly thereafter. Although the presence of CAN in protocol renal biopsies is a predictor of outcome, the reliability of this diagnosis according to Banff criteria has not been characterized. Renal lesions were evaluated according to the Banff criteria in sequential protocol biopsies performed at 4 and 14 months in 310 biopsies obtained from 155 patients. CAN progressed from 40 to 53% (P=0.001) while serum creatinine remained stable (146 +/- 44 vs. 147 +/- 48 micromol/L, P=NS). Graft survival in patients with and without CAN in the first biopsy was 74 versus 91% (P < 0.05), and in the second biopsy 75 versus 94% (P < 0.05). In 54 patients (35%) no CAN was present in both biopsies, 39 (25%) showed progression to CAN, 19 (12%) showed regression of CAN, and 43 (28%) showed CAN in both biopsies. Graft survival was: 100%, 81.6%, 82.6% and 69.4%, respectively (P < 0.01). Assuming that CAN does not regress and sampling error is normally distributed, we estimated that 25% of biopsies cannot be properly classified. The increase in the incidence of CAN between the 4th and 14th month is lower than the proportion of misclassified biopsies. Thus, monitoring the progression of CAN by means of two sequential biopsies at 4 and 14 months is inaccurate. We suggest that progression of scarring be monitored by means of a donor and a protocol biopsy performed during the first year evaluated with a quantitative approach.

Multicenter Phase II Trial of Temsirolimus and Bevacizumab in Pancreatic Neuroendocrine Tumors

PubMed Central

Hobday, Timothy J.; Qin, Rui; Reidy-Lagunes, Diane; Moore, Malcolm J.; Strosberg, Jonathan; Kaubisch, Andreas; Shah, Manisha; Kindler, Hedy Lee; Lenz, Heinz-Josef; Chen, Helen; Erlichman, Charles

2015-01-01

Purpose There are few effective therapies for pancreatic neuroendocrine tumors (PNETs). Recent placebo-controlled phase III trials of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the vascular endothelial growth factor (VEGF)/platelet-derived growth factor receptor inhibitor sunitinib have noted improved progression-free survival (PFS). Preclinical studies have suggested enhanced antitumor effects with combined mTOR and VEGF pathway–targeted therapy. We conducted a clinical trial to evaluate combination therapy against these targets in PNETs. Patients and Methods We conducted a two-stage single-arm phase II trial of the mTOR inhibitor temsirolimus 25 mg intravenously (IV) once per week and the VEGF-A monoclonal antibody bevacizumab 10 mg/kg IV once every 2 weeks in patients with well or moderately differentiated PNETs and progressive disease by RECIST within 7 months of study entry. Coprimary end points were tumor response rate and 6-month PFS. Results A total of 58 patients were enrolled, and 56 patients were eligible for response assessment. Confirmed response rate (RR) was 41% (23 of 56 patients). PFS at 6 months was 79% (44 of 56). Median PFS was 13.2 months (95% CI, 11.2 to 16.6). Median overall survival was 34 months (95% CI, 27.1 to not reached). For evaluable patients, the most common grade 3 to 4 adverse events attributed to therapy were hypertension (21%), fatigue (16%), lymphopenia (14%), and hyperglycemia (14%). Conclusion The combination of temsirolimus and bevacizumab had substantial activity and reasonable tolerability in a multicenter phase II trial, with RR of 41%, well in excess of single targeted agents in patients with progressive PNETs. Six-month PFS was a notable 79% in a population of patients with disease progression by RECIST criteria within 7 months of study entry. On the basis of this trial, continued evaluation of combination mTOR and VEGF pathway inhibitors is warranted. PMID:25488966

Crack-cocaine use accelerates HIV disease progression in a cohort of HIV-positive drug users.

PubMed

Baum, Marianna K; Rafie, Carlin; Lai, Shenghan; Sales, Sabrina; Page, Bryan; Campa, Adriana

2009-01-01

HIV infection is prevalent among substance abusers. The effects of specific illicit drugs on HIV disease progression have not been established. We evaluated the relationship between substances of abuse and HIV disease progression in a cohort of HIV-1-positive active drug users. A prospective, 30-month, longitudinal study was conducted on 222 HIV-1 seropositive drug users in Miami, FL. History of illicit drug, alcohol, and medication use, CD4+ cell count, and viral load were performed every 6 months. Crack-cocaine users were 2.14 times [95% confidence interval (CI): 1.08 to 4.25, P = 0.029] more likely to present a decline of CD4 to

Continued EGFR-TKI with concurrent radiotherapy to improve time to progression (TTP) in patients with locally progressive non-small cell lung cancer (NSCLC) after front-line EGFR-TKI treatment.

PubMed

Wang, Y; Li, Y; Xia, L; Niu, K; Chen, X; Lu, D; Kong, R; Chen, Z; Sun, J

2018-03-01

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment. Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression. Medical data were analyzed for time to progression (TTP), progression-free survival (PFS), tumor response rate, overall survival (OS) and adverse events. A total of 50 irradiated lesions from 44 patients were included. Median TTP and PFS of measurable lesions (n = 31) were both significantly prolonged after local radiotherapy (TTP1 + TTP2 vs. TTP1: 21.7 vs. 16.0 months, P = 0.010; PFS1 + PFS2 vs. PFS1: 21.3 vs. 16.0 months, P = 0.027). For all lesions (n = 50), objective response rate (ORR) and local tumor control rate (LCR) were 54.0 and 84.0%, respectively. Median OS was 26.6 months. There were no serious adverse events before or after radiotherapy. The treatment modality of CTCRT is considerable and effective for EGFR-mutant NSCLC patients even with local failure from front-line EGFR-TKI treatment.

A phase 2 study of vatalanib in metastatic melanoma patients.

PubMed

Cook, Natalie; Basu, Bristi; Biswas, Swethajit; Kareclas, Paula; Mann, Colette; Palmer, Cheryl; Thomas, Anne; Nicholson, Steve; Morgan, Bruno; Lomas, David; Sirohi, Bhawna; Mander, Adrian P; Middleton, Mark; Corrie, Pippa G

2010-10-01

A phase 2 study of vatalanib (PTK787/ZK222584) an oral tyrosine kinase inhibitor of VEGFR 1, 2 and 3 was undertaken in patients with metastatic melanoma. Adults with pathologically confirmed metastatic melanoma, WHO Performance status 0-2, and adequate haematological, hepatic and renal function, were treated with vatalanib until disease progression. The trial used Fleming's single stage design. Tumour control rate (CR+PR+SD) was 35% at 16 weeks, with objective response seen in only 1 patient. Median progression-free survival was 1.8 months (95% CI 1.8-3.7 months) and median overall survival was 6.5 months (95% CI 3.9-10.2 months). Vatalanib stabilised disease in a proportion of patients, although overall survival was disappointing. Copyright © 2010 Elsevier Ltd. All rights reserved.

Menogaril in the treatment of relapsed multiple myeloma. A phase II trial of the Cancer Center of Wake Forest University.

PubMed

Cruz, J M; Case, L D; Dalton, H B; Ramseur, W L; Richards, F; Jackson, D V; Muss, H B; Zekan, P J; Brodkin, R A; Brown, R C

1992-04-01

Fifteen patients with relapsed multiple myeloma (MM) were treated with menogaril 160 mg/m2 intravenously (IV) every 28 days. No responses were seen: 8 patients had stable disease, 4 progressed after one course of therapy, and 3 patients were removed from study after 1 course for other reasons. Four of the 8 patients with stable disease had an improved performance status, and 3 had a decrease in analgesic use. The major toxicity was myelosuppression. The median progression-free interval was 3.0 months with a range of 0.7 to 22 months and median survival was 11.3 months with a range of 0.7 to 39+ months. Menogaril displays little activity in patients with previously treated MM.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janssens, Geert O.R.J.; Gidding, Corrie E.M.; Lindert, Erik J. van

Purpose: Most children with a diffuse intrinsic brainstem glioma will die within 1 year after diagnosis. To reduce patient burden, we investigated the feasibility of a radical hypofractionation radiotherapy schedule, given over 3 weeks, as an alternative to the standard regimen (30 fractions over 6 weeks). Methods and Materials: Nine children, ages 3-13, were treated by 13 fractions of 3 Gy (n = 8) or 6 fractions of 5.5 Gy (n = 1) given over 3 weeks. All patients had symptoms for {<=}3 months and {>=}2 signs of the neurologic triad (long tract signs, ataxia, cranial nerve deficit). Bilateral involvementmore » of the pons (n = 8), encasement of the basilar artery (n = 7) and extension into the cerebellar peduncle (n = 6) was visible on magnetic resonance imaging. Results: Symptom improvement occurred in all patients within 2 weeks after start of radiotherapy. At a mean follow-up time of 15 months, 7 patients have died. Median time to progression and overall survival was 4.9 and 8.6 months, respectively. Median time to death after progression was 3.6 months. No Grade 3 or 4 toxicity was observed. In a recently published review of clinical trials, median time to progression, overall survival, and time between progression and death ranged from 5.0-8.8, 7.0-16, and 1.0-4.5 months, respectively, with more aggressive regimens. Conclusion: This radical hypofractionation radiotherapy regimen for children with diffuse intrinsic brainstem glioma is feasible and associated with no Grade 3 or 4 toxicities. With a minimal overall treatment time, it offers quick symptom relief and outcome results within the range of published data.« less

Glioblastoma Recurrence Patterns After Radiation Therapy With Regard to the Subventricular Zone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adeberg, Sebastian, E-mail: Sebastian.adeberg@med.uni-heidelberg; König, Laila; Bostel, Tilman

Purpose: We evaluated the influence of tumor location and tumor spread in primary glioblastoma (GBM), with respect to the subventricular zone (SVZ), on recurrence behavior, progression-free survival (PFS), and overall survival (OS). Methods and Materials: 607 patients (376 male and 231 female) with a median age of 61.3 years (range, 3.0-87.9 years) and primary GBM treated with radiation therapy (RT) from 2004 to 2012 at a single institution were included in this retrospective study. Preoperative images and follow-up examination results were assessed to evaluate tumor location. Tumors were classified according to the tumor location in relation to the SVZ. Results: The medianmore » PFS of the study population was 5.2 months (range, 1-91 months), and the median OS was 13.8 months (range, 1-102 months). Kaplan-Meier analysis showed that tumor location in close proximity to the SVZ was associated with a significant decline in PFS and OS (4.8 and 12.3 months, respectively; each P<.001). Furthermore, in cases where tumors were involved with the SVZ, distant cerebral progression (43.8%; P=.005) and multifocal progression (39.8%; P=.008) were more common. Interestingly, opening of the ventricle during the previous surgery showed no impact on PFS and OS. Conclusion: GBM in close proximity to the SVZ was associated with decreased survival and had a higher risk of multifocal or distant progression. Ventricle opening during surgery had no effect on survival rates.« less

Still a role for surgery as first-line therapy of splenic marginal zone lymphoma? Results of a prospective observational study.

PubMed

Pata, Giacomo; Bartoli, Michele; Damiani, Enrico; Solari, Stefano; Anastasia, Antonella; Pagani, Chiara; Tucci, Alessandra

2017-05-01

Assessment of hematologic improvement, survival and peri-operative morbidity after first-line splenectomy for splenic marginal zone lymphoma (SMZL). Forty-three patients undergoing open splenectomy were prospectively analyzed. Perioperative clinical course, overall and progression-free survival (OS-PFS) were evaluated. Risk factors analyzed were gender, age, ASA-grade, ECOG performance status, presence of B-symptoms, body mass index, steroidal treatment, serum albumin concentration, IIL-score, operative time, spleen size and weight. The median follow-up was 31 months (IQR 15-76; range 24-154). Anemia and thrombocytopenia resolved in 80% of patients at 6 months; in 60% at 2 years. The 5-year and 10-year PFS were 35% and 13% respectively, with a median of 35 months (shorter in patients with ECOG performance status ≥2 and B-symptoms). Nineteen cases (44.2%) had a progression of disease within 2 years. Of these, 14 (32.6%) received adjuvant chemotherapy (mainly R-FC or R-CVP). Progression was attributed to high-grade B lymphoma in 7 (16.3%) patients. The median time between diagnosis and progression to aggressive lymphoma was 25.5 months (range 18.8-81.8). The median time to next treatment was 83.5 months (95% CI 49-118). The 5-year and 10-year OS were 75% and 53% respectively. Mortality was due to disease progression and histological transformation in high-grade B lymphoma in 50% of cases, myelodisplastic syndrome in 15%, recurrence of hemolytic anemia in 15%, Hodgkin lymphoma in 7% and to infections (mainly pulmonary) in the remaining 13% of cases. Post-operative morbidity was 2.3% (1 patient with grade-3 complication). Overall grade ≥2 complication rate was 32.5% (mainly hemorrhagic and pulmonary complications). Spleen weight was the only independent risk factor for morbidity. Mortality was nil. Splenectomy is safe and effective as regards cytopenia resolution and OS, although disease progression is frequently observed at follow-up. Such results are strictly linked to accurate pre- and post-operative clinical management and optimal anesthesiologic approach. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Convective Transport of Very-short-lived Bromocarbons to the Stratosphere

NASA Technical Reports Server (NTRS)

Liang, Qing; Atlas, Elliot Leonard; Blake, Donald Ray; Dorf, Marcel; Pfeilsticker, Klaus August; Schauffler, Sue Myhre

2014-01-01

We use the NASA GEOS Chemistry Climate Model (GEOSCCM) to quantify the contribution of two most important brominated very short-lived substances (VSLS), bromoform (CHBr3) and dibromomethane (CH2Br2), to stratospheric bromine and its sensitivity to convection strength. Model simulations suggest that the most active transport of VSLS from the marine boundary layer through the tropopause occurs over the tropical Indian Ocean, the Western Pacific warm pool, and off the Pacific coast of Mexico. Together, convective lofting of CHBr3 and CH2Br2 and their degradation products supplies 8 ppt total bromine to the base of the Tropical Tropopause Layer (TTL, 150 hPa), similar to the amount of VSLS organic bromine available in the marine boundary layer (7.8-8.4 ppt) in the above active convective lofting regions. Of the total 8 ppt VSLS-originated bromine that enters the base of TTL at 150 hPa, half is in the form of source gas injection (SGI) and half as product gas injection (PGI). Only a small portion (< 10%) the VSLS-originated bromine is removed via wet scavenging in the TTL before reaching the lower stratosphere. On global and annual average, CHBr3 and CH2Br2, together, contribute 7.7 pptv to the present-day inorganic bromine in the stratosphere. However, varying model deep convection strength between maximum and minimum convection conditions can introduce a 2.6 pptv uncertainty in the contribution of VSLS to inorganic bromine in the stratosphere (BryVSLS). Contrary to the conventional wisdom, minimum convection condition leads to a larger BryVSLS as the reduced scavenging in soluble product gases, thus a significant increase in PGI (2-3 ppt), greatly exceeds the relative minor decrease in SGI (a few 10ths ppt.

Airborne detection of diffuse carbon dioxide emissions at Mammoth Mountain, California

USGS Publications Warehouse

Gerlach, T.M.; Doukas, M.P.; McGee, K.A.; Kessler, R.

1999-01-01

We report the first airborne detection of CO2 degassing from diffuse volcanic sources. Airborne measurement of diffuse CO2 degassing offers a rapid alternative for monitoring CO2 emission rates at Mammoth Mountain. CO2 concentrations, temperatures, and barometric pressures were measured at ~2,500 GPS-referenced locations during a one-hour, eleven-orbit survey of air around Mammoth Mountain at ~3 km from the summit and altitudes of 2,895-3,657 m. A volcanic CO2 anomaly 4-5 km across with CO2 levels ~1 ppm above background was revealed downwind of tree-kill areas. It contained a 1-km core with concentrations exceeding background by >3 ppm. Emission rates of ~250 t d-1 are indicated. Orographic winds may play a key role in transporting the diffusely degassed CO2 upslope to elevations where it is lofted into the regional wind system.We report the first airborne detection of CO2 degassing from diffuse volcanic sources. Airborne measurement of diffuse CO2 degassing offers a rapid alternative for monitoring CO2 emission rates at Mammoth Mountain. CO2 concentrations, temperatures, and barometric pressures were measured at approximately 2,500 GPS-referenced locations during a one-hour, eleven-orbit survey of air around Mammoth Mountain at approximately 3 km from the summit and altitudes of 2,895-3,657 m. A volcanic CO2 anomaly 4-5 km across with CO2 levels approximately 1 ppm above background was revealed downwind of tree-kill areas. It contained a 1-km core with concentrations exceeding background by >3 ppm. Emission rates of approximately 250 t d-1 are indicated. Orographic winds may play a key role in transporting the diffusely degassed CO2 upslope to elevations where it is lofted into the regional wind system.

ACCRETION DISK SIGNATURES IN TYPE I X-RAY BURSTS: PROSPECTS FOR FUTURE MISSIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keek, L.; Wolf, Z.; Ballantyne, D. R., E-mail: laurens.keek@nasa.gov

2016-07-20

Type I X-ray bursts and superbursts from accreting neutron stars illuminate the accretion disk and produce a reflection signal that evolves as the burst fades. Examining the evolution of reflection features in the spectra will provide insight into the burst–disk interaction, a potentially powerful probe of accretion disk physics. At present, reflection has been observed during only two bursts of exceptional duration. We investigate the detectability of reflection signatures with four of the latest well-studied X-ray observatory concepts: Hitomi , Neutron Star Interior Composition Explorer ( NICER ), Athena , and Large Observatory For X-ray Timing ( LOFT ). Burstmore » spectra are modeled for different values for the flux, temperature, and the disk ionization parameter, which are representative for most known bursts and sources. The effective area and throughput of a Hitomi -like telescope are insufficient for characterizing burst reflection features. NICER and Athena will detect reflection signatures in Type I bursts with peak fluxes ≳10{sup 7.5} erg cm{sup 2} s{sup 1} and also effectively constrain the reflection parameters for bright bursts with fluxes of ∼10{sup 7} erg cm{sup 2} s{sup 1} in exposures of several seconds. Thus, these observatories will provide crucial new insight into the interaction of accretion flows and X-ray bursts. For sources with low line-of-sight absorption, the wide bandpass of these instruments allows for the detection of soft X-ray reflection features, which are sensitive to the disk metallicity and density. The large collecting area that is part of the LOFT design would revolutionize the field by tracing the evolution of the accretion geometry in detail throughout short bursts.« less

Deep Convective Cloud Top Heights and Their Thermodynamic Control During CRYSTAL-FACE

NASA Technical Reports Server (NTRS)

Sherwood, Steven C.; Minnis, Patrick; McGill, Matthew

2004-01-01

Infrared (11 micron) radiances from GOES-8 and local radiosonde profiles, collected during the Cirrus Regional Study of Tropical Anvils and Cirrus Layers-Florida Area Cirrus Experiment (CRYSTAL-FACE) in July 2002, are used to assess the vertical distribution of Florida-area deep convective cloud top height and test predictions as to its variation based on parcel theory. The highest infrared tops (Z(sub 11)) reached approximately to the cold point, though there is at least a 1-km uncertainty due to unknown cloud-environment temperature differences. Since lidar shows that visible 'tops' are 1 km or more above Z(sub 11), visible cloud tops frequently penetrated the lapse-rate tropopause (approx. 15 km). Further, since lofted ice content may be present up to approx. 1 km above the visible tops, lofting of moisture through the mean cold point (15.4 km) was probably common. Morning clouds, and those near Key West, rarely penetrated the tropopause. Non-entraining parcel theory (i.e., CAPE) does not successfully explain either of these results, but can explain some of the day-to-day variations in cloud top height over the peninsula. Further, moisture variations above the boundary layer account for most of the day-today variability not explained by CAPE, especially over the oceans. In all locations, a 20% increase in mean mixing ratio between 750 and 500 hPa was associated with about 1 km deeper maximum cloud penetration relative to the neutral level. These results suggest that parcel theory may be useful for predicting changes in cumulus cloud height over time, but that parcel entrainment must be taken into account even for the tallest clouds. Accordingly, relative humidity above the boundary layer may exert some control on the height of the tropical troposphere.

Searching for Lunar Horizon Glow With the Lunar Orbiter Laser Altimeter (LOLA)

NASA Astrophysics Data System (ADS)

Barker, M. K.; Mazarico, E. M.; McClanahan, T. P.; Sun, X.; Smith, D. E.; Neumann, G. A.; Zuber, M. T.; Head, J. W., III

2017-12-01

The dust environment of the Moon is sensitive to the interplanetary meteoroid population and dust transport processes near the lunar surface, and this affects many aspects of lunar surface science and planetary exploration. The interplanetary meteoroid population poses a significant risk to spacecraft, yet it remains one of the more uncertain constituents of the space environment. Observed and hypothesized lunar dust transport mechanisms have included impact-generated dust plumes, electrostatic levitation, and dynamic lofting. Many details of the impactor flux and impact ejection process are poorly understood, a fact highlighted by recent discrepant estimates of the regolith mixing rate. Apollo-era observations of lunar horizon glow (LHG) were interpreted as sunlight forward-scattered by exospheric dust grains levitating in the top meter above the surface or lofted to tens of kilometers in altitude. However, recent studies have placed limits on the dust density orders of magnitude less than what was originally inferred, raising new questions on the time variability of the dust environment. Motivated by the need to better understand dust transport processes and the meteoroid population, the Lunar Orbiter Laser Altimeter (LOLA) aboard the Lunar Reconnaissance Orbiter (LRO) is conducting a campaign to search for LHG with the LOLA Laser Ranging (LR) system. Advantages of this LOLA LHG search include: (1) the LOLA-LR telescope can observe arbitrarily close to the Sun at any time during the year without damaging itself or the other instruments, (2) a long temporal baseline with observations both during and outside of meteor streams, which will improve the chances of detecting LHG, and (3) a focus on altitudes < 20 km, the same range as the majority of Apollo 15 LHG measurements. In this contribution, we describe the instrument, methodology, and preliminary results.

Experimental Study of Lunar Dust Transportation due to Electrostatic Forces and Micro-meteorite Impacts

NASA Astrophysics Data System (ADS)

Orger, N. C.; Toyoda, K.; Cho, M.

2017-12-01

Lunar dust particles can be transported via several physical mechanisms above the surface, and the electrostatic dust lofting was suspected to be the responsible mechanism for the high-altitude lunar horizon glow above the terminator region. Most of the recent studies have shown that contact forces acting on the dust grains of sub-micrometer and micrometer sizes are much larger than the electrostatic forces resulting from the ambient plasma conditions; however, the electrostatic forces are strong enough to accelerate the lunar dust grains to high altitudes once the dust particles are separated from the surface by an initial mechanism. In this study our purpose is to investigate if the dust particles can be transported under the electrostatic forces after they are released from the surface by the micrometeorite impacts. It is expected to be the most of the dust grains will be launched from the elastic deformation regions, and the contact forces will be canceled after they are moved tens of nanometers. For the experiments, silica particles are used in a cavity with 2 cm diameter and 5 mm depth on the graphite plates. First, the dust particles are baked under an infrared lamp to release the absorbed atmospheric particles in the vacuum chamber. Second, the electron beam source emits electrons with 100 - 200 eV energies, and a Faraday cup measures the electron current in the vacuum chamber. Third, a laser beam is used to simulate micro-meteorite impacts, and the results are monitored with a high speed camera mostly focusing on the elastic deformation region. Therefore, this study investigates how the impacts modify the dust transportation as an initial mechanism for electrostatic dust lofting to high altitudes.

Time Variability of the Dust Sublimation Zones in Pre-Main Sequence Disk Systems

NASA Technical Reports Server (NTRS)

Sitko, Michael L.; Carpenter, W. J.; Grady, C. A.; Russel, R. W.; Lynch, D. K.; Rudy, R. J.; Mazuk, S. M.; Venturini, C. C.; Kimes, R. L.; Beerman, L. C.;

A climatology of stratospheric aerosol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hitchman, M.H.; Mckay, M.; Trepte, C.R.

1994-10-01

A global climatology of stratospheric aerosol is created by combining nearly a decade (1979-1981 and 1984-1990) of contemporaneous observations from the Stratospheric Aerosol and Gas Experiment (SAGE I and II) and Stratospheric Aerosol Measurement (SAM II) instruments. One goal of this work is to provide a representative distribution of the aerosol layer for use in radiative and chemical modeling. A table of decadal average 1 micron extinction values is included, extending from the tropopause to 35 km and 80 deg S to 85 deg N, which allows estimation of surface area density. We find that the aerosol layer is distinctlymore » volcanic in nature and suggest that the decadal average is a more useful estimate of future aerosol loading than a `background` loading, which is never clearly achieved during the data record. This climatology lends insight into the general circulation of the stratosphere. Latitude - altitude sections of extinction radio at 1 micron are shown, average by decade, season, and phase of the quasi-biennial oscillation (QBO). A tropical reservoir region is diagnosed, with an `upper` and a `lower` transport regime. In the tropics above 22 km (upper regime), enhanced lofting occurs in the summer, with suppressed lofting or eddy dilution in the winter. In the extratropics within two scale heights of the tropopause (lower regime), poleward and downward transport is most robust during winter, especially in the northern hemisphere. The transport patterns persist into the subsequent equinoctial season. Ascent associated with QBO easterly shear favors detrainment in the upper regime, while relative descent and poleward spreading during QBO westerly shear favors detrainment in the lower regime. Extinction radio differences between the winter-spring and summer-fall hemispheres, and differences between the two phases of the QBO, are typically 20-50%.« less

Predictive value of early magnetic resonance imaging measures is differentially affected by the dose of interferon beta-1a given subcutaneously three times a week: an exploratory analysis of the PRISMS study.

PubMed

Traboulsee, Anthony; Li, David K B; Cascione, Mark; Fang, Juanzhi; Dangond, Fernando; Miller, Aaron

2018-05-11

On-treatment magnetic resonance imaging lesions may predict long-term clinical outcomes in patients receiving interferon β-1a. This study aimed to assess the effect of active T2 and T1 gadolinium-enhancing (Gd+) lesions on relapses and 3-month confirmed Expanded Disability Status Scale (EDSS) progression in the PRISMS clinical trial. Exploratory analyses assessed whether active T2 and T1 Gd + lesions at Month 6, or active T2 lesions at Month 12, predicted clinical outcomes over 4 years in PRISMS. Mean active T2 lesion number at Month 6 was significantly lower with interferon beta-1a given subcutaneously (IFN β-1a SC) 44 μg and 22 μg 3×/week (tiw) than with placebo (p < 0.0001). The presence of ≥4 versus 0 active T2 lesions predicted disability progression at Years 3-4 in the IFN β-1a SC 22 μg group only (p < 0.05), whereas the presence of ≥2 versus 0-1 active T2 lesions predicted disability progression in the placebo/delayed treatment (DTx) (Years 2-4; p < 0.05) and IFN β-1a SC 22 μg groups (Years 3-4; p < 0.05). Greater active T2 lesion number at 6 months predicted relapses in the placebo/DTx group only (≥4 vs. 0, Years 1-4; ≥2 vs. 0-1, Years 2-4; p < 0.05), and the presence of T1 Gd + lesions at 6 months predicted disability progression in the IFN β-1a SC 44 μg group only (Year 1; p < 0.05). The presence of ≥2 versus 0-1 active T2 lesions at 12 months predicted disability progression over 3 and 4 years in the IFN β-1a SC 44 μg group. Active T2 lesions at 6 months predicted clinical outcomes in patients receiving placebo or IFN β-1a SC 22 μg, but not in those receiving IFN β-1a SC 44 μg. Active T2 lesions at 12 months may predict outcomes in those receiving IFN β-1a SC 44 μg and are possibly more suggestive of poor response to therapy than T2 results at 6 months.

Changes in Retinal Nonperfusion Associated with Suppression of Vascular Endothelial Growth Factor in Retinal Vein Occlusion

PubMed Central

Mir, Tahreem A.; Kherani, Saleema; Hafiz, Gulnar; Scott, Adrienne W.; Zimmer-Galler, Ingrid; Wenick, Adam S.; Solomon, Sharon; Han, Ian; Poon, David; He, Lingmin; Shah, Syed Mahmood; Brady, Christopher J.; Meyerle, Catherine; Sodhi, Akrit; Linz, Marguerite O.; Sophie, Raafay; Campochiaro, Peter A.

2017-01-01

Purpose To assess changes in retinal nonperfusion (RNP) in patients with retinal vein occlusion (RVO) treated with ranibizumab (RBZ) Design Secondary outcome measure in randomized double-masked controlled clinical trial Subjects Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO) Methods Subjects were randomized to 0.5mg or 2.0mg RBZ every month for 6 months and then re-randomized to pro re nata (prn) groups RBZ+scatter photocoagulation (laser) or RBZ alone for an additional 30 months. Main Outcome Measures Comparison of percentage of patients with increased or decreased area of RNP in patients with RVO treated with 0.5mg versus 2.0mg RBZ, during monthly injections versus prn RBZ, and in patients treated with prn RBZ versus prn RBZ+laser. Results In RVO patients given monthly injections of 0.5mg or 2.0mg RBZ for 6 months there was no significant difference in the percentage who showed reduction or increase in area of RNP. However, regardless of dose, during the 6 month period of monthly injections, a higher percentage of patients showed a reduction in area of RNP and a lower percentage showed an increase in area of RNP compared to subsequent time periods of prn RBZ treatment. After the 6 month period of monthly injections, BRVO, but not CRVO patients randomized to prn RBZ+laser showed significantly less progression of RNP compared to patients treated with prn RBZ. Conclusions Regardless of dose of ranibizumab (0.5mg or 2.0mg), monthly injections promote improvement and reduce progression of RNP compared to prn injections. Addition of scatter photocoagulation to prn RBZ may reduce progression of RNP in patients with BRVO, but a statistically significant reduction was not seen in patients with CRVO. PMID:26712560

Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice.

PubMed

Blancas, I; Fontanillas, M; Conde, V; Lao, J; Martínez, E; Sotelo, M J; Jaen, A; Bayo, J L; Carabantes, F; Illarramendi, J J; Gordon, M M; Cruz, J; García-Palomo, A; Mendiola, C; Pérez-Ruiz, E; Bofill, J S; Baena-Cañada, J M; Jáñez, N M; Esquerdo, G; Ruiz-Borrego, M

2018-07-01

This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%). Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.

Etiology of Ibrutinib Discontinuation and Outcomes in Chronic Lymphocytic Leukemia Patients

PubMed Central

Maddocks, Kami J.; Ruppert, Amy S.; Lozanski, Gerard; Heerema, Nyla A.; Zhao, Weiqiang; Abruzzo, Lynne; Lozanski, Arletta; Davis, Melanie; Gordon, Amber; Smith, Lisa L.; Mantel, Rose; Jones, Jeffrey A.; Flynn, Joseph M.; Jaglowski, Samantha M.; Andritsos, Leslie A.; Awan, Farrukh; Blum, Kristie A.; Grever, Michael R.; Johnson, Amy J.; Byrd, John C.; Woyach, Jennifer A.

2015-01-01

Importance The Bruton’s Tyrosine Kinase inhibitor ibrutinib is effective in patients with chronic lymphocytic leukemia (CLL). Reasons for discontinuation from this drug and outcomes following discontinuation have not been evaluated outside of clinical trials with relatively short follow-up. Objective To determine features associated with discontinuation of ibrutinib and outcomes. Design 308 patients participating in four sequential trials of ibrutinib were included. These trials accrued patients included in this analysis from May 2010 until April 2014, and data were locked in June 2014. Setting The Ohio State University Comprehensive Cancer Center Participants Patients with CLL enrolled on 4 sequential clinical trials. Main Outcome Measure Patients were evaluated for time to discontinuation, reasons for discontinuation, and survival following discontinuation. For patients who discontinued due to progression, targeted deep sequencing was performed in samples at baseline and relapse. Results With a median follow-up of 20 months, 232 patients remain on therapy, 31 have discontinued because of progression, and 45 have discontinued for other reasons. Disease progression includes Richter’s transformation or progressive CLL. Richter’s appeared to occur early and CLL progressions later (cumulative incidence at 12 months: 4.5% (95% CI: 2.0% to 7.0%) and 0.3% (95% CI: 0% to 1.0%), respectively). Median survival following Richter’s transformation was 3.5 months (95% CI: 0.3–6.0), and 17.6 months (95% CI: 4.7-not reached) following CLL progression. Sequencing on peripheral blood from 8 patients with Richter’s transformation revealed 2 with mutations in BTK, and a lymph node sample showed no mutations in BTK or PLCγ2. Deep sequencing on 11 patients with CLL progression revealed BTK or PLCγ2 mutations in all. These mutations were not identified pre-treatment in any patient. Conclusions and Relevance This single institution experience with ibrutinib confirms it to be an effective therapy and identifies, for the first time, baseline factors associated with ibrutinib discontinuation. Outcomes data show poor prognosis after discontinuation, especially for those patients with Richter’s transformation. Finally, sequencing data confirm initial reports associating mutations in BTK and PLCγ2 with progression and clearly show that CLL progressions are associated with these mutations, while Richter’s transformation is likely not. PMID:26182309

Efficacy of icotinib in lung squamous-cell cancer: A real-world experience from single institution.

PubMed

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-12-01

Squamous cell carcinoma is a less common type of nonsmall cell lung cancer (NSCLC) which associates with a poor clinical prognosis and lacks specific therapy. This study aimed to evaluate the efficacy and safety of icotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has proven to be effective in EGFR-mutated NSCLC, in patients with lung squamous-cell cancer. Retrospective analysis was conducted in patients who had advanced lung squamous-cell cancer confirmed by cytology or histology. Patients were treated orally with icotinib (125 mg, three times daily) until event of unacceptable toxicity, disease progression or death. The primary endpoint was overall survival. The secondary endpoints were progression-free survival, overall response rate and disease control rate. Between January 2014 and May 2016, 20 patients were enrolled and evaluated for the efficacy and safety of icotinib. Overall, the median overall survival and progression-free survival were 9.93 months (95% confidence interval (CI): 3.46-16.40) and 3.0 months (95% CI: 0.00-8.35), respectively. The overall response rate and disease control rate were 20% and 70%, respectively. For treatment-naive patients (n = 11), the overall survival and progression-free survival were 9.93 months (95% CI: 0.00-23.49) and 6.27 months (95% CI: 0.00-12.61); the response rate and disease control rate were 27.3% and 54.5%, respectively. The overall survival and progression-free survival of patients treated with second- or multiple-line icotinib treatment (n = 9) were 6.5 months (95% CI: 0.80-12.20) and 1.2 months (95% CI: 1.10-1.30). A total of 11 patients experienced at least one treatment-related adverse event, most of which were mild to moderate. The most common manifestations were rash (n = 6, 30%) followed by diarrhea (n = 2, 10%). Icotinib has demonstrated a favorable efficacy and safety profile in patients with advanced lung squamous-cell cancer. © 2017 John Wiley & Sons Australia, Ltd.

Hanford Works monthly report, December 1950

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1951-01-22

This is a progress report of the production reactors on the Hanford Reservation for the month of December 1950. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, April 1952

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1952-05-20

This is a progress report of the production reactors on the Hanford Reservation for the month of April 1952. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, August 1950

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1950-09-18

This is a progress report of the production reactors on the Hanford Reservation for the month of August 1950. This report takes each division (e.g. manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, May 1951

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1951-06-21

This is a progress report of the production reactors on the Hanford Reservation for the month of May 1951. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, December 1951

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1952-01-22

This is a progress report of the production reactors on the Hanford Reservation for the month of December 1951. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, March 1951

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1951-04-20

This is a progress report of the production reactors on the Hanford Reservation for the month of March 1951. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, July 1951

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

This is a progress report of the production reactors on the Hanford Reservation for the month of July 1951. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, March 1952

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1952-04-18

This is a progress report of the production reactors on the Hanford Reservation for the month of April 1952. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, July 1952

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1952-08-15

This is a progress report of the production reactors on the Hanford Reservation for the month of July 1952. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford works monthly report, September 1951

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

This is a progress report of the production reactors on the Hanford Reservation for the month of September 1951. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, January 1952

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

This is a progress report of the production reactors on the Hanford Reservation for the month of January 1952. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, August 1951

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1951-09-24

This is a progress report of the production reactors on the Hanford Reservation for the month of August 1951. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, July 1950

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1950-08-18

This is a progress report of the production reactors on the Hanford Reservation for the month of July 1950. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, November 1951

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1951-12-21

This is a progress report of the production reactors on the Hanford Reservation for the month of November 1951. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, October 1950

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1950-11-20

This is a progress report of the production reactors on the Hanford Reservation for the month of October 1950. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, September 1950

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1950-10-20

This is a progress report of the production reactors on the Hanford Reservation for the month of September 1950. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Works monthly report, November 1950

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prout, G.R.

1950-12-20

This is a progress report of the production reactors on the Hanford Reservation for the month of November 1950. This report takes each division (e.g. manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Common Progress Monitoring Omissions: Planning and Practice. Progress Monitoring Brief #1

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2013

2013-01-01

Progress monitoring, one of the essential components of Response to Intervention (RTI), is characterized by repeated measurement of academic performance that is conducted at least monthly. The process may be used to assess students' academic performance over time, to quantify student rates of improvement or responsiveness to instruction, and to…

Common Progress Monitoring Omissions: Reporting Information to Parents. Progress Monitoring Brief #4

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2013

2013-01-01

Progress monitoring, one of the essential components of Response to Intervention (RTI), is characterized by repeated measurement of academic performance that is conducted at least monthly. The process may be used to assess students' academic performance over time, to quantify student rates of improvement or responsiveness to instruction, and to…

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study.

PubMed

Herrick, Ariane L; Peytrignet, Sebastien; Lunt, Mark; Pan, Xiaoyan; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan J; Dinsdale, Graham; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon C; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jobanputra, Paresh; Jordan, Alison C; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja S; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susanna M; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

2018-04-01

Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. NCT02339441. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients naive to antiangiogenic therapy

PubMed Central

Drappatz, Jan; de Groot, John; Prados, Michael D; Reardon, David A; Schiff, David; Chamberlain, Marc; Mikkelsen, Tom; Desjardins, Annick; Holland, Jaymes; Ping, Jerry; Weitzman, Ron; Cloughesy, Timothy F

2018-01-01

Abstract Background Cabozantinib is a tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 (VEGFR2) and MET that has demonstrated clinical activity in advanced solid tumors. This open-label, phase II trial evaluated cabozantinib in patients with recurrent or refractory glioblastoma (GBM). Methods Patients were initially enrolled at a starting dose of 140 mg/day, but the starting dose was amended to 100 mg/day because of toxicity. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by an independent radiology facility using modified Response Assessment in Neuro-Oncology criteria. Additional endpoints included duration of response, 6-month and median progression-free survival, overall survival, and safety. Results Among 152 patients naive to prior antiangiogenic therapy, the objective response rate was 17.6% and 14.5% in the 140 mg/day and 100 mg/day groups, respectively, which did not meet the predefined statistical target for success. The proportions of patients alive and progression free at 6 months were 22.3% and 27.8%, respectively. Median progression-free survival was 3.7 months in both groups, and median overall survival was 7.7 months and 10.4 months, respectively. The incidence of grade 3/4 adverse events (AEs) was 79.4% and 84.7% in the 140 mg/day and 100 mg/day groups, respectively, and dose reductions due to AEs were experienced by 61.8% and 72.0%, respectively. Common grade 3/4 AEs included fatigue, diarrhea, and palmar-plantar erythrodysesthesia syndrome. Conclusions Cabozantinib showed evidence of clinical activity in patients with recurrent GBM naive to antiangiogenic therapy, although the predefined statistical target for success was not met. At the starting doses assessed, AEs were frequently managed with dose reductions. Clinical Trials Registration Number NCT00704288 (https://www.clinicaltrials.gov/ct2/show/NCT00704288) PMID:29016998

Jet Propulsion Laboratory: Annual Report 2009

NASA Technical Reports Server (NTRS)

2010-01-01

2009 was truly the year of astronomy at the Jet Propulsion Laboratory. While the world at large was celebrating the International Year of Astronomy, we were sending more telescopes into space than in any other year, ever. As these missions unfold, the astronomers are sure to change the way we see the universe. One of the newly lofted observatories is on a quest to find planets like our own Earth orbiting other stars. Another is a telescope that gathers infrared light to help discover objects ranging from near-Earth asteroids to galaxies in the deepest universe. We also contributed critical enabling technologies to yet two other telescopes sent into space by our partners in Europe. And astronauts returned to Earth with a JPL-built camera that had captured the Hubble Space Telescope's most memorable pictures over many years. And while it was an epic time for these missions, we were no less busy in our other research specialties. Earth's moon drew much attention from our scientists and engineers, with two JPL instruments riding on lunar orbiters; previously unseen views of shadowed craters were provided by radar imaging conducted with the giant dish antennas of the Deep Space Network, our worldwide communication portal to spacecraft around the solar system. At Mars, our rovers and orbiters were highly productive, as were missions targeting Saturn, comets and the asteroid belt. Here at our home planet, satellites and instruments continued to serve up important information on global climate change. But our main business is, of course, exploring. Many initiatives will keep us busy for years. In 2009, NASA gave approval to start planning a major flagship mission to Jupiter's moon Europa in search of conditions that could host life, working with our partners in Europe. In addition to our prospective Earth science projects, we have full slates of missions in Mars exploration, planetary exploration and space-based astronomy. This year's annual report continues our recent direction of recounting the Laboratory's accomplishments throughout the year month by month.

Home is where the hearth is: grant recipients' views of England's home energy efficiency scheme (Warm Front).

PubMed

Gilbertson, Jan; Stevens, Maryjane; Stiell, Bernadette; Thorogood, Nicki

2006-08-01

This paper reports the results of research carried out as part of the national health impact evaluation of the Warm Front Scheme, a government initiative aimed at alleviating fuel poverty in England. Semi-structured interviews were carried out in a purposive sample of 49 households which received home energy improvements under the Scheme from five urban areas (Birmingham, Liverpool, Manchester, Newcastle, Southampton). Each household had received installation, replacement or refurbishment of the heating system and, in some cases, also insulation of the cavity wall or loft or both, and draught-proofing measures. Most householders reported improved and more controllable warmth and hot water. Many also reported perceptions of improved physical health and comfort, especially of mental health and emotional well-being and, in several cases, the easing of symptoms of chronic illness. There were reports of improved family relations, an expansion of the domestic space used during cold months, greater use of kitchens and improved nutrition, increased privacy, improved social interaction, and an increase in comfort and atmosphere within the home. Greater warmth and comfort also enhanced emotional security, and recipients were more content and at ease in their homes. However there was little evidence of substantially lower heating bills. These results provide evidence that Warm Front home energy improvements are accompanied by appreciable benefits in terms of use of living space, comfort and quality of life, physical and mental well-being, although there is only limited evidence of change in health behaviour.

Assessment of aerosol's mass concentrations from measured linear particle depolarization ratio (vertically resolved) and simulations

NASA Astrophysics Data System (ADS)

Nemuc, A.; Vasilescu, J.; Talianu, C.; Belegante, L.; Nicolae, D.

2013-11-01

Multi-wavelength depolarization Raman lidar measurements from Magurele, Romania are used in this study along with simulated mass-extinction efficiencies to calculate the mass concentration profiles of different atmospheric components, due to their different depolarization contribution to the 532 nm backscatter coefficient. Linear particle depolarization ratio (δpart) was computed using the relative amplification factor and the system-dependent molecular depolarization. The low depolarizing component was considered as urban/smoke, with a mean δpart of 3%, while for the high depolarizing component (mineral dust) a mean δpart of 35% was assumed. For this study 11 months of lidar measurements were analysed. Two study cases are presented in details: one for a typical Saharan dust aerosol intrusion, 10 June 2012 and one for 12 July 2012 when a lofted layer consisting of biomass burning smoke extended from 3 to 4.5 km height. Optical Properties of Aerosols and Clouds software package (OPAC) classification and conversion factors were used to calculate mass concentrations. We found that calibrated depolarization measurements are critical in distinguishing between smoke-reach aerosol during the winter and dust-reach aerosol during the summer, as well as between elevated aerosol layers having different origins. Good agreement was found between lidar retrievals and DREAM- Dust REgional Atmospheric Model forecasts in cases of Saharan dust. Our method was also compared against LIRIC (The Lidar/Radiometer Inversion Code) and very small differences were observed.

Assessment of aerosol's mass concentrations from measured linear particle depolarization ratio (vertically resolved) and simulations

NASA Astrophysics Data System (ADS)

Nemuc, A.; Vasilescu, J.; Talianu, C.; Belegante, L.; Nicolae, D.

2013-06-01

Multiwavelength depolarization Raman lidar measurements from Magurele, Romania are used in this study along with simulated mass-extinction efficiencies to calculate the mass concentrations profiles of different atmospheric components, due to their different depolarization contribution to the 532 nm backscatter coefficient. Linear particle depolarization ratio (δpart) was computed using the relative amplification factor and the system-dependent molecular depolarization. The low depolarizing component was considered as urban/smoke, with a mean δpart of 3%, while for the high depolarizing component (mineral dust) a mean δpart of 35% was assumed. For this study 11 months of lidar measurements were analyzed. Two study cases are presented in details: one for a typical Saharan dust aerosol intrusion, 10 June 2012 and one for 12 July 2012 when a lofted layer consisting of biomass burning smoke extended from 3 to 4.5 km height. Optical Properties of Aerosols and Clouds software package (OPAC) classification and conversion factors were used to calculate mass concentrations. We found that calibrated depolarization measurements are critical to distinguish between smoke-reach aerosol during the winter and dust-reach aerosol during the summer, as well as between elevated aerosol layers having different origins. Good agreement was found between lidar retrievals and DREAM- Dust REgional Atmospheric Model forecasts in cases of Saharan dust. Our method was also compared against LIRIC (The Lidar/Radiometer Inversion Code) and very small differences were observed.

Tissue polypeptide-specific antigen (TPS) determinations before and during intermittent maximal androgen blockade in patients with metastatic prostatic carcinoma.

PubMed

Kil, P J M; Goldschmidt, H M J; Wieggers, B J A; Kariakine, O B; Studer, U E; Whelan, P; Hetherington, J; de Reijke, Th M; Hoekstra, J W; Collette, L

2003-01-01

To evaluate the prognostic significance of serially measured tissue polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic carcinoma treated with intermittent maximal androgen blockade (MAB). To determine its value with respect to predicting response to treatment and time to clinical progression. Finally to compare TPS with prostate-specific antigen (PSA) measurements in terms of prognostic impact in patients with metastatic prostatic carcinoma. TPS and PSA measurements were performed before start of and monthly during intermittent MAB in 68 patients participating in EORTC protocol 30954. Both TPS and PSA were measured in serum. Fifty-six patients from eight centers were included in the final analysis because at least three TPS values were available. TPS and PSA values were correlated with clinical course of the disease. Median follow-up was 21.3 months. Three patient groups were defined on clinical grounds: (a) clinically progressive disease (n=18); (b) clinically stable disease (n=33); and (c) patients who did not reach a predefined nadir PSA value following 9 months of treatment (n=5). Pretreatment TPS was significantly higher in the clinically progressive patients than in the other patient groups (p=0.0041). When grouping patients according to their pretreatment TPS values (cut-off value of 100 U/l) the pretreatment TPS value (>100 U/l) proved to be a statistically significant prognostic factor with respect to time to progression: elevated TPS was associated with a 3.8 increased risk for progressive disease (p=0.0055). Pretreatment PSA (>100 ng/ml) was of no prognostic value for time to progression. In five patients increase of TPS coincided with or preceded clinical progression during treatment, whereas PSA remained normal. Additional value of pretreatment TPS measurements in metastatic prostate cancer patients is found in defining the patients with rapid clinical progression. Following MAB an increase in TPS signifies clinical progression even if PSA is found to remain normal.

Gas-turbine critical research and advanced technology support project

NASA Technical Reports Server (NTRS)

Clark, J. S.; Lowell, C. E.; Niedzwiecki, R. W.; Nainiger, J. J.

1979-01-01

The technical progress made during the first 15 months of a planned 40-month project to provide a critical-technology data base for utility gas-turbine systems capable of burning coal-derived fuels is summarized. Tasks were included in the following areas: (1) combustion, to study the combustion of coal-derived fuels and conversion of fuel-bound nitrogen to NOx; (2) materials, to understand and prevent hot corrosion; and (3) system studies, to integrate and guide the other technologies. Significant progress was made.

[Lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement].

PubMed

Caliez, J; Monnet, I; Pujals, A; Rousseau-Bussac, G; Jabot, L; Boudjemaa, A; Leroy, K; Chouaid, C

2017-05-01

Among patients with non-small-cell lung cancer, coexistence of EGFR mutation and ALK rearrangement is rare. We describe the clinical features of two patients with this double anomaly. A 62-year-old Caucasian non-smoking woman was diagnosed with cT4N0M0 lung adenocarcinoma. Initial biopsy showed EGFR mutation and ALK rearrangement. She received cisplatin-gemcitabine, followed by 17 months of gemcitabine. Owing to progression, she received erlotinib for 14 months, then paclitaxel for 6 months and finally crizotinib. A partial response was achieved and maintained for 24 months. A 45-year-old Caucasian woman, light smoker, was diagnosed with cT2N3M0 lung adenocarcinoma. Only EGFR mutation was found on initial analysis. She underwent treatment with cisplatin-gemcitabine and thoracic radiotherapy. Progression occurred after 8 months and afatinbib was started. Eight months later, progression was observed with a neoplasic pleural effusion in which tumor cells expressing ALK rearrangement were found. A new FISH analysis was performed on the initial tumor but did not find this rearrangement. Despite a third line of crizotinib, the patient died one month later. The literature shows 45 other cases of these two abnormalities, observed either from the start or during follow-up. EGFR's TKI were almost always given before ALK's TKI. Therapeutic strategy needs to be clarified in cases of double alteration. With regard to the second patient, appearance of ALK rearrangement may constitute a resistance mechanism to EGFR's TKI. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Hanford Atomic Products Operation monthly report, April 1954

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCune, F.K.

1954-05-21

This is a progress report of the production reactors on the Hanford Reservation for the month of April 1954. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Atomic Products Operation monthly report, March 1953

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCune, F.K.

1953-04-22

This is a progress report of the production reactors on the Hanford Reservation for the month of March 1953. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

78 FR 26223 - National Physical Fitness and Sports Month, 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-03

... Physical Fitness and Sports Month, 2013 By the President of the United States of America A Proclamation... life. During National Physical Fitness and Sports Month, we celebrate that progress and keep striving... at work. Through Let's Move! and the President's Council on Fitness, Sports, and Nutrition, we...

Hanford Atomic Products Operation monthly report, April 1953

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCune, F.K.

1953-05-20

This is a progress report of the production reactors on the Hanford Reservation for the month of April 1951. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes its accomplishments and employee relations for that month.

Hanford Atomic Products Operation monthly report, January 1954

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCune, F.K.

1954-02-25

This is a progress report of the production reactors on the Hanford Reservation for the month of January 1954. This report takes each division (e.g., manufacturing, medical, accounting, occupational safety, security, reactor operations, etc.) of the site and summarizes the accomplishments and employee relations for that month.

Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models

PubMed Central

Mdala, Ibrahimu; Olsen, Ingar; Haffajee, Anne D; Socransky, Sigmund S; Thoresen, Magne; de Blasio, Birgitte Freiesleben

2014-01-01

Aim To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis. Material and Methods Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP. Results In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87–97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4–5 months and sites recovered with a high probability (96–98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased. Conclusion Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression. PMID:24888705

Prognostic Value of [18F]-Fluoromethylcholine Positron Emission Tomography/Computed Tomography Before Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer.

PubMed

Cysouw, Matthijs; Bouman-Wammes, Esther; Hoekstra, Otto; van den Eertwegh, Alfons; Piet, Maartje; van Moorselaar, Jeroen; Boellaard, Ronald; Dahele, Max; Oprea-Lager, Daniela

2018-06-01

To investigate the predictive value of [ 18 F]-fluoromethylcholine positron emission tomography/computed tomography (PET/CT)-derived parameters on progression-free survival (PFS) in oligometastatic prostate cancer patients treated with stereotactic body radiation therapy (SBRT). In [ 18 F]-fluoromethylcholine PET/CT scans of 40 consecutive patients with ≤4 metachronous metastases treated with SBRT we retrospectively measured the number of metastases, standardized uptake values (SUV mean , SUV max , SUV peak ), metabolically active tumor volume (MATV), and total lesion choline uptake. Partial-volume correction was applied using the iterative deconvolution Lucy-Richardson algorithm. Thirty-seven lymph node and 13 bone metastases were treated with SBRT. Thirty-three patients (82.5%) had 1 lesion, 4 (10%) had 2 lesions, and 3 (7.5%) had 3 lesions. After a median follow-up of 32.6 months (interquartile range, 35.5 months), the median PFS was 11.5 months (95% confidence interval 8.4-14.6 months). Having more than a single metastasis was a significant prognostic factor (hazard ratio 2.74; P = .03), and there was a trend in risk of progression for large MATV (hazard ratio 1.86; P = .10). No SUV or total lesion choline uptake was significantly predictive for PFS, regardless of partial-volume correction. All PET semiquantitative parameters were significantly correlated with each other (P ≤ .013). The number of choline-avid metastases was a significant prognostic factor for progression after [ 18 F]-fluormethylcholine PET/CT-guided SBRT for recurrent oligometastatic prostate cancer, and there seemed to be a trend in risk of progression for patients with large MATVs. The lesional level of [ 18 F]-fluoromethylcholine uptake was not prognostic for progression. Copyright © 2018 Elsevier Inc. All rights reserved.

Dacarbazine in combination with bevacizumab for the treatment of unresectable/metastatic melanoma: a phase II study.

PubMed

Ferrucci, Pier F; Minchella, Ida; Mosconi, Massimo; Gandini, Sara; Verrecchia, Francesco; Cocorocchio, Emilia; Passoni, Claudia; Pari, Chiara; Testori, Alessandro; Coco, Paola; Munzone, Elisabetta

2015-06-01

The combined treatment of dacarbazine with an antiangiogenic drug such as bevacizumab may potentiate the therapeutic effects of dacarbazine in metastatic melanoma (MM). Preliminary antitumour activity of dacarbazine plus bevacizumab is evaluated, together with the toxicity and safety profile, in MM patients. This prospective, open-label, phase II study included patients with previously untreated MM or unresectable melanoma. Patients received dacarbazine and bevacizumab until progressive disease or unacceptable toxicity. The primary efficacy variable was the overall response rate. The secondary efficacy parameters included duration of response, duration of stable disease, time to progression/progression-free survival, time to treatment failure and overall survival. The safety analysis included recordings of adverse events and exposure to study treatment. The intention-to-treat population included 37 patients (24 men and 13 women, mean age 54.2±13.1 years). Overall response rate was 18.9% (seven patients achieved a response) and clinical benefit was 48.6%. In patients who achieved a response, the median duration of response was 16.9 months and the median duration of stable disease was 12.5 months. The median time to progression/progression-free survival and time to treatment failure were 5.5 and 3.1 months, respectively. The median overall survival was 11.4 months. Almost all patients (94.6%) experienced at least one adverse event; however, no new area of toxicity of bevacizumab emerged. The dacarbazine/bevacizumab combination provides benefits compared with dacarbazine monotherapy in historical controls, with an acceptable safety profile. This combination appears to be a valid option in specific subgroups of patients, namely, those triple negative (BRAF, C-KIT and NRAS wild type) or with a BRAF mutation who have already received, or are not eligible for, immunomodulating or targeted agents.

Evaluation of Liver Function After Proton Beam Therapy for Hepatocellular Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mizumoto, Masashi; Okumura, Toshiyuki; Hashimoto, Takayuki

Purpose: Our previous results for treatment of hepatocellular carcinoma with proton beam therapy (PBT) revealed excellent local control. In this study, we focused on the impact of PBT on normal liver function. Methods and Materials: The subjects were 259 patients treated with PBT at University of Tsukuba between January 2001 and December 2007. We evaluated the Child-Pugh score pretreatment, on the final day of PBT, and 6, 12, and 24 months after treatment with PBT. Patients who had disease progression or who died with tumor progression at each evaluation point were excluded from the analysis to rule out an effectmore » of tumor progression. An increase in the Child-Pugh score of 1 or more was defined as an adverse event. Results: Of the 259 patients, 241 had no disease progression on the final day of PBT, and 91 had no progression within 12 months after PBT. In univariate analysis, the percentage volumes of normal liver receiving at least 0, 10, 20, and 30 GyE in PBT (V0, 10, 20, and 30) were significantly associated with an increase of Child-Pugh score at 12 months after PBT. Of the 91 patients evaluated at 12 months, 66 had no increase of Child-Pugh score, 15 had a 1-point increase, and 10 had an increase of {>=}2 points. For the Youden index, the optimal cut-offs for V0, V10, V20, and V30 were 30%, 20%, 26%, and 18%, respectively. Conclusion: Our findings indicate that liver function after PBT is significantly related to the percentage volume of normal liver that is not irradiated. This suggests that further study of the relationship between liver function and PBT is required.« less

Long-term outcome in BRAF(V600E) melanoma patients treated with vemurafenib: Patterns of disease progression and clinical management of limited progression.

PubMed

Puzanov, Igor; Amaravadi, Ravi K; McArthur, Grant A; Flaherty, Keith T; Chapman, Paul B; Sosman, Jeffrey A; Ribas, Antoni; Shackleton, Mark; Hwu, Patrick; Chmielowski, Bartosz; Nolop, Keith B; Lin, Paul S; Kim, Kevin B

2015-07-01

Vemurafenib induces tumour regression in most patients with BRAF(V600E)-mutant melanoma; eventually, most experience progressive disease (PD). Long-term follow-up of patients with BRAF(V600E) melanoma treated in the phase 1 vemurafenib trial is reported. Patients received vemurafenib 240-1120 mg (dose escalation cohort) or 960 mg (extension cohort) orally twice daily. Clinical response was evaluated every 8 weeks by Response Evaluation Criteria In Solid Tumors (RECIST). Patients with PD amenable to local therapy (surgery or radiotherapy) were allowed to continue vemurafenib after progression. Overall survival (OS) from time of treatment initiation and from PD was estimated. Sites of PD were recorded. Forty-eight patients (escalation cohort, n = 16; extension cohort, n = 32) received therapeutic doses of vemurafenib (⩾ 240 mg twice daily). Forty-four patients had PD by the time of this analysis and four remained progression free (follow-up time, 1.2-56.1 months). Median OS was 14 months (range, 1.2-56.1); 3- and 4-year melanoma-specific survival rate in the extension cohort was 26% and 19%, respectively. Median OS was 26.0 months (range, 7.7-56.1) among 20 patients who continued vemurafenib after local therapy. Median treatment duration beyond initial PD was 3.8 months (range, 1.1-26.6). In the extension cohort, six and five patients were alive after 3 and 4 years, respectively, on vemurafenib monotherapy. Some patients with melanoma achieved long-term survival with vemurafenib monotherapy. Continuation of vemurafenib after PD might be beneficial in some patients because remaining disease might continue to respond to BRAF inhibition. Copyright © 2015 Elsevier Ltd. All rights reserved.

A PHASE II TRIAL OF THALIDOMIDE IN PATIENTS WITH REFRACTORY ENDOMETRIAL CANCER AND CORRELATION WITH ANGIOGENESIS BIOMARKERS: A GYNECOLOGIC ONCOLOGY GROUP STUDY

PubMed Central

McMeekin, D. Scott; Sill, Michael W.; Benbrook, Doris; Darcy, Kathleen M.; Stearns-Kurosawa, Deborah J.; Eaton, Lynne; Yamada, S. Diane

2007-01-01

Objectives A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of thalidomide in persistent or recurrent endometrial cancer refractory to cytotoxic chemotherapy, and to correlate angiogenesis biomarker expression with clinical outcome. Methods Consenting patients were treated until progression or intolerable toxicity with an oral starting dose of 200 mg thalidomide/day that was to increase by 200 mg every 2 weeks to a target dose of 1000 mg/day. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and soluble endothelial protein C receptor (sEPCR) were analyzed by ELISA in pre and post-treatment specimens. Results Twenty-four of 27 patients enrolled in the study were eligible, of whom 2 reached the target dose, 8 progressed before achieving the target dose and 14 refused or had toxicity that prohibited escalation. Two patients (8.3%) remained progression-free ≥ 6 months. There were 3 (12.5%) with partial responses, 2 (8.3%) with stable disease, 15 (62.5%) with increasing disease, and 4 (16.7%) who were inevaluable for response. Median progression-free survival and overall survival were 1.7 months and 6.3 months, respectively. No grade 4 toxicities were observed. Common grade 3 toxicities included hematologic (n=3), cardiovascular (n=3), constitutional (n=3), and neurologic (n=4). Thalidomide did not decrease VEGF or bFGF levels but reduced sEPCR levels in serum. Elevated plasma vascular endothelial growth factor levels were associated with increased risk of progression and death. Conclusions Thalidomide demonstrated limited ability to delay progression (as measured by PFS at 6 months), produce objective responses or reduce angiogenic marker levels in chemotherapy refractory endometrial cancer. VEGF level appears to be prognostically significant in such patients, independent of thalidomide treatment. PMID:17306350

Vegetarian low-protein diets supplemented with keto analogues: a niche for the few or an option for many?

PubMed

Piccoli, Giorgina B; Ferraresi, Martina; Deagostini, Maria C; Vigotti, Federica Neve; Consiglio, Valentina; Scognamiglio, Stefania; Moro, Irene; Clari, Roberta; Fassio, Federica; Biolcati, Marilisa; Porpiglia, Francesco

2013-09-01

Low-protein diets are often mentioned but seldom used to slow chronic kidney disease (CKD) progression. The aim of the study was to investigate the potential for implementation of a simplified low-protein diet supplemented with alpha-keto analogues (LPD-KA) as part of the routine work-up in CKD patients. In an implementation study (December 2007-November 2011), all patients with CKD Stages IV-V not on dialysis, rapidly progressive Stage III and/or refractory proteinuria, were offered either a simplified LPD-KA, or commercially available low-protein food. LPD-KA consisted of proteins 0.6 g/kg/day, supplementation with Ketosteril 1 pill/10 Kg, 1-3 free-choice meals/week and a simplified schema based on 'allowed' and 'forbidden' foods. 'Success' was defined as at least 6 months on LPD-KA. Progression was defined as reduction in glomerular filtration rate (GFR)[(Chronic Kidney Disease Epidemiology Collaboration) formula CKD-EPI] in patients with at least 6 months of follow-up. Of about 2500 patients referred (8% CKD Stages IV-V), 139 started LPD-KA; median age (70 years) and prevalence of comorbidity (79%) were in line with the dialysis population. Start of dialysis was the main reason for discontinuation (40 cases, unplanned in 7); clinical reasons were recorded in 7, personal preference in 14 and improvement and death in 8 each. The low gross mortality (4% per year) and the progression rate (from -8 to 0 mL/min/year at 6 months) are reassuring concerning safety. None of the baseline conditions, including age, educational level, comorbidity or kidney function, discriminated the patients who followed the diet for at least 6 months. Our data suggest a wider offer of LPD-KA to patients with severe and progressive CKD. The promising results in terms of mortality and progression need confirmation with different study designs.

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu; Schipper, Matthew; Zalupski, Mark M.

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less

Characterization of Retinal Disease Progression in a 1-Year Longitudinal Study of Eyes With Mild Nonproliferative Retinopathy in Diabetes Type 2.

PubMed

Ribeiro, Luisa; Bandello, Francesco; Tejerina, Amparo Navea; Vujosevic, Stela; Varano, Monica; Egan, Catherine; Sivaprasad, Sobha; Menon, Geeta; Massin, Pascale; Verbraak, Frank D; Lund-Andersen, Henrik; Martinez, Jose P; Jürgens, Ignasi; Smets, Erica; Coriat, Caroline; Wiedemann, Peter; Ágoas, Victor; Querques, Giuseppe; Holz, Frank G; Nunes, Sandrina; Neves, Catarina; Cunha-Vaz, José

2015-08-01

To identify eyes of patients with diabetes type 2 that show progression of retinal disease within a 1-year period using noninvasive techniques. Three hundred seventy-four type 2 diabetic patients with mild nonproliferative diabetic retinopathy (Early Treatment Diabetic Retinopathy Study [ETDRS] level 20 or 35) were included in a 12-month prospective observational study to identify retinopathy progression. Four visits were scheduled at 0, 3, 6, and 12 months. Microaneurysm (MA) activity using the RetmarkerDR and retinal thickness using spectral-domain optical coherence tomography (SD-OCT) were assessed by a central reading center at all visits and ETDRS severity level in the first and last visits. Three hundred thirty-one eyes/patients completed the study. Microaneurysm formation rate greater than or equal to 2 was present in 68.1% of the eyes and MA turnover greater than or equal to 6 in 54.0% at month 6. Higher MA turnover values were registered in eyes that showed progression in ETDRS severity level (P < 0.03). There were also significant correlations between increased microaneurysm activity and increases in retinal thickness. Spectral-domain OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Progression of retinal thickening was registered in eyes that had either subclinical or clinical macular edema at baseline. Changes in MA activity measured with RetmarkerDR and in central retinal thickness in eyes with mild nonproliferative diabetic retinopathy and diabetes type 2 are able to identify eyes at risk of progression. These eyes/patients should be selected for inclusion in future clinical trials of drugs targeted to prevent diabetic retinopathy progression to vision-threatening complications. (ClinicalTrials.gov number, NCT01145599.)

The role of early magnetic resonance imaging in predicting survival on bevacizumab for recurrent glioblastoma: Results from a prospective clinical trial (CABARET).

PubMed

Field, Kathryn M; Phal, Pramit M; Fitt, Greg; Goh, Christine; Nowak, Anna K; Rosenthal, Mark A; Simes, John; Barnes, Elizabeth H; Sawkins, Kate; Cher, Lawrence M; Hovey, Elizabeth J; Wheeler, Helen

2017-09-15

Bevacizumab has been associated with prolonged progression-free survival for patients with recurrent glioblastoma; however, not all derive a benefit. An early indicator of efficacy or futility may allow early discontinuation for nonresponders. This study prospectively assessed the role of early magnetic resonance imaging (eMRI) and its correlation with subsequent routine magnetic resonance imaging (MRI) results and survival. Patients were part of a randomized phase 2 clinical trial (CABARET) comparing bevacizumab with bevacizumab plus carboplatin for recurrent glioblastoma. eMRI was conducted after 4 weeks in the trial (after 2 treatments with bevacizumab [10 mg/kg every 2 weeks]). The results were compared with the results of the subsequent 8-week MRI standard. For 119 of 122 patients, eMRI was available, and 111 had subsequent MRI for comparison. Thirty-six (30%) had an early radiological response, and 17 (14%) had progressive disease. The concordance between eMRI and 8-week MRI was moderate (κ = 0.56), with most providing the same result (n = 79 [71%]). There was strong evidence that progression-free survival and overall survival were predicted by the eMRI response (both P values < .001). The median survival was 8.6 months for an eMRI response, 6.6 months for stable disease, and 3.7 months for progressive disease; the hazard ratio (progressive disease vs stable disease) was 3.4 (95% confidence interval, 1.9-6.0). Landmark analyses showed that eMRI progression was a strong predictor of mortality independent of other potential baseline predictors. In this study, early progression on MRI appears to be a robust marker of a poor prognosis for patients on bevacizumab. Cancer 2017;123:3576-82. © 2017 American Cancer Society. © 2017 American Cancer Society.

Systems integration of marketable subsystems: A collection of progress reports

NASA Technical Reports Server (NTRS)

1978-01-01

Monthly progress reports are given in the areas of marketable subsystems integration; development, design, and building of site data acquisition subsystems and data processing systems; operation of the solar test facility and a systems analysis.

Stabilization of a progressive hemangioblastoma under treatment with thalidomide.

PubMed

Piribauer, Maria; Czech, Thomas; Dieckmann, Karin; Birner, Peter; Hainfellner, Johannes A; Prayer, Daniela; Fazeny-Dörner, Barbara; Weinländer, Georg; Marosi, Christine

2004-02-01

After the second recurrence of spinal seeding in hemangioblastoma not associated to von-Hippel-Lindau disease, we treated an adult female patient with thalidomide 200 mg orally/day at night for longer than 1 year. The patient reported subjective relief of symptoms after 1 month. Magnetic resonance imaging (MRI) controls 1,6 and 11 months after begin of thalidomide treatment did not show further tumor progression. She remained wheelchair-bound, but mobility of her arms continuously improved. There was no thalidomide associated side-effect in this patient until her death from pneumonia due to legionnaire's disease. Antiangiogenic treatment with interferon (IFN) alpha-2a and IFN alpha-2b and with SU 5416 has been reported to be effective and well tolerated in several patients with previously progressive angioblastomas and hemangioblastomas. This case adds further evidence of the efficacy of an antiangiogenic treatment concept in a progressive hemangioblastoma.

Gaussian Processes for Prediction of Homing Pigeon Flight Trajectories

NASA Astrophysics Data System (ADS)

Mann, Richard; Freeman, Robin; Osborne, Michael; Garnett, Roman; Meade, Jessica; Armstrong, Chris; Biro, Dora; Guilford, Tim; Roberts, Stephen

2009-12-01

We construct and apply a stochastic Gaussian Process (GP) model of flight trajectory generation for pigeons trained to home from specific release sites. The model shows increasing predictive power as the birds become familiar with the sites, mirroring the animal's learning process. We show how the increasing similarity between successive flight trajectories can be used to infer, with increasing accuracy, an idealised route that captures the repeated spatial aspects of the bird's flight. We subsequently use techniques associated with reduced-rank GP approximations to objectively identify the key waypoints used by each bird to memorise its idiosyncratic habitual route between the release site and the home loft.

Investigation of diurnal variability of water vapor in Enceladus' plume by the Cassini ultraviolet imaging spectrograph

NASA Astrophysics Data System (ADS)

Hansen, C. J.; Esposito, L. W.; Aye, K.-M.; Colwell, J. E.; Hendrix, A. R.; Portyankina, G.; Shemansky, D.

2017-01-01

An occultation of ɛ Orionis by Enceladus' plume was observed with Enceladus at an orbital longitude near apoapsis in order to investigate whether water vapor flow is modulated diurnally, similar to ice particles. The occultation showed that the bulk water vapor emanating from Enceladus changes little with orbital position. The amount of gas in at least one supersonic jet increased significantly, implying that the increase in the number of particles lofted at apoapsis could be due to more gas coming from the supersonic jets and not the overall gas flux from the tiger stripe fissures that cross Enceladus' south polar region.

Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study.

PubMed

Necchi, A; Joseph, R W; Loriot, Y; Hoffman-Censits, J; Perez-Gracia, J L; Petrylak, D P; Derleth, C L; Tayama, D; Zhu, Q; Ding, B; Kaiser, C; Rosenberg, J E

2017-12-01

Conventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1-directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma. Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator's discretion: this analysis assessed post-progression outcomes in these patients. Patients were treated with atezolizumab 1200 mg i.v. every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively. In total, 220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% versus 31.3%), less likely to have had baseline liver metastases (27.0% versus 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% versus 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure-adjusted adverse event frequencies were generally similar before and following progression. In this single-arm study, patients who continued atezolizumab beyond RECIST v1.1 progression derived prolonged clinical benefit without additional safety signals. Identification of patients most likely to benefit from atezolizumab beyond progression remains an important challenge in the management of metastatic urothelial carcinoma. NCT02108652. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Phase III, randomised, multicentre trial of maintenance immunotherapy with low-dose interleukin-2 and interferon-alpha for metastatic renal cell cancer.

PubMed

Passalacqua, Rodolfo; Buzio, Carlo; Buti, Sebastiano; Porta, Camillo; Labianca, Roberto; Pezzuolo, Debora; Camisa, Roberta; Sabbatini, Roberto; Benecchi, Luigi; Messina, Caterina; Cengarle, Rita; Vaglio, Augusto; Dalla Chiesa, Matteo; Tomasello, Gianluca; Caminiti, Caterina

2010-04-01

This is the first phase III randomised trial to evaluate maintenance immunotherapy in metastatic renal cell cancer (mRCC). Patients were randomised to receive treatment with a 4-week cycle of subcutaneous low doses IL-2 + IFN in months 1, 3 and 5, and then every 3 months until the first documented disease progression (arm A, suspension), or the same regimen, with chronic maintenance of immunotherapy, regardless of tumour response, until death or intolerable toxicity (arm B, maintenance). The primary endpoint was overall survival (OS); secondary endpoints were time from first progression to death (TFPTD) and tolerability. One hundred and eighty-three patients were enrolled between January 1998 and November 2003. After a median follow-up of 53.9 months, response rate, median OS and median TFPTD were 14.7% (6.3% CR) versus 11.3% (5.5% CR), 14 versus 14 months, 6 versus 5 months, in arms A and B, respectively with no significant differences between the groups. Cox regression analysis showed that the use of chemotherapy after first progression (HR 0.54; 95% CI 0.35-0.86; p = 0.008), PS = 0 (HR 0.53; 95% CI 0.35-0.81; p = 0.001) and female gender (HR 0.63; 95% CI 0.41-0.98; p = 0.038) were significantly associated with a longer TFPTD; treatment arm was not significant (HR 0.88; 95% CI 0.60-1.31; p = 0.54). Toxicity was mainly limited to WHO grades 1 or 2. Chronic maintenance immunotherapy after disease progression is feasible, but does not significantly increase OS or the TFPTD.

Bicuspid Aortic Valve Stenosis and the Effect of Vitamin K2 on Calcification Using 18F-Sodium Fluoride Positron Emission Tomography/Magnetic Resonance: The BASIK2 Rationale and Trial Design.

PubMed

Peeters, Frederique E C M; van Mourik, Manouk J W; Meex, Steven J R; Bucerius, Jan; Schalla, Simon M; Gerretsen, Suzanne C; Mihl, Casper; Dweck, Marc R; Schurgers, Leon J; Wildberger, Joachim E; Crijns, Harry J G M; Kietselaer, Bas L J H

2018-03-21

BASIK2 is a prospective, double-blind, randomized placebo-controlled trial investigating the effect of vitamin K2 (menaquinone-7;MK7) on imaging measurements of calcification in the bicuspid aortic valve (BAV) and calcific aortic valve stenosis (CAVS). BAV is associated with early development of CAVS. Pathophysiologic mechanisms are incompletely defined, and the only treatment available is valve replacement upon progression to severe symptomatic stenosis. Matrix Gla protein (MGP) inactivity is suggested to be involved in progression. Being a vitamin K dependent protein, supplementation with MK7 is a pharmacological option for activating MGP and intervening in the progression of CAVS. Forty-four subjects with BAV and mild-moderate CAVS will be included in the study, and baseline 18 F-sodiumfluoride ( 18 F-NaF) positron emission tomography (PET)/ magnetic resonance (MR) and computed tomography (CT) assessments will be performed. Thereafter, subjects will be randomized (1:1) to MK7 (360 mcg/day) or placebo. During an 18-month follow-up period, subjects will visit the hospital every 6 months, undergoing a second 18 F-NaF PET/MR after 6 months and CT after 6 and 18 months. The primary endpoint is the change in PET/MR 18 F-NaF uptake (6 months minus baseline) compared to this delta change in the placebo arm. The main secondary endpoints are changes in calcium score (CT), progression of the left ventricularremodeling response and CAVS severity (echocardiography). We will also examine the association between early calcification activity (PET) and later changes in calcium score (CT).

GM2 gangliosidosis in a UK study of children with progressive neurodegeneration: 73 cases reviewed.

PubMed

Smith, Nicholas J; Winstone, Anne Marie; Stellitano, Lesley; Cox, Timothy M; Verity, Christopher M

2012-02-01

To report the demographic, phenotypic, and time-to-diagnosis characteristics of children with GM2 gangliosidosis referred to the UK study of Progressive Intellectual and Neurological Deterioration. Case notification is made via monthly surveillance card, administered by the British Paediatric Surveillance Unit to all UK-based paediatricians; children with GM2 gangliosidosis were identified from cases satisfying inclusion in the UK study of Progressive Intellectual and Neurological Deterioration and analysed according to phenotypic and biochemical categories. Between May 1997 and January 2010, 73 individuals with GM2 gangliosidoses were reported: 40 with Tay-Sachs disease, 31 with Sandhoff disease, and two with GM2 activator protein deficiency. Together they account for 6% (73/1164) of all diagnosed cases of progressive intellectual and neurological deterioration. The majority (62/73) were sporadic index cases with no family history. Children of Pakistani ancestry were overrepresented in all subtypes, particularly juvenile Sandhoff disease, accounting for 10 of 11 notified cases. Infantile-onset variants predominated (55/73); the mean age at onset of symptoms was 6.2 and 4.7 months for infantile-onset Tay-Sachs and Sandhoff disease respectively, and 26.2 and 34.7 months for the corresponding juvenile-onset variants. Time to diagnosis averaged 7.4 months and 28.0 months in infantile- and juvenile-onset disease respectively. GM2 gangliosidosis is a significant cause of childhood neurodegenerative disease; timely diagnosis relies upon improved clinical recognition, which may be increasingly important as specific therapies become available. There is a potential benefit from the introduction of screening programmes for high-risk ethnic groups. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

Vascular calcification on plain radiographs is associated with carotid intima media thickness, malnutrition and cardiovascular events in dialysis patients: a prospective observational study

PubMed Central

2013-01-01

Background Vascular calcification (VC) and carotid intima media thickness (CIMT) are strongly associated with cardiovascular (CV) disease. We hypothesized that significant VC on plain radiographs is associated with CIMT and CV events in dialysis patients. In addition, we evaluated risk factors for VC progression on plain radiographs in dialysis patients. Methods In this 2-year observational, prospective study, 67 dialysis patients were included. We checked plain radiographs at baseline and after 2 years. Laboratory tests and malnutrition score were obtained at baseline, after 12 months, and after 24 months. Results The mean age of patients was 56.3 ± 10.3 years and duration of dialysis was 41.3 ± 34.5 months. The prevalence of significant VC was 61.2% and the prevalence of carotid artery atheromatous plaques was 55.6%. Mean CIMT, malnutrition scores, CRP level and prevalence of carotid atheromatous plaques were significantly higher in patients with significant VC. Serum albumin and total iron binding capacity were significantly lower in patients with significant VC compared to patients without significant VC. During a mean observational period of 22 months, patients without significant VC showed lower CV events by the Kaplan-Meyer method (p = 0.010). Progression of VC was found in 35.7% among 56 patients followed up. Hemoglobin after 24 months was an independent factor for progression of VC (Exp(B) = 0.344, 95% Confidence Interval = 0.13 – 0.96, p = 0.034). Conclusions Significant VC on plain radiograph was associated with CIMT, malnutrition, inflammation, and CV events in dialysis patients. Conditions which increase hemoglobin level may retard progression of VC in dialysis patients. PMID:23360132

A comparative analysis of EGFR mutation status in association with the efficacy of TKI in combination with WBRT/SRS/surgery plus chemotherapy in brain metastasis from non-small cell lung cancer.

PubMed

Cai, Ling; Zhu, Jian-fei; Zhang, Xue-wen; Lin, Su-xia; Su, Xiao-dong; Lin, Peng; Chen, Kai; Zhang, Lan-jun

2014-11-01

We proposed to identify the efficacy of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) using whole brain radiotherapy (WBRT)/stereotactic radiosurgery (SRS)/surgery in brain metastases from patients with non-small cell lung cancer (NSCLC) and clarify the association between treatment outcome and EGFR gene mutation status. A total of 282 patients with NSCLC brain metastases who underwent WBRT/SRS/surgery alone or in combination with TKI were enrolled in our study from 2003-2013. Amplification mutation refractory system technology was used to determine the EGFR mutation status in 109 tissue samples. EGFR mutation detection was performed in 109 patients with tumor tissues. The EGFR positive rate was 50 % (55/109), including 26 exon 19 deletions and 24 L858R mutations. The median follow-up time was 28 months. The median overall survival, median progression-free survival of intracranial disease, and median progression-free survival of extracranial disease was significantly longer for patients with TKI treatment (31.9 vs 17.0 months, P < 0.0001; 19.8 vs 12.0 months, P < 0.0001; and 19.6 vs 12.3 months, P < 0.0001; respectively). In subgroup analysis within the TKI group, patients harboring EGFR mutations had better extracranial disease control (20.4 vs 14.1 months, P = 0.032). Administration of TKI agents with conventional therapy compared with conventional therapy alone might be beneficial for overall survival, progression-free survival of intracranial disease and progression-free survival of extracranial disease in patients with brain metastases from NSCLC independent of EGFR mutations.

A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wuthrick, Evan J., E-mail: evan.wuthrick@osumc.edu; Curran, Walter J.; Camphausen, Kevin

Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acutemore » toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival.« less

Mycophenolate mofetil combined with systemic corticosteroids prevents progression to chronic recurrent inflammation and development of 'sunset glow fundus' in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease.

PubMed

Abu El-Asrar, Ahmed M; Dosari, Mona; Hemachandran, Suhail; Gikandi, Priscilla W; Al-Muammar, Abdulrahman

2017-02-01

To evaluate the effectiveness and safety of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. This prospective study included 38 patients (76 eyes). The main outcome measures were final visual acuity, corticosteroid-sparing effect, progression to chronic recurrent granulomatous uveitis and development of complications, particularly 'sunset glow fundus'. The mean follow-up period was 37.0 ± 29.3 (range 9-120 months). Visual acuity of 20/20 was achieved by 93.4% of the eyes. Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering to 10 mg or less daily was 3.8 ± 1.3 months (range 3-7 months). Twenty-two patients (57.9%) discontinued treatment without relapse of inflammation. The mean time observed off of treatment was 28.1 ± 19.6 months (range 1-60 months). None of the eyes progressed to chronic recurrent granulomatous uveitis. The ocular complications encountered were glaucoma in two eyes (2.6%) and cataract in five eyes (6.6%). None of the eyes developed 'sunset glow fundus', and none of the patients developed any systemic adverse events associated with the treatment. Use of MMF as first-line therapy combined with systemic corticosteroids in patients with initial-onset acute VKH disease prevents progression to chronic recurrent granulomatous inflammation and development of 'sunset glow fundus'. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Chemosaturation with Percutaneous Hepatic Perfusion for Unresectable Isolated Hepatic Metastases from Sarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deneve, Jeremiah L., E-mail: Jeremiah.Deneve@Moffitt.org; Choi, Junsung; Gonzalez, Ricardo J.

Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significantmore » improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.« less

Clinical and biomechanical changes following a 4-month toe-out gait modification program for people with medial knee osteoarthritis: a randomized controlled trial.

PubMed

Hunt, M A; Charlton, J M; Krowchuk, N M; Tse, C T F; Hatfield, G L

2018-04-27

To compare changes in knee pain, function, and loading following a 4-month progressive walking program with or without toe-out gait modification in people with medial tibiofemoral knee osteoarthritis. Individuals with medial knee osteoarthritis were randomized to a 4-month program to increase walking activity with (toe-out) or without (progressive walking) concomitant toe-out gait modification. The walking program was similar between the two groups, except that the gait modification group was trained to walk with 15° more toe-out. Primary outcomes included: knee joint pain (WOMAC), foot progression angles and knee joint loading during gait (knee adduction moment (KAM)). Secondary outcomes included WOMAC function, timed stair climb, and knee flexion moments during gait. Seventy-nine participants (40 in toe-out group, 39 in progressive walking group) were recruited. Intention-to-treat analysis showed no between-group differences in knee pain, function, or timed stair climb. However, the toe-out group exhibited significantly greater changes in foot progression angle (mean difference = -9.04° (indicating more toe-out), 95% CI: -11.22°, -6.86°; P < 0.001), late stance KAM (mean difference = -0.26 %BW*ht, 95% CI: -0.39 %BW*ht, -0.12 %BW*ht, P < 0.001) and KAM impulse (-0.06 %BW*ht*s, 95% CI: -0.11 %BW*ht*s, -0.01 %BW*ht*s; P = 0.031) compared to the progressive walking group at follow-up. The only between-group difference that remained at a 1-month retention assessment was foot progression angle, with greater changes in the toe-out group (mean difference = -6.78°, 95% CI: -8.82°, -4.75°; P < 0.001). Though both groups experienced improvements in self-reported pain and function, only the toe-out group experienced biomechanical improvements. NCT02019108. Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology).

PubMed

Soffietti, Riccardo; Trevisan, Elisa; Bertero, Luca; Cassoni, Paola; Morra, Isabella; Fabrini, Maria Grazia; Pasqualetti, Francesco; Lolli, Ivan; Castiglione, Anna; Ciccone, Giovannino; Rudà, Roberta

2014-02-01

The optimal combination of bevacizumab with cytotoxic or cytostatic drugs in recurrent glioblastoma is unknown. We performed a phase 2 trial of combined bevacizumab and fotemustine for patients with glioblastoma at first relapse after radiotherapy and temozolomide. The primary endpoint was 6-month progression-free survival (PFS), while secondary endpoints were overall survival (OS), response rate based on RANO criteria and toxicity. Fifty-four patients with recurrent GBM were enrolled. The authors observed a 6-month PFS rate of 42.6% (95% CI 29.3-55.2) and a median PFS of 5.2 months (95% CI 3.8-6.6). The median OS was 9.1 months (95% CI 7.3-10.3). Twenty-eight patients (52%) had a radiographic response, and a significant neurological improvement with steroid reduction was observed in 25/42 symptomatic patients (60%). MGMT promoter methylation was significantly associated with improved PFS in univariate analysis. Most unifocal tumors at baseline had a focal enhancing progression (76%), while the diffuse non-enhancing progression accounted for 9.5%. Response or survival were not associated with any pattern of progression. Survival after failure of treatment was short. Twelve out of 54 patients (22%) discontinued fotemustine for grade 3/4 myelotoxicity, while 4/54 (7.4%) discontinued bevacizumab. This study failed to demonstrate a superiority of the combination of bevacizumab and fotemustine over either bevacizumab or fotemustine alone as historical controls. Future studies should explore alternative regimens of combination of the two drugs.

Stereotactic Ablative Radiation Therapy as First Local Therapy for Lung Oligometastases From Colorectal Cancer: A Single-Institution Cohort Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it; Badellino, Serena; Ceccarelli, Manuela

2015-03-01

Purpose: To estimate stereotactic ablative radiation therapy (SABR) efficacy and its potential role as an alternative to surgery for the treatment of lung metastases from colorectal cancer. Methods and Materials: Forty consecutive patients who received SABR as first local therapy at the time of lung progression were included, from 2004 to 2014. The primary study endpoint was overall survival. Secondary endpoints were progression-free survival and safety. Results: A single nodule was treated in 26 patients (65%), 2 nodules in 10 patients (25%), 3 in 3 patients (7.5%), and 4 in 1 patient (2.5%), for a total of 59 lesions. The medianmore » delivered biological effective dose was 96 Gy, in 1 to 8 daily fractions. Median follow-up time was 20 months (range, 3-72 months). Overall survival rates at 1, 2, and 5 years were, respectively, 84%, 73%, and 39%, with 14 patients (35%) dead. Median overall survival was 46 months. Progression occurred in 25 patients (62.5%), at a median interval of 8 months; failure at SABR site was observed in 3 patients (7.5%). Progression-free survival rates were 49% and 27% at 1 and 2 years, respectively. Discussion: The results of this retrospective exploratory analysis suggest safety and efficacy of SABR in patients affected with colorectal cancer lung oligometastases and urge inclusion of SABR in prospective clinical trials.« less

Urothelial papilloma of the bladder: a review of 34 de novo cases.

PubMed

Magi-Galluzzi, Cristina; Epstein, Jonathan I

2004-12-01

Urothelial papilloma of the bladder is an uncommon entity when using restrictive diagnostic criteria. We retrospectively studied 34 patients who were diagnosed with urothelial papilloma of the bladder using the criteria of the 1998 WHO/ISUP classification system. Six cases were in-house and the remaining 28 were referred from other institutions as consults to one of the authors. In all cases, the diagnosis of papilloma was the first manifestation of urothelial neoplasia. The mean age of the patients at diagnosis was 57.8 years (range, 23-87 years). The male-to-female ratio was 2.4:1 (24 males and 10 females). The tumor size averaged 3.3 mm (range, 1-20 mm; median, 2 mm). Simple papillary fronds were seen in all cases; in 5 cases the additional finding of secondary budding off of small fronds from larger ones was also seen. In all cases, the fronds had a round morphology; yet in 4 cases elongated fronds were also noted. In 5 cases, dilated lymphatics within the fibrovascular fronds were apparent. One case had foamy histiocytes within the fibrovascular stalks. In all cases, the lining consisted of normal-appearing urothelium without hyperplasia, dysplasia, and/or mitotic figures. Some of the distinctive histologic features seen were changes in the umbrella cells: vacuolization (n = 4), prominence with cytologic atypia (n = 2), eosinophilic syncytial morphology (n = 1), apocrine-like morphology (n = 1), and mucinous metaplasia (n = 1). Follow-up was available in 26 cases with a mean follow-up for those without evidence of progression of 28.9 months (range, 3-127 months). Three patients (8.8%) developed recurrent papilloma 4, 15, and 18 months after the initial diagnosis of papilloma; 1 of these patients also showed progression to noninvasive low-grade urothelial carcinoma at the time of recurrence (15 months). Three patients (8.8%) progressed to higher-grade disease: 2 to noninvasive low grade urothelial carcinoma (11 and 15 months after the original diagnosis) and 1 to a papillary urothelial neoplasm of low malignant potential at 104 months and a noninvasive low-grade urothelial carcinoma at 141 months from the initial diagnosis of papilloma. None of the patients demonstrated progression to either lamina propria (T1) or muscularis propria (T2) invasion. Two patients died of unrelated causes. None of the patients died of bladder cancer. Patients with urothelial papillomas have a low incidence of recurrence and rarely progress to develop urothelial carcinoma. It seems reasonable to avoid labeling these patients as having cancer. It remains to be studied whether and when patients with papillomas who have no evidence of recurrence or progression no longer need to be followed.

SERAPHIN haemodynamic substudy: the effect of the dual endothelin receptor antagonist macitentan on haemodynamic parameters and NT-proBNP levels and their association with disease progression in patients with pulmonary arterial hypertension

PubMed Central

Galiè, Nazzareno; Jansa, Pavel; Pulido, Tomás; Channick, Richard N.; Delcroix, Marion; Ghofrani, Hossein-Ardeschir; Le Brun, Franck-Olivier; Mehta, Sanjay; Perchenet, Loïc; Rubin, Lewis J.; Sastry, B.K.S.; Simonneau, Gérald; Sitbon, Olivier; Souza, Rogério; Torbicki, Adam

2017-01-01

Aims The effect of macitentan on haemodynamic parameters and NT-proBNP levels was evaluated in pulmonary arterial hypertension (PAH) patients in the SERAPHIN study. Association between these parameters and disease progression, assessed by the primary endpoint (time to first morbidity/mortality event), was explored. Methods and results Of the 742 randomized patients, 187 with right heart catheterization at baseline and month 6 participated in a haemodynamic sub-study. Prespecified endpoints included change from baseline to month 6 in cardiac index (CI), right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), mixed-venous oxygen saturation, and NT-proBNP. Exploratory analyses examined associations between CI, RAP, and NT-proBNP and disease progression using the Kaplan-Meier method and Cox regression models. Macitentan improved CI, RAP, mPAP, PVR and NT-proBNP vs. placebo at month 6. Absolute levels of CI, RAP and NT-proBNP at baseline and month 6, but not their changes, were associated with morbidity/mortality events. Patients with CI > 2.5 L/min/m2, RAP < 8 mmHg, or NT-proBNP < 750 fmol/ml at month 6 had a lower risk of morbidity/mortality than those not meeting these thresholds (HR 0.49, 95% CL 0.28–0.86; HR 0.72, 95% CL 0.42–1.22; and HR 0.22, 95% CL 0.15–0.33, respectively). Conclusions For all treatment groups, baseline and month 6 values of CI, RAP, and NT-proBNP, but not their changes, were associated with morbidity/mortality events, confirming their relevance in predicting disease progression in patients with PAH. By improving those parameters, macitentan increased the likelihood of reaching threshold values associated with lower risk of morbidity/mortality. PMID:28329315

Cryoablation combined with allogenic natural killer cell immunotherapy improves the curative effect in patients with advanced hepatocellular cancer.

PubMed

Lin, Mao; Liang, Shuzhen; Wang, Xiaohua; Liang, Yinqing; Zhang, Mingjie; Chen, Jibing; Niu, Lizhi; Xu, Kecheng

2017-10-10

In this study, the clinical efficacy of cryosurgery combined with allogenic natural killer cell immunotherapy for advanced hepatocellular cancer was evaluated. From October 2015 to March 2017, we enrolled 61 patients who met the enrollment criteria and divided them into two groups: 1) the simple cryoablation group (Cryo group, n = 26); and 2) the cryoablation combined with allogenic natural killer cells group (Cryo-NK group, n = 35), the safety and short-term effects were evaluated firstly, then the median progression-free survival, response rate and disease control rate were assessed. All adverse events experienced by the patients were recorded, and included local (e.g., pain, pleural effusion, and ascites) and systemic (e.g., chills, fatigue, and fever) reactions, fever was more frequent. Other possible seriously side effects (e.g., blood or bone marrow changes) were not detected. Combining allogeneic natural killer cells with cryoablation had a synergistic effect, not only enhancing the immune function, improving the quality of life of the patients, but also reducing the expression of AFP and significantly exhibiting good clinical efficacy of the patients. After a median follow-up of 8.7 months (3.9 -15.1months), median progression-free survival was higher in Cryo-NK (9.1 months) than in Cryo (7.6 months, P = 0.0107), median progression-free survival who received multiple natural killer was higher than who just received single natural killer (9.7 months vs.8.4 months, P = 0.0011, respectively), the response rate in Cryo-NK (60.0%) was higher than in Cryo (46.1%, P < 0.05), the disease control rate in Cryo-NK (85.7%) was higher than in Cryo group (69.2%, P < 0.01). Percutaneous cryoablation combined with allogeneic natural killer cell immunotherapy significantly increased median progression-free survival of advanced hepatocellular cancer patients. Multiple allogeneic natural killer cells infusion was associated with better prognosis to advanced hepatocellular cancer.

Cryoablation combined with allogenic natural killer cell immunotherapy improves the curative effect in patients with advanced hepatocellular cancer

PubMed Central

Lin, Mao; Liang, Shuzhen; Wang, Xiaohua; Liang, Yinqing; Zhang, Mingjie; Chen, Jibing; Niu, Lizhi; Xu, Kecheng

2017-01-01

In this study, the clinical efficacy of cryosurgery combined with allogenic natural killer cell immunotherapy for advanced hepatocellular cancer was evaluated. From October 2015 to March 2017, we enrolled 61 patients who met the enrollment criteria and divided them into two groups: 1) the simple cryoablation group (Cryo group, n = 26); and 2) the cryoablation combined with allogenic natural killer cells group (Cryo-NK group, n = 35), the safety and short-term effects were evaluated firstly, then the median progression-free survival, response rate and disease control rate were assessed. All adverse events experienced by the patients were recorded, and included local (e.g., pain, pleural effusion, and ascites) and systemic (e.g., chills, fatigue, and fever) reactions, fever was more frequent. Other possible seriously side effects (e.g., blood or bone marrow changes) were not detected. Combining allogeneic natural killer cells with cryoablation had a synergistic effect, not only enhancing the immune function, improving the quality of life of the patients, but also reducing the expression of AFP and significantly exhibiting good clinical efficacy of the patients. After a median follow-up of 8.7 months (3.9 –15.1months), median progression-free survival was higher in Cryo-NK (9.1 months) than in Cryo (7.6 months, P = 0.0107), median progression-free survival who received multiple natural killer was higher than who just received single natural killer (9.7 months vs.8.4 months, P = 0.0011, respectively), the response rate in Cryo-NK (60.0%) was higher than in Cryo (46.1%, P < 0.05), the disease control rate in Cryo-NK (85.7%) was higher than in Cryo group (69.2%, P < 0.01). Percutaneous cryoablation combined with allogeneic natural killer cell immunotherapy significantly increased median progression-free survival of advanced hepatocellular cancer patients. Multiple allogeneic natural killer cells infusion was associated with better prognosis to advanced hepatocellular cancer. PMID:29137237

SERAPHIN haemodynamic substudy: the effect of the dual endothelin receptor antagonist macitentan on haemodynamic parameters and NT-proBNP levels and their association with disease progression in patients with pulmonary arterial hypertension.

PubMed

Galiè, Nazzareno; Jansa, Pavel; Pulido, Tomás; Channick, Richard N; Delcroix, Marion; Ghofrani, Hossein-Ardeschir; Le Brun, Franck-Olivier; Mehta, Sanjay; Perchenet, Loïc; Rubin, Lewis J; Sastry, B K S; Simonneau, Gérald; Sitbon, Olivier; Souza, Rogério; Torbicki, Adam

2017-04-14

The effect of macitentan on haemodynamic parameters and NT-proBNP levels was evaluated in pulmonary arterial hypertension (PAH) patients in the SERAPHIN study. Association between these parameters and disease progression, assessed by the primary endpoint (time to first morbidity/mortality event), was explored. Of the 742 randomized patients, 187 with right heart catheterization at baseline and month 6 participated in a haemodynamic sub-study. Prespecified endpoints included change from baseline to month 6 in cardiac index (CI), right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), mixed-venous oxygen saturation, and NT-proBNP. Exploratory analyses examined associations between CI, RAP, and NT-proBNP and disease progression using the Kaplan-Meier method and Cox regression models. Macitentan improved CI, RAP, mPAP, PVR and NT-proBNP vs. placebo at month 6. Absolute levels of CI, RAP and NT-proBNP at baseline and month 6, but not their changes, were associated with morbidity/mortality events. Patients with CI > 2.5 L/min/m2, RAP < 8 mmHg, or NT-proBNP < 750 fmol/ml at month 6 had a lower risk of morbidity/mortality than those not meeting these thresholds (HR 0.49, 95% CL 0.28-0.86; HR 0.72, 95% CL 0.42-1.22; and HR 0.22, 95% CL 0.15-0.33, respectively). For all treatment groups, baseline and month 6 values of CI, RAP, and NT-proBNP, but not their changes, were associated with morbidity/mortality events, confirming their relevance in predicting disease progression in patients with PAH. By improving those parameters, macitentan increased the likelihood of reaching threshold values associated with lower risk of morbidity/mortality. © The Author 2017. Published on behalf of the European Society of Cardiology

Doxorubicin-Loaded 70–150 μm Microspheres for Liver-Dominant Metastatic Breast Cancer: Results and Outcomes of a Pilot Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yen-Ting, E-mail: ymerically@gmail.com; Médioni, Jacques, E-mail: jacques.medioni@aphp.fr; Amouyal, Grégory, E-mail: gregory.amouyal@aphp.fr

PurposePatients with breast cancer liver metastasis have a poor prognosis. Local therapy for liver metastasis increases survival. The purpose of this pilot prospective study was to evaluate the efficacy and safety of doxorubicin drug-eluting beads chemoembolization for liver-dominant breast cancer metastasis (LdBM) refractory to chemotherapy.Materials and MethodsAll patients with LdBM refractory to of two or more lines of systemic chemotherapy were screened. Two chemoembolizations at 1-month intervals were scheduled for each patient. Tumor responses were evaluated by MRI every 3 months until progression or death. Adverse events were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.02)more » 1 month after each chemoembolization. All patients were free from systemic treatment until progression. Patients with hormone-positive receptors and/or HER-positive disease status continued their targeted therapy.ResultsOut of 23 patients enrolled (mean age: 57.5 ± 11.5 years), 17 completed two chemoembolizations and six underwent only one because of severe adverse events. At 3-month follow-up, the disease control rate was 83 %. The median progression-free survival from the first chemoembolization was 8 months, and the median overall survival was 17 months. Nineteen patients remained free from any systemic chemotherapy for a mean of 209 ± 92 days until progression. Eight grade 3 (asthenia n = 3, anemia n = 2, thrombocythemia n = 2, liver toxicity n = 1) (Rev 1 Comment 1) occurred after the first procedure. No patient died directly due to the procedure.ConclusionWhile chemoembolization with doxorubicin eluding beads for refractory LdBM leads to an 83 % disease control rate, it also causes severe side effects that need to be adequately managed.« less

Effectiveness study of atropine for progressive myopia in Europeans.

PubMed

Polling, J R; Kok, R G W; Tideman, J W L; Meskat, B; Klaver, C C W

2016-07-01

PurposeRandomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a non-Asian country.MethodsAn effectiveness study was performed in Rotterdam, the Netherlands. Overall 77 children (mean age 10.3 years±2.3), of European (n=53), Asian (n=18), and African (n=6) descent with progressive myopia were prescribed atropine 0.5% eye drops daily. Both parents and children filled in a questionnaire regarding adverse events and adherence to therapy. A standardized eye examination including cycloplegic refraction and axial length was performed at baseline and 1, 4, and 12 months after initiation of therapy.ResultsMean spherical equivalent at baseline was -6.6D (±3.3). The majority (60/77, 78%) of children adhered to atropine treatment for 12 months; 11 of the 17 children who discontinued therapy did so within 1 month after the start of therapy. The most prominent reported adverse events were photophobia (72%), followed by reading problems (38%), and headaches (22%). The progression rate of spherical equivalent before treatment (-1.0D/year±0.7) diminished substantially during treatment (-0.1D/year±0.7) compared to those who ceased therapy (-0.5D/year±0.6; P=0.03).ConclusionsDespite the relatively high occurrence of adverse events, our study shows that atropine can be an effective and sustainable treatment for progressive high myopia in Europeans.

Progression-free survival as primary endpoint in randomized clinical trials of targeted agents for advanced renal cell carcinoma. Correlation with overall survival, benchmarking and power analysis.

PubMed

Bria, Emilio; Massari, Francesco; Maines, Francesca; Pilotto, Sara; Bonomi, Maria; Porta, Camillo; Bracarda, Sergio; Heng, Daniel; Santini, Daniele; Sperduti, Isabella; Giannarelli, Diana; Cognetti, Francesco; Tortora, Giampaolo; Milella, Michele

2015-01-01

A correlation, power and benchmarking analysis between progression-free and overall survival (PFS, OS) of randomized trials with targeted agents or immunotherapy for advanced renal cell carcinoma (RCC) was performed to provide a practical tool for clinical trial design. For 1st-line of treatment, a significant correlation was observed between 6-month PFS and 12-month OS, between 3-month PFS and 9-month OS and between the distributions of the cumulative PFS and OS estimates. According to the regression equation derived for 1st-line targeted agents, 7859, 2873, 712, and 190 patients would be required to determine a 3%, 5%, 10% and 20% PFS advantage at 6 months, corresponding to an absolute increase in 12-month OS rates of 2%, 3%, 6% and 11%, respectively. These data support PFS as a reliable endpoint for advanced RCC receiving up-front therapies. Benchmarking and power analyses, on the basis of the updated survival expectations, may represent practical tools for future trial' design. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Prototype solar heating and cooling systems

NASA Technical Reports Server (NTRS)

1979-01-01

A combination of monthly progress reports are presented. It contains a summary of activities and progress made from November 1, 1978, to February 28, 1979. The effort calls for the development, manufacture, test, system installation, maintenance, problem resolution, and performance evaluation.

Mass Transportation in Massachusetts : demonstration project progress report no. 4

DOT National Transportation Integrated Search

1963-09-01

This fourth Progress Report presents the results of the first eight months of the program of demonstration experiments which the MTC is conducting in cooperation wit the Office of Transportation of the Housing and Home Finance Agency.

Association between Smoking and the Progression of Computed Tomography Findings in Chronic Pancreatitis.

PubMed

Lee, Jeong Woo; Kim, Ho Gak; Lee, Dong Wook; Han, Jimin; Kwon, Hyuk Yong; Seo, Chang Jin; Oh, Ji Hye; Lee, Joo Hyoung; Jung, Jin Tae; Kwon, Joong Goo; Kim, Eun Young

2016-05-23

Smoking and alcohol intake are two wellknown risk factors for chronic pancreatitis. However, there are few studies examining the association between smoking and changes in computed tomography (CT) findings in chronic pancreatitis. The authors evaluated associations between smoking, drinking and the progression of calcification on CT in chronic pancreatitis. In this retrospective study, 59 patients with chronic pancreatitis who had undergone initial and follow-up CT between January 2002 and September 2010 were included. Progression of calcification among CT findings was compared according to the amount of alcohol intake and smoking. The median duration of followup was 51.6 months (range, 17.1 to 112.7 months). At initial CT findings, there was pancreatic calcification in 35 patients (59.3%). In the follow-up CT, progression of calcification was observed in 37 patients (62.7%). Progression of calcification was more common in smokers according to the multivariate analysis (odds ratio [OR], 9.987; p=0.006). The amount of smoking was a significant predictor for progression of calcification in the multivariate analysis (OR, 6.051 in less than 1 pack per day smokers; OR, 36.562 in more than 1 pack per day smokers; p=0.008). Continued smoking accelerates pancreatic calcification, and the amount of smoking is associated with the progression of calcification in chronic pancreatitis.

Incidence of infection in 39-month-old ewes with TMEM154 diplotypes "1 1," "1 3," and "3 3" after natural exposure to ovine progressive pneumonia virus

USDA-ARS?s Scientific Manuscript database

Production and well-being of sheep and goats in many countries are harmfully impacted by small ruminant lentiviruses (SRLV) that cause incurable, progressive diseases. Susceptibility to ovine progressive pneumonia virus (OPPV), the North American form of SRLV, is influenced by variants of the ovine...

Applied technology section. Monthly report, December 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buckner, M.R.

1994-01-28

This monthly report contains abstracts of the progress made in various projects from the applied technology section at the Savannah River Plant. Research areas include engineering modeling and simulation, applied physics, experimental thermal hydraulics, and packaging and transportation.

Phase II study of Gleevec® plus hydroxyurea in adults with progressive or recurrent low-grade glioma1

PubMed Central

Reardon, David A.; Desjardins, Annick; Vredenburgh, James J.; Herndon, James E.; Coan, April; Gururangan, Sridharan; Peters, Katherine B.; McLendon, Roger; Sathornsumetee, Sith; Rich, Jeremy N.; Lipp, Eric S.; Janney, Dorothea; Friedman, Henry S.

2013-01-01

Background We evaluated the efficacy of imatinib plus hydroxyurea in patients with progressive/recurrent low-grade glioma. Methods A total of 64 patients with recurrent/progressive low-grade glioma were enrolled in this single-center study that stratified patients into astrocytoma and oligodendroglioma cohorts. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary endpoint was progression-free survival at 12 months (PFS-12) and secondary endpoints were safety, median progression-free survival and radiographic response rate. Results Thirty-two patients were enrolled into each cohort. Eleven patients (17%) had prior radiotherapy and 24 (38%) had received prior chemotherapy. The median PFS and PFS-12 were 11 months and 39%, respectively. Outcome did not differ between the histologic cohorts. No patient achieved a radiographic response. The most common grade 3 or greater adverse events were neutropenia (11%), thrombocytopenia (3%) and diarrhea (3%). Conclusions Imatinib plus hydroxyurea was well tolerated among recurrent/progressive LGG patients but this regimen demonstrated negligible anti-tumor activity. PMID:22371319

Progressive outer retinal necrosis associated with occlusive vasculitis in acquired immunodeficiency syndrome.

PubMed

Tseng, Chien-Chi; Chen, San-Ni; Hwang, Jiunn-Feng; Lin, Chun-Ju; Chen, Huan-Sheng

2015-05-01

A 45-year-old man, a case of acquired immunodeficiency syndrome, received a highly active antiretroviral therapy at the outpatient service for 4 years without regular follow-up. He experienced progressively blurred vision for 6 months and a cutaneous zoster on his back 3 months ago. He was diagnosed with progressive outer retinal necrosis by polymerase chain reaction-restriction fragment length polymorphism using an aqueous humor sample, which revealed an existence of varicella zoster virus. He was given a combination of systemic, intravitreal antiviral and a highly active antiretroviral therapy. Occlusive vasculitis, an unusual finding for progressive outer retinal necrosis, developed in both eyes 1 week after the secondary intravitreal injection. Unfortunately, his vision deteriorated to no light perception in both eyes within 2 weeks. Progressive outer retinal necrosis is characterized clinically as showing minimal or no inflammation in the aqueous and vitreous humors, absence of retinal vasculitis, and patches of yellowish spots located deep in the retina. Physicians should pay attention to this rare case of progressive outer retinal necrosis associated occlusive vasculitis with very poor prognosis in spite of aggressive treatment. Copyright © 2015. Published by Elsevier B.V.

Standardized Treatment of Neonatal Status Epilepticus Improves Outcome.

PubMed

Harris, Mandy L; Malloy, Katherine M; Lawson, Sheena N; Rose, Rebecca S; Buss, William F; Mietzsch, Ulrike

2016-12-01

We aimed to decrease practice variation in treatment of neonatal status epilepticus by implementing a standardized protocol. Our primary goal was to achieve 80% adherence to the algorithm within 12 months. Secondary outcome measures included serum phenobarbital concentrations, number of patients progressing from seizures to status epilepticus, and length of hospital stay. Data collection occurred for 6 months prior and 12 months following protocol implementation. Adherence of 80% within 12 months was partially achieved in patients diagnosed in our hospital; in pretreated patients, adherence was not achieved. Maximum phenobarbital concentrations were decreased (56.8 vs 41.0 µg/mL), fewer patients progressed from seizures to status epilepticus (46% vs 36%), and hospital length of stay decreased by 9.7 days in survivors. In conclusion, standardized, protocol-driven treatment of neonatal status epilepticus improves consistency and short-term outcome. © The Author(s) 2016.

[Nutrition and attention deficit hyperactivity disorder: developmental follow-up of the anthropometric variables of a group of patients receiving treatment with osmotic controlled-release methylphenidate].

PubMed

Dura-Trave, T; Yoldi-Petri, M E; Zardoya-Santos, P

2011-09-01

To perform a developmental analysis of the anthropometric variables of a group of patients diagnosed with attention deficit hyperactivity disorder (ADHD) in order to determine the repercussions of treatment with osmotic controlled-release methylphenidate (MTF-OROS). The medical records of 187 patients with ADHD under treatment with MTF-OROS over a period of 30 months were reviewed. Data collected included weight, height and body mass index at diagnosis (baseline) and at 6, 12, 18, 24 and 30 months' follow-up. The mean age at diagnosis was 8.14 ± 1.6 years. The dose of MTF-OROS was progressively increased until 36.9 ± 12.1 mg/day (1.05 mg/kg/day) at day 30 of the follow-up. At diagnosis, 34.9% of patients had a deficient nutritional situation (subnutrition or malnutrition), which affected 50.3% of the patients at 30 months. The baseline value for weight (Z-score) progressively decreased during treatment until values that were significantly lower than the baseline value at 12 months were reached (p < 0.05); these values remained significantly lower until 30 months. The baseline value for height (Z-score) also progressively decreased during treatment until values that were significantly lower than the baseline value at 24 and 30 months were reached (p < 0.05). At the time they were diagnosed with ADHD, one out of every three patients was in a deficient nutritional situation (subnutrition or malnutrition). Continued treatment with MTF-OROS for 30 months had a negative influence on height, which could perhaps be attenuated by improving the patients' nutrition.

Initiation and progression of physical activity after laparoscopic and open gastric bypass surgery.

PubMed

Evans, Ronald K; Bond, Dale S; Demaria, Eric J; Wolfe, Luke G; Meador, Jill G; Kellum, John M

2004-12-01

This study compared postoperative physical activity participation among patients who underwent laparoscopic (LGBS) or open gastric bypass surgery (OGBS). Postoperative physical activity participation is considered important for achieving optimal weight loss and maintenance after gastric bypass surgery. However, no study has examined the relationship between surgery type and postoperative physical activity. Minimal invasiveness and reduced recovery time associated with LGBS compared with OGBS may permit earlier initiation and faster progression of postsurgical physical activity and potentially contribute to greater long-term adherence rates. Self-reported physical activity participation and aerobic physical activity hours per week at 2-weeks, 3-months, and 6-months postsurgery were assessed among LGBS and OGBS patients (presurgical body mass index of 35 to 70 kg/m(2)) at a university hospital from 1988-2002. Of the 2,235 patients, 531 (24%) and 1704 (76%) underwent LGBS and OGBS, respectively. A greater proportion of LGBS patients reported physical activity participation at each time point compared with OGBS patients (2 week, 76% vs 62%; 3 months, 84% vs 74%; 6 months, 85% vs 76%). Furthermore, LGBS patients reported a significantly greater physical activity duration at 2-weeks postsurgery compared with OGBS patients. A nonsignificant trend toward greater physical activity duration was observed in the LGBS patients at 3 months, whereas 6-month physical activity duration was similar between groups. LGBS, compared with OGBS, may promote earlier onset, progression, and maintenance of physical activity until 6 months postsurgery. Future studies need to prospectively determine whether LGBS, via facilitation of greater engagement in postsurgical physical activity, contributes to more successful weight loss and weight maintenance compared with OGBS.

Progression of Pro23His Retinopathy in a Miniature Swine Model of Retinitis Pigmentosa

PubMed Central

Scott, Patrick A.; de Castro, Juan P. Fernandez; DeMarco, Paul J.; Ross, Jason W.; Njoka, Josephat; Walters, Eric; Prather, Randall S.; McCall, Maureen A.; Kaplan, Henry J.

2017-01-01

Purpose We characterize the progression of retinopathy in Filial 1 (F1) progeny of a transgenic (Tg) founder miniswine exhibiting severe Pro23His (P23H) retinopathy. Methods The F1 TgP23H miniswine progeny were created by crossing TgP23H founder miniswine 53-1 with wild type (WT) inbred miniature swine. Scotopic (rod-driven) and photopic (cone-driven) retinal functions were evaluated in F1 TgP23H and WT littermates using full field electroretinograms (ffERGs) at 1, 2, 3, 6, 9, 12, and 18 months of age, as well as the Tg founder miniswine at 6 years of age. Miniswine were euthanized and their retinas processed for morphologic evaluation at the light and electron microscopic level. Retinal morphology of a 36-month-old Tg miniswine also was examined. Results Wild type littermates reached mature scotopic and photopic retinal function by 3 months, while TgP23H miniswine showed abnormal scotopic ffERGs at the earliest time point, 1 month, and depressed photopic ffERGs after 2 months. Rod and cone photoreceptors (PR) exhibited morphologic abnormalities and dropout from the outer nuclear layer at 1 month, with only a monolayer of cone PR somata remaining after 2 months. The retinas showed progressive neural remodeling of the outer retina that included dendritic retraction of rod bipolar cells and glial seal formation by Müller cells. The TgP23H founder miniswine showed cone PR with relatively intact morphology exclusive to the area centralis. Conclusions The F1 Tg miniswine and the TgP23H founder miniswine exhibit similar retinopathy. Translational Relevance TgP23H miniswine are a useful large-eye model to study pathogenesis and preservation cone PRs in humans with retinitis pigmentosa. PMID:28316877

[Liver and lung metastases of colorectal cancer. Long-term survival and prognostic factors].

PubMed

Sponholz, S; Bölükbas, S; Schirren, M; Oguzhan, S; Kudelin, N; Schirren, J

2016-02-01

The resection of liver and lung metastases from colorectal cancer has not yet been completely investigated. The aim of this study was to investigate the overall survival and prognostic factors for patients with liver and lung metastases from colorectal cancer. A retrospective review of a prospective database of 52 patients with liver and lung metastases from colorectal cancer, undergoing metastasectomy with curative intent from 1999-2009 at a single institution was carried out. The mean overall survival (OS) was 64 months. For synchronous liver and lung metastases the mean overall survival was 63 months (5-year survival 54 %) and for metachronous liver and lung metastases 74 months (5-year survival 58 %, p = 0.451). A poor prognostic outcome was observed in cases of localization of the primary tumor in the rectum (OS 81 vs. 38 months, p = 0.004), with multiple lung metastases (≥ 2 metastases, OS 74 vs. 59 months, p = 0.032) and with disease progression after premetastasectomy chemotherapy (OS 74 vs. 63 vs. 15 months, p < 0.001). No influence on overall survival was detected for bilateral lung metastases, thoracic lymph node metastases, disease recurrence and disease-free interval < 36 months. Metastasectomy for liver and lung metastases of colorectal cancer is associated with a good overall survival in selected cases. Patients with liver and lung metastases should not be routinely excluded from metastasectomy and patients with thoracic lymph node metastases should also not be routinely excluded. Negative prognostic factors for survival are localization of the tumor in the rectum, multiple metastases and disease progression after premetastasectomy chemotherapy. Patients with disease progression after premetastasectomy chemotherapy should be excluded from metastasectomy.

NASA's Space Launch System: A Transformative Capability for Deep Space Missions

NASA Technical Reports Server (NTRS)

Creech, Stephen D.

2017-01-01

Already making substantial progress toward its first launches, NASA’s Space Launch System (SLS) exploration-class launch vehicle presents game-changing new opportunities in spaceflight, enabling human exploration of deep space, as well as a variety of missions and mission profiles that are currently impossible. Today, the initial configuration of SLS, able to deliver more than 70 metric tons of payload to low Earth orbit (LEO), is well into final production and testing ahead of its planned first flight, which will send NASA’s new Orion crew vehicle around the moon and will deploy 13 CubeSats, representing multiple disciplines, into deep space. At the same time, production work is already underway toward the more-capable Block 1B configuration, planned to debut on the second flight of SLS, and capable of lofting 105 tons to LEO or of co-manifesting large exploration systems with Orion on launches to the lunar vicinity. Progress being made on the vehicle for that second flight includes initial welding of its core stage and testing of one of its engines, as well as development of new elements such as the powerful Exploration Upper Stage and the Universal Stage Adapter “payload bay.” Ultimately, SLS will evolve to a configuration capable of delivering more than 130 tons to LEO to support humans missions to Mars. In order to enable human deep-space exploration, SLS provides unrivaled mass, volume, and departure energy for payloads, offering numerous benefits for a variety of other missions. For robotic science probes to the outer solar system, for example, SLS can cut transit times to less than half that of currently available vehicles or substantially increased spacecraft mass. In the field of astrophysics, SLS’ high payload volume, in the form of payload fairings with a diameter of up to 10 meters, creates the opportunity for launch of large-aperture telescopes providing an unprecedented look at our universe. This presentation will give an overview of SLS’ capabilities and its current status, and discuss the vehicle’s potential for human exploration of deep space and other game-changing utilization opportunities.

Early-onset, slow progression of cone photoreceptor dysfunction and degeneration in CNG channel subunit CNGB3 deficiency.

PubMed

Xu, Jianhua; Morris, Lynsie; Fliesler, Steven J; Sherry, David M; Ding, Xi-Qin

2011-06-01

To investigate the progression of cone dysfunction and degeneration in CNG channel subunit CNGB3 deficiency. Retinal structure and function in CNGB3(-/-) and wild-type (WT) mice were evaluated by electroretinography (ERG), lectin cytochemistry, and correlative Western blot analysis of cone-specific proteins. Cone and rod terminal integrity was assessed by electron microscopy and synaptic protein immunohistochemical distribution. Cone ERG amplitudes (photopic b-wave) in CNGB3(-/-) mice were reduced to approximately 50% of WT levels by postnatal day 15, decreasing further to approximately 30% of WT levels by 1 month and to approximately 20% by 12 months of age. Rod ERG responses (scotopic a-wave) were not affected in CNGB3(-/-) mice. Average CNGB3(-/-) cone densities were approximately 80% of WT levels at 1 month and declined slowly thereafter to only approximately 50% of WT levels by 12 months. Expression levels of M-opsin, cone transducin α-subunit, and cone arrestin in CNGB3(-/-) mice were reduced by 50% to 60% by 1 month and declined to 35% to 45% of WT levels by 9 months. In addition, cone opsin mislocalized to the outer nuclear layer and the outer plexiform layer in the CNGB3(-/-) retina. Cone and rod synaptic marker expression and terminal ultrastructure were normal in the CNGB3(-/-) retina. These findings are consistent with an early-onset, slow progression of cone functional defects and cone loss in CNGB3(-/-) mice, with the cone signaling deficits arising from disrupted phototransduction and cone loss rather than from synaptic defects.

Longitudinal patterns of youth access to cigarettes and smoking progression: Minnesota Adolescent Community Cohort (MACC) study (2000 – 2003)

PubMed Central

Widome, Rachel; Forster, Jean L.; Hannan, Peter J.; Perry, Cheryl L.

2008-01-01

OBJECTIVES To measure community-level changes in the methods youth use to obtain cigarettes over time and to relate these methods to the progression of smoking. METHODS We analyzed 2000-2003 data from the Minnesota Adolescent Community Cohort study, where youth (beginning at age 12), who were living in Minnesota at baseline, were surveyed every six months via telephone. We conducted mixed model repeated measures logistic regression to obtain probabilities of cigarette access methods among past 30-day smokers (n = 340 at baseline). RESULTS The probability of obtaining cigarettes from a commercial source in the past month declined from 0.36 at baseline to 0.22 at the sixth survey point while the probability of obtaining cigarettes from a social source during the previous month increased from 0.54 to 0.76 (p for both trends = 0.0001). At the community level, the likelihood of adolescents obtaining cigarettes from social sources was inversely related to the likelihood of progressing to heavy smoking (p < 0.001). CONCLUSIONS During this time, youth shifted to greater reliance on social sources and less on commercial sources. A trend toward less commercial access to cigarettes accompanied by an increase in social access may translate to youth being less likely to progress to heavier smoking. PMID:17719080

Hormone profiling, WHO 2010 grading, and AJCC/UICC staging in pancreatic neuroendocrine tumor behavior

PubMed Central

Morin, Emilie; Cheng, Sonia; Mete, Ozgur; Serra, Stefano; Araujo, Paula B; Temple, Sara; Cleary, Sean; Gallinger, Steven; Greig, Paul D; McGilvray, Ian; Wei, Alice; Asa, Sylvia L; Ezzat, Shereen

2013-01-01

Pancreatic neuroendocrine tumors (pNETs) are the second most common pancreatic neoplasms, exhibiting a complex spectrum of clinical behaviors. To examine the clinico-pathological characteristics associated with long-term prognosis we reviewed 119 patients with pNETs treated in a tertiary referral center using the WHO 2010 grading and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems, with a median follow-up of 38 months. Tumor size, immunohistochemistry (IHC) profiling and patient characteristics-determining stage were analyzed. Primary clinical outcomes were disease progression or death. The mean age at presentation was 52 years; 55% were female patients, 11% were associated with MEN1 (multiple endocrine neoplasia 1) or VHL (Von Hippel–Lindau); mean tumor diameter was 3.3 cm (standard deviation, SD) (2.92). The clinical presentation was incidental in 39% with endocrine hypersecretion syndromes in only 24% of cases. Nevertheless, endocrine hormone tissue immunoreactivity was identified in 67 (56.3%) cases. According to WHO 2010 grading, 50 (42%), 38 (31.9%), and 3 (2.5%) of tumors were low grade (G1), intermediate grade (G2), and high grade (G3), respectively. Disease progression occurred more frequently in higher WHO grades (G1: 6%, G2: 10.5%, G3: 67%, P = 0.026) and in more advanced AJCC stages (I: 2%, IV: 63%, P = 0.033). Shorter progression free survival (PFS) was noted in higher grades (G3 vs. G2; 21 vs. 144 months; P = 0.015) and in more advanced AJCC stages (stage I: 218 months, IV: 24 months, P < 0.001). Liver involvement (20 vs. 173 months, P < 0.001) or histologically positive lymph nodes (33 vs. 208 months, P < 0.001) were independently associated with shorter PFS. Conversely, tissue endocrine hormone immunoreactivity, independent of circulating levels was significantly associated with less aggressive disease. Age, gender, number of primary tumors, and heredity were not significantly associated with prognosis. Although the AJCC staging and WHO 2010 grading systems are useful in predicting disease progression, tissue endocrine hormone profiling provides additional information of potentially important prognostic value. Although the AJCC staging and WHO 2010 grading systems are useful in predicting disease progression, tissue endocrine hormone profiling provides additional information of potentially important prognostic value. PMID:24403235

Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models.

PubMed

Mdala, Ibrahimu; Olsen, Ingar; Haffajee, Anne D; Socransky, Sigmund S; Thoresen, Magne; de Blasio, Birgitte Freiesleben

2014-09-01

To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis. Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP. In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87-97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4-5 months and sites recovered with a high probability (96-98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased. Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression. © 2014 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

A method to detect progression of glaucoma using the multifocal visual evoked potential technique

PubMed Central

Wangsupadilok, Boonchai; Kanadani, Fabio N.; Grippo, Tomas M.; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

2010-01-01

Purpose To describe a method for monitoring progression of glaucoma using the multifocal visual evoked potential (mfVEP) technique. Methods Eighty-seven patients diagnosed with open-angle glaucoma were divided into two groups. Group I, comprised 43 patients who had a repeat mfVEP test within 50 days (mean 0.9 ± 0.5 months), and group II, 44 patients who had a repeat test after at least 6 months (mean 20.7 ± 9.7 months). Monocular mfVEPs were obtained using a 60-sector pattern reversal dartboard display. Monocular and interocular analyses were performed. Data from the two visits were compared. The total number of abnormal test points with P < 5% within the visual field (total scores) and number of abnormal test points within a cluster (cluster size) were calculated. Data for group I provided a measure of test–retest variability independent of disease progression. Data for group II provided a possible measure of progression. Results The difference in the total scores for group II between visit 1 and visit 2 for the interocular and monocular comparison was significant (P < 0.05) as was the difference in cluster size for the interocular comparison (P < 0.05). Group I did not show a significant change in either total score or cluster size. Conclusion The change in the total score and cluster size over time provides a possible method for assessing progression of glaucoma with the mfVEP technique. PMID:18830654

Frequency doubling technology perimetry for detection of visual field progression in glaucoma: a pointwise linear regression analysis.

PubMed

Liu, Shu; Yu, Marco; Weinreb, Robert N; Lai, Gilda; Lam, Dennis Shun-Chiu; Leung, Christopher Kai-Shun

2014-05-02

We compared the detection of visual field progression and its rate of change between standard automated perimetry (SAP) and Matrix frequency doubling technology perimetry (FDTP) in glaucoma. We followed prospectively 217 eyes (179 glaucoma and 38 normal eyes) for SAP and FDTP testing at 4-month intervals for ≥36 months. Pointwise linear regression analysis was performed. A test location was considered progressing when the rate of change of visual sensitivity was ≤-1 dB/y for nonedge and ≤-2 dB/y for edge locations. Three criteria were used to define progression in an eye: ≥3 adjacent nonedge test locations (conservative), any three locations (moderate), and any two locations (liberal) progressed. The rate of change of visual sensitivity was calculated with linear mixed models. Of the 217 eyes, 6.1% and 3.9% progressed with the conservative criteria, 14.5% and 5.6% of eyes progressed with the moderate criteria, and 20.1% and 11.7% of eyes progressed with the liberal criteria by FDTP and SAP, respectively. Taking all test locations into consideration (total, 54 × 179 locations), FDTP detected more progressing locations (176) than SAP (103, P < 0.001). The rate of change of visual field mean deviation (MD) was significantly faster for FDTP (all with P < 0.001). No eyes showed progression in the normal group using the conservative and the moderate criteria. With a faster rate of change of visual sensitivity, FDTP detected more progressing eyes than SAP at a comparable level of specificity. Frequency doubling technology perimetry can provide a useful alternative to monitor glaucoma progression.

The Chronopsychological Aspects of College Students' Academic Progress

ERIC Educational Resources Information Center

Barbarash, N.; Chichilenko, M.; Tarasenko, N.; Dvurechenskaia, G.; Kuvshinov, D.

2006-01-01

The idea of the human "individual year" (IY) refers to the span of time from one birthday to the next and provisionally divided into trimesters: the first trimester consisting of months one through three from the date of birth, the second consisting of months four through six, the third consisting of months seven through nine, and the…

Identification of a prospective early motor progression cluster of Parkinson's disease: Data from the PPMI study.

PubMed

Vavougios, George D; Doskas, Triantafyllos; Kormas, Constantinos; Krogfelt, Karen A; Zarogiannis, Sotirios G; Stefanis, Leonidas

2018-04-15

The aim of our study is to phenotype PD motor progression, and to detect whether serum, cerebrospinal fluid (CSF), neuroimaging biomarkers and neuropsychological measures characterize PD motor progression phenotypes. We defined motor progression as a difference of at least one point in the Hoehn & Yahr (H&Y) scale between the baseline (Visit 0, V0), 12 months (Visit 04, V04) and 36 months (Visit 08, V08) milestones of the Progression Markers Initiative (PPMI) study. H&Y progression events were recorded at each milestone in order to be used as cluster analysis variables, in order to produce progression phenotypes. Subsequently, cross-cluster comparisons prior to and following (pairwise) propensity score matching were performed in order to assess phenotype - defining characteristics. Four progression clusters where identified: SPPD: Secondarily Progressive PD, H&Y progression between V04 and V08; EPPD: Early Progressive PD. H&Y progression between V0 and V04; NPPD: Non Progressive PD, no H&Y progression; MIPD: Minimally Improving PD, i.e. Minimal H&Y improvement H&Y progression between V04 and V08;. Independent Samples Mann Whitney U tests determined CSF aSyn (p = 0.006, adj p-value = 0.036. I) and Semantic Animal fluency T-score (SFT, p = 0.003, adjusted p-value = 0.016.) as statistically significant cross-cluster characteristics. Following Propensity Score Matching, SFT, Hopkins Verbal Learning Test (Retention/Recall), Serum IGF1, CSF aSyn, DaT-SPECT binding ratios (SBRs) and the Benton Judgement of Line Orientation Test (BJLOT) were determined as statistically significant predictors of cluster differentiation (p < 0.05). SFT, Serum IGF1, CSF aSyn and DaT-SPECT-derived, basal ganglia Striatal Binding Ratios warrant further investigation as possible motor progression biomarkers. Copyright © 2018 Elsevier B.V. All rights reserved.

Mass transportation in Massachusetts : demonstration project progress report no. 3

DOT National Transportation Integrated Search

1963-06-25

The Third Progress Report marks the completion of six months experiments in the program conducted by the Mass Transportation Commission, with the cooperation of the Office of Transportation of the Housing and Home Finance Agency. As of mid-June, expe...

Outcomes After Whole Brain Reirradiation in Patients With Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, Christina H.; Jimenez, Rachel; Niemierko, Andrzej

Purpose: Patients with brain metastases are often treated with whole brain radiation therapy (WBRT) for purposes of palliation. The treatment of those who experience subsequent intracranial disease progression can include a second course of WBRT, although there is controversy surrounding its safety and efficacy. This study examines the outcomes in patients at Massachusetts General Hospital who underwent reirradiation. Patients and Methods: We examined the medical records of 17 patients at Massachusetts General Hospital with brain metastases who were initially treated with WBRT between 2002 and 2008 and were subsequently retreated with a second course of WBRT. The median dose formore » the first course of WBRT was 35 Gy (range, 28-40 Gy), with a fraction size of 2 to 3 Gy (median, 2.5 Gy). The median dose at reirradiation was 21.6 Gy (range, 14-30 Gy), with a fraction size of 1.5 to 2 Gy (median, 1.8 Gy). Results: The second course of WBRT was administered upon radiographic disease progression in all patients. Of 10 patients with complete follow-up data, 8 patients experienced complete or partial symptom resolution, and 2 did not show clinical improvement. The time to radiographic progression was 5.2 months. The median overall survival for all patients after diagnosis of metastases was 24.7 months. The median survival time after initiation of reirradiation was 5.2 months (95% CI, 1.3-8.7). In 6 patients with stable extracranial disease, the median survival time after retreatment was 19.8 months (95% CI, 2.7-{infinity}), compared with 2.5 months (95% CI, 0.8-5.5) for those with extracranial disease progression (p = 0.05). Acute adverse reactions occurred in 70.5% of patients but were mild to moderate in severity. Conclusion: In select patients and especially those with stable extracranial disease, reirradiation may be an appropriate and effective intervention to provide symptomatic relief and slow intracranial disease progression. Side effects were minimal and did not cause substantial changes in quality of life.« less

Rapidly Progressive Maxillary Atelectasis.

PubMed

Elkhatib, Ahmad; McMullen, Kyle; Hachem, Ralph Abi; Carrau, Ricardo L; Mastros, Nicholas

2017-07-01

Report of a patient with rapidly progressive maxillary atelectasis documented by sequential imaging. A 51-year-old man, presented with left periorbital and retro-orbital pain associated with left nasal obstruction. An initial computed tomographic (CT) scan of the paranasal sinuses failed to reveal any significant abnormality. A subsequent CT scan, indicated for recurrence of symptoms 11 months later, showed significant maxillary atelectasis. An uncinectomy, maxillary antrostomy, and anterior ethmoidectomy resulted in a complete resolution of the symptoms. Chronic maxillary atelectasis is most commonly a consequence of chronic rhinosinusitis. All previous reports have indicated a chronic process but lacked documentation of the course of the disease. This report documents a patient of rapidly progressive chronic maxillary atelectasis with CT scans that demonstrate changes in the maxillary sinus (from normal to atelectatic) within 11 months.

Progressive ataxia in a Charolais bull.

PubMed

Zicker, S C; Kasari, T R; Scruggs, D W; Read, W K; Edwards, J F

1988-06-01

A 20-month-old Charolais bull was referred for evaluation of progressive hind limb ataxia. Clinical findings suggested a neuroanatomic lesion caudal to T2. Postmortem histologic examination revealed multifocal, acellular, pale, eosinophilic plaques throughout the cerebellum, which were diagnostic for the disease progressive ataxia of Charolais cattle. This disease is presumed to have a hereditary transmission and is not commonly recognized in the United States.

Effect of rimonabant on carotid intima-media thickness (CIMT) progression in patients with abdominal obesity and metabolic syndrome: the AUDITOR Trial.

PubMed

O'Leary, Daniel H; Reuwer, Anne Q; Nissen, Steven E; Després, Jean-Pierre; Deanfield, John E; Brown, Michael W; Zhou, Rong; Zabbatino, Salvatore M; Job, Bernard; Kastelein, John J P; Visseren, Frank L J

2011-07-01

The aim of this trial was to determine whether obese patients benefit from treatment with rimonabant in terms of progression of carotid atherosclerosis. Rimonabant, a selective cannabinoid-1 receptor blocker, reduces body weight and improves cardiometabolic risk factors in patients who are obese. A prospective, double-blind, placebo-controlled trial (Atherosclerosis Underlying Development assessed by Intima-media Thickness in patients On Rimonabant (AUDITOR)) randomised 661 patients with abdominal obesity and metabolic syndrome to rimonabant or placebo for 30 months of treatment. The absolute change in the average value for six segments of far wall carotid intima-media thickness from baseline to month 30 was 0.010 ± 0.095 mm in the rimonabant group and 0.012 ± 0.091 mm in the placebo group (p=0.67). The annualised change was an increase of 0.005 ± 0.042 mm for the rimonabant-treated group and 0.007 ± 0.043 mm for the placebo-treated group (p=0.45). There was no difference in atherosclerosis progression between patients receiving rimonabant for 30 months and those receiving placebo for the primary efficacy measure (absolute change in carotid intima-media thickness). These findings are consistent with a similar study using coronary intravascular ultrasound and another study evaluating the occurrence of cardiovascular events. Our findings suggest that a 5% loss of body weight over a 30-month period with rimonabant is insufficient to modify atherosclerosis progression in the carotid artery in obese patients with metabolic syndrome. Clinical trial registration information clinicaltrials.gov Identifier: NCT00228176.

Spiral ganglion degeneration and hearing loss as a consequence of satellite cell death in saposin B-deficient mice.

PubMed

Akil, Omar; Sun, Ying; Vijayakumar, Sarath; Zhang, Wujuan; Ku, Tiffany; Lee, Chi-Kyou; Jones, Sherri; Grabowski, Gregory A; Lustig, Lawrence R

2015-02-18

Saposin B (Sap B) is an essential activator protein for arylsulfatase A in the hydrolysis of sulfatide, a lipid component of myelin. To study Sap B's role in hearing and balance, a Sap B-deficient (B(-/-)) mouse was evaluated. At both light and electron microscopy (EM) levels, inclusion body accumulation was seen in satellite cells surrounding spiral ganglion (SG) neurons from postnatal month 1 onward, progressing into large vacuoles preceding satellite cell degeneration, and followed by SG degeneration. EM also revealed reduced or absent myelin sheaths in SG neurons from postnatal month 8 onwards. Hearing loss was initially seen at postnatal month 6 and progressed thereafter for frequency-specific stimuli, whereas click responses became abnormal from postnatal month 13 onward. The progressive hearing loss correlated with the accumulation of inclusion bodies in the satellite cells and their subsequent degeneration. Outer hair cell numbers and efferent function measures (distortion product otoacoustic emissions and contralateral suppression) were normal in the B(-/-) mice throughout this period. Alcian blue staining of SGs demonstrated that these inclusion bodies corresponded to sulfatide accumulation. In contrast, changes in the vestibular system were much milder, but caused severe physiologic deficits. These results demonstrate that loss of Sap B function leads to progressive sulfatide accumulation in satellite cells surrounding the SG neurons, leading to satellite cell degeneration and subsequent SG degeneration with a resultant loss of hearing. Relative sparing of the efferent auditory and vestibular neurons suggests that alternate glycosphingolipid metabolic pathways predominate in these other systems. Copyright © 2015 the authors 0270-6474/15/353263-13$15.00/0.

Restrictive allograft syndrome after lung transplantation: new radiological insights.

PubMed

Dubbeldam, Adriana; Barthels, Caroline; Coolen, Johan; Verschakelen, Johny A; Verleden, Stijn E; Vos, Robin; Verleden, Geert M; De Wever, Walter

2017-07-01

To describe the CT changes in patients with restrictive allograft syndrome (RAS) after lung transplantation, before and after clinical diagnosis. This retrospective study included 22 patients with clinical diagnosis of RAS. Diagnosis was based on a combination of forced expiratory volume (FEV1) decline (≥20 %) and total lung capacity (TLC) decline (≥10 %). All available CT scans after transplantation were analyzed for the appearance and evolution of lung abnormalities. In 14 patients, non-regressing nodules and reticulations predominantly affecting the upper lobes developed an average of 13.9 months prior to the diagnosis of RAS. Median graft survival after onset of non-regressing abnormalities was 33.5 months, with most patients in follow-up (9/14). In eight patients, a sudden appearance of diffuse consolidations mainly affecting both upper and lower lobes was seen an average of 2.8 months prior to the diagnosis of RAS. Median graft survival was 6.4 months after first onset of non-regressing abnormalities, with graft loss in most patients (6/8). RAS has been previously described as a homogenous group. However, our study shows two different groups of RAS-patients: one with slow progression and one with fast progression. The two groups show different onset and progression patterns of CT abnormalities. • RAS is the newest discovered form of chronic lung allograft dysfunction (CLAD). • RAS is not a homogenous group, as survival varies greatly between patients. • In this study, we see two different CT onset and progression patterns. • These two different CT patterns also correlate with a different survival rate.

Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients.

PubMed

Buda-Nowak, Anna; Kucharz, Jakub; Dumnicka, Paulina; Kuzniewski, Marek; Herman, Roman Maria; Zygulska, Aneta L; Kusnierz-Cabala, Beata

2017-04-01

Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in 'good' or 'intermediate' MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan-Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4-36.2 months] versus 9.8 months (6.4-13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly.

Effectiveness study of atropine for progressive myopia in Europeans

PubMed Central

Polling, J R; Kok, R G W; Tideman, J W L; Meskat, B; Klaver, C C W

2016-01-01

Purpose Randomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a non-Asian country. Methods An effectiveness study was performed in Rotterdam, the Netherlands. Overall 77 children (mean age 10.3 years±2.3), of European (n=53), Asian (n=18), and African (n=6) descent with progressive myopia were prescribed atropine 0.5% eye drops daily. Both parents and children filled in a questionnaire regarding adverse events and adherence to therapy. A standardized eye examination including cycloplegic refraction and axial length was performed at baseline and 1, 4, and 12 months after initiation of therapy. Results Mean spherical equivalent at baseline was −6.6D (±3.3). The majority (60/77, 78%) of children adhered to atropine treatment for 12 months; 11 of the 17 children who discontinued therapy did so within 1 month after the start of therapy. The most prominent reported adverse events were photophobia (72%), followed by reading problems (38%), and headaches (22%). The progression rate of spherical equivalent before treatment (−1.0D/year±0.7) diminished substantially during treatment (−0.1D/year±0.7) compared to those who ceased therapy (−0.5D/year±0.6; P=0.03). Conclusions Despite the relatively high occurrence of adverse events, our study shows that atropine can be an effective and sustainable treatment for progressive high myopia in Europeans. PMID:27101751

Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma.

PubMed

González-Calle, Verónica; Cerdá, Seila; Labrador, Jorge; Sobejano, Eduardo; González-Mena, Beatriz; Aguilera, Carmen; Ocio, Enrique María; Vidriales, María Belén; Puig, Noemí; Gutiérrez, Norma Carmen; García-Sanz, Ramón; Alonso, José María; López, Rosa; Aguilar, Carlos; de Coca, Alfonso García; Hernández, Roberto; Hernández, José Mariano; Escalante, Fernando; Mateos, María-Victoria

2017-05-01

Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not yet been explored. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated according to immunoglobulin recovery at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression free, 88 patients (52%) showed immunoglobulin recovery and 81 (48%) did not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; Hazard Ratio: 0.45, 95%Confidence Interval: 0.31-0.66; P <0.001), and improved overall survival (11.3 vs. 7.3 years; Hazard Ratio: 0.45, 95%Confidence Interval: 0.27-0.74; P =0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: nine months and one year. In conclusion, the recovery of polyclonal immunoglobulins one year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival. Copyright© Ferrata Storti Foundation.

Routine Computer Tomography Imaging for the Detection of Recurrences in High-Risk Melanoma Patients.

PubMed

Park, Tristen S; Phan, Giao Q; Yang, James C; Kammula, Udai; Hughes, Marybeth S; Trebska-McGowan, Kasia; Morton, Kathleen E; White, Donald E; Rosenberg, Steven A; Sherry, Richard M

2017-04-01

The use of routine CT imaging for surveillance in asymptomatic patients with cutaneous melanoma is controversial. We report our experience using a surveillance strategy that included CT imaging for a cohort of patients with high-risk melanoma. A total of 466 patients with high-risk cutaneous melanoma enrolled in adjuvant immunotherapy trials were followed for tumor progression by physical examination, labs, and CT imaging as defined by protocol. Evaluations were obtained at least every 6 months for year 1, every 6 months for year 2, and then annually for the remainder of the 5-year study. Time to tumor progression, sites of recurrence, and the method of relapse detection were identified. The patient cohort consisted of 115 stage II patients, 328 stage III patients, and 23 patients with resected stage IV melanoma. The medium time to progression for the 225 patients who developed tumor progression was 7 months. Tumor progression was detected by patients, physician examination or routine labs, or by CT imaging alone in 27, 14, and 59% of cases respectively. Melanoma recurrences were noted to be locoregional in 36% of cases and systemic in 64% of cases. Thirty percent of patients with locoregional relapse and 75% of patients with systemic relapse were detected solely by CT imaging. CT imaging alone detected the majority of sites of disease progression in our patients with high-risk cutaneous melanoma. This disease was not heralded by symptoms, physical examination, or blood work. Although the benefit of the early detection of advanced melanoma is unknown, this experience is relevant because of the rapid development and availability of potentially curative immunotherapies.

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer.

PubMed

Singla, Nirmish; Haddad, Ahmed Q; Passoni, Niccolo M; Meissner, Matthew; Lotan, Yair

2017-01-01

To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n = 32), low-grade pathology (n = 4), underwent early cystectomy within 3 months (n = 25), had <3 months of follow-up (n = 11), or did not receive an induction course of intravesical BCG (n = 32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS). Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4 months. There were 20 (20.2 %) deaths, including 6 (6.1 %) patients with bladder cancer-related mortality. 13 % patients experienced tumor progression and 27 % underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65 %), aspirin (63 %), or non-aspirin NSAIDs/COX inhibitors (26 %). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality. Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC.

Treatment with Sunitinib for Patients with Progressive Metastatic Pheochromocytomas and Sympathetic Paragangliomas

PubMed Central

Ayala-Ramirez, Montserrat; Chougnet, Cecile N.; Habra, Mouhammed Amir; Palmer, J. Lynn; Leboulleux, Sophie; Cabanillas, Maria E.; Caramella, Caroline; Anderson, Pete; Al Ghuzlan, Abir; Waguespack, Steven G.; Deandreis, Desirée

2012-01-01

Context: Patients with progressive metastatic pheochromocytomas (PHEOs) or sympathetic paragangliomas (SPGLs) face a dismal prognosis. Current systemic therapies are limited. Objectives: The primary end point was progression-free survival determined by RECIST 1.1 criteria or positron emission tomography with [18F]fluorodeoxyglucose/computed tomography ([18F]FDG-PET/CT), in the absence of measurable soft tissue targets. Secondary endpoints were tumor response according to RECIST criteria version 1.1 or FDG uptake, blood pressure control, and safety. Design: We conducted a retrospective review of medical records of patients with metastatic PHEO/SPGL treated with sunitinib from December 2007 through December 2011. An intention-to-treat analysis was performed. Patients and Setting: Seventeen patients with progressive metastatic PHEO/SPGLs treated at the Institut Gustave-Roussy and MD Anderson Cancer Center. Interventions: Patients treated with sunitinib. Results: According to RECIST 1.1, eight patients experienced clinical benefit; three experienced partial response, and five had stable disease, including four with predominant skeletal metastases that showed a 30% or greater reduction in glucose uptake on [18F]FDG-PET/CT. Of 14 patients who had hypertension, six became normotensive and two discontinued antihypertensives. One patient treated with sunitinib and rapamycin experienced a durable benefit beyond 36 months. The median overall survival from the time sunitinib was initiated was 26.7 months with a progression-free survival of 4.1 months (95% confidence interval = 1.4–11.0). Most patients who experienced a clinical benefit were carriers of SDHB mutations. Conclusion: Sunitinib is associated with tumor size reduction, decreased [18F]FDG-PET/CT uptake, disease stabilization, and hypertension improvement in some patients with progressive metastatic PHEO/PGL. Prospective multi-institutional clinical trials are needed to determine the true benefits of sunitinib. PMID:22965939

Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma.

PubMed

Lonial, Sagar; Dimopoulos, Meletios; Palumbo, Antonio; White, Darrell; Grosicki, Sebastian; Spicka, Ivan; Walter-Croneck, Adam; Moreau, Philippe; Mateos, Maria-Victoria; Magen, Hila; Belch, Andrew; Reece, Donna; Beksac, Meral; Spencer, Andrew; Oakervee, Heather; Orlowski, Robert Z; Taniwaki, Masafumi; Röllig, Christoph; Einsele, Hermann; Wu, Ka Lung; Singhal, Anil; San-Miguel, Jesus; Matsumoto, Morio; Katz, Jessica; Bleickardt, Eric; Poulart, Valerie; Anderson, Kenneth C; Richardson, Paul

2015-08-13

Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma. In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival. Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients. Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797.).

Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

PubMed

Mazza, Elena; Brandes, Alba; Zanon, Silvia; Eoli, Marika; Lombardi, Giuseppe; Faedi, Marina; Franceschi, Enrico; Reni, Michele

2016-01-01

Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. Patients with recurrent or progressive WHO grade I-III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18-75 years, ECOG performance status 0-2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient's refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75%, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75%, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.

Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine.

PubMed

Lee, Choong-kun; Jung, Minkyu; Choi, Hye Jin; Kim, Hye Ryun; Kim, Hyo Song; Roh, Mi Ryung; Ahn, Joong Bae; Chung, Hyun Cheol; Heo, Su Jin; Rha, Sun Young; Shin, Sang Joon

2015-10-01

There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m(2) on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR). Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.

Irradiation of Pediatric High-Grade Spinal Cord Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tendulkar, Rahul D.; Pai Panandiker, Atmaram S., E-mail: atmaram.pai-panandiker@stjude.or; Wu Shengjie

2010-12-01

Purpose: To report the outcome using radiation therapy (RT) for pediatric patients with high-grade spinal cord tumors. Methods and Materials: A retrospective chart review was conducted that included 17 children with high-grade spinal cord tumors treated with RT at St. Jude Children's Research Hospital between 1981 and 2007. Three patients had gross total resection, 11 had subtotal resection, and 3 underwent biopsy. The tumor diagnosis was glioblastoma multiforme (n = 7), anaplastic astrocytoma (n = 8), or anaplastic oligodendroglioma (n = 2). Seven patients received craniospinal irradiation (34.2-48.6 Gy). The median dose to the primary site was 52.2 Gy (range,more » 38-66 Gy). Results: The median progression-free and overall survivals were 10.8 and 13.8 months, respectively. Local tumor progression at 12 months (79% vs. 30%, p = 0.02) and median survival (13.1 vs. 27.2 months, p = 0.09) were worse for patients with glioblastoma multiforme compared with anaplastic astrocytoma or oligodendroglioma. The median overall survival was shorter for patients when failure included neuraxis dissemination (n = 8) compared with local failure alone (n = 5), 9.6 vs. 13.8 months, p = 0.08. Three long-term survivors with World Health Organization Grade III tumors were alive with follow-up, ranging from 88-239 months. Conclusions: High-grade spinal cord primary tumors in children have a poor prognosis. The propensity for neuraxis metastases as a component of progression after RT suggests the need for more aggressive therapy.« less

Indolent anti-Hu-associated paraneoplastic sensory neuropathy.

PubMed

Graus, F; Bonaventura, I; Uchuya, M; Valls-Solé, J; Reñé, R; Leger, J M; Tolosa, E; Delattre, J Y

1994-12-01

Paraneoplastic sensory neuropathy (PSN) usually runs a subacute progressive course, leaving the patient with severe sensory dysfunction in weeks to months. We describe five patients with PSN, high titers of anti-Hu antibodies (type 1 antineuronal nuclear autoantibodies), and an indolent clinical course. The patients had a median age of 55 years (range, 41 to 72). Four had small-cell (3) or undifferentiated large-cell (1) lung cancer. Patients presented with mild, asymmetric sensory symptoms; in two, the neuropathy was predominant in the arms. Two patients also had a visceral neuropathy causing gastrointestinal dysfunction. The PSN was stable or progressed very slowly without treatment for a median of 18 months (range, 5 to 32) and remained so after treatment with immunoglobulins (1 patient), chemotherapy (3), or both therapies (1). All patients were ambulatory, leading an independent life up until the time of the last visit or until death from the tumor (2 patients). The median follow-up was 36 months (range, 22 to 52). A paraneoplastic origin should be considered in patients with mild, very slowly progressive sensory neuropathies.

A randomized phase 2 study exploring the role of bevacizumab and a chemotherapy-free approach in HER2-positive metastatic breast cancer: The HAT study (BOOG 2008-2003), a Dutch Breast Cancer Research Group trial.

PubMed

Drooger, Jan C; van Tinteren, Harm; de Groot, Steffen M; Ten Tije, Albert J; de Graaf, Hiltje; Portielje, Johanneke E A; Jager, Agnes; Honkoop, Aafke; Linn, Sabine C; Kroep, Judith R; Erdkamp, Frans L G; Hamberg, Paul; Imholz, Alex L T; van Rossum-Schornagel, Quirine C; Heijns, Joan B; van Leeuwen-Stok, A Elise; Sleijfer, Stefan

2016-10-01

To explore the role of bevacizumab and a chemotherapy-free approach, the authors evaluated the combination of bevacizumab, trastuzumab, and paclitaxel (HAT) and the regimen of trastuzumab and bevacizumab (HA) with the addition of paclitaxel after progression (HA-HAT) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. In a noncomparative phase 2 trial, patients were randomized between HAT and HA-HAT. The primary endpoint was the progression-free rate at 1 year (1-year PFR). In the HA-HAT group, progression-free survival (PFS) was separately established for HA (PFS1) and HAT (PFS2). Eighty-four patients received HAT (n = 39) or HA-HAT (n = 45). The 1-year PFR was 74.4% (95% confidence interval [CI], 61.8%-89.4%) and 62.2% (95% CI, 49.6%-89.4%) in the HAT and HA-HAT arms, respectively. The median PFS was 19.8 months (95% CI, 14.9-25.6 months) in the HAT arm and 19.6 months (95% CI, 12.0-32.0 months) in the HA-HAT arm. In the HA-HAT arm, the median PFS1 was 10.4 months (95% CI, 6.2-15.0 months), and the median PFS2 was 8.2 months (95% CI, 7.0-12.6 months). The number and severity of adverse events were comparable between the arms. Both HAT and HA-HAT have promising activity in patients with HER2-positive metastatic breast cancer. In particular, starting with only targeted agents and delaying chemotherapy is worth further exploration. Cancer 2016;122:2961-2970. © 2016 American Cancer Society. © 2016 American Cancer Society.

Enzalutamide in Patients With Castration-Resistant Prostate Cancer Progressing After Docetaxel: Retrospective Analysis of the Swiss Enzalutamide Named Patient Program.

PubMed

Papazoglou, Dimitrios; Wannesson, Luciano; Berthold, Dominik; Cathomas, Richard; Gillessen, Silke; Rothermundt, Christian; Hasler, Loretta; Winterhalder, Ralph; Barth, Andreas; Mingrone, Walter; Nussbaum, Catrina Uhlmann; von Rohr, Lukas; von Burg, Philippe; Schmid, Mathias; Richner, Jürg; Baumann, Sylvia; Kühne, Reto; Stenner, Frank; Rothschild, Sacha I

2017-06-01

Enzalutamide is a second-generation androgen receptor (AR) inhibitor that binds to and blocks the AR with higher affinity than previously available AR inhibitors. High activity has been proven in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and in chemotherapy-naive patients with mCRPC. However, its activity in patients previously treated with other novel agents (for example, abiraterone and/or cabazitaxel), remains controversial. The aim of this retrospective analysis of the Swiss Enzalutamide Named Patient Program was to evaluate clinical efficacy and safety of enzalutamide treatment in patients with mCRPC progressing after docetaxel and other lines of therapy considering different treatment sequences. We report on 44 patients treated with enzalutamide. The median survival time from diagnosis of CPRC was 41.1 months (95% confidence interval [CI], 32.3-49.8 months). Enzalutamide was used as a second, third, fourth, fifth, sixth, or seventh-line therapy in 13%, 20%, 31%, 20%, 11%, and 2% of patients. The median duration of enzalutamide treatment was 3.0 months (range, 1-21 months). Median progression-free survival was 3.0 months (95% CI, 2.4-3.7 months). The estimated median overall survival was 6.3 months (95% CI, 4.6-8.1 months). Sixteen patients (36.4%) had a prostate-specific antigen decrease of ≥ 30%, and 11 patients (25.0%) of ≥ 50%, respectively. In multivariate analysis, the absence of previous therapy with abiraterone and a prostate-specific antigen response of ≥ 50% on enzalutamide therapy were significantly associated with overall survival on enzalutamide treatment. Our results show that enzalutamide has modest activity in extensively pretreated patients. However, there is a subgroup of patients achieving benefit from enzalutamide therapy even after pretreatment with abiraterone. Copyright © 2016 Elsevier Inc. All rights reserved.

Sulfur, chlorine, and fluorine degassing and atmospheric loading by the 1783 1784 AD Laki (Skaftár Fires) eruption in Iceland

NASA Astrophysics Data System (ADS)

Thordarson, T.; Self, S.; Óskarsson, N.; Hulsebosch, T.

1996-09-01

The 1783 1784 Laki tholeiitic basalt fissure eruption in Iceland was one of the greatest atmospheric pollution events of the past 250 years, with widespread effects in the northern hemisphere. The degassing history and volatile budget of this event are determined by measurements of pre-eruption and residual contents of sulfur, chlorine, and fluorine in the products of all phases of the eruption. In fissure eruptions such as Laki, degassing occurs in two stages: by explosive activity or lava fountaining at the vents, and from the lava as it flows away from the vents. Using the measured sulfur concentrations in glass inclusions in phenocrysts and in groundmass glasses of quenched eruption products, we calculate that the total accumulative atmospheric mass loading of sulfur dioxide was 122 Mt over a period of 8 months. This volatile release is sufficient to have generated ˜250 Mt of H2SO4 aerosols, an amount which agrees with an independent estimate of the Laki aerosol yield based on atmospheric turbidity measurements. Most of this volatile mass (˜60 wt.%) was released during the first 1.5 months of activity. The measured chlorine and fluorine concentrations in the samples indicate that the atmospheric loading of hydrochloric acid and hydrofluoric acid was ˜7.0 and 15.0 Mt, respectively. Furthermore, ˜75% of the volatile mass dissolved by the Laki magma was released at the vents and carried by eruption columns to altitudes between 6 and 13 km. The high degree of degassing at the vents is attributed to development of a separated two-phase flow in the upper magma conduit, and implies that high-discharge basaltic eruptions such as Laki are able to loft huge quantities of gas to altitudes where the resulting aerosols can reside for months or even 1 2 years. The atmospheric volatile contribution due to subsequent degassing of the Laki lava flow is only 18 wt.% of the total dissolved in the magma, and these emissions were confined to the lowest regions of the troposphere and therefore important only over Iceland. This study indicates that determination of the amount of sulfur degassed from the Laki magma batch by measurements of sulfur in the volcanic products (the petrologic method) yields a result which is sufficient to account for the mass of aerosols estimated by other methods.

Sulfur, Chlorine, and Flourine Degassing and Atmospheric Loading by the 1783 - 1784 AD Laki (Skaftar Fires) Eruption in Iceland

NASA Technical Reports Server (NTRS)

Thordarson, T.; Self, S.; Hulsebosch, T.; Oskarsson, N.; McPhie, Jocelyn (Editor)

1996-01-01

The 1783-1784 Laki tholeiitic basalt fissure eruption in Iceland was one of the greatest atmospheric pollution events of the past 250 years, with widespread effects in the northern hemisphere. The degassing history and volatile budget of this event are determined by measurements of pre-eruption and residual contents of sulfur, chlorine, and fluorine in the products of all phases of the eruption. In fissure eruptions such as Laki, degassing occurs in two stages: by explosive activity or lava fountaining at the vents, and from the lava as it flows away from the vents. Using the measured sulfur concentrations in glass inclusions in phenocrysts and in groundmass glasses of quenched eruption products, we calculate that the total accumulative atmospheric mass loading of sulfur dioxide was 122 Mt over a period of 8 months. This volatile release is sufficient to have generated approximately 250 Mt of H2SO4 aerosols, an amount which agrees with an independent estimate of the Laki aerosol yield based on atmospheric turbidity measurements. Most of this volatile mass (approximately 60 wt.%) was released during the first 1.5 months of activity. The measured chlorine and fluorine concentrations in the samples indicate that the atmospheric loading of hydrochloric acid and hydrofluoric acid was approximately 7.0 and 15.0 Mt, respectively. Furthermore, approximately 75% of the volatile mass dissolved by the Laki magma was released at the vents and carried by eruption columns to altitudes between 6 and 13 km. The high degree of degassing at the vents is attributed to development of a separated two-phase flow in the upper magma conduit, and implies that high-discharge basaltic eruptions such as Laki are able to loft huge quantities of gas to altitudes where the resulting aerosols can reside for months, or even 1-2 years. The atmospheric volatile contribution due to subsequent degassing of the Laki lava flow is only 18 wt.% of the total dissolved in the magma, and these emissions were confined to the lowest regions of the troposhere and therefore important only over Iceland. This study indicates that determination of the amount of sulfur degassed from the Laki magma batch by measurements of sulfur in the volcanic products (the petrologic method) yields a result which is sufficient to account for the mass of aerosols estimated by other methods.

Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial

PubMed Central

Martín-Martorell, P; Roselló, S; Rodríguez-Braun, E; Chirivella, I; Bosch, A; Cervantes, A

2008-01-01

This is a phase II institutional exploratory trial of biweekly irinotecan and cetuximab administration regimen in metastatic colorectal cancer patients progressing to at least one previous chemotherapy line. A total of 40 patients were treated between November 2005 and November 2007 with irinotecan 180 mg m−2 and cetuximab 500 mg m−2 q2w (every 2 weeks), in every 21-day cycles, until unacceptable toxicity or progressive disease. An overall response rate of 22.5% was obtained (two complete and seven partial responses). The disease control rate was 60%. The time to progression was 3.4 months and the overall survival was 8 months. The toxicity compared very favourably to weekly cetuximab combination schedules. Grade 3/4 adverse effects were observed in 12 patients. Overall, our results turn up very similar both in terms of toxicity and efficacy to those obtained by weekly and biweekly administration regimens. PMID:18665167

Aversive and non-aversive memory impairment in the mucopolysaccharidosis II mouse model.

PubMed

Azambuja, Amanda Stapenhorst; Correa, Lilian; Gabiatti, Bernardo Pappi; Martins, Giselle Renata; de Oliveira Franco, Álvaro; Ribeiro, Maria Flávia Marques; Baldo, Guilherme

2018-02-01

Hunter syndrome (MPS II, OMIM 309900) is a lysosomal storage disorder due to deficient iduronate sulphatase activity. Patients present multiple cognitive alterations, and the aim of this work was to verify if MPS II mice also present some progressive cognitive alterations. For that, MPS II mice from 2 to 6 months of age were submitted to repeated open field and inhibitory avoidance tests to evaluate memory parameters. MPS II mice presented impaired memory at 6 months evaluated by open field test. They also performed poorly in the inhibitory avoidance test from 4 months. We conclude that MPS II mice develop cognitive alterations as the disease progresses. These tests can be used in the future to study the efficacy of therapeutic approaches in the central nervous system.

Lymphocyte-conditioned medium in combination with interleukin-2 effectively induces antitumour autoimmunity by adoptive transfer of short activated killer (SHAK) cells.

PubMed

Buer, J; Hilse, R; Dallmann, I; Grosse, J; Kirchner, H; Zorn, U; Hänninen, E L; Franzke, A; Duensing, S; Poliwoda, H

1995-03-01

In this study, effective antitumour immunity was transferred by autologous short activated killer (SHAK) cells induced over four hours with lymphocyte conditioned medium (LCM) and recombinant interleukin-2 (rIL-2). Among eight patients with progressive metastatic renal cell carcinoma refractory to standard therapy, there were six objective tumour responses to SHAKs. Progression-free survival ranged from 0 to 8+ months, and overall survival ranged from 2 to 14+ months, with a median of 9+ months. Systemic toxicity of SHAKs was limited to flulike symptoms. Patient SHAKs provided a tumour-specific immunity, both cellular and humoral (expression and secretion of secondary cytokines, including IL-2, GM-CSF, INF-gamma and TNF-alpha), far superior to rIL-2 activated killer cells.

Sequencing of Local Therapy Affects the Pattern of Treatment Failure and Survival in Children With Atypical Teratoid Rhabdoid Tumors of the Central Nervous System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pai Panandiker, Atmaram S., E-mail: atmaram.pai-panandiker@stjude.org; Merchant, Thomas E.; Beltran, Chris

Purpose: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT). Methods and Materials: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. Results: Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolledmore » into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% {+-} 9%; progression-free survival was 33.2% {+-} 10%; and OS was 53.5% {+-} 10%. Children receiving delayed RT ({>=}1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. Conclusions: Delayed RT is associated with a higher rate of local and metastatic disease progression in children with AT/RT. Current treatment regimens for pediatric patients with AT/RT are distinctly age stratified; novel protocols investigating RT volumes and sequencing are needed.« less

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer.

PubMed

Fizazi, Karim; Tran, NamPhuong; Fein, Luis; Matsubara, Nobuaki; Rodriguez-Antolin, Alfredo; Alekseev, Boris Y; Özgüroğlu, Mustafa; Ye, Dingwei; Feyerabend, Susan; Protheroe, Andrew; De Porre, Peter; Kheoh, Thian; Park, Youn C; Todd, Mary B; Chi, Kim N

2017-07-27

Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer. In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival. After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001). The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantly better outcomes in all secondary end points were observed in the abiraterone group, including the time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, and prostate-specific antigen progression (P<0.001 for all comparisons), along with next symptomatic skeletal events (P=0.009). These findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone. Rates of grade 3 hypertension and hypokalemia were higher in the abiraterone group. The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer. (Funded by Janssen Research and Development; LATITUDE ClinicalTrials.gov number, NCT01715285 .).

Managing human error in aviation.

PubMed

Helmreich, R L

1997-05-01

Crew resource management (CRM) programs were developed to address team and leadership aspects of piloting modern airplanes. The goal is to reduce errors through team work. Human factors research and social, cognitive, and organizational psychology are used to develop programs tailored for individual airlines. Flight crews study accident case histories, group dynamics, and human error. Simulators provide pilots with the opportunity to solve complex flight problems. CRM in the simulator is called line-oriented flight training (LOFT). In automated cockpits CRM promotes the idea of automation as a crew member. Cultural aspects of aviation include professional, business, and national culture. The aviation CRM model has been adapted for training surgeons and operating room staff in human factors.

Dust motions in quasi-statically charged binary asteroid systems

NASA Astrophysics Data System (ADS)

Maruskin, Jared M.; Bellerose, Julie; Wong, Macken; Mitchell, Lara; Richardson, David; Mathews, Douglas; Nguyen, Tri; Ganeshalingam, Usha; Ma, Gina

2013-03-01

In this paper, we discuss dust motion and investigate possible mass transfer of charged particles in a binary asteroid system, in which the asteroids are electrically charged due to solar radiation. The surface potential of the asteroids is assumed to be a piecewise function, with positive potential on the sunlit half and negative potential on the shadow half. We derive the nonautonomous equations of motion for charged particles and an analytic representation for their lofting conditions. Particle trajectories and temporary relative equilibria are examined in relation to their moving forbidden regions, a concept we define and discuss. Finally, we use a Monte Carlo simulation for a case study on mass transfer and loss rates between the asteroids.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bauböck, Michi; Psaltis, Dimitrios; Özel, Feryal, E-mail: mbaubock@email.arizona.edu

We calculate the effects of spot size on pulse profiles of moderately rotating neutron stars. Specifically, we quantify the bias introduced in radius measurements from the common assumption that spots are infinitesimally small. We find that this assumption is reasonable for spots smaller than 10°–18° and leads to errors that are ≤10% in the radius measurement, depending on the location of the spot and the inclination of the observer. We consider the implications of our results for neutron star radius measurements with the upcoming and planned X-ray missions NICER and LOFT. We calculate the expected spot size for different classesmore » of sources and investigate the circumstances under which the assumption of a small spot is justified.« less

Be/X-ray Binary Science for Future X-ray Timing Missions

NASA Technical Reports Server (NTRS)

Wilson-Hodge, Colleen A.

2011-01-01

For future missions, the Be/X-ray binary community needs to clearly define our science priorities for the future to advocate for their inclusion in future missions. In this talk, I will describe current designs for two potential future missions and Be X-ray binary science enabled by these designs. The Large Observatory For X-ray Timing (LOFT) is an X-ray timing mission selected in February 2011 for the assessment phase from the 2010 ESA M3 call for proposals. The Advanced X-ray Timing ARray (AXTAR) is a NASA explorer concept X-ray timing mission. This talk is intended to initiate discussions of our science priorities for the future.

Airline Crew Training

NASA Technical Reports Server (NTRS)

1989-01-01

The discovery that human error has caused many more airline crashes than mechanical malfunctions led to an increased emphasis on teamwork and coordination in airline flight training programs. Human factors research at Ames Research Center has produced two crew training programs directed toward more effective operations. Cockpit Resource Management (CRM) defines areas like decision making, workload distribution, communication skills, etc. as essential in addressing human error problems. In 1979, a workshop led to the implementation of the CRM program by United Airlines, and later other airlines. In Line Oriented Flight Training (LOFT), crews fly missions in realistic simulators while instructors induce emergency situations requiring crew coordination. This is followed by a self critique. Ames Research Center continues its involvement with these programs.

Characterization of Moving Dust Particles

NASA Technical Reports Server (NTRS)

Bos, Brent J.; Antonille, Scott R.; Memarsadeghi, Nargess

2010-01-01

A large depth-of-field Particle Image Velocimeter (PIV) has been developed at NASA GSFC to characterize dynamic dust environments on planetary surfaces. This instrument detects and senses lofted dust particles. We have been developing an autonomous image analysis algorithm architecture for the PIV instrument to greatly reduce the amount of data that it has to store and downlink. The algorithm analyzes PIV images and reduces the image information down to only the particle measurement data we are interested in receiving on the ground - typically reducing the amount of data to be handled by more than two orders of magnitude. We give a general description of PIV algorithms and describe only the algorithm for estimating the velocity of the traveling particles.

Developmental Progression of Looking and Reaching Performance on the A-not-B Task

PubMed Central

Cuevas, Kimberly; Bell, Martha Ann

2013-01-01

From a neuropsychological perspective, the cognitive skills of working memory, inhibition, and attention and the maturation of the frontal lobe are requisites for successful A-not-B performance on both the looking and reaching versions of the task. This study used a longitudinal design to examine the developmental progression of infants’ performance on the looking and reaching versions of the A-not-B task. Twenty infants were tested on both versions of the task once a month from 5 to 10 months of age. Infants had higher object permanence scores on the looking version of the task from 5 to 8 months, with comparable performance across response modalities at 9 and 10 months. The same pattern of performance was found on nonreversal (A) trials: Infants performed better on looking trials from 5 to 7 months and they performed equally on both response trials from 8 to 10 months. Overall, infants performed better on looking reversal (B) trials than reaching reversal trials. These data suggest that performance differences between response modalities early in development can be attributed to major differences in the maturation of brain circuitry associated with the actual task response. PMID:20822245

A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE).

PubMed

Radwan, Noura; Phillips, Ryan; Ross, Ashley; Rowe, Steven P; Gorin, Michael A; Antonarakis, Emmanuel S; Deville, Curtiland; Greco, Stephen; Denmeade, Samuel; Paller, Channing; Song, Daniel Y; Diehn, Maximilian; Wang, Hao; Carducci, Michael; Pienta, Kenneth J; Pomper, Martin G; DeWeese, Theodore L; Dicker, Adam; Eisenberger, Mario; Tran, Phuoc T

2017-06-29

We describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints will include local control at 6 months post-SABR, toxicity and quality of life, and androgen deprivation therapy (ADT)-free survival (ADT-FS). Further fundamental analysis of the oligometastatic state with be achieved through correlation with investigational 18 F-DCFPyL PET/CT imaging and measurement of circulating tumor cells, circulating tumor DNA, and circulating T-cell receptor repertoires, facilitating an unprecedented opportunity to characterize, in isolation, the effects of SABR on the dynamics of and immunologic response to oligometastatic disease. Patients will be randomized 2:1 to SABR or observation with minimization to balance assignment by primary intervention, prior hormonal therapy, and PSA doubling time. Progression after 6 months will be compared using Fisher's exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival (PFS), ADT free survival (ADT-FS), time to locoregional progression (TTLP) and time to distant progression (TTDP) will be calculated based on an intention-to-treat. Local control will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Withdrawal from the study prior to 6 months will be counted as progression. Adverse events will be summarized by type and grade. Quality of life pre- and post- SABR will be measured by Brief Pain Inventory. The ORIOLE trial is the first randomized, non-blinded Phase II interventional study in the North America evaluating the safety and efficacy of SABR in oligometastatic hormone-sensitive prostate cancer. Leading-edge laboratory and imaging correlates will provide unique insight into the effects of SABR on the oligometastatic state. ClinicalTrials.gov Identifier: NCT02680587. URL of Registry: https://clinicaltrials.gov/show/NCT02680587 Date of Registration: 02/08/2016. Date of First Participant Enrollment: 05/23/2016.

Bevacizumab salvage therapy following progression in high-grade glioma patients treated with VEGF receptor tyrosine kinase inhibitors

PubMed Central

Scott, Brian J.; Quant, Eudocia C.; McNamara, Margaret B.; Ryg, Peter A.; Batchelor, Tracy T.; Wen, Patrick Y.

2010-01-01

Agents targeting the vascular endothelial growth factor (VEGF) pathway are being used with increasing frequency in patients with recurrent high-grade glioma. The effect of more than one antiangiogenic therapy given in succession has not been established. We reviewed the efficacy of bevacizumab, a VEGF-A monoclonal antibody, in patients who progressed following prior therapy with VEGF receptor tyrosine kinase inhibitors (R-TKi). Seventy-three patients with recurrent high-grade gliomas received VEGF R-TKi (cediranib, sorafenib, pazopanib, or sunitinib) as part of phase I or II clinical trials. Twenty-four of these patients with glioblastoma progressed and received bevacizumab-containing regimens immediately after R-TKi. Those who stopped R-TKi therapy for reasons other than disease progression, or received a treatment that did not include bevacizumab, were excluded from the analysis. The efficacy of bevacizumab-containing regimens in these 24 patients was evaluated. During R-TKi therapy, 6 of 24 patients (25%) had a partial response (PR) to treatment. The 6-month progression-free survival (APF6) was 16.7% and median time-to-progression (TTP) was 14.3 weeks. Grade III/IV toxicities were seen in 13 of 24 patients (54%). Subsequently with bevacizumab salvage therapy, 5 of 24 patients (21%) had a PR, the APF6 was 12.5%, and the median TTP was 8 weeks. Five of 24 patients had grade III/IV toxicities (21%). The median overall survival (OS) from the start of R-TKi therapy was 9.2 months (range: 2.8–34.1+), whereas the median OS after bevacizumab was 5.2 months (range: 1.3–28.9+). Bevacizumab retains modest activity in high-grade glioma patients who progress on R-TKi. However, the APF6 of 12.5% in this cohort of patients indicates that durable tumor control is not achieved for most patients. PMID:20156808

Aortic elasticity indices by magnetic resonance predict progression of ascending aorta dilation.

PubMed

Aquaro, Giovanni Donato; Briatico Vangosa, Alessandra; Toia, Patrizia; Barison, Andrea; Ait-Ali, Lamia; Midiri, Massimo; Cotroneo, Antonio Raffaele; Emdin, Michele; Festa, Pierluigi

2017-04-01

Aortic distensibility and pulse-wave velocity (PWV) are under investigation as parameters by which to evaluate the indication for ascending aorta (AA) replacement. The maximum rate of systolic distension (MRSD) was proposed as a new index of aortic elasticity. The aim of this study was to assess the role of aortic elasticity parameters to predict AA growth rates in patients with AA dilation (AAD). Magnetic resonance imaging (MRI) was performed annually in 65 patients with AA dilation (median follow-up 17 months; 25-75th percentile; range 12-30 months). A significant increase in AA diameter was defined as a ≥2-mm increase. An increase in AA diameter was found in 42 (68 %) patients (AAD+ group) and absent in 20. Median increase was 0.16 (25-75th percentile; range 0.32-0.7) mm/month. The AAD+ group had a lower MRSD (4.6 ± 2.2 vs 7.4 ± 2.0, p < 0.001) but the same PWV and distensibility. MRSD showed 93.7 % specificity and 75.6 % sensitivity for prediction of increase. Patients with MRSD ≤ 6 had lower progression-free survival times (p < 0.002). After a follow-up of 4.1 years, patients who underwent surgical therapy had lower MRSD and distensibility than others. MRSD is an index of aorta elastic properties and is a valuable predictor for progression in AAD. • MRI-derived parameters of aortic wall elasticity predict progression of ascending aorta dilation. • Maximal rate of systolic distension (MRSD) was the best predictor of progression. • Patients with MRSD ≤ 6 had lower progression-free survival (PFS) times. • Patients who underwent surgical therapy had lower MRSD and distensibility. • MRI-derived parameters identify patients with fast progression of Ascending Aorta Dilation.

Association between Smoking and the Progression of Computed Tomography Findings in Chronic Pancreatitis

PubMed Central

Lee, Jeong Woo; Kim, Ho Gak; Lee, Dong Wook; Han, Jimin; Kwon, Hyuk Yong; Seo, Chang Jin; Oh, Ji Hye; Lee, Joo Hyoung; Jung, Jin Tae; Kwon, Joong Goo; Kim, Eun Young

2016-01-01

Background/Aims Smoking and alcohol intake are two well-known risk factors for chronic pancreatitis. However, there are few studies examining the association between smoking and changes in computed tomography (CT) findings in chronic pancreatitis. The authors evaluated associations between smoking, drinking and the progression of calcification on CT in chronic pancreatitis. Methods In this retrospective study, 59 patients with chronic pancreatitis who had undergone initial and follow-up CT between January 2002 and September 2010 were included. Progression of calcification among CT findings was compared according to the amount of alcohol intake and smoking. Results The median duration of follow-up was 51.6 months (range, 17.1 to 112.7 months). At initial CT findings, there was pancreatic calcification in 35 patients (59.3%). In the follow-up CT, progression of calcification was observed in 37 patients (62.7%). Progression of calcification was more common in smokers according to the multivariate analysis (odds ratio [OR], 9.987; p=0.006). The amount of smoking was a significant predictor for progression of calcification in the multivariate analysis (OR, 6.051 in less than 1 pack per day smokers; OR, 36.562 in more than 1 pack per day smokers; p=0.008). Conclusions Continued smoking accelerates pancreatic calcification, and the amount of smoking is associated with the progression of calcification in chronic pancreatitis. PMID:26601825

Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.

PubMed

Byrd, John C; Brown, Jennifer R; O'Brien, Susan; Barrientos, Jacqueline C; Kay, Neil E; Reddy, Nishitha M; Coutre, Steven; Tam, Constantine S; Mulligan, Stephen P; Jaeger, Ulrich; Devereux, Steve; Barr, Paul M; Furman, Richard R; Kipps, Thomas J; Cymbalista, Florence; Pocock, Christopher; Thornton, Patrick; Caligaris-Cappio, Federico; Robak, Tadeusz; Delgado, Julio; Schuster, Stephen J; Montillo, Marco; Schuh, Anna; de Vos, Sven; Gill, Devinder; Bloor, Adrian; Dearden, Claire; Moreno, Carol; Jones, Jeffrey J; Chu, Alvina D; Fardis, Maria; McGreivy, Jesse; Clow, Fong; James, Danelle F; Hillmen, Peter

2014-07-17

In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome. In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P=0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.).