Science.gov

Sample records for accelerated phase chronic

  1. 3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-12-16

    Accelerated Phase Chronic Myelogenous Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Polycythemia Vera; Primary Myelofibrosis; Relapsing Chronic Myelogenous Leukemia

  2. Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib

    PubMed Central

    Hochhaus, Andreas; le Coutre, Philipp D.; Rosti, Gianantonio; Pinilla-Ibarz, Javier; Jabbour, Elias; Gillis, Kathryn; Woodman, Richard C.; Blakesley, Rick E.; Giles, Francis J.; Kantarjian, Hagop M.; Baccarani, Michele

    2011-01-01

    Nilotinib has significant efficacy in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and in patients with CML-CP or CML in accelerated phase (CML-AP) after imatinib failure. We investigated the occurrence of cross-intolerance to nilotinib in imatinib-intolerant patients with CML. Only 1/75 (1%) patients with nonhematologic imatinib intolerance experienced a similar grade 3/4 adverse event (AE), and 3/75 (4%) experienced a similar persistent grade 2 nonhematologic AE on nilotinib. Only 7/40 (18%) patients with hematologic imatinib intolerance discontinued nilotinib, all because of grade 3/4 thrombocytopenia. Ninety percent of imatinib-intolerant patients with CML-CP who did not have complete hematologic response (CHR) at baseline (n = 52) achieved CHR on nilotinib. Nilotinib induced a major cytogenetic response in 66% and 41% of patients with imatinib-intolerant CML-CP and CML-AP (complete cytogenetic response in 51% and 30%), respectively. Minimal cross-intolerance was confirmed in patients with imatinib-intolerant CML. The favorable tolerability of nilotinib in patients with imatinib intolerance leads to alleviation of AE-related symptoms and significant and durable responses. In addition to its established clinical benefit in patients with newly diagnosed CML and those resistant to imatinib, nilotinib is effective and well-tolerated for long-term use in patients with imatinib intolerance. This study is registered at http://www.clinicaltrials.gov as NCT00471497 PMID:21467546

  3. Dasatinib in the Treatment of Chronic Myeloid Leukemia in Accelerated Phase After Imatinib Failure: The START A Trial

    PubMed Central

    Apperley, Jane F.; Cortes, Jorge E.; Kim, Dong-Wook; Roy, Lydia; Roboz, Gail J.; Rosti, Gianantonio; Bullorsky, Eduardo O.; Abruzzese, Elisabetta; Hochhaus, Andreas; Heim, Dominik; de Souza, Carmino A.; Larson, Richard A.; Lipton, Jeffrey H.; Khoury, H. Jean; Kim, Hyeoung-Joon; Sillaber, Christian; Hughes, Timothy P.; Erben, Philipp; Van Tornout, Jan; Stone, Richard M.

    2009-01-01

    Purpose Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population. Patients and Methods Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%). Conclusion Dasatinib is effective in patients with CML-AP after imatinib treatment failure. PMID:19487385

  4. Chronic acceleration and brain density

    NASA Technical Reports Server (NTRS)

    Hoffman, L. F.; Smith, A. H.

    1982-01-01

    Tests carried out on rabbits show that the effect of chronic acceleration is not uniform among the various tissues studied. Although body mass is reduced by the treatment, as expected, no change is apparent in brain mass or in the density of cerebrospinal fluid. Acceleration-induced changes are encountered in tissue density, the myocardium exhibiting a transient increase followed by an exponential decrease toward a limit and the brain showing an arithmetic increase in density with continued exposure to 2.5 G. The data are seen as suggesting that a specific brain load is not a regulated phenomenon and that no physiological processes occur to attenuate the increased load imposed by the hyperdynamic environment. An equation is derived indicating that the stimulus potential per unit of brain load increases with body size, even though brain density decreases and cerebrospinal fluid density increases.

  5. Body size and chronic acceleration

    NASA Technical Reports Server (NTRS)

    Pitts, G. C.

    1976-01-01

    Experiments were conducted to study body composition as a function of acceleration (1-4.7 G) in mice and rats. It is shown that fat-free body mass is a predictable function of acceleration, and that of nine components of the fat-free body mass only skeletal muscle, liver and heart contributed to observed changes induced by delta G. Fat-free body mass was found to pass through a maximum at 1 G when it was plotted vs G for mice, rats and monkeys (1-4.7 G) and men (0-1 G).

  6. The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up

    PubMed Central

    Palandri, Francesca; Castagnetti, Fausto; Alimena, Giuliana; Testoni, Nicoletta; Breccia, Massimo; Luatti, Simona; Rege-Cambrin, Giovanna; Stagno, Fabio; Specchia, Giorgina; Martino, Bruno; Levato, Luciano; Merante, Serena; Liberati, Anna Maria; Pane, Fabrizio; Saglio, Giuseppe; Alberti, Daniele; Martinelli, Giovanni; Baccarani, Michele; Rosti, Gianantonio

    2009-01-01

    Background Imatinib mesylate is the first line treatment for chronic myeloid leukemia. The advent of imatinib increased survival significantly in patients in an advanced phase of the disease. However, few long-term data on the outcome of these patients based on large, prospective and controlled trials are available. Design and Methods A phase 2 multicenter trial of the use of imatinib 600 mg/daily in patients with accelerated phase chronic myeloid leukemia was sponsored and promoted by the Italian Cooperative Study Group on Chronic Myeloid Leukemia in 2001. Results One hundred and eleven patients were enrolled; the median follow-up of the 41 living patients is 82 months (range, 73–87). One hundred and seven patients (96%) returned to chronic phase and 79 patients (71%) achieved a complete hematologic response. Cumulative best rates of major cytogenetic response and complete cytogenetic response were 30% and 21%, respectively. All responses were maintained for a minimum of 4 weeks. At last follow-up, four patients were alive in complete remission after allogeneic transplant, 16 patients (14%) had switched to a second generation tyrosine kinase inhibitor and 21 patients (19%) were alive on imatinib therapy. No late toxicities were observed. Progression-free survival and event-free survival rates were 36.5% and 15%, respectively, at 7 years. The median survival time was 37 months, and was significantly associated with the achievement of a complete hematologic response or a complete cytogenetic response. Conclusions Imatinib may induce durable responses, associated with prolonged survival, in patients with accelerated phase chronic myeloid leukemia PMID:19144656

  7. Accelerated Adaptive MGS Phase Retrieval

    NASA Technical Reports Server (NTRS)

    Lam, Raymond K.; Ohara, Catherine M.; Green, Joseph J.; Bikkannavar, Siddarayappa A.; Basinger, Scott A.; Redding, David C.; Shi, Fang

    2011-01-01

    The Modified Gerchberg-Saxton (MGS) algorithm is an image-based wavefront-sensing method that can turn any science instrument focal plane into a wavefront sensor. MGS characterizes optical systems by estimating the wavefront errors in the exit pupil using only intensity images of a star or other point source of light. This innovative implementation of MGS significantly accelerates the MGS phase retrieval algorithm by using stream-processing hardware on conventional graphics cards. Stream processing is a relatively new, yet powerful, paradigm to allow parallel processing of certain applications that apply single instructions to multiple data (SIMD). These stream processors are designed specifically to support large-scale parallel computing on a single graphics chip. Computationally intensive algorithms, such as the Fast Fourier Transform (FFT), are particularly well suited for this computing environment. This high-speed version of MGS exploits commercially available hardware to accomplish the same objective in a fraction of the original time. The exploit involves performing matrix calculations in nVidia graphic cards. The graphical processor unit (GPU) is hardware that is specialized for computationally intensive, highly parallel computation. From the software perspective, a parallel programming model is used, called CUDA, to transparently scale multicore parallelism in hardware. This technology gives computationally intensive applications access to the processing power of the nVidia GPUs through a C/C++ programming interface. The AAMGS (Accelerated Adaptive MGS) software takes advantage of these advanced technologies, to accelerate the optical phase error characterization. With a single PC that contains four nVidia GTX-280 graphic cards, the new implementation can process four images simultaneously to produce a JWST (James Webb Space Telescope) wavefront measurement 60 times faster than the previous code.

  8. Phase motion of accelerated electrons in vacuum laser acceleration

    SciTech Connect

    Hua, J. F.; Lin, Y. Z.; Tang, Ch. X.; Ho, Y. K.; Kong, Q.

    2007-01-15

    The phase stability in the capture and acceleration scenario (CAS) is studied and compared with that of conventional linear electron accelerators (CLEAs). For the CAS case, it has been found that a slow phase slippage occurs due to the difference between the electron velocity and the phase velocity of the longitudinal accelerating electric field. Thus, CAS electrons cannot remain in a fixed small phase region of the accelerating field to obtain a quasimonoenergy gain in contrast to the stability of phase oscillation in CLEAs. Also, the energy spread of the output electron beam for the CAS case cannot be kept as small as the CLEA because there is no good phase bunching phenomenon generated by phase oscillation.

  9. Chronic erythroid hyperplasia and accelerated bone turnover.

    PubMed

    Weinstein, R S; Lutcher, C L

    Bone atrophy is generally thought to be the etiology of the decreased skeletal mass and fractures found in patients with ineffective hematopoiesis and associated erythroid hyperplasia. A bone biopsy from a patient with chronic erythroid hyperplasia and diffuse cortical osteopenia revealed a normal trabecular bone volume, excess osteoid, numerous osteoblasts, and increased osteoclastic resorptive surface. The increased fractional labeled surfaces and widely spaced double tetracycline labels indicated accelerated bone turnover, despite demonstrable iron deposits at the calcification front and cement lines and a low serum level of 25-hydroxyvitamin D. The relationship between the expanded marrow space and trabecular bone suggests that local marrow factors may be responsible for the rapid bone remodeling.

  10. Temsirolimus and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-11

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Relapsing Chronic Myelogenous Leukemia

  11. Phase Stable Net Acceleration of Electrons From a Two-Stage Optical Accelerator

    SciTech Connect

    Sears, Christopher M.S.; Colby, Eric; England, R.J.; Ischebeck, Rasmus; McGuinness, Christopher; Nelson, Janice; Noble, Robert; Siemann, Robert H.; Spencer, James; Walz, Dieter; Plettner, Tomas; Byer, Robert L.; /Stanford U., Phys. Dept.

    2011-11-11

    In this article we demonstrate the net acceleration of relativistic electrons using a direct, in-vacuum interaction with a laser. In the experiment, an electron beam from a conventional accelerator is first energy modulated at optical frequencies in an inverse-free-electron-laser and bunched in a chicane. This is followed by a second stage optical accelerator to obtain net acceleration. The optical phase between accelerator stages is monitored and controlled in order to scan the accelerating phase and observe net acceleration and deceleration. Phase jitter measurements indicate control of the phase to {approx}13{sup o} allowing for stable net acceleration of electrons with lasers.

  12. Squirrel Monkey Requirements for Chronic Acceleration

    NASA Technical Reports Server (NTRS)

    Fuller, Charles A.

    1996-01-01

    This study examined: (1) the ability of a small non-human primate to tolerate chronic centrifugation on a centrifuge with a radius of 0.9 m, and (2) the influence of centrifuge radius on the response of primates to hyperdynamic fields. Eight adult male squirrel monkeys were exposed to 1.5 g via centrifugation at two different radii (0.9 m and 3.0 m). Body temperature, activity, feeding and drinking were monitored. These primates did tolerate and adapt to 1.5G via centrifugation on either radius centrifuge. The results show, however, that centrifuge radius does have an effect on the responses of the primate to the hyperdynamic environment. Adaptation to the hyperdynamic environment occurred more quickly on the larger centrifuge. This study demonstrates that a small, non-human primate model, such as the squirrel monkey, could be used on a 0.9 m radius centrifuge such as is being considered by the NASA Space Station Program.

  13. Phase I/II Study of Nilotinib/Ruxolitinb Therapy for TKI Resistant Ph-Leukemia

    ClinicalTrials.gov

    2016-03-04

    Chronic Phase Chronic Myeloid Leukemia; Accelerated Phase Chronic Myeloid Leukemia; Blastic Phase Chronic Myeloid Leukemia; Philadelphia Positive Acute Lymphoblastic Leukemia; Resistant to Tyrosine Kinase Inhibitor Therapy

  14. Chronic acceleration and egg production in domestic fowl

    NASA Technical Reports Server (NTRS)

    Smith, A. H.; Besch, E. L.; Burton, R. R.

    1985-01-01

    A study of the influence of chronic acceleration on egg production of commercially raised hens placed on a large animal centrifuge at 90 days of age, was performed. S8 generation hens were stepped up from 1.25 G to 2 G, which was maintained for 30 days. Fifty percent ceased to be in the laying condition at 1.5 G, and 10.8 percent suffered oviduct prolapse above 1.8 G. S21 generation hens had no incidents of oviduct prolapse despite 170-day retention at 2 G, and, assuming a 30 percent population not in the laying condition, approximated the commercial production rate. Chronic acceleration did not appear to affect the relative sizes of albumen or yolk, but it did appear to reduce the relative shell size, consistent with a decrease in plasma calcium. Dry matter content was not affected.

  15. NeutroPhase(®) in chronic non-healing wounds.

    PubMed

    Crew, John; Varilla, Randell; Rocas, Thomas Allandale; Debabov, Dmitri; Wang, Lu; Najafi, Azar; Rani, Suriani Abdul; Najafi, Ramin Ron; Anderson, Mark

    2012-01-01

    Chronic non-healing wounds, such as venous stasis ulcers, diabetic ulcers, and pressure ulcers are serious unmet medical needs that affect a patient's morbidity and mortality. Common pathogens observed in chronic non-healing wounds are Staphylococcus including MRSA, Pseudomonas, Enterobacter, Stenotrophomonas, and Serratia spp. Topical and systemically administered antibiotics do not adequately decrease the level of bacteria or the associated biofilm in chronic granulating wounds and the use of sub-lethal concentrations of antibiotics can lead to resistant phenotypes. Furthermore, topical antiseptics may not be fully effective and can actually impede wound healing. We show 5 representative examples from our more than 30 clinical case studies using NeutroPhase(®) as an irrigation solution with chronic non-healing wounds with and without the technique of negative pressure wound therapy (NPWT). NeutroPhase(®) is pure 0.01% hypochlorous acid (i.e. >97% relative molar distribution of active chlorine species as HOCl) in a 0.9% saline solution at pH 4-5 and is stored in glass containers. NovaBay has three FDA cleared 510(k)s. Patients showed a profound improvement and marked accelerated rates of wound healing using NeutroPhase(®) with and without NPWT. NeutroPhase(®) was non-toxic to living tissues.

  16. [Tolerance of +Gz accelerations in chronic compensated cardiac muscle disease].

    PubMed

    Suvorov, P M; Bykova, Iu I

    1975-01-01

    The functional potentialities of the cardiovascular system were investigated during an exposure of people with compensated chronic diseases of the cardiac muscle to acceleration (+Gz). The test subjects were exposed to acceleration of 3 and 5 g for 30 sec with an interval of 5 min. The parameters of hemodynamics, ECG and visual perception were recorded. The systolic blood volume, cardiac output and specific peripheral resistance were derived from the Bremser-Ranke formula. Seventy one subjects with heart diseases and 23 healthy subjects were examined. The subjects with myocardiodystrophy and myocarditic cardiosclerosis (12+/-16) showed a reduced tolerance to accelerations. During an exposure the subjects with atherosclerotic cardiosclerosis showed a higher pressure in vessels of ear conch than the healthy subjects. The myocardiodystrophic subjects frequently (20%) exhibited an inversion of electrocardiographic T2. The subjects with heart diseases (27-33%) showed extrasystolic disturbances. The results may be used in medical expertise of pilots.

  17. [Tolerance of +Gz accelerations in chronic compensated cardiac muscle disease].

    PubMed

    Suvorov, P M; Bykova, Iu I

    1975-01-01

    The functional potentialities of the cardiovascular system were investigated during an exposure of people with compensated chronic diseases of the cardiac muscle to acceleration (+Gz). The test subjects were exposed to acceleration of 3 and 5 g for 30 sec with an interval of 5 min. The parameters of hemodynamics, ECG and visual perception were recorded. The systolic blood volume, cardiac output and specific peripheral resistance were derived from the Bremser-Ranke formula. Seventy one subjects with heart diseases and 23 healthy subjects were examined. The subjects with myocardiodystrophy and myocarditic cardiosclerosis (12+/-16) showed a reduced tolerance to accelerations. During an exposure the subjects with atherosclerotic cardiosclerosis showed a higher pressure in vessels of ear conch than the healthy subjects. The myocardiodystrophic subjects frequently (20%) exhibited an inversion of electrocardiographic T2. The subjects with heart diseases (27-33%) showed extrasystolic disturbances. The results may be used in medical expertise of pilots. PMID:1214489

  18. A phase I study of danusertib (PHA-739358) in adult patients with accelerated or blastic phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant to imatinib and/or other second generation c-ABL therapy.

    PubMed

    Borthakur, Gautam; Dombret, Herve; Schafhausen, Philippe; Brummendorf, Tim Henrik; Boissel, Nicolas; Jabbour, Elias; Mariani, Mariangela; Capolongo, Laura; Carpinelli, Patrizia; Davite, Cristina; Kantarjian, Hagop; Cortes, Jorge E

    2015-07-01

    Danusertib is a pan-aurora kinase inhibitor with potent activity against Abl kinase including the gatekeeper T315I mutant. A phase 1 dose escalation study of danusertib was conducted in patients with accelerated or blastic phase chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Two dosing schedules were studied: schedule A, in which danusertib was given by 3-hour intravenous infusion daily for 7 consecutive days (days 1-7) in a 14-day cycle, and schedule B, in which the danusertib was given by 3-hour intravenous infusion daily for 14 consecutive days (days 1-14) in a 21-day cycle. A total of 37 patients were treated, 29 with schedule A and eight with schedule B. The recommended phase 2 dose for schedule A was 180 mg/m(2). Enrollment to schedule B was stopped early because of logistical problems with the frequency of infusions. Febrile neutropenia and mucositis were dose-limiting toxicities in schedule A. Four patients with T315I ABL kinase mutation, all treated with schedule A, responded. Danusertib has an acceptable toxicity profile and is active in patients with Bcr-Abl-associated advanced hematologic malignancies. This study was registered with the European Clinical Trails Data Base (EudraCT number 2007-004070-18). PMID:25887498

  19. A phase I study of danusertib (PHA-739358) in adult patients with accelerated or blastic phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant to imatinib and/or other second generation c-ABL therapy

    PubMed Central

    Borthakur, Gautam; Dombret, Herve; Schafhausen, Philippe; Brummendorf, Tim Henrik; Boissel, Nicolas; Jabbour, Elias; Mariani, Mariangela; Capolongo, Laura; Carpinelli, Patrizia; Davite, Cristina; Kantarjian, Hagop; Cortes, Jorge E.

    2015-01-01

    Danusertib is a pan-aurora kinase inhibitor with potent activity against Abl kinase including the gatekeeper T315I mutant. A phase 1 dose escalation study of danusertib was conducted in patients with accelerated or blastic phase chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Two dosing schedules were studied: schedule A, in which danusertib was given by 3-hour intravenous infusion daily for 7 consecutive days (days 1–7) in a 14-day cycle, and schedule B, in which the danusertib was given by 3-hour intravenous infusion daily for 14 consecutive days (days 1–14) in a 21-day cycle. A total of 37 patients were treated, 29 with schedule A and eight with schedule B. The recommended phase 2 dose for schedule A was 180 mg/m2. Enrollment to schedule B was stopped early because of logistical problems with the frequency of infusions. Febrile neutropenia and mucositis were dose-limiting toxicities in schedule A. Four patients with T315I ABL kinase mutation, all treated with schedule A, responded. Danusertib has an acceptable toxicity profile and is active in patients with Bcr-Abl-associated advanced hematologic malignancies. This study was registered with the European Clinical Trails Data Base (EudraCT number 2007-004070-18). PMID:25887498

  20. Regulation of body mass in rats exposed to chronic acceleration

    NASA Technical Reports Server (NTRS)

    Pitts, G. C.; Bull, L. S.; Oyama, J.

    1975-01-01

    Female rats approximately 6 mo old were chronically centrifuged for up to 30 days at 2.76 G or 3.18 G and sacrificed at intervals for body-composition study. Both fat and the fat-free body mass (FFBM) were reduced during the 1st wk of centrifugation, with the fat showing considerably more variation both within and between groups. The FFBM was reduced below control level to the same extent in rats fed commercial chow, a high-fat diet, or a high-protein diet or in rats prefasted to produce a body-mass deficit at the start of centrifugation. There were no centrifugation-associated changes in body water content. It was concluded that body fat showed no evidence of regulation, FFBM is regulated at any constant level of acceleration between 1 and 4.15 G, and the change in FFBM induced by a change in acceleration is probably not regulated.

  1. Induction accelerators for the phase rotator system

    SciTech Connect

    Reginato, Lou; Yu, Simon; Vanecek, Dave

    2001-07-30

    The principle of magnetic induction has been applied to the acceleration of high current beams in betatrons and a variety of induction accelerators. The linear induction accelerator (LIA) consists of a simple nonresonant structure where the drive voltage is applied to an axially symmetric gap that encloses a toroidal ferromagnetic material. The change in flux in the magnetic core induces an axial electric field that provides particle acceleration. This simple nonresonant (low Q) structure acts as a single turn transformer that can accelerate from hundreds of amperes to tens of kiloamperes, basically only limited by the drive impedance. The LIA is typically a low gradient structure that can provide acceleration fields of varying shapes and time durations from tens of nanoseconds to several microseconds. The efficiency of the LIA depends on the beam current and can exceed 50% if the beam current exceeds the magnetization current required by the ferromagnetic material. The acceleration voltage available is simply given by the expression V=A dB/dt. Hence, for a given cross section of material, the beam pulse duration influences the energy gain. Furthermore, a premium is put on minimizing the diameter, which impacts the total weight or cost of the magnetic material. The diameter doubly impacts the cost of the LIA since the power (cost) to drive the cores is proportional to the volume as well. The waveform requirements during the beam pulse makes it necessary to make provisions in the pulsing system to maintain the desired dB/dt during the useful part of the acceleration cycle. This is typically done two ways, by using the final stage of the pulse forming network (PFN) and by the pulse compensation network usually in close proximity of the acceleration cell. The choice of magnetic materials will be made by testing various materials both ferromagnetic and ferrimagnetic. These materials will include the nickel-iron, silicon steel amorphous and various types of ferrites not

  2. Accelerated atherosclerosis in patients with chronic inflammatory rheumatologic conditions

    PubMed Central

    Hong, Jison; Maron, David J; Shirai, Tsuyoshi; Weyand, Cornelia M

    2015-01-01

    Atherosclerosis is a complex inflammatory disease involving aberrant immune and tissue healing responses, which begins with endothelial dysfunction and ends with plaque development, instability and rupture. The increased risk for coronary artery disease in patients with rheumatologic diseases highlights how aberrancy in the innate and adaptive immune system may be central to development of both disease states and that atherosclerosis may be on a spectrum of immune-mediated conditions. Recognition of the tight association between chronic inflammatory disease and complications of atherosclerosis will impact the understanding of underlying pathogenic mechanisms and change diagnostic and therapeutic approaches in patients with rheumatologic syndromes as well as patients with coronary artery disease. In this review, we provide a summary of the role of the immune system in atherosclerosis, discuss the proposed mechanisms of accelerated atherosclerosis seen in association with rheumatologic diseases, evaluate the effect of immunosuppression on atherosclerosis and provide updates on available risk assessment tools, biomarkers and imaging modalities. PMID:27042216

  3. Accelerated Superposition State Molecular Dynamics for Condensed Phase Systems.

    PubMed

    Ceotto, Michele; Ayton, Gary S; Voth, Gregory A

    2008-04-01

    An extension of superposition state molecular dynamics (SSMD) [Venkatnathan and Voth J. Chem. Theory Comput. 2005, 1, 36] is presented with the goal to accelerate timescales and enable the study of "long-time" phenomena for condensed phase systems. It does not require any a priori knowledge about final and transition state configurations, or specific topologies. The system is induced to explore new configurations by virtue of a fictitious (free-particle-like) accelerating potential. The acceleration method can be applied to all degrees of freedom in the system and can be applied to condensed phases and fluids. PMID:26620930

  4. Pharyngeal swallowing phase and chronic cough

    PubMed Central

    Drozdz, Daniela Rejane Constantino; Costa, Cintia Conceição; Jesus, Paulo Roberto de Oliveira; Trindade, Mateus Silva; Weiss, Guilherme; Neto, Abdias Baptista M.; da Silva, Ana Maria T.; Mancopes, Renata

    2012-01-01

    Summary Introduction: The act of swallowing depends on a complex and dynamic process which uses common structures to the act of breathing; respiratory problems can cause swallowing difficulties. Aim: To assess the swallowing pharyngeal phase in patients with chronic cough. Method: Retrospective study with 15 patients of both genders, patients with chronic cough and risk factors for aspiration defined by the pneumologic diagnosis. The patients were submitted to anamnesis on complaints related to swallowing, chewing and breathing, or related to food and to videofluoroscopic examination. Results: It was observed that 33.3% had normal and functional swallowing, being the last one of most prevalence. The mild dysphagia was observed in 20% of the patients, the mild to moderate dysphagia in 6.7% of them. In relation to the Rosenbek scale, 73.3% of patients presented degree 1, 6.7% presented degrees 2 and 3, and 13.3% presented degree 8. The most found pathology was the chronic cough with 40%, followed by asthma with 20%; 69.2% of patients presented stasis and of these, five used protection maneuvers, of these, seven were effective and only three were used in the presence of stasis. The most used maneuver was the multiple swallowing, being effective in 100%. Conclusion: There are peculiarities in the patients' swallowing with chronic cough that, although not presenting complaints relating to swallowing, it presents an important aspiration risk due to the presence of changes in breathing pattern that can intervene in the coordination between breathing and swallowing, which is essential to protect the lower airway. PMID:25991980

  5. Acceleration of electrons during the flash phase of solar flares

    NASA Technical Reports Server (NTRS)

    Kane, S. R.

    1974-01-01

    The characteristics of the electron acceleration process operating during the flash phase of solar flares are deduced from the high time resolution observations of impulsive solar X rays greater than or equal to 10 keV and other flash phase emissions from small solar flares, and the implications of these findings are discussed.

  6. ACCELERATION PHASES OF A SOLAR FILAMENT DURING ITS ERUPTION

    SciTech Connect

    Song, H. Q.; Chen, Y.; Fu, H.; Zhang, J.; Cheng, X.; LI, G.

    2015-05-10

    Filament eruptions often lead to coronal mass ejections (CMEs), which can affect critical technological systems in space and on the ground when they interact with the geo-magnetosphere at high speeds. Therefore, it is important to investigate the acceleration mechanisms of CMEs in solar/space physics. Based on observations and simulations, the resistive magnetic reconnection and the ideal instability of magnetic flux ropes have been proposed to accelerate CMEs. However, it remains uncertain whether both of them play a comparable role during a particular eruption. It has been extremely difficult to separate their contributions as they often work in a close time sequence during one fast acceleration phase. Here we report an intriguing filament eruption event, which shows two apparently separated fast acceleration phases and provides us an excellent opportunity to address the issue. Through analyzing the correlations between velocity (acceleration) and soft (hard) X-ray profiles, we suggest that the instability and magnetic reconnection make a major contribution during the first and second fast acceleration phases, respectively. Further, we find that both processes have a comparable contribution to the filament acceleration in this event.

  7. Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina

    PubMed Central

    Wang, Jianxiang; Shen, Zhi-Xiang; Saglio, Giuseppe; Jin, Jie; Huang, He; Hu, Yu; Du, Xin; Li, Jianyong; Meng, Fanyi; Zhu, Huanling; Hu, Jianda; Wang, Jianmin; Hou, Ming; Hertle, Sabine; Menssen, Hans D.; Ortmann, Christine-Elke; Tribouley, Catherine; Yuan, Ye; Baccarani, Michele

    2015-01-01

    Treatment with a tyrosine kinase inhibitor (TKI) targeting BCR-ABL1 is currently the standard of care for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP). In this study, we present results of the ENESTchina (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–China) that was conducted to investigate nilotinib 300 mg twice daily vs imatinib 400 mg once daily in a Chinese population. ENESTchina met its primary end point with a statistically significant higher rate of major molecular response (MMR; BCR-ABL1 ≤0.1% on the International Scale) at 12 months in the nilotinib arm vs the imatinib arm (52.2% vs 27.8%; P < .0001), and MMR rates remained higher with nilotinib vs imatinib throughout the follow-up period. Rates of complete cytogenetic response (0% Philadelphia chromosome–positive [Ph+] metaphases by standard cytogenetics) were comparable and ≥80% by 24 months in both arms. The estimated rate of freedom from progression to accelerated phase/blast crisis at 24 months was 95.4% in each arm. The safety profiles of both drugs were similar to those from previous studies. In conclusion, rates of MMR at 12 months were superior with nilotinib vs imatinib in Chinese patients with newly diagnosed Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov as #NCT01275196. PMID:25766724

  8. Tipifarnib in Treating Patients With Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or Undifferentiated Myeloproliferative Disorders

    ClinicalTrials.gov

    2016-07-20

    Accelerated Phase of Disease; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase of Disease; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Recurrent Disease

  9. Phase distribution of chronic myeloid leukemia in Bangladesh

    PubMed Central

    2014-01-01

    Background Here, we report the phase distribution of chronic myeloid leukemia (CML), defined based on the World Health Organization criteria, among 63 patients in Bangladesh. All patients were diagnosed based on complete blood count, bone marrow examination including bone marrow aspiration and reverse-transcriptase polymerase chain reaction (RT-PCR). Out of 63 patients, 42 were male and 21 were female. The mean age of the subjects was 37.4 years, with an age range of 17-60 years. The majority of patients (86%) were classified in the chronic phase (CP), 7 (11%) in the accelerated phase (AP) and two (3%) in blast crisis (BC). The most frequent patient age ranges were 21-30 years for CP, 41-50 years for AP and 41-50 years for BC. Results The Philadelphia chromosome was detected in 48 patients by RT-PCR. The mean total leukocyte counts, platelet counts, hemoglobin levels and marrow blast frequencies were 101 × 109/L, 409 × 109/L, 12.2 g/dl and 2.8% for CP; 121 × 109/L, 418 × 109/L, 8.7 g/dl and 15% for AP and 311 × 109/L, 396 × 109/L, 9.2 g/dl and 26% for BC, respectively. Conclusion This study concluded that most CML patients in Bangladesh are from a younger age group (31-40 years). In addition, males were more commonly affected, although females were afflicted with this disease at a younger age. PMID:24621354

  10. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

    PubMed Central

    Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

    2014-01-01

    Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

  11. Tapered plasma channels to phase-lock accelerating and focusing forces in laser-plasma accelerators

    SciTech Connect

    Rittershofer, W.; Schroeder, C.B.; Esarey, E.; Gruner, F.J.; Leemans, W.P.

    2010-05-17

    Tapered plasma channels are considered for controlling dephasing of a beam with respect to a plasma wave driven by a weakly-relativistic, short-pulse laser. Tapering allows for enhanced energy gain in a single laser plasma accelerator stage. Expressions are derived for the taper, or longitudinal plasma density variation, required to maintain a beam at a constant phase in the longitudinal and/or transverse fields of the plasma wave. In a plasma channel, the phase velocities of the longitudinal and transverse fields differ, and, hence, the required tapering differs. The length over which the tapered plasma density becomes singular is calculated. Linear plasma tapering as well as discontinuous plasma tapering, which moves beams to adjacent plasma wave buckets, are also considered. The energy gain of an accelerated electron in a tapered laser-plasma accelerator is calculated and the laser pulse length to optimize the energy gain is determined.

  12. Accelerated sintering in phase-separating nanostructured alloys

    PubMed Central

    Park, Mansoo; Schuh, Christopher A.

    2015-01-01

    Sintering of powders is a common means of producing bulk materials when melt casting is impossible or does not achieve a desired microstructure, and has long been pursued for nanocrystalline materials in particular. Acceleration of sintering is desirable to lower processing temperatures and times, and thus to limit undesirable microstructure evolution. Here we show that markedly enhanced sintering is possible in some nanocrystalline alloys. In a nanostructured W–Cr alloy, sintering sets on at a very low temperature that is commensurate with phase separation to form a Cr-rich phase with a nanoscale arrangement that supports rapid diffusional transport. The method permits bulk full density specimens with nanoscale grains, produced during a sintering cycle involving no applied stress. We further show that such accelerated sintering can be evoked by design in other nanocrystalline alloys, opening the door to a variety of nanostructured bulk materials processed in arbitrary shapes from powder inputs. PMID:25901420

  13. Accelerated nanoscale magnetic resonance imaging through phase multiplexing

    SciTech Connect

    Moores, B. A.; Eichler, A. Takahashi, H.; Navaretti, P.; Degen, C. L.; Tao, Y.

    2015-05-25

    We report a method for accelerated nanoscale nuclear magnetic resonance imaging by detecting several signals in parallel. Our technique relies on phase multiplexing, where the signals from different nuclear spin ensembles are encoded in the phase of an ultrasensitive magnetic detector. We demonstrate this technique by simultaneously acquiring statistically polarized spin signals from two different nuclear species ({sup 1}H, {sup 19}F) and from up to six spatial locations in a nanowire test sample using a magnetic resonance force microscope. We obtain one-dimensional imaging resolution better than 5 nm, and subnanometer positional accuracy.

  14. Cytomegalovirus-induced Hemorrhagic Colitis in a Patient with Chronic Myeloid Leukemia (Chronic Phase) on Dasatinib as an Upfront Therapy

    PubMed Central

    Yassin, Mohamed A; Nashwan, Abdulqadir J; Soliman, Ashraf T; Yousif, Anil; Moustafa, Afra; AlBattah, Afaf; Mohamed, Shehab F; Mudawi, Deena S; Elkourashy, Sarah; Asaari, Deena-Raiza; Gutierrez, Hope-Love G; Almusharaf, Mohamed; Hussein, Radwa M; Moustafa, Abbas H; Derhoubi, Hatim El; Boukhris, Sarra; Kohla, Samah; AlDewik, Nader

    2015-01-01

    Dasatinib is a kinase inhibitor indicated for the treatment of newly diagnosed adults with Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) in chronic phase and accelerated (myeloid or lymphoid blast) phase, and CML with resistance or intolerance to prior therapy including imatinib and in adults with Ph+ acute lymphoblastic leukemia1 The most common adverse reactions (≥15%) in patients with newly diagnosed chronic-phase (CP) CML include myelosuppression, fluid retention, and diarrhea, whereas in patients with resistance or intolerance to prior imatinib therapy, side effects include myelosuppression, fluid retention, diarrhea, headache, dyspnea, skin rash, fatigue, nausea, and hemorrhage. We report a 39-year-old Ethiopian female patient who received dasatinib as upfront therapy for the treatment of CP-CML who experienced chronic diarrhea for two months, which progressed to hemorrhagic colitis due to cytomegalovirus (CMV) infection of the colon. To our knowledge, this is the first case of CMV colitis in a patient receiving dasatinib as upfront therapy. PMID:26379451

  15. Activated natural killer cells accelerate liver damage in patients with chronic hepatitis B virus infection.

    PubMed

    Zheng, Q; Zhu, Y Y; Chen, J; Ye, Y B; Li, J Y; Liu, Y R; Hu, M L; Zheng, Y C; Jiang, J J

    2015-06-01

    Emerging evidence indicates that natural killer (NK) cells may contribute to liver injury in patients with hepatitis B virus (HBV) infection. Because HBV infection progresses through various disease phases, the cytolytic profiles of peripheral and intrahepatic NK cells in HBV-infected patients remain to be defined. In this study, we comprehensively characterized intrahepatic and peripheral NK cells in a cohort of HBV-infected individuals, and investigated their impact on liver pathogenesis during chronic HBV infection. The study population included 34 immune-clearance (IC) patients, 36 immune-tolerant (IT) carriers and 10 healthy subjects. We found that the activity of peripheral NK cells from IC patients was functionally elevated compared to IT carriers and controls, and NK cell activation was indicated by an increased expression of CD69, CD107a, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Further analysis showed that the increased activity of both peripheral and hepatic NK cells was correlated positively with liver injury, which was assessed by serum alanine aminotransferase levels (ALT) and the liver histological activity index (HAI). Interestingly, the frequency of peripheral NK cells was reduced in IC patients (especially those with higher HAI scores of 3-4), but there was a concomitant increase in hepatic NK cells. The functionally activated NK cells are enriched preferentially in the livers of IC patients and skew towards cytolytic activity that accelerates liver injury in chronic hepatitis B (CHB) patients.

  16. Phase and Radial Motion in Ion Linear Accelerators

    2007-03-29

    Parmila is an ion-linac particle-dynamics code. The name comes from the phrase, "Phase and Radial Motion in Ion Linear Accelerators." The code generates DTL, CCDTL, and CCL accelerating cells and, using a "drift-kick" method, transforms the beam, represented by a collection of particles, through the linac. The code includes a 2-D and 3-D space-charge calculations. Parmila uses data generated by the Poisson Superfish postprocessor SEC. This version of Parmila was written by Harunori Takeda andmore » was supported through Feb. 2006 by James H. Billen. Setup installs executable programs Parmila.EXE, Lingraf.EXE, and ReadPMI.EXE in the LANL directory. The directory LANL\\Examples\\Parmila contains several subdirectories with sample files for Parmila.« less

  17. Characterising the acceleration phase of blast wave formation

    SciTech Connect

    Fox, T. E. Pasley, J.; Robinson, A. P. L.; Schmitz, H.

    2014-10-15

    Intensely heated, localised regions in uniform fluids will rapidly expand and generate an outwardly propagating blast wave. The Sedov-Taylor self-similar solution for such blast waves has long been studied and applied to a variety of scenarios. A characteristic time for their formation has also long been identified using dimensional analysis, which by its very nature, can offer several interpretations. We propose that, rather than simply being a characteristic time, it may be interpreted as the definitive time taken for a blast wave resulting from an intense explosion in a uniform media to contain its maximum kinetic energy. A scaling relation for this measure of the acceleration phase, preceding the establishment of the blast wave, is presented and confirmed using a 1D planar hydrodynamic model.

  18. Firstline treatment for chronic phase chronic myeloid leukemia patients should be based on a holistic approach.

    PubMed

    Breccia, Massimo; Alimena, Giuliana

    2015-02-01

    New selective and more potent drugs for the cure of chronic phase chronic myeloid leukemia patients are now available: physicians in some countries must decide the best option, selecting one of the drugs available. What the main prognostic factors are in order to make this selection remains a matter of discussion. Introducing a 'holistic approach' for the first time in chronic myeloid leukemia, as practiced in other diseases, and looking at the patient in a complete picture, considering several variables, such as comorbidities, age, concomitant drugs, lifestyle and patient expectations, may be of help to understand, patient by patient, the best therapeutic strategy.

  19. Firstline treatment for chronic phase chronic myeloid leukemia patients should be based on a holistic approach.

    PubMed

    Breccia, Massimo; Alimena, Giuliana

    2015-02-01

    New selective and more potent drugs for the cure of chronic phase chronic myeloid leukemia patients are now available: physicians in some countries must decide the best option, selecting one of the drugs available. What the main prognostic factors are in order to make this selection remains a matter of discussion. Introducing a 'holistic approach' for the first time in chronic myeloid leukemia, as practiced in other diseases, and looking at the patient in a complete picture, considering several variables, such as comorbidities, age, concomitant drugs, lifestyle and patient expectations, may be of help to understand, patient by patient, the best therapeutic strategy. PMID:25431965

  20. Chronic stress impairs learning and hippocampal cell proliferation in senescence-accelerated prone mice.

    PubMed

    Yan, Weihong; Zhang, Ting; Jia, Weiping; Sun, Xiaojiang; Liu, Xueyuan

    2011-02-25

    Chronic stress can induce cognitive impairment. It is unclear whether a higher susceptibility to chronic stress is associated with the progression of pathological brain aging. Senescence-accelerated prone mouse 8 (SAMP8) is a naturally occurring animal model of accelerated brain aging. Senescence-accelerated resistant mouse 1 (SAMR1) is usually used as the normal control. In this study, we examined the effects of chronic restraint stress (CRS) on learning in the Y-maze, hippocampal cell proliferation, and the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of 4-month-old SAMP8 and SAMR1. The results showed that exposure to CRS impaired learning and hippocampal cell proliferation in SAMP8 and SAMR1 but to a much greater extent in SAMP8. Furthermore, CRS significantly decreased the expression of BDNF protein and mRNA in the hippocampus of SAMP8 and SAMR1. These data indicated that SAMP8 is more sensitive to the deleterious effects of CRS on learning than SAMR1. A greater decrease in hippocampal cell proliferation caused by chronic stress may be part of the underlying mechanism for the more severe learning deficit observed in SAMP8. In addition, our findings suggested a role of BDNF in the stress-induced impairment of learning and hippocampal cell proliferation in both strains.

  1. Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  2. Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study

    PubMed Central

    Hochhaus, A; Rosti, G; Cross, N C P; Steegmann, J L; le Coutre, P; Ossenkoppele, G; Petrov, L; Masszi, T; Hellmann, A; Griskevicius, L; Wiktor-Jedrzejczak, W; Rea, D; Coriu, D; Brümmendorf, T H; Porkka, K; Saglio, G; Gastl, G; Müller, M C; Schuld, P; Di Matteo, P; Pellegrino, A; Dezzani, L; Mahon, F-X; Baccarani, M; Giles, F J

    2016-01-01

    The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic myeloid leukemia in chronic phase. The rate of deep molecular response (MR4 (BCR-ABL1⩽0.01% on the International Scale or undetectable BCR-ABL1 with ⩾10 000 ABL1 transcripts)) at 18 months was evaluated as the primary end point, with molecular responses monitored by the European Treatment and Outcome Study network of standardized laboratories. This analysis was conducted after all patients had completed 24 months of study treatment (80.9% of patients) or discontinued early. In patients with typical BCR-ABL1 transcripts and ⩽3 months of prior imatinib therapy, 38.4% (404/1052) achieved MR4 at 18 months. Six patients (0.6%) developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of nilotinib was consistent with that of previous studies, although the frequencies of some nilotinib-associated adverse events were lower (for example, rash, 21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine monitoring of lipid and glucose levels was not mandated in the protocol. These results support the use of frontline nilotinib, particularly when achievement of a deep molecular response (a prerequisite for attempting treatment-free remission in clinical trials) is a treatment goal. PMID:26437782

  3. Biomechanical Insights Into Differences Between the Mid-Acceleration and Maximum Velocity Phases of Sprinting.

    PubMed

    Yu, Jiabin; Sun, Yuliang; Yang, Chen; Wang, Donghai; Yin, Keyi; Herzog, Walter; Liu, Yu

    2016-07-01

    Yu, J, Sun, Y, Yang, C, Wang, D, Yin, K, Herzog, W, and Liu, Y. Biomechanical insights into differences between the mid-acceleration and maximum velocity phases of sprinting. J Strength Cond Res 30(7): 1906-1916, 2016-Investigating the differences between distinct phases of sprint running may increase the knowledge about the specific physical abilities needed for different phases of sprinting. Differences between the mid-acceleration and maximum velocity phases of sprint running have not yet been adequately investigated. Twenty male sprinters performed maximum-effort sprint runs, and measurements were made at 12 m from start for the mid-acceleration phase and at 40 m from the start for the maximum velocity phase. Kinematic data and ground reaction forces (GRFs) were collected at a rate of 200 and 1000 Hz, respectively. Intersegmental dynamics analysis was performed to investigate the interaction of muscle torque (MUS) with other passive torques. The peak horizontal braking force was significantly lower for the acceleration compared with that for the maximal velocity phase, whereas the peak horizontal propulsive force was similar for both phases. The peak MUS at the hip and knee joints for the braking phase was significantly smaller in the acceleration phase than in the maximum velocity phase. In conclusion, compared with the maximum velocity phase, the lower horizontal braking force was the primary cause for the increase in running velocity during the mid-acceleration phase. The force produced by lower limb muscles required to counteract external torques caused by the horizontal braking force in the braking phase was smaller during the acceleration phase than the maximum velocity phase. Therefore, training aimed at reducing the horizontal braking force might be more important than increasing the force produced by the lower limb muscles for success of the mid-acceleration phase.

  4. The principle of phase stability and the accelerator program at Berkeley, 1945--1954

    SciTech Connect

    Lofgren, E.J.

    1994-07-01

    The discovery of the Principle of Phase Stability by Vladimir Veksler and Edwin McMillian and the end of the war released a surge of accelerator activity at the Lawrence Berkeley Laboratory (then The University of California Radiation Laboratory). Six accelerators incorporating the Principle of Phase Stability were built in the period 1945--1954.

  5. Tyrosine kinase inhibition: A therapeutic target for the management of chronic-phase chronic myeloid leukemia

    PubMed Central

    Jabbour, Elias J; Cortes, Jorge E; Kantarjian, Hagop M

    2014-01-01

    Chronic myeloid leukemia (CML) is a hematologic neoplasm with a progressive, ultimately terminal, disease course. In most cases, CML arises owing to the aberrant formation of a chimeric gene for a constitutively active tyrosine kinase. Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target transforming the prognosis of patients with CML. New tyrosine kinase inhibitors (TKIs) continue to improve the management of CML, offering alternative options for those resistant to or intolerant of standard TKIs. Here we review the pathobiology of CML and explore emerging strategies to optimize the management of chronic-phase CML, particularly first-line treatment. PMID:24236822

  6. Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia.

    PubMed

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Gozzini, Antonella; Usala, Emilio; Carella, Angelo M; Rege-Cambrin, Giovanna; Martino, Bruno; Abruzzese, Elisabetta; Albano, Francesco; Stagno, Fabio; Luciano, Luigia; D'Adda, Mariella; Bocchia, Monica; Cavazzini, Francesco; Tiribelli, Mario; Lunghi, Monia; Pia Falcone, Antonietta; Musolino, Caterina; Levato, Luciano; Venturi, Claudia; Soverini, Simona; Cavo, Michele; Alimena, Giuliana; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Rosti, Gianantonio; Baccarani, Michele

    2016-06-01

    The introduction of second-generation tyrosine-kinase inhibitors (TKIs) has generated a lively debate on the choice of first-line TKI in chronic phase, chronic myeloid leukemia (CML). Despite the TKIs have different efficacy and toxicity profiles, the planned use of two TKIs has never been investigated. We report on a phase 2 study that was designed to evaluate efficacy and safety of a treatment alternating nilotinib and imatinib, in newly diagnosed BCR-ABL1 positive, chronic phase, CML patients. One hundred twenty-three patients were enrolled. Median age was 56 years. The probabilities of achieving a complete cytogenetic response, a major molecular response, and a deep molecular response (MR 4.0) by 2 years were 93%, 87%, and 61%, respectively. The 5-year overall survival and progression-free survival were 89%. Response rates and survival are in the range of those reported with nilotinib alone. Moreover, we observed a relatively low rate of cardiovascular adverse events (5%). These data show that the different efficacy and toxicity profiles of TKIs could be favorably exploited by alternating their use. Am. J. Hematol. 91:617-622, 2016. © 2016 Wiley Periodicals, Inc.

  7. Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia.

    PubMed

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Gozzini, Antonella; Usala, Emilio; Carella, Angelo M; Rege-Cambrin, Giovanna; Martino, Bruno; Abruzzese, Elisabetta; Albano, Francesco; Stagno, Fabio; Luciano, Luigia; D'Adda, Mariella; Bocchia, Monica; Cavazzini, Francesco; Tiribelli, Mario; Lunghi, Monia; Pia Falcone, Antonietta; Musolino, Caterina; Levato, Luciano; Venturi, Claudia; Soverini, Simona; Cavo, Michele; Alimena, Giuliana; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Rosti, Gianantonio; Baccarani, Michele

    2016-06-01

    The introduction of second-generation tyrosine-kinase inhibitors (TKIs) has generated a lively debate on the choice of first-line TKI in chronic phase, chronic myeloid leukemia (CML). Despite the TKIs have different efficacy and toxicity profiles, the planned use of two TKIs has never been investigated. We report on a phase 2 study that was designed to evaluate efficacy and safety of a treatment alternating nilotinib and imatinib, in newly diagnosed BCR-ABL1 positive, chronic phase, CML patients. One hundred twenty-three patients were enrolled. Median age was 56 years. The probabilities of achieving a complete cytogenetic response, a major molecular response, and a deep molecular response (MR 4.0) by 2 years were 93%, 87%, and 61%, respectively. The 5-year overall survival and progression-free survival were 89%. Response rates and survival are in the range of those reported with nilotinib alone. Moreover, we observed a relatively low rate of cardiovascular adverse events (5%). These data show that the different efficacy and toxicity profiles of TKIs could be favorably exploited by alternating their use. Am. J. Hematol. 91:617-622, 2016. © 2016 Wiley Periodicals, Inc. PMID:26971721

  8. Management of Advanced-Phase Chronic Myelogenous Leukemia.

    PubMed

    Radich, Jerald P

    2016-05-01

    Chronic myelogenous leukemia represents the poster child of successful precision medicine in cancer, with amazing survival results achieved with targeted tyrosine kinase inhibitors (TKIs) in many patients with chronic-phase disease. Unfortunately, however, this good news has not extended to patients in blast crisis, for whom survival has not clearly been improved with TKIs. During his presentation at the NCCN 21st Annual Conference, Jerald P. Radich, MD, briefly explored the biology behind advanced-stage disease and several of the molecular findings in disease progression. He also reviewed some of the therapeutic options in advanced disease, emphasizing that transplantation, although fraught with some difficulties, offers the best long-term prognosis for patients in blast crisis. PMID:27226510

  9. Accelerating dual cardiac phase images using undersampled radial phase encoding trajectories.

    PubMed

    Letelier, Karis; Urbina, Jesus; Andía, Marcelo; Tejos, Cristián; Irarrazaval, Pablo; Prieto, Claudia; Uribe, Sergio

    2016-09-01

    A three-dimensional dual-cardiac-phase (3D-DCP) scan has been proposed to acquire two data sets of the whole heart and great vessels during the end-diastolic and end-systolic cardiac phases in a single free-breathing scan. This method has shown accurate assessment of cardiac anatomy and function but is limited by long acquisition times. This work proposes to accelerate the acquisition and reconstruction of 3D-DCP scans by exploiting redundant information of the outer k-space regions of both cardiac phases. This is achieved using a modified radial-phase-encoding trajectory and gridding reconstruction with uniform coil combination. The end-diastolic acquisition trajectory was angularly shifted with respect to the end-systolic phase. Initially, a fully-sampled 3D-DCP scan was acquired to determine the optimal percentage of the outer k-space data that can be combined between cardiac phases. Thereafter, prospectively undersampled data were reconstructed based on this percentage. As gold standard images, the undersampled data were also reconstructed using iterative SENSE. To validate the method, image quality assessments and a cardiac volume analysis were performed. The proposed method was tested in thirteen healthy volunteers (mean age, 30years). Prospectively undersampled data (R=4) reconstructed with 50% combination led high quality images. There were no significant differences in the image quality and in the cardiac volume analysis between our method and iterative SENSE. In addition, the proposed approach reduced the reconstruction time from 40min to 1min. In conclusion, the proposed method obtains 3D-DCP scans with an image quality comparable to those reconstructed with iterative SENSE, and within a clinically acceptable reconstruction time. PMID:27067473

  10. Harnessing collaborative technology to accelerate achievement of chronic disease management objectives for Canada.

    PubMed

    Thompson, Leslee J; Healey, Lindsay; Falk, Will

    2007-01-01

    Morgan and colleagues put forth a call to action for the transformation of the Canadian healthcare system through the adoption of a national chronic disease prevention and management (CDPM) strategy. They offer examples of best practices and national solutions including investment in clinical information technologies to help support improved care and outcomes. Although we acknowledge that the authors propose CDPM solutions that are headed in the right direction, more rapid deployment of solutions that harness the potential of advanced collaborative technologies is required. We provide examples of how technologies that exist today can help to accelerate the achievement of some key CDPM objectives.

  11. Chediak-Higashi syndrome presenting in accelerated phase: A case report and literature review.

    PubMed

    Maaloul, I; Talmoudi, J; Chabchoub, I; Ayadi, L; Kamoun, T H; Boudawara, T; Kallel, C H; Hachicha, M

    2016-06-01

    Chediak-Higashi syndrome (CHS) is a rare autosomal recessive lysosomal disorder characterized by frequent infections, oculocutaneous albinism, bleeding diathesis, and progressive neurologic deterioration. In 85% of cases, CHS patients develop the accelerated phase characterized by pancytopenia, high fever, and lymphohistiocytic infiltration of liver, spleen, and lymph nodes. Treatment of accelerated-phase CHS is difficult and the prognosis is poor. Here, we report a case of CHS in a 2-year-old boy who presented in the accelerated phase of the disease. CHS diagnosis was made on the basis of clinical characteristics, hair analysis, and identification of pathognomonic giant azurophilic granules in peripheral blood and bone marrow. PMID:26254864

  12. Phase control of the microwave radiation in free electron laser two-beam accelerator

    SciTech Connect

    Goren, Y.; Sessler, A.M.

    1987-07-01

    A phase control system for the FEL portion of Two-Beam Accelerator is proposed. The control keeps the phase error within acceptable bounds. The control mechanism is analyzed, both analytically in a ''resonant particle'' approximation and numerically in a multi-particle simulation code. Sensitivity of phase errors to the FEL parameters has been noticed.

  13. Force-Time Characteristics and Running Velocity of Male Sprinters During the Acceleration Phase of Sprinting.

    ERIC Educational Resources Information Center

    Mero, Antti

    1988-01-01

    Investigation of the force-time characteristics of eight male sprinters during the acceleration phase of the sprint start suggested that the braking and propulsion phases occur immediately after the block phase and that muscle strength strongly affects running velocity in the sprint start. (Author/CB)

  14. Phase and amplitude control system for Stanford Linear Accelerator

    SciTech Connect

    Yoo, S.J.

    1983-09-26

    The computer controlled phase and amplitude detection system measures the instantaneous phase and amplitude of a 1 micro-second 2856 MHz rf pulse at a 180 Hz rate. This will be used for phase feedback control, and also for phase and amplitude jitter measurement. The program, which was originally written by John Fox and Keith Jobe, has been modified to improve the function of the system. The software algorithms used in the measurement are described, as is the performance of the prototype phase and amplitude detector system.

  15. Ponatinib as first-line treatment for patients with chronic myeloid leukaemia in chronic phase: a phase 2 study

    PubMed Central

    Jain, Preetesh; Kantarjian, Hagop; Jabbour, Elias; Gonzalez, Graciela Nogueras; Borthakur, Gautam; Pemmaraju, Naveen; Daver, Naval; Gachimova, Evguenia; Ferrajoli, Alessandra; Kornblau, Steven; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge

    2015-01-01

    Summary Background Ponatinib has shown efficacy in patients with refractory chronic myeloid leukaemia (CML) and in those with CML with a Thr315Ile mutation. We aimed to investigate the activity and safety of ponatinib as first-line treatment for patients with chronic-phase CML. Methods We did a single-arm, phase 2 trial at MD Anderson Cancer Center in Houston, TX, USA. Between May 3, 2012, and Sept 24, 2013, we enrolled patients with early (<6 months) chronic-phase CML and treated them with oral ponatinib once a day. Patients enrolled before July 25, 2013, were given a starting dose of 45 mg per day; we lowered this due to tolerability issues and patients enrolled after this date were given a starting dose of 30 mg per day. After a warning by the US Food and Drug Administration (FDA) in Oct 6, 2013, for vascular complications with ponatinib, we started all patients on aspirin 81 mg daily and reduced the dose of ponatinib to 30 mg or 15 mg per day for all patients. The primary endpoint was the proportion of patients who achieved complete cytogenetic response by 6 months in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01570868. Findings We enrolled 51 patients. Median follow-up was 20.9 months (IQR 14.9–25.2). 43 patients were started on 45 mg ponatinib every day; eight patients were started on 30 mg per day. 43 (94%) of 46 evaluable patients achieved complete cytogenetic response at 6 months. Most frequent toxicities included skin-related effects (n=35; 69%) and elevated lipase (n=32; 63%). Cardiovascular events (mainly hypertension) occurred in 25 (49%) patients. Grade 3–4 myelosuppression occurred in 15 (29%) patients. Five (10%) patients developed cerebrovascular or vaso-occlusive disease. 43 (85%) patients needed treatment interruptions at some time and 45 (88%) needed dose reductions. The study was terminated June 18, 2014, at the recommendation of the FDA due to concern about the increased risk of thromboembolism

  16. Ram acceleration from a two phase detonative system

    NASA Technical Reports Server (NTRS)

    Cambier, Jean-Luc; Bogdanoff, David W.

    1993-01-01

    A concept for ram acceleration is presented here, which uses a combination of a gas core and a layer of solid explosive or propellant to generate high thrust densities. The concept can be either self-synchronized or externally synchronized, and may be reusable. It has the potential to achieve very high acceleration rates, higher exit velocities and to lower the tube length requirements. Preliminary numerical simulations are presented and discussed, which show the characteristics of the flow fields. Stable conditions can be achieved for low mass loadings of solid explosive, and relatively slow combustion. Accurate knowledge of the thermo-chemical properties and the equations of state of the gas and solid components is essential for further tuning of the concept.

  17. Accelerated life testing effects on CMOS microcircuit characteristics, phase 1

    NASA Technical Reports Server (NTRS)

    Maximow, B.

    1976-01-01

    An accelerated life test of sufficient duration to generate a minimum of 50% cumulative failures in lots of CMOS devices was conducted to provide a basis for determining the consistency of activation energy at 250 C. An investigation was made to determine whether any thresholds were exceeded during the high temperature testing, which could trigger failure mechanisms unique to that temperature. The usefulness of the 250 C temperature test as a predictor of long term reliability was evaluated.

  18. Three-dimensional kinematic analysis of baseball pitching in acceleration phase.

    PubMed

    Wang, Y T; Ford, H T; Ford, H T; Shin, D M

    1995-02-01

    To examine the relationships of pitching performance to maximum external rotation of the shoulder and to time in the acceleration phase, 3 male baseball pitchers were tested using three-dimensional cinematography. Analysis indicated that increasing maximum external rotation of the shoulder at the very beginning of the acceleration phase would help to generate a higher pitching ball velocity since a greater linear and angular displacement could be used to accelerate the throwing forearm. Slowing the wrist action just before ball-release may be a key technique to increasing pitching velocity of the ball.

  19. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study

    PubMed Central

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-01-01

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011–2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

  20. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study.

    PubMed

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-08-01

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011-2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

  1. Deformed phase space Kaluza-Klein cosmology and late time acceleration

    NASA Astrophysics Data System (ADS)

    Sabido, M.; Yee-Romero, C.

    2016-06-01

    The effects of phase space deformations on Kaluza-Klein cosmology are studied. The deformation is introduced by modifying the symplectic structure of the minisuperspace variables. In the deformed model, we find an accelerating scale factor and therefore infer the existence of an effective cosmological constant from the phase space deformation parameter β.

  2. Chronic stress accelerates ligature-induced periodontitis by suppressing glucocorticoid receptor-α signaling

    PubMed Central

    Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan; Zhao, Lisheng

    2016-01-01

    Periodontitis is a common chronic inflammatory disease. Recent studies have shown that chronic stress (CS) might modulate periodontal disease, but there are few models of CS-induced periodontitis, and the underlying mechanisms are unclear. The present study established a rat model of periodontitis associated with CS induced by nylon thread ligatures. The severity of periodontitis was evaluated in this model by radiographic and pathological examination. The inflammatory reaction indicated by the elevated serum levels of interleukin (IL)-1β, IL-6 and IL-8 was assessed by enzyme-linked immunosorbent assay. Toll-like receptor-4 (TLR4) and glucocorticoid receptor-α (GR-α) expressions were detected by reverse transcriptase-PCR and western blotting. Open-field tests and serum corticosterone were used to evaluate CS. The results showed that CS induced behavioral changes and increased corticosterone levels of the animals with periodontitis. CS stimulation markedly increased alveolar bone loss, periodontal pocket depth and the number of plaques. It also enhanced the inflammatory reaction. These results suggest that CS accelerated the ligature-induced pathological changes associated with periodontitis. Further analysis of the mechanisms involved showed that GR-α expression was significantly downregulated in periodontal tissues of the animals undergoing CS. Blocking GR-α signaling in lipopolysaccharide and corticosteroid-treated human periodontal ligament fibroblast cells in vitro significantly upregulated the expression of p-Akt (protein kinase B) and TLR4, promoted nuclear factor-κB activity and increased levels of IL-1β, IL-6 and IL-8. This research suggests that CS might accelerate the pathological progression of periodontitis by a GR-α signaling-mediated inflammatory response and that this may be a potential therapeutic target for the treatment of periodontal disease, particularly in patients with CS. PMID:27012709

  3. Chronic stress accelerates ligature-induced periodontitis by suppressing glucocorticoid receptor-α signaling.

    PubMed

    Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan; Zhao, Lisheng

    2016-03-25

    Periodontitis is a common chronic inflammatory disease. Recent studies have shown that chronic stress (CS) might modulate periodontal disease, but there are few models of CS-induced periodontitis, and the underlying mechanisms are unclear. The present study established a rat model of periodontitis associated with CS induced by nylon thread ligatures. The severity of periodontitis was evaluated in this model by radiographic and pathological examination. The inflammatory reaction indicated by the elevated serum levels of interleukin (IL)-1β, IL-6 and IL-8 was assessed by enzyme-linked immunosorbent assay. Toll-like receptor-4 (TLR4) and glucocorticoid receptor-α (GR-α) expressions were detected by reverse transcriptase-PCR and western blotting. Open-field tests and serum corticosterone were used to evaluate CS. The results showed that CS induced behavioral changes and increased corticosterone levels of the animals with periodontitis. CS stimulation markedly increased alveolar bone loss, periodontal pocket depth and the number of plaques. It also enhanced the inflammatory reaction. These results suggest that CS accelerated the ligature-induced pathological changes associated with periodontitis. Further analysis of the mechanisms involved showed that GR-α expression was significantly downregulated in periodontal tissues of the animals undergoing CS. Blocking GR-α signaling in lipopolysaccharide and corticosteroid-treated human periodontal ligament fibroblast cells in vitro significantly upregulated the expression of p-Akt (protein kinase B) and TLR4, promoted nuclear factor-κB activity and increased levels of IL-1β, IL-6 and IL-8. This research suggests that CS might accelerate the pathological progression of periodontitis by a GR-α signaling-mediated inflammatory response and that this may be a potential therapeutic target for the treatment of periodontal disease, particularly in patients with CS.

  4. Peripheral artery occlusive disease in chronic phase chronic myeloid leukemia patients treated with nilotinib or imatinib.

    PubMed

    Kim, T D; Rea, D; Schwarz, M; Grille, P; Nicolini, F E; Rosti, G; Levato, L; Giles, F J; Dombret, H; Mirault, T; Labussière, H; Lindhorst, R; Haverkamp, W; Buschmann, I; Dörken, B; le Coutre, P D

    2013-06-01

    Several retrospective studies have described the clinical manifestation of peripheral artery occlusive disease (PAOD) in patients receiving nilotinib. We thus prospectively screened for PAOD in patients with chronic phase chronic myeloid leukemia (CP CML) being treated with tyrosine kinase inhibitors (TKI), including imatinib and nilotinib. One hundred and fifty-nine consecutive patients were evaluated for clinical and biochemical risk factors for cardiovascular disease. Non-invasive assessment for PAOD included determination of the ankle-brachial index (ABI) and duplex ultrasonography. A second cohort consisted of patients with clinically manifest PAOD recruited from additional collaborating centers. Pathological ABI were significantly more frequent in patients on first-line nilotinib (7 of 27; 26%) and in patients on second-line nilotinib (10 of 28; 35.7%) as compared with patients on first-line imatinib (3 of 48; 6.3%). Clinically manifest PAOD was identified in five patients, all with current or previous nilotinib exposure only. Relative risk for PAOD determined by a pathological ABI in first-line nilotinib-treated patients as compared with first-line imatinib-treated patients was 10.3. PAOD is more frequently observed in patients receiving nilotinib as compared with imatinib. Owing to the severe nature of clinically manifest PAOD, longitudinal non-invasive monitoring and careful assessment of risk factors is warranted.

  5. The Simpsons program 6-D phase space tracking with acceleration

    SciTech Connect

    Machida, S. )

    1993-12-25

    A particle tracking code, Simpsons, in 6-D phase space including energy ramping has been developed to model proton synchrotrons and storage rings. We take time as the independent variable to change machine parameters and diagnose beam quality in a quite similar way as real machines, unlike existing tracking codes for synchrotrons which advance a particle element by element. Arbitrary energy ramping and rf voltage curves as a function of time are read as an input file for defining a machine cycle. The code is used to study beam dynamics with time dependent parameters. Some of the examples from simulations of the Superconducting Super Collider (SSC) boosters are shown.

  6. The Simpsons program 6-D phase space tracking with acceleration

    SciTech Connect

    Machida, S.

    1993-02-01

    A particle tracking code, Simpsons, in 6-D phase space including energy ramping has been developed to model proton synchrotrons and storage rings. We take time as the independent variable to change machine parameters and diagnose beam quality in a quite similar way as real machines, unlike existing tracking codes for synchrotrons which advance a particle element by element. Arbitrary energy ramping and rf voltage curves as a function of time are read as an input file for defining a machine cycle. The code is used to study beam dynamics with time dependent parameters. Some of the examples from simulations of the Superconducting Super Collider (SSC) boosters are shown.

  7. The Simpsons program 6-D phase space tracking with acceleration

    NASA Astrophysics Data System (ADS)

    Machida, S.

    1993-12-01

    A particle tracking code, Simpsons, in 6-D phase space including energy ramping has been developed to model proton synchrotrons and storage rings. We take time as the independent variable to change machine parameters and diagnose beam quality in a quite similar way as real machines, unlike existing tracking codes for synchrotrons which advance a particle element by element. Arbitrary energy ramping and rf voltage curves as a function of time are read as an input file for defining a machine cycle. The code is used to study beam dynamics with time dependent parameters. Some of the examples from simulations of the Superconducting Super Collider (SSC) boosters are shown.

  8. Peculiarities of laser phase behavior associated with the accelerated electron in a chirped laser pulse

    SciTech Connect

    Song, Q.; Wu, X. Y.; Wang, J. X.; Kawata, S.; Wang, P. X.

    2014-05-15

    In this paper, we qualitatively analyzed peculiarities of laser phase behavior associated with the accelerated electron in a chirped laser pulse. We unveiled the relationship between the changes in the orientation of the electron trajectory and the cusps in magnitude of the phase velocity of the optical field along the electron trajectory in a chirped laser pulse. We also explained how the chirp effect induced the singular point of the phase velocity. Finally, we discussed the phase velocity and phase witnessed by the electron in the particle's moving instantaneous frame.

  9. Correlated histogram representation of Monte Carlo derived medical accelerator photon-output phase space

    DOEpatents

    Schach Von Wittenau, Alexis E.

    2003-01-01

    A method is provided to represent the calculated phase space of photons emanating from medical accelerators used in photon teletherapy. The method reproduces the energy distributions and trajectories of the photons originating in the bremsstrahlung target and of photons scattered by components within the accelerator head. The method reproduces the energy and directional information from sources up to several centimeters in radial extent, so it is expected to generalize well to accelerators made by different manufacturers. The method is computationally both fast and efficient overall sampling efficiency of 80% or higher for most field sizes. The computational cost is independent of the number of beams used in the treatment plan.

  10. Patients with chronic obstructive pulmonary disease and chronically colonized with Haemophilus influenzae during stable disease phase have increased airway inflammation

    PubMed Central

    Tufvesson, Ellen; Bjermer, Leif; Ekberg, Marie

    2015-01-01

    Background Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase. The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations. Methods Forty-three patients with COPD were included while in a stable state and followed up monthly until exacerbation or for a maximum of 6 months. The patients completed the Clinical COPD Questionnaire and Medical Research Council dyspnea scale questionnaires, and exhaled breath condensate was collected, followed by spirometry, impulse oscillometry, and sputum induction. Results Ten patients were chronically colonized (ie, colonized at all visits) with Haemophilus influenzae during stable phase. These patients had higher sputum levels of leukotriene B4 (P<0.001), 8-isoprostane (P=0.002), myeloperoxidase activity (P=0.028), and interleukin-8 (P=0.02) during stable phase when compared with other patients. In addition, they had lower forced vital capacity (P=0.035) and reactance at 5 Hz (P=0.034), but there was no difference in forced expiratory volume in 1 second (FEV1), FEV1 % predicted, forced vital capacity % predicted, exhaled breath condensate biomarkers, C-reactive protein, or Clinical COPD Questionnaire and Medical Research Council dyspnea scale results. Three patients had intermittent colonization (colonized at only some visits) of H. influenzae during stable phase, and had lower levels of inflammatory biomarkers in sputum when compared with the chronically colonized patients. The difference in airway inflammation seen during stable phase in patients chronically colonized with H. influenzae was not observed during exacerbations. Conclusion Some COPD patients who were chronically colonized with H. influenzae during stable phase showed increased airway

  11. Prompt particle acceleration around moving X-point magnetic field during impulsive phase of solar flares

    NASA Technical Reports Server (NTRS)

    Sakai, Jun-Ichi

    1992-01-01

    We present a model for high-energy solar flares to explain prompt proton and electron acceleration, which occurs around moving X-point magnetic field during the implosion phase of the current sheet. We derive the electromagnetic fields during the strong implosion phase of the current sheets, which is driven by the converging flow derived from the magnetohydrodynamic equations. It is shown that both protons and electrons can be promptly (within 1 second) accelerated to approximately 70 MeV and approximately 200 MeV, respectively. This acceleration mechanism can be applicable for the impulsive phase of the gradual gamma ray and proton flares (gradual GR/P flare), which have been called two-ribbon flares.

  12. Cytarabine added to interferon improves the cost-effectiveness of initial therapy for patients with early chronic phase chronic myelogenous leukemia.

    PubMed

    Beck, J R; Guilhot, J; Giles, F J; Aoki, N; Wirt, D P; Guilhot, F

    2001-03-01

    The French Chronic Myeloid Leukemia Study Group prospective randomized study results indicate that the addition of cytarabine to alpha interferon (IFN-alpha) increases the rate of major cytogenetic response and prolongs survival in patients with early chronic phase chronic myelogenous leukemia (CML). The French group study design permitted a single crossover to include or discontinue cytarabine or interferon. Endpoints were overall survival, complete hematologic remission (CHR) at six months, and major cytogenetic response at 12 months. We modified a published Markov model that compared IFN-alpha alone to IFN-alpha plus cytarabine and included the possibility of crossover as in the French study. The model permits allogeneic and autologous stem cell transplantation (SCT), and follows cytogenetic response and acceleration of CML through death. Treatment response, toxicity, and survival are drawn from the French Chronic Myeloid Leukemia Study Group population of 810 patients on an intention-to-treat model. Survivals are extended to 62 months based on currently available follow-up. Costs from a United States oncology specialty institution, and state utilities from previous research and a quality-adjusted Time Without Symptoms or Toxicity analysis of the subject study were discounted at 3% per annum. At the median cohort age of 50, cytarabine offers 21 months of added median survival to IFN-alpha, which itself is superior to conventional chemotherapy by 21 months. Cost-effectiveness estimates for cytarabine added to IFN-alpha range from $7,000 per quality-adjusted life year (QALY) to $35,000 per QALY, under all plausible assumptions superior to IFN-alpha alone. The model is sensitive to the quality of life on therapy, as well as to remission rate with additive cytarabine, although the cost-effectiveness calculations are robust over the entire range of clinical assumptions. Based on data from the French study, cytarabine added to IFN-alpha substantially improves the cost

  13. Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group

    PubMed Central

    Cervantes, Francisco; López-Garrido, Pilar; Montero, María-Isabel; Jonte, Fermín; Martínez, Jesús; Hernández-Boluda, Juan-Carlos; Calbacho, María; Sureda, Anna; Pérez-Rus, Gloria; Nieto, José B.; Pérez-López, Cristina; Román-Gómez, José; González, Marcos; Pereira, Arturo; Colomer, Dolors

    2010-01-01

    Background Despite the favorable results of imatinib front line in chronic-phase chronic myeloid leukemia there is room for improvement. Design and Methods Early intervention during imatinib therapy was undertaken in 210 adults with chronic-phase chronic myeloid leukemia less than three months from diagnosis (Sokal high risk: 16%). Patients received imatinib 400 mg/day. At three months, dose was increased if complete hematologic response was not achieved. At six months, patients in complete cytogenetic response were kept on 400 mg and the remainder randomized to higher imatinib dose or 400 mg plus interferon-alfa. At 18 months, randomized patients were switched to a 2nd generation tyrosine kinase inhibitor if not in complete cytogenetic response and imatinib dose increased in non-randomized patients not in major molecular response. Results Seventy-two percent of patients started imatinib within one month from diagnosis. Median follow-up is 50.5 (range: 1.2–78) months. At three months 4 patients did not have complete hematologic response; at six months 73.8% were in complete cytogenetic response; among the remainder, 9 could not be randomized (toxicity or consent withdrawal), 17 were assigned to high imatinib dose, and 15 to 400 mg + interferon-alpha. The low number of randomized patients precluded comparison between the two arms. Cumulative response at three years was: complete hematologic response 98.6%, complete cytogenetic response 90% and major molecular response 82%. On an intention-to-treat basis, complete cytogenetic response was 78.8% at 18 months. At five years, survival was 97.5%, survival free from accelerated/blastic phase 94.3%, failure free survival 82.5%, and event free survival (including permanent imatinib discontinuation) 71.5%. Conclusions These results indicate the benefit of early intervention during imatinib therapy (ClinicalTrials.gov Identifier: NCT00390897). PMID:20220063

  14. Ionic liquid acceleration of solid-phase suzuki-miyaura cross-coupling reactions.

    PubMed

    Revell, Jefferson D; Ganesan, A

    2002-09-01

    [reaction: see text] Room-temperature ionic liquids promote various transition metal-catalyzed reactions in the solution phase. Here, for the first time, we show that these effects are translatable to solid-phase reactions. The Suzuki-Miyaura cross-coupling of 4-iodophenol immobilized on polystyrene-Wang resin with various arylboronic acids was significantly accelerated by the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF(4)(-)]).

  15. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial

    PubMed Central

    Hochhaus, A; Saglio, G; Hughes, T P; Larson, R A; Kim, D-W; Issaragrisil, S; le Coutre, P D; Etienne, G; Dorlhiac-Llacer, P E; Clark, R E; Flinn, I W; Nakamae, H; Donohue, B; Deng, W; Dalal, D; Menssen, H D; Kantarjian, H M

    2016-01-01

    In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54% 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR4.5; BCR-ABL⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP. PMID:26837842

  16. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial.

    PubMed

    Hochhaus, A; Saglio, G; Hughes, T P; Larson, R A; Kim, D-W; Issaragrisil, S; le Coutre, P D; Etienne, G; Dorlhiac-Llacer, P E; Clark, R E; Flinn, I W; Nakamae, H; Donohue, B; Deng, W; Dalal, D; Menssen, H D; Kantarjian, H M

    2016-05-01

    In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR(4.5); BCR-ABL⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.

  17. Chronic exogenous kisspeptin administration accelerates gonadal development in basses of the genus Morone.

    PubMed

    Beck, Benjamin H; Fuller, S Adam; Peatman, Eric; McEntire, Matthew E; Darwish, Ahmed; Freeman, Donald W

    2012-07-01

    The present study assesses the effects of chronic administration of peptides to fish, termed kisspeptins, which are the products of the KISS1 and KISS2 genes, and have been shown to control the development of puberty in animals. Using ecologically and commercially important species (white bass, Morone chrysops, striped bass, Morone saxatilis, and their hybrid) as comparative models, we determined that repeated bi-weekly injections (over 7 weeks) differentially accelerate puberty, as evidenced by increases in the prevalence of spermatozoa in the testes of juvenile fish. Moreover, in sexually mature fish, kisspeptin treatment led to increased gonad weight, gonadosomatic index, and spermatocrit in some white and striped bass. Additionally, mature white bass treated with kisspeptins showed an advancement in oocyte development as determined by histological examination. These gonadal changes occurred in the absence of any photothermal manipulation or hormone injections. To date, this is the first description of kisspeptin-mediated pubertal initiation in fish, and the first evidence that kisspeptins could modulate gonad maturation. Although it remains to be determined how kisspeptins may best be utilized in practice, our findings are a basis for future studies to characterize the molecular underpinnings of the KISS system in various fish species. PMID:22497780

  18. Pharmacological inhibitors of NF-kappaB accelerate apoptosis in chronic lymphocytic leukaemia cells.

    PubMed

    Pickering, B M; de Mel, S; Lee, M; Howell, M; Habens, F; Dallman, C L; Neville, L A; Potter, K N; Mann, J; Mann, D A; Johnson, P W M; Stevenson, F K; Packham, G

    2007-02-22

    Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays a critical role in the inappropriate survival of various types of malignant cells. Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the Western world. Although overexpression and regulation of NF-kappaB has been described in CLL, its function remains unclear. Exposure of CLL cells to BAY117082 or Kamebakaurin, potent pharmacological inhibitors of the NF-kappaB pathway, accelerated apoptosis in approximately 70% of cases. Sensitivity to NF-kappaB pathway inhibitors was not related to the prognostic markers VH status, CD38 or Zap70 expression, or to the levels of nuclear NF-kappaB. Normal peripheral B cells were resistant to the apoptosis-inducing effects of these compounds. Cell death induced by the inhibitors was associated with activation of caspase-9 and -3, and loss of mitochondrial membrane polarization, but did not involve changes in the expression of Bcl-2 or Mcl-1. Inhibitors caused an increase in c-jun NH2-terminal kinase activity in CLL, but this did not appear to be important for apoptosis. Microarray analysis identified some potential novel NF-kappaB target genes, including interleukin-16- and the Bcl-2- related survival protein Bcl-w. These results demonstrate that a substantial proportion of CLL are dependent on NF-kappaB for enhanced survival and suggest that inhibition of NF-kappaB may have therapeutic potential.

  19. Phases of chronic pain: a model for assessment and treatment.

    PubMed

    Fisher, L B; Goldstein, L S; Buongiorno, P A

    1990-09-01

    Chronic pain can be described as a syndrome or process of decompensation not unlike any other chronic disease or illness. As such, chronic pain patients are often difficult to work with because of the pervasive personal, social, emotional, and physical impact of the syndrome on their lives and the lives of their families. The pain curve was developed to be used as an educational instrument to assist patients in understanding the disease process, confronting denial, and self-diagnosing their illness. This curve now in use at our institution describes both the progression and the recovery of the illness. The pain curve is used as an educational tool to aid patients in addressing important recovery issues such as denial and the disease process, the progression of symptoms in a chronic illness, medication and alcohol use and abuse in the management of chronic pain, the impact on and from the family and the importance of peer support.

  20. Transfection-mediated cell synchronization: acceleration of G1-S phase transition by gamma irradiation.

    PubMed

    Jung, E J; Flemington, E K

    2001-11-01

    We have previously provided evidence that the uptake of DNA into cells is cell cycle specific following transfection. We show here that, immediately after transfection, successfully transfected cells are greatly enriched for cells in early G1 or G0 phase and that, upon removal of the DNA precipitates, cells progress through G1 and enter S phase in a synchronous fashion. We also demonstrate that this approach can be utilized in meaningful cell-cycle experiments, and we show that gamma irradiation accelerates the G1-S phase transition in a cell line with a functionally inactive p53 protein. PMID:11730009

  1. Alternating-phase-focused IH-DTL for an injector of heavy-ion medical accelerators

    NASA Astrophysics Data System (ADS)

    Iwata, Y.; Yamada, S.; Murakami, T.; Fujimoto, T.; Fujisawa, T.; Ogawa, H.; Miyahara, N.; Yamamoto, K.; Hojo, S.; Sakamoto, Y.; Muramatsu, M.; Takeuchi, T.; Mitsumoto, T.; Tsutsui, H.; Watanabe, T.; Ueda, T.

    2006-12-01

    A compact Drift-Tube-Linac (DTL) using an Interdigital H-mode (IH) cavity was designed for an injector of medical accelerators. For beam focusing, the method of Alternating-Phase-Focusing (APF) was applied. The APF IH-DTL can accelerate heavy ions having a charge-to-mass ratio of q/m={1}/{3} up to 4.0 MeV/u. Having optimized an array of synchronous phases for cells, namely arranging drift tubes and gaps appropriately, both longitudinal and transverse focusing strengths were produced just with the rf acceleration field, and therefore no focusing element or cooling equipments had to be installed in the cavity. This allowed us to employ a rather high operating frequency, and hence to design a compact and cost-effective cavity. A further advantage of the APF linac can be found in its operation. Since the parameters to be adjusted are just the level and phase of the input rf, beam tuning can be made with ease. Consequently, the APF linac is suitable for an injector for medical accelerators. Tuning methods of the gap voltages and cavity frequency as well as the design of the cavity for APF IH-DTL have been developed. After constructing the cavity, measurements of the electric field and tuning of the gap voltages were performed. Finally, the rf power was fed into the cavity. In this paper, the design and results of the measurements are described.

  2. Direct acceleration of electrons by a circular polarized laser pulse with phase modulation

    SciTech Connect

    Zhu, Lun-Wu; Sheng, Zheng-Mao; Yu, M. Y.

    2013-11-15

    Electron acceleration by transversely echelon phase-modulated (EPM) circularly polarized (CP) intense laser pulse is investigated. Solution of the relativistic electron equations of motion shows that the CP EPM light wave structure can disrupt the harmonic response of a trapped electron not only in the transverse direction but also in the direction of laser propagation. In each laser cycle, there can be a net gain in the electron's transverse momentum, which is promptly converted into the forward direction by the Lorentz force. As a result, the electron can be trapped and accelerated in the favorable phase of the laser for a rather long time. Its momentum gain then accumulates and can eventually reach high levels. It is also found that with the CP EPM laser, the net acceleration of the electron is not sensitive to its initial position and velocity relative to the phase of the laser fields, so that such a laser can also be useful for accelerating thermal electron bunches to high energies.

  3. Pion-decay radiation and two-phase acceleration in the June 3, 1982 solar flare

    NASA Technical Reports Server (NTRS)

    Ramaty, R.; Dermer, C. D.; Murphy, R. J.

    1986-01-01

    The June 3, 1982 flare is unique in the wealth of observed neutron, gamma-ray and energetic-particle emission that it produced. Using calculations of high-energy emissions to fit the various time-dependent gamma-ray fluxes, a self-consistent interaction model for the June 3 flare is constructed in which the observed fluxes are produced by two distinct particle populations with different acceleration and interaction time histories as well as different but time-independent energy spectra. The two populations are associated with first- and second-phase particle acceleration, respectively.

  4. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up.

    PubMed

    Larson, R A; Hochhaus, A; Hughes, T P; Clark, R E; Etienne, G; Kim, D-W; Flinn, I W; Kurokawa, M; Moiraghi, B; Yu, R; Blakesley, R E; Gallagher, N J; Saglio, G; Kantarjian, H M

    2012-10-01

    Evaluating Nilotinib Efficacy and Safety in Clinical Trials Newly Diagnosed Patients compares nilotinib and imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). With a minimum follow-up of 3 years, major molecular response, molecular response of BCR-ABL≤ 0.01% expressed on the international scale (BCR-ABL(IS); MR(4)) and BCR-ABL(IS)≤ 0.0032% (MR(4.5)) rates were significantly higher with nilotinib compared with imatinib, and differences in the depth of molecular response between nilotinib and imatinib have increased over time. No new progressions occurred on treatment since the 2-year analysis. Nilotinib was associated with a significantly lower probability of progression to accelerated phase/blast crisis vs imatinib (two (0.7%) progressions on nilotinib 300 mg twice daily, three (1.1%) on nilotinib 400 mg twice daily and 12 (4.2%) on imatinib). When considering progressions occurring after study treatment discontinuation, the advantage of nilotinib over imatinib in preventing progression remained significant (nine (3.2%) progressions on nilotinib 300 mg twice daily, six (2.1%) on nilotinib 400 mg twice daily and 19 (6.7%) on imatinib). Both nilotinib and imatinib were well tolerated, with minimal changes in safety over time. Nilotinib continues to demonstrate superior efficacy in all key response and outcome parameters compared with imatinib for the treatment of patients with newly diagnosed CML-CP.

  5. Measurement of Beryllium in Biological Samples by Accelerator Mass Spectrometry: Applications for Studying Chronic Beryllium Disease

    SciTech Connect

    Chiarappa-Zucca, M L; Finkel, R C; Martinelli, R E; McAninch, J E; Nelson, D O; Turtletaub, K W

    2004-04-15

    A method using accelerator mass spectrometry (AMS) has been developed for quantifying attomoles of beryllium (Be) in biological samples. This method provides the sensitivity to trace Be in biological samples at very low doses with the purpose of identifying the molecular targets involved in chronic beryllium disease. Proof of the method was tested by administering 0.001, 0.05, 0.5 and 5.0 {micro}g {sup 9}Be and {sup 10}Be by intraperitoneal injection to male mice and removing spleen, liver, femurs, blood, lung, and kidneys after 24 h exposure. These samples were prepared for AMS analysis by tissue digestion in nitric acid, followed by further organic oxidation with hydrogen peroxide and ammonium persulfate and lastly, precipitation of Be with ammonium hydroxide, and conversion to beryllium oxide at 800 C. The {sup 10}Be/{sup 9}Be ratio of the extracted beryllium oxide was measured by AMS and Be in the original sample was calculated. Results indicate that Be levels were dose-dependent in all tissues and the highest levels were measured in the spleen and liver. The measured {sup 10}Be/{sup 9}Be ratios spanned 4 orders of magnitude, from 10{sup -10} to 10{sup -14}, with a detection limit of 3.0 x 10{sup -14}, which is equivalent to 0.8 attomoles of {sup 10}Be. These results show that routine quantification of nanogram levels of Be in tissues is possible and that AMS is a sensitive method that can be used in biological studies to understand the molecular dosimetry of Be and mechanisms of toxicity.

  6. Proposal for a study of laser acceleration of electrons using micrograting structures at ATF (Phase 1)

    SciTech Connect

    Chen, W.; Claus, J.; Fernow, R.C.; Fischer, J.; Gallardo, J.C.; Kirk, H.G.; Kramer, H.; Li, Z.; Palmer, R.B.; Rogers, J.; Shrinvasan-Rao, T.; Tsang, T.; Ulc, S.; Veligdan, J.; Warren, J.; Bigio, I.; Kurnit, N.; Shimada, T.; Wang, X.; McDonald, K.T.; Russell, D.P.; Los Alamos National Lab., NM; Princeton Univ., NJ; California Univ., Los Angeles, CA )

    1989-10-29

    We propose to investigate new methods of particle acceleration using a short-pulse CO{sub 2} laser as the power source and grating-like structures as accelerator cavities''. Phase I of this program is intended to demonstrate the principle of the method. We will focus the laser light to a 3 mm line on the surface of the microstructure. The structure is used to transform the electric field pattern of the incoming transversely polarized laser beam to a mode which has a component along the electron beam direction in the vicinity of the surface. With 6 mJ of laser energy and a 6 ps pulse length, the electric field in the spot will be around 1 GV/m. The electron beam from the Brookhaven Accelerator Test Facility (ATF) will be focused transversely within the few micron transverse dimension of the microstructure. The maximum expected acceleration for a 1 GV/m field and a 3 mm acceleration length is 3 MeV. 17 refs., 11 figs., 2 tabs.

  7. Aberrant activation of CaMKIIγ accelerates chronic myeloid leukemia blast crisis.

    PubMed

    Gu, Y; Zheng, W; Zhang, J; Gan, X; Ma, X; Meng, Z; Chen, T; Lu, X; Wu, Z; Huang, W; Xu, R

    2016-06-01

    Blast crisis (BC) is the final deadly phase of chronic myeloid leukemia (CML), but its molecular basis remains poorly understood. Here, we show that CML BC is regulated by calcium-calmodulin-dependent kinase IIγ (CaMKIIγ). Genetic deletion of CaMKIIγ greatly inhibits disease progression via selectively impairing the self-renewal of leukemia stem cells (LSCs) in mouse models, whereas overexpression of CaMKIIγ has the opposite effects. In human CML, phosphorylated CaMKIIγ abundance is significantly associated with BC. Moreover, CaMKIIγ phosphorylates and reduces the nuclear cyclin-dependent kinase inhibitor p27Kip1, a critical brake that maintains LSC quiescence. These findings suggest that CaMKIIγ might be an important switch for the transition of CML BC and identify a unique mechanism by which CaMKIIγ promotes the self-renewal of LSCs by deceasing nuclear p27Kip1 to wake up dormant LSCs. Therefore, CaMKIIγ may provide a new therapeutic target to treat CML BC.

  8. Aberrant activation of CaMKIIγ accelerates chronic myeloid leukemia blast crisis.

    PubMed

    Gu, Y; Zheng, W; Zhang, J; Gan, X; Ma, X; Meng, Z; Chen, T; Lu, X; Wu, Z; Huang, W; Xu, R

    2016-06-01

    Blast crisis (BC) is the final deadly phase of chronic myeloid leukemia (CML), but its molecular basis remains poorly understood. Here, we show that CML BC is regulated by calcium-calmodulin-dependent kinase IIγ (CaMKIIγ). Genetic deletion of CaMKIIγ greatly inhibits disease progression via selectively impairing the self-renewal of leukemia stem cells (LSCs) in mouse models, whereas overexpression of CaMKIIγ has the opposite effects. In human CML, phosphorylated CaMKIIγ abundance is significantly associated with BC. Moreover, CaMKIIγ phosphorylates and reduces the nuclear cyclin-dependent kinase inhibitor p27Kip1, a critical brake that maintains LSC quiescence. These findings suggest that CaMKIIγ might be an important switch for the transition of CML BC and identify a unique mechanism by which CaMKIIγ promotes the self-renewal of LSCs by deceasing nuclear p27Kip1 to wake up dormant LSCs. Therefore, CaMKIIγ may provide a new therapeutic target to treat CML BC. PMID:27012864

  9. Phase-space dynamics of ionization injection in plasma-based accelerators.

    PubMed

    Xu, X L; Hua, J F; Li, F; Zhang, C J; Yan, L X; Du, Y C; Huang, W H; Chen, H B; Tang, C X; Lu, W; Yu, P; An, W; Joshi, C; Mori, W B

    2014-01-24

    The evolution of beam phase space in ionization injection into plasma wakefields is studied using theory and particle-in-cell simulations. The injection process involves both longitudinal and transverse phase mixing, leading initially to a rapid emittance growth followed by oscillation, decay, and a slow growth to saturation. An analytic theory for this evolution is presented and verified through particle-in-cell simulations. This theory includes the effects of injection distance (time), acceleration distance, wakefield structure, and nonlinear space charge forces, and it also shows how ultralow emittance beams can be produced using ionization injection methods.

  10. Relationship between Lower Limb Angular Kinematic Variables and the Effectiveness of Sprinting during the Acceleration Phase

    PubMed Central

    Konieczny, Grzegorz; Winiarski, Sławomir; Rokita, Andrzej

    2016-01-01

    The ability to reach a high running velocity over a short distance is essential to a high playing performance in team games. The aim of this study was to determine the relationship between running time over a 10-meter section of a 30-meter sprint along a straight line and changes in the angle and angular velocity that were observed in the ankle, knee, and hip joints. The possible presence may help to optimize motion efficiency during acceleration sprint phase. Eighteen girls involved in team sports were examined in the study. The Fusion Smart Speed System was employed for running time measurements. The kinematic data were recorded using the Noraxon MyoMotion system. Statistically significant relationships were found between running time over a 10-meter section and the kinematic variables of hip and ankle joints. An excessively large flexion in hip joints might have an unfavorable effect on running time during the acceleration phase. Furthermore, in order to minimize running time during the acceleration phase, stride should be maintained along a line (a straight line) rather than from side to side. It is also necessary to ensure an adequate range of motion in the hip and ankle joints with respect to the sagittal axis. PMID:27516724

  11. Relationship between Lower Limb Angular Kinematic Variables and the Effectiveness of Sprinting during the Acceleration Phase.

    PubMed

    Struzik, Artur; Konieczny, Grzegorz; Stawarz, Mateusz; Grzesik, Kamila; Winiarski, Sławomir; Rokita, Andrzej

    2016-01-01

    The ability to reach a high running velocity over a short distance is essential to a high playing performance in team games. The aim of this study was to determine the relationship between running time over a 10-meter section of a 30-meter sprint along a straight line and changes in the angle and angular velocity that were observed in the ankle, knee, and hip joints. The possible presence may help to optimize motion efficiency during acceleration sprint phase. Eighteen girls involved in team sports were examined in the study. The Fusion Smart Speed System was employed for running time measurements. The kinematic data were recorded using the Noraxon MyoMotion system. Statistically significant relationships were found between running time over a 10-meter section and the kinematic variables of hip and ankle joints. An excessively large flexion in hip joints might have an unfavorable effect on running time during the acceleration phase. Furthermore, in order to minimize running time during the acceleration phase, stride should be maintained along a line (a straight line) rather than from side to side. It is also necessary to ensure an adequate range of motion in the hip and ankle joints with respect to the sagittal axis. PMID:27516724

  12. Two-phase turbine engines. [using gas-liquid mixture accelerated in nozzles

    NASA Technical Reports Server (NTRS)

    Elliott, D. G.; Hays, L. G.

    1976-01-01

    A description is given of a two-phase turbine which utilizes a uniform mixture of gas and liquid accelerated in nozzles of the types reported by Elliott and Weinberg (1968). The mixture acts directly on an axial flow or tangential impulse turbine or is separated into gas and liquid streams which operate separately on a gas turbine and a hydraulic turbine. The basic two-phase cycles are examined, taking into account working fluids, aspects of nozzle expansion, details of turbine cycle operation, and the effect of mixture ratio variation. Attention is also given to two-phase nozzle efficiency, two-phase turbine operating characteristics and efficiencies, separator turbines, and impulse turbine experiments.

  13. Accelerating Energy Efficiency in Indian Data Centers. Final Report for Phase I Activities

    SciTech Connect

    Ganguly, Suprotim; Raje, Sanyukta; Kumar, Satish; Sartor, Dale; Greenberg, Steve

    2016-01-01

    This report documents Phase 1 of the “Accelerating Energy Efficiency in Indian Data Centers” initiative to support the development of an energy efficiency policy framework for Indian data centers. The initiative is being led by the Confederation of Indian Industry (CII), in collaboration with Lawrence Berkeley National Laboratory (LBNL)-U.S. Department of Energy’s Office of Energy Efficiency and Renewable Energy, and under the guidance of Bureau of Energy Efficiency (BEE). It is also part of the larger Power and Energy Efficiency Working Group of the US-India Bilateral Energy Dialogue. The initiative consists of two phases: Phase 1 (November 2014 – September 2015) and Phase 2 (October 2015 – September 2016).

  14. Accelerated phase-contrast cine MRI using k-t SPARSE-SENSE.

    PubMed

    Kim, Daniel; Dyvorne, Hadrien A; Otazo, Ricardo; Feng, Li; Sodickson, Daniel K; Lee, Vivian S

    2012-04-01

    Phase-contrast (PC) cine MRI is a promising method for assessment of pathologic hemodynamics, including cardiovascular and hepatoportal vascular dynamics, but its low data acquisition efficiency limits the achievable spatial and temporal resolutions within clinically acceptable breath-hold durations. We propose to accelerate PC cine MRI using an approach which combines compressed sensing and parallel imaging (k-t SPARSE-SENSE). We validated the proposed 6-fold accelerated PC cine MRI against 3-fold accelerated PC cine MRI with parallel imaging (generalized autocalibrating partially parallel acquisitions). With the programmable flow pump, we simulated a time varying waveform emulating hepatic blood flow. Normalized root mean square error between two sets of velocity measurements was 2.59%. In multiple blood vessels of 12 control subjects, two sets of mean velocity measurements were in good agreement (mean difference = -0.29 cm/s; lower and upper 95% limits of agreement = -5.26 and 4.67 cm/s, respectively). The mean phase noise, defined as the standard deviation of the phase in a homogeneous stationary region, was significantly lower for k-t SPARSE-SENSE than for generalized autocalibrating partially parallel acquisitions (0.05 ± 0.01 vs. 0.19 ± 0.06 radians, respectively; P < 0.01). The proposed 6-fold accelerated PC cine MRI pulse sequence with k-t SPARSE-SENSE is a promising investigational method for rapid velocity measurement with relatively high spatial (1.7 mm × 1.7 mm) and temporal (∼35 ms) resolutions.

  15. High-resolution simulations of downslope gravity currents in the acceleration phase

    NASA Astrophysics Data System (ADS)

    Dai, Albert

    2015-07-01

    Gravity currents generated from an instantaneous buoyancy source propagating down a slope in the range of 0∘ ≤ θ < 90∘ have been investigated in the acceleration phase by means of high-resolution two-dimensional simulations of the incompressible Navier-Stokes equations with the Boussinesq approximation. Front velocity history shows that, after the heavy fluid is released from rest, the flow goes through the acceleration phase, reaching a maximum front velocity Uf,max, and followed by the deceleration phase. The existence of a maximum of Uf,max is found near θ = 40∘, which is supported by the improved theory. It is identified for the first time that the time of acceleration decreases as the slope angle increases, when the slope angle is approximately greater than 10∘, and the time of acceleration increases as the slope angle increases for gravity currents on lower slope angles. A fundamental difference in flow patterns, which helps explain the distinct characteristics of gravity currents on high and low slope angles using scaling arguments, is revealed. Energy budgets further show that, as the slope angle increases, the ambient fluid is more easily engaged in the gravitational convection and the potential energy loss is more efficiently converted into the kinetic energy associated with ambient fluid. The propagation of gravity currents on a slope is found to be qualitatively modified as the depth ratio, i.e., the lock height to channel height ratio, approaches unity. As the depth ratio increases, the conversion of potential energy loss into the kinetic energy associated with heavy fluid is inhibited and the conversion into the kinetic energy associated with ambient fluid is enhanced by the confinement of the top wall.

  16. Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-12-09

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  17. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

    PubMed Central

    Shah, Neil P.; Kim, Dong-Wook; Kantarjian, Hagop; Rousselot, Philippe; Llacer, Pedro Enrique Dorlhiac; Enrico, Alicia; Vela-Ojeda, Jorge; Silver, Richard T.; Khoury, Hanna Jean; Müller, Martin C.; Lambert, Alexandre; Matloub, Yousif; Hochhaus, Andreas

    2010-01-01

    Background Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here. Design and Methods In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily. Results Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase. Conclusions Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition. PMID:20139391

  18. ACCELERATORS: Tuning of RF amplitude and phase for the drift tube linac in J-PARC

    NASA Astrophysics Data System (ADS)

    Shen, Guo-Bao; Masanori, Ikegami

    2009-07-01

    The J-PARC linac has three DTL tanks to accelerate the negative hydrogen ions from 3 MeV to 50 MeV. The RF phase and amplitude are adjusted for each cavity with a phase scan method within the accuracy of 1? in phase and 1% in amplitude. The experimental results show a remarkable agreement with the numerical model within a sufficient margin in the tuning of the last two DTL tanks. However, a notable discrepancy between the experiment and the numerical model is seen in the tuning of the first DTL tank. After studying with a three-dimensional multi-particle simulation, the generation of the low energy component and the pronounced filamentation are identified as the main causes of the discrepancy. The optimization of the tuning scheme is also discussed to attain the tuning goal accuracy for the first DTL tank.

  19. Graphics processing unit-accelerated double random phase encoding for fast image encryption

    NASA Astrophysics Data System (ADS)

    Lee, Jieun; Yi, Faliu; Saifullah, Rao; Moon, Inkyu

    2014-11-01

    We propose a fast double random phase encoding (DRPE) algorithm using a graphics processing unit (GPU)-based stream-processing model. A performance analysis of the accelerated DRPE implementation that employs the Compute Unified Device Architecture programming environment is presented. We show that the proposed methodology executed on a GPU can dramatically increase encryption speed compared with central processing unit sequential computing. Our experimental results demonstrate that in encryption data of an image with a pixel size of 1000×1000, where one pixel has a 32-bit depth, our GPU version of the DRPE scheme can be approximately two times faster than the advanced encryption standard algorithm implemented on a GPU. In addition, the quality of parallel processing on the presented DRPE acceleration method is evaluated with performance parameters, such as speedup, efficiency, and redundancy.

  20. Dasatinib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Did Not Respond to Imatinib Mesylate

    ClinicalTrials.gov

    2013-02-04

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Meningeal Chronic Myelogenous Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  1. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial

    PubMed Central

    Brümmendorf, Tim H; Cortes, Jorge E; de Souza, Cármino Antonio; Guilhot, Francois; Duvillié, Ladan; Pavlov, Dmitri; Gogat, Karïn; Countouriotis, Athena M; Gambacorti-Passerini, Carlo

    2015-01-01

    Bosutinib is an oral, dual SRC/ABL1 tyrosine kinase inhibitor for resistant/intolerant chronic myeloid leukaemia (CML). We assessed the efficacy and safety of bosutinib 500 mg/d (n = 250) versus imatinib 400 mg/d (n = 252) after >24 months from accrual completion in newly diagnosed chronic phase (CP)-CML (Bosutinib Efficacy and Safety in Newly Diagnosed CML trial [BELA]). Cumulative complete cytogenetic response (CCyR) rates by 24 months were similar (bosutinib, 79%; imatinib, 80%); cumulative major molecular response (MMR) rates were 59% for bosutinib and 49% for imatinib. Responses were durable; 151/197 vs. 172/204 and 125/153 vs. 117/131 responders remained on treatment and maintained CCyR and MMR, respectively. Since the 12-month primary analysis, no new accelerated-/blast-phase transformations occurred with bosutinib; four occurred with imatinib. Early response (BCR-ABL1/ABL1 ≤ 10%, 3 months) was associated with better CCyR and MMR rates by 12 and 24 months (both arms). Gastrointestinal events and liver function test elevations were more common, and neutropenia, musculoskeletal events and oedema were less common with bosutinib. Discontinuations due to adverse events were more common with bosutinib versus imatinib (most commonly alanine aminotransferase elevation: 4% vs. <1%); most occurred within the first 12 months. Cardiovascular adverse events were similar in both arms. Bosutinib continues to demonstrate good efficacy and manageable tolerability in newly diagnosed CP-CML patients. PMID:25196702

  2. Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase.

    PubMed

    Hochhaus, Andreas; Saglio, Giuseppe; Larson, Richard A; Kim, Dong-Wook; Etienne, Gabriel; Rosti, Gianantonio; De Souza, Carmino; Kurokawa, Mineo; Kalaycio, Matt E; Hoenekopp, Albert; Fan, Xiaolin; Shou, Yaping; Kantarjian, Hagop M; Hughes, Timothy P

    2013-05-01

    In patients with chronic myeloid leukemia, BCR-ABL mutations contribute to resistance to tyrosine kinase inhibitor therapy. We examined the occurrence of treatment-emergent mutations and their impact on response in patients from the ENESTnd phase 3 trial. At the 3-year data cutoff, mutations were detected in approximately twice as many patients (21) on imatinib 400 mg once daily as on nilotinib (11 patients each on nilotinib 300 mg twice daily and nilotinib 400 mg twice daily). The majority of mutations occurred in patients with intermediate or high Sokal scores. Most mutations (14 [66.7%]) emerging during imatinib treatment were imatinib-resistant and nilotinib-sensitive. Incidence of the T315I mutation was low (found in 3, 2, and 3 patients on nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, and imatinib, respectively) and mostly occurred in patients with high Sokal scores. Of the patients with emergent mutations, 1 of 11, 2 of 11, and 7 of 21 patients on nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, and imatinib, respectively, progressed to accelerated phase/blast crisis (AP/BC) on treatment. Overall, nilotinib led to fewer treatment-emergent BCR-ABL mutations than imatinib and reduced rates of progression to AP/BC in patients with these mutations. (Clinicaltrials.gov NCT00471497).

  3. Acceleration and deceleration phase nonlinear Rayleigh-Taylor growth at spherical interfaces

    SciTech Connect

    Clark, D S; Tabak, M

    2005-04-08

    The Layzer model for the nonlinear evolution of bubbles in the Rayleigh-Taylor instability has recently been generalized to the case of spherically imploding interfaces [D. S. Clark and M. Tabak, to appear, PRE (2005).]. The spherical case is more relevant to, e.g., inertial confinement fusion or various astrophysical phenomena when the convergence is strong or the perturbation wavelength is comparable to the interface curvature. Here, the model is further extended to the case of bubble growth during the deceleration (stagnation) phase of a spherical implosion and to the growth of spikes during both the acceleration and deceleration phases. Differences in the nonlinear growth rates for both bubbles and spikes are found when compared with planar results. The model predictions are verified by comparison with numerical hydrodynamics simulations.

  4. Orbit determination and estimation of non-gravitational accelerations for the GOCE reentry phase

    NASA Astrophysics Data System (ADS)

    Visser, P. N. A. M.; van den IJssel, J. A. A.

    2016-11-01

    During its reentry phase from 21 October to 10 November 2013, the European Space Agency (ESA) Gravity field and steady-state Ocean Circulation Explorer (GOCE) continued to provide high-quality, dual-frequency observations by its Global Positioning System (GPS) receiver, star tracker and accelerometers. This resulted in a unique data set for testing high-precision orbit determination at altitudes down to as low as 137 km. In addition, the accelerometers kept working down to this altitude as well, be it with growing periods during which they were saturated. This made it possible to test the capability of estimating non-gravitational accelerations in high drag environments by GPS. A reduced-dynamic orbit determination based on an extended Kalman filter approach was adopted to cope with the estimation of the orbit parameters, including the exponentially growing non-gravitational accelerations. The orbits were found to be consistent with Satellite Laser Ranging (SLR) observations at a level of just a few centimeters for a few passes collected up to 2 November 2013. Also orbit overlap comparisons and comparisons with external orbit solutions indicate a 3-dimensional orbit quality at the dm level or better. In addition, high correlations were found between the estimated non-gravitational accelerations and those from the accelerometers during all periods when they were not saturated: typically close to 0.99 for the X axis of the gradiometer reference frame (close to the flight direction), for which the non-gravitational acceleration signal is by far the largest. High correlations were found as well for the Y axis (0.68-0.96) and Z axis (0.61-0.93), predominantly aligned with respectively the cross-track and height direction. The highest correlations were found for the last days, as long as the accelerometers were not saturated.

  5. Is the short follicular phase in older women secondary to advanced or accelerated dominant follicle development?

    PubMed

    Klein, Nancy A; Harper, Andrew J; Houmard, Brenda S; Sluss, Patrick M; Soules, Michael R

    2002-12-01

    This study sought to determine whether the shortened follicular phase in ovulatory older women is secondary to advanced (i.e. earlier) or accelerated (i.e. more rapid) folliculogenesis. Normal ovulatory women, aged 40-45 yr (n = 15) and 20-25 yr (n = 13), underwent daily venipuncture and transvaginal ultrasonography throughout the follicular phase of a spontaneous menstrual cycle (control cycle) and after pituitary down-regulation with a GnRH agonist (study cycle). As expected, the older subjects in the control cycles demonstrated an elevated d 3 FSH and a shortened follicular phase compared with the younger subjects. After release from hypothalamic-pituitary-ovarian axis suppression, the early follicular phase FSH peak occurred earlier (6.8 vs. 9.8 d; P < 0.01) and was of a greater magnitude (12.1 vs. 6.5 mIU/ml; P < 0.01) in the older subjects. The time from release of suppression until the subsequent LH surge was also shorter (17.5 vs. 20.8 d; P < 0.01) in the older group. However, the time from FSH peak to LH surge was similar in the older and younger groups (10.7 vs. 11.0 d; P = 0.74). Compared with younger women, older subjects had normal follicular phase levels of estradiol and inhibin A and lower levels of inhibin B in both control and study cycles. We conclude that the shortened follicular phase observed in older ovulatory women is due to earlier dominant follicle selection, independent of hormonal influences from the preceding luteal phase.

  6. Endogenous Delta/Theta Sound-Brain Phase Entrainment Accelerates the Buildup of Auditory Streaming.

    PubMed

    Riecke, Lars; Sack, Alexander T; Schroeder, Charles E

    2015-12-21

    In many natural listening situations, meaningful sounds (e.g., speech) fluctuate in slow rhythms among other sounds. When a slow rhythmic auditory stream is selectively attended, endogenous delta (1‒4 Hz) oscillations in auditory cortex may shift their timing so that higher-excitability neuronal phases become aligned with salient events in that stream [1, 2]. As a consequence of this stream-brain phase entrainment [3], these events are processed and perceived more readily than temporally non-overlapping events [4-11], essentially enhancing the neural segregation between the attended stream and temporally noncoherent streams [12]. Stream-brain phase entrainment is robust to acoustic interference [13-20] provided that target stream-evoked rhythmic activity can be segregated from noncoherent activity evoked by other sounds [21], a process that usually builds up over time [22-27]. However, it has remained unclear whether stream-brain phase entrainment functionally contributes to this buildup of rhythmic streams or whether it is merely an epiphenomenon of it. Here, we addressed this issue directly by experimentally manipulating endogenous stream-brain phase entrainment in human auditory cortex with non-invasive transcranial alternating current stimulation (TACS) [28-30]. We assessed the consequences of these manipulations on the perceptual buildup of the target stream (the time required to recognize its presence in a noisy background), using behavioral measures in 20 healthy listeners performing a naturalistic listening task. Experimentally induced cyclic 4-Hz variations in stream-brain phase entrainment reliably caused a cyclic 4-Hz pattern in perceptual buildup time. Our findings demonstrate that strong endogenous delta/theta stream-brain phase entrainment accelerates the perceptual emergence of task-relevant rhythmic streams in noisy environments. PMID:26628008

  7. Endogenous Delta/Theta Sound-Brain Phase Entrainment Accelerates the Buildup of Auditory Streaming.

    PubMed

    Riecke, Lars; Sack, Alexander T; Schroeder, Charles E

    2015-12-21

    In many natural listening situations, meaningful sounds (e.g., speech) fluctuate in slow rhythms among other sounds. When a slow rhythmic auditory stream is selectively attended, endogenous delta (1‒4 Hz) oscillations in auditory cortex may shift their timing so that higher-excitability neuronal phases become aligned with salient events in that stream [1, 2]. As a consequence of this stream-brain phase entrainment [3], these events are processed and perceived more readily than temporally non-overlapping events [4-11], essentially enhancing the neural segregation between the attended stream and temporally noncoherent streams [12]. Stream-brain phase entrainment is robust to acoustic interference [13-20] provided that target stream-evoked rhythmic activity can be segregated from noncoherent activity evoked by other sounds [21], a process that usually builds up over time [22-27]. However, it has remained unclear whether stream-brain phase entrainment functionally contributes to this buildup of rhythmic streams or whether it is merely an epiphenomenon of it. Here, we addressed this issue directly by experimentally manipulating endogenous stream-brain phase entrainment in human auditory cortex with non-invasive transcranial alternating current stimulation (TACS) [28-30]. We assessed the consequences of these manipulations on the perceptual buildup of the target stream (the time required to recognize its presence in a noisy background), using behavioral measures in 20 healthy listeners performing a naturalistic listening task. Experimentally induced cyclic 4-Hz variations in stream-brain phase entrainment reliably caused a cyclic 4-Hz pattern in perceptual buildup time. Our findings demonstrate that strong endogenous delta/theta stream-brain phase entrainment accelerates the perceptual emergence of task-relevant rhythmic streams in noisy environments.

  8. Tables of phase functions, opacities, albedos, equilibrium temperatures, and radiative accelerations of dust grains in exoplanets

    NASA Astrophysics Data System (ADS)

    Budaj, J.; Kocifaj, M.; Salmeron, R.; Hubeny, I.

    2015-11-01

    There has been growing observational evidence for the presence of condensates in the atmospheres and/or comet-like tails of extrasolar planets. As a result, systematic and homogeneous tables of dust properties are useful in order to facilitate further observational and theoretical studies. In this paper we present calculations and analysis of non-isotropic phase functions, asymmetry parameter (mean cosine of the scattering angle), absorption and scattering opacities, single scattering albedos, equilibrium temperatures, and radiative accelerations of dust grains relevant for extrasolar planets. Our assumptions include spherical grain shape, Deirmendjian particle size distribution, and Mie theory. We consider several species: corundum/alumina, perovskite, olivines with 0 and 50 per cent iron content, pyroxenes with 0, 20, and 60 per cent iron content, pure iron, carbon at two different temperatures, water ice, liquid water, and ammonia. The presented tables cover the wavelength range of 0.2-500 μm and modal particle radii from 0.01 to 100 μm. Equilibrium temperatures and radiative accelerations assume irradiation by a non-blackbody source of light with temperatures from 7000 to 700 K seen at solid angles from 2π to 10-6 sr. The tables are provided to the community together with a simple code which allows for an optional, finite, angular dimension of the source of light (star) in the phase function.

  9. Is there a best TKI for chronic phase CML?

    PubMed

    Larson, Richard A

    2015-11-19

    The development of BCR/ABL1 tyrosine kinase inhibitors (TKIs) over the past 20 years has dramatically improved the outcomes for patients with every stage of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML). Clinicians now have access to 5 oral, generally well-tolerated, and highly effective TKIs. How should these agents be used for an individual patient to ensure the best possible duration and quality-of-life, to avoid treatment-related complications, and potentially to achieve a cure at an affordable cost? Because CML patients may need to continue TKI therapy indefinitely, the long-term safety of each treatment option must be considered. Evidence-based care requires an understanding of the optimal use of these drugs, their specific early and late toxicities, the prognostic significance of achieving treatment milestones, and the critical importance of molecular monitoring. Efficacy is important, but treatment choice does not depend only on efficacy. Choosing among various treatment options is informed by understanding the distinct benefits and risks of each agent, along with careful consideration of patient-specific factors, such as risk status, age, and comorbidities. PMID:26585806

  10. Is there a best TKI for chronic phase CML?

    PubMed

    Larson, Richard A

    2015-01-01

    The development of BCR/ABL1 tyrosine kinase inhibitors (TKIs) over the past 20 years has dramatically improved the outcomes for patients with every stage of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML). Clinicians now have access to 5 oral, generally well-tolerated, and highly effective TKIs. How should these agents be used for an individual patient to ensure the best possible duration and quality-of-life, to avoid treatment-related complications, and potentially to achieve a cure at an affordable cost? Because CML patients may need to continue TKI therapy indefinitely, the long-term safety of each treatment option must be considered. Evidence-based care requires an understanding of the optimal use of these drugs, their specific early and late toxicities, the prognostic significance of achieving treatment milestones, and the critical importance of molecular monitoring. Efficacy is important, but treatment choice does not depend only on efficacy. Choosing among various treatment options is informed by understanding the distinct benefits and risks of each agent, along with careful consideration of patient-specific factors, such as risk status, age, and comorbidities.

  11. Is there a best TKI for chronic phase CML?

    PubMed

    Larson, Richard A

    2015-11-19

    The development of BCR/ABL1 tyrosine kinase inhibitors (TKIs) over the past 20 years has dramatically improved the outcomes for patients with every stage of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML). Clinicians now have access to 5 oral, generally well-tolerated, and highly effective TKIs. How should these agents be used for an individual patient to ensure the best possible duration and quality-of-life, to avoid treatment-related complications, and potentially to achieve a cure at an affordable cost? Because CML patients may need to continue TKI therapy indefinitely, the long-term safety of each treatment option must be considered. Evidence-based care requires an understanding of the optimal use of these drugs, their specific early and late toxicities, the prognostic significance of achieving treatment milestones, and the critical importance of molecular monitoring. Efficacy is important, but treatment choice does not depend only on efficacy. Choosing among various treatment options is informed by understanding the distinct benefits and risks of each agent, along with careful consideration of patient-specific factors, such as risk status, age, and comorbidities.

  12. Using 2nd generation tyrosine kinase inhibitors in frontline management of chronic phase chronic myeloid leukemia

    PubMed Central

    Jayakar, Vishal

    2014-01-01

    Choices in medicine come with responsibility. With several TKI's (Tyrosine kinase inhibitors) available for front-line management of CML (Chronic Myeloid Leukemia), an astute clinician has to personalise, rationalise and take a pragmatic approach towards selection of the best drug for the ‘patient in question’. Though it is hotly debated as to which TKI will triumph, the truth of this debate lies in individualising treatment rather than a general ‘all size fits all’ approach with imatinib. I personally believe that the second generation TKI's will suit most patient clinical profiles rather than prescribing imatinib to all and I have strived to make a strong case for them in front line treatment of CML. Though Imatinib may remain the first line choice for some patients, my efforts in this debate are mainly geared towards breaking the myth that imatinib is the sole ‘block buster’ on the CML landscape PMID:24665456

  13. Accelerated safety analyses - structural analyses Phase I - structural sensitivity evaluation of single- and double-shell waste storage tanks

    SciTech Connect

    Becker, D.L.

    1994-11-01

    Accelerated Safety Analyses - Phase I (ASA-Phase I) have been conducted to assess the appropriateness of existing tank farm operational controls and/or limits as now stipulated in the Operational Safety Requirements (OSRs) and Operating Specification Documents, and to establish a technical basis for the waste tank operating safety envelope. Structural sensitivity analyses were performed to assess the response of the different waste tank configurations to variations in loading conditions, uncertainties in loading parameters, and uncertainties in material characteristics. Extensive documentation of the sensitivity analyses conducted and results obtained are provided in the detailed ASA-Phase I report, Structural Sensitivity Evaluation of Single- and Double-Shell Waste Tanks for Accelerated Safety Analysis - Phase I. This document provides a summary of the accelerated safety analyses sensitivity evaluations and the resulting findings.

  14. Tyrosine Kinase Inhibitors for the Treatment of Chronic-Phase Chronic Myeloid Leukemia: Long-Term Patient Care and Management

    PubMed Central

    Bauer,1, Stephanie; Buchanan,2, Susan; Ryan,3, Irene

    2016-01-01

    Several tyrosine kinase inhibitors (TKIs) are now approved for the treatment of chronic myeloid leukemia in chronic phase. The efficacy of these drugs has been repeatedly demonstrated, as has their tolerability in most patients. However, late and chronic toxicities become an important issue for many patients facing long-term TKI exposure. For patients on long-term imatinib, gastrointestinal events, fluid retention, muscle cramps, fatigue, and hepatotoxicity are among the most common and most clinically relevant adverse events (AEs). A few of these have also emerged as important AEs with some of the newer TKIs. Distinct long-term toxicity concerns have emerged for dasatinib (pleural effusion, pulmonary hypertension, headache, and dyspnea) and nilotinib (rash, headache, myalgia, alopecia, and hyperglycemia), whereas due to the recent approval of bosutinib and ponatinib, their long-term toxicity profiles have not been fully characterized. Clinical experience with each of these drugs is accumulating, and ensuring proper adherence and monitoring for potential AEs is essential for effective treatment. PMID:27713843

  15. Nilotinib 300 mg twice daily: an academic single-arm study of newly diagnosed chronic phase chronic myeloid leukemia patients

    PubMed Central

    Castagnetti, Fausto; Breccia, Massimo; Gugliotta, Gabriele; Martino, Bruno; D’Adda, Mariella; Stagno, Fabio; Carella, Angelo Michele; Avanzini, Paolo; Tiribelli, Mario; Trabacchi, Elena; Visani, Giuseppe; Gobbi, Marco; Salvucci, Marzia; Levato, Luciano; Binotto, Gianni; Capalbo, Silvana Franca; Bochicchio, Maria Teresa; Soverini, Simona; Cavo, Michele; Martinelli, Giovanni; Alimena, Giuliana; Pane, Fabrizio; Saglio, Giuseppe; Rosti, Gianantonio; Baccarani, Michele

    2016-01-01

    The introduction and the extended clinical use of nilotinib in the first-line treatment of chronic myeloid leukemia have been based on company-sponsored trials. Independent confirmations are extremely important. We report an investigator-sponsored study of nilotinib 300 mg twice daily in 130 chronic myeloid leukemia patients in early chronic phase. A deep molecular response was achieved in 46% (MR4.0) and 17% (MR4.5) of patients at 2 years; 58% of the enrolled patients achieved a MR4.0 at least once, with a sustained MR4.0 in 52% of them. With a median observation of 29 months (range 24–37 months), 77% of patients were still on treatment with nilotinib. The reasons for permanent discontinuation were: 3% progression, 5% failure or suboptimal response, 8% adverse events, 1% treatment-free remission, and 5% other reasons. Thirteen thrombotic arterial events were reported in 12 patients. A prospective evaluation of metabolic effects showed an increase of fasting glucose without significant variations of glycated hemoglobin, an increase of total cholesterol (both low density lipoprotein and high density lipoprotein fractions) and a decrease of triglycerides. This study confirms a high and rapid efficacy of nilotinib 300 mg twice daily and provides detailed information on the type and incidence of non-hematologic and metabolic adverse events (clinicaltrials.gov identifier: 01535391). PMID:27470600

  16. Chronic phase advance alters circadian physiological rhythms and peripheral molecular clocks

    PubMed Central

    Wolff, Gretchen; Duncan, Marilyn J.

    2013-01-01

    Shifting the onset of light, acutely or chronically, can profoundly affect responses to infection, tumor progression, development of metabolic disease, and mortality in mammals. To date, the majority of phase-shifting studies have focused on acute exposure to a shift in the timing of the light cycle, whereas the consequences of chronic phase shifts alone on molecular rhythms in peripheral tissues such as skeletal muscle have not been studied. In this study, we tested the effect of chronic phase advance on the molecular clock mechanism in two phenotypically different skeletal muscles. The phase advance protocol (CPA) involved 6-h phase advances (earlier light onset) every 4 days for 8 wk. Analysis of the molecular clock, via bioluminescence recording, in the soleus and flexor digitorum brevis (FDB) muscles and lung demonstrated that CPA advanced the phase of the rhythm when studied immediately after CPA. However, if the mice were placed into free-running conditions (DD) for 2 wk after CPA, the molecular clock was not phase shifted in the two muscles but was still shifted in the lung. Wheel running behavior remained rhythmic in CPA mice; however, the endogenous period length of the free-running rhythm was significantly shorter than that of control mice. Core body temperature, cage activity, and heart rate remained rhythmic throughout the experiment, although the onset of the rhythms was significantly delayed with CPA. These results provide clues that lifestyles associated with chronic environmental desynchrony, such as shift work, can have disruptive effects on the molecular clock mechanism in peripheral tissues, including both types of skeletal muscle. Whether this can contribute, long term, to increased incidence of insulin resistance/metabolic disease requires further study. PMID:23703115

  17. Accelerated growth of skin carcinoma following fludarabine therapy for chronic lymphocytic leukemia.

    PubMed

    Rashid, Kamran; Ng, Richard; Mastan, Alina; Sager, Dianne; Hirschman, Richard

    2005-07-01

    We present four patients with chronic lymphocytic leukemia treated with fludarabine, who developed aggressive skin cancer after years of quiescence, a short time after institution of treatment. Their leukemias responded well to therapy with fludarabine with initial treatment as well as relapse. Three patients had recurrence with basal cell carcinomas with multiple, rapidly growing tumors and one had recurrence of both basal and squamous cancers and eventually died of metastatic squamous cell carcinoma. Fludarabine induces prolonged period of lymphopenia, affecting especially the T cell population, which is crucial in the defense against skin cancers. There appears to be a direct association between fludarabine and the flare up of skin cancers in these patients, possibly analogous to the increased incidence of these malignancies in patients on chronic cyclosporine immunosuppression.

  18. Acceleration of vertical migration of corneal epithelial cells in albino rats during chronic immobilization stress

    SciTech Connect

    Timoshin, S.S.; Berezhnova, N.I.

    1986-01-01

    This paper studies the effect of chronic immobilization stress on the kinetics of corneal epithelial cells from the basal layer into higher layers. Experiments were carried out on 49 male rats. The animals were given an intraperitoneal injection of tritium-thymidine and an additional application of 5 microCi of tritium-thymidine was made to its surface because the cornea has no blood supply. The animals were killed and the cornea removed for investigation. Values of the index of labeled nuclei and intensity of thymidine labeling, characterizing DNA synthesis in the corneas of the control and experimental animals showed no significant change compared with their values in a pervious series of experiments. Chronic exposure to stress increased the velocity of vertical migration of the cells from the basal layer toward the outer layers of the cornea.

  19. Magnetic Shielding Accelerates the Proliferation of Human Neuroblastoma Cell by Promoting G1-Phase Progression

    PubMed Central

    Liu, Ying; Bartlett, Perry F.; He, Rong-qiao

    2013-01-01

    Organisms have been exposed to the geomagnetic field (GMF) throughout evolutionary history. Exposure to the hypomagnetic field (HMF) by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y) cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF. PMID:23355897

  20. Magnetic shielding accelerates the proliferation of human neuroblastoma cell by promoting G1-phase progression.

    PubMed

    Mo, Wei-chuan; Zhang, Zi-jian; Liu, Ying; Bartlett, Perry F; He, Rong-qiao

    2013-01-01

    Organisms have been exposed to the geomagnetic field (GMF) throughout evolutionary history. Exposure to the hypomagnetic field (HMF) by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y) cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF. PMID:23355897

  1. Effect of driver over-acceleration on traffic breakdown in three-phase cellular automaton traffic flow models

    NASA Astrophysics Data System (ADS)

    Kerner, Boris S.; Klenov, Sergey L.; Hermanns, Gerhard; Schreckenberg, Michael

    2013-09-01

    Based on simulations with cellular automaton (CA) traffic flow models, a generic physical feature of the three-phase models studied in the paper is disclosed. The generic feature is a discontinuous character of driver over-acceleration caused by a combination of two qualitatively different mechanisms of over-acceleration: (i) Over-acceleration through lane changing to a faster lane, (ii) over-acceleration occurring in car-following without lane changing. Based on this generic feature a new three-phase CA traffic flow model is developed. This CA model explains the set of the fundamental empirical features of traffic breakdown in real heterogeneous traffic flow consisting of passenger vehicles and trucks. The model simulates also quantitative traffic pattern characteristics as measured in real heterogeneous flow.

  2. PTCH1 expression at diagnosis predicts imatinib failure in chronic myeloid leukaemia patients in chronic phase.

    PubMed

    Alonso-Dominguez, Juan M; Grinfeld, Jacob; Alikian, Mary; Marin, David; Reid, Alistair; Daghistani, Mustafa; Hedgley, Corinne; O'Brien, Stephen; Clark, Richard E; Apperley, Jane; Foroni, Letizia; Gerrard, Gareth

    2015-01-01

    The tyrosine kinase inhibitor (TKI) imatinib has revolutionized the management of chronic myeloid leukaemia (CML). However, around 25% of patients fail to sustain an adequate response. We sought to identify gene-expression biomarkers that could be used to predict imatinib response. The expression of 29 genes, previously implicated in CML pathogenesis, were measured by TaqMan Low Density Array in 73 CML patient samples. Patients were divided into low and high expression for each gene and imatinib failure (IF), probability of achieving CCyR, progression free survival and CML related OS were compared by Kaplan-Meier and log-rank. Results were validated in a second cohort of 56 patients, with a further technical validation using custom gene-expression assays in a conventional RT-qPCR in a sub-cohort of 37 patients. Patients with low PTCH1 expression showed a worse clinical response for all variables in all cohorts. PTCH1 was the most significant predictor in the multivariate analysis compared with Sokal, age and EUTOS. PTCH1 expression assay showed the adequate sensitivity, specificity and predictive values to predict for IF. Given the different treatments available for CML, measuring PTCH1 expression at diagnosis may help establish who will benefit best from imatinib and who is better selected for second generation TKI. PMID:25250944

  3. Informed Practice: Students' Clinical Experiences in the Undergraduate Phase of an Accelerated Physician Assistant Program.

    PubMed

    Dereczyk, Amy; DeWitt, Rachel

    2016-06-01

    This qualitative study explored the clinical experiences of students in an accelerated physician assistant (PA) program. The participants were either certified nursing assistants (CNAs) or emergency medical technicians-basic (EMTs-B). The study was designed to elicit (1) how the participants perceived their older patients and (2) how the participants' experiences might affect their own future communications, bedside manner, and clinical preparedness as PAs. This study used a focus group to explore students' clinical experiences before the graduate phase of their accelerated PA program. Five female and 2 male PA students (N = 7) participated in the study. All participants were 23 years old and worked as either a CNA or an EMT-B. Results fell into 2 basic themes: informing practice and forming relationships. Regarding the first theme, participants felt that their experience as entry-level health care providers allowed them to improve their communication skills and bedside manner and to provide greater comfort to patients. Regarding the second theme, participants gained appreciation for older people and began to recognize the knowledge deficits and learning needs of their patients. The results suggested that a student's clinical experience as a CNA or an EMT-B before entering a PA program has a positive effect on the student's personal and professional development. The participants acquired greater appreciation and respect for older patients and members of the health care team. PMID:27123599

  4. A GPU-accelerated flow solver for incompressible two-phase fluid flows

    NASA Astrophysics Data System (ADS)

    Codyer, Stephen; Raessi, Mehdi; Khanna, Gaurav

    2011-11-01

    We present a numerical solver for incompressible, immiscible, two-phase fluid flows that is accelerated by using Graphics Processing Units (GPUs). The Navier-Stokes equations are solved by the projection method, which involves solving a pressure Poisson problem at each time step. A second-order discretization of the Poisson problem leads to a sparse matrix with five and seven diagonals for two- and three-dimensional simulations, respectively. Running a serial linear algebra solver on a single CPU can take 50-99.9% of the total simulation time to solve the above system for pressure. To remove this bottleneck, we utilized the large parallelization capabilities of GPUs; we developed a linear algebra solver based on the conjugate gradient iterative method (CGIM) by using CUDA 4.0 libraries and compared its performance with CUSP, an open-source, GPU library for linear algebra. Compared to running the CGIM solver on a single CPU core, for a 2D case, our GPU solver yields speedups of up to 88x in solver time and 81x overall time on a single GPU card. In 3D cases, the speedups are up to 81x (solver) and 15x (overall). Speedup is faster at higher grid resolutions and our GPU solver outperforms CUSP. Current work examines the acceleration versus a parallel CGIM CPU solver.

  5. A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation.

    PubMed

    Patel, Avinash; Lee, Hyun O; Jawerth, Louise; Maharana, Shovamayee; Jahnel, Marcus; Hein, Marco Y; Stoynov, Stoyno; Mahamid, Julia; Saha, Shambaditya; Franzmann, Titus M; Pozniakovski, Andrej; Poser, Ina; Maghelli, Nicola; Royer, Loic A; Weigert, Martin; Myers, Eugene W; Grill, Stephan; Drechsel, David; Hyman, Anthony A; Alberti, Simon

    2015-08-27

    Many proteins contain disordered regions of low-sequence complexity, which cause aging-associated diseases because they are prone to aggregate. Here, we study FUS, a prion-like protein containing intrinsically disordered domains associated with the neurodegenerative disease ALS. We show that, in cells, FUS forms liquid compartments at sites of DNA damage and in the cytoplasm upon stress. We confirm this by reconstituting liquid FUS compartments in vitro. Using an in vitro "aging" experiment, we demonstrate that liquid droplets of FUS protein convert with time from a liquid to an aggregated state, and this conversion is accelerated by patient-derived mutations. We conclude that the physiological role of FUS requires forming dynamic liquid-like compartments. We propose that liquid-like compartments carry the trade-off between functionality and risk of aggregation and that aberrant phase transitions within liquid-like compartments lie at the heart of ALS and, presumably, other age-related diseases. PMID:26317470

  6. The surface quasiliquid melt acceleration and the role of thermodynamic phase in the thermal decomposition of crystalline organic explosives

    SciTech Connect

    Henson, Bryan F

    2010-01-01

    We show that melt acceleration in the thermal decomposition of crystalline organic solids is a manifestation of the surface quasiliquid phase. We derive a single universal rate law for melt acceleration that is a simple function of the metastable liquid activity below the melting point, and has a zero order term proportional to the quasiliquid thickness. We argue that the underlying mechanisms of this model will provide a molecular definition for the stability of the class of secondary explosives.

  7. Differential role of CD4+ cells in the sensitization and effector phases of accelerated graft rejection.

    PubMed

    Sablinski, T; Sayegh, M H; Hancock, W W; Kut, J P; Kwok, C A; Milford, E L; Tilney, N L; Kupiec-Weglinski, J W

    1991-01-01

    Although CD4-targeted therapy markedly prolongs survival of organ allografts in naive rodents, its effects in primed hosts have not been studied. In our model of accelerated rejection (ACCR) of cardiac Tx in rats, treatment with BWH-4, a CD4 mAb (IgG2a), in the sensitization (between skin and heart Tx) but not in the effector (after cardiac Tx) phase, abrogated fulminant less than 36 hr rejection response and prolonged Tx survival to ca. 11 days. This effect correlated with decreased frequency of circulating CD4+ cells, but it did not depend upon their total depletion. It was also related to BWH-4 mAb-mediated elimination/depression of strong anti-donor humoral responses and cellular responses as determined by lymphocyte-mediated cytotoxicity and mixed lymphocyte reaction and mounted otherwise at the time of engraftment by untreated sensitized hosts. Immunoperoxidase studies of cardiac Tx from BWH-4-conditioned recipients revealed reduced T and B cell activities, reflected in abolition/reduction in deposition of humoral mediators, infiltrating cells, intra-Tx elaboration of interleukin-2 and interferon-gamma, and cell activation. This first report of the successful use of CD4 mAb in sensitized recipients of vascularized organ Tx, stresses the role of CD4+ cells as potential targets for immunosuppression in the sensitization phase of accelerated Tx injury. The beneficial therapeutic effect, probably due to both depletion and functional inhibition of CD4+ T cells, has been achieved by using relatively low doses of BWH-4 mAb. PMID:1824805

  8. Cryptosporidiosis in rhesus macaques challenged during acute and chronic phases of SIV infection.

    PubMed

    Singh, Inderpal; Carville, Angela; Tzipori, Saul

    2011-09-01

    The intestinal immune dysfunction due to loss of mucosal and peripheral CD4(+) T cells in individuals with HIV/AIDS is presumably responsible for the establishment of persistent cryptosporidiosis. Simian immunodeficiency virus (SIV)-infected macaques were used to investigate the phase/timing in SIV infection, which permits a self-limiting Cryptosporidium parvum infection to become persistent in immunodeficient hosts because of significant mucosal immune defects. Two groups of SIV-infected macaques were challenged with C. parvum; one was challenged during the acute SIV infection phase (2 weeks post-SIV infection) and the second was challenged during the chronic SIV phase (CD4 counts 200-500 cells/μl of blood). Samples (fecal, blood, biopsy, and necropsy) were collected at different time points after infection to correlate the progression of disease with the immune status of the animals. All seven SIV-infected macaques challenged during the acute phase of SIV infection became persistently infected and excreted oocysts for 1-4 months. However, four of the six in the chronic SIV phase became infected with cryptosporidiosis, of which one survived 2 weeks and one became naturally infected. Sequential analysis of CD4(+) in blood and intestines of coinfected macaques exhibited pronounced losses of CD4 T cells during the first 2 weeks after SIV infection, followed by transient rebound of CD4 T cells in the gut after C. parvum infection, and then a gradual loss over subsequent months. Persistent cryptosporidiosis was more consistently induced during the acute SIV phase indicating that profound viral damage to gut lymphoid tissue during the acute phase was more conducive, compared with the chronic phase, to establishing persistent cryptosporidiosis than low circulating CD4 T cells.

  9. Phase Recovery Acceleration of Quantum-Dot Semiconductor Optical Amplifiers by Optical Pumping to Quantum-Well Wetting Layer

    NASA Astrophysics Data System (ADS)

    Kim, Jungho

    2013-11-01

    We theoretically investigate the phase recovery acceleration of quantum-dot (QD) semiconductor optical amplifiers (SOAs) by means of the optical pump injection to the quantum-well (QW) wetting layer (WL). We compare the ultrafast gain and phase recovery responses of QD SOAs in either the electrical or the optical pumping scheme by numerically solving 1088 coupled rate equations. The ultrafast gain recovery responses on the order of sub-picosecond are nearly the same for the two pumping schemes. The ultrafast phase recovery is not significantly accelerated by increasing the electrical current density, but greatly improved by increasing the optical pumping power to the QW WL. Because the phase recovery time of QD SOAs with the optical pumping scheme can be reduced down to several picoseconds, the complete phase recovery can be achieved when consecutive pulse signals with a repetition rate of 100 GHz is injected.

  10. Fifty communities putting prevention to work: accelerating chronic disease prevention through policy, systems and environmental change.

    PubMed

    Bunnell, Rebecca; O'Neil, Dara; Soler, Robin; Payne, Rebecca; Giles, Wayne H; Collins, Janet; Bauer, Ursula

    2012-10-01

    The burden of preventable chronic diseases is straining our nation's health and economy. Diseases caused by obesity and tobacco use account for the largest portions of this preventable burden. CDC funded 50 communities in 2010 to implement policy, systems, and environmental (PSE) interventions in a 2-year initiative. Funded communities developed PSE plans to reduce obesity, tobacco use, and second-hand smoke exposure for their combined 55 million residents. Community outcome objectives and milestones were categorized by PSE interventions as they related to media, access, promotion, pricing, and social support. Communities estimated population reach based on their jurisdiction's census data and target populations. The average proportion of each community's population that was reached was calculated for each intervention category. Outcome objectives that were achieved within 12 months of program initiation were identified from routine program records. The average proportion of a community's jurisdictional population reached by a specific intervention varied across interventions. Mean population reach for obesity-prevention interventions was estimated at 35%, with 14 (26%) interventions covering over 50% of the jurisdictional populations. For tobacco prevention, mean population reach was estimated at 67%, with 16 (84%) interventions covering more than 50% of the jurisdictional populations. Within 12 months, communities advanced over one-third of their obesity and tobacco-use prevention strategies. Tobacco interventions appeared to have higher potential population reach than obesity interventions within this initiative. Findings on the progress and potential reach of this major initiative may help inform future chronic disease prevention efforts.

  11. Chronic Cerebral Hypoperfusion Accelerates Alzheimer's Disease Pathology with Cerebrovascular Remodeling in a Novel Mouse Model.

    PubMed

    Zhai, Yun; Yamashita, Toru; Nakano, Yumiko; Sun, Zhuoran; Shang, Jingwei; Feng, Tian; Morihara, Ryuta; Fukui, Yusuke; Ohta, Yasuyuki; Hishikawa, Nozomi; Abe, Koji

    2016-06-13

    Recently, aging societies have been showing an increasingly strong relationship between Alzheimer's disease (AD) and chronic cerebral hypoperfusion (HP). In the present study, we created a new mouse model for AD with HP, and investigated its clinical and pathological characteristics. Alzheimer's disease transgenic mice (APP23) were subjected to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive cerebral HP. In contrast to simple APP23 mice, cerebral HP exacerbated motor and cognitive dysfunctions with white matter lesions and meningo-parenchymal amyloid-β (Aβ) burdens. Strong cerebrovascular inflammation and severe amyloid angiopathy with cerebrovascular remodeling were also observed in APP23 + HP mouse brains. An acetylcholinesterase inhibitor galantamine improved such clinical dysfunctions, retrieved above neuropathological characteristics, and enhanced nicotinic acetylcholine receptor (nAChR)-binding activity. The present study demonstrates that chronic cerebral HP enhanced cognitive/motor dysfunctions with parenchymal/cerebrovascular Aβ accumulation and cerebrovascular remodeling. These neuropathological abnormalities were greatly ameliorated by galantamine treatment associated with nAChR-mediated neuroprotection by allosterically potentiating ligand action. PMID:27314529

  12. Different adaptation of the motor activity rhythm to chronic phase shifts between adolescent and adult rats.

    PubMed

    Albert, Nerea; da Silva, Crhistiane; Díez-Noguera, Antoni; Cambras, Trinitat

    2013-09-01

    Chronic phase shifts is a common feature in modern societies, which may induce sleep alterations and other health problems. The effects of phase shift on the circadian rhythms have been described to be more pronounced in old than in young animals. However, few works address the effects of chronic phase shifts during adolescence. Here we tested the development of the motor activity circadian rhythm of young rats under chronic phase shifts, which consisted on 6-h advances (A), 6h delays (D) or 6h advances and delays alternated every 5 days (AD) during the first 60 days after weaning. Moreover, the rhythmic pattern was compared to that of adult rats under the same lighting conditions. Results indicate that adolescent rats, independently on the lighting environment, developed a clear circadian rhythm, whose amplitude increased the first 50 days after weaning and showed a more stable circadian rhythm than adults under the same lighting conditions. In the case of A and AD groups, circadian disruption was observed only in adult rats. In all groups, the offset of activity correlated with light pattern better than the onset, and this correlation was always higher in the case of the rhythm of the pubertal rats. When AD groups were transferred to constant darkness, the group submitted to this condition during adolescence showed shorter period than that submitted in their adulthood. In conclusion, differently from adult rats, adolescent rats submitted to chronic phase shifts did not show circadian disruption and developed a single circadian rhythm, suggesting permanent changes in the circadian system.

  13. Different adaptation of the motor activity rhythm to chronic phase shifts between adolescent and adult rats.

    PubMed

    Albert, Nerea; da Silva, Crhistiane; Díez-Noguera, Antoni; Cambras, Trinitat

    2013-09-01

    Chronic phase shifts is a common feature in modern societies, which may induce sleep alterations and other health problems. The effects of phase shift on the circadian rhythms have been described to be more pronounced in old than in young animals. However, few works address the effects of chronic phase shifts during adolescence. Here we tested the development of the motor activity circadian rhythm of young rats under chronic phase shifts, which consisted on 6-h advances (A), 6h delays (D) or 6h advances and delays alternated every 5 days (AD) during the first 60 days after weaning. Moreover, the rhythmic pattern was compared to that of adult rats under the same lighting conditions. Results indicate that adolescent rats, independently on the lighting environment, developed a clear circadian rhythm, whose amplitude increased the first 50 days after weaning and showed a more stable circadian rhythm than adults under the same lighting conditions. In the case of A and AD groups, circadian disruption was observed only in adult rats. In all groups, the offset of activity correlated with light pattern better than the onset, and this correlation was always higher in the case of the rhythm of the pubertal rats. When AD groups were transferred to constant darkness, the group submitted to this condition during adolescence showed shorter period than that submitted in their adulthood. In conclusion, differently from adult rats, adolescent rats submitted to chronic phase shifts did not show circadian disruption and developed a single circadian rhythm, suggesting permanent changes in the circadian system. PMID:23792134

  14. Interferometric determination of broadband ELF wave phase velocity within a region of transverse auroral ion acceleration

    NASA Astrophysics Data System (ADS)

    Bonnell, J.; Kintner, P.; Wahlund, J.-E.; Lynch, K.; Arnoldy, R.

    Broadband electric field fluctuations with typical amplitudes of 10-20 mV/m peak-to-peak and frequencies from 0 Hz to 3 kHz (BB-ELF) were observed coincident with a region of ≤200 eV transverse H+ acceleration (TAI) near the poleward edge of the pre-midnight aurora. The coherence and phase velocity of the electric fields were measured using a interferometric antenna array over the frequency range of ≈ 100 Hz to 3 kHz. These electric field fluctuations were found to have the following characteristics: 1) incoherence perpendicular to the geomagnetic field, 2) coherence parallel to the the geomagnetic field, 3) parallel phase velocity (ω/k∥) of 30-35 km/s upwards, 4) 0 < |k∥/k⊥| < 0.22. We show that these properties are compatible with the emission being electrostatic H+ cyclotron (EHC) waves. We also discuss possible generation mechanisms for the waves, and their relationship to the TAI.

  15. Decay-Accelerating Factor 1 Deficiency Exacerbates Leptospiral-Induced Murine Chronic Nephritis and Renal Fibrosis

    PubMed Central

    Ferrer, María F.; Scharrig, Emilia; Alberdi, Lucrecia; Cedola, Maia; Pretre, Gabriela; Drut, Ricardo; Song, Wen-Chao; Gomez, Ricardo M.

    2014-01-01

    Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1−/− mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1−/− mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1−/− mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1−/− mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1. PMID:25032961

  16. Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

    PubMed

    Ferrer, María F; Scharrig, Emilia; Alberdi, Lucrecia; Cedola, Maia; Pretre, Gabriela; Drut, Ricardo; Song, Wen-Chao; Gomez, Ricardo M

    2014-01-01

    Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

  17. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib

    PubMed Central

    Saglio, Giuseppe; Kantarjian, Hagop M.; Guilhot, François; Niederwieser, Dietger; Rosti, Gianantonio; Nakaseko, Chiaki; De Souza, Carmino Antonio; Kalaycio, Matt E.; Meier, Stephan; Fan, Xiaolin; Menssen, Hans D.; Larson, Richard A.; Hochhaus, Andreas

    2014-01-01

    We explored the impact of early molecular response (EMR; BCR-ABL ≤10% on the international scale [BCR-ABLIS] at 3 or 6 months) on outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with nilotinib or imatinib based on 4 years of follow up in Evaluating Nilotinib Efficacy and Safety in Clinical Trials—Newly Diagnosed Patients. Patients (n = 846) received nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, or imatinib 400 mg once daily. At 3 months, more patients had EMR failure (ie, BCR-ABLIS >10%) on imatinib (33%) than on nilotinib (9%-11%); similarly at 6 months, 16% of patients in the imatinib arm vs 3% and 7% in the nilotinib arms had EMR failure. In all arms, EMR failure was associated with lower rates of molecular response, an increased risk of progression, and lower overall survival compared with EMR achievement. We also analyzed patient and treatment characteristics associated with EMR and found distinct patterns in the nilotinib arms vs the imatinib arm. High Sokal risk score was associated with a high rate of EMR failure on imatinib, but not on nilotinib. In contrast, reduced dose intensity and dose interruptions were strongly associated with EMR failure in nilotinib-treated, but not imatinib-treated, patients. This study is registered at www.clinicaltrials.gov as #NCT00471497. PMID:24335106

  18. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia.

    PubMed

    Irvine, David A; Zhang, Bin; Kinstrie, Ross; Tarafdar, Anuradha; Morrison, Heather; Campbell, Victoria L; Moka, Hothri A; Ho, Yinwei; Nixon, Colin; Manley, Paul W; Wheadon, Helen; Goodlad, John R; Holyoake, Tessa L; Bhatia, Ravi; Copland, Mhairi

    2016-01-01

    Targeting the Hedgehog (Hh) pathway represents a potential leukaemia stem cell (LSC)-directed therapy which may compliment tyrosine kinase inhibitors (TKIs) to eradicate LSC in chronic phase (CP) chronic myeloid leukaemia (CML). We set out to elucidate the role of Hh signaling in CP-CML and determine if inhibition of Hh signaling, through inhibition of smoothened (SMO), was an effective strategy to target CP-CML LSC. Assessment of Hh pathway gene and protein expression demonstrated that the Hh pathway is activated in CD34(+) CP-CML stem/progenitor cells. LDE225 (Sonidegib), a small molecule, clinically investigated SMO inhibitor, used alone and in combination with nilotinib, inhibited the Hh pathway in CD34(+) CP-CML cells, reducing the number and self-renewal capacity of CML LSC in vitro. The combination had no effect on normal haemopoietic stem cells. When combined, LDE225 + nilotinib reduced CD34(+) CP-CML cell engraftment in NSG mice and, upon administration to EGFP(+) /SCLtTA/TRE-BCR-ABL mice, the combination enhanced survival with reduced leukaemia development in secondary transplant recipients. In conclusion, the Hh pathway is deregulated in CML stem and progenitor cells. We identify Hh pathway inhibition, in combination with nilotinib, as a potentially effective therapeutic strategy to improve responses in CP-CML by targeting both stem and progenitor cells. PMID:27157927

  19. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia

    PubMed Central

    Irvine, David A.; Zhang, Bin; Kinstrie, Ross; Tarafdar, Anuradha; Morrison, Heather; Campbell, Victoria L.; Moka, Hothri A.; Ho, Yinwei; Nixon, Colin; Manley, Paul W.; Wheadon, Helen; Goodlad, John R.; Holyoake, Tessa L.; Bhatia, Ravi; Copland, Mhairi

    2016-01-01

    Targeting the Hedgehog (Hh) pathway represents a potential leukaemia stem cell (LSC)-directed therapy which may compliment tyrosine kinase inhibitors (TKIs) to eradicate LSC in chronic phase (CP) chronic myeloid leukaemia (CML). We set out to elucidate the role of Hh signaling in CP-CML and determine if inhibition of Hh signaling, through inhibition of smoothened (SMO), was an effective strategy to target CP-CML LSC. Assessment of Hh pathway gene and protein expression demonstrated that the Hh pathway is activated in CD34+ CP-CML stem/progenitor cells. LDE225 (Sonidegib), a small molecule, clinically investigated SMO inhibitor, used alone and in combination with nilotinib, inhibited the Hh pathway in CD34+ CP-CML cells, reducing the number and self-renewal capacity of CML LSC in vitro. The combination had no effect on normal haemopoietic stem cells. When combined, LDE225 + nilotinib reduced CD34+ CP-CML cell engraftment in NSG mice and, upon administration to EGFP+ /SCLtTA/TRE-BCR-ABL mice, the combination enhanced survival with reduced leukaemia development in secondary transplant recipients. In conclusion, the Hh pathway is deregulated in CML stem and progenitor cells. We identify Hh pathway inhibition, in combination with nilotinib, as a potentially effective therapeutic strategy to improve responses in CP-CML by targeting both stem and progenitor cells. PMID:27157927

  20. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib.

    PubMed

    Hughes, Timothy P; Saglio, Giuseppe; Kantarjian, Hagop M; Guilhot, François; Niederwieser, Dietger; Rosti, Gianantonio; Nakaseko, Chiaki; De Souza, Carmino Antonio; Kalaycio, Matt E; Meier, Stephan; Fan, Xiaolin; Menssen, Hans D; Larson, Richard A; Hochhaus, Andreas

    2014-02-27

    We explored the impact of early molecular response (EMR; BCR-ABL ≤10% on the international scale [BCR-ABL(IS)] at 3 or 6 months) on outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with nilotinib or imatinib based on 4 years of follow up in Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients. Patients (n = 846) received nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, or imatinib 400 mg once daily. At 3 months, more patients had EMR failure (ie, BCR-ABL(IS) >10%) on imatinib (33%) than on nilotinib (9%-11%); similarly at 6 months, 16% of patients in the imatinib arm vs 3% and 7% in the nilotinib arms had EMR failure. In all arms, EMR failure was associated with lower rates of molecular response, an increased risk of progression, and lower overall survival compared with EMR achievement. We also analyzed patient and treatment characteristics associated with EMR and found distinct patterns in the nilotinib arms vs the imatinib arm. High Sokal risk score was associated with a high rate of EMR failure on imatinib, but not on nilotinib. In contrast, reduced dose intensity and dose interruptions were strongly associated with EMR failure in nilotinib-treated, but not imatinib-treated, patients. This study is registered at www.clinicaltrials.gov as #NCT00471497.

  1. The acceleration of amygdala kindling epileptogenesis by chronic low-dose corticosterone involves both mineralocorticoid and glucocorticoid receptors.

    PubMed

    Kumar, Gaurav; Couper, Abbie; O'Brien, Terence J; Salzberg, Michael R; Jones, Nigel C; Rees, Sandra M; Morris, Margaret J

    2007-08-01

    We have previously demonstrated that low-dose corticosterone (CS) administration, used as a model of the effect of chronic stress, accelerates epileptogenesis in the electrical amygdala kindling rat model of temporal lobe epilepsy (TLE). This current study examined the relative contributions to this effect of mineralocorticoid (MR) and glucocorticoid (GR) subtypes of glucocorticoid receptors. Female non-epileptic wistar rats 10-13 weeks of age were implanted with a bipolar electrode into the left amygdala. Five treatment groups were subjected to rapid amygdala kindling: water-control (n=9), CS treated (6 mg/100 ml added to drinking water; n=9), CS+spironolactone (MR antagonist, 50 mg/kg sc; n=9), CS+mifepristone (GR antagonist, 25 mg/kg sc; n=9), and CS+both antagonists (n=7). Rats were injected with vehicle or the relevant antagonist twice daily for the entire kindling period. Experimental groups differed significantly in the number of stimulations required to reach the 'fully kindled state' (Racine, 1972) ANOVA, F(4,38)=2.73, p=0.04). Amygdala kindling was accelerated in the CS-treated group compared with water controls (mean stimulations for full kindling: 45.2 vs. 86.5, p<0.01). This acceleration was inhibited by both the MR and GR antagonist treatments (mean stimulations: 69.6 and 70.4, p=0.04 and 0.04 vs. CS group, respectively), with the kindling rates in these groups not significantly different from water-treated subjects (p=0.26 and 0.29, respectively). The kindling rates in the MR and GR antagonist treatment groups did not significantly differ from each other (p=0.93), nor from the combined treatment group (mean stimulations: 62.8, p=0.59 and 0.54, respectively). This study demonstrates that activation of both high-affinity (MR) and low-affinity (GR) glucocorticoid receptors are involved in mediating CS-induced acceleration of amygdala kindling epileptogenesis.

  2. Trajectories of electrons with large longitudinal momenta in the phase plane during surfatron acceleration by an electromagnetic wave

    SciTech Connect

    Mkrtichyan, G. S.

    2015-07-15

    The trajectories of electrons with large longitudinal momenta in the phase plane in the course of their surfatron acceleration by an electromagnetic wave propagating in space plasma across the external magnetic field are analyzed. Electrons with large longitudinal momenta are trapped immediately if the initial wave phase Ψ(0) on the particle trajectory is positive. For negative values of Ψ(0), no electrons trapping by the wave is observed over the available computational times. According to numerical calculations, the trajectories of trapped particles in the phase plane have a singular point of the stable focus type and the behavior of the trajectory corresponds to the motion in a complex nonstationary effective potential well. For some initial phases, electrons are confined in the region of the accelerating electric field for relatively short time, the energy gain being about 50–130% and more.

  3. Hippocampal dysfunction during the chronic phase following a single exposure to cranial irradiation.

    PubMed

    Son, Yeonghoon; Yang, Miyoung; Kim, Joong-Sun; Kim, Juhwan; Kim, Sung-Ho; Kim, Jong-Choon; Shin, Taekyun; Wang, Hongbing; Jo, Sung-Kee; Jung, Uhee; Moon, Changjong

    2014-04-01

    Ionizing radiation can significantly affect brain functioning in adults. The present study assessed depression-like behaviors in adult C57BL/6 mice using the tail suspension test (TST) at 30 and 90days following a single cranial exposure to γ-rays (0, 1, or 10Gy) to evaluate hippocampus-related behavioral dysfunction during the chronic phase following cranial irradiation. Additionally, hippocampal neurogenesis, inflammatory cytokines, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) were analyzed. At 30 and 90days following irradiation with 10Gy, mice displayed significant depression-like behaviors. We observed a persistent decrease in the number of cells positive for doublecortin, an immunohistochemical marker for neurogenesis, in the hippocampus from 1 to 90days after irradiation with 10Gy. Changes in the mRNA expression of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and interferon-γ, were not correlated with the decrease in hippocampal neurogenesis or the appearance of depression-like behavior during the chronic phase following irradiation. However, at 30 and 90days after irradiation with 10Gy, the number of microglia was significantly decreased compared with age-matched sham-irradiated controls. The reduction in the chronic phase was consistent with the significant down-regulation in the mRNA expression of iNOS, COX-2, BDNF, and GDNF in the hippocampus. Therefore, hippocampal dysfunction during the chronic phase following cranial irradiation may be associated with decreases in the neurogenesis- and synaptic plasticity-related signals, concomitant with microglial reduction in the hippocampus.

  4. The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia

    PubMed Central

    Cuartero, María Isabel; de la Parra, Juan; García-Culebras, Alicia; Ballesteros, Iván; Lizasoain, Ignacio; Moro, María Ángeles

    2016-01-01

    Kynurenines are a wide range of catabolites which derive from tryptophan through the “Kynurenine Pathway” (KP). In addition to its peripheral role, increasing evidence shows a role of the KP in the central nervous system (CNS), mediating both physiological and pathological functions. Indeed, an imbalance in this route has been associated with several neurodegenerative disorders such as Alzheimer’s and Huntington’s diseases. Altered KP catabolism has also been described during both acute and chronic phases of stroke; however the contribution of the KP to the pathophysiology of acute ischemic damage and of post-stroke disorders during the chronic phase including depression and vascular dementia, and the exact mechanisms implicated in the regulation of the KP after stroke are not well established yet. A better understanding of the regulation and activity of the KP after stroke could provide new pharmacological tools in both acute and chronic phases of stroke. In this review, we will make an overview of CNS modulation by the KP. We will detail the KP contribution in the ischemic damage, how the unbalance of the KP might trigger an alteration of the cognitive function after stroke as well as potential targets for the development of new drugs. PMID:25248805

  5. Chronic Ethanol Intake Alters Circadian Phase Shifting and Free-Running Period in Mice

    PubMed Central

    Seggio, Joseph A.; Fixaris, Michael C.; Reed, Jeffrey D.; Logan, Ryan W.; Rosenwasser, Alan M.

    2011-01-01

    Chronic alcohol intake is associated with widespread disruptions in sleep and circadian rhythms in both human alcoholics and in experimental animals. Recent studies have demonstrated that chronic and acute ethanol treatments alter fundamental properties of the circadian pacemaker—including free-running period and responsiveness to photic and nonphotic phase-shifting stimuli—in rats and hamsters. In the present work, the authors extend these observations to the C57BL/6J mouse, an inbred strain characterized by very high levels of voluntary ethanol intake and by reliable and stable free-running circadian activity rhythms. Mice were housed individually in running-wheel cages under conditions of either voluntary or forced ethanol intake, whereas controls were maintained on plain water. Forced ethanol intake significantly attenuated photic phase delays (but not phase advances) and shortened free-running period in constant darkness, but voluntary ethanol intake failed to affect either of these parameters. Thus, high levels of chronic ethanol intake, beyond those normally achieved under voluntary drinking conditions, are required to alter fundamental circadian pacemaker properties in C57BL/6J mice. These observations may be related to the relative ethanol insensitivity displayed by this strain in several other phenotypic domains, including ethanol-induced sedation, ataxia, and withdrawal. Additional experiments will investigate chronobiological sensitivity to ethanol in a range of inbred strains showing diverse ethanol-related phenotypes. PMID:19625732

  6. Chronic ethanol intake alters circadian phase shifting and free-running period in mice.

    PubMed

    Seggio, Joseph A; Fixaris, Michael C; Reed, Jeffrey D; Logan, Ryan W; Rosenwasser, Alan M

    2009-08-01

    Chronic alcohol intake is associated with widespread disruptions in sleep and circadian rhythms in both human alcoholics and in experimental animals. Recent studies have demonstrated that chronic and acute ethanol treatments alter fundamental properties of the circadian pacemaker--including free-running period and responsiveness to photic and nonphotic phase-shifting stimuli--in rats and hamsters. In the present work, the authors extend these observations to the C57BL/6J mouse, an inbred strain characterized by very high levels of voluntary ethanol intake and by reliable and stable free-running circadian activity rhythms. Mice were housed individually in running-wheel cages under conditions of either voluntary or forced ethanol intake, whereas controls were maintained on plain water. Forced ethanol intake significantly attenuated photic phase delays (but not phase advances) and shortened free-running period in constant darkness, but voluntary ethanol intake failed to affect either of these parameters. Thus, high levels of chronic ethanol intake, beyond those normally achieved under voluntary drinking conditions, are required to alter fundamental circadian pacemaker properties in C57BL/6J mice. These observations may be related to the relative ethanol insensitivity displayed by this strain in several other phenotypic domains, including ethanol-induced sedation, ataxia, and withdrawal. Additional experiments will investigate chronobiological sensitivity to ethanol in a range of inbred strains showing diverse ethanol-related phenotypes. PMID:19625732

  7. Chronic NOS inhibition accelerates NAFLD progression in an obese rat model

    PubMed Central

    Sheldon, Ryan D.; Padilla, Jaume; Jenkins, Nathan T.; Laughlin, M. Harold

    2015-01-01

    The progression in nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis is a serious health concern, but the underlying mechanisms remain unclear. We hypothesized that chronic inhibition of nitric oxide (NO) synthase (NOS) via Nω-nitro-l-arginine methyl ester (l-NAME) would intensify liver injury in a rat model of obesity, insulin resistance, and NAFLD. Obese Otsuka Long-Evans Tokushima fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats received control or l-NAME (65–70 mg·kg−1·day−1)-containing drinking water for 4 wk. l-NAME treatment significantly (P < 0.05) reduced serum NO metabolites and food intake in both groups. Remarkably, despite no increase in body weight, l-NAME treatment increased hepatic triacylglycerol content (+40%, P < 0.05) vs. control OLETF rats. This increase was associated with impaired (P < 0.05) hepatic mitochondrial state 3 respiration. Interestingly, the opposite effect was found in LETO rats, where l-NAME increased (P < 0.05) hepatic mitochondrial state 3 respiration. In addition, l-NAME induced a shift toward proinflammatory M1 macrophage polarity, as indicated by elevated hepatic CD11c (P < 0.05) and IL-1β (P = 0.07) mRNA in OLETF rats and reduced expression of the anti-inflammatory M2 markers CD163 and CD206 (P < 0.05) in LETO rats. Markers of total macrophage content (CD68 and F4/80) mRNA were unaffected by l-NAME in either group. In conclusion, systemic NOS inhibition in the obese OLETF rats reduced hepatic mitochondrial respiration, increased hepatic triacylglycerol accumulation, and increased hepatic inflammation. These findings suggest an important role for proper NO metabolism in the hepatic adaptation to obesity. PMID:25573175

  8. Chronic NOS inhibition accelerates NAFLD progression in an obese rat model.

    PubMed

    Sheldon, Ryan D; Padilla, Jaume; Jenkins, Nathan T; Laughlin, M Harold; Rector, R Scott

    2015-03-15

    The progression in nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis is a serious health concern, but the underlying mechanisms remain unclear. We hypothesized that chronic inhibition of nitric oxide (NO) synthase (NOS) via N(ω)-nitro-L-arginine methyl ester (L-NAME) would intensify liver injury in a rat model of obesity, insulin resistance, and NAFLD. Obese Otsuka Long-Evans Tokushima fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats received control or L-NAME (65-70 mg·kg(-1)·day(-1))-containing drinking water for 4 wk. L-NAME treatment significantly (P < 0.05) reduced serum NO metabolites and food intake in both groups. Remarkably, despite no increase in body weight, L-NAME treatment increased hepatic triacylglycerol content (+40%, P < 0.05) vs. control OLETF rats. This increase was associated with impaired (P < 0.05) hepatic mitochondrial state 3 respiration. Interestingly, the opposite effect was found in LETO rats, where L-NAME increased (P < 0.05) hepatic mitochondrial state 3 respiration. In addition, L-NAME induced a shift toward proinflammatory M1 macrophage polarity, as indicated by elevated hepatic CD11c (P < 0.05) and IL-1β (P = 0.07) mRNA in OLETF rats and reduced expression of the anti-inflammatory M2 markers CD163 and CD206 (P < 0.05) in LETO rats. Markers of total macrophage content (CD68 and F4/80) mRNA were unaffected by L-NAME in either group. In conclusion, systemic NOS inhibition in the obese OLETF rats reduced hepatic mitochondrial respiration, increased hepatic triacylglycerol accumulation, and increased hepatic inflammation. These findings suggest an important role for proper NO metabolism in the hepatic adaptation to obesity. PMID:25573175

  9. Accelerated three-dimensional cine phase contrast imaging using randomly undersampled echo planar imaging with compressed sensing reconstruction.

    PubMed

    Basha, Tamer A; Akçakaya, Mehmet; Goddu, Beth; Berg, Sophie; Nezafat, Reza

    2015-01-01

    The aim of this study was to implement and evaluate an accelerated three-dimensional (3D) cine phase contrast MRI sequence by combining a randomly sampled 3D k-space acquisition sequence with an echo planar imaging (EPI) readout. An accelerated 3D cine phase contrast MRI sequence was implemented by combining EPI readout with randomly undersampled 3D k-space data suitable for compressed sensing (CS) reconstruction. The undersampled data were then reconstructed using low-dimensional structural self-learning and thresholding (LOST). 3D phase contrast MRI was acquired in 11 healthy adults using an overall acceleration of 7 (EPI factor of 3 and CS rate of 3). For comparison, a single two-dimensional (2D) cine phase contrast scan was also performed with sensitivity encoding (SENSE) rate 2 and approximately at the level of the pulmonary artery bifurcation. The stroke volume and mean velocity in both the ascending and descending aorta were measured and compared between two sequences using Bland-Altman plots. An average scan time of 3 min and 30 s, corresponding to an acceleration rate of 7, was achieved for 3D cine phase contrast scan with one direction flow encoding, voxel size of 2 × 2 × 3 mm(3) , foot-head coverage of 6 cm and temporal resolution of 30 ms. The mean velocity and stroke volume in both the ascending and descending aorta were statistically equivalent between the proposed 3D sequence and the standard 2D cine phase contrast sequence. The combination of EPI with a randomly undersampled 3D k-space sampling sequence using LOST reconstruction allows a seven-fold reduction in scan time of 3D cine phase contrast MRI without compromising blood flow quantification.

  10. Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study

    PubMed Central

    Guilhot, François; Cortes, Jorge E.; Schiffer, Charles A.; le Coutre, Philipp; Brümmendorf, Tim H.; Kantarjian, Hagop M.; Hochhaus, Andreas; Rousselot, Philippe; Mohamed, Hesham; Healey, Diane; Cunningham, Michael; Saglio, Giuseppe

    2014-01-01

    We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia (CML). In the CA180-034 study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML-CP) received dasatinib 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. At 6 years, 188 (28%) of 670 patients remained on study treatment. Estimated 6-year protocol-defined progression-free survival (PFS) rates were 49%, 51%, 40%, and 47%, respectively, and estimated 6-year overall survival (OS) rates were 71%, 74%, 77%, and 70%, respectively (intent-to-treat population, including protocol-defined progression or death after discontinuation). Estimated 6-year rates of survival without transformation on study treatment were 76%, 80%, 83%, and 74%, respectively. Major molecular response was achieved in 43% (100 mg once daily) and 40% (all other arms) of patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on ≤1%, >1% to 10%, and >10% BCR-ABL transcripts at 3 months were 68%, 58%, and 26%, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy, particularly if achieving BCR-ABL ≤10% at 3 months. This study was registered at ClinicalTrials.gov: NCT00123474. PMID:24569263

  11. Swimming exercise in the acute or late phase after sciatic nerve crush accelerates nerve regeneration.

    PubMed

    Teodori, Rosana Macher; Betini, Joice; de Oliveira, Larissa Salgado; Sobral, Luciane Lobato; Takeda, Sibele Yoko Mattozo; de Lima Montebelo, Maria Imaculada

    2011-01-01

    There is no consensus about the best time to start exercise after peripheral nerve injury. We evaluated the morphological and functional characteristics of the sciatic nerves of rats that began to swim immediately after crush nerve injury (CS1), those that began to swim 14 days after injury (CS14), injured rats not submitted to swimming (C), and uninjured rats submitted to swimming (S). After 30 days the number of axons in CS1 and CS14 was lower than in C (P < 0.01). The diameter of axons and nerve fibers was larger in CS1 (P < 0.01) and CS14 (P < 0.05) than in C, and myelin sheath thickness was lower in all crushed groups (P < 0.05). There was no functional difference between CS1 and CS14 (P > 0.05). Swimming exercise applied during the acute or late phase of nerve injury accelerated nerve regeneration and synaptic elimination after axonotmesis, suggesting that exercise may be initiated immediately after injury.

  12. Swimming Exercise in the Acute or Late Phase after Sciatic Nerve Crush Accelerates Nerve Regeneration

    PubMed Central

    Teodori, Rosana Macher; Betini, Joice; de Oliveira, Larissa Salgado; Sobral, Luciane Lobato; Takeda, Sibele Yoko Mattozo; Montebelo, Maria Imaculada de Lima

    2011-01-01

    There is no consensus about the best time to start exercise after peripheral nerve injury. We evaluated the morphological and functional characteristics of the sciatic nerves of rats that began to swim immediately after crush nerve injury (CS1), those that began to swim 14 days after injury (CS14), injured rats not submitted to swimming (C), and uninjured rats submitted to swimming (S). After 30 days the number of axons in CS1 and CS14 was lower than in C (P < 0.01). The diameter of axons and nerve fibers was larger in CS1 (P < 0.01) and CS14 (P < 0.05) than in C, and myelin sheath thickness was lower in all crushed groups (P < 0.05). There was no functional difference between CS1 and CS14 (P > 0.05). Swimming exercise applied during the acute or late phase of nerve injury accelerated nerve regeneration and synaptic elimination after axonotmesis, suggesting that exercise may be initiated immediately after injury. PMID:21876821

  13. Anti-phase action between the angular accelerations of trunk and leg is reduced in the elderly.

    PubMed

    Kato, Tomohisa; Yamamoto, Shin-ichiro; Miyoshi, Tasuku; Nakazawa, Kimitaka; Masani, Kei; Nozaki, Daichi

    2014-01-01

    Quiet standing posture in humans has often been modeled as a single inverted pendulum pivoting around the ankle joint. However, recent studies have suggested that anti-phase action between leg and trunk segments plays a significant role in stabilizing posture by reducing the acceleration of the center of mass (COM) of the body. The aim of this study is to test the hypothesis that anti-phase action is attenuated in the elderly compared to the young. The anterior-posterior movements of leg and trunk segments were measured using 4 laser displacement sensors from 22 healthy young subjects (age range, 20-35 years) and 38 healthy elderly subjects (age range, 57-80 years) standing quietly for 30s twice. To focus on the segmental action between trunk and legs, we applied constraints (i.e., wooden splints) on each segment. We found that the velocity and acceleration of the COM (standard deviation of the time series was evaluated) were significantly higher for the elderly subjects than for young subjects. The increase in the acceleration of the COM resulted not only from an increase in the angular acceleration of the segments but also from the reduction of their anti-phase relationship, as demonstrated by an index that quantifies the degree of cancelation between both segments. We conclude that the degree of anti-phase action between trunk and leg segments during quiet standing is smaller for elderly subjects than for young subjects, and that this change of the anti-phase action due to aging resulted in increased COM acceleration in the elderly subjects.

  14. BCR-ABL transcript variations in chronic phase chronic myelogenous leukemia patients on imatinib first-line: Possible role of the autologous immune system.

    PubMed

    Clapp, Geoffrey D; Lepoutre, Thomas; Nicolini, Franck E; Levy, Doron

    2016-05-01

    Many chronic myelogenous leukemia (CML) patients in chronic phase who respond well to imatinib therapy show fluctuations in their leukemic loads in the long-term. We developed a mathematical model of CML that incorporates the intervention of an autologous immune response. Our results suggest that the patient's immune system plays a crucial role in imatinib therapy in maintaining disease control over time. The observed BCR-ABL/ABL oscillations in such patients provide a signature of the autologous immune response. PMID:27467931

  15. Acceleration amplitude-phase regulation for electro-hydraulic servo shaking table based on LMS adaptive filtering algorithm

    NASA Astrophysics Data System (ADS)

    Yao, Jianjun; Di, Duotao; Jiang, Guilin; Gao, Shuang

    2012-10-01

    Electro-hydraulic servo shaking table usually requires good control performance for acceleration replication. The poles of the electro-hydraulic servo shaking table are placed by three-variable control method using pole placement theory. The system frequency band is thus extended and the system stability is also enhanced. The phase delay and amplitude attenuation phenomenon occurs in electro-hydraulic servo shaking table corresponding to an acceleration sinusoidal input. The method for phase delay and amplitude attenuation elimination based on LMS adaptive filtering algorithm is proposed here. The task is accomplished by adjusting the weights using LMS adaptive filtering algorithm when there exits phase delay and amplitude attenuation between the input and its corresponding acceleration response. The reference input is weighted in such a way that it makes the system output track the input efficiently. The weighted input signal is inputted to the control system such that the output phase delay and amplitude attenuation are all cancelled. The above concept is used as a basis for the development of amplitude-phase regulation (APR) algorithm. The method does not need to estimate the system model and has good real-time performance. Experimental results demonstrate the efficiency and validity of the proposed APR control scheme.

  16. DC-like Phase Space Manipulation and Particle Acceleration Using Chirped AC Fields

    SciTech Connect

    P.F. Schmit and N.J. Fisch

    2009-06-17

    Waves in plasmas can accelerate particles that are resonant with the wave. A DC electric field also accelerates particles, but without a resonance discrimination, which makes the acceleration mechanism profoundly different. We investigate the effect on a Hamiltonian distribution of an accelerating potential waveform, which could, for example, represent the average ponderomotive effect of two counterpropagating electromagnetic waves. In particular, we examine the apparent DC-like time-asymptotic response of the distribution in regimes where the potential structure is accelerated adiabatically. A highly resonant population within the distribution is always present, and we characterize its nonadiabatic response during wave-particle resonance using an integral method in the noninertial reference frame moving with the wave. Finally, we show that in the limit of infinitely slow acceleration of the wave, these highly resonant particles disappear and the response

  17. CML in Chronic Phase with Novel Secondary Cytogenetic Abnormalities: A Case Report.

    PubMed

    Patel, Hiral S; Brahmbhatt, Manisha M; Trivedi, Pina J; Patel, Dharmesh M; Sugandhi, Ankita A; Patel, Binita V; Patel, Prabhudas S

    2016-01-01

    The clonal evolution in t(9;22)-positive Chronic Myelocytic Leukemia (CML) patients is well established. Four major changes occur in more than 70% of patients: +8, i(17q), +19, and an extra Philadelphia chromosome. Here, we present a case with CML-Chronic phase (CML-CP) and novel t(9;13)(q34;q12~13) in addition to t(9;22)(q34;q11.2). Fluorescence in situ hybridization (FISH) using dual color dual fusion probe analysis on interphase and metaphase cells confirmed the t(9;13)(q34;q12~13) as clonal evolution and secondary event to Philadelphia chromosome. This suggests minor route additional chromosomal aberrations which might affect prognosis. Further studies are required to ascertain the expression of genes that play a role in CML-blast crisis in order to to explore its therapeutic significance and prognostic value. PMID:27584557

  18. A Framework for a General Purpose Intelligent Control System for Particle Accelerators. Phase II Final Report

    SciTech Connect

    Dr. Robert Westervelt; Dr. William Klein; Dr. Michael Kroupa; Eric Olsson; Rick Rothrock

    1999-06-28

    Vista Control Systems, Inc. has developed a portable system for intelligent accelerator control. The design is general in scope and is thus configurable to a wide range of accelerator facilities and control problems. The control system employs a multi-layer organization in which knowledge-based decision making is used to dynamically configure lower level optimization and control algorithms.

  19. Short-Course Accelerated Radiotherapy in Palliative Treatment of Advanced Pelvic Malignancies: A Phase I Study

    SciTech Connect

    Caravatta, Luciana; Padula, Gilbert D.A.; Macchia, Gabriella; Ferrandina, Gabriella; Bonomo, Pierluigi; Deodato, Francesco; Massaccesi, Mariangela; Mignogna, Samantha; Tambaro, Rosa; Rossi, Marco; Flocco, Mariano; Scapati, Andrea; and others

    2012-08-01

    Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of {<=}3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

  20. Acceleration and deceleration of neutrons: From the phase modulation of a neutron wave to a neutron turbine with refracting prisms

    SciTech Connect

    Frank, A. I.

    2013-05-15

    The possibility of the acceleration and deceleration of neutrons undergoing diffraction at a moving grating is discussed. It is shown that, in contrast to phase {pi} gratings used at the present time, which form a discrete spectrum featuring a large number of lines, a grating that has a special profile may shift, under certain conditions, the entire spectrum of diffracted neutrons. A blazing grating of this type may be used in efficiently accelerating and decelerating neutrons. As the scale of the structure becomes larger, a description based on the idea of neutron-wave refraction at its elements becomes valid, a system of moving prims forming a 'neutron turbine,' which is also able to accelerate or decelerate neutrons, being a classical limit of this enlargement.

  1. A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia

    PubMed Central

    Seymour, J F; Kim, D W; Rubin, E; Haregewoin, A; Clark, J; Watson, P; Hughes, T; Dufva, I; Jimenez, J L; Mahon, F-X; Rousselot, P; Cortes, J; Martinelli, G; Papayannidis, C; Nagler, A; Giles, F J

    2014-01-01

    Aurora kinase overexpression has been observed in patients with hematologic malignancies. MK-0457, a pan-aurora kinase inhibitor that also inhibits the ABL T315I mutant, was evaluated to treat patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) with the T315I mutation. Adults with Ph+ chronic phase (CP)-, accelerated phase (AP)- or blast phase (BP)-CML, or ALL and documented BCR-ABL T315I mutation were treated with a 5-day continuous infusion of MK-0457 administered every 14 days at 40 mg/m2/h, 32 mg/m2/h or 24 mg/m2/h. Fifty-two patients (CP, n=15; AP, n=14; BP, n=11; Ph+ ALL, n=12) were treated. Overall, 8% of patients achieved major cytogenetic response; 6% achieved unconfirmed complete or partial response; 39% had no response. Two patients (CP CML) achieved complete hematologic response. No patients with advanced CML or Ph+ ALL achieved major hematologic response. The most common adverse event (AE) was neutropenia (50%). The most common grade 3/4 AEs were neutropenia (46%) and febrile neutropenia (35%). MK-0457 demonstrated minimal efficacy and only at higher, intolerable doses; lower doses were tolerated and no unexpected toxicities were observed. These data will assist in the development of future aurora kinase inhibitors and in the selection of appropriate target patient populations. PMID:25127392

  2. Physics of Phase Space Matching for Staging Plasma and Traditional Accelerator Components Using Longitudinally Tailored Plasma Profiles

    NASA Astrophysics Data System (ADS)

    Xu, X. L.; Hua, J. F.; Wu, Y. P.; Zhang, C. J.; Li, F.; Wan, Y.; Pai, C.-H.; Lu, W.; An, W.; Yu, P.; Hogan, M. J.; Joshi, C.; Mori, W. B.

    2016-03-01

    Phase space matching between two plasma-based accelerator (PBA) stages and between a PBA and a traditional accelerator component is a critical issue for emittance preservation. The drastic differences of the transverse focusing strengths as the beam propagates between stages and components may lead to a catastrophic emittance growth even when there is a small energy spread. We propose using the linear focusing forces from nonlinear wakes in longitudinally tailored plasma density profiles to control phase space matching between sections with negligible emittance growth. Several profiles are considered and theoretical analysis and particle-in-cell simulations show how these structures may work in four different scenarios. Good agreement between theory and simulation is obtained, and it is found that the adiabatic approximation misses important physics even for long profiles.

  3. Impedance-based analysis and study of phase sensitivity in slow-wave two-beam accelerators

    SciTech Connect

    Wurtele, J.S. ); Whittum, D.H. , Tsukuba, Oho, Ibaraki, 305 ); Sessler, A.M. )

    1992-07-01

    This paper presents a new formalism which makes the analysis and understanding of both the relativistic klystron (RK) and the standing-wave free-electron laser (SWFEL) two-beam accelerator (TBA) available to a wide audience of accelerator physicists. A coupling impedance'' for both the RK and SWFEWL is introduced, which can include realistic cavity features, such as beam and vacuum ports, in a simple manner. The RK and SWFEL macroparticle equations, which govern the energy and phase evolution of successive bunches in the beam, are of identical form, differing only by multiplicative factors. Expressions are derived for the phase and amplitude sensitivities of the TBA schemes to errors (shot-to-shot jitter) in current and energy. The analysis allows, for the first time, relative comparisons of the RK and the SWFEL TBAs.

  4. Physics of Phase Space Matching for Staging Plasma and Traditional Accelerator Components Using Longitudinally Tailored Plasma Profiles.

    PubMed

    Xu, X L; Hua, J F; Wu, Y P; Zhang, C J; Li, F; Wan, Y; Pai, C-H; Lu, W; An, W; Yu, P; Hogan, M J; Joshi, C; Mori, W B

    2016-03-25

    Phase space matching between two plasma-based accelerator (PBA) stages and between a PBA and a traditional accelerator component is a critical issue for emittance preservation. The drastic differences of the transverse focusing strengths as the beam propagates between stages and components may lead to a catastrophic emittance growth even when there is a small energy spread. We propose using the linear focusing forces from nonlinear wakes in longitudinally tailored plasma density profiles to control phase space matching between sections with negligible emittance growth. Several profiles are considered and theoretical analysis and particle-in-cell simulations show how these structures may work in four different scenarios. Good agreement between theory and simulation is obtained, and it is found that the adiabatic approximation misses important physics even for long profiles.

  5. Physics of Phase Space Matching for Staging Plasma and Traditional Accelerator Components Using Longitudinally Tailored Plasma Profiles.

    PubMed

    Xu, X L; Hua, J F; Wu, Y P; Zhang, C J; Li, F; Wan, Y; Pai, C-H; Lu, W; An, W; Yu, P; Hogan, M J; Joshi, C; Mori, W B

    2016-03-25

    Phase space matching between two plasma-based accelerator (PBA) stages and between a PBA and a traditional accelerator component is a critical issue for emittance preservation. The drastic differences of the transverse focusing strengths as the beam propagates between stages and components may lead to a catastrophic emittance growth even when there is a small energy spread. We propose using the linear focusing forces from nonlinear wakes in longitudinally tailored plasma density profiles to control phase space matching between sections with negligible emittance growth. Several profiles are considered and theoretical analysis and particle-in-cell simulations show how these structures may work in four different scenarios. Good agreement between theory and simulation is obtained, and it is found that the adiabatic approximation misses important physics even for long profiles. PMID:27058082

  6. Impedance-based analysis and study of phase sensitivity in slow-wave two-beam accelerators

    SciTech Connect

    Wurtele, J.S.; Whittum, D.H.; Sessler, A.M.

    1992-06-01

    This paper presents a new formalism which makes the analysis and understanding of both the relativistic klystron (RK) and the standing-wave free-electron laser (SWFEL) two-beam accelerator (TBA) available to a wide audience of accelerator physicists. A ``coupling impedance`` for both the RK and SWFEWL is introduced, which can include realistic cavity features, such as beam and vacuum ports, in a simple manner. The RK and SWFEL macroparticle equations, which govern the energy and phase evolution of successive bunches in the beam, are of identical form, differing only by multiplicative factors. Expressions are derived for the phase and amplitude sensitivities of the TBA schemes to errors (shot-to-shot jitter) in current and energy. The analysis allows, for the first time, relative comparisons of the RK and the SWFEL TBAs.

  7. White matter microstructure in chronic moderate-to-severe traumatic brain injury: Impact of acute-phase injury-related variables and associations with outcome measures.

    PubMed

    Håberg, A K; Olsen, A; Moen, K G; Schirmer-Mikalsen, K; Visser, E; Finnanger, T G; Evensen, K A I; Skandsen, T; Vik, A; Eikenes, L

    2015-07-01

    This study examines how injury mechanisms and early neuroimaging and clinical measures impact white matter (WM) fractional anisotropy (FA), mean diffusivity (MD), and tract volumes in the chronic phase of traumatic brain injury (TBI) and how WM integrity in the chronic phase is associated with different outcome measures obtained at the same time. Diffusion tensor imaging (DTI) at 3 T was acquired more than 1 year after TBI in 49 moderate-to-severe-TBI survivors and 50 matched controls. DTI data were analyzed with tract-based spatial statistics and automated tractography. Moderate-to-severe TBI led to widespread FA decreases, MD increases, and tract volume reductions. In severe TBI and in acceleration/deceleration injuries, a specific FA loss was detected. A particular loss of FA was also present in the thalamus and the brainstem in all grades of diffuse axonal injury. Acute-phase Glasgow Coma Scale scores, number of microhemorrhages on T2*, lesion volume on fluid-attenuated inversion recovery, and duration of posttraumatic amnesia were associated with more widespread FA loss and MD increases in chronic TBI. Episodes of cerebral perfusion pressure <70 mmHg were specifically associated with reduced MD. Neither episodes of intracranial pressure >20 mmHg nor acute-phase Rotterdam CT scores were associated with WM changes. Glasgow Outcome Scale Extended scores and performance-based cognitive control functioning were associated with FA and MD changes, but self-reported cognitive control functioning was not. In conclusion, FA loss specifically reflects the primary injury severity and mechanism, whereas FA and MD changes are associated with objective measures of general and cognitive control functioning. PMID:25641684

  8. Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006)

    PubMed Central

    Hjorth-Hansen, Henrik; Stenke, Leif; Söderlund, Stina; Dreimane, Arta; Ehrencrona, Hans; Gedde-Dahl, Tobias; Gjertsen, Bjørn Tore; Höglund, Martin; Koskenvesa, Perttu; Lotfi, Kourosh; Majeed, Waleed; Markevärn, Berit; Ohm, Lotta; Olsson-Strömberg, Ulla; Remes, Kari; Suominen, Merja; Simonsson, Bengt; Porkka, Kimmo; Mustjoki, Satu; Richter, Johan

    2015-01-01

    We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100 mg QD or imatinib 400 mg QD and report outcome as an intention-to-treat analysis with 36 months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR3.0 was reached at 3 months in 36% vs. 8% (P = 0.02), at 12 months in 81% vs. 46% (P = 0.02) and at 18 months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR4.5 was consistently superior in the dasatinib group at all time points from 6 months onwards, reaching 61% vs. 21% (P < 0.05) at 36 months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation. PMID:25082346

  9. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

    PubMed

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-11-13

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

  10. Molecular Diagnosis of Chagas Disease in Colombia: Parasitic Loads and Discrete Typing Units in Patients from Acute and Chronic Phases

    PubMed Central

    Hernández, Carolina; Cucunubá, Zulma; Flórez, Carolina; Olivera, Mario; Valencia, Carlos; Zambrano, Pilar; León, Cielo; Ramírez, Juan David

    2016-01-01

    Background The diagnosis of Chagas disease is complex due to the dynamics of parasitemia in the clinical phases of the disease. The molecular tests have been considered promissory because they detect the parasite in all clinical phases. Trypanosoma cruzi presents significant genetic variability and is classified into six Discrete Typing Units TcI-TcVI (DTUs) with the emergence of foreseen genotypes within TcI as TcIDom and TcI Sylvatic. The objective of this study was to determine the operating characteristics of molecular tests (conventional and Real Time PCR) for the detection of T. cruzi DNA, parasitic loads and DTUs in a large cohort of Colombian patients from acute and chronic phases. Methodology/Principal Findings Samples were obtained from 708 patients in all clinical phases. Standard diagnosis (direct and serological tests) and molecular tests (conventional PCR and quantitative PCR) targeting the nuclear satellite DNA region. The genotyping was performed by PCR using the intergenic region of the mini-exon gene, the 24Sa, 18S and A10 regions. The operating capabilities showed that performance of qPCR was higher compared to cPCR. Likewise, the performance of qPCR was significantly higher in acute phase compared with chronic phase. The median parasitic loads detected were 4.69 and 1.33 parasite equivalents/mL for acute and chronic phases. The main DTU identified was TcI (74.2%). TcIDom genotype was significantly more frequent in chronic phase compared to acute phase (82.1% vs 16.6%). The median parasitic load for TcIDom was significantly higher compared with TcI Sylvatic in chronic phase (2.58 vs.0.75 parasite equivalents/ml). Conclusions/Significance The molecular tests are a precise tool to complement the standard diagnosis of Chagas disease, specifically in acute phase showing high discriminative power. However, it is necessary to improve the sensitivity of molecular tests in chronic phase. The frequency and parasitemia of TcIDom genotype in chronic

  11. Secondary hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss in the subacute and chronic phases.

    PubMed

    Ohno, Kazuchika; Noguchi, Yoshihiro; Kawashima, Yoshiyuki; Yagishita, Kazuyoshi; Kitamura, Ken

    2010-06-01

    This study investigated the efficacy of hyperbaric oxygen therapy (HBOT) as a secondary treatment for patients with idiopathic sudden sensorineural hearing loss (ISSNHL) in the subacute and chronic phases. Forty-eight ISSNHL patients (HBOT group) who had received primary conventional treatment within 4 weeks after onset and underwent HBOT between 4 and 20 weeks post-onset were retrospectively compared with 44 ISSNHL patients (control group) with primary conventional treatment alone. Mean hearing gain was slight, with gains of 5.2 +/- 8.9 dB in the HBOT group and 2.0 +/- 7.6 dB in the control group. However, no significant difference was recognized between the two groups. In the HBOT group, no significant difference was observed in hearing gain among patients with HBOT initial time at 4-7, 8-11, 12-15 or 16-20 weeks after onset. Meanwhile, hearing gain was significantly higher in patients with profound hearing loss than in the other patients. We conclude that the effectiveness of secondary HBOT for ISSNHL patients in either subacute or chronic phase remains unproven, and thus, the decision administer HBOT should be made with caution.

  12. EFFECTS OF VITAMIN C SUPPLEMENTATION ON THE CHRONIC PHASE OF CHAGAS DISEASE

    PubMed Central

    MARIM, Ricardo Guimarães; de GUSMÃO, Alex Silva; CASTANHO, Roberto Esteves Pires; DEMINICE, Rafael; THEREZO, Altino Luiz Silva; JORDÃO, Alceu Afonso; de ASSIS, Marcos Renato; TAIPEIRO, Elane de Fátima; MARTINS, Luciamare Perinetti Alves

    2015-01-01

    Introduction: In order to examine the effectiveness of vitamin C (ascorbic acid) in combating the oxidative insult caused by Trypanosoma cruzi during the development of the chronic phase of Chagas disease, Swiss mice were infected intraperitoneally with 5.0 × 104 trypomastigotes of T. cruzi QM1strain. Methods: Mice were given supplements of two different doses of vitamin C for 180 days. Levels of lipid oxidation (as indicated by thiobarbituric acid reactive substances-TBARS), total peroxide, vitamin C, and reduced glutathione were measured in the plasma, TBARS, total peroxide and vitamin C were measured in the myocardium and histopathologic analysis was undertaken in heart, colon and skeletal muscle. Results: Animals that received a dose equivalent to 500 mg of vitamin C daily showed increased production of ROS in plasma and myocardium and a greater degree of inflammation and necrosis in skeletal muscles than those that received a lower dose or no vitamin C whatsoever. Conclusion: Although some research has shown the antioxidant effect of vitamin C, the results showed that animals subject to a 500 mg dose of vitamin C showed greater tissue damage in the chronic phase of Chagas disease, probably due to the paradoxical actions of the substance, which in this pathology, will have acted as a pro-oxidant or pro-inflammatory. PMID:26200966

  13. Pyrvinium selectively targets blast phase-chronic myeloid leukemia through inhibition of mitochondrial respiration

    PubMed Central

    Ang, Shi Hui; Teo, Bryan; Xu, Peng; Asari, Kartini; Sun, Wen Tian; Than, Hein; Bunte, Ralph M.; Virshup, David M.; Chuah, Charles

    2015-01-01

    The use of BCR-ABL1 tyrosine kinase inhibitors (TKI) has led to excellent clinical responses in patients with chronic phase chronic myeloid leukemia (CML). However these inhibitors have been less effective as single agents in the terminal blast phase (BP). We show that pyrvinium, a FDA-approved anthelminthic drug, selectively targets BP-CML CD34+ progenitor cells. Pyrvinium is effective in inducing apoptosis, inhibiting colony formation and self-renewal capacity of CD34+ cells from TKI-resistant BP-CML patients, while cord blood CD34+ are largely unaffected. The effects of pyrvinium are further enhanced upon combination with dasatinib, a second generation BCR-ABL1 TKI. In a CML xenograft model pyrvinium significantly inhibits tumor growth as a single agent, with complete inhibition in combination with dasatinib. While pyrvinium has been shown to inhibit the Wnt/β-catenin signalling pathway via activation of casein kinase 1α, we find its activity in CML is not dependent on this pathway. Instead, we show that pyrvinium localizes to mitochondria and induces apoptosis by inhibiting mitochondrial respiration. Our study suggests that pyrvinium is a useful addition to the treatment armamentarium for BP-CML and that targeting mitochondrial respiration may be a potential therapeutic strategy in aggressive leukemia. PMID:26378050

  14. Topical treatment with the opioid antagonist naltrexone accelerates the remodeling phase of full-thickness wound healing in type 1 diabetic rats.

    PubMed

    Immonen, Jessica A; Zagon, Ian S; Lewis, Gregory S; McLaughlin, Patricia J

    2013-10-01

    Wound repair involves a series of overlapping phases that include inflammation, proliferation, and tissue remodeling, with the latter phase requiring months for proper healing. Delays in any of these processes can result in infection, chronic ulceration, and possible amputation. Diabetes is a major risk factor for improper wound repair, and impaired wound healing is a major complication for more than 26 million people in the US diagnosed with diabetes. Previous studies have demonstrated that the opioid antagonist naltrexone (NTX) dissolved in moisturizing cream reverses delays in wound closure in streptozotocin-induced type 1 diabetic (T1D) rats. NTX accelerated DNA synthesis and increased the number of epithelial and mast cells, as well as new blood vessel formation. In this study, remodeling was evaluated in T1D rats up to eight weeks after initial wounding. Twenty days following wounding, diabetic rats treated with vehicle had elevated numbers of MMP-2+ fibroblasts, suggesting delayed healing processes; birefringence of granulation tissue stained with Sirius red revealed diminished collagen formation and maturation. Wound tissue from NTX-treated T1D rats had comparable numbers of MMP-2+ fibroblasts to control specimens, as well as accelerated maturation of granulation tissue. The integrity of wounded skin was evaluated by tensile strength measurements. T1D resulted in delayed wound healing, and wounded skin that displayed reduced tensile strength relative to normal rats. Topical NTX applied to wounds in T1D rats resulted in enhanced collagen formation and maturation over a 60-day period of time. Moreover, the force required to tear skin of NTX-treated T1D rats was elevated relative to the force necessary to tear the skin of vehicle-treated T1D rats, and comparable to that for normal rats. These data reveal that complications in wound healing associated with T1D involve the novel OGF-OGFr pathway, and that topical NTX is an effective treatment to enhance wound

  15. Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitors

    PubMed Central

    Kim, Sung-Hyun; Menon, Hari; Jootar, Saengsuree; Saikia, Tapan; Kwak, Jae-Yong; Sohn, Sang-Kyun; Park, Joon Seong; Jeong, Seong Hyun; Kim, Hyeoung Joon; Kim, Yeo-Kyeoung; Oh, Suk Joong; Kim, Hawk; Zang, Dae Young; Chung, Joo Seop; Shin, Ho Jin; Do, Young Rok; Kim, Jeong-A; Kim, Dae-Young; Choi, Chul Won; Park, Sahee; Park, Hye Lin; Lee, Gong Yeal; Cho, Dae Jin; Shin, Jae Soo; Kim, Dong-Wook

    2014-01-01

    Radotinib (IY5511HCL), a novel and selective BCR-ABL1 tyrosine kinase inhibitor, has shown pre-clinical and phase I activity and safety in chronic myeloid leukemia. This phase II study investigated the efficacy and safety of radotinib in Philadelphia chromosome-positive chronic phase-chronic myeloid leukemia patients with resistance and/or intolerance to BCR-ABL1 tyrosine kinase inhibitors. Patients received radotinib 400 mg twice daily for 12 cycles based on results from the phase I trial. The primary end point was rate of major cytogenetic response by 12 months. A total of 77 patients were enrolled. Major cytogenetic response was achieved in 50 (65%; cumulative 75%) patients, including 36 (47%) patients with complete cytogenetic response by 12 months. Median time to major cytogenetic response and complete cytogenetic response were 85 days and 256 days, respectively. Major cytogenetic response and complete cytogenetic response rates were similar between imatinib-resistant and imatinib-intolerant patients, but were higher in patients without BCR-ABL1 mutations. Overall and progression-free survival rates at 12 months were 96.1% and 86.3%, respectively. All newly-occurring or worsening grade 3/4 hematologic abnormalities included thrombocytopenia (24.7%) and anemia (5.2%); grade 3/4 drug-related non-hematologic adverse events included fatigue (3.9%), asthenia (3.9%), and nausea (2.6%). The most common biochemistry abnormality was hyperbilirubinemia (grade 3/4 23.4%), and 12 of 18 cases were managed with dose modification. Study findings suggest radotinib is effective and well tolerated in chronic phase-chronic myeloid leukemia patients with resistance and/or intolerance to BCR-ABL1 tyrosine kinase inhibitors and may represent a promising alternative for these patients. (clinicaltrials.gov identifier: 01602952) PMID:24705186

  16. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  17. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

    ClinicalTrials.gov

    2016-10-07

    Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

  18. Influence of optical pumping wavelength on the ultrafast gain and phase recovery acceleration of quantum-dot semiconductor optical amplifiers

    NASA Astrophysics Data System (ADS)

    Kim, Jungho

    2013-10-01

    We numerically investigate the influence of the optical pumping wavelength on the ultrafast gain and phase recovery acceleration of quantum-dot (QD) semiconductor optical amplifiers (SOAs) by solving 1088 coupled rate equations. The temporal variations of the gain and phase recovery response at the ground state (GS) of QDs are calculated at various signal wavelengths when the optical pumping wavelengths at the excited state (ES) of QDs are varied. The phase recovery response is fastest when the wavelength of the signal and pumping beams corresponds to the respective emission wavelength of the GS and the ES in the same size of QDs. The absorption efficiency of the optical pumping beam at the ES is determined by the Lorentzian line shape function of the homogeneous broadening.

  19. Neuromuscular onset succession of high level gymnasts during dynamic leg acceleration phases on high bar.

    PubMed

    von Laßberg, Christoph; Rapp, Walter; Mohler, Betty; Krug, Jürgen

    2013-10-01

    In several athletic disciplines there is evidence that for generating the most effective acceleration of a specific body part the transfer of momentum should run in a "whip-like" consecutive succession of body parts towards the segment which shall be accelerated most effectively (e.g. the arm in throwing disciplines). This study investigated the question how this relates to the succession of neuromuscular activation to induce such "whip like" leg acceleration in sports like gymnastics with changed conditions concerning the body position and momentary rotational axis of movements (e.g. performing giant swings on high bar). The study demonstrates that during different long hang elements, performed by 12 high level gymnasts, the succession of the neuromuscular activation runs primarily from the bar (punctum fixum) towards the legs (punctum mobile). This demonstrates that the frequently used teaching instruction, first to accelerate the legs for a successful realization of such movements, according to a high level kinematic output, is contradictory to the neuromuscular input patterns, being used in high level athletes, realizing these skills with high efficiency. Based on these findings new approaches could be developed for more direct and more adequate teaching methods regarding to an earlier optimization and facilitation of fundamental movement requirements.

  20. Accelerated Reader as a Literacy Catch-Up Intervention during Primary to Secondary School Transition Phase

    ERIC Educational Resources Information Center

    Siddiqui, Nadia; Gorard, Stephen; See, Beng Huat

    2016-01-01

    This paper describes an evaluation of an internet-based reading programme called Accelerated Reader (AR), which is widely used in UK schools and worldwide. AR is a whole-group reading management and monitoring programme that aims to stimulate the habit of independent reading among primary and secondary age pupils. The evaluation involved 349…

  1. Use of IAEA's phase-space files for the implementation of a clinical accelerator virtual source model.

    PubMed

    Rucci, Alexis; Carletti, Claudia; Cravero, Walter; Strbac, Bojan

    2014-03-01

    In the present work, phase-space data files (phsp) provided by the International Atomic Energy Agency (IAEA) for different accelerators were used in order to develop a Virtual Source Model (VSM) for clinical photon beams. Spectral energy distributions extracted from supplied phsp files were used to define the radiation pattern of a virtual extended source in a hybrid model which is completed with a virtual diaphragm used to simulate both electron contamination and the shape of the penumbra region. This simple virtual model was used as the radiation source for dosimetry calculations in a water phantom. The proposed model proved easy to build and test, and good agreement with clinical accelerators dosimetry measurements were obtained for different field sizes. Our results suggest this simple method could be useful for treatment planning systems (TPS) verification purposes.

  2. Multi-Directional Sprinting and Acceleration Phase in Basketball and Handball Players Aged 14 and 15 Years.

    PubMed

    Popowczak, Marek; Rokita, Andrzej; Struzik, Artur; Cichy, Ireneusz; Dudkowski, Andrzej; Chmura, Paweł

    2016-10-01

    An important role in handball and basketball is played by ability to accelerate and ability to repeat multiple sprints. The aim of the study was to assess level of ability in multi-directional sprinting and running time over the first 5 m of the 30 m sprint in 93 basketball and handball players (46 boys and 47 girls) aged 14 to 15 years. The attempts were also made to find the relationships between the time of a 5-m run to evaluate initial acceleration phase and multi-directional sprinting evaluated using Five-Time Shuttle Run To Gates Test Statistical analysis revealed no important differences in times of 5-m runs and times of multi-directional sprinting between groups with different ages, genders, and sports specialties. Furthermore, no significant correlations were found based on Spearman's rank correlation coefficient between times of 5-m run and multi-directional sprinting in the most of subgroups studied.

  3. Acute phase proteins: a potential approach for diagnosing chronic infection by Trypanosoma vivax.

    PubMed

    Almeida, Katyane de Sousa; Costa, Alinny Ferreira; Silva, Paulo Cesar da; Fagliari, José Jurandir; Machado, Rosangela Zacarias; Nascimento, Adjair Antonio do

    2012-01-01

    The present study aimed to assess potential changes in acute phase proteins in sheep experimentally infected with Trypanosoma vivax. There were studied eight male sheep, four used as controls and four infected with 10(5) T. vivax trypomastigotes. Blood samples were collected at two points times before infection and then at 5,7, 9, 11, 13, 15, 20, 30, 45, 60, 75, 90, 105 and 120 days post-infection (dpi). Blood samples were centrifuged and allotted, and acute phase proteins were then separated by electrophoresis on acrylamide gel containing sodium dodecyl sulfate. Protein concentrations were determined by computer-assisted densitometry. Total protein was determined by colorimetric biuret method. Trypanosomes were counted daily using a 5 mL aliquot of blood smear on a glass slide under a 22 × 22 mm coverslip. Parasites were counted in 100 microscopic fields (40× magnification), and then multiplied by a correction factor. The results were expressed as parasites per mL of blood. For statistical analyses, we used the Wilcoxon test at 5% significance level. There was found a reduction in several acute phase proteins and increase in antitrypsin and transferrin. This finding can be used for the diagnosis of T. vivax infection, especially in chronic infection.

  4. Caspr3-Deficient Mice Exhibit Low Motor Learning during the Early Phase of the Accelerated Rotarod Task

    PubMed Central

    Hirata, Haruna; Takahashi, Aki; Shimoda, Yasushi; Koide, Tsuyoshi

    2016-01-01

    Caspr3 (Contactin-associated protein-like 3, Cntnap3) is a neural cell adhesion molecule belonging to the Caspr family. We have recently shown that Caspr3 is expressed abundantly between the first and second postnatal weeks in the mouse basal ganglia, including the striatum, external segment of the globus pallidus, subthalamic nucleus, and substantia nigra. However, its physiological role remains largely unknown. In this study, we conducted a series of behavioral analyses on Capsr3-knockout (KO) mice and equivalent wild-type (WT) mice to investigate the role of Caspr3 in brain function. No significant differences were observed in most behavioral traits between Caspr3-KO and WT mice, but we found that Caspr3-KO mice performed poorly during the early phase of the accelerated rotarod task in which latency to falling off a rod rotating with increasing velocity was examined. In the late phase, the performance of the Caspr3-KO mice caught up to the level of WT mice, suggesting that the deletion of Caspr3 caused a delay in motor learning. We then examined changes in neural activity after training on the accelerated rotarod by conducting immunohistochemistry using antibody to c-Fos, an indirect marker for neuronal activity. Experience of the accelerated rotarod task caused increases in the number of c-Fos-positive cells in the dorsal striatum, cerebellum, and motor cortex in both Caspr3-KO and WT mice, but the number of c-Fos-positive cells was significantly lower in the dorsal striatum of Caspr3-KO mice than in that of WT mice. The expression of c-Fos in the ventral striatum of Caspr3-KO and WT mice was not altered by the training. Our findings suggest that reduced activation of neural cells in the dorsal striatum in Caspr3-KO mice leads to a decline in motor learning in the accelerated rotarod task. PMID:26807827

  5. Inhibitory and Excitatory Motor Cortex Dysfunction Persists in the Chronic Post-Stroke Recovery Phase

    PubMed Central

    Malcolm, M.P.; Vaughn, H.N.; Greene, D.

    2014-01-01

    Purpose Establish differences in intracortical facilitation (ICF) and inhibition (ICI) between survivors of stroke and healthy individuals. Methods Fourteen chronic stroke survivors and 19 healthy subjects were investigated using single and paired-pulse transcranial magnetic stimulation (TMS). TMS was applied over the motor cortex in thelesioned (stroke survivors) or left (healthy subjects) hemisphere. Motor evoked potentials (MEPs) were collected from the contra lateral first dorsal interosseus. Subjects received 40 pseudo-randomized trials consisting of 10 trials for each: conditioning stimulus, test stimulus (TS), ICF, and ICI. Between the groups, we compared MEP amplitudes for TS, ICF, and ICI, motor threshold (MT), and ICF/ICI ratio. Results Compared to healthy individuals, the stroke group exhibited higher MT and lower ICI; the difference ICF neared significance. The ICF/ICI ratio was significantly lower in the stroke group and close to 1, indicating little difference between ICF and ICI responses. These differences demonstrate that motor cortex excitatory and inhibitory mechanisms are impaired for individuals in the chronic post-stroke recovery phase. Conclusions Compared to healthy individuals, both global and intracortical TMS measures reveal reduced motor cortex excitability in survivors of stroke. Interventions that normalize motor cortex excitability may promote better neurophysiological conditions for motor recovery to occur. PMID:25350636

  6. The relationship between visfatin, liver inflammation, and acute phase reactants in chronic viral hepatitis B.

    PubMed

    Yüksel, Enver; Akbal, Erdem; Koçak, Erdem; Akyürek, Ömer; Köklü, Seyfettin; Ekiz, Fuat; Yılmaz, Barış

    2016-09-01

    Chronic viral hepatitis B (CHB) is an important cause of morbidity and mortality. Adipokine stimulation might play an important role in the pathogenesis of chronic inflammation. The aim of this study was to evaluate serum visfatin concentrations and the relationship between visfatin, fibrosis, liver inflammation, and acute phase reactants in CHB patients.The sampling universe of the study consisted of 41 CHB patients and 25 healthy controls. All patients had positive hepatitis B surface antigen (Hepatitis e antigen (HBeAg) positive n: 7, n: 34 HBeAg negative) for at least 6 months and detectable serum HBV DNA. Serum visfatin concentrations were significantly higher in the CHB patients [18.0 ± 10.9 ng dL(-1)] than in the healthy controls [9.4 ± 1.6 ng dL(-1)] [P < 0.001]. On the other hand, fibrinogen and haptoglobin concentrations were significantly lower in CHB patients. A strong negative correlation was observed between serum visfatin concentration, haptoglobin, and fibrinogen levels; however, there was no significant correlation between visfatin, glucose, alanine aminotransferase, aspartate aminotransferase, BMI, Knodell score, fibrosis score, hepatitis B virus DNA, sedimentation, and C-reactive protein. Visfatin concentrations were elevated and visfatin was negatively correlated with haptoglobin and fibrinogen levels in CHB patients.

  7. Effect of corticosteroids on sputum sol-phase protease inhibitors in chronic obstructive pulmonary disease.

    PubMed Central

    Wiggins, J; Elliott, J A; Stevenson, R D; Stockley, R A

    1982-01-01

    Corticosteroids caused a reduction in the ratio of sol-phase sputum concentration to serum concentration of albumin in 12 patients with chronic obstructive bronchitis, suggesting a reduction in protein transudation. Alpha-1-antitrypsin values followed the same pattern as those of albumin in both the control and treatment periods, confirming the similar behaviour of the two proteins. The alpha 1-antichymotrypsin ratios were on average three times higher than those of albumin in the control period, confirming the presence of local mechanisms in the lung for preferentially concentrating this protein. The sputum-to-serum ratio of alpha 1-antichymotrypsin, however, rose during steroid treatment with the result that there was a selective increase in this protease inhibitor, which may be of potential benefit to such patients. PMID:6984237

  8. Gamma-ray and microwave evidence for two phases of acceleration in solar flares

    NASA Technical Reports Server (NTRS)

    Bai, T.; Ramaty, R.

    1976-01-01

    Relativistic electrons in large solar flares produce gamma ray continuum by bremsstrahlung and microwave emission by gyrosynchrotron radiation. Using observations of the 1972, August 4 flare, the electron spectrum and the physical properties of the common emitting region of these radiations were evaluated. Information was also obtained on energetic protons in this flare by using gamma ray lines. From the electron spectrum, the proton-to-electron ratio, and the time dependences of the microwave emission, the 2.2 MeV line and the gamma ray continuum, it was concluded that in large solar flares relativistic electrons and energetic nuclei are accelerated by a mechanism which is different from the mechanism which accelerates approximately less than 100 keV electrons in flares.

  9. Myocardial longitudinal peak systolic acceleration (pSac): relationship to ejection phase, pressure, and contractility.

    PubMed

    Odland, Hans Henrik; Brun, Henrik; Sejersted, Yngve; Dalen, Marit; Edvardsen, Thor; Saugstad, Ola Didrik; Thaulow, Erik

    2012-05-01

    Acceleration has been measured both noninvasively and invasively, during both isovolumic contraction and early ejection and has been shown to reflect contractility, especially through correlation with dP/dt(max) . In this study timing and amplitude of mitral valve annulus acceleration assessed by tissue Doppler were measured and related to diastolic and systolic events. Invasive load independent measures of contractility, based on pressure-volume relationships, were derived, and pacing was done to modulate and control heart rate. Peak systolic acceleration (pSac) of the mitral valve annulus was shown to occur slightly later but timely related to dP/dt(max) (P < 0.05), while peak preejection acceleration (pPac) was related to diastolic events. During inotropy and preload modulation dP/dt(max) was found to be the strongest determinant of pSac (β= 0.9 ± 0.1; P < 0.001 and β= 1.3 ± 0.4; P < 0.001, respectively, log-transformed variables). PSac increased with pacing at a higher rate (β= 0.1 ± 0.0 cm/sec(2), P = 0.03). Furthermore, pSac indexed to end-diastolic volume (EDV) was linearly correlated to load independent contractility parameters (E(max), R = 0.7; ESPVR, R = 0.7; and PRSW, R = 0.5), and proved stable toward changes in preload and afterload. The relation between dP/dt(max)/EDV and pSac/EDV was stable throughout the study. In conclusion we found that peak systolic longitudinal acceleration (pSac) of the mitral valve annulus during aortic valve opening is strongly associated with dP/dt(max). Indexed to EDV, pSac may represent a load independent noninvasive contractility parameter. We consider pSac a candidate marker of long-axis contractility which should be viewed upon as the long-axis contribution to dP/dt(max).

  10. Studies of Particle Acceleration, Transport and Radiation in Impulsive Phase of Solar Flares

    NASA Technical Reports Server (NTRS)

    Petrosian, Vahe

    2005-01-01

    Solar activity and its most prominent aspect, the solar flares, have considerable influence on terrestrial and space weather. Solar flares also provide a suitable laboratory for the investigation of many plasma and high energy processes important in the magnetosphere of the Earth and many other space and astrophysical situations. Hence, progress in understanding of flares will have considerable scientific and societal impact. The primary goal of this grant is the understanding of two of the most important problems of solar flare physics, namely the determination of the energy release mechanism and how this energy accelerates particles. This is done through comparison of the observations with theoretical models, starting from observations and gradually proceeding to theoretically more complex situations as the lower foundations of our understanding are secured. It is generally agreed that the source of the flare energy is the annihilation of magnetic fields by the reconnection process. Exactly how this energy is released or how it is dissipated remains controversial. Moreover, the exact mechanism of the acceleration of the particles is still a matter of debate. Data from many spacecrafts and ground based instruments obtained over the past decades have given us some clues. Theoretical analyses of these data have led to the standard thick target model (STT) where most of the released energy goes into an (assumed) power law spectrum of accelerated particles, and where all the observed radiations are the consequence of the interaction of these particles with the flare plasma. However, some theoretical arguments, and more importantly some new observations, have led us to believe that the above picture is not complete. It appears that plasma turbulence plays a more prominent role than suspected previously, and that it is the most likely agent for accelerating particles. The model we have developed is based on production of a high level of plasma waves and turbulence in

  11. The Association between Platelet Count and Acute Phase Response in Chronic Spontaneous Urticaria

    PubMed Central

    Kasperska-Zając, Alicja; Grzanka, Alicja; Jarzab, Jerzy; Misiołek, Maciej; Wyszyńska-Chłap, Magdalena; Kasperski, Jacek; Machura, Edyta

    2014-01-01

    Background. The platelet parameters and C-reactive protein (CRP) are markers reflecting a systemic inflammatory response. Among those, CRP is one of the major proteins helpful in determination of severity/activity of chronic spontaneous urticaria (CSU). Aim. To determine relationships between platelet activation indices and serum concentration of CRP, the best marker of acute phase response, and their potential clinical use in CSU patients. Methods. Mean platelet volume (MPV), platelet distribution width (PDW), and platelet count as well as serum CRP concentration were measured in CSU patients, showing different degrees of urticarial severity, and in the healthy subjects. Results. No significant differences were found in MPV and PDW between CSU group and the healthy subjects. The platelet count was significantly higher in moderate-severe CSU than that of the controls and mild CSU patients. Serum CRP concentrations were significantly higher in CSU patients as compared with the healthy subjects and significantly correlated with the platelet count in CSU patients. Conclusions. Acute phase response in CSU is associated with the increased number of circulating platelets in patients with more severe symptoms. It seems that simple determination of platelet size indices is not a reliable indicator of CSU severity/activity. PMID:25025065

  12. Functional Data Analysis of Spaceflight-Induced Changes in Coordination and Phase in Head Pitch Acceleration During Treadmill Walking

    NASA Technical Reports Server (NTRS)

    Miller, Christopher; Peters, Brian; Feiveson, Alan; Bloomberg, Jacob

    2011-01-01

    Astronauts returning from spaceflight experience neurovestibular disturbances during head movements and attempt to mitigate them by limiting head motion. Analyses to date of the head movements made during walking have concentrated on amplitude and variability measures extracted from ensemble averages of individual gait cycles. Phase shifts within each gait cycle can be determined by functional data analysis through the computation of time-warping functions. Large, localized variations in the timing of peaks in head kinematics may indicate changes in coordination. The purpose of this study was to determine timing changes in head pitch acceleration of astronauts during treadmill walking before and after flight. Six astronauts (5M/1F; age = 43.5+/-6.4yr) participated in the study. Subjects walked at 1.8 m/sec (4 mph) on a motorized treadmill while reading optotypes displayed on a computer screen 4 m in front of their eyes. Three-dimensional motion of the subject s head was recorded with an Inertial Measurement Unit (IMU) device. Data were recorded twice before flight and four times after landing. The head pitch acceleration was calculated by taking the time derivative of the pitch velocity data from the IMU. Data for each session with each subject were time-normalized into gait cycles, then registered to align significant features and create a mean curve. The mean curves of each postflight session for each subject were re-registered based on their preflight mean curve to create time-warping functions. The root mean squares (RMS) of these warping functions were calculated to assess the deviation of head pitch acceleration mean curves in each postflight session from the preflight mean curve. After landing, most crewmembers exhibited localized shifts within their head pitch acceleration regimes, with the greatest deviations in RMS occurring on landing day or 1 day after landing. These results show that the alteration of head pitch coordination due to spaceflight may be

  13. Optical control of electron phase space in plasma accelerators with incoherently stacked laser pulses

    SciTech Connect

    Kalmykov, S. Y. Shadwick, B. A.; Davoine, X.; Lehe, R.; Lifschitz, A. F.

    2015-05-15

    It is demonstrated that synthesizing an ultrahigh-bandwidth, negatively chirped laser pulse by incoherently stacking pulses of different wavelengths makes it possible to optimize the process of electron self-injection in a dense, highly dispersive plasma (n{sub 0}∼10{sup 19} cm{sup −3}). Avoiding transformation of the driving pulse into a relativistic optical shock maintains a quasi-monoenergetic electron spectrum through electron dephasing and boosts electron energy far beyond the limits suggested by existing scaling laws. In addition, evolution of the accelerating bucket in a plasma channel is shown to produce a background-free, tunable train of femtosecond-duration, 35–100 kA, time-synchronized quasi-monoenergetic electron bunches. The combination of the negative chirp and the channel permits acceleration of electrons beyond 1 GeV in a 3 mm plasma with 1.4 J of laser pulse energy, thus offering the opportunity of high-repetition-rate operation at manageable average laser power.

  14. Ion Beam Driven Shock Device Using Accelerated High Density Plasmoid by Phased Z-Pinch

    NASA Astrophysics Data System (ADS)

    Horioka, Kazuhiko; Aizawa, Tatsuhiko; Tsuchida, Minoru

    1997-07-01

    Different from three methods to generate high shock pressure by acceleration of high density plasma or particles (intense ion beams, plasma gun and rail gun) having their intrinsic deficiencies, new frontier is proposed to propel the shock physics and chemistry by using the high density plasma. In the present paper, new scheduled Z-pinch method is developed as a new device to generate high shock pressure. In the present method, plasma density can be compressed to the order of 10^18 to 10^19 cm-3, and high density plasma can be accelerated by zippering together with axial shock pressure, resulting in high-velocity launching of flyer. In the present paper, systematic experimental works are performed to demonstrate that high energy plasma flow can be electro-magnetically driven by the scheduled capillary Z-pinch, and to characterize the ion velocity and its current density. The estimated value of ion speed from the plasma-measurement reaches to 7 x 10^7 cm/s corresponding to 70 to 100 KeV for Ar. Copper flyer can be shot with the velocity range from 1km/s to 3km/s in the standard condition.

  15. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery.

    PubMed

    Zhang, Shao-jie; Ke, Zheng; Li, Le; Yip, Shea-ping; Tong, Kai-yu

    2013-04-01

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague-Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely

  16. Accelerated exploration of multi-principal element alloys with solid solution phases

    PubMed Central

    Senkov, O.N.; Miller, J.D.; Miracle, D.B.; Woodward, C.

    2015-01-01

    Recent multi-principal element, high entropy alloy (HEA) development strategies vastly expand the number of candidate alloy systems, but also pose a new challenge—how to rapidly screen thousands of candidate alloy systems for targeted properties. Here we develop a new approach to rapidly assess structural metals by combining calculated phase diagrams with simple rules based on the phases present, their transformation temperatures and useful microstructures. We evaluate over 130,000 alloy systems, identifying promising compositions for more time-intensive experimental studies. We find the surprising result that solid solution alloys become less likely as the number of alloy elements increases. This contradicts the major premise of HEAs—that increased configurational entropy increases the stability of disordered solid solution phases. As the number of elements increases, the configurational entropy rises slowly while the probability of at least one pair of elements favouring formation of intermetallic compounds increases more rapidly, explaining this apparent contradiction. PMID:25739749

  17. Simulation Study Using an Injection Phase-locked Magnetron as an Alternative Source for SRF Accelerators

    SciTech Connect

    Wang, Haipeng; Plawski, Tomasz E.; Rimmer, Robert A.

    2015-09-01

    As a drop-in replacement for the CEBAF CW klystron system, a 1497 MHz, CW-type high-efficiency magnetron using injection phase lock and amplitude variation is attractive. Amplitude control using magnetic field trimming and anode voltage modulation has been studied using analytical models and MATLAB/Simulink simulations. Since the 1497 MHz magnetron has not been built yet, previously measured characteristics of a 2.45GHz cooker magnetron are used as reference. The results of linear responses to the amplitude and phase control of a superconducting RF (SRF) cavity, and the expected overall benefit for the current CEBAF and future MEIC RF systems are presented in this paper.

  18. Final safety analysis report for the Ground Test Accelerator (GTA), Phase 2

    SciTech Connect

    1994-10-01

    This document is the first volume of a 3 volume safety analysis report on the Ground Test Accelerator (GTA). The GTA program at the Los Alamos National Laboratory (LANL) is the major element of the national Neutral Particle Beam (NPB) program, which is supported by the Strategic Defense Initiative Office (SDIO). A principal goal of the national NPB program is to assess the feasibility of using hydrogen and deuterium neutral particle beams outside the Earth`s atmosphere. The main effort of the NPB program at Los Alamos concentrates on developing the GTA. The GTA is classified as a low-hazard facility, except for the cryogenic-cooling system, which is classified as a moderate-hazard facility. This volume consists of an introduction, summary/conclusion, site description and assessment, description of facility, and description of operation.

  19. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    PubMed

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.

  20. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    PubMed

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain. PMID:26490459

  1. Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial.

    PubMed

    Braun, Thorsten; Itzykson, Raphael; Renneville, Aline; de Renzis, Benoit; Dreyfus, François; Laribi, Kamel; Bouabdallah, Krimo; Vey, Norbert; Toma, Andrea; Recher, Christian; Royer, Bruno; Joly, Bertrand; Vekhoff, Anne; Lafon, Ingrid; Sanhes, Laurence; Meurice, Guillaume; Oréar, Cédric; Preudhomme, Claude; Gardin, Claude; Ades, Lionel; Fontenay, Michaela; Fenaux, Pierre; Droin, Nathalie; Solary, Eric

    2011-10-01

    Hydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With a median follow-up of 23 months, overall survival was 48% at 2 years. Mutations in ASXL1, TET2, AML1, NRAS, KRAS, CBL, FLT3, and janus kinase 2 (JAK2) genes, and hypermethylation of the promoter of the tumor suppressor gene TIF1γ, did not predict response or survival on DAC therapy. Lower CJUN and CMYB gene expression levels independently predicted improved overall survival. This trial confirmed DAC efficacy in approximately 40% of CMML patients with advanced myeloproliferative or myelodysplastic features and suggested that CJUN and CMYB expression could be potential biomarkers in this setting. This trial is registered at EudraCT (eudract.ema.europa.eu) as #2008-000470-21 and www.clinicaltrials.gov as #NCT01098084.

  2. Pulse evolution and plasma-wave phase velocity in channel-guided laser-plasma accelerators.

    PubMed

    Benedetti, C; Rossi, F; Schroeder, C B; Esarey, E; Leemans, W P

    2015-08-01

    The self-consistent laser evolution of an intense, short-pulse laser exciting a plasma wave and propagating in a preformed plasma channel is investigated, including the effects of pulse steepening and energy depletion. In the weakly relativistic laser intensity regime, analytical expressions for the laser energy depletion, pulse self-steepening rate, laser intensity centroid velocity, and phase velocity of the plasma wave are derived and validated numerically. PMID:26382537

  3. One-phase methods for accelerating the production of biodiesel methyl esters

    SciTech Connect

    Boocock, D.G.B.; Konar, S.K.; Mao, V.

    1995-11-01

    The base-catalysed (methoxide or hydroxide) methanolysis of vegetable oils (6:1 methanol/oil molar ratio), such as soybean, occurs 15-20 times slower than butanolysis because the former starts out as a two-phase system, in which the solubility of the oil in the methanol phase, where the catalyst is located, is very low. The addition of a cosolvent, such as 1.27 volumes of tetrahydrofuran (THF) per volume of methanol, forms an oil-rich, one phase system in which methanolysis is as fast as butanolysis. Other suitable cosolvents include 1,4-dioxane, diethyl ether and t-butyl methyl ether. THF has a boiling point very close to that of methanol and can be flashed and recycled along with unused alcohol. Glycerol separation usually occurs faster in the presence of cosolvent (4-5 times faster in the case of THF). The sudden and abnormal slowing of both hydroxide and alkoxide transesterifications may be caused by a number of factors including polarity of the mixture, the formation of undesired intermediates and structural differences in the substrates. Simple appropriate measures can dramatically lower 98% conversion times to twenty minutes and less, in which case continuous processes employing centrifuges for glycerol separation become very attractive.

  4. Effect of additional optical pumping injection into the ground-state ensemble on the gain and the phase recovery acceleration of quantum-dot semiconductor optical amplifiers

    NASA Astrophysics Data System (ADS)

    Kim, Jungho

    2014-02-01

    The effect of additional optical pumping injection into the ground-state ensemble on the ultrafast gain and the phase recovery dynamics of electrically-driven quantum-dot semiconductor optical amplifiers is numerically investigated by solving 1088 coupled rate equations. The ultrafast gain and the phase recovery responses are calculated with respect to the additional optical pumping power. Increasing the additional optical pumping power can significantly accelerate the ultrafast phase recovery, which cannot be done by increasing the injection current density.

  5. Microbially-accelerated consolidation of oil sands tailings. Pathway II: solid phase biogeochemistry

    PubMed Central

    Siddique, Tariq; Kuznetsov, Petr; Kuznetsova, Alsu; Li, Carmen; Young, Rozlyn; Arocena, Joselito M.; Foght, Julia M.

    2014-01-01

    Consolidation of clay particles in aqueous tailings suspensions is a major obstacle to effective management of oil sands tailings ponds in northern Alberta, Canada. We have observed that microorganisms indigenous to the tailings ponds accelerate consolidation of mature fine tailings (MFT) during active metabolism by using two biogeochemical pathways. In Pathway I, microbes alter porewater chemistry to indirectly increase consolidation of MFT. Here, we describe Pathway II comprising significant, direct and complementary biogeochemical reactions with MFT mineral surfaces. An anaerobic microbial community comprising Bacteria (predominantly Clostridiales, Synergistaceae, and Desulfobulbaceae) and Archaea (Methanolinea/Methanoregula and Methanosaeta) transformed FeIII minerals in MFT to amorphous FeII minerals during methanogenic metabolism of an added organic substrate. Synchrotron analyses suggested that ferrihydrite (5Fe2O3. 9H2O) and goethite (α-FeOOH) were the dominant FeIII minerals in MFT. The formation of amorphous iron sulfide (FeS) and possibly green rust entrapped and masked electronegative clay surfaces in amended MFT. Both Pathways I and II reduced the surface charge potential (repulsive forces) of the clay particles in MFT, which aided aggregation of clays and formation of networks of pores, as visualized using cryo-scanning electron microscopy (SEM). These reactions facilitated the egress of porewater from MFT and increased consolidation of tailings solids. These results have large-scale implications for management and reclamation of oil sands tailings ponds, a burgeoning environmental issue for the public and government regulators. PMID:24711806

  6. Final safety analysis report for the Ground Test Accelerator (GTA), Phase 2

    SciTech Connect

    1994-10-01

    This document is the second volume of a 3 volume safety analysis report on the Ground Test Accelerator (GTA). The GTA program at the Los Alamos National Laboratory (LANL) is the major element of the national Neutral Particle Beam (NPB) program, which is supported by the Strategic Defense Initiative Office (SDIO). A principal goal of the national NPB program is to assess the feasibility of using hydrogen and deuterium neutral particle beams outside the Earth`s atmosphere. The main effort of the NPB program at Los Alamos concentrates on developing the GTA. The GTA is classified as a low-hazard facility, except for the cryogenic-cooling system, which is classified as a moderate-hazard facility. This volume consists of failure modes and effects analysis; accident analysis; operational safety requirements; quality assurance program; ES&H management program; environmental, safety, and health systems critical to safety; summary of waste-management program; environmental monitoring program; facility expansion, decontamination, and decommissioning; summary of emergency response plan; summary plan for employee training; summary plan for operating procedures; glossary; and appendices A and B.

  7. Angiopoietin-like protein 2 increases renal fibrosis by accelerating transforming growth factor-β signaling in chronic kidney disease.

    PubMed

    Morinaga, Jun; Kadomatsu, Tsuyoshi; Miyata, Keishi; Endo, Motoyoshi; Terada, Kazutoyo; Tian, Zhe; Sugizaki, Taichi; Tanigawa, Hiroki; Zhao, Jiabin; Zhu, Shunshun; Sato, Michio; Araki, Kimi; Iyama, Ken-ichi; Tomita, Kengo; Mukoyama, Masashi; Tomita, Kimio; Kitamura, Kenichiro; Oike, Yuichi

    2016-02-01

    Renal fibrosis is a common pathological consequence of chronic kidney disease (CKD) with tissue fibrosis closely associated with chronic inflammation in numerous pathologies. However, molecular mechanisms underlying that association, particularly in the kidney, remain unclear. Here, we determine whether there is a molecular link between chronic inflammation and tissue fibrosis in CKD progression. Histological analysis of human kidneys indicated abundant expression of angiopoietin-like protein 2 (ANGPTL2) in renal tubule epithelial cells during progression of renal fibrosis. Numerous ANGPTL2-positive renal tubule epithelial cells colocalized with cells positive for transforming growth factor (TGF)-β1, a critical mediator of tissue fibrosis. Analysis of M1 collecting duct cells in culture showed that TGF-β1 increases ANGPTL2 expression by attenuating its repression through microRNA-221. Conversely, ANGPTL2 increased TGF-β1 expression through α5β1 integrin-mediated activation of extracellular signal-regulated kinase. Furthermore, ANGPTL2 deficiency in a mouse unilateral ureteral obstruction model significantly reduced renal fibrosis by decreasing TGF-β1 signal amplification in kidney. Thus, ANGPTL2 and TGF-β1 positively regulate each other as renal fibrosis progresses. Our study provides insight into molecular mechanisms underlying chronic inflammation and tissue fibrosis and identifies potential therapeutic targets for CKD treatment.

  8. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up

    PubMed Central

    Gambacorti-Passerini, Carlo; Brümmendorf, Tim H; Kim, Dong-Wook; Turkina, Anna G; Masszi, Tamas; Assouline, Sarit; Durrant, Simon; Kantarjian, Hagop M; Khoury, H Jean; Zaritskey, Andrey; Shen, Zhi-Xiang; Jin, Jie; Vellenga, Edo; Pasquini, Ricardo; Mathews, Vikram; Cervantes, Francisco; Besson, Nadine; Turnbull, Kathleen; Leip, Eric; Kelly, Virginia; Cortes, Jorge E

    2014-01-01

    Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib as second-line therapy in 288 patients with chronic phase CML resistant (n = 200) or intolerant (n = 88) to imatinib. The cumulative response rates to bosutinib were as follows: 85% achieved/maintained complete hematologic response, 59% achieved/maintained major cytogenetic response (including 48% with complete cytogenetic response), and 35% achieved major molecular response. Responses were durable, with 2-year estimates of retaining response >70%. Two-year probabilities of progression-free survival and overall survival were 81% and 91%, respectively. The most common toxicities were primarily gastrointestinal adverse events (diarrhea [84%], nausea [45%], vomiting [37%]), which were primarily mild to moderate, typically transient, and first occurred early during treatment. Thrombocytopenia was the most common grade 3/4 hematologic laboratory abnormality (24%). Outcomes were generally similar among imatinib-resistant and imatinib-intolerant patients and did not differ with age. The longer-term results of the present analysis confirm that bosutinib is an effective and tolerable second-line therapy for patients with imatinib-resistant or imatinib-intolerant chronic phase CML. http://ClinicalTrials.gov Identifier: NCT00261846. Am. J. Hematol. 89:732–742, 2014. © 2014 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc. PMID:24711212

  9. Evaluation of the Acceleration and Deceleration Phase-Rectified Slope to Detect and Improve IUGR Clinical Management

    PubMed Central

    Tagliaferri, Salvatore; Fanelli, Andrea; Esposito, Giuseppina; Esposito, Francesca Giovanna; Magenes, Giovanni; Signorini, Maria Gabriella; Campanile, Marta; Martinelli, Pasquale

    2015-01-01

    Objective. This study used a new method called Acceleration (or Deceleration) Phase-Rectified Slope, APRS (or DPRS) to analyze computerized Cardiotocographic (cCTG) traces in intrauterine growth restriction (IUGR), in order to calculate acceleration- and deceleration-related fluctuations of the fetal heart rate, and to enhance the prediction of neonatal outcome. Method. Cardiotocograms from a population of 59 healthy and 61 IUGR fetuses from the 30th gestation week matched for gestational age were included. APRS and DPRS analysis was compared to the standard linear and nonlinear cCTG parameters. Statistical analysis was performed through the t-test, ANOVA test, Pearson correlation test and receiver operator characteristic (ROC) curves (p < 0, 05). Results. APRS and DPRS showed high performance to discriminate between Healthy and IUGR fetuses, according to gestational week. A linear correlation with the fetal pH at birth was found in IUGR. The area under the ROC curve was 0.865 for APRS and 0.900 for DPRS before the 34th gestation week. Conclusions. APRS and DPRS could be useful in the identification and management of IUGR fetuses and in the prediction of the neonatal outcome, especially before the 34th week of gestation. PMID:26779279

  10. Multi-Directional Sprinting and Acceleration Phase in Basketball and Handball Players Aged 14 and 15 Years.

    PubMed

    Popowczak, Marek; Rokita, Andrzej; Struzik, Artur; Cichy, Ireneusz; Dudkowski, Andrzej; Chmura, Paweł

    2016-10-01

    An important role in handball and basketball is played by ability to accelerate and ability to repeat multiple sprints. The aim of the study was to assess level of ability in multi-directional sprinting and running time over the first 5 m of the 30 m sprint in 93 basketball and handball players (46 boys and 47 girls) aged 14 to 15 years. The attempts were also made to find the relationships between the time of a 5-m run to evaluate initial acceleration phase and multi-directional sprinting evaluated using Five-Time Shuttle Run To Gates Test Statistical analysis revealed no important differences in times of 5-m runs and times of multi-directional sprinting between groups with different ages, genders, and sports specialties. Furthermore, no significant correlations were found based on Spearman's rank correlation coefficient between times of 5-m run and multi-directional sprinting in the most of subgroups studied. PMID:27565172

  11. Phase-space moment-equation model of highly relativistic electron-beams in plasma-wakefield accelerators

    SciTech Connect

    Robson, R.E.; Mehrling, T.; Osterhoff, J.

    2015-05-15

    We formulate a new procedure for modelling the transverse dynamics of relativistic electron beams with significant energy spread when injected into plasma-based accelerators operated in the blow-out regime. Quantities of physical interest, such as the emittance, are furnished directly from solution of phase space moment equations formed from the relativistic Vlasov equation. The moment equations are closed by an Ansatz, and solved analytically for prescribed wakefields. The accuracy of the analytic formulas is established by benchmarking against the results of a semi-analytic/numerical procedure which is described within the scope of this work, and results from a simulation with the 3D quasi-static PIC code HiPACE.

  12. Acceleration of the matrix multiplication of Radiance three phase daylighting simulations with parallel computing on heterogeneous hardware of personal computer

    SciTech Connect

    Zuo, Wangda; McNeil, Andrew; Wetter, Michael; Lee, Eleanor S.

    2013-05-23

    Building designers are increasingly relying on complex fenestration systems to reduce energy consumed for lighting and HVAC in low energy buildings. Radiance, a lighting simulation program, has been used to conduct daylighting simulations for complex fenestration systems. Depending on the configurations, the simulation can take hours or even days using a personal computer. This paper describes how to accelerate the matrix multiplication portion of a Radiance three-phase daylight simulation by conducting parallel computing on heterogeneous hardware of a personal computer. The algorithm was optimized and the computational part was implemented in parallel using OpenCL. The speed of new approach was evaluated using various daylighting simulation cases on a multicore central processing unit and a graphics processing unit. Based on the measurements and analysis of the time usage for the Radiance daylighting simulation, further speedups can be achieved by using fast I/O devices and storing the data in a binary format.

  13. Phase-scan analysis results for the first drift tube linac module in the ground test accelerator: Data reproducibility and comparison to simulations

    SciTech Connect

    Johnson, K.F.; Sander, O.R.; Bolme, G.O.

    1995-05-01

    The Ground Test Accelerator (GTA) had the objective of producing a high-brightness, high-current H- beam. The major accelerator components were a 35 keV injector, a Radio Frequency Quadrupole, an intertank matching section, and a drift tube linac (DTL), consisting of 10 modules. This paper discusses the phase-scan technique which was used to experimentally determine the rf operating parameters for the commissioning and routine operation of the first DTL module.

  14. Preleukemic phase of chronic myelogenous leukemia: morphologic and immunohistochemical characterization of 7 cases.

    PubMed

    Aye, Le Le; Loghavi, Sanam; Young, Ken H; Siddiqi, Imran; Yin, C Cameron; Routbort, Mark J; Liang, Mei; Eilerman, Keith; Medeiros, L Jeffrey; Brynes, Russell K; Bueso-Ramos, Carlos

    2016-04-01

    Patients with chronic myelogenous leukemia (CML) present typically with an elevated white blood cell count (WBC) and cytogenetic or molecular genetic evidence of t(9;22)/BCR-ABL1 fusion gene. Rarely, CML patients may present with a normal or mildly elevated WBC and are asymptomatic, and we describe 7 patients in this study. The WBC in these patients ranged from 3.6 to 14.3 K/mm(3) with 50% to 73% granulocytes and 0% blasts. In all patients, t(9;22)(q34;q11.2) was detected by conventional cytogenetics, and BCR-ABL1 fusion was shown, supporting the diagnosis of preleukemic CML (pre-CML). We compared these patients with a group of 5 cases of CML in chronic phase (CML-CP) and 5 bone marrow specimens with a leukemoid reaction (n=5). Reticulin, CD34, and CD61 immunostains were performed on all bone marrow biopsy specimens. Peripheral blood absolute basophilia (≥200/mm(3)) was noted in only 4 of 7 pre-CML cases, whereas it was present in all CML-CP cases and absent in leukemoid reaction cases. The mean ±SD of microvascular density of pre-CML cases (10.0 ± 4.3 vessels/200× field) was twice that of leukemoid reaction cases (5.0 ± 1.0) (P=.02; Student t test) but similar to that of CML-CP cases (12.5 ± 3.6). Microvessels in pre-CML, highlighted by CD34, were tortuous with abnormal branching, although to a lesser extent than those found in CML-CP. Microvessels in leukemoid reaction were generally straight. The percentage of small, hypolobated megakaryocytes, highlighted by CD61 in pre-CML, was 40%, 3 times that found in leukemoid reaction cases (13%) but less than that of CML-CP cases (86%). We conclude that pre-CML should be suspected in patients with a normal to mildly elevated WBC and absolute basophilia. Bone marrow examination can usually distinguish pre-CML from a leukemoid reaction based on the percentage of small, hypolobated megakaryocytes; microvascular density; and morphologic features. PMID:27040932

  15. Effects of Sled Towing on Peak Force, the Rate of Force Development and Sprint Performance During the Acceleration Phase.

    PubMed

    Martínez-Valencia, María Asunción; Romero-Arenas, Salvador; Elvira, José L L; González-Ravé, José María; Navarro-Valdivielso, Fernando; Alcaraz, Pedro E

    2015-06-27

    Resisted sprint training is believed to increase strength specific to sprinting. Therefore, the knowledge of force output in these tasks is essential. The aim of this study was to analyze the effect of sled towing (10%, 15% and 20% of body mass (Bm)) on sprint performance and force production during the acceleration phase. Twenty-three young experienced sprinters (17 men and 6 women; men = 17.9 ± 3.3 years, 1.79 ± 0.06 m and 69.4 ± 6.1 kg; women = 17.2 ± 1.7 years, 1.65 ± 0.04 m and 56.6 ± 2.3 kg) performed four 30 m sprints from a crouch start. Sprint times in 20 and 30 m sprint, peak force (Fpeak), a peak rate of force development (RFDpeak) and time to RFD (TRFD) in first step were recorded. Repeated-measures ANOVA showed significant increases (p ≤ 0.001) in sprint times (20 and 30 m sprint) for each resisted condition as compared to the unloaded condition. The RFDpeak increased significantly when a load increased (3129.4 ± 894.6 N·s-1, p ≤ 0.05 and 3892.4 ± 1377.9 N·s-1, p ≤ 0.01). Otherwise, no significant increases were found in Fpeak and TRFD. The RFD determines the force that can be generated in the early phase of muscle contraction, and it has been considered a factor that influences performance of force-velocity tasks. The use of a load up to 20% Bm might provide a training stimulus in young sprinters to improve the RFDpeak during the sprint start, and thus, early acceleration.

  16. Effects of Sled Towing on Peak Force, the Rate of Force Development and Sprint Performance During the Acceleration Phase

    PubMed Central

    Martínez-Valencia, María Asunción; Romero-Arenas, Salvador; Elvira, José L.L.; González-Ravé, José María; Navarro-Valdivielso, Fernando; Alcaraz, Pedro E.

    2015-01-01

    Resisted sprint training is believed to increase strength specific to sprinting. Therefore, the knowledge of force output in these tasks is essential. The aim of this study was to analyze the effect of sled towing (10%, 15% and 20% of body mass (Bm)) on sprint performance and force production during the acceleration phase. Twenty-three young experienced sprinters (17 men and 6 women; men = 17.9 ± 3.3 years, 1.79 ± 0.06 m and 69.4 ± 6.1 kg; women = 17.2 ± 1.7 years, 1.65 ± 0.04 m and 56.6 ± 2.3 kg) performed four 30 m sprints from a crouch start. Sprint times in 20 and 30 m sprint, peak force (Fpeak), a peak rate of force development (RFDpeak) and time to RFD (TRFD) in first step were recorded. Repeated-measures ANOVA showed significant increases (p ≤ 0.001) in sprint times (20 and 30 m sprint) for each resisted condition as compared to the unloaded condition. The RFDpeak increased significantly when a load increased (3129.4 ± 894.6 N·s−1, p ≤ 0.05 and 3892.4 ± 1377.9 N·s−1, p ≤ 0.01). Otherwise, no significant increases were found in Fpeak and TRFD. The RFD determines the force that can be generated in the early phase of muscle contraction, and it has been considered a factor that influences performance of force-velocity tasks. The use of a load up to 20% Bm might provide a training stimulus in young sprinters to improve the RFDpeak during the sprint start, and thus, early acceleration. PMID:26240657

  17. Quantification of hepatic blood flow using a high-resolution phase-contrast MRI sequence with compressed sensing acceleration.

    PubMed

    Dyvorne, Hadrien A; Knight-Greenfield, Ashley; Besa, Cecilia; Cooper, Nancy; Garcia-Flores, Julio; Schiano, Thomas D; Markl, Michael; Taouli, Bachir

    2015-03-01

    OBJECTIVE. The objective of our study was to evaluate the performance of a high-spatial-resolution 2D phase-contrast (PC) MRI technique accelerated with compressed sensing for portal vein (PV) and hepatic artery (HA) flow quantification in comparison with a standard PC MRI sequence. SUBJECTS AND METHODS. In this prospective study, two PC MRI sequences were compared, one with parallel imaging acceleration and low spatial resolution (generalized autocalibrating partial parallel acquisition [GRAPPA]) and one with compressed sensing acceleration and high spatial resolution (sparse). Seventy-six patients were assessed, including 37 patients with cirrhosis. Two observers evaluated PC image quality. Quantitative analyses yielded a mean velocity, flow, and vessel area for the PV and HA and an arterial fraction. The PC techniques were compared using the paired Wilcoxon test and Bland-Altman statistics. The sensitivity of the flow parameters to the severity of cirrhosis was also assessed. RESULTS. Vessel delineation was significantly improved using the PC sparse sequence (p < 0.034). For both in vitro and in vivo measurements, PC sparse yielded lower estimates for vessel area and flow, and larger differences between PC GRAPPA and PC sparse were observed in the HA. PV velocity and flow were significantly lower in patients with cirrhosis on both PC sparse (p < 0.001 and p = 0.042, respectively) and PC GRAPPA (p < 0.001 and p = 0.005, respectively). PV velocity correlated negatively with Child-Pugh class (r = -0.50, p < 0.001), whereas the arterial fraction measured with PC sparse was higher in patients with Child-Pugh class B or C disease than in those with Child-Pugh class A disease, with a trend toward significance (p = 0.055). CONCLUSION. A high-spatial-resolution highly accelerated compressed sensing technique (PC sparse) allows total hepatic blood flow measurements obtained in 1 breath-hold, provides improved delineation of the hepatic vessels compared with a standard PC

  18. Accelerated Phase of Chediak-Higashi Syndrome at Initial Presentation: A Case Report of an Uncommon Occurrence in a Rare Disorder

    PubMed Central

    Jaiswal, Pooja; Bhasker, Nilam; Kushwaha, Rashmi

    2015-01-01

    Chediak-Higashi syndrome (CHS) is an uncommon and fatal congenital disorder. The characteristic features of CHS are partial oculocutaneous albinism, increased vulnerability to infections, presence of abnormal large granules in leukocytes and an accelerated lymphohistiocytic phase. Accelerated phase at initial presentation is rarely seen as it is usually preceded by repeated episodes of infections. Hence this interesting case of a four-month-old Indian child born to consanguineous parents in accelerated phase at initial presentation is described. The boy presented with fever, hepatosplenomegaly, and cleft lip. Clinical diagnosis was leukemia or a lysosomal storage disorder. Cytopaenias, lymphohistiocytic infiltration in bone marrow, and the characteristic large granules in leucocytes helped in the diagnosis, emphasizing the importance of bone marrow in diagnosis of unusual presentation of this rare disorder. PMID:26816903

  19. Accelerated Phase of Chediak-Higashi Syndrome at Initial Presentation: A Case Report of an Uncommon Occurrence in a Rare Disorder.

    PubMed

    Jaiswal, Pooja; Yadav, Yogesh Kumar; Bhasker, Nilam; Kushwaha, Rashmi

    2015-12-01

    Chediak-Higashi syndrome (CHS) is an uncommon and fatal congenital disorder. The characteristic features of CHS are partial oculocutaneous albinism, increased vulnerability to infections, presence of abnormal large granules in leukocytes and an accelerated lymphohistiocytic phase. Accelerated phase at initial presentation is rarely seen as it is usually preceded by repeated episodes of infections. Hence this interesting case of a four-month-old Indian child born to consanguineous parents in accelerated phase at initial presentation is described. The boy presented with fever, hepatosplenomegaly, and cleft lip. Clinical diagnosis was leukemia or a lysosomal storage disorder. Cytopaenias, lymphohistiocytic infiltration in bone marrow, and the characteristic large granules in leucocytes helped in the diagnosis, emphasizing the importance of bone marrow in diagnosis of unusual presentation of this rare disorder. PMID:26816903

  20. Chronic Psychological Stress Disrupted the Composition of the Murine Colonic Microbiota and Accelerated a Murine Model of Inflammatory Bowel Disease

    PubMed Central

    Watanabe, Yohei; Arase, Sohei; Nagaoka, Noriko; Kawai, Mitsuhisa; Matsumoto, Satoshi

    2016-01-01

    The effect of psychological stress on the gastrointestinal microbiota is widely recognized. Chronic psychological stress may be associated with increased disease activity in inflammatory bowel disease, but the relationships among psychological stress, the gastrointestinal microbiota, and the severity of colitis is not yet fully understood. Here, we examined the impact of 12-week repeated water-avoidance stress on the microbiota of two inbred strains of T cell receptor alpha chain gene knockout mouse (background, BALB/c and C57BL/6) by means of next-generation sequencing of bacterial 16S rRNA genes. In both mouse strains, knockout of the T cell receptor alpha chain gene caused a loss of gastrointestinal microbial diversity and stability. Chronic exposure to repeated water-avoidance stress markedly altered the composition of the colonic microbiota of C57BL/6 mice, but not of BALB/c mice. In C57BL/6 mice, the relative abundance of genus Clostridium, some members of which produce the toxin phospholipase C, was increased, which was weakly positively associated with colitis severity, suggesting that expansion of specific populations of indigenous pathogens may be involved in the exacerbation of colitis. However, we also found that colitis was not exacerbated in mice with a relatively diverse microbiota even if their colonic microbiota contained an expanded phospholipase C-producing Clostridium population. Exposure to chronic stress also altered the concentration of free immunoglobulin A in colonic contents, which may be related to both the loss of bacterial diversity in the colonic microbiota and the severity of the colitis exacerbation. Together, these results suggest that long-term exposure to psychological stress induces dysbiosis in the immunodeficient mouse in a strain-specific manner and also that alteration of microbial diversity, which may be related to an altered pattern of immunoglobulin secretion in the gastrointestinal tract, might play a crucial role in the

  1. Chronic Psychological Stress Disrupted the Composition of the Murine Colonic Microbiota and Accelerated a Murine Model of Inflammatory Bowel Disease.

    PubMed

    Watanabe, Yohei; Arase, Sohei; Nagaoka, Noriko; Kawai, Mitsuhisa; Matsumoto, Satoshi

    2016-01-01

    The effect of psychological stress on the gastrointestinal microbiota is widely recognized. Chronic psychological stress may be associated with increased disease activity in inflammatory bowel disease, but the relationships among psychological stress, the gastrointestinal microbiota, and the severity of colitis is not yet fully understood. Here, we examined the impact of 12-week repeated water-avoidance stress on the microbiota of two inbred strains of T cell receptor alpha chain gene knockout mouse (background, BALB/c and C57BL/6) by means of next-generation sequencing of bacterial 16S rRNA genes. In both mouse strains, knockout of the T cell receptor alpha chain gene caused a loss of gastrointestinal microbial diversity and stability. Chronic exposure to repeated water-avoidance stress markedly altered the composition of the colonic microbiota of C57BL/6 mice, but not of BALB/c mice. In C57BL/6 mice, the relative abundance of genus Clostridium, some members of which produce the toxin phospholipase C, was increased, which was weakly positively associated with colitis severity, suggesting that expansion of specific populations of indigenous pathogens may be involved in the exacerbation of colitis. However, we also found that colitis was not exacerbated in mice with a relatively diverse microbiota even if their colonic microbiota contained an expanded phospholipase C-producing Clostridium population. Exposure to chronic stress also altered the concentration of free immunoglobulin A in colonic contents, which may be related to both the loss of bacterial diversity in the colonic microbiota and the severity of the colitis exacerbation. Together, these results suggest that long-term exposure to psychological stress induces dysbiosis in the immunodeficient mouse in a strain-specific manner and also that alteration of microbial diversity, which may be related to an altered pattern of immunoglobulin secretion in the gastrointestinal tract, might play a crucial role in the

  2. Studies on solar hard X-Rays and gamma-rays: Compton backscatter, anisotropy, polarization and evidence for two phases of acceleration. Ph.D. Thesis - Maryland Univ.

    NASA Technical Reports Server (NTRS)

    Bai, T.

    1977-01-01

    Observations of solar X-rays and gamma-rays from large flares show that the hard X-ray spectrum extends into the gamma ray region, where a flattening in the spectrum of the continuum emission is observed above about 1 MeV. This emission is believed to be due to bremsstrahlung. In addition to electron-proton collisions, at energies greater than approximately 500 keV, bremsstrahlung due to electron-electron collisions becomes significant. Bremsstrahlung production was calculated for a variety of electron spectra extending from the nonrelativistic region to relativistic energies and electron-electron bremsstrahlung is taken into account. By comparing these calculations with data, it is shown that the flattening in the spectrum of the continuum emission can be best explained by an electron spectrum consisting of two distinctive components. This evidence, together with information on the X-ray and gamma ray time profiles, implied the existence of two phases of acceleration. The first phase accelerates electrons mainly up to about several hundred keV; the second phase accelerates a small fraction of the electrons accelerated in the first phase to relativistic energies and accelerates protons to tens and hundreds of MeV.

  3. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia

    PubMed Central

    Flynn, Joseph M.; Kipps, Thomas J.; Boxer, Michael; Kolibaba, Kathryn S.; Carlile, David J.; Fingerle-Rowson, Guenter; Tyson, Nicola; Hirata, Jamie; Sharman, Jeff P.

    2016-01-01

    Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at www.clinicaltrials.gov as #NCT01414205. PMID:26472752

  4. Proposition of a Classification of Adult Patients with Hemiparesis in Chronic Phase

    PubMed Central

    Filipetti, Paul; Remacle, Angélique; Kolanowski, Elisabeth

    2016-01-01

    Background Patients who have developed hemiparesis as a result of a central nervous system lesion, often experience reduced walking capacity and worse gait quality. Although clinically, similar gait patterns have been observed, presently, no clinically driven classification has been validated to group these patients’ gait abnormalities at the level of the hip, knee and ankle joints. This study has thus intended to put forward a new gait classification for adult patients with hemiparesis in chronic phase, and to validate its discriminatory capacity. Methods and Findings Twenty-six patients with hemiparesis were included in this observational study. Following a clinical examination, a clinical gait analysis, complemented by a video analysis, was performed whereby participants were requested to walk spontaneously on a 10m walkway. A patient’s classification was established from clinical examination data and video analysis. This classification was made up of three groups, including two sub-groups, defined with key abnormalities observed whilst walking. Statistical analysis was achieved on the basis of 25 parameters resulting from the clinical gait analysis in order to assess the discriminatory characteristic of the classification as displayed by the walking speed and kinematic parameters. Results revealed that the parameters related to the discriminant criteria of the proposed classification were all significantly different between groups and subgroups. More generally, nearly two thirds of the 25 parameters showed significant differences (p<0.05) between the groups and sub-groups. However, prior to being fully validated, this classification must still be tested on a larger number of patients, and the repeatability of inter-operator measures must be assessed. Conclusions This classification enables patients to be grouped on the basis of key abnormalities observed whilst walking and has the advantage of being able to be used in clinical routines without necessitating

  5. A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy.

    PubMed

    Awan, Farrukh T; Jones, Jeffrey A; Maddocks, Kami; Poi, Ming; Grever, Michael R; Johnson, Amy; Byrd, John C; Andritsos, Leslie A

    2016-06-01

    Patients with chronic lymphocytic leukemia (CLL) who receive chemoimmunotherapy and do not achieve complete remission experience significantly shortened progression-free interval (PFS). Additionally, the majority of patients treated for relapsed disease demonstrate evidence of measurable disease. Eradication of minimal residual disease (MRD) results in improved PFS and overall survival. Maintenance therapy might result in eradication of MRD and improve response duration but might be associated with an increase in incidence of infectious complications. Flavopiridol is a broad cyclin-dependent kinase (CDK) inhibitor with established safety and efficacy in patients with relapsed CLL, particularly patients with high-risk cytogenetic features. A pharmacologically derived schedule was utilized as consolidation therapy in this phase I study to assess the safety and feasibility of outpatient therapy with flavopiridol in patients with low tumor burden. Flavopiridol was administered as a 30-min loading dose of 30 mg/m(2) followed by a 4-h infusion of 30 mg/m(2) once weekly for 3 weeks every 5 weeks (1 cycle) for planned 2 cycles in ten patients. Therapy was extremely well tolerated and no patient developed acute tumor lysis syndrome. The most common toxicities were gastrointestinal. Of the patients, 22 % improved their response from a PR to CR. Eighty-eight percent experienced a reduction in tumor burden as measured by extent of bone marrow involvement including patients with del17p and complex karyotype. The study establishes the safety and efficacy of flavopiridol as consolidation therapy after chemoimmunotherapy for patients with CLL. Further evaluation is required in larger trials for the utility of CDK inhibitors as consolidation or maintenance strategies.Registration number at ClinicalTrials.gov: NCT00377104. PMID:27118540

  6. Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a phase IV, non-interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia.

    PubMed

    Moreno, Carol; Montillo, Marco; Panayiotidis, Panayiotis; Dimou, Maria; Bloor, Adrian; Dupuis, Jehan; Schuh, Anna; Norin, Stefan; Geisler, Christian; Hillmen, Peter; Doubek, Michael; Trněný, Marek; Obrtlikova, Petra; Laurenti, Luca; Stilgenbauer, Stephan; Smolej, Lukas; Ghia, Paolo; Cymbalista, Florence; Jaeger, Ulrich; Stamatopoulos, Kostas; Stavroyianni, Niki; Carrington, Patrick; Zouabi, Hamadi; Leblond, Veronique; Gomez-Garcia, Juan C; Rubio, Martin; Marasca, Roberto; Musuraca, Gerardo; Rigacci, Luigi; Farina, Lucia; Paolini, Rossella; Pospisilova, Sarka; Kimby, Eva; Bradley, Colm; Montserrat, Emili

    2015-04-01

    We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. Total number of patients was 103; median age was 65 years (range 39-85). Median number of prior lines of therapy was 4 (range 1-13), including, in most cases, rituximab-, fludarabine- and alemtuzumab-based regimens; 13 patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3-4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. This study is registered at clinicaltrials.gov identifier:01453062.

  7. Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a Phase IV, non-interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia

    PubMed Central

    Moreno, Carol; Montillo, Marco; Panayiotidis, Panayiotis; Dimou, Maria; Bloor, Adrian; Dupuis, Jehan; Schuh, Anna; Norin, Stefan; Geisler, Christian; Hillmen, Peter; Doubek, Michael; Trněný, Marek; Obrtlikova, Petra; Laurenti, Luca; Stilgenbauer, Stephan; Smolej, Lukas; Ghia, Paolo; Cymbalista, Florence; Jaeger, Ulrich; Stamatopoulos, Kostas; Stavroyianni, Niki; Carrington, Patrick; Zouabi, Hamadi; Leblond, Veronique; Gomez-Garcia, Juan C.; Rubio, Martin; Marasca, Roberto; Musuraca, Gerardo; Rigacci, Luigi; Farina, Lucia; Paolini, Rossella; Pospisilova, Sarka; Kimby, Eva; Bradley, Colm; Montserrat, Emili

    2015-01-01

    We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. Total number of patients was 103; median age was 65 years (range 39–85). Median number of prior lines of therapy was 4 (range 1–13), including, in most cases, rituximab-, fludarabine- and alemtuzumab-based regimens; 13 patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3–4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. This study is registered at clinicaltrials.gov identifier:01453062. PMID:25596264

  8. IFAT and ELISA phase I/phase II as tools for the identification of Q fever chronic milk shedders in cattle.

    PubMed

    Lucchese, Laura; Capello, Katia; Barberio, Antonio; Zuliani, Federica; Stegeman, Arjan; Ceglie, Letizia; Guerrini, Eulalia; Marangon, Stefano; Natale, Alda

    2015-08-31

    Q fever is a widespread zoonotic disease caused by Coxiella burnetii. In cattle the bacterial shedding can persist without symptoms for several months and the shedders identification is a critical issue in the control of the infection at herd level. Following the example of the human protocols for the assessment of Q fever infection status, the aim of this study was the evaluation of the antibody response dynamics to phase I and phase II antigens in C. burnetii shedder dairy cows by means of a phase-specific serology, to verify the suitability of the investigated tools in recognising milk shedders. A total of 99 cows were monitored during time and classified on the basis of serological and PCR results in five groups identifying different shedding patterns. The 297 sera collected in three sampling times were tested by means of ELISA IgG for differential phase I and phase II antibodies detection, while a selection of 107 sera were tested by means of phase specific IgM and IgG IFAT. Both ELISA IgG and IFAT IgG highlighted a low reactivity in non-shedder seropositive animals compared to chronic milk shedder animals. ELISA IgG seemed to perform better than IFAT IgG-IgM, showing significant serological differences among groups that allowed recognising specific serological group patterns, in particular for chronic and occasional milk shedders. These results supported the hypothesis that an animal classification based on phase patterns is reasonable, although it needs to be further investigated.

  9. A low bioimpedance phase angle predicts a higher mortality and lower nutritional status in chronic dialysis patients

    NASA Astrophysics Data System (ADS)

    Dumler Md, Francis

    2010-04-01

    Bioelectrical impedance analysis is an established technique for body composition analysis. The phase angle parameter, an index of body cell mass, tissue hydration, and membrane integrity, makes it suitable for assessing nutritional status and survivability. We evaluated the significance of a low phase angle value on nutritional status and mortality in 285 chronic dialysis patients during a longitudinal prospective observational study. Patients in the lower phase angle tertile had decreased body weight, body mass index, fat free mass, body cell mass, and lower serum albumin concentrations than those in the higher tertile (P<001). In addition, mortality rates were significantly lower (P=0.05) in the highest tertile patients. In conclusion, the phase angle is a useful method for identifying dialysis patients at high risk for malnutrition and increased mortality.

  10. Phase II study of accelerated fractionation radiation therapy with carboplatin followed by vincristine chemotherapy for the treatment of glioblastoma multiforme

    SciTech Connect

    Levin, V.A.; Yung, W.K.A.; Kyritsis, A.P.

    1995-09-30

    The purpose of this investigation was to conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with intravenous carboplatin for patients with previously untreated glioblastoma multiforme tumors. Between 1988 and 1992, 83 patients received 1.9-2.0 Gy radiation three times a day with 2-h infusions of 33 mg/m{sup 2} carboplatin for two 5-day cycles separated by 2 weeks. Seventy-four of the 83 patients (89%) received one or more courses of PCV; their median survival was 55 weeks. Total resection was performed in 20% (15 of 74), subtotal resection in 69% (51 or 74), and biospy in 11% (8 of 74); reoperation (total or subtotal resection) was performed in 28 patients (37%). Survival was worst for those {ge} 61 year old (median 35 weeks). Fits of the Cox proportional hazards regression model showed covariated individually predictive of improved survival were younger age (p <0.01), smaller log of radiation volume (p = 0.008), total or subtotal resection vs. biopsy (p = 0.056), and higher Karnofsky performance status (p = 0.055). A multivariate analysis showed that age (p = 0.013) and extent of initial surgery (p = 0.003) together were predictive of a better survival with no other variables providing additional significance. Only 8.4% (7 of 83) of patients had clinically documented therapy-associated neurotoxicity ({open_quotes}radiation necrosis{close_quotes}). When comparable selection criteria were applied, the survival in this study is similar to the results currently attainable with other chemoradiation approaches. The relative safety of accelerated fractionated radiotherapy, as used in this study with carboplatin, enables concomitant full-dose administration of chemotherapy or radiosensitizing agents in glioblastoma multiforme patients. 42 refs., 3 figs., 5 tabs.

  11. Chronic Central Nervous System Expression of HIV-1 Tat Leads to Accelerated Rarefaction of Neocortical Capillaries and Loss of Red Blood Cell Velocity Heterogeneity

    PubMed Central

    Silva, Jharon N.; Polesskaya, Oksana; Wei, Helen S.; Rasheed, Izad-Yar D.; Chamberlain, Jeffrey M.; Nishimura, Christopher; Feng, Changyong; Dewhurst, Stephen

    2014-01-01

    Objectives HIV-1 infection of the central nervous system is associated with impairment of cerebral blood flow and neurocognitive function, and accelerated signs of aging. Since normal aging is associated with rarefaction of the cerebral vasculature, we set out to examine chronic viral effects on the cerebral vasculature. Methods Doxycycline-inducible HIV-1 Tat transgenic (Tat-tg) and wild-type (WT) control mice were used. Animals were treated with doxycycline for 3 weeks or 5–7 months. Cerebral vessel density and capillary segment length were determined from quantitative image analyses of sectioned cortical tissue. In addition, movement of red blood cells in individual capillaries was imaged in vivo using multiphoton microscopy, to determine red blood cell velocity and flux. Results Mean RBCV was not different between Tat-tg mice and age matched WT controls. However, cortical capillaries from Tat-tg mice showed a significant loss of RBCV heterogeneity and increased RBCF that was attributed to a marked decrease in total cortical capillary length (35–40%) compared to WT mice. Conclusions Cerebrovascular rarefaction is accelerated in HIV-1 Tat transgenic mice, and this is associated with alterations in red cell blood velocity. These changes may have relevance to the pathogenesis of HIV-associated neurocognitive disorders in an aging HIV positive population. PMID:24813724

  12. A Critical Review of Trials of First-Line BCR-ABL Inhibitor Treatment in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase

    PubMed Central

    Jabbour, Elias; Lipton, Jeffrey H.

    2015-01-01

    The characteristic expression of the constitutively active oncoprotein, BCR-ABL tyrosine kinase, in chronic myeloid leukemia (CML) was the basis for the development of BCR-ABL tyrosine kinase inhibitors for treatment. Three BCR-ABL inhibitors, imatinib, nilotinib, and dasatinib, have been approved by the US Food and Drug Administration for first-line treatment of patients with newly diagnosed CML in chronic phase (CML-CP). This article reviews the key phase III clinical trials supporting the use of first-line imatinib, nilotinib, and dasatinib in patients with CML-CP as well as findings of supportive phase II studies. At the time of its approval in 2001, imatinib induced unprecedented response rates in patients with CML-CP; however, resistance and intolerance to imatinib prevent 20% to 30% of patients from deriving full therapeutic benefit. Nilotinib and dasatinib, both approved in 2010 for first-line CML-CP treatment, are more potent than imatinib and less susceptible to imatinib resistance mechanisms. Comparative clinical trials of each agent with imatinib have shown that they are associated with significantly deeper and more rapid responses than standard-dose imatinib, without compromising safety. Given that evidence suggests achievement of an early response is predictive of improved long-term outcomes, earlier use of these compounds may lead to more rapid, deeper responses corresponding with improvements in patient outcome. Although future studies will benefit from more uniform definitions of endpoints and methods of analysis, data from published studies of first-line BCR-ABL inhibitor treatment for patients with newly diagnosed CML-CP support the use of either dasatinib or nilotinib in place of imatinib. PMID:24095296

  13. RBC-/Cr-51/ half-life and albumin turnover in growing Beagle dogs during chronic radial acceleration

    NASA Technical Reports Server (NTRS)

    Beckman, D. A.; Evans, J. W.; Oyama, J.

    1979-01-01

    The effects of chronic centrifugation on growing Beagle dogs exposed to -2 or -2.6 Gx on albumin and RBC turnover rates, albumin concentration and space, and total blood volume were determined and compared with caged and run control of animals. Albumin-(I-125) and autologous RBC-(Cr-51) preparations were injected into all dogs at day 82 of the centrifugation periods, and the disappearance curves were determined by successive bleedings of the animals over the next 35 d, during which the centrifugation was continued. There were no differences in albumin turnover rates or space. Two populations of RBCs were found in both centrifugated groups, one with a normal half-life of 27 + or - 1 S.E.M. d, and one with a significantly (p less than 0.01) shorter half-life of 15 + or - 2 S.E.M. d. An absolute polycythemia was also observed in both centrifuged groups. The results suggest that chronic centrifugation acts through some as-yet unknown mechanism to affect RBC population kinetics.

  14. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment.

    PubMed

    Kim-Fuchs, Corina; Le, Caroline P; Pimentel, Matthew A; Shackleford, David; Ferrari, Davide; Angst, Eliane; Hollande, Frédéric; Sloan, Erica K

    2014-08-01

    Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of β-adrenergic signaling induced similar effects to chronic stress, and pharmacological β-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural β-adrenergic signaling regulates pancreatic cancer progression and suggest β-blockade as a novel strategy to complement existing therapies for pancreatic cancer.

  15. Clinical significance of serum pancreatic enzymes in the quiescent phase of chronic pancreatitis.

    PubMed

    Lesi, C; Melzi D'Eril, G V; Pavesi, F; Scandellari, A; Faccenda, F; Grazia Casertano, M; Savoia, M; Zoni, L; Peppi, M

    1985-08-01

    The most commonly used serum enzymes in pancreatic diseases are total amylase, pancreatic isoamylase, lipase and trypsin. To determine which of these enzymes is the most useful in the diagnosis of clinically quiescent chronic pancreatitis and which enzyme best reflects exocrine functional reserve, we studied 22 healthy control subjects, 44 patients with gastrointestinal, liver and biliary tract diseases, and 25 patients with chronic pancreatitis. On the basis of duodenal intubation, the latter were divided into two subgroups: one group of 13 patients with slight to moderate secretion deficiency and another of 12 patients with severe exocrine insufficiency. Of the enzymes studied, lipase, trypsin and pancreatic isoamylase are equally suitable for the evaluation of function in severe chronic pancreatitis, but not for the early diagnosis of the disease. Results for total amylase are not reliable so that its use in the study of chronic pancreatitis is not advisable.

  16. A Phase I Study of Short-Course Accelerated Whole Brain Radiation Therapy for Multiple Brain Metastases

    SciTech Connect

    Caravatta, Luciana; Deodato, Francesco; Ferro, Marica; Macchia, Gabriella; Massaccesi, Mariangela; Cilla, Savino; Padula, Gilbert D.A.; Mignogna, Samantha; Tambaro, Rosa; Carrozza, Francesco; Flocco, Mariano; Cantore, Giampaolo; Scapati, Andrea; Buwenge, Milly; and others

    2012-11-15

    Purpose: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Methods and Materials: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class > or =2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status {<=}3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity {>=}grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. Results: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). Conclusions: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

  17. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  18. Effect of insertion of xanthan-based chlorhexidine gel in the maintenance phase following the treatment of chronic periodontitis

    PubMed Central

    Verma, Ashish; Sanghi, Swati; Grover, Dimple; Aggarwal, Shweta; Gupta, Rajan; Pandit, Nymphea

    2012-01-01

    Objectives: The aim of this study was to evaluate the efficacy of subgingivally administered xanthan-based chlorhexidine gel when used in the maintenance phase following scaling and root planing (SRP) in the treatment of chronic periodontitis. Materials and Methods: A randomized, controlled, single-center study was conducted involving 92 sites in 46 systemically healthy patients suffering from moderate to advanced chronic periodontitis with isolated pockets. The selected sites were randomized to two treatment arms: Group A (SRP alone) and Group B (SRP + insertion of chlorhexidine gel after 1 month). The gingival index, plaque index, probing pocket depth (PPD) and clinical attachment level (CAL) were recorded at baseline and subsequently after 1 month and 3 months. Results: Both the groups showed significant reductions in PPD and CAL at both follow-up visits when compared with the baseline values (P<0.001). Conclusions: The results suggest that the application of xanthan based chlorhexidine gel following SRP in the maintenance phase might be beneficial in treatment of the chronic periodontitis in comparison to SRP alone. Greater improvements may be achieved when antimicrobial agents are used following SRP. PMID:23162333

  19. BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase

    PubMed Central

    Hughes, T P; Saglio, G; Quintás-Cardama, A; Mauro, M J; Kim, D-W; Lipton, J H; Bradley-Garelik, M B; Ukropec, J; Hochhaus, A

    2015-01-01

    BCR-ABL1 mutations are a common, well-characterized mechanism of resistance to imatinib as first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). Less is known about mutation development during first-line treatment with dasatinib and nilotinib, despite increased use because of higher response rates compared with imatinib. Retrospective analyses were conducted to characterize mutation development in patients with newly diagnosed CML-CP treated with dasatinib (n=259) or imatinib (n=260) in DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML-CP), with 3-year minimum follow-up. Mutation screening, including patients who discontinued treatment and patients who had a clinically relevant on-treatment event (no confirmed complete cytogenetic response (cCCyR) and no major molecular response (MMR) within 12 months; fivefold increase in BCR-ABL1 with loss of MMR; loss of CCyR), yielded a small number of patients with mutations (dasatinib, n=17; imatinib, n=18). Dasatinib patients had a narrower spectrum of mutations (4 vs 12 sites for dasatinib vs imatinib), fewer phosphate-binding loop mutations (1 vs 9 mutations), fewer multiple mutations (1 vs 6 patients) and greater occurrence of T315I (11 vs 0 patients). This trial was registered at www.clinicaltrials.gov as NCT00481247. PMID:26118315

  20. The long-term clinical implications of clonal chromosomal abnormalities in newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib mesylate.

    PubMed

    Lee, Sung-Eun; Choi, Soo Young; Bang, Ju-Hee; Kim, Soo-Hyun; Jang, Eun-Jung; Byeun, Ji-Young; Park, Jin Eok; Jeon, Hye-Rim; Oh, Yun Jeong; Kim, Myungshin; Kim, Dong-Wook

    2012-11-01

    The aim of this study was to evaluate the long-term clinical significance of an additional chromosomal abnormality (ACA), variant Philadelphia chromosome (vPh) at diagnosis, and newly developed other chromosomal abnormalities (OCA) in patients with chronic myeloid leukemia (CML) on imatinib (IM) therapy. Sequential cytogenetic data from 281 consecutive new chronic phase CML patients were analyzed. With a median follow-up of 78.6 months, the 22 patients with vPh (P = 0.034) or ACA (P = 0.034) at diagnosis had more events of IM failure than did the patients with a standard Ph. The 5-year overall survival (OS), event-free survival (EFS), and failure-free survival (FFS) rates for patients with vPh at diagnosis were 77.8%, 75.0%, and 53.3%, respectively; for patients with ACA at diagnosis, 100%, 66.3%, and 52.1%, respectively; and for patients with a standard Ph, 96.0%, 91.3%, and 83.7%, respectively. During IM therapy, eight patients developed an OCA, which had no impact on outcomes as a time-dependent covariate in our Cox proportional hazards regression models. This study showed that vPh was associated with poor OS and FFS and that ACA had adverse effects on EFS and FFS. In addition, no OCA, except monosomy 7, had any prognostic impact, suggesting that the development of OCA may not require a change in treatment strategy. PMID:23111092

  1. Long-term results of high-dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience.

    PubMed

    Giona, Fiorina; Putti, Maria C; Micalizzi, Concetta; Menna, Giuseppe; Moleti, Maria L; Santoro, Nicola; Iaria, Grazia; Ladogana, Saverio; Burnelli, Roberta; Consarino, Caterina; Varotto, Stefania; Tucci, Francesca; Messina, Chiara; Nanni, Mauro; Diverio, Daniela; Biondi, Andrea; Pession, Andrea; Locatelli, Franco; Piciocchi, Alfonso; Gottardi, Enrico; Saglio, Giuseppe; Foà, Robin

    2015-08-01

    Imatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its long-term efficacy in children are not well defined. The purpose of this multicentre study is to report on the long-term results of high-dose IM (340 mg/m2 /d) in CML patients in chronic phase (CP-CML) aged <18 years at diagnosis. A total of 47 CP-CML patients with a median age at diagnosis of 11 years 9 months were enrolled in nine Italian centres. Complete cytogenetic response was achieved in 91.5% of the evaluable patients at a median time of 6 months. BCR-ABL1 International Scale ≤ 0.1% (major molecular response; MMR) and ≤0.01% (molecular response; MR) at 12 months were 66.6% and 33%, respectively. During follow-up, MMR and MR were achieved in 78.6% and 61% of children, respectively. IM was safely discontinued in 3 long-term treated children with a durable MR. Twelve patients (eight cytogenetic/molecular responders) underwent stem cell transplantation. The progression-free survival probabilities at 96 months for responding patients who continued IM and for those transplanted were 60% and 50%, respectively. After a median follow-up of 52 months (range 3-146), all patients are alive. High-dose IM is a long-term effective therapy in children and adolescents with CP-CML.

  2. Higher Red Blood Cell Distribution Width Is an Adverse Prognostic Factor in Chronic-phase Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors.

    PubMed

    Iriyama, Noriyoshi; Hatta, Yoshihiro; Kobayashi, Sumiko; Uchino, Yoshihito; Miura, Katsuhiro; Kurita, Daisuke; Kodaira, Hitomi; Takahashi, Hiromichi; Iizuka, Yoshikazu; Inoue, Mitsuru; Takei, Masami

    2015-10-01

    The significance of red blood cell distribution width (RDW) was evaluated in patients with chronic myeloid leukemia (CML) in the chronic phase (CP). Eighty-four patients with newly-diagnosed CML-CP treated with any tyrosine kinase inhibitor (TKI) were analyzed. Patients were divided into two groups: a low-RDW group (RDW values ≤15%, n=31) and a high-RDW group (RDW values >15%, n=53). The 5-year event-free survival (EFS) and transformation-free survival (TFS) rates differed significantly between the low- and high-RDW groups (100% and 68%, respectively, in EFS, p=0.0071 and 100% and 81%, respectively, in TFS, p=0.039). The stratification by RDW had an impact on overall 5-year survival (100% in the low and 77% in the high RDW groups, p=0.047). We conclude that the RDW has a critical role in risk stratification of CML-CP patients for predicting treatment responses and outcomes.

  3. Preliminary results of a phase I/II study of sodium pentosanpolysulfate in the treatment of chronic radiation-induced proctitis

    SciTech Connect

    Grigsby, P.W.; Pilepich, M.V.; Parsons, C.L. )

    1990-02-01

    This is a report of a phase I/II study of 13 patients treated with sodium pentosanpolysulfate (PPS) for chronic radiation-induced proctitis. A complete response was obtained in 82%, a partial response occurred in 9%, and 9% failed to respond to therapy. No significant toxicity was observed. It is concluded that PPS is an effective treatment for chronic radiation-induced proctitis and a phase III randomized, double-blind study of PPS versus placebo is planned.

  4. Evaluation of acceleration and deceleration cardiac processes using phase-rectified signal averaging in healthy and idiopathic dilated cardiomyopathy subjects.

    PubMed

    Bas, Rosana; Vallverdú, Montserrat; Valencia, Jose F; Voss, Andreas; de Luna, Antonio Bayés; Caminal, Pere

    2015-02-01

    The aim of the present study was to investigate the suitability of the Phase-Rectified Signal Averaging (PRSA) method for improved risk prediction in cardiac patients. Moreover, this technique, which separately evaluates acceleration and deceleration processes of cardiac rhythm, allows the effect of sympathetic and vagal modulations of beat-to-beat intervals to be characterized. Holter recordings of idiopathic dilated cardiomyopathy (IDC) patients were analyzed: high-risk (HR), who suffered sudden cardiac death (SCD) during the follow-up; and low-risk (LR), without any kind of cardiac-related death. Moreover, a control group of healthy subjects was analyzed. PRSA indexes were analyzed, for different time scales T and wavelet scales s, from RR series of 24 h-ECG recordings, awake periods and sleep periods. Also, the behavior of these indexes from simulated data was analyzed and compared with real data results. Outcomes demonstrated the PRSA capacity to significantly discriminate healthy subjects from IDC patients and HR from LR patients on a higher level than traditional temporal and spectral measures. The behavior of PRSA indexes agrees with experimental evidences related to cardiac autonomic modulations. Also, these parameters reflect more regularity of the autonomic nervous system (ANS) in HR patients. PMID:25585858

  5. Moving on up: Second-Line Agents as Initial Treatment for Newly-Diagnosed Patients with Chronic Phase CML

    PubMed Central

    Shieh, Marie P.; Mitsuhashi, Masato; Lilly, Michael

    2011-01-01

    The treatment of chronic myelogenous leukemia (CML) was revolutionized by the development of imatinib mesylate, a small molecule inhibitor of several protein tyrosine kinases, including the ABL1 protein tyrosine kinase. The current second generation of FDA-approved ABL tyrosine kinase inhibitors, dasatinib and nilotinib, are more potent inhibitors of BCR-ABL1 kinase in vitro. Originally approved for the treatment of patients who were refractory to or intolerant of imatinib, dasatinib and nilotinib are now also FDA approved in the first-line setting. The choice of tyrosine kinase inhibitor (ie, standard or high dose imatinib, dasatinib, nilotinib) to use for initial therapy in chronic-phase CML (CML-CP) will not always be obvious. Therapy selection will depend on both clinical and molecular factors, which we will discuss in this review. PMID:21792346

  6. TM4SF5 accelerates G1/S phase progression via cytosolic p27Kip1 expression and RhoA activity.

    PubMed

    Kim, Hyeonjung; Kang, Minkyung; Lee, Sin-Ae; Kwak, Tae Kyoung; Jung, Oisun; Lee, Hyo Jeong; Kim, Sung-Hoon; Lee, Jung Weon

    2010-08-01

    Transmembrane 4 L six family member 5 (TM4SF5) causes epithelial-mesenchymal transition (EMT) for aberrant cell proliferation. However, the effects of TM4SF5 expression on cell cycle are unknown so far. In this study, using hepatocytes that either ectopically or endogenously express TM4SF5 and human hepatocarcinoma tissues, the role of TM4SF5 in G1/S phase progression was examined. We found that TM4SF5 expression accelerated G1/S phase progression with facilitated cyclin D1 and E expression and Rb phosphorylation. Furthermore, TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. However, TM4SF5-facilitated G1/S phase progression was blocked by silencing of p27Kip1 using siRNA or by infection of active RhoA. Pharmacological inhibition of ROCK accelerated the G1/S phase progression of control TM4SF5-unexpressing cells. Altogether, these observations suggest that TM4SF5 accelerates G1/S phase progression with facilitated CDK4/cyclin D1 entry into the nucleus, which might be supported by TM4SF5-mediated actin reorganization through cytosolic p27Kip1 expression and Rho GTPase activity.

  7. Should trypanocidal therapy be used to treat patients in the chronic phase of Chagas disease?

    PubMed

    Popoff, Federico; Izcovich, Ariel

    2015-10-26

    Antiparasitic treatment of patients with Chagas’ disease in chronic stage could prevent the complications related to the disease. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including eight randomized trials and 11 observational studies. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether antiparasitic treatment improves survival or reduces complications related to chronic Chagas’ disease because the certainty of the evidence is very low.

  8. X-ray phase contrast imaging of biological specimens with femtosecond pulses of betatron radiation from a compact laser plasma wakefield accelerator

    SciTech Connect

    Kneip, S.; McGuffey, C.; Dollar, F.; Chvykov, V.; Kalintchenko, G.; Krushelnick, K.; Maksimchuk, A.; Mangles, S. P. D.; Matsuoka, T.; Schumaker, W.; Thomas, A. G. R.; Yanovsky, V.; Bloom, M. S.; Najmudin, Z.; Palmer, C. A. J.; Schreiber, J.

    2011-08-29

    We show that x-rays from a recently demonstrated table top source of bright, ultrafast, coherent synchrotron radiation [Kneip et al., Nat. Phys. 6, 980 (2010)] can be applied to phase contrast imaging of biological specimens. Our scheme is based on focusing a high power short pulse laser in a tenuous gas jet, setting up a plasma wakefield accelerator that accelerates and wiggles electrons analogously to a conventional synchrotron, but on the centimeter rather than tens of meter scale. We use the scheme to record absorption and phase contrast images of a tetra fish, damselfly and yellow jacket, in particular highlighting the contrast enhancement achievable with the simple propagation technique of phase contrast imaging. Coherence and ultrafast pulse duration will allow for the study of various aspects of biomechanics.

  9. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation

    PubMed Central

    Lipton, Jeff H.; Rea, Delphine; Digumarti, Raghunadharao; Chuah, Charles; Nanda, Nisha; Benichou, Annie-Claude; Craig, Adam R.; Michallet, Mauricette; Nicolini, Franck E.; Kantarjian, Hagop

    2012-01-01

    Chronic myeloid leukemia (CML) patients with the BCR-ABL T315I mutation do not benefit from therapy with currently approved tyrosine kinase inhibitors. Omacetaxine mepesuccinate is a protein synthesis inhibitor that has demonstrated activity in cells harboring the T315I mutation. This phase 2 trial assessed the efficacy of omacetaxine in CML patients with T315I and tyrosine kinase inhibitor failure. Patients received subcutaneous omacetaxine 1.25 mg/m2 twice daily, days 1-14, every 28 days until hematologic response or a maximum of 6 cycles, and then days 1-7 every 28 days as maintenance. Results for patients treated in chronic phase are reported here. Patients (n = 62) received a median of 7 (range, 1-41) cycles. Complete hematologic response was achieved in 48 patients (77%; 95% lower confidence limit, 65%); median response duration was 9.1 months. Fourteen patients (23%; 95% lower confidence limit, 13%) achieved major cytogenetic response, including complete cytogenetic response in 10 (16%). Median progression free-survival was 7.7 months. Grade 3/4 hematologic toxicity included thrombocytopenia (76%), neutropenia (44%), and anemia (39%) and was typically manageable by dose reduction. Nonhematologic adverse events were mostly grade 1/2 and included infection (42%), diarrhea (40%), and nausea (34%). Omacetaxine may provide a safe and effective treatment for CML patients with T315I mutation. This study is registered at www.clinicaltrials.gov as NCT00375219. PMID:22896000

  10. Treatment of nasopharyngeal carcinoma using simultaneous modulated accelerated radiation therapy via helical tomotherapy: a phase II study

    PubMed Central

    Du, Lei; Zhang, Xin Xin; Feng, Lin Chun; Chen, Jing; Yang, Jun; Liu, Hai Xia; Xu, Shou Ping; Xie, Chuan Bin

    2016-01-01

    Abstract Background The aim of the study was to evaluate short-term safety and efficacy of simultaneous modulated accelerated radiation therapy (SMART) delivered via helical tomotherapy in patients with nasopharyngeal carcinoma (NPC). Methods Between August 2011 and September 2013, 132 newly diagnosed NPC patients were enrolled for a prospective phase II study. The prescription doses delivered to the gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), were 67.5 Gy (2.25 Gy/F), 60 Gy (2.0 Gy/F), and 54 Gy (1.8 Gy/F), in 30 fractions, respectively. Acute toxicities were evaluated according to the established RTOG/EORTC criteria. This group of patients was compared with the 190 patients in the retrospective P70 study, who were treated between September 2004 and August 2009 with helical tomotherapy, with a dose of 70-74 Gy/33F/6.5W delivered to pGTVnx and pGTVnd. Results The median follow-up was 23.7 (12–38) months. Acute radiation related side-effects were mainly problems graded as 1 or 2. Only a small number of patients suffered from grade 4 leucopenia (4.5%) or thrombocytopenia (2.3%). The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), local-nodal relapse-free survival (LNRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.7%, 95.5%, 92.2%, 92.7% and 93.2%, at 2 years, respectively, with no significant difference compared with the P70 study. Conclusions Smart delivered via the helical tomotherapy technique appears to be associated with an acceptable acute toxicity profile and favorable short-term outcomes for patients with NPC. Long-term toxicities and patient outcomes are under investigation. PMID:27247555

  11. Radiation dose escalation by simultaneous modulated accelerated radiotherapy combined with chemotherapy for esophageal cancer: a phase II study

    PubMed Central

    Zhai, Tiantian; Chang, Daniel; Chen, Zhijian; Huang, Ruihong; Zhang, Wuzhe; Lin, Kun; Guo, Longjia; Zhou, Mingzhen; Li, Dongsheng; Li, Derui; Chen, Chuangzhen

    2016-01-01

    The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common ≥ grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed ≥ Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities. PMID:26992206

  12. Order-parameter-aided temperature-accelerated sampling for the exploration of crystal polymorphism and solid-liquid phase transitions

    SciTech Connect

    Yu, Tang-Qing Vanden-Eijnden, Eric; Chen, Pei-Yang; Chen, Ming; Samanta, Amit; Tuckerman, Mark

    2014-06-07

    The problem of predicting polymorphism in atomic and molecular crystals constitutes a significant challenge both experimentally and theoretically. From the theoretical viewpoint, polymorphism prediction falls into the general class of problems characterized by an underlying rough energy landscape, and consequently, free energy based enhanced sampling approaches can be brought to bear on the problem. In this paper, we build on a scheme previously introduced by two of the authors in which the lengths and angles of the supercell are targeted for enhanced sampling via temperature accelerated adiabatic free energy dynamics [T. Q. Yu and M. E. Tuckerman, Phys. Rev. Lett. 107, 015701 (2011)]. Here, that framework is expanded to include general order parameters that distinguish different crystalline arrangements as target collective variables for enhanced sampling. The resulting free energy surface, being of quite high dimension, is nontrivial to reconstruct, and we discuss one particular strategy for performing the free energy analysis. The method is applied to the study of polymorphism in xenon crystals at high pressure and temperature using the Steinhardt order parameters without and with the supercell included in the set of collective variables. The expected fcc and bcc structures are obtained, and when the supercell parameters are included as collective variables, we also find several new structures, including fcc states with hcp stacking faults. We also apply the new method to the solid-liquid phase transition in copper at 1300 K using the same Steinhardt order parameters. Our method is able to melt and refreeze the system repeatedly, and the free energy profile can be obtained with high efficiency.

  13. Order-parameter-aided temperature-accelerated sampling for the exploration of crystal polymorphism and solid-liquid phase transitions

    NASA Astrophysics Data System (ADS)

    Yu, Tang-Qing; Chen, Pei-Yang; Chen, Ming; Samanta, Amit; Vanden-Eijnden, Eric; Tuckerman, Mark

    2014-06-01

    The problem of predicting polymorphism in atomic and molecular crystals constitutes a significant challenge both experimentally and theoretically. From the theoretical viewpoint, polymorphism prediction falls into the general class of problems characterized by an underlying rough energy landscape, and consequently, free energy based enhanced sampling approaches can be brought to bear on the problem. In this paper, we build on a scheme previously introduced by two of the authors in which the lengths and angles of the supercell are targeted for enhanced sampling via temperature accelerated adiabatic free energy dynamics [T. Q. Yu and M. E. Tuckerman, Phys. Rev. Lett. 107, 015701 (2011)]. Here, that framework is expanded to include general order parameters that distinguish different crystalline arrangements as target collective variables for enhanced sampling. The resulting free energy surface, being of quite high dimension, is nontrivial to reconstruct, and we discuss one particular strategy for performing the free energy analysis. The method is applied to the study of polymorphism in xenon crystals at high pressure and temperature using the Steinhardt order parameters without and with the supercell included in the set of collective variables. The expected fcc and bcc structures are obtained, and when the supercell parameters are included as collective variables, we also find several new structures, including fcc states with hcp stacking faults. We also apply the new method to the solid-liquid phase transition in copper at 1300 K using the same Steinhardt order parameters. Our method is able to melt and refreeze the system repeatedly, and the free energy profile can be obtained with high efficiency.

  14. Unpredictable chronic stress decreases inhibitory avoidance learning in Tuebingen long-fin zebrafish: stronger effects in the resting phase than in the active phase.

    PubMed

    Manuel, Remy; Gorissen, Marnix; Zethof, Jan; Ebbesson, Lars O E; van de Vis, Hans; Flik, Gert; van den Bos, Ruud

    2014-11-01

    Zebrafish (Danio rerio Hamilton) are increasingly used as a model to study the effects of chronic stress on brain and behaviour. In rodents, unpredictable chronic stress (UCS) has a stronger effect on physiology and behaviour during the active phase than during the resting phase. Here, we applied UCS during the daytime (active phase) for 7 and 14 days or during the night-time (resting phase) for 7 nights in an in-house-reared Tuebingen long-fin (TLF) zebrafish strain. Following UCS, inhibitory avoidance learning was assessed using a 3 day protocol where fish learn to avoid swimming from a white to a black compartment where they will receive a 3 V shock. Latencies of entering the black compartment were recorded before training (day 1; first shock) and after training on day 2 (second shock) and day 3 (no shock, tissue sampling). Fish whole-body cortisol content and expression levels of genes related to stress, fear and anxiety in the telencephalon were quantified. Following 14 days of UCS during the day, inhibitory avoidance learning decreased (lower latencies on days 2 and 3); minor effects were found following 7 days of UCS. Following 7 nights of UCS, inhibitory avoidance learning decreased (lower latency on day 3). Whole-body cortisol levels showed a steady increase compared with controls (100%) from 7 days of UCS (139%), to 14 days of UCS (174%) to 7 nights of UCS (231%), suggestive of an increasing stress load. Only in the 7 nights of UCS group did expression levels of corticoid receptor genes (mr, grα, grβ) and of bdnf increase. These changes are discussed as adaptive mechanisms to maintain neuronal integrity and prevent overload, and as being indicative of a state of high stress load. Overall, our data suggest that stressors during the resting phase have a stronger impact than during the active phase. Our data warrant further studies on the effect of UCS on stress axis-related genes, especially grβ; in mammals this receptor has been implicated in

  15. Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response: a single center facing the dilemma.

    PubMed

    Iliakis, Theodoros; Papadopoulou, Vasiliki; Diamantopoulos, Panagiotis T; Panayiotidis, Panayiotis; Zervakis, Konstantinos; Giannakopoulou, Nefeli; Tilimidos, Gerassimos; Angelopoulou, Maria; Siakantaris, Marina P; Pangalis, Gerassimos; Mantzourani, Marina; Variami, Eleni; Viniou, Nora Athina

    2013-08-01

    Tyrosine kinase inhibitors (TKIs), namely imatinib mesylate (IM) and recently approved second-generation TKIs dasatinib and nilotinib, are currently considered the treatment of choice for newly-diagnosed chronic phase chronic myelogenous leukemia (CP-CML). Although treatment with TKIs has not yet been proven curative, it certainly accomplishes a sustained control of the disease in the vast majority of patients. More than a decade after the successful launching of IM in first-line treatment of CP-CML and the subsequent introduction of second-generation TKIs in this setting, the question of the possibility of TKI cessation in a specific subset of patients has emerged. Side-effects of TKIs, along with some patients' wish to abandon the drugs and the rising financial burden upon healthcare systems, have led to the dilemma whether IM can be safely withdrawn after achieving deep molecular remissions and which patients are suitable for this discontinuation. We examined the data of our patients with CML in search of potential canditates for cessation of TKI therapy and identified their characteristics. We also performed a thorough review of the relevant literature. Eight out of fifty patients were discriminated on grounds of sustained complete molecular response (CMR) exceeding 12 months, most of them with a low or intermediate Sokal score at diagnosis. The median interval from IM initiation to CMR was almost 2 years and the median duration of detected CMR reached 6.5 years. Based on the promising results of prospective clinical trials reporting successful cessation of treatment with TKIs on selected subgroups of patients, we decided to proceed to interruption of therapy in the specific subset of our patients and closely monitor their response. PMID:23898127

  16. Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

    PubMed Central

    Padula, William V.; Larson, Richard A.; Dusetzina, Stacie B.; Apperley, Jane F.; Hehlmann, Rudiger; Baccarani, Michele; Eigendorff, Ekkehard; Guilhot, Joelle; Guilhot, Francois; Hehlmann, Rudiger; Mahon, Francois-Xavier; Martinelli, Giovanni; Mayer, Jiri; Müller, Martin C.; Niederwieser, Dietger; Saussele, Susanne; Schiffer, Charles A.; Silver, Richard T.; Simonsson, Bengt

    2016-01-01

    Background: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib’s price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness (“imatinib-first”) would be cost-effective compared with the current standard of care: “physicians’ choice” of initiating treatment with any one of the three TKIs. Methods: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician’s choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models’ clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven’s MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study’s conduct. Results: Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician’s choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. Conclusion: When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP. PMID:26944912

  17. Chronic transplantation immunity in newts: temperature susceptibility of an effector phase in allo-skin graft rejection.

    PubMed

    Kinefuchi, Kenjiroh; Kushida, Yoshihiro; Johnouchi, Masato; Shimizu, Yuiko; Ohneda, Hikaru; Fujii, Masato; Hosono, Masamichi

    2011-07-01

    Urodele amphibians are unique due to their greatly reduced immune responsiveness compared to bony fishes, which show acute immune responsiveness. In newts, the mean survival time of allogenic skin grafts in the transplantation immunity was 48.8 ± 8.3 days at 25°C, suggesting that it occurs in a chronic manner. The graft rejection process was categorized into three stages: a latent stage with frequent blood circulation, or the immune induction phase; a vascular stoppage stage with dominant infiltrating cells of T cells; and a rejection stage showing the change of the dominant cells to monocytes/macrophages, probably as effector cells, tetntatively referred to as the immune effector phase. The immune induction phase is susceptible to the cyclophosphamide (CY) mitosis inhibitor, but not to a temperature shift from 18 to 27°C, while the immune effector phase is susceptible to temperature shifts, but not CY-treatment, although the temperature shift failed to shorten the graft survival time to less than 25 days, which nearly equals that of the secondary set of grafts where the lack of complete blood circulation is remarkable and graft rejection is resistant to CY-treatment. In contrast, a very low temperature (5-10°C) completely prevented effector generation in newts; in frogs, however, it is reported that such low temperatures did not prevent the generation of effectors. Taken together, these data suggest that chronic responses in newts are due to effector cells other than cytotoxic T cells; possible effector cells are discussed.

  18. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    PubMed Central

    2012-01-01

    Objective Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments. PMID:23351279

  19. A matter of timing: early, not chronic phase intestinal nematode infection restrains control of a concurrent enteric protozoan infection.

    PubMed

    Rausch, Sebastian; Held, Josephin; Stange, Joerg; Lendner, Matthias; Hepworth, Matthew R; Klotz, Christian; Lucius, Richard; Pogonka, Thomas; Hartmann, Susanne

    2010-10-01

    Infections with parasitic worms are often long lasting and associated with modulated immune responses. We analyzed the influence of the nematode Heligmosomoides polygyrus bakeri dwelling in the small intestine on concurrent protozoan infection with Eimeria falciformis residing in the cecum. To dissect the effects of a nematode infection in the early versus chronic phase, we infected animals with E. falciformis 6 or 28 days post H. p. bakeri infection. Only a concurrent early nematode infection led to an increased replication of the protozoan parasite, whereas a chronic worm infection had no influence on the control of E. falciformis. Increased protozoan replication correlated with the reduced production of IFN-γ, IL-12/23, CCL4, CXCL9 and CXCL10, reduced migration of T cells and increased expression of Foxp3 at the site of protozoan infection. This was accompanied by a stronger nematode-specific Th2 response in gut-draining LN. Protection of mice against challenge infections with the protozoan parasite was not altered. Hence, the detrimental effect of a nematode infection on the control of a concurrent protozoan infection is transient and occurs only in the narrow time window of the early phase of infection.

  20. Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

    PubMed

    Kloner, Robert A; Dai, Wangde; Hale, Sharon L; Shi, Jianru

    2016-07-01

    While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function.

  1. Sequential combined treatment with allopurinol and benznidazole in the chronic phase of Trypanosoma cruzi infection: a pilot study

    PubMed Central

    Perez-Mazliah, D. E.; Alvarez, M. G.; Cooley, G.; Lococo, B. E.; Bertocchi, G.; Petti, M.; Albareda, M. C.; Armenti, A. H.; Tarleton, R. L.; Laucella, S. A.; Viotti, R.

    2013-01-01

    Objectives Even though the use of combined drugs has been proved to be effective in other chronic infections, assessment of combined treatment of antiparasitic drugs in human Chagas' disease has not been performed. Herein, a pilot study was conducted to evaluate the tolerance and side effects of a sequential combined treatment of two antiparasitic drugs, allopurinol and benznidazole, in the chronic phase of Trypanosoma cruzi infection. Patients and methods Changes in total and T. cruzi-specific T and B cells were monitored during a median follow-up of 36 months. Allopurinol was administered for 3 months (600 mg/day) followed by 30 days of benznidazole (5 mg/kg/day) in 11 T. cruzi-infected subjects. Results The combined sequential treatment of allopurinol and benznidazole was well tolerated. The levels of T. cruzi-specific antibodies significantly decreased after sequential combined treatment, as determined by conventional serology and by a multiplex assay using recombinant proteins. The frequency of T. cruzi-specific interferon-γ-producing T cells significantly increased after allopurinol treatment and decreased to background levels following benznidazole administration in a substantial proportion of subjects evaluated. The levels of total naive (CD45RA + CCR7 + CD62L+) CD4 + and CD8 + T cells were restored after allopurinol administration and maintained after completion of the combined drug protocol, along with a decrease in T cell activation in total peripheral CD4 + and CD8 + T cells. Conclusions This pilot study shows that the combination of allopurinol and benznidazole induces significant modifications in T and B cell responses indicative of a reduction in parasite burden, and sustains the feasibility of administration of two antiparasitic drugs in the chronic phase of Chagas' disease. PMID:23104493

  2. In vitro effects of imatinib on CD34(+) cells of patients with chronic myeloid leukemia in the megakaryocytic crisis phase.

    PubMed

    Meng, Fankai; Zeng, Wen; Huang, Lifang; Qin, Shuang; Miao, Ningning; Sun, Hanying; Li, Chunrui

    2014-03-01

    Imatinib is a tailored drug for the treatment of chronic myeloid leukemia (CML), and has substantial activity and a favorable safety profile when used as a single agent in patients with CML in myeloid blast crisis. The megakaryocytic blast crisis in CML occurs rarely and carries a poor prognosis. The aim of the present study was to investigate the effects of imatinib on cluster of differentiation (CD)34(+) cells from patients with CML in the megakaryocytic crisis phase. Bone marrow mononuclear cells (BMNCs) were isolated from patients with CML in the megakaryocytic crisis phase. CD34(+) cells were selected from BMNCs by positive immunomagnetic column separation. Imatinib significantly induced G1 arrest, reduced the phosphorylation of cyclin-dependent kinase 1 and retinoblastoma proteins and inhibited the proliferation of CD34(+) cells from patients with CML in the megakaryocytic crisis phase. Annexin V/propidium iodide and caspase-3 activity showed that imatinib induced apoptosis. Western blot analysis and protein tyrosine kinase activity assays showed that imatinib inhibited BCR-ABL protein tyrosine kinase activity. The in vitro data thus markedly indicate a potential clinical application of imatinib for patients with CML in the megakaryocytic crisis phase.

  3. GPU-Accelerated Molecular Dynamics Simulation to Study Liquid Crystal Phase Transition Using Coarse-Grained Gay-Berne Anisotropic Potential.

    PubMed

    Chen, Wenduo; Zhu, Youliang; Cui, Fengchao; Liu, Lunyang; Sun, Zhaoyan; Chen, Jizhong; Li, Yunqi

    2016-01-01

    Gay-Berne (GB) potential is regarded as an accurate model in the simulation of anisotropic particles, especially for liquid crystal (LC) mesogens. However, its computational complexity leads to an extremely time-consuming process for large systems. Here, we developed a GPU-accelerated molecular dynamics (MD) simulation with coarse-grained GB potential implemented in GALAMOST package to investigate the LC phase transitions for mesogens in small molecules, main-chain or side-chain polymers. For identical mesogens in three different molecules, on cooling from fully isotropic melts, the small molecules form a single-domain smectic-B phase, while the main-chain LC polymers prefer a single-domain nematic phase as a result of connective restraints in neighboring mesogens. The phase transition of side-chain LC polymers undergoes a two-step process: nucleation of nematic islands and formation of multi-domain nematic texture. The particular behavior originates in the fact that the rotational orientation of the mesogenes is hindered by the polymer backbones. Both the global distribution and the local orientation of mesogens are critical for the phase transition of anisotropic particles. Furthermore, compared with the MD simulation in LAMMPS, our GPU-accelerated code is about 4 times faster than the GPU version of LAMMPS and at least 200 times faster than the CPU version of LAMMPS. This study clearly shows that GPU-accelerated MD simulation with GB potential in GALAMOST can efficiently handle systems with anisotropic particles and interactions, and accurately explore phase differences originated from molecular structures. PMID:26986851

  4. GPU-Accelerated Molecular Dynamics Simulation to Study Liquid Crystal Phase Transition Using Coarse-Grained Gay-Berne Anisotropic Potential

    PubMed Central

    Cui, Fengchao; Liu, Lunyang; Sun, Zhaoyan; Chen, Jizhong; Li, Yunqi

    2016-01-01

    Gay-Berne (GB) potential is regarded as an accurate model in the simulation of anisotropic particles, especially for liquid crystal (LC) mesogens. However, its computational complexity leads to an extremely time-consuming process for large systems. Here, we developed a GPU-accelerated molecular dynamics (MD) simulation with coarse-grained GB potential implemented in GALAMOST package to investigate the LC phase transitions for mesogens in small molecules, main-chain or side-chain polymers. For identical mesogens in three different molecules, on cooling from fully isotropic melts, the small molecules form a single-domain smectic-B phase, while the main-chain LC polymers prefer a single-domain nematic phase as a result of connective restraints in neighboring mesogens. The phase transition of side-chain LC polymers undergoes a two-step process: nucleation of nematic islands and formation of multi-domain nematic texture. The particular behavior originates in the fact that the rotational orientation of the mesogenes is hindered by the polymer backbones. Both the global distribution and the local orientation of mesogens are critical for the phase transition of anisotropic particles. Furthermore, compared with the MD simulation in LAMMPS, our GPU-accelerated code is about 4 times faster than the GPU version of LAMMPS and at least 200 times faster than the CPU version of LAMMPS. This study clearly shows that GPU-accelerated MD simulation with GB potential in GALAMOST can efficiently handle systems with anisotropic particles and interactions, and accurately explore phase differences originated from molecular structures. PMID:26986851

  5. Accelerated test methods for life prediction of hermetic motor insulation systems exposed to alternative refrigerant/lubricant mixtures. Phase 3: Reproducibility and discrimination testing. Final report

    SciTech Connect

    Ellis, P.F. II; Ferguson, A.F.; Fuentes, K.T.

    1996-05-06

    In 1992, the Air-Conditioning and Refrigeration Technology Institute, Inc. (ARTI) contracted Radian Corporation to ascertain whether an improved accelerated test method or procedure could be developed that would allow prediction of the life of motor insulation materials used in hermetic motors for air-conditioning and refrigeration equipment operated with alternative refrigerant/lubricant mixtures. This report presents the results of phase three concerning the reproducibility and discrimination testing.

  6. Quantifying factors determining the rate of CTL escape and reversion during acute and chronic phases of HIV infection

    SciTech Connect

    Ganusov, Vitaly V; Korber, Bette M; Perelson, Alan S

    2009-01-01

    Human immunodeficiency virus (HIV) often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. However, the importance and quantitative details of CTL escape in humans are poorly understood. In part, this is because most studies looking at escape of HIV from CTL responses are cross-sectional and are limited to early or chronic phases of the infection. We use a novel technique of single genome amplification (SGA) to identify longitudinal changes in the transmitted/founder virus from the establishment of infection to the viral set point at 1 year after the infection. We find that HIV escapes from virus-specific CTL responses as early as 30-50 days since the infection, and the rates of viral escapes during acute phase of the infection are much higher than was estimated in previous studies. However, even though with time virus acquires additional escape mutations, these late mutations accumulate at a slower rate. A poor correlation between the rate of CTL escape in a particular epitope and the magnitude of the epitope-specific CTL response suggests that the lower rate of late escapes is unlikely due to a low efficacy of the HIV-specific CTL responses in the chronic phase of the infection. Instead, our results suggest that late and slow escapes are likely to arise because of high fitness cost to the viral replication associated with such CTL escapes. Targeting epitopes in which virus escapes slowly or does not escape at all by CTL responses may, therefore, be a promising direction for the development of T cell based HIV vaccines.

  7. Stochastic shock response spectrum decomposition method based on probabilistic definitions of temporal peak acceleration, spectral energy, and phase lag distributions of mechanical impact pyrotechnic shock test data

    NASA Astrophysics Data System (ADS)

    Hwang, James Ho-Jin; Duran, Adam

    2016-08-01

    Most of the times pyrotechnic shock design and test requirements for space systems are provided in Shock Response Spectrum (SRS) without the input time history. Since the SRS does not describe the input or the environment, a decomposition method is used to obtain the source time history. The main objective of this paper is to develop a decomposition method producing input time histories that can satisfy the SRS requirement based on the pyrotechnic shock test data measured from a mechanical impact test apparatus. At the heart of this decomposition method is the statistical representation of the pyrotechnic shock test data measured from the MIT Lincoln Laboratory (LL) designed Universal Pyrotechnic Shock Simulator (UPSS). Each pyrotechnic shock test data measured at the interface of a test unit has been analyzed to produce the temporal peak acceleration, Root Mean Square (RMS) acceleration, and the phase lag at each band center frequency. Maximum SRS of each filtered time history has been calculated to produce a relationship between the input and the response. Two new definitions are proposed as a result. The Peak Ratio (PR) is defined as the ratio between the maximum SRS and the temporal peak acceleration at each band center frequency. The ratio between the maximum SRS and the RMS acceleration is defined as the Energy Ratio (ER) at each band center frequency. Phase lag is estimated based on the time delay between the temporal peak acceleration at each band center frequency and the peak acceleration at the lowest band center frequency. This stochastic process has been applied to more than one hundred pyrotechnic shock test data to produce probabilistic definitions of the PR, ER, and the phase lag. The SRS is decomposed at each band center frequency using damped sinusoids with the PR and the decays obtained by matching the ER of the damped sinusoids to the ER of the test data. The final step in this stochastic SRS decomposition process is the Monte Carlo (MC

  8. Phase I/II Study Evaluating Early Tolerance in Breast Cancer Patients Undergoing Accelerated Partial Breast Irradiation Treated With the MammoSite Balloon Breast Brachytherapy Catheter Using a 2-Day Dose Schedule

    SciTech Connect

    Wallace, Michelle; Martinez, Alvaro; Mitchell, Christina; Chen, Peter Y.; Ghilezan, Mihai; Benitez, Pamela; Brown, Eric; Vicini, Frank

    2010-06-01

    Purpose: Initial Phase I/II results using balloon brachytherapy to deliver accelerated partial breast irradiation (APBI) in 2 days in patients with early-stage breast cancer are presented. Materials and Methods: Between March 2004 and August 2007, 45 patients received adjuvant radiation therapy after lumpectomy with balloon brachytherapy in a Phase I/II trial delivering 2800 cGy in four fractions of 700 cGy. Toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria for Adverse Events v3.0 scale and cosmesis was documented at >=6 months. Results: The median age was 66 years (range, 48-83) and median skin spacing was 12 mm (range, 8-24). The median follow-up was 11.4 months (5.4-48 months) with 21 patients (47%) followed >=1 year, 11 (24%) >=2 years, and 7 (16%) >=3 years. At <6 months (n = 45), Grade II toxicity rates were 9% radiation dermatitis, 13% breast pain, 2% edema, and 2% hyperpigmentation. Grade III breast pain was reported in 13% (n = 6). At >=6 months (n = 43), Grade II toxicity rates were: 2% radiation dermatitis, 2% induration, and 2% hypopigmentation. Grade III breast pain was reported in 2%. Infection was 13% (n = 6) at <6 months and 5% (n = 2) at >=6 months. Persistent seroma >=6 months was 30% (n = 13). Fat necrosis developed in 4 cases (2 symptomatic). Rib fractures were seen in 4% (n = 2). Cosmesis was good/excellent in 96% of cases. Conclusions: Treatment with balloon brachytherapy using a 2-day dose schedule resulted acceptable rates of Grade II/III chronic toxicity rates and similar cosmetic results observed with a standard 5-day accelerated partial breast irradiation schedule.

  9. Intra-cyclic distance per stroke phase, velocity fluctuations and acceleration time ratio of a breaststroker's hip: a comparison between elite and nonelite swimmers at different race paces.

    PubMed

    Leblanc, H; Seifert, L; Tourny-Chollet, C; Chollet, D

    2007-02-01

    The aim of this study was to compare the intra-cyclic velocity graphs of breaststroke swimmers at two skill levels in relation to their movement phases. Two groups of nine male swimmers were videotaped underwater at three swimming race paces corresponding to their actual competitive times for the 200-m, 100-m and 50-m breaststroke. Their forward intra-cyclic hip velocity was recorded with a velocity-meter. The breaststroke cycle was divided into four phases: leg propulsion, leg-arm lag phase, arm propulsion, and arm and leg recovery. From the velocity-time data, the following parameters were computed: an index of velocity fluctuations (IVF), the distance covered during each stroke phase, and an acceleration-deceleration time ratio (ADTR). The main results showed that in both groups of swimmers, when the race pace increased, the distance covered during the leg-arm lag phase decreased, while the other swimming phases remained stable. When expressed in relative values, the percentage of distance covered during the leg-arm lag phase decreased. In nonelite swimmers, the percentage of distance covered in the other stroke phases increased significantly, while only a tendency was noted in the elite group. Elite swimmers demonstrated a higher ADTR at the 50-m pace than at their 100-m and 200-m paces. An inter-group comparison showed that elite swimmers had higher values for the IVF and ADTR, which indicated their capacity to accelerate to boost the swim and highlighted the relevancy of these factors to discriminate skill level. PMID:16835822

  10. Promoting state health department evidence-based cancer and chronic disease prevention: a multi-phase dissemination study with a cluster randomized trial component

    PubMed Central

    2013-01-01

    Background Cancer and other chronic diseases reduce quality and length of life and productivity, and represent a significant financial burden to society. Evidence-based public health approaches to prevent cancer and other chronic diseases have been identified in recent decades and have the potential for high impact. Yet, barriers to implement prevention approaches persist as a result of multiple factors including lack of organizational support, limited resources, competing emerging priorities and crises, and limited skill among the public health workforce. The purpose of this study is to learn how best to promote the adoption of evidence based public health practice related to chronic disease prevention. Methods/design This paper describes the methods for a multi-phase dissemination study with a cluster randomized trial component that will evaluate the dissemination of public health knowledge about evidence-based prevention of cancer and other chronic diseases. Phase one involves development of measures of practitioner views on and organizational supports for evidence-based public health and data collection using a national online survey involving state health department chronic disease practitioners. In phase two, a cluster randomized trial design will be conducted to test receptivity and usefulness of dissemination strategies directed toward state health department chronic disease practitioners to enhance capacity and organizational support for evidence-based chronic disease prevention. Twelve state health department chronic disease units will be randomly selected and assigned to intervention or control. State health department staff and the university-based study team will jointly identify, refine, and select dissemination strategies within intervention units. Intervention (dissemination) strategies may include multi-day in-person training workshops, electronic information exchange modalities, and remote technical assistance. Evaluation methods include pre

  11. IMATINIB 800MG DAILY INDUCES DEEPER MOLECULAR RESPONSES THAN IMATINIB 400MG DAILY: RESULTS OF SWOG S0325, AN INTERGROUP RANDOMIZED PHASE II TRIAL IN NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKAEMIA

    PubMed Central

    Deininger, Michael W.; Kopecky, Kenneth J.; Radich, Jerald P.; Kamel-Reid, Suzanne; Stock, Wendy; Paietta, Elisabeth; Emanuel, Peter D.; Tallman, Martin; Wadleigh, Martha; Larson, Richard A.; Lipton, Jeffrey H.; Slovak, Marilyn L.; Appelbaum, Frederick R.; Druker, Brian J.

    2014-01-01

    The standard dose of imatinib for newly diagnosed patients with chronic phase chronic myeloid leukemia (CP-CML) is 400mg daily (IM400), but the optimal dose is unknown. This randomized phase II study compared the rates of molecular, haematologic and cytogenetic response to IM400 vs. imatinib 400mg twice daily (IM800) in 153 adult patients with CP-CML. Dose adjustments for toxicity were flexible to maximize retention on study. Molecular response (MR) at 12 months was deeper in the IM800 arm (4-log reduction of BCR-ABL1 mRNA: 25% vs. 10% of patients, P=0.038; 3-log reduction: 53% vs. 35%, P=0.049). During the first 12 months BCR-ABL1 levels in the IM800 arm were an average 2.9-fold lower than in the IM400 arm (P=0.010). Complete haematologic response was similar, but complete cytogenetic response was higher with IM800 (85% vs. 67%, P=0.040). Grade 3–4 toxicities were more common for IM800 (58% vs. 31%, P=0.0007), and were most commonly haematologic. Few patients have relapsed, progressed or died, but progression-free (P=0.048) and relapse-free (P=0.031) survival were superior for IM800. In newly diagnosed CP-CML patients, IM800 induced deeper molecular responses than IM400, with a trend for improved progression-free and overall survival, but was associated with more severe toxicity. PMID:24383843

  12. CCI-779 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, or Chronic Myelogenous Leukemia in Blastic Phase

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes

  13. 1Alpha,25-(OH)2D3 acts in the early phase of osteoblast differentiation to enhance mineralization via accelerated production of mature matrix vesicles.

    PubMed

    Woeckel, V J; Alves, R D A M; Swagemakers, S M A; Eijken, M; Chiba, H; van der Eerden, B C J; van Leeuwen, J P T M

    2010-11-01

    1Alpha,25-dihydroxyitamin D(3) (1,25D3) deficiency leads to impaired bone mineralization. We used the human pre-osteoblastic cell line SV-HFO, which forms within 19 days of culture an extracellular matrix that starts to mineralize around day 12, to examine the mechanism by which 1,25D3 regulates osteoblasts and directly stimulates mineralization. Time phase studies showed that 1,25D3 treatment prior to the onset of mineralization, rather than during mineralization led to accelerated and enhanced mineralization. This is supported by the observation of unaltered stimulation by 1,25D3 even when osteoblasts were devitalized just prior to onset of mineralization and after 1,25D3 treatment. Gene Chip expression profiling identified the pre-mineralization and mineralization phase as two strongly distinctive transcriptional periods with only 0.6% overlap of genes regulated by 1,25D3. In neither phase 1,25D3 significantly altered expression of extracellular matrix genes. 1,25D3 significantly accelerated the production of mature matrix vesicles (MVs) in the pre-mineralization. Duration rather than timing determined the extent of the 1,25D3 effect. We propose the concept that besides indirect effects via intestinal calcium uptake 1,25D3 directly accelerates osteoblast-mediated mineralization via increased production of mature MVs in the period prior to mineralization. The accelerated deposition of mature MVs leads to an earlier onset and higher rate of mineralization. These effects are independent of changes in extracellular matrix protein composition. These data on 1,25D3, mineralization, and MV biology add new insights into the role of 1,25D3 in bone metabolism and emphasize the importance of MVs in bone and maintaining bone health and strength by optimal mineralization status.

  14. In Vivo Antiprotozoal Activity of the Chloroform Extract from Carica papaya Seeds against Amastigote Stage of Trypanosoma cruzi during Indeterminate and Chronic Phase of Infection

    PubMed Central

    Ortega-Pacheco, Antonio; Perez-Gutierrez, Salud; Guzman-Marin, Eugenia

    2014-01-01

    In order to evaluate the antiprotozoal activity of the chloroform extract of Carica papaya seeds during the subacute and chronic phase of infection of Trypanosoma cruzi, doses of 50 and 75 mg/kg were evaluated during the subacute phase, including a mixture of their main components (oleic, palmitic, and stearic acids). Subsequently, doses of 50 and 75 mg/kg in mice during the chronic phase of infection (100 dpi) were also evaluated. It was found that chloroform extract was able to reduce the amastigote nests numbers during the subacute phase in 55.5 and 69.7% (P > 0.05) as well as in 56.45% in animals treated with the mixture of fatty acids. Moreover, the experimental groups treated with 50 and 75 mg/kg during the chronic phase of the infection showed a significant reduction of 46.8 and 53.13% respectively (P < 0.05). It is recommended to carry out more studies to determine if higher doses of chloroformic extract or its administration in combination with other antichagasic drugs allows a better response over the intracellular stage of T. cruzi in infected animal models and determine if the chloroform extract of C. papaya could be considered as an alternative for treatment during the indeterminate and chronic phase of the infection. PMID:25276216

  15. Murine schistosomiasis mansoni: process of blood coagulation at pre-patent, acute and chronic phases, and consequence of chemotherapeutic cure on the reversion of changes.

    PubMed

    Carvalho, Maria G; Mello, Rômulo T; Soares, Anna L; Bicalho, Rosilene S; Lima e Silva, Francisco C; Coelho, Paulo M Z

    2005-10-01

    The present study aims to elucidate in a sequential manner the changes of the blood coagulation process at different phases of experimental schistosomiasis, comprising the pre-patent, acute, intermediate and chronic phases, and the effect of chemotherapeutic cure, at the acute and chronic phases, on reversion of changes related to the coagulation factors. Mice were infected with Schistosoma mansoni cercariae, and were divided into four groups. Blood samples from these groups were collected 32, 70, 100, and 140 days after infection, corresponding to the pre-patent, acute, intermediate and chronic phases, respectively. Simultaneously, other infected groups were given oxamniquine, 70 and 140 days after infection. At the same time as blood collection from infected and/or treated animal groups, other uninfected control animal groups were punctured and maintained under the same conditions as the infected animals. The vitamin-K-dependent clotting factors were found to be more sensitive to infection at different phases, while factors VIII and XI presented hyperactivity. Results obtained 90 days after chemotherapeutic treatment with oxamniquine, administered at the acute and chronic phases, presented noticeable reversion of the main alterations in the coagulation mechanism. The present study provides unquestionable data on the development of hemostatic changes throughout the course of S. mansoni infection.

  16. In Vivo Antiprotozoal Activity of the Chloroform Extract from Carica papaya Seeds against Amastigote Stage of Trypanosoma cruzi during Indeterminate and Chronic Phase of Infection.

    PubMed

    Jimenez-Coello, Matilde; Acosta-Viana, Karla Y; Ortega-Pacheco, Antonio; Perez-Gutierrez, Salud; Guzman-Marin, Eugenia

    2014-01-01

    In order to evaluate the antiprotozoal activity of the chloroform extract of Carica papaya seeds during the subacute and chronic phase of infection of Trypanosoma cruzi, doses of 50 and 75 mg/kg were evaluated during the subacute phase, including a mixture of their main components (oleic, palmitic, and stearic acids). Subsequently, doses of 50 and 75 mg/kg in mice during the chronic phase of infection (100 dpi) were also evaluated. It was found that chloroform extract was able to reduce the amastigote nests numbers during the subacute phase in 55.5 and 69.7% (P > 0.05) as well as in 56.45% in animals treated with the mixture of fatty acids. Moreover, the experimental groups treated with 50 and 75 mg/kg during the chronic phase of the infection showed a significant reduction of 46.8 and 53.13% respectively (P < 0.05). It is recommended to carry out more studies to determine if higher doses of chloroformic extract or its administration in combination with other antichagasic drugs allows a better response over the intracellular stage of T. cruzi in infected animal models and determine if the chloroform extract of C. papaya could be considered as an alternative for treatment during the indeterminate and chronic phase of the infection. PMID:25276216

  17. Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis

    PubMed Central

    Verstovsek, Srdan; Tefferi, Ayalew; Cortes, Jorge; O’Brien, Susan; Garcia-Manero, Guillermo; Pardanani, Animesh; Akin, Cem; Faderl, Stefan; Manshouri, Taghi; Thomas, Deborah; Kantarjian, Hagop

    2016-01-01

    Molecular characterization of Philadelphia chromosome-negative (Ph−) chronic myeloproliferative disorders, such as systemic mastocytosis (SM), has provided a clear rationale for investigating novel targeted therapies. The tyrosine kinase (TK) inhibitor dasatinib is 325-fold more potent against Bcr-Abl TK than imatinib in vitro, significantly inhibiting wild-type KIT and PDGFR-B TKs, and is active against cells carrying the mutant KIT-D816V gene. In this phase 2, open-label study, the efficacy of dasatinib (140 mg/day) was investigated in 67 patients with various Ph− myeloid disorders, including SM (N=33; 28 KIT-D816V positive). The overall response rate to dasatinib in patients with SM was 33%. Only two patients, one with SM-myelofibrosis and one with SM-chronic eosinophilic leukemia, achieved complete response (elimination of mastocytosis) lasting for 5 and 16 months, respectively. Both patients were negative for KIT-D816V mutation, had low tryptase levels, abnormal WBC counts, and anemia, and had failed prior therapy with erythropoietin. Additional 9 SM patients had symptomatic response, lasting 3 to 18+ months. Complete responses were achieved in two other patients (acute myeloid leukemia, hypereosinophilic syndrome). No responses were observed among patients with myelodysplastic syndromes and primary myelofibrosis. The majority of adverse events were grade 1/2. These data show that dasatinib may benefit a selected group of SM patients, primarily by improving their symptoms. PMID:18559612

  18. A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction

    PubMed Central

    Shinohara, Yoshinori; Takahashi, Naoto; Nishiwaki, Kaichi; Hino, Masayuki; Kashimura, Makoto; Wakita, Hisashi; Hatano, Yoshiaki; Hirasawa, Akira; Nakagawa, Yasuaki; Itoh, Kuniaki; Masuoka, Hidekazu; Aotsuka, Nobuyuki; Matsuura, Yasuhiro; Takahara, Sinobu; Sano, Koji; Kuroki, Jun; Hata, Tomoko; Nakamae, Hirohisa; Mugitani, Atsuko; Nakane, Takahiko; Miyazaki, Yasushi; Niioka, Takenori; Miura, Masatomo; Sawada, Kenichi

    2013-01-01

    Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935). PMID:23716542

  19. A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction.

    PubMed

    Shinohara, Yoshinori; Takahashi, Naoto; Nishiwaki, Kaichi; Hino, Masayuki; Kashimura, Makoto; Wakita, Hisashi; Hatano, Yoshiaki; Hirasawa, Akira; Nakagawa, Yasuaki; Itoh, Kuniaki; Masuoka, Hidekazu; Aotsuka, Nobuyuki; Matsuura, Yasuhiro; Takahara, Sinobu; Sano, Koji; Kuroki, Jun; Hata, Tomoko; Nakamae, Hirohisa; Mugitani, Atsuko; Nakane, Takahiko; Miyazaki, Yasushi; Niioka, Takenori; Miura, Masatomo; Sawada, Kenichi

    2013-09-01

    Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).

  20. [THE ATOMIC-FORCE MICROSCOPY STUDY OF STRUCTURAL FUNCTIONAL CHARACTERISTICS OF NEUTROPHILS IN PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASES IN PHASE OF EXACERBATION].

    PubMed

    Gainitdinova, V V; Sharafutdinova, L A; Kamaltdinov, I M; Avdeev, S N

    2015-05-01

    The technique of atomic-force microscopy was applied to analyze the structural functional characteristics (morphology, force of adhesion, rigidity of membrane) of neutrophils in patients with chronic obstructive disease of lungs in phase of exacerbation. The regimen of force spectroscopy was applied to implement quantitative evaluation of module of elasticity (Young module) of cell membrane and force of adhesion of neutrophils. The study established decreasing of size of neutrophils, increasing of granularity of cytoplasm, increasing of Young module and force of adhesion in patients with chronic obstructive disease of lungs in phase of exacerbation.

  1. NOTE: A software tool for 2D/3D visualization and analysis of phase-space data generated by Monte Carlo modelling of medical linear accelerators

    NASA Astrophysics Data System (ADS)

    Neicu, Toni; Aljarrah, Khaled M.; Jiang, Steve B.

    2005-10-01

    A computer program has been developed for novel 2D/3D visualization and analysis of the phase-space parameters of Monte Carlo simulations of medical accelerator radiation beams. The software is written in the IDL language and reads the phase-space data generated in the BEAMnrc/BEAM Monte Carlo code format. Contour and colour-wash plots of the fluence, mean energy, energy fluence, mean angle, spectra distribution, energy fluence distribution, angular distribution, and slices and projections of the 3D ZLAST distribution can be calculated and displayed. Based on our experience of using it at Massachusetts General Hospital, the software has proven to be a useful tool for analysis and verification of the Monte Carlo generated phase-space files. The software is in the public domain.

  2. Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure.

    PubMed

    Hosseinzadeh, Mahshid; Nikseresht, Sara; Khodagholi, Fariba; Naderi, Nima; Maghsoudi, Nader

    2016-04-01

    Abnormal and sometimes severe behavioral and molecular symptoms are usually observed in epileptic humans and animals. To address this issue, we examined the behavioral and molecular aspects of seizure evoked by pilocarpine. Autophagy can promote both cell survival and death, but there are controversial reports about the neuroprotective or neurodegenerative effects of autophagy in seizure. Cannabidiol has anticonvulsant properties in some animal models when used as a pretreatment. In this study, we investigated alteration of seizure scores, autophagy pathway proteins, and antioxidant status in hippocampal cells during the chronic phase of pilocarpine-induced epilepsy after treatment with cannabidiol. Cannabidiol (100 ng, intracerebroventricular injection) delayed the chronic phase of epilepsy. Single administration of cannabidiol during the chronic phase of seizure significantly diminished seizure scores such as mouth clonus, head nodding, monolateral and bilateral forelimb clonus and increased the activity of catalase enzyme and reduced glutathione content. Such a protective effect in the behavioral scores of epileptic rats was also observed after repeated administrations of cannabidiol at the onset of the silent phase. Moreover, the amount of Atg7, conjugation of Atg5/12, Atg12, and LC3II/LC3I ratio increased significantly in epileptic rats treated with repeated injections of cannabidiol. In short, our results suggest that post-treatment of Cannabidiol could enhance the induction of autophagy pathway and antioxidant defense in the chronic phase of epilepsy, which could be considered as the protective mechanisms of cannabidiol in a temporal lobe epilepsy model.

  3. Phase III, Randomized, Open-Label Study of Daily Imatinib Mesylate 400 mg Versus 800 mg in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase Using Molecular End Points: Tyrosine Kinase Inhibitor Optimization and Selectivity Study

    PubMed Central

    Cortes, Jorge E.; Baccarani, Michele; Guilhot, François; Druker, Brian J.; Branford, Susan; Kim, Dong-Wook; Pane, Fabrizio; Pasquini, Ricardo; Goldberg, Stuart L.; Kalaycio, Matt; Moiraghi, Beatriz; Rowe, Jacob M.; Tothova, Elena; De Souza, Carmino; Rudoltz, Marc; Yu, Richard; Krahnke, Tillmann; Kantarjian, Hagop M.; Radich, Jerald P.; Hughes, Timothy P.

    2010-01-01

    Purpose To evaluate the safety and efficacy of initial treatment with imatinib mesylate 800 mg/d (400 mg twice daily) versus 400 mg/d in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Patients and Methods A total of 476 patients were randomly assigned 2:1 to imatinib 800 mg (n = 319) or 400 mg (n = 157) daily. The primary end point was the major molecular response (MMR) rate at 12 months. Results At 12 months, differences in MMR and complete cytogenetic response (CCyR) rates were not statistically significant (MMR, 46% v 40%; P = .2035; CCyR, 70% v 66%; P = .3470). However, MMR occurred faster among patients randomly assigned to imatinib 800 mg/d, who had higher rates of MMR at 3 and 6 months compared with those in the imatinib 400-mg/d arm (P = .0035 by log-rank test). CCyR also occurred faster in the 800-mg/d arm (CCyR at 6 months, 57% v 45%; P = .0146). The most common adverse events were edema, gastrointestinal problems, and rash, and all were more common in patients in the 800-mg/d arm. Grades 3 to 4 hematologic toxicity also occurred more frequently in patients receiving imatinib 800 mg/d. Conclusion MMR rates at 1 year were similar with imatinib 800 mg/d and 400 mg/d, but MMR and CCyR occurred earlier in patients treated with 800 mg/d. Continued follow-up is needed to determine the clinical significance of earlier responses on high-dose imatinib. PMID:20008622

  4. Elevated ejection-phase myocardial wall stress in children with chronic kidney disease.

    PubMed

    Gu, Haotian; Sinha, Manish D; Li, Ye; Simpson, John; Chowienczyk, Phil J

    2015-10-01

    Myocardial wall stress (MWS) is thought to be the mechanical stimulus to ventricular hypertrophy. The objective of this study was to examine whether MWS is elevated in children with chronic kidney disease (CKD) who are at high risk of developing adverse cardiovascular events related to left ventricular (LV) hypertrophy. MWS, a function of left ventricular pressure, myocardial wall volume, and cavity volume, was obtained using carotid tonometry to estimate ventricular pressure and 2-dimensional transthoracic echocardiographic wall-tracking to obtain LV cavity and wall volumes. Ninety-two children (50 boys) aged 11.2±3.2 (mean±SD) years, including healthy controls (n=16), and those with CKD disease divided into 3 groups according to estimated glomerular filtration rate (mL/min per 1.73 m2) >90 (CKD 1, n=26), 60 to 90(CKD 2, n=23), and <60 (CKD≥3, n=27) were studied. There was no significant difference in age, height, weight, central or peripheral blood pressure, LV mass, or mass index in the 4 study groups. By contrast, peak, mean, and end-systolic MWS were higher in children with CKD and increased across stages of CKD (peak MWS, 338.8±18.5 and 397.5±14.3 s/cm2 in controls and CKD≥3, respectively; P=0.01). Higher systolic MWS was explained by a form of LV dysfunction whereby dynamic values of the ratio of wall volume/cavity size during systole were lower in children with CKD than in those without (P=0.001). Children with CKD exhibit blood pressure–independent LV dysfunction which results in increased systolic MWS and which may predispose to LV hypertrophy in later life. PMID:26324503

  5. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

    ClinicalTrials.gov

    2015-04-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  6. A phase II study of bortezomib plus prednisone for initial therapy of chronic graft-versus-host disease.

    PubMed

    Herrera, Alex F; Kim, Haesook T; Bindra, Bhavjot; Jones, Kyle T; Alyea, Edwin P; Armand, Philippe; Cutler, Corey S; Ho, Vincent T; Nikiforow, Sarah; Blazar, Bruce R; Ritz, Jerome; Antin, Joseph H; Soiffer, Robert J; Koreth, John

    2014-11-01

    Chronic graft-versus-host disease (GVHD) induces significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Corticosteroids are standard initial therapy, despite limited efficacy and long-term toxicity. Based on our experience using bortezomib as effective acute GVHD prophylaxis, we hypothesized that proteasome-inhibition would complement the immunomodulatory effects of corticosteroids to improve outcomes in chronic GVHD (cGVHD). We undertook a single-arm phase II trial of bortezomib plus prednisone for initial therapy of cGVHD. Bortezomib was administered at 1.3 mg/m(2) i.v. on days 1, 8, 15, and 22 of each 35-day cycle for 3 cycles (15 weeks). Prednisone was dosed at .5 to 1 mg/kg/day, with a suggested taper after cycle 1. All 22 enrolled participants were evaluable for toxicity; 20 were evaluable for response. Bortezomib plus prednisone therapy was well tolerated, with 1 occurrence of grade 3 sensory peripheral neuropathy possibly related to bortezomib. The overall response rate at week 15 in evaluable participants was 80%, including 2 (10%) complete and 14 (70%) partial responses. The organ-specific complete response rate was 73% for skin, 53% for liver, 75% for gastrointestinal tract, and 33% for joint, muscle, or fascia involvement. The median prednisone dose decreased from 50 mg/day to 20 mg/day at week 15 (P < .001). The combination of bortezomib and prednisone for initial treatment of cGVHD is feasible and well tolerated. We observed a high response rate to combined bortezomib and prednisone therapy; however, in this single-arm study, we could not directly measure the impact of bortezomib. Proteasome inhibition may offer benefit in the treatment of cGVHD and should be further evaluated. PMID:25017765

  7. Chronic Artificial Blue-Enriched White Light Is an Effective Countermeasure to Delayed Circadian Phase and Neurobehavioral Decrements

    PubMed Central

    Najjar, Raymond P.; Wolf, Luzian; Taillard, Jacques; Schlangen, Luc J. M.; Salam, Alex

    2014-01-01

    Studies in Polar Base stations, where personnel have no access to sunlight during winter, have reported circadian misalignment, free-running of the sleep-wake rhythm, and sleep problems. Here we tested light as a countermeasure to circadian misalignment in personnel of the Concordia Polar Base station during the polar winter. We hypothesized that entrainment of the circadian pacemaker to a 24-h light-dark schedule would not occur in all crew members (n = 10) exposed to 100–300 lux of standard fluorescent white (SW) light during the daytime, and that chronic non-time restricted daytime exposure to melanopsin-optimized blue-enriched white (BE) light would establish an a stable circadian phase, in participants, together with increased cognitive performance and mood levels. The lighting schedule consisted of an alternation between SW lighting (2 weeks), followed by a BE lighting (2 weeks) for a total of 9 weeks. Rest-activity cycles assessed by actigraphy showed a stable rest-activity pattern under both SW and BE light. No difference was found between light conditions on the intra-daily stability, variability and amplitude of activity, as assessed by non-parametric circadian analysis. As hypothesized, a significant delay of about 30 minutes in the onset of melatonin secretion occurred with SW, but not with BE light. BE light significantly enhanced well being and alertness compared to SW light. We propose that the superior efficacy of blue-enriched white light versus standard white light involves melanopsin-based mechanisms in the activation of the non-visual functions studied, and that their responses do not dampen with time (over 9-weeks). This work could lead to practical applications of light exposure in working environment where background light intensity is chronically low to moderate (polar base stations, power plants, space missions, etc.), and may help design lighting strategies to maintain health, productivity, and personnel safety. PMID:25072880

  8. Chronic artificial blue-enriched white light is an effective countermeasure to delayed circadian phase and neurobehavioral decrements.

    PubMed

    Najjar, Raymond P; Wolf, Luzian; Taillard, Jacques; Schlangen, Luc J M; Salam, Alex; Cajochen, Christian; Gronfier, Claude

    2014-01-01

    Studies in Polar Base stations, where personnel have no access to sunlight during winter, have reported circadian misalignment, free-running of the sleep-wake rhythm, and sleep problems. Here we tested light as a countermeasure to circadian misalignment in personnel of the Concordia Polar Base station during the polar winter. We hypothesized that entrainment of the circadian pacemaker to a 24-h light-dark schedule would not occur in all crew members (n = 10) exposed to 100-300 lux of standard fluorescent white (SW) light during the daytime, and that chronic non-time restricted daytime exposure to melanopsin-optimized blue-enriched white (BE) light would establish an a stable circadian phase, in participants, together with increased cognitive performance and mood levels. The lighting schedule consisted of an alternation between SW lighting (2 weeks), followed by a BE lighting (2 weeks) for a total of 9 weeks. Rest-activity cycles assessed by actigraphy showed a stable rest-activity pattern under both SW and BE light. No difference was found between light conditions on the intra-daily stability, variability and amplitude of activity, as assessed by non-parametric circadian analysis. As hypothesized, a significant delay of about 30 minutes in the onset of melatonin secretion occurred with SW, but not with BE light. BE light significantly enhanced well being and alertness compared to SW light. We propose that the superior efficacy of blue-enriched white light versus standard white light involves melanopsin-based mechanisms in the activation of the non-visual functions studied, and that their responses do not dampen with time (over 9-weeks). This work could lead to practical applications of light exposure in working environment where background light intensity is chronically low to moderate (polar base stations, power plants, space missions, etc.), and may help design lighting strategies to maintain health, productivity, and personnel safety. PMID:25072880

  9. Multicenter phase II clinical trial of nilotinib for patients with imatinib-resistant or -intolerant chronic myeloid leukemia from the East Japan CML study group evaluation of molecular response and the efficacy and safety of nilotinib

    PubMed Central

    2014-01-01

    Background Nilotinib is a second-generation tyrosine kinase inhibitor that exhibits significant efficacy as first- or second-line treatment in patients with chronic myeloid leukemia (CML). We conducted a multicenter Phase II Clinical Trial to evaluate the safety and efficacy of nilotinib among Japanese patients with imatinib-resistant or -intolerant CML-chronic phase (CP) or accelerated phase (AP). Results We analyzed 49 patients (33 imatinib-resistant and 16 imatinib-intolerant) treated with nilotinib 400 mg twice daily. The major molecular response (MMR) rate was 47.8% at 12 months among 35 patients who did not demonstrate an MMR at study entry. Somatic BCR-ABL1 mutations (Y253H, I418V, and exon 8/9 35-bp insertion [35INS]) were detected in 3 patients at 12 months or upon discontinuation of nilotinib. Although 75.5% of patients were still being treated at 12 months, nilotinib treatment was discontinued because of progressing disease in 1 patient, insufficient effect in 2, and adverse events in 9. There was no statistically significant correlation between MMR and trough concentrations of nilotinib. Similarly, no correlation was observed between trough concentrations and adverse events, except for pruritus and hypokalemia. Hyperbilirubinemia was frequently observed (all grades, 51.0%; grades 2–4, 29%; grades 3–4, 4.1%). Hyperbilirubinemia higher than grade 2 was significantly associated with the uridine diphosphate glucuronosyltransferase (UGT)1A9 I399C/C genotype (P = 0.0086; Odds Ratio, 21.2; 95% Confidence Interval 2.2–208.0). Conclusions Nilotinib was efficacious and well tolerated by patients with imatinib-resistant or -intolerant CML-CP/AP. Hyperbilirubinemia may be predicted before nilotinib treatment, and may be controlled by reducing the daily dose of nilotinib in patients with UGT1A9 polymorphisms. Trial registration clinicaltrials.gov: UMIN000002201 PMID:24650752

  10. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  11. A three-dimensional phase field model coupled with lattice kinetics solver for modeling crystal growth in furnaces with accelerated crucible rotation and traveling magnetic field

    SciTech Connect

    Lin, Guang; Bao, Jie; Xu, Zhijie

    2014-11-01

    In this study, which builds on other related work, we present a new three-dimensional numerical model for crystal growth in a vertical solidification system. This model accounts for buoyancy, accelerated crucible rotation technique (ACRT), and traveling magnetic field (TMF) induced convective flow and their effect on crystal growth and the chemical component's transport process. The evolution of the crystal growth interface is simulated using the phase field method. A semi-implicit lattice kinetics solver based on the Boltzmann equation is employed to model the unsteady incompressible flow. A one-way coupled concentration transport model is used to simulate the component fraction variation in both the liquid and solid phases, which can be used to check the quality of the crystal growth.

  12. Accelerated proton echo planar spectroscopic imaging (PEPSI) using GRAPPA with a 32-channel phased-array coil.

    PubMed

    Tsai, Shang-Yueh; Otazo, Ricardo; Posse, Stefan; Lin, Yi-Ru; Chung, Hsiao-Wen; Wald, Lawrence L; Wiggins, Graham C; Lin, Fa-Hsuan

    2008-05-01

    Parallel imaging has been demonstrated to reduce the encoding time of MR spectroscopic imaging (MRSI). Here we investigate up to 5-fold acceleration of 2D proton echo planar spectroscopic imaging (PEPSI) at 3T using generalized autocalibrating partial parallel acquisition (GRAPPA) with a 32-channel coil array, 1.5 cm(3) voxel size, TR/TE of 15/2000 ms, and 2.1 Hz spectral resolution. Compared to an 8-channel array, the smaller RF coil elements in this 32-channel array provided a 3.1-fold and 2.8-fold increase in signal-to-noise ratio (SNR) in the peripheral region and the central region, respectively, and more spatial modulated information. Comparison of sensitivity-encoding (SENSE) and GRAPPA reconstruction using an 8-channel array showed that both methods yielded similar quantitative metabolite measures (P > 0.1). Concentration values of N-acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (mI), and the sum of glutamate and glutamine (Glx) for both methods were consistent with previous studies. Using the 32-channel array coil the mean Cramer-Rao lower bounds (CRLB) were less than 8% for NAA, tCr, and Cho and less than 15% for mI and Glx at 2-fold acceleration. At 4-fold acceleration the mean CRLB for NAA, tCr, and Cho was less than 11%. In conclusion, the use of a 32-channel coil array and GRAPPA reconstruction can significantly reduce the measurement time for mapping brain metabolites.

  13. Accelerated proton echo planar spectroscopic imaging (PEPSI) using GRAPPA with a 32-channel phased-array coil.

    PubMed

    Tsai, Shang-Yueh; Otazo, Ricardo; Posse, Stefan; Lin, Yi-Ru; Chung, Hsiao-Wen; Wald, Lawrence L; Wiggins, Graham C; Lin, Fa-Hsuan

    2008-05-01

    Parallel imaging has been demonstrated to reduce the encoding time of MR spectroscopic imaging (MRSI). Here we investigate up to 5-fold acceleration of 2D proton echo planar spectroscopic imaging (PEPSI) at 3T using generalized autocalibrating partial parallel acquisition (GRAPPA) with a 32-channel coil array, 1.5 cm(3) voxel size, TR/TE of 15/2000 ms, and 2.1 Hz spectral resolution. Compared to an 8-channel array, the smaller RF coil elements in this 32-channel array provided a 3.1-fold and 2.8-fold increase in signal-to-noise ratio (SNR) in the peripheral region and the central region, respectively, and more spatial modulated information. Comparison of sensitivity-encoding (SENSE) and GRAPPA reconstruction using an 8-channel array showed that both methods yielded similar quantitative metabolite measures (P > 0.1). Concentration values of N-acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (mI), and the sum of glutamate and glutamine (Glx) for both methods were consistent with previous studies. Using the 32-channel array coil the mean Cramer-Rao lower bounds (CRLB) were less than 8% for NAA, tCr, and Cho and less than 15% for mI and Glx at 2-fold acceleration. At 4-fold acceleration the mean CRLB for NAA, tCr, and Cho was less than 11%. In conclusion, the use of a 32-channel coil array and GRAPPA reconstruction can significantly reduce the measurement time for mapping brain metabolites. PMID:18429025

  14. MRI-based brain atrophy rates in ADNI phase 2: acceleration and enrichment considerations for clinical trials.

    PubMed

    Hua, Xue; Ching, Christopher R K; Mezher, Adam; Gutman, Boris A; Hibar, Derrek P; Bhatt, Priya; Leow, Alex D; Jack, Clifford R; Bernstein, Matt A; Weiner, Michael W; Thompson, Paul M

    2016-01-01

    The goal of this work was to assess statistical power to detect treatment effects in Alzheimer's disease (AD) clinical trials using magnetic resonance imaging (MRI)-derived brain biomarkers. We used unbiased tensor-based morphometry (TBM) to analyze n = 5,738 scans, from Alzheimer's Disease Neuroimaging Initiative 2 participants scanned with both accelerated and nonaccelerated T1-weighted MRI at 3T. The study cohort included 198 healthy controls, 111 participants with significant memory complaint, 182 with early mild cognitive impairment (EMCI) and 177 late mild cognitive impairment (LMCI), and 155 AD patients, scanned at screening and 3, 6, 12, and 24 months. The statistical power to track brain change in TBM-based imaging biomarkers depends on the interscan interval, disease stage, and methods used to extract numerical summaries. To achieve reasonable sample size estimates for potential clinical trials, the minimal scan interval was 6 months for LMCI and AD and 12 months for EMCI. TBM-based imaging biomarkers were not sensitive to MRI scan acceleration, which gave results comparable with nonaccelerated sequences. ApoE status and baseline amyloid-beta positron emission tomography data improved statistical power. Among healthy, EMCI, and LMCI participants, sample size requirements were significantly lower in the amyloid+/ApoE4+ group than for the amyloid-/ApoE4- group. ApoE4 strongly predicted atrophy rates across brain regions most affected by AD, but the remaining 9 of the top 10 AD risk genes offered no added predictive value in this cohort.

  15. GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-12-03

    Acute Undifferentiated Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance testing

    PubMed Central

    Pietarinen, P O; Pemovska, T; Kontro, M; Yadav, B; Mpindi, J P; Andersson, E I; Majumder, M M; Kuusanmäki, H; Koskenvesa, P; Kallioniemi, O; Wennerberg, K; Heckman, C A; Mustjoki, S; Porkka, K

    2015-01-01

    Chronic myeloid leukemia in blast crisis (CML BC) remains a challenging disease to treat despite the introduction and advances in tyrosine kinase inhibitor (TKI) therapy. In this study we set out to identify novel candidate drugs for CML BC by using an unbiased high-throughput drug testing platform. We used three CML cell lines representing different types of CML blast phases (K562, EM-2 and MOLM-1) and primary leukemic cells from three CML BC patients. Profiling of drug responses was performed with a drug sensitivity and resistance testing platform comprising 295 anticancer agents. Overall, drug sensitivity scores and the drug response profiles of cell line and primary cell samples correlated well and were distinct from other types of leukemia samples. The cell lines were highly sensitive to TKIs and the clinically TKI-resistant patient samples were also resistant ex vivo. Comparison of cell line and patient sample data identified new candidate drugs for CML BC, such as vascular endothelial growth factor receptor and nicotinamide phosphoribosyltransferase inhibitors. Our results indicate that these drugs in particular warrant further evaluation by analyzing a larger set of primary patient samples. The results also pave way for designing rational combination therapies. PMID:25933373

  17. Twisted waveguide accelerating structure.

    SciTech Connect

    Kang, Y. W.

    2000-08-15

    A hollow waveguide with a uniform cross section may be used for accelerating charged particles if the phase velocity of an accelerating mode is equal to or less than the free space speed of light. Regular straight hollow waveguides have phase velocities of propagating electromagnetic waves greater than the free-space speed of light. if the waveguide is twisted, the phase velocities of the waveguide modes become slower. The twisted waveguide structure has been modeled and computer simulated in 3-D electromagnetic solvers to show the slow-wave properties for the accelerating mode.

  18. Late course accelerated hyperfractionated radiotherapy plus concurrent chemotherapy for squamous cell carcinoma of the esophagus: A phase III randomized study

    SciTech Connect

    Zhao Kuaile; Shi Xuehui; Jiang Guoliang . E-mail: jianggl@21cn.com; Yao Weiqiang; Guo Xiaomao; Wu Gendi; Zhu Longxiang

    2005-07-15

    Purpose: Late course accelerated hyperfractionated (LCAF) radiotherapy (RT) is as effective as standard chemoradiotherapy for nonsurgical management of locally advanced esophageal squamous cell carcinoma (SCC). We have evaluated further the efficacy of concurrent LCAF RT and chemotherapy. Methods and Materials: In all, 111 eligible patients with esophageal SCC were randomized to receive LCAF alone (LCAF) or concurrent LCAF and chemotherapy (LCAT+CT) between March 1998 and July 2000. All patients received conventional fractionation irradiation of 1.8 Gy per day, to a dose of 41.4 Gy/23 fractions in 4-5 weeks, followed by accelerated hyperfractionated irradiation using reduced fields, 1.5 Gy/fractions twice a day, to a dose of 27 Gy in 18 days. Thus, the total dose was 68.4 Gy/41 fractions in 44 days. Fifty-four patients in the LCAF+CT arm had an additional four cycles of chemotherapy using cisplatin 25 mg/m{sup 2} daily and fluorouracil (5-FU) 600 mg/m{sup 2} daily on Days 1-3 every 4 weeks starting on the same day that LCAF was delivered. Results: The median survival was 23.9 months (95% confidence [CI], 20.1-27.7) for the LCAF arm and 30.8 months (95% CI, 17.6-44.1) for the LCAF+CT arm, respectively. Survival rates at 1, 3, and 5 years of the LCAF arm were 77%, 39%, and 28%, respectively, while those of the LCAF+CT arm were 67%, 44%, and 40%, respectively (p = 0.310). Grades 3 and 4 acute toxicities occurred in 46% and 25% of the patients in the LCAF arm and the LCAF+CT arm, respectively; 6% of the patients in the combined arm had Grade 5 acute toxicities, whereas none was noted in the LCAF alone arm. Conclusions: Late course accelerated hyperfractionation was effective for locally advanced esophageal SCC. There was a trend toward better survival among patients who received intensified treatment with concurrent chemotherapy. Further randomized studies with a larger number of patients should be carried out, but additional measures must be taken to reduce the higher

  19. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: Results of a multicenter Phase III study

    SciTech Connect

    Sanguineti, Giuseppe . E-mail: gisangui@utmb.edu; Richetti, Antonella; Bignardi, Mario; Corvo, Renzo; Gabriele, Pietro; Sormani, Maria Pia; Antognoni, Paolo

    2005-03-01

    Purpose: To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx. Methods and materials: Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a 'biphasic concomitant boost' schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis. Results: From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% {+-} 4% for CF and 78% {+-} 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% {+-} 5% for CF and 64% {+-} 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% {+-} 4% and 27% {+-} 6% for CF

  20. Phase II trial of hyper CVAD and dasatinib in patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia or blast phase chronic myeloid leukemia.

    PubMed

    Benjamini, Ohad; Dumlao, Theresa Liu; Kantarjian, Hagop; O'Brien, Susan; Garcia-Manero, Guillermo; Faderl, Stefan; Jorgensen, Jeffrey; Luthra, Rajyalakshmi; Garris, Rebecca; Thomas, Deborah; Kebriaei, Partow; Champlin, Richard; Jabbour, Elias; Burger, Jan; Cortes, Jorge; Ravandi, Farhad

    2014-03-01

    Dasatinib is a second generation tyrosine kinase inhibitor, with activity in imatinib resistant Ph-positive ALL.We have treated 34 patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia(ALL) (n519) or lymphoid blast phase of chronic myelogenous leukemia (CML-LB) (n515) with the combination of dasatinib and the hyper CVAD regimen. Prior regimens included hyper CVAD plus imatinib(n511, 4 had transplant in first CR), other combination chemotherapy (n512), monotherapy with kinase inhibitors other than dasatinib (n59), and investigational agents (n52). Pretreatment ABL mutations were noted in 10 patients. The overall response rate was 91%, with 24 patients (71%) achieving complete response(CR), and 7(21%) CR with incomplete platelet recovery (CRp). Two patients died during induction and one had progressive disease. Twenty-six patients (84%) achieved complete cytogenetic remission after one cycle of therapy. Overall, 13 patients (42%) achieved complete molecular response, and 11 patients (35%) had major molecular response (BCR-ABL/ABL<0.1%). Nine patients proceeded to allogeneic transplantation.Grades 3 and 4 toxicities included hemorrhage, pleural and pericardial effusions and infections. The median follow-up for patients with CML-LB is 37.5 months (range, 7–70 months) with a 3-year overall survival of 70%;68% remained in CR at 3 years. For ALL patients, the median follow-up is 52 months (range, 45–59 months)with a 3-year survival of 26%; 30% remain in CR at 3 years. The combination of Hyper CVAD regimen with dasatinib is effective in patients with relapsed Ph-positive ALL and CML-LB. PMID:24779033

  1. MRI-based brain atrophy rates in ADNI phase 2: acceleration and enrichment considerations for clinical trials.

    PubMed

    Hua, Xue; Ching, Christopher R K; Mezher, Adam; Gutman, Boris A; Hibar, Derrek P; Bhatt, Priya; Leow, Alex D; Jack, Clifford R; Bernstein, Matt A; Weiner, Michael W; Thompson, Paul M

    2016-01-01

    The goal of this work was to assess statistical power to detect treatment effects in Alzheimer's disease (AD) clinical trials using magnetic resonance imaging (MRI)-derived brain biomarkers. We used unbiased tensor-based morphometry (TBM) to analyze n = 5,738 scans, from Alzheimer's Disease Neuroimaging Initiative 2 participants scanned with both accelerated and nonaccelerated T1-weighted MRI at 3T. The study cohort included 198 healthy controls, 111 participants with significant memory complaint, 182 with early mild cognitive impairment (EMCI) and 177 late mild cognitive impairment (LMCI), and 155 AD patients, scanned at screening and 3, 6, 12, and 24 months. The statistical power to track brain change in TBM-based imaging biomarkers depends on the interscan interval, disease stage, and methods used to extract numerical summaries. To achieve reasonable sample size estimates for potential clinical trials, the minimal scan interval was 6 months for LMCI and AD and 12 months for EMCI. TBM-based imaging biomarkers were not sensitive to MRI scan acceleration, which gave results comparable with nonaccelerated sequences. ApoE status and baseline amyloid-beta positron emission tomography data improved statistical power. Among healthy, EMCI, and LMCI participants, sample size requirements were significantly lower in the amyloid+/ApoE4+ group than for the amyloid-/ApoE4- group. ApoE4 strongly predicted atrophy rates across brain regions most affected by AD, but the remaining 9 of the top 10 AD risk genes offered no added predictive value in this cohort. PMID:26545631

  2. Accelerated long-term assessment of thermal and chemical stability of bio-based phase change materials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Thermal energy storage (TES) systems incorporated with phase change materials (PCMs) have potential applications to control energy use by building envelopes. However, it is essential to evaluate long term performance of the PCMs and cost effectiveness prior to full scale implementation. For this rea...

  3. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  4. Can Accelerators Accelerate Learning?

    SciTech Connect

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-10

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ)[1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  5. High brightness electron accelerator

    DOEpatents

    Sheffield, Richard L.; Carlsten, Bruce E.; Young, Lloyd M.

    1994-01-01

    A compact high brightness linear accelerator is provided for use, e.g., in a free electron laser. The accelerator has a first plurality of acclerating cavities having end walls with four coupling slots for accelerating electrons to high velocities in the absence of quadrupole fields. A second plurality of cavities receives the high velocity electrons for further acceleration, where each of the second cavities has end walls with two coupling slots for acceleration in the absence of dipole fields. The accelerator also includes a first cavity with an extended length to provide for phase matching the electron beam along the accelerating cavities. A solenoid is provided about the photocathode that emits the electons, where the solenoid is configured to provide a substantially uniform magnetic field over the photocathode surface to minimize emittance of the electons as the electrons enter the first cavity.

  6. An inhibitor of interleukin-6 trans-signalling, sgp130, contributes to impaired acute phase response in human chronic liver disease

    PubMed Central

    Lemmers, A; Gustot, T; Durnez, A; Evrard, S; Moreno, C; Quertinmont, E; Vercruysse, V; Demetter, P; Franchimont, D; Le Moine, O; Geerts, A; Devière, J

    2009-01-01

    In chronic liver disease, high circulating interleukin (IL)-6 contrasts with a poor acute phase response. We evaluated the impact of liver and circulating IL-6-receptor (IL-6R) forms on IL-6 bioactivity in chronic liver disease. IL-6, soluble IL-6-receptor and sgp130 levels were assayed in plasma from 45 patients with alcoholic liver disease, 84 with hepatitis C virus (HCV) infection undergoing transjugular liver biopsies and 15 healthy subjects. IL-6R mRNA was quantified on liver extracts from 54 patients with alcoholic liver disease with or without cirrhosis and 18 HCV-infected patients. The effect of gp130–Fc on fibrinogen secretion induced by IL-6 trans-signalling was evaluated on hepatocyte cultures. Levels of plasma IL-6 and sgp130, but not soluble IL-6R, increased with the stage of chronic liver disease, and correlated significantly with disease severity. Alcoholic liver disease patients had higher plasma IL-6 levels than hepatitis C, but lower liver IL-6R expression. In alcoholic and HCV-related liver diseases, liver IL-6R expression decreased with advanced fibrosis stage. In vitro, on hepatocytes, gp130–Fc blunted the acute phase response while soluble IL-6R enhanced IL-6 stimulation. In advanced chronic liver disease, high plasma IL-6 is associated with low liver IL-6R expression. This situation enables high plasma sgp130 to act as a major negative regulator of liver IL-6 trans-signalling, as demonstrated functionally here on hepatocytes. This might explain the poor acute phase response induced by IL-6 in chronic liver disease. PMID:19438606

  7. k-t Acceleration in pure phase encode MRI to monitor dynamic flooding processes in rock core plugs

    NASA Astrophysics Data System (ADS)

    Xiao, Dan; Balcom, Bruce J.

    2014-06-01

    Monitoring the pore system in sedimentary rocks with MRI when fluids are introduced is very important in the study of petroleum reservoirs and enhanced oil recovery. However, the lengthy acquisition time of each image, with pure phase encode MRI, limits the temporal resolution. Spatiotemporal correlations can be exploited to undersample the k-t space data. The stacked frames/profiles can be well approximated by an image matrix with rank deficiency, which can be recovered by nonlinear nuclear norm minimization. Sparsity of the x-t image can also be exploited for nonlinear reconstruction. In this work the results of a low rank matrix completion technique were compared with k-t sparse compressed sensing. These methods are demonstrated with one dimensional SPRITE imaging of a Bentheimer rock core plug and SESPI imaging of a Berea rock core plug, but can be easily extended to higher dimensionality and/or other pure phase encode measurements. These ideas will enable higher dimensionality pure phase encode MRI studies of dynamic flooding processes in low magnetic field systems.

  8. k-t acceleration in pure phase encode MRI to monitor dynamic flooding processes in rock core plugs.

    PubMed

    Xiao, Dan; Balcom, Bruce J

    2014-06-01

    Monitoring the pore system in sedimentary rocks with MRI when fluids are introduced is very important in the study of petroleum reservoirs and enhanced oil recovery. However, the lengthy acquisition time of each image, with pure phase encode MRI, limits the temporal resolution. Spatiotemporal correlations can be exploited to undersample the k-t space data. The stacked frames/profiles can be well approximated by an image matrix with rank deficiency, which can be recovered by nonlinear nuclear norm minimization. Sparsity of the x-t image can also be exploited for nonlinear reconstruction. In this work the results of a low rank matrix completion technique were compared with k-t sparse compressed sensing. These methods are demonstrated with one dimensional SPRITE imaging of a Bentheimer rock core plug and SESPI imaging of a Berea rock core plug, but can be easily extended to higher dimensionality and/or other pure phase encode measurements. These ideas will enable higher dimensionality pure phase encode MRI studies of dynamic flooding processes in low magnetic field systems.

  9. k-t acceleration in pure phase encode MRI to monitor dynamic flooding processes in rock core plugs.

    PubMed

    Xiao, Dan; Balcom, Bruce J

    2014-06-01

    Monitoring the pore system in sedimentary rocks with MRI when fluids are introduced is very important in the study of petroleum reservoirs and enhanced oil recovery. However, the lengthy acquisition time of each image, with pure phase encode MRI, limits the temporal resolution. Spatiotemporal correlations can be exploited to undersample the k-t space data. The stacked frames/profiles can be well approximated by an image matrix with rank deficiency, which can be recovered by nonlinear nuclear norm minimization. Sparsity of the x-t image can also be exploited for nonlinear reconstruction. In this work the results of a low rank matrix completion technique were compared with k-t sparse compressed sensing. These methods are demonstrated with one dimensional SPRITE imaging of a Bentheimer rock core plug and SESPI imaging of a Berea rock core plug, but can be easily extended to higher dimensionality and/or other pure phase encode measurements. These ideas will enable higher dimensionality pure phase encode MRI studies of dynamic flooding processes in low magnetic field systems. PMID:24809307

  10. Modelling multi-phase liquid-sediment scour and resuspension induced by rapid flows using Smoothed Particle Hydrodynamics (SPH) accelerated with a Graphics Processing Unit (GPU)

    NASA Astrophysics Data System (ADS)

    Fourtakas, G.; Rogers, B. D.

    2016-06-01

    A two-phase numerical model using Smoothed Particle Hydrodynamics (SPH) is applied to two-phase liquid-sediments flows. The absence of a mesh in SPH is ideal for interfacial and highly non-linear flows with changing fragmentation of the interface, mixing and resuspension. The rheology of sediment induced under rapid flows undergoes several states which are only partially described by previous research in SPH. This paper attempts to bridge the gap between the geotechnics, non-Newtonian and Newtonian flows by proposing a model that combines the yielding, shear and suspension layer which are needed to predict accurately the global erosion phenomena, from a hydrodynamics prospective. The numerical SPH scheme is based on the explicit treatment of both phases using Newtonian and the non-Newtonian Bingham-type Herschel-Bulkley-Papanastasiou constitutive model. This is supplemented by the Drucker-Prager yield criterion to predict the onset of yielding of the sediment surface and a concentration suspension model. The multi-phase model has been compared with experimental and 2-D reference numerical models for scour following a dry-bed dam break yielding satisfactory results and improvements over well-known SPH multi-phase models. With 3-D simulations requiring a large number of particles, the code is accelerated with a graphics processing unit (GPU) in the open-source DualSPHysics code. The implementation and optimisation of the code achieved a speed up of x58 over an optimised single thread serial code. A 3-D dam break over a non-cohesive erodible bed simulation with over 4 million particles yields close agreement with experimental scour and water surface profiles.

  11. Acceleration of the loss of the first-phase insulin response during the progression to type 1 diabetes in diabetes prevention trial-type 1 participants.

    PubMed

    Sosenko, Jay M; Skyler, Jay S; Beam, Craig A; Krischer, Jeffrey P; Greenbaum, Carla J; Mahon, Jeffrey; Rafkin, Lisa E; Matheson, Della; Herold, Kevan C; Palmer, Jerry P

    2013-12-01

    We studied the change in the first-phase insulin response (FPIR) during the progression to type 1 diabetes (T1D). Seventy-four oral insulin trial progressors to T1D from the Diabetes Prevention Trial-Type 1 with at least one FPIR measurement after baseline and before diagnosis were studied. The FPIR was examined longitudinally in 26 progressors who had FPIR measurements during each of the 3 years before diagnosis. The association between the change from the baseline FPIR to the last FPIR and time to diagnosis was studied in the remainder (n = 48). The 74 progressors had lower baseline FPIR values than nonprogressors (n = 270), with adjustments made for age and BMI. In the longitudinal analysis of the 26 progressors, there was a greater decline in the FPIR from 1.5 to 0.5 years before diagnosis than from 2.5 to 1.5 years before diagnosis. This accelerated decline was also evident in a regression analysis of the 48 remaining progressors in whom the rate of decline became more marked with the approaching diagnosis. The patterns of decline were similar between the longitudinal and regression analyses. There is an acceleration of decline in the FPIR during the progression to T1D, which becomes especially marked between 1.5 and 0.5 years before diagnosis. PMID:23863814

  12. Acceleration of the loss of the first-phase insulin response during the progression to type 1 diabetes in diabetes prevention trial-type 1 participants.

    PubMed

    Sosenko, Jay M; Skyler, Jay S; Beam, Craig A; Krischer, Jeffrey P; Greenbaum, Carla J; Mahon, Jeffrey; Rafkin, Lisa E; Matheson, Della; Herold, Kevan C; Palmer, Jerry P

    2013-12-01

    We studied the change in the first-phase insulin response (FPIR) during the progression to type 1 diabetes (T1D). Seventy-four oral insulin trial progressors to T1D from the Diabetes Prevention Trial-Type 1 with at least one FPIR measurement after baseline and before diagnosis were studied. The FPIR was examined longitudinally in 26 progressors who had FPIR measurements during each of the 3 years before diagnosis. The association between the change from the baseline FPIR to the last FPIR and time to diagnosis was studied in the remainder (n = 48). The 74 progressors had lower baseline FPIR values than nonprogressors (n = 270), with adjustments made for age and BMI. In the longitudinal analysis of the 26 progressors, there was a greater decline in the FPIR from 1.5 to 0.5 years before diagnosis than from 2.5 to 1.5 years before diagnosis. This accelerated decline was also evident in a regression analysis of the 48 remaining progressors in whom the rate of decline became more marked with the approaching diagnosis. The patterns of decline were similar between the longitudinal and regression analyses. There is an acceleration of decline in the FPIR during the progression to T1D, which becomes especially marked between 1.5 and 0.5 years before diagnosis.

  13. Laser acceleration with open waveguides

    SciTech Connect

    Xie, Ming

    1999-03-01

    A unified framework based on solid-state open waveguides is developed to overcome all three major limitations on acceleration distance and hence on the feasibility of two classes of laser acceleration. The three limitations are due to laser diffraction, acceleration phase slippage, and damage of waveguide structure by high power laser. The two classes of laser acceleration are direct-field acceleration and ponderomotive-driven acceleration. Thus the solutions provided here encompass all mainstream approaches for laser acceleration, either in vacuum, gases or plasmas.

  14. Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia.

    PubMed

    Schulz, Holger; Klein, Saskia Karina; Rehwald, Ute; Reiser, Marcel; Hinke, Axel; Knauf, Wolfgang-Ulrich; Aulitzky, Walter-Erich; Hensel, Manfred; Herold, Michael; Huhn, Dieter; Hallek, Michael; Diehl, Volker; Engert, Andreas

    2002-11-01

    This multicenter phase 2 trial investigated safety and efficacy of a new immunochemotherapeutic regimen combining rituximab (R) and fludarabine (F) in patients with fludarabine- and anthracycline-naive chronic lymphocytic leukemia (CLL). The rationale for using R + F includes single-agent efficacy of both drugs, in vitro synergism of R and F, and no apparent overlapping toxicity. Of 31 eligible patients with B-CLL enrolled, 20 were previously untreated and 11 relapsed. Treatment consisted of fludarabine administered at standard doses (25 mg/m(2)/d; days 1-5, 29-33, 57-61, and 85-89) and rituximab (375 mg/m(2)/d) given on days 57, 85, 113, and 151. Side effects such as fever, chills, and exanthema were generally mild (National Cancer Institute Common Toxicity Criteria [NCI-CTC] grade 1/2 in 48% and grade 3 and/or 4 in 3% of patients). Fever and chills were mainly associated with the first rituximab infusion. Hematologic toxicity included neutropenia (grade 1 and/or 2 in 26%, grade 3 and/or 4 in 42%) and thrombocytopenia (grade 1 and/or 2 in 19%, grade 3 and/or 4 in 9%). One patient died of cerebral bleeding during prolonged thrombocytopenia after the second cycle of fludarabine. There were a total of 32 infections in 16 patients, none of which was fatal. The overall response rate (complete remission [CR] and partial remission [PR]) was 87% (27 of 31 evaluable patients). In 20 previously untreated patients, 17 (85%) responded. Ten of 31 patients achieved CR (5 of 20 untreated; 5 of 11 pretreated; 9 of 21 Binet stage B, 1 of 10 Binet stage C). The median duration of response was 75 weeks. We conclude that the combination of rituximab and fludarabine is feasible and effective in patients with B-CLL. PMID:12384407

  15. Epidemiologic investigation to identify chronic health effects of ambient air pollutants in Southern California. Phase 2. Final report

    SciTech Connect

    Peters, J.M.

    1997-09-01

    The Phase II cross-sectional study was conducted to provide early information on the possible chronic effects of air pollution in Southern California children and to determine, if effects are found, which pollutant (or pollutants) is responsible. Annual questionnaires were completed on these children which covered health history (including history of wheezing, asthma, bronchitis, pneumonia and other respiratory conditions), residential history, housing characteristics (such as heating and air conditioning practices), and history of exposure to other possibly harmful agents, such as tobacco smoke (both active and passive smoking). In addition, the usual physical and outdoor/indoor activity of each subject was ascertained. The lung function of each subject was assessed annually to determine ventilatory capacity. School absenses were recorded to determine frequency and severity of respiratory illnesses. After the development and deployment of the instrumentation, monitoring for air pollutants was conducted for the twelve communities, the schools and a sample of the subject`s residences. Ozone, PM{sub 10}, PM{sub 2.5}, NO{sub 2}, and acid vapor concentrations were determined at the community level, and indoor ozone concentrations were measured at schools. A sample of homes was measured for indoor ozone, PM{sub 10}, PM{sub 2.5}, acid and formaldehyde. The information from the questionnaire on residential history allowed for the construction of an estimated life-time exposure level for the different pollutants based on existing data. The information collected at schools and homes allowed for adjustments for exposures based on whether the subjects were indoors or outdoors.

  16. [Analysis of volatile components in Qingshanlvshui tea using solid-phase microextraction/accelerated solvent extraction-gas chromatography-mass spectrometry].

    PubMed

    Zhan, Jiafen; Lu, Sheming; Meng, Zhaoyu; Xiang, Nengjun; Cao, Qiu'e; Miao, Mingming

    2008-05-01

    The volatile components of Qingshanlvshui Tea were extracted using solid phase micro-extraction (SPME) and accelerated solvent extraction (ASE), and then were identified by gas chromatography-mass spectrometry (GC-MS). It showed that ninety-one compounds were identified, including forty-nine by SPME, fifty-six by ASE, and fourteen by both of them. The main constituents were beta-myrcene, 3,5,5-trimethyl-1,5-heptadiene, L-limonene, alpha-ocimene, beta-ocimene, beta-pinene, 2-methylbenzaldehyde, 5-(hydroxymethyl)-2-furfural. Both SPME and ASE have their advantages. SPME is excellent at simplicity, rapidity, solvent-free, high enrichment, low detection limit, environment friendly etc. ASE has characteristics of time and solvent saving, automation, simplicity, as well as high efficiency.

  17. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia

    PubMed Central

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Levato, Luciano; D’Adda, Mariella; Stagno, Fabio; Tiribelli, Mario; Salvucci, Marzia; Fava, Carmen; Martino, Bruno; Cedrone, Michele; Bocchia, Monica; Trabacchi, Elena; Cavazzini, Francesco; Usala, Emilio; Rossi, Antonella Russo; Bochicchio, Maria Teresa; Soverini, Simona; Alimena, Giuliana; Cavo, Michele; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Baccarani, Michele; Rosti, Gianantonio

    2015-01-01

    Nilotinib is a second-generation tyrosine kinase inhibitor that has been approved for the first-line treatment of chronic-phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib versus imatinib (ENESTnd). Apart from this registration study, very few data are currently available on first-line nilotinib treatment. We report here the long-term, 6-year results of the first investigator-sponsored, GIMEMA multicenter phase 2, single-arm trial with nilotinib 400 mg twice daily as first-line treatment in 73 patients with chronic-phase chronic myeloid leukemia. Six-year overall survival and progression-free survival rates were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose of nilotinib (400 mg twice daily): it highlights the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052). PMID:26113419

  18. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia.

    PubMed

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Levato, Luciano; D'Adda, Mariella; Stagno, Fabio; Tiribelli, Mario; Salvucci, Marzia; Fava, Carmen; Martino, Bruno; Cedrone, Michele; Bocchia, Monica; Trabacchi, Elena; Cavazzini, Francesco; Usala, Emilio; Russo Rossi, Antonella; Bochicchio, Maria Teresa; Soverini, Simona; Alimena, Giuliana; Cavo, Michele; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Baccarani, Michele; Rosti, Gianantonio

    2015-09-01

    Nilotinib is a second-generation tyrosine kinase inhibitor that has been approved for the first-line treatment of chronic-phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib versus imatinib (ENESTnd). Apart from this registration study, very few data are currently available on first-line nilotinib treatment. We report here the long-term, 6-year results of the first investigator-sponsored, GIMEMA multicenter phase 2, single-arm trial with nilotinib 400 mg twice daily as first-line treatment in 73 patients with chronic-phase chronic myeloid leukemia. Six-year overall survival and progression-free survival rates were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥ 2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose of nilotinib (400 mg twice daily): it highlights the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052). PMID:26113419

  19. Increased A20 mRNA Level in Peripheral Blood Mononuclear Cells is Associated With Immune Phases of Patients With Chronic Hepatitis B.

    PubMed

    Sun, Yan-Yan; Fan, Yu-Chen; Wang, Na; Xia, Harry Hua-Xiang; Xiao, Xiao-Yan; Wang, Kai

    2015-12-01

    The zinc finger protein A20 is a newly identified negative regulator of immune response and mediates signal pathway of NF-κB in liver inflammation. However, the role of A20 in the natural history of patients with chronic hepatitis B (CHB) has not been demonstrated. In this present study, we aimed to investigate the dynamic expression of A20 and determine the potential association of A20 in the progression of chronic hepatitis B virus infection.This retrospective study contained 136 patients with chronic hepatitis B and 30 healthy controls (HCs). The mRNA level of A20, TNF-α, NF-κB p65 and toll-like receptor (TLR) 4 in peripheral blood mononuclear cells (PBMCs) was determined using a relative quantitative real-time polymerase chain reaction. The hepatic A20 protein expression was determined by immunohistochemistry. Clinical and laboratory parameters were obtained.In the present study, the relative expression of A20 mRNA was significantly increased in CHB patients compared with HCs and was positively associated with alanine aminotransferase, aspartate aminotransferase, and total bilirubin. In CHB patients, the levels of A20 mRNA in the immune clearance (IC) phase and hepatitis B negative (ENH) phase were significantly higher than that in immune tolerance (IT) phase and low-replicative (LR) phase (P < 0.001). Furthermore, the A20 mRNA level was significantly correlated with TNF-α/ NF-κB p65/TLR4 mRNA levels in CHB patients. Of note, we reported that cutoff values of 4.19 and 3.97 for the level of A20 mRNA have significant power in discriminating IC from IT, and ENH from LR in CHB patients respectively.In conclusion, our results suggested that increased levels of A20 mRNA and protein contribute to disease progression of chronic hepatitis B virus infection. PMID:26717404

  20. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia.

    PubMed

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Levato, Luciano; D'Adda, Mariella; Stagno, Fabio; Tiribelli, Mario; Salvucci, Marzia; Fava, Carmen; Martino, Bruno; Cedrone, Michele; Bocchia, Monica; Trabacchi, Elena; Cavazzini, Francesco; Usala, Emilio; Russo Rossi, Antonella; Bochicchio, Maria Teresa; Soverini, Simona; Alimena, Giuliana; Cavo, Michele; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Baccarani, Michele; Rosti, Gianantonio

    2015-09-01

    Nilotinib is a second-generation tyrosine kinase inhibitor that has been approved for the first-line treatment of chronic-phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib versus imatinib (ENESTnd). Apart from this registration study, very few data are currently available on first-line nilotinib treatment. We report here the long-term, 6-year results of the first investigator-sponsored, GIMEMA multicenter phase 2, single-arm trial with nilotinib 400 mg twice daily as first-line treatment in 73 patients with chronic-phase chronic myeloid leukemia. Six-year overall survival and progression-free survival rates were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥ 2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose of nilotinib (400 mg twice daily): it highlights the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052).

  1. Acceleration gradient of a plasma wakefield accelerator

    SciTech Connect

    Uhm, Han S.

    2008-02-25

    The phase velocity of the wakefield waves is identical to the electron beam velocity. A theoretical analysis indicates that the acceleration gradient of the wakefield accelerator normalized by the wave breaking amplitude is K{sub 0}({xi})/K{sub 1}({xi}), where K{sub 0}({xi}) and K{sub 1}({xi}) are the modified Bessel functions of the second kind of order zero and one, respectively and {xi} is the beam parameter representing the beam intensity. It is also shown that the beam density must be considerably higher than the diffuse plasma density for the large radial velocity of plasma electrons that are required for a high acceleration gradient.

  2. Analysis of tetragonal to monoclinic phase transformation caused by accelerated artificial aging and the effects of microstructure in stabilized zirconia

    NASA Astrophysics Data System (ADS)

    Lucas, Thomas J.

    This investigation addresses the issue that yttria stabilized zirconia is being used as a dental biomaterial without substantial evidence of its long-term viability. Furthermore, stabilized zirconia (SZ) undergoes low temperature degradation (LTD), which can lead to roughening of the surface. A rougher exterior can lead to increased wear of the antagonist in the oral environment. Despite the LTD concerns, SZ is now widely used in restorative dentistry, including full contour crowns. A comparison of aging methods to determine the role of artificial aging on inducing the transformation has not been extensively studied. Therefore, simulations of the transformation process were investigated by comparing different methods of accelerated aging. The rejected null hypothesis is that the temperature of aging treatment will not affect the time required to cause measurable monoclinic transformation of yttria stabilized zirconia. The transformation of SZ starts at the surface and progresses inward; however, it is unclear whether the progression is constant for different aging conditions. This investigation analyzed the depth of transformation as a function of aging conditions for stabilized zirconia in the top 5-6 mum from the surface. The rejected null hypothesis is that the transformation amount is constant throughout the first six micrometers from the surface. The effects of grain size on the amount of monoclinic transformation were also investigated. This study aimed to determine if the grain size of partially stabilized zirconia affects the amount of monoclinic transformation, surface roughness, and property degradation due to aging. The rejected null hypothesis is that the grain size will not affect the amount of monoclinic transformation, thus have no effect on surface roughening or property degradation. The final part of this study addresses the wear of enamel when opposing zirconia by observing how grain size and aging affected the wear rate of an enamel antagonist

  3. Preliminary results of a phase I/II study of simultaneous modulated accelerated radiotherapy for nondisseminated nasopharyngeal carcinoma

    SciTech Connect

    Lee, Sang-wook . E-mail: lsw@amc.seoul.kr; Back, Geum Mun; Yi, Byong Yong; Choi, Eun Kyung; Ahn, Seung Do; Shin, Seong Soo; Kim, Jung-hun; Kim, Sang Yoon; Lee, Bong-Jae; Nam, Soon Yuhl; Choi, Seung-Ho; Kim, Seung-Bae; Park, Jin-hong; Lee, Kang Kyoo; Park, Sung Ho; Kim, Jong Hoon

    2006-05-01

    Purpose: To present preliminary results of intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Methods and Materials: Twenty patients who underwent IMRT for nondisseminated NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. Intensity-modulated radiotherapy was delivered with the 'step and shoot' SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume, 60 Gy (2 Gy/day) to the clinical target volume and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received cisplatin once per week. Results: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had Radiation Therapy Oncology Group Grade 3 mucositis, whereas 9 (45%) had Grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no Grade 3 or 4 xerostomia. All patients showed complete response. Two patients had distant metastases and locoregional recurrence, respectively. Conclusion: Intensity-modulated radiotherapy with the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and might also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

  4. Bevacizumab, Capecitabine, Amifostine, and Preoperative Hypofractionated Accelerated Radiotherapy (HypoArc) for Rectal Cancer: A Phase II Study

    SciTech Connect

    Koukourakis, Michael I.; Tsoutsou, Pelagia; Chloropoulou, Pelagia A.; Manolas, Kostantinos; Sivridis, Efthimios

    2011-06-01

    Purpose: Bevacizumab has established therapeutic activity in patients with metastatic colorectal cancer, and anti-vascular endothelial growth factor therapy enhances the activity of radiotherapy in experimental models. We assessed the feasibility and efficacy of preoperative radiochemotherapy combined with bevacizumab in patients with rectal cancer. Methods and Materials: Nineteen patients with radiologic T3 and/or N+ rectal carcinoma were treated with preoperative conformal hypofractionated accelerated radiotherapy (3.4 Gy in 10 consecutive fractions) supported with amifostine (500-1,000 mg daily), capecitabine (600 mg/m{sup 2} twice daily, 5 days per week), and bevacizumab (5 mg/kg every 2 weeks for 2 cycles). Surgery followed 6 weeks after the end of radiotherapy. A cohort of 14 sequential patients treated with the same regimen without bevacizumab was available for comparison. Results: Grade 2 or 3 diarrhea was noted in 7 of 19 patients (36.8%), which was statistically worse than patients receiving the same regimen without bevacizumab (p = 0.01). A higher incidence of Grade 2 or 3 proctalgia was also noted (21.1%) (p = 0.03). Bladder and skin toxicity was negligible. All toxicities regressed completely within 2 weeks after the end of therapy. Pathologic complete and partial response was noted in 7 of 19 cases (36.8%) and 8 of 19 cases (42.1%). Within a median follow-up of 21 months, none of the patients has had late complications develop and only 1 of 18 evaluable cases (5.5%) has had locoregional relapse. Conclusions: Bevacizumab can be safely combined with hypofractionated radiotherapy and capecitabine as a preoperative radiochemotherapy regimen for patients with rectal cancer. The high pathologic complete response rates urges the testing of bevacizumab in randomized studies.

  5. Particle acceleration in flares

    NASA Technical Reports Server (NTRS)

    Benz, Arnold O.; Kosugi, Takeo; Aschwanden, Markus J.; Benka, Steve G.; Chupp, Edward L.; Enome, Shinzo; Garcia, Howard; Holman, Gordon D.; Kurt, Victoria G.; Sakao, Taro

    1994-01-01

    Particle acceleration is intrinsic to the primary energy release in the impulsive phase of solar flares, and we cannot understand flares without understanding acceleration. New observations in soft and hard X-rays, gamma-rays and coherent radio emissions are presented, suggesting flare fragmentation in time and space. X-ray and radio measurements exhibit at least five different time scales in flares. In addition, some new observations of delayed acceleration signatures are also presented. The theory of acceleration by parallel electric fields is used to model the spectral shape and evolution of hard X-rays. The possibility of the appearance of double layers is further investigated.

  6. Measurements of the temporal and spatial phase variations of a 33 GHz pulsed free electron laser amplifier and application to high gradient RF acceleration

    SciTech Connect

    Volfbeyn, P.; Bekefi, G.

    1995-12-31

    We report the results of temporal and spatial measurements of phase of a pulsed free electron laser amplifier (FEL) operating in combined wiggler and axial guide magnetic fields. The 33 GHz FEL is driven by a mildly relativistic electron beam (750 kV, 90-300 A, 30 ns) and generates 61 MW of radiation with a high power magnetron as the input source. The phase is measured by an interferometric technique from which frequency shifting is determined. The results are simulated with a computer code. Experimental studies on a CERN-CLIC 32.98 GHz 26-cell high gradient accelerating section (HGA) were carried out for input powers from 0.1 MW to 35 MW. The FEL served as the r.f. power source for the HGA. The maximum power in the transmitted pulse was measured to be 15 MW for an input pulse of 35 MW. The theoretically calculated shunt impedance of 116 M{Omega}/m predicts a field gradient of 65 MeV/m inside the HGA. For power levels >3MW the pulse transmitted through the HGA was observed to be shorter than the input pulse and pulse shortening became more serious with increasing power input. At the highest power levels the output pulse length (about 5 nsec) was about one quarter of the input pulse length. Various tests suggest that these undesirable effects occur in the input coupler to the HGA. Light and X-ray production inside the HGA have been observed.

  7. Phase I trial of tirapazamine, cisplatin, and concurrent accelerated boost reirradiation in patients with recurrent head and neck cancer

    SciTech Connect

    Cohen, Ezra E.W.; Haraf, Daniel J.; Loh, Elwyn; Shen, Liji; Lusinchi, Antoine; Vokes, Everett E.; Bourhis, Jean

    2007-03-01

    Purpose: Reirradiation (re-RT) with concurrent chemotherapy offers a therapeutic option in patients who have locoregional recurrence of head and neck cancer (HNC). The hypoxic cell sensitizer, tirapazamine (TPZ), has demonstrated promising results in first-line therapy for HNC. This phase I trial was designed to test the feasibility of giving TPZ in the re-RT setting. Methods and Materials: Patients with recurrent HNC who received prior radiotherapy (RT) were enrolled and received TPZ (260 mg/m{sup 2}) and cisplatin (50 mg/m{sup 2}) Weeks 1, 3, and 5 concurrently with RT (72 Gy, 42 fractions over 6 weeks). TPZ (160 mg/m{sup 2}) alone was added on Days 1, 3, and 5 of Week 2 (cohort 1) or Weeks 2 and 4 (cohort 2). Results: Twenty-five subjects were enrolled, 7 and 18 on cohorts 1 and 2, respectively. Significant toxicities included Grade 3 dermatitis (20%) and Grade 3 mucositis (40%). Dose-limiting toxicity was observed on cohort 2 (1 patient with aspiration pneumonia). Four deaths occurred during treatment. Two fatalities occurred after completing therapy as a result of carotid artery rupture. With a minimum and median follow-up of 14 and 24 months, respectively, median overall survival was 14 months with actuarial 1-year and 2-year survival of 56% and 27%, respectively. Conclusion: Reirradiation with concomitant chemotherapy including TPZ in patients with unresectable recurrent HNC is feasible and results in long-term survival in a significant proportion of patients.

  8. Local release of pioglitazone (a peroxisome proliferator-activated receptor γ agonist) accelerates proliferation and remodeling phases of wound healing.

    PubMed

    Sakai, Shigeki; Sato, Keisuke; Tabata, Yasuhiko; Kishi, Kazuo

    2016-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily known for its anti-inflammatory and macrophage differentiation effects, as well as its ability to promote fat cell differentiation and reduce insulin resistance. Pioglitazone (Pio) is a PPARγ agonist used clinically as an anti-diabetic agent for improving insulin sensitivity in patients with diabetes. The objective of this study was to develop a drug delivery system (DDS) for the local release of Pio to promote wound healing. Pio of low aqueous solubility was water-solubilized by micelles formed from gelatin grafted with L-lactic acid oligomers, and incorporated into a biodegradable gelatin hydrogel. An 8-mm punch biopsy tool was used to prepare two skin wounds on either side of the midline of 8-week-old mice. Wounds were treated by the hydrogels with (Pio-hydrogel group) or without (control group) Pio, and the wound area were observed 1, 4, 7, and 14 days after treatment. In addition, a protein assay and immunohistological stain were performed to determine the effects of the Pio-hydrogel on inflammation and macrophage differentiation. The Pio-hydrogels promote wound healing. Moreover, Western blotting analysis demonstrated that treatment with Pio-hydrogels resulted in decreased levels of the cytokines MIP-2 and TGF-β, and increased levels of glucose-regulating adiponectin. It is concluded that Pio-incorporated hydrogels promote the proliferation and remodeling phases of wound healing, and may prove to be effective as wound dressings. PMID:26710090

  9. Morphometric age estimate of the last phase of accelerated uplift in the Kazdag area (Biga Peninsula, NW Turkey)

    NASA Astrophysics Data System (ADS)

    Demoulin, A.; Altin, T. Bayer; Beckers, A.

    2013-11-01

    While the Plio-Quaternary uplift of the Kazdag mountain range (Biga Peninsula, NW Turkey) is generally acknowledged, little is known about its detailed timing. Partly because of this lack of data, the cause of this uplift phase is also debated, being associated either to back-arc extension in the rear of the Hellenic subduction zone, to transpression along the northern edge of the west-moving Anatolian microplate, or to extension driven by gravitational collapse. Here, we perform a morphometric study of the fluvial landscape at the scale of the Biga Peninsula, coupling the recently developed R/SR analysis of the drainage network with concavity and steepness measures of a set of 29 rivers of all sizes. While the dependence of profile concavity on basin size confirms that the landscape of the peninsula is still in a transient state, the spatial distribution of profile steepness values characterized by higher values for streams flowing down from the Kazdag massif shows that the latter undergoes higher uplift rates than the rest of the peninsula. We obtain a SR value of 0.324 ± 0.035 that, according to the relation established by Demoulin (2012), yields an age range of 0.5-1.3 Ma and a most probable value of 0.8 Ma for the time of the last tectonic perturbation in the region. In agreement with the analysis of knickpoint migration in a subset of rivers, this suggests that a pulse of uplift occurred at that time and, corroborated by sparse published observations in the Bayramiç and Çanakkale depressions, that the peninsula was uplifted as a whole from that time. This uplift pulse might have been caused by transient compressive conditions in the Anatolian plate when the Eratosthenes seamount came to subduct beneath the Cyprus arc around the early-to-mid Pleistocene transition (Schattner, 2010).

  10. Autoxidation and acetylene-accelerated oxidation of NO in a 2-phase system; implications for the expression of denitrification in ex situ experiments

    NASA Astrophysics Data System (ADS)

    Nadeem, Shahid; Dörsch, Peter; Bakken, Lars

    2013-04-01

    Denitrification allows microorganisms to sustain respiration under anoxic conditions. The typical niche for denitrification is an environment with fluctuating oxygen concentrations such as soils and borders between anoxic and oxic zones of biofilms and sediments. In such environments, the organisms need adequate regulation of denitrification in response to changing oxygen availability to tackle both oxic and anoxic spells. The regulation of denitrification in soils has environmental implications, since it affects the proportions of N2, N2O and NO emitted to the atmosphere. The expression of denitrification enzymes is regulated by a complex regulatory network involving one or several positive feedback loops via the intermediate nitrogen oxides. Nitric oxide (NO) is known to induce denitrification in model organisms, but the quantitative effect of NO and its concentration dependency has not been assessed for denitrification in soils. NO is chemically unstable in the presence of oxygen due to autoxidation, and the oxidation of NO is accelerated by acetylene (C2H2) which is commonly used as an inhibitor of N2O reductase in denitrification studies. As a first step to a better understanding of NO's role in soil denitrification, we investigated NO oxidation kinetics for a closed "two phase" system (i.e. liquid phase + headspace) typically used for denitrification experiments with soil slurries, with and without acetylene present. Models were developed to adequately predict autoxidation and acetylene-accelerated oxidation. The minimum oxygen concentration in the headspace ([O2]min, mL L-1) for acetylene-accelerated NO oxidation was found to increase linearly with the NO concentration ([NO], mL L-1); [O2]min= 0.192 + [NO]*0.1 (r2=0.978). The models for NO oxidation were then used to assess NO-oxidation rates in denitrification experiments with batches of bacterial cells extracted from soil. The batches were exposed to low initial oxygen concentrations in gas tight serum

  11. Effects of sensorimotor foot training on the symmetry of weight distribution on the lower extremities of patients in the chronic phase after stroke

    PubMed Central

    Goliwas, Magdalena; Kocur, Piotr; Furmaniuk, Lech; Majchrzycki, Marian; Wiernicka, Marzena; Lewandowski, Jacek

    2015-01-01

    [Purpose] To assess the effects of sensorimotor foot stimulation on the symmetry of weight distribution on the feet of patients in the chronic post-stroke phase. [Subjects and Methods] This study was a prospective, single blind, randomized controlled trial. In the study we examined patients with chronic stroke (post-stroke duration > 1 year). They were randomly allocated to the study group (n=8) or to the control group (n=12). Both groups completed a standard six-week rehabilitation programme. In the study group, the standard rehabilitation programme was supplemented with sensorimotor foot stimulation training. Each patient underwent two assessments of symmetry of weight distribution on the lower extremities with and without visual control, on a treadmill, with stabilometry measurements, and under static conditions. [Results] Only the study group demonstrated a significant increase in the weight placed on the leg directly affected by stroke, and a reduction in asymmetry of weight-bearing on the lower extremities. [Conclusion] Sensorimotor stimulation of the feet enhanced of weight bearing on the foot on the side of the body directly affected by stroke, and a decreased asymmetry of weight distribution on the lower extremities of patients in the chronic post-stroke phase. PMID:26504326

  12. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    SciTech Connect

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; Ende, Piet van den; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  13. Accelerated Partial Breast Irradiation: 5-Year Results of the German-Austrian Multicenter Phase II Trial Using Interstitial Multicatheter Brachytherapy Alone After Breast-Conserving Surgery

    SciTech Connect

    Strnad, Vratislav; Hildebrandt, Guido; Poetter, Richard; Hammer, Josef; Hindemith, Marion; Resch, Alexandra; Spiegl, Kurt; Lotter, Michael; Uter, Wolfgang; Bani, Mayada; Kortmann, Rolf-Dieter; Beckmann, Matthias W.; Fietkau, Rainer; Ott, Oliver J.

    2011-05-01

    Purpose: To evaluate the impact of accelerated partial breast irradiation on local control, side effects, and cosmesis using multicatheter interstitial brachytherapy as the sole method for the adjuvant local treatment of patients with low-risk breast cancer. Methods and Materials: 274 patients with low-risk breast cancer were treated on protocol. Patients were eligible for the study if the tumor size was < 3 cm, resection margins were clear by at least 2 mm, no lymph node metastases existed, age was >35 years, hormone receptors were positive, and histologic grades were 1 or 2. Of the 274 patients, 175 (64%) received pulse-dose-rate brachytherapy (D{sub ref} = 50 Gy). and 99 (36%) received high-dose-rate brachytherapy (D{sub ref} = 32.0 Gy). Results: Median follow-up was 63 months (range, 9-103). Only 8 of 274 (2.9%) patients developed an ipsilateral in-breast tumor recurrence at the time of analysis. The 5-year actuarial local recurrence-free survival probability was 98%. The 5- year overall and disease-free survival probabilities of all patients were 97% and 96%, respectively. Contralateral in-breast malignancies were detected in 2 of 274 (0.7%) patients, and distant metastases occurred in 6 of 274 (2.2%). Late side effects {>=}Grade 3 (i.e., breast tissue fibrosis and telangiectasia) occurred in 1 patient (0.4%, 95%CI:0.0-2.0%) and 6 patients (2.2%, 95%CI:0.8-4.7%), respectively. Cosmetic results were good to excellent in 245 of 274 patients (90%). Conclusions: The long-term results of this prospective Phase II trial confirm that the efficacy of accelerated partial breast irradiation using multicatheter brachytherapy is comparable with that of whole breast irradiation and that late side effects are negligible.

  14. Phase-plane analysis of gaze stabilization to high acceleration head thrusts: a continuum across normal subjects and patients with loss of vestibular function.

    PubMed

    Peng, Grace C Y; Zee, David S; Minor, Lloyd B

    2004-04-01

    We investigated the vestibulo-ocular reflex (VOR) during high-acceleration, yaw-axis, head rotations in 12 normals and 15 patients with vestibular loss [7 unilateral vestibular deficient (UVD) and 8 bilateral vestibular deficient (BVD)]. We analyzed gaze stabilization within a 200-ms window after head rotation began, using phase planes, which allowed simultaneous analysis of gaze velocity and gaze position. These "gaze planes" revealed critical dynamic information not easily gleaned from traditional gain measurements. We found linear relationships between peak gaze-velocity and peak gaze-position error when normalized to peak head speed and position, respectively. Values fell on a continuum, increasing from normals, to normals tested with very high acceleration (VHA = 10,000-20,000 degrees/s2), to UVD patients during rotations toward the intact side, to UVD patients during rotations toward the lesioned side, to BVD patients. We classified compensatory gaze corrections as gaze-position corrections (GPCs) or gaze-velocity error corrections (GVCs). We defined patients as better-compensated when the value of their end gaze position was low relative to peak gaze position. In the gaze plane this criterion corresponded to relatively stereotyped patterns over many rotations, and appearance of high velocity (100-400 degrees/s) GPCs in the gaze plane ending quadrant (150-200 ms after head movement onset). In less-compensated patients, and normals at VHA, more GVCs were generated, and GPCs were generated only after gaze-velocity error was minimized. These findings suggest that challenges to compensatory vestibular function can be from vestibular deficiency or novel stimuli not previously experienced. Similar patterns of challenge and compensation were observed in both patients with vestibular loss and normal subjects.

  15. Accelerated Partial Breast Irradiation With IMRT: New Technical Approach and Interim Analysis of Acute Toxicity in a Phase III Randomized Clinical Trial

    SciTech Connect

    Livi, Lorenzo; Buonamici, Fabrizio Banci; Simontacchi, Gabriele; Scotti, Vieri; Fambrini, Massimiliano; Compagnucci, Antonella; Paiar, Fabiola; Scoccianti, Silvia; Pallotta, Stefania; Detti, Beatrice; Agresti, Benedetta; Talamonti, Cinzia; Mangoni, Monica; Bianchi, Simonetta; Cataliotti, Luigi; Marrazzo, Livia; Bucciolini, Marta; Biti, Giampaolo

    2010-06-01

    Purpose: To evaluate with a randomized clinical trial the possibility of treating the index quadrant with external intensity-modulated radiotherapy (IMRT) in a selected group of patients with early-stage breast cancer and to analyze the acute toxicity. Methods and Materials: From September 2005, a randomized Phase III clinical trial has been conducted to compare conventional (tangential field) fractionated whole breast treatment (Arm A) with accelerated partial breast irradiation plus intensity-modulated radiotherapy (Arm B). For intensity-modulated radiotherapy, the clinical target volume was drawn with a uniform 1-cm margin around the surgical clips in three dimensions. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk. All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations. Results: In September 2008, 259 patients were randomized and treated. The mean clinical target volume in Arm B was 44 cm{sup 3} and the mean planning target volume was 123 cm{sup 3}. The mean value of the ratio between the planning target volume and the ipsilateral breast volume was 21%. The rate of Grade 1 and Grade 2 acute skin toxicity was 22% and 19% in Arm A (Radiation Therapy Oncology Group scale), respectively. The tolerance in Arm B was excellent with only 5% Grade 1 and 0.8% Grade 2 acute skin toxicity. The planning constraints were fully satisfied in most patients. In a very few cases, this was not possible because of very unfavorable anatomy. Quality assurance procedures were performed according to our internal quality assurance protocol, with excellent results. Conclusion: In the present preliminary analysis, we have demonstrated that accelerated partial breast irradiation is feasible, with very low acute toxicity.

  16. Peroxisome Proliferator-Activated Receptor γ Deficiency in T Cells Accelerates Chronic Rejection by Influencing the Differentiation of CD4+ T Cells and Alternatively Activated Macrophages

    PubMed Central

    Ye, Ping; Cheng, Chao; Wu, Jie; Wang, Sihua; Sun, Yuan; Liu, Zheng; Xie, Aini; Xia, Jiahong

    2014-01-01

    Background In a previous study, activation of the peroxisome proliferator–activated receptor γ (PPARγ) inhibited chronic cardiac rejection. However, because of the complexity of chronic rejection and the fact that PPARγ is widely expressed in immune cells, the mechanism of the PPARγ - induced protective effect was unclear. Materials and Methods A chronic rejection model was established using B6.C-H-2bm12KhEg (H-2bm12) mice as donors, and MHC II-mismatched T-cell-specific PPARγ knockout mice or wild type (WT) littermates as recipients. The allograft lesion was assessed by histology and immunohistochemistry. T cells infiltrates in the allograft were isolated, and cytokines and subpopulations were detected using cytokine arrays and flow cytometry. Transcription levels in the allograft were measured by RT-PCR. In vitro, the T cell subset differentiation was investigated after culture in various polarizing conditions. PPARγ-deficient regularory T cells (Treg) were cocultured with monocytes to test their ability to induce alternatively activated macrophages (AAM). Results T cell-specific PPARγ knockout recipients displayed reduced cardiac allograft survival and an increased degree of pathology compared with WT littermates. T cell-specific PPARγ knockout resulted in more CD4+ T cells infiltrating into the allograft and altered the Th1/Th2 and Th17/Treg ratios. The polarization of AAM was also reduced by PPARγ deficiency in T cells through the action of Th2 and Treg. PPARγ-deficient T cells eliminated the pioglitazone-induced polarization of AAM and reduced allograft survival. Conclusions PPARγ-deficient T cells influenced the T cell subset and AAM polarization in chronic allograft rejection. The mechanism of PPARγ activation in transplantation tolerance could yield a novel treatment without side effects. PMID:25383620

  17. The role of CD8+T cells in the acute and chronic phases of Theiler's murine encephalomyelitis virus-induced disease in mice.

    PubMed

    Borrow, P; Tonks, P; Welsh, C J; Nash, A A

    1992-07-01

    The technique of in vivo depletion with T cell subset-specific monoclonal antibodies was used to study the involvement of CD8+T cells in protection/pathogenesis during the acute and chronic demyelinating phases of Theiler's murine encephalomyelitis virus (TMEV)-induced disease. Mice rendered CD8-deficient prior to infection with TMEV were less efficient at clearing virus from the central nervous system compared to intact animals and also suffered demyelinating disease of earlier onset and increased severity. This indicates that CD8+ cells have a protective role in virus clearance at early times post-infection, and may also be involved in downregulating the severity of the chronic demyelinating disease. How CD8+ T cells function to produce these effects is discussed.

  18. Future accelerators (?)

    SciTech Connect

    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  19. [One of the Mechanisms in Blastic Transformation of Chronic Myeloid Leukemia: Epigenetics Abnormality--Review].

    PubMed

    Meng, Zhen; Li, Ying-Hua

    2016-02-01

    Chronic myeloid leukemia is a myeloproliferative disorder characterized by excessive cloning of bone marrow multipotent stem cells. According to the disease course, the CML may be divided into chronic phase (CP), accelerated phase (AP) and blastic phase (BP). At present, the molecular mechanisms of acute transformation of CML has not been fully understood. The recent studies have shown that the epigenetics is one of mechanisms in blastic transformation of CML, including three molecular mechanisms such as DNA modification, histone modifications and RNA-related dysregulation. The molecular mechanisms for epigenetics leading to the transformation of CML are discussed in this review. PMID:26913431

  20. Near infrared lymphatic imaging demonstrates the dynamics of lymph flow and lymphangiogenesis during the acute vs. chronic phases of arthritis in mice

    PubMed Central

    Zhou, Quan; Wood, Ronald; Schwarz, Edward M.; Wang, Yong-Jun; Xing, Lianping

    2010-01-01

    Objective Development of an in vivo imaging method to assess lymphatic draining function in the K/B×N mouse model of inflammatory arthritis. Methods Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye, was injected intradermally into the footpad of wild-type mice, the limb was illuminated with an 806 nm NIR laser, and the movement of ICG from the injection site to the draining popliteal lymph node (PLN) was recorded with a CCD camera. ICG-NIR images were analyzed to obtain 5 measures of lymphatic function across time. K/B×N arthritic mice and control non-arthritic littermates were imaged at one-month of age when acute joint inflammation commenced, and repeated at 3 months when joint inflammation became chronic. Lymphangiogenesis in PLNs was assessed by immunochemistry. Results ICG and its transport within lymphatic vessels were readily visualized and quantitative measures derived. During the acute phase of arthritis, the lymphatic vessels were dilated with increased ICG signal intensity and lymphatic pulses, and PLNs became fluorescent quickly. During the chronic phase, new lymphatic vessels were present near the foot. However, ICG appearance in lymphatic vessels was delayed. The size and area of PLN lymphatic sinuses progressively increased in the K/B×N mice. Conclusion ICG-NIR lymphatic imaging is a valuable method to assess the lymphatic draining function in mice with inflammatory arthritis. ICG-NIR imaging of K/B×N mice identified two distinct lymphatic phenotypes during the acute and chronic phase of inflammation. This technique can be used to assess new therapies for lymphatic disorders. PMID:20309866

  1. Long-term evaluation of combined prolonged-release oxycodone and naloxone in patients with moderate-to-severe chronic pain: pooled analysis of extension phases of two Phase III trials

    PubMed Central

    Blagden, M; Hafer, J; Duerr, H; Hopp, M; Bosse, B

    2014-01-01

    Background While opioids provide effective analgesia, opioid-induced constipation (OIC) can severely impact quality of life and treatment compliance. This pooled analysis evaluated the maintenance of efficacy and safety during long-term treatment with combined oxycodone/naloxone prolonged-release tablets (OXN PR) in adults with moderate-to-severe chronic pain. Methods Patients (N = 474) received open-label OXN PR during 52-week extension phases of two studies, having completed 12-week, double-blind, randomized treatment with oxycodone prolonged-release tablets (Oxy PR) or OXN PR. Analgesia and bowel function were assessed at each study visit using ‘Average pain over last 24 h scale and Bowel Function Index (BFI), respectively. Treatment Satisfaction Questionnaire for Medication was assessed at study end only. Key Results Improvement in bowel function was particularly marked in patients who switched from Oxy PR in the double-blind phase to OXN PR during the extension phase, resulting in a clinically meaningful reduction (≥12 points) in BFI score: at the start of the extension phases, mean (SD) BFI score was 44.3 (28.13), and was 29.8 (26.36) for patients who had received OXN PR in the double-blind phase. One week later, BFI scores were similar for the two groups (26.5 [24.40] and 27.5 [25.60], respectively), as was observed throughout the following months. Fewer than 10% of patients received laxatives regularly. Mean 24-h pain scores were low and stable throughout the extension phases. No unexpected adverse events were observed. Conclusions & Inferences Pooled data demonstrate OXN PR is an effective long-term therapy for patients with chronic non-cancer pain, and can address symptoms of OIC. No new safety issues were observed which were attributable to the long-term administration of OXN PR. PMID:25346155

  2. Fucosylation and galactosylation of IgG heavy chains differ between acute and remission phases of juvenile chronic arthritis.

    PubMed

    Flögel, M; Lauc, G; Gornik, I; Macek, B

    1998-02-01

    Oligosaccharide structures are attached to nearly all membrane and serum proteins, and their composition changes significantly in many diseases. We have analysed glycosylation of IgG heavy chains in 34 patients with juvenile chronic arthritis and 13 control individuals. IgG was purified from 0.7 ml of serum, separated by electrophoresis and transferred on to polyvinylidene difluoride (PVDF) membrane. Ricinus communis agglutinin (RCA I) and Bandeirea simplicifolia (BSA II) and Ulex europaeus (UEA I) lectins were used to measure galactose, N-acetylglucosamine and fucose, respectively. While there was no significant difference in average levels of galactose and N-acetylglucosamine, patients with juvenile chronic arthritis had 2.4 times more fucose attached to IgG heavy chains than control individuals. A different picture emerged when patients were divided into those with acute disease and those in remission. Patients in whom juvenile chronic arthritis was currently active had significantly lower levels of galactose than those in remission, in whom galactose levels were comparable to the control group. Fucose levels in both groups of patients were significantly higher than in the control group. These results show that whereas de-galactosylation is a good test to detect and measure the activity of juvenile chronic arthritis, increased fucosylation is a much more reliable measure for diagnosis of the disease itself.

  3. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase.

    PubMed

    Badar, Talha; Kantarjian, Hagop M; Ravandi, Farhad; Jabbour, Elias; Borthakur, Gautam; Cortes, Jorge E; Pemmaraju, Naveen; Pierce, Sherry R; Newberry, Kate J; Daver, Naval; Verstovsek, Srdan

    2015-09-01

    Myeloproliferative neoplasm (MPN) transformed to acute myeloid leukemia (MPN-AML), MPN in accelerated phase (MPN-AP), and high-risk primary myelofibrosis (PMF) are associated with a poor response to therapy and very short survival. Several reports have suggested clinical activity of hypomethylating agents in these patients. We conducted a retrospective study of 21 patients with MPN-AML, 13 with MPN-AP and 11 with DIPSS-plus high-risk PMF treated with decitabine at our institution over the last 7 years and evaluated their clinical outcomes. Six patients (29%) with MPN-AML responded to decitabine (3 CR, 2 CRi, and 1 PR); median response duration was 7 months. The median overall survival (OS) was significantly higher in those who responded (10.5 vs 4 months). Among patients with MPN-AP, 8 patients (62%) benefited; the median response duration was 6.5 months. The median OS was 11.8 months in responders vs 4.7 months in non-responders. Among patients with DIPSS-plus high-risk PMF, 9 (82%) benefited; the median response duration was 9 months. The median OS was 32 months in responders vs 16.3 months in non-responders. Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other clinically active agents are needed to improve overall outcome.

  4. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase

    PubMed Central

    Badar, Talha; Kantarjian, Hagop M.; Ravandi, Farhad; Jabbour, Elias; Borthakur, Gautam; Cortes, Jorge E.; Pemmaraju, Naveen; Pierce, Sherry R.; Newberry, Kate J.; Daver, Naval; Verstovsek, Srdan

    2015-01-01

    Myeloproliferative neoplasm (MPN) transformed to acute myeloid leukemia (MPN-AML), MPN in accelerated phase (MPN-AP), and high-risk primary myelofibrosis (PMF) are associated with a poor response to therapy and very short survival. Several reports have suggested clinical activity of hypomethylating agents in these patients. We conducted a retrospective study of 21 patients with MPN-AML, 13 with MPN-AP and 11 with DIPSS-plus high-risk PMF treated with decitabine at our institution over the last 7 years and evaluated their clinical outcomes. Six patients (29%) with MPN-AML responded to decitabine (3 CR, 2 CRi, and 1 PR); median response duration was 7 months. The median overall survival (OS) was significantly higher in those who responded (10.5 vs 4 months). Among patients with MPN-AP, 8 patients (62%) benefited; median response duration was 6.5 months. The median OS was 11.8 months in responders vs 4.7 months in non-responders. Among patients with DIPSS-plus high-risk PMF, 9 (82%) benefited; median response duration was 9 months. The median OS was 32 months in responders vs 16.3 months in non-responders. Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other clinically active agents are needed to improve overall outcome. PMID:26183878

  5. Determination of fluoroquinolone antibacterial agents in sewage sludge and sludge-treated soil using accelerated solvent extraction followed by solid-phase extraction.

    PubMed

    Golet, Eva M; Strehler, Adrian; Alder, Alfredo C; Giger, Walter

    2002-11-01

    A method for the quantitative determination of humanuse fluoroquinolone antibacterial agents (FQs) ciprofloxacin and norfloxacin in sewage sludge and sludge-treated soil samples was developed. The accelerated solvent extraction was optimized with regard to solvents and operational parameters, such as temperature, pressure, and extraction time. A 50 mM aqueous phosphoric acid/ acetonitrile mixture (1:1) was found to be optimum in combination with an extraction temperature of 100 degrees C at 100 bar, during 60 and 90 min for sewage sludge and sludge-treated soil samples, respectively. A cleanup step using solid-phase extraction substantially improved the selectivity of the method. Overall recovery rates for FQs ranged from 82 to 94% for sewage sludge and from 75 to 92% for sludge-treated soil, with relative standard deviations between 8 and 11%. Limits of quantification were 0.45 and 0.18 mg/kg of dry matter for sewage sludge and sludge-treated soils, respectively. The presented method was successfully applied to untreated and anaerobically digested sewage sludges and sludge-treated soils. Ciprofloxacin and norfloxacin were determined in sewage sludges from several wastewater treatment plants with concentrations ranging from 1.40 to 2.42 mg/kg of dry matter. Therefore, contrary to what may be expected for human-use pharmaceuticals, FQs may reach the terrestrial environment as indicated by the occurrence of FQs in topsoil samples from experimental fields, to which sewage sludge had been applied. PMID:12433073

  6. International clinical trials of HIV vaccines: II. phase I trial of an HIV-1 synthetic peptide vaccine evaluating an accelerated immunization schedule in Yunnan, China.

    PubMed

    Li, D; Forrest, B D; Li, Z; Xue, P; Hanson, C V; Duan, S; Cheng, H; Li, M; Wang, C Y; Koff, W C

    1997-06-01

    A Phase 1, double-blind, placebo controlled trial was conducted in Longchuan County, China, to evaluate the safety and immunogenicity of a prototype HIV-1 synthetic peptide vaccine in a target population at risk for HIV infection, and to establish the infrastructure for future large-scale HIV vaccine efficacy trials. Subjects were randomly assigned to receive 100 microg or 500 microg of vaccine or alum placebo, and were given three injections at an accelerated 0, 1, and 2 month schedule. The vaccine was well tolerated with no significant local or systemic reactions observed in any subjects. Fifty-five percent (100 microg dose) and 64% (500 microg dose) of subjects who received the vaccine produced binding antibody to the immunogen as determined by ELISA. However, HIV-1 (MN) neutralizing antibody was detected in only 23% (3/13) of subjects with detectable HIV-1 specific binding antibody. It was concluded that this prototype HIV-1 synthetic peptide vaccine was well tolerated, safe and immunogenic, and that a 0, 1, 2 month schedule was not as effective in stimulating HIV-1 specific neutralizing antibodies compared with previous trials utilizing a 0, 1, 6 month schedule. Finally, this trial demonstrated that well-designed HIV vaccine trials can be performed at this clinical trials site in Yunnan, China, and that this site should be considered for conducting larger safety, immunogenicity and efficacy trials of candidate HIV vaccines.

  7. Determination of acetanilide herbicides in cereal crops using accelerated solvent extraction, solid-phase extraction and gas chromatography-electron capture detector.

    PubMed

    Zhang, Yaping; Yang, Jun; Shi, Ronghua; Su, Qingde; Yao, Li; Li, Panpan

    2011-07-01

    A method was developed to determine eight acetanilide herbicides from cereal crops based on accelerated solvent extraction (ASE) and solid-phase extraction (SPE) followed by gas chromatography-electron capture detector (GC-ECD) analysis. During the ASE process, the effect of four parameters (temperature, static time, static cycles and solvent) on the extraction efficiency was considered and compared with shake-flask extraction method. After extraction with ASE, four SPE tubes (graphitic carbon black/primary secondary amine (GCB/PSA), GCB, Florisil and alumina-N) were assayed for comparison to obtain the best clean-up efficiency. The results show that GCB/PSA cartridge gave the best recoveries and cleanest chromatograms. The analytical process was validated by the analysis of spiked blank samples. Performance characteristics such as linearity, limit of detection (LOD), limit of quantitation (LOQ), precision and recovery were studied. At 0.05 mg/kg spiked level, recoveries and precision values for rice, wheat and maize were 82.3-115.8 and 1.1-13.6%, respectively. For all the herbicides, LOD and LOQ ranged from 0.8 to 1.7 μg/kg and from 2.4 to 5.3 μg/kg, respectively. The proposed analytical methodology was applied for the analysis of the targets in samples; only three herbicides, propyzamid, metolachlor and diflufenican, were detected in two samples. PMID:21656677

  8. Pharmacokinetics, absorption, and excretion of radiolabeled revexepride: a Phase I clinical trial using a microtracer and accelerator mass spectrometry-based approach

    PubMed Central

    Flach, Stephen; Croft, Marie; Ding, Jie; Budhram, Ron; Pankratz, Todd; Pennick, Mike; Scarfe, Graeme; Troy, Steven; Getsy, Jay

    2016-01-01

    Purpose Gastroesophageal reflux disease involves the reflux of gastric and/or duodenal content into the esophagus. Prokinetic therapies, such as the selective 5-hydroxytryptamine receptor 4 agonist revexepride, may aid gastric emptying. This Phase I study evaluated the pharmacokinetics and excretion pathways of [14C]revexepride in healthy individuals using a microtracer approach with accelerator mass spectrometry. Participants and methods Six healthy men received a single oral dose of 2 mg [14C]revexepride containing ~200 nCi of radioactivity; blood, urine, and fecal samples were collected over a 10-day period. Results Almost 100% of 14C was recovered: 38.2%±10.3% (mean ± standard deviation) was recovered in urine, and 57.3%±0.4% was recovered in feces. Blood cell uptake was low, based on the blood plasma total radioactivity ratio of 0.8. The mean revexepride renal clearance was 8.6 L/h, which was slightly higher than the typical glomerular filtration rate in healthy individuals. Time to reach maximal concentration was 1.75±1.17 hours (mean ± standard deviation). No safety signals were identified. Conclusion This study demonstrated that revexepride had rapid and moderate-to-good oral absorption. Excretion of radioactivity was completed with significant amounts in feces and urine. Renal clearance slightly exceeded the typical glomerular filtration rate, suggesting the involvement of active transportation in the renal tubules. PMID:27729771

  9. Early onset hypercholesterolemia induced by the 2nd-generation tyrosine kinase inhibitor nilotinib in patients with chronic phase-chronic myeloid leukemia

    PubMed Central

    Rea, Delphine; Mirault, Tristan; Cluzeau, Thomas; Gautier, Jean-François; Guilhot, François; Dombret, Hervé; Messas, Emmanuel

    2014-01-01

    Despite a well-recognized clinical benefit of the 2nd-generation tyrosine kinase inhibitor nilotinib in patients with imatinib-resistant/-intolerant or newly diagnosed chronic myeloid leukemia, recent evidence suggests that nilotinib has a propensity to increase the risk of occlusive arterial events, especially in patients with pre-existing cardiovascular risk factors. Given the key role of lipids in cardiovascular diseases, we studied the plasma lipid profile and global cardiovascular risk prior to and during nilotinib therapy in a series of 27 patients in the setting of a prospective single center study. Data from a minimum 1-year follow up showed that nilotinib significantly increased total, low- and high-density lipoprotein cholesterol within three months. Consequently, the proportion of patients with non-optimal low-density lipoprotein cholesterol increased from 48.1% to 88.9% by 12 months, leading to cholesterol-lowering drug intervention in 22.2% of patients. The proportion of patients with low levels of high-density lipoprotein cholesterol decreased from 40.7% to 7.4% by 12 months. In contrast, a significant decrease in triglycerides was observed. Global cardiovascular risk worsened in 11.1% of patients due to diabetes or occlusive arterial events. Whether hypercholesterolemia was the main driver of occlusive arterial events was uncertain: a longer follow up is necessary to ask whether nilotinib-induced hypercholesterolemia increases long-term risk of atherosclerotic diseases. Nevertheless, given key atherogenic properties of low-density lipoprotein cholesterol, we conclude that when prescribing nilotinib, commitment to detect lipid disorders at baseline and during follow up is mandatory given their frequency, requirement for changes in lifestyle or drug intervention, and potential for long-term cardiovascular complications. PMID:24658819

  10. Adherence and future discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia. A patient-based survey on 1133 patients.

    PubMed

    Breccia, Massimo; Efficace, Fabio; Sica, Simona; Abruzzese, Elisabetta; Cedrone, Michele; Turri, Diamante; Gobbi, Marco; Carella, Angelo Michele; Gozzini, Antonella; Usala, Emilio; Cavazzini, Francesco; Danise, Paolo; Tiribelli, Mario; Binotto, Gianni; Pregno, Patrizia; Bocchia, Monica; Gaidano, Gianluca; Crugnola, Monica; Bonifacio, Massimiliano; Avanzini, Paolo; Celesti, Francesca; Guella, Anna; Martino, Bruno; Annunziata, Mario; Luciano, Luigiana; Stagno, Fabio; Vallisa, Daniele; Pungolino, Esther; Iurlo, Alessandra; Rambaldi, Alessandro; Nardiello, Ida; Orlandi, Esther; Gambacorti-Passerini, Carlo; Alimena, Giuliana

    2015-10-01

    Therapeutic approach for chronic myeloid leukemia (CML) patients has undergone a revolutionary change with the introduction of tyrosine kinase inhibitors, which improved overall survival and quality of life. Optimal therapy adherence has become of paramount importance to maximize the benefits in the long-term outcome. Several evidences have been reported that personal factors, such as social support, psychological and subjective perceptions about the drug used and the future, could influence adherence. We here report the results of a questionnaire specifically designed to evaluate factors influencing adherence and perceptions about the future, distributed to patients during regional Italian meetings. Overall, 1133 patients compiled the questionnaire: median age was 57 years. High rate of adherence was reported, but 42% of interviewed patients admitted that they had occasionally postponed a dose and 58% had discontinued therapy mainly for forgetfulness. The majority of patients discussed with personal physician about the importance of adherence and received sufficient information about illness and treatment, but would like to have discussed more about discomfort, anxiety and fear of the future. Summarizing personal drug compliance and estimating how many days a month, on average, the patients did not take the drug, the majority answered that it was less than 3 days (55%) and only a minority (4%) admitted that it was more than 7 days. Interviewed about discontinuation, 49% of patients answered that wouldn't interrupt because of fear of losing all the results achieved so far. This study suggests a higher level of satisfaction with more information received but the need of improving communication about possible future treatment free remission.

  11. Adherence and future discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia. A patient-based survey on 1133 patients.

    PubMed

    Breccia, Massimo; Efficace, Fabio; Sica, Simona; Abruzzese, Elisabetta; Cedrone, Michele; Turri, Diamante; Gobbi, Marco; Carella, Angelo Michele; Gozzini, Antonella; Usala, Emilio; Cavazzini, Francesco; Danise, Paolo; Tiribelli, Mario; Binotto, Gianni; Pregno, Patrizia; Bocchia, Monica; Gaidano, Gianluca; Crugnola, Monica; Bonifacio, Massimiliano; Avanzini, Paolo; Celesti, Francesca; Guella, Anna; Martino, Bruno; Annunziata, Mario; Luciano, Luigiana; Stagno, Fabio; Vallisa, Daniele; Pungolino, Esther; Iurlo, Alessandra; Rambaldi, Alessandro; Nardiello, Ida; Orlandi, Esther; Gambacorti-Passerini, Carlo; Alimena, Giuliana

    2015-10-01

    Therapeutic approach for chronic myeloid leukemia (CML) patients has undergone a revolutionary change with the introduction of tyrosine kinase inhibitors, which improved overall survival and quality of life. Optimal therapy adherence has become of paramount importance to maximize the benefits in the long-term outcome. Several evidences have been reported that personal factors, such as social support, psychological and subjective perceptions about the drug used and the future, could influence adherence. We here report the results of a questionnaire specifically designed to evaluate factors influencing adherence and perceptions about the future, distributed to patients during regional Italian meetings. Overall, 1133 patients compiled the questionnaire: median age was 57 years. High rate of adherence was reported, but 42% of interviewed patients admitted that they had occasionally postponed a dose and 58% had discontinued therapy mainly for forgetfulness. The majority of patients discussed with personal physician about the importance of adherence and received sufficient information about illness and treatment, but would like to have discussed more about discomfort, anxiety and fear of the future. Summarizing personal drug compliance and estimating how many days a month, on average, the patients did not take the drug, the majority answered that it was less than 3 days (55%) and only a minority (4%) admitted that it was more than 7 days. Interviewed about discontinuation, 49% of patients answered that wouldn't interrupt because of fear of losing all the results achieved so far. This study suggests a higher level of satisfaction with more information received but the need of improving communication about possible future treatment free remission. PMID:26282944

  12. Early onset hypercholesterolemia induced by the 2nd-generation tyrosine kinase inhibitor nilotinib in patients with chronic phase-chronic myeloid leukemia.

    PubMed

    Rea, Delphine; Mirault, Tristan; Cluzeau, Thomas; Gautier, Jean-François; Guilhot, François; Dombret, Hervé; Messas, Emmanuel

    2014-07-01

    Despite a well-recognized clinical benefit of the 2(nd)-generation tyrosine kinase inhibitor nilotinib in patients with imatinib-resistant/-intolerant or newly diagnosed chronic myeloid leukemia, recent evidence suggests that nilotinib has a propensity to increase the risk of occlusive arterial events, especially in patients with pre-existing cardiovascular risk factors. Given the key role of lipids in cardiovascular diseases, we studied the plasma lipid profile and global cardiovascular risk prior to and during nilotinib therapy in a series of 27 patients in the setting of a prospective single center study. Data from a minimum 1-year follow up showed that nilotinib significantly increased total, low- and high-density lipoprotein cholesterol within three months. Consequently, the proportion of patients with non-optimal low-density lipoprotein cholesterol increased from 48.1% to 88.9% by 12 months, leading to cholesterol-lowering drug intervention in 22.2% of patients. The proportion of patients with low levels of high-density lipoprotein cholesterol decreased from 40.7% to 7.4% by 12 months. In contrast, a significant decrease in triglycerides was observed. Global cardiovascular risk worsened in 11.1% of patients due to diabetes or occlusive arterial events. Whether hypercholesterolemia was the main driver of occlusive arterial events was uncertain: a longer follow up is necessary to ask whether nilotinib-induced hypercholesterolemia increases long-term risk of atherosclerotic diseases. Nevertheless, given key atherogenic properties of low-density lipoprotein cholesterol, we conclude that when prescribing nilotinib, commitment to detect lipid disorders at baseline and during follow up is mandatory given their frequency, requirement for changes in lifestyle or drug intervention, and potential for long-term cardiovascular complications.

  13. Chronic pancreatitis

    MedlinePlus

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  14. Confronting Twin Paradox Acceleration

    NASA Astrophysics Data System (ADS)

    Murphy, Thomas W.

    2016-05-01

    The resolution to the classic twin paradox in special relativity rests on the asymmetry of acceleration. Yet most students are not exposed to a satisfactory analysis of what exactly happens during the acceleration phase that results in the nonaccelerated observer's more rapid aging. The simple treatment presented here offers both graphical and quantitative solutions to the problem, leading to the correct result that the acceleration-induced age gap is 2Lβ years when the one-way distance L is expressed in light-years and velocity β ≡v/c .

  15. Multiple actions of Lucilia sericata larvae in hard-to-heal wounds: larval secretions contain molecules that accelerate wound healing, reduce chronic inflammation and inhibit bacterial infection.

    PubMed

    Cazander, Gwendolyn; Pritchard, David I; Nigam, Yamni; Jung, Willi; Nibbering, Peter H

    2013-12-01

    In Europe ≈15,000 patients receive larval therapy for wound treatment annually. Over the past few years, clinical studies have demonstrated the success of larvae of Lucilia sericata as debridement agents. This is based on a combination of physical and biochemical actions. Laboratory investigations have advanced our understanding of the biochemical mechanisms underlying the beneficial effects of larval secretions, including removal of dead tissue, reduction of the bacterial burden, and promotion of tissue regeneration. The present article summarizes our current understanding of the microbiological, immunological, and wound healing actions of larval therapy, and the molecules involved in these beneficial effects. Future studies will focus on the isolation, identification, and (pre)clinical testing of the effective molecules of L. sericata larvae. These molecules may be candidates for the development of new agents for the treatment of several infectious and inflammatory diseases, including chronic wounds.

  16. Allogeneic stem cell transplantation in a blast-phase chronic myeloid leukemia patient with carbapenem-resistant Klebsiella pneumoniae tricuspid valve endocarditis: A case report

    PubMed Central

    Kantarcioglu, Bulent; Bekoz, Huseyin Saffet; Olgun, Fatih Erkam; Cakal, Beytullah; Arkan, Burak; Turkoglu, Halil; Mert, Ali; Sargin, Deniz

    2016-01-01

    In chronic myeloid leukemia (CML), the occurrence of blastic transformation is rare. Treatment outcome is generally poor. Allogeneic stem cell transplantation (allo-SCT) is the only potentially curative treatment option for advanced-phase CML. Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates are associated with high morbidity and mortality rates, particularly in patients with haematological malignancies. Infection and colonization by these multiresistant bacteria may represent a challenge in SCT recipients for the management of post-transplantation complications, as well as for the eligibility to receive a transplant in patients who acquire the pathogen prior to the procedure. We herein report the case of a blast-phase CML patient with a highly resistant, CRKP-associated tricuspid valve endocarditis, who was treated with a combination of systemic antimicrobial therapy and surgical valve repair, and subsequently underwent a successful allo-SCT.

  17. Allogeneic stem cell transplantation in a blast-phase chronic myeloid leukemia patient with carbapenem-resistant Klebsiella pneumoniae tricuspid valve endocarditis: A case report

    PubMed Central

    Kantarcioglu, Bulent; Bekoz, Huseyin Saffet; Olgun, Fatih Erkam; Cakal, Beytullah; Arkan, Burak; Turkoglu, Halil; Mert, Ali; Sargin, Deniz

    2016-01-01

    In chronic myeloid leukemia (CML), the occurrence of blastic transformation is rare. Treatment outcome is generally poor. Allogeneic stem cell transplantation (allo-SCT) is the only potentially curative treatment option for advanced-phase CML. Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates are associated with high morbidity and mortality rates, particularly in patients with haematological malignancies. Infection and colonization by these multiresistant bacteria may represent a challenge in SCT recipients for the management of post-transplantation complications, as well as for the eligibility to receive a transplant in patients who acquire the pathogen prior to the procedure. We herein report the case of a blast-phase CML patient with a highly resistant, CRKP-associated tricuspid valve endocarditis, who was treated with a combination of systemic antimicrobial therapy and surgical valve repair, and subsequently underwent a successful allo-SCT. PMID:27699025

  18. Comparison of seven diagnostic tests to detect Trypanosoma cruzi infection in patients in chronic phase of Chagas disease

    PubMed Central

    Duarte, Luisa Fernanda; Flórez, Oscar; Rincón, Giovanna

    2014-01-01

    Objective: To compare the diagnostic performance of seven methods to determine Trypanosoma cruzi infection in patients with chronic Chagas disease. Methods: Analytical study, using the case-control design, which included 205 people (patients with Chagasic cardiomyopathy, n= 100; control group, n= 105). Three enzyme linked immunosorbent assays, one indirect hemagglutination assay and one immunochromatographic test were assessed. Additionally, DNA amplification was performed via the PCR method using kinetoplast and nuclear DNA as target sequences. For the comparative analysis of diagnostic tests, the parameters used were sensitivity, specificity, positive and negative predictive values, Receiver Operator Characteristic (ROC), positive and negative likelihood ratio, as well as κ quality analysis. Results: The commercial Bioelisa Chagas test showed the highest sensitivity (98%), specificity (100%), and positive and negative predictive values; ​​additionally, it had the highest discriminatory power. Otherwise, the amplification of T. cruzi DNA in blood samples showed low values of sensitivity (kinetoplast DNA = 51%, nuclear DNA = 22%), but high values of specificity (100%), and moderate to low discriminatory ability. Conclusion: The comparative analysis among the different methods suggests that the diagnostic strategy of T. cruzi infection in patients with chronic Chagas disease can be performed using ELISA assays based on recombinant proteins and/or synthetic peptides, which show higher diagnosis performance and can confirm and exclude the diagnosis of T. cruzi infection. The molecular methods show poor performance when used in the diagnosis of patients with chronic Chagas disease. PMID:25100890

  19. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION)

    PubMed Central

    Jabbour, Elias; Saglio, Giuseppe; Steegmann, Juan Luis; Shah, Neil P.; Boqué, Concepción; Chuah, Charles; Pavlovsky, Carolina; Mayer, Jiří; Cortes, Jorge; Baccarani, Michele; Kim, Dong-Wook; Bradley-Garelik, M. Brigid; Mohamed, Hesham; Wildgust, Mark; Hochhaus, Andreas

    2014-01-01

    This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase (CML-CP) in the phase 3 DASatinib versus Imatinib Study In treatment-Naive CML patients trial with a minimum follow-up of 3 years. Patients with newly diagnosed CML-CP were randomized to receive 100 mg dasatinib (n = 259) or 400 mg imatinib (n = 260) once daily. The retrospective landmark analysis included patients evaluable at the relevant time point (3, 6, or 12 months). Median time to complete cytogenetic response was 3 vs 6 months with dasatinib vs imatinib. At 3 and 6 months, the proportion of patients with BCR-ABL transcript levels ≤10% was higher in the dasatinib arm. Deeper responses at 3, 6, and 12 months were observed in a higher proportion of patients on dasatinib therapy and were associated with better 3-year progression-free survival and overall survival in both arms. First-line dasatinib resulted in faster and deeper responses compared with imatinib. The achievement of an early molecular response was predictive of improved progression-free survival and overall survival, supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors. This study was registered at www.clinicaltrials.gov as NCT00481247. PMID:24311723

  20. Early Side Effects of Three-Dimensional Conformal External Beam Accelerated Partial Breast Irradiation to a Total Dose of 40 Gy in One Week (A Phase II Trial)

    SciTech Connect

    Bourgier, Celine; Pichenot, Charlotte; Verstraet, Rodolfe; El Nemr, Mohamed; Heymann, Steve; Biron, Bruno; Delaloge, Suzette; Mathieu, Marie-Christine; Garbay, Jean-Remy; Bourhis, Jean; Taghian, Alphonse G.; Marsiglia, Hugo

    2011-12-01

    Purpose: Several accelerated partial breast irradiation (APBI) techniques are described in the literature, and apparently, the three-dimensional (3D)-conformal technique is being used increasingly. Nonetheless, the optimal radiation dose is not yet known. Here, we report feasibility and early toxicities of APBI delivering 40 Gy over 5 days, in a phase II trial. Methods and Materials: From October 2007 to September 2008, 25 patients with pT1N0 cancer received 3D-conformal APBI. The prescribed radiation dose was 40 Gy in 4-Gy fractions given twice daily. This technique used two minitangents and an 'en face' electron field. Toxicities were systematically assessed at 1, 2, and 6 months and then once every 6 months. Results: The planning tumor volume for evaluation (PTV{sub E}VAL) coverage was adequate: the mean dose to the PTV{sub E}VAL was 41.8 Gy (range, 41-42.4 Gy). Mean doses to the ipsilateral lung and heart were 1.6 Gy (range, 1.0-2.3 Gy) and 1.2 Gy (range, 1.0-1.6 Gy), respectively. One and two months after completion of APBI, most patients had no or mild erythema (n = 16 patients at 1 month; n = 25 patients at 2 months); none of these patients developed moist desquamation. After a median follow-up of 12 months, only 1 patient had a significant moderate field contracture (grade 2). Other reported late toxicities were grade 1. Conclusions: 3D-conformal APBI (with two minitangents and an 'en face' electron field) using a total dose of 40 Gy in 10 fractions twice daily over 5 days achieved appropriate PTV{sub E}VAL coverage and offered significant sparing of normal tissue. Early tolerance was excellent.

  1. Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily

    PubMed Central

    Hughes, Timothy P.; Hochhaus, Andreas; Kantarjian, Hagop M.; Cervantes, Francisco; Guilhot, François; Niederwieser, Dietger; le Coutre, Philipp D.; Rosti, Gianantonio; Ossenkoppele, Gert; Lobo, Clarisse; Shibayama, Hirohiko; Fan, Xiaolin; Menssen, Hans D.; Kemp, Charisse; Larson, Richard A.; Saglio, Giuseppe

    2014-01-01

    In a randomized, phase III trial of nilotinib versus imatinib in patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in chronic phase, more patients had suboptimal response or treatment failure on front-line imatinib than on nilotinib. Patients with suboptimal response/treatment failure on imatinib 400 mg once or twice daily or nilotinib 300 mg twice daily could enter an extension study to receive nilotinib 400 mg twice daily. After a 19-month median follow up, the safety profile of nilotinib 400 mg twice daily in patients switching from imatinib (n=35) was consistent with previous reports, and few new adverse events occurred in patients escalating from nilotinib 300 mg twice daily (n=19). Of patients previously treated with imatinib or nilotinib 300 mg twice daily, respectively, 15 of 26 (58%) and 2 of 6 (33%) without complete cytogenetic response at extension study entry, and 11 of 34 (32%) and 7 of 18 (39%) without major molecular response at extension study entry, achieved these responses at any time on nilotinib 400 mg twice daily. Estimated 18-month rates of freedom from progression and overall survival after entering the extension study were lower for patients switched from imatinib (85% and 87%, respectively) versus nilotinib 300 mg twice daily (95% and 94%, respectively). Nilotinib dose escalation was generally well tolerated and improved responses in about one-third of patients with suboptimal response/treatment failure. Switch to nilotinib improved responses in some patients with suboptimal response/treatment failure on imatinib, but many did not achieve complete cytogenetic response (clinicaltrials.gov identifiers:00718263, 00471497 - extension). PMID:24532039

  2. Initial Molecular Response at 3 Months May Predict Both Response and Event-Free Survival at 24 Months in Imatinib-Resistant or -Intolerant Patients With Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase Treated With Nilotinib

    PubMed Central

    Branford, Susan; Kim, Dong-Wook; Soverini, Simona; Haque, Ariful; Shou, Yaping; Woodman, Richard C.; Kantarjian, Hagop M.; Martinelli, Giovanni; Radich, Jerald P.; Saglio, Giuseppe; Hochhaus, Andreas; Hughes, Timothy P.; Müller, Martin C.

    2012-01-01

    Purpose The association between initial molecular response and longer-term outcomes with nilotinib was examined. Patients and Methods Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237). Results BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of > 1% to ≤ 10% at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of > 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of > 0.1% to ≤ 1%, > 1% to ≤ 10%, and > 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR–ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of ≤ 1% had an estimated 24-month EFS rate of 82%, compared with 70% for patients with BCR-ABL1 (IS) of > 1% to ≤ 10% and 48% for patients with BCR-ABL1 (IS) of > 10%. Conclusion Patients with BCR-ABL1 (IS) of > 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10%. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response. PMID:23109697

  3. Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily.

    PubMed

    Hughes, Timothy P; Hochhaus, Andreas; Kantarjian, Hagop M; Cervantes, Francisco; Guilhot, François; Niederwieser, Dietger; le Coutre, Philipp D; Rosti, Gianantonio; Ossenkoppele, Gert; Lobo, Clarisse; Shibayama, Hirohiko; Fan, Xiaolin; Menssen, Hans D; Kemp, Charisse; Larson, Richard A; Saglio, Giuseppe

    2014-07-01

    In a randomized, phase III trial of nilotinib versus imatinib in patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in chronic phase, more patients had suboptimal response or treatment failure on front-line imatinib than on nilotinib. Patients with suboptimal response/treatment failure on imatinib 400 mg once or twice daily or nilotinib 300 mg twice daily could enter an extension study to receive nilotinib 400 mg twice daily. After a 19-month median follow up, the safety profile of nilotinib 400 mg twice daily in patients switching from imatinib (n=35) was consistent with previous reports, and few new adverse events occurred in patients escalating from nilotinib 300 mg twice daily (n=19). Of patients previously treated with imatinib or nilotinib 300 mg twice daily, respectively, 15 of 26 (58%) and 2 of 6 (33%) without complete cytogenetic response at extension study entry, and 11 of 34 (32%) and 7 of 18 (39%) without major molecular response at extension study entry, achieved these responses at any time on nilotinib 400 mg twice daily. Estimated 18-month rates of freedom from progression and overall survival after entering the extension study were lower for patients switched from imatinib (85% and 87%, respectively) versus nilotinib 300 mg twice daily (95% and 94%, respectively). Nilotinib dose escalation was generally well tolerated and improved responses in about one-third of patients with suboptimal response/treatment failure. Switch to nilotinib improved responses in some patients with suboptimal response/treatment failure on imatinib, but many did not achieve complete cytogenetic response (clinicaltrials.gov identifiers: 00718263, 00471497 - extension).

  4. Rates and risk factors for hepatitis B reactivation in a cohort of persons in the inactive phase of chronic hepatitis B—Alaska, 2001–2010

    PubMed Central

    Tohme, Rania A.; Bulkow, Lisa; Homan, Chriss E.; Negus, Susan; McMahon, Brian J.

    2015-01-01

    Background A high prevalence of reactivation of hepatitis B has been documented among immunosuppressed individuals in the inactive phase of chronic hepatitis B; However, the proportion of and the risk factors for reactivation are largely unknown among non-immunosuppressed persons. Objectives Estimate the incidence rate of and risk factors for hepatitis B reactivation in a population-based cohort of persons in the inactive phase of chronic hepatitis B in Alaska. Study design A cohort of 414 Alaska Native Persons in the inactive phase of hepatitis B (HBV DNA < 2000 IU/mL and normal alanine aminotransferase (ALT) for 12 months) was followed-up for 10 years. Reactivation of hepatitis B was defined as HBV DNA ≥ 2000 IU/mL and ALT ≥ 40 IU/L. Cox-proportional hazards regression models were used to identify factors associated with reactivation. Results A total of 36 (9%) persons had reactivation during 2984 person-years of follow-up, with an annual incidence of 1.2%. Persons aged ≥50 years (1.8%) at study entry had the highest incidence rates of reactivation although incidence rates were not significantly different by age group. Risk factors for hepatitis B reactivation were male sex (Hazard Ratio (HR) = 2.41; 95% Confidence Interval (CI): 1.17–4.96), HBV DNA ≥ 1000 IU/mL at study entry (HR = 7.61; 95% CI: 2.81–20.6), and HBV genotype B (HR = 6.08; 95% CI: 1.32–28.0). Conclusions The incidence of hepatitis B reactivation was low during the 10 years of follow-up. However, given the higher risk of reactivation than their counterparts, males, and those with HBV DNA ≥ 1000 IU/mL need to be followed-up more frequently. PMID:24001884

  5. Chronic unpredictable stress (CUS) enhances the carcinogenic potential of 7,12-dimethylbenz(a)anthracene (DMBA) and accelerates the onset of tumor development in Swiss albino mice.

    PubMed

    Suhail, Nida; Bilal, Nayeem; Hasan, Shirin; Ahmad, Ausaf; Ashraf, Ghulam Md; Banu, Naheed

    2015-11-01

    Social stressors evolving from individual and population interactions produce stress reactions in many organisms (including humans), influencing homeostasis, altering the activity of the immunological system, and thus leading to various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) in cancer promotion and to assess oxidative stress outcomes in terms of various in vivo biochemical parameters, oxidative stress markers, DNA damage, and the development of skin tumors in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz(a)anthracene (DMBA) alone (topical), and DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical) and exposure to CUS prior to DMBA or DMBA-TPA treatments and sacrificed after 16 weeks of treatment. Prior exposure to CUS significantly increased the pro-oxidant effect of carcinogen, depicted by compromised levels of antioxidants in the circulation and skin, accompanied by enhanced lipid peroxidation, plasma corticosterone, and marker enzymes as compared to DMBA-alone or DMBA-TPA treatments. DNA damage results corroborated the above biochemical outcomes. Also, the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice in the presence and absence of stress further strongly supported our above biochemical measurements. CUS may work as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Further studies may be aimed at the development of interventions for disease prevention by identifying the relations between psychological factors and DNA damage.

  6. Addition of hydrochlorothiazide to angiotensin receptor blocker therapy can achieve a lower sodium balance with no acceleration of intrarenal renin angiotensin system in patients with chronic kidney disease

    PubMed Central

    Fuwa, Daisuke; Fukuda, Michio; Ogiyama, Yoshiaki; Sato, Ryo; Mizuno, Masashi; Miura, Toshiyuki; Abe-Dohmae, Sumiko; Michikawa, Makoto; Kobori, Hiroyuki; Ohte, Nobuyuki

    2016-01-01

    Objective Angiotensin receptor blockers (ARBs) produce a lower sodium (Na) balance, and the natriuretic effect is enhanced under Na deprivation, despite falls in blood pressure (BP) and glomerular filtration rate (GFR). Methods The effect of additional hydrochlorothiazide (HCTZ; 12.5 mg/day) to ARB treatment (valsartan; 80 mg/day) on glomerulotubular Na balance was evaluated in 23 patients with chronic kidney disease. Results Add-on HCTZ decreased GFR, tubular Na load, and tubular Na reabsorption (tNa), although 24-hour urinary Na excretion (UNaV) remained constant. Daily urinary angiotensinogen excretion (UAGTV, 152±10→82±17 μg/g Cre) reduced (p=0.02). Changes in tubular Na load (r2=0.26) and tNa (r2=0.25) correlated with baseline 24-hour UAGTV. Changes in filtered Na load correlated with changes in nighttime systolic BP (r2=0.17), but not with changes in daytime systolic BP. The change in the tNa to filtered Na load ratio was influenced by the change in daytime UNaV (β=−0.67, F=16.8), rather than the change in nighttime UNaV. Conclusions Lower Na balance was produced by add-on HCTZ to ARB treatment without an increase of intra-renal renin-angiotensin system activity, leading to restoration of nocturnal hypertension. A further study is needed to demonstrate that the reduction of UAGTV by additional diuretics to ARBs prevents the progression of nephropathy or cardiovascular events. PMID:27283968

  7. Chronic unpredictable stress (CUS) enhances the carcinogenic potential of 7,12-dimethylbenz(a)anthracene (DMBA) and accelerates the onset of tumor development in Swiss albino mice.

    PubMed

    Suhail, Nida; Bilal, Nayeem; Hasan, Shirin; Ahmad, Ausaf; Ashraf, Ghulam Md; Banu, Naheed

    2015-11-01

    Social stressors evolving from individual and population interactions produce stress reactions in many organisms (including humans), influencing homeostasis, altering the activity of the immunological system, and thus leading to various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) in cancer promotion and to assess oxidative stress outcomes in terms of various in vivo biochemical parameters, oxidative stress markers, DNA damage, and the development of skin tumors in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz(a)anthracene (DMBA) alone (topical), and DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical) and exposure to CUS prior to DMBA or DMBA-TPA treatments and sacrificed after 16 weeks of treatment. Prior exposure to CUS significantly increased the pro-oxidant effect of carcinogen, depicted by compromised levels of antioxidants in the circulation and skin, accompanied by enhanced lipid peroxidation, plasma corticosterone, and marker enzymes as compared to DMBA-alone or DMBA-TPA treatments. DNA damage results corroborated the above biochemical outcomes. Also, the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice in the presence and absence of stress further strongly supported our above biochemical measurements. CUS may work as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Further studies may be aimed at the development of interventions for disease prevention by identifying the relations between psychological factors and DNA damage. PMID:26272695

  8. Perturbations for transient acceleration

    SciTech Connect

    Vargas, Cristofher Zuñiga; Zimdahl, Winfried; Hipólito-Ricaldi, Wiliam S. E-mail: hipolito@ceunes.ufes.br

    2012-04-01

    According to the standard ΛCDM model, the accelerated expansion of the Universe will go on forever. Motivated by recent observational results, we explore the possibility of a finite phase of acceleration which asymptotically approaches another period of decelerated expansion. Extending an earlier study on a corresponding homogeneous and isotropic dynamics, in which interactions between dark matter and dark energy are crucial, the present paper also investigates the dynamics of the matter perturbations both on the Newtonian and General Relativistic (GR) levels and quantifies the potential relevance of perturbations of the dark-energy component. In the background, the model is tested against the Supernova type Ia (SNIa) data of the Constitution set and on the perturbative level against growth rate data, among them those of the WiggleZ survey, and the data of the 2dFGRS project. Our results indicate that a transient phase of accelerated expansion is not excluded by current observations.

  9. Polarization-phase diagnostics of latent course of cholelithiasis in patients with chronic cholecystitis combined with diabetes mellitus type 2

    NASA Astrophysics Data System (ADS)

    Fediv, O. I.; Ivashchuk, O. I.; Marchuk, Yu. F.; Andriychuk, D. R.

    2012-01-01

    The principles of optical model of human bile polycrystalline structure are described. The three optical levels - isotropic, liquid-crystal and solid-crystal have been proposed. It has been introduced and proposed the scenarios of phase distribution formation in the boundary field of laser radiation, transformed by bile layers. The experimental scheme of direct measurement of coordinate phase distributions has been presented. The results of investigating the interrelation between the values of correlation and fractal parameters are presented. They characterize the coordinate distributions of phase shifts between the orthogonal components of the amplitude in the points of laser images of bile smears of cholelithiasis patients in combination with other pathologies. The diagnostic criteria of the cholelithiasis nascency and its severity degree differentiation are determined.

  10. Polarization-phase diagnostics of latent course of cholelithiasis in patients with chronic cholecystitis combined with diabetes mellitus type 2

    NASA Astrophysics Data System (ADS)

    Fediv, O. I.; Ivashchuk, O. I.; Marchuk, Yu. F.; Andriychuk, D. R.

    2011-09-01

    The principles of optical model of human bile polycrystalline structure are described. The three optical levels - isotropic, liquid-crystal and solid-crystal have been proposed. It has been introduced and proposed the scenarios of phase distribution formation in the boundary field of laser radiation, transformed by bile layers. The experimental scheme of direct measurement of coordinate phase distributions has been presented. The results of investigating the interrelation between the values of correlation and fractal parameters are presented. They characterize the coordinate distributions of phase shifts between the orthogonal components of the amplitude in the points of laser images of bile smears of cholelithiasis patients in combination with other pathologies. The diagnostic criteria of the cholelithiasis nascency and its severity degree differentiation are determined.

  11. Particle acceleration in solar flares

    NASA Technical Reports Server (NTRS)

    Ramaty, R.; Forman, M. A.

    1987-01-01

    The most direct signatures of particle acceleration in flares are energetic particles detected in interplanetary space and in the Earth atmosphere, and gamma rays, neutrons, hard X-rays, and radio emissions produced by the energetic particles in the solar atmosphere. The stochastic and shock acceleration theories in flares are reviewed and the implications of observations on particle energy spectra, particle confinement and escape, multiple acceleration phases, particle anistropies, and solar atmospheric abundances are discussed.

  12. Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial.

    PubMed

    Lepretre, Stephane; Aurran, Therese; Mahé, Beatrice; Cazin, Bruno; Tournilhac, Olivier; Maisonneuve, Herve; Casasnovas, Olivier; Delmer, Alain; Leblond, Veronique; Royer, Bruno; Corront, Bernadette; Chevret, Sylvie; Delépine, Roselyne; Vaudaux, Sandrine; Van Den Neste, Eric; Béné, Marie Christine; Letestu, Remi; Cymbalista, Florence; Feugier, Pierre

    2012-05-31

    A French and Belgian multicenter phase 3 trial was conducted in medically fit patients with untreated chronic lymphocytic leukemia. Of 178 patients enrolled in the study, 165 were randomly assigned to receive 6 courses of oral fludarabine and cyclophosphamide (FC) in combination with rituximab (FCR; 375 mg/m(2) in cycle one, 500 mg/m(2) in all subsequent cycles) or alemtuzumab (FCCam; 30 mg subcutaneously injected on cycle days 1-3); each cycle was 28 days. Recruitment was halted prematurely because of excess toxicity; 8 patients died in the FCCam group, 3 from lymphoma and 5 from in-fection. Overall response rates were 91% with FCR and 90% with FCCam (P = .79). Complete remission rates were 33.75% with FCR and 19.2% with FCCam (P = .04). Three-year progression-free survival was 82.6% with FCR and 72.5% with FCCam (P = .21). Three-year overall survival was similar between the 2 arms at 90.1% in the FCR arm and 86.4% in the FCCam arm (P = .27). These results indicate that the FCCam regimen for the treatment of advanced chronic lymphocytic leukemia was not more effective than the FCR regimen and was associated with an unfavorable safety profile, representing a significant limitation of its use. This study is registered with www.clinicaltrials.gov as number NCT00564512. PMID:22337714

  13. A Randomized Controlled Phase III Trial of Recombinant Human Granulocyte Colony-Stimulating Factor (Filgrastim) for Treatment of Severe Chronic Neutropenia

    PubMed Central

    Dale, David C.; Bonilla, Mary Ann; Davis, Mark W.; Nakanishi, Arline M.; Hammond, William P.; Kurtzberg, Joanne; Wang, Winfred; Jakubowski, Ann; Winton, Elliott; Lalezari, Parviz; Robinson, William; Glaspy, John A.; Emerson, Steve; Gabrilove, Janice; Vincent, Martha; Boxer, Laurence A.

    2014-01-01

    Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 × 109/L) due to these diseases were enrolled in this multi-center phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony-stimulating factor (filgrastim) (3.45 to 11.50 μg/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of ≥ 1.5 × 109/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently: adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events. PMID:8490166

  14. [Accelerated partial breast irradiation with image-guided intensity-modulated radiotherapy following breast-conserving surgery - preliminary results of a phase II clinical study].

    PubMed

    Mészáros, Norbert; Major, Tibor; Stelczer, Gábor; Zaka, Zoltán; Mózsa, Emõke; Fodor, János; Polgár, Csaba

    2015-06-01

    The purpose of the study was to implement accelerated partial breast irradiation (APBI) by means of image-guided intensity-modulated radiotherapy (IG-IMRT) following breast-conserving surgery (BCS) for low-risk early invasive breast cancer. Between July 2011 and March 2014, 60 patients with low-risk early invasive (St I-II) breast cancer who underwent BCS were enrolled in our phase II prospective study. Postoperative APBI was given by means of step and shoot IG-IMRT using 4 to 5 fields to a total dose of 36.9 Gy (9×4.1 Gy) using a twice-a-day fractionation. Before each fraction, series of CT images were taken from the region of the target volume using a kV CT on-rail mounted in the treatment room. An image fusion software was used for automatic image registration of the planning and verification CT images. Patient set-up errors were detected in three directions (LAT, LONG, VERT), and inaccuracies were adjusted by automatic movements of the treatment table. Breast cancer related events, acute and late toxicities, and cosmetic results were registered and analysed. At a median follow-up of 24 months (range 12-44) neither locoregional nor distant failure was observed. Grade 1 (G1), G2 erythema, G1 oedema, and G1 and G2 pain occurred in 21 (35%), 2 (3.3%), 23 (38.3%), 6 (10%) and 2 (3.3%) patients, respectively. No G3-4 acute side effects were detected. Among late radiation side effects G1 pigmentation, G1 fibrosis, and G1 fat necrosis occurred in 5 (8.3%), 7 (11.7%), and 2 (3.3%) patients, respectively. No ≥G2 late toxicity was detected. Excellent and good cosmetic outcome was detected in 45 (75%) and 15 (25%) patients. IG-IMRT is a reproducible and feasible technique for the delivery of APBI following conservative surgery for the treatment of low-risk, early-stage invasive breast carcinoma. Preliminary results are promising, early radiation side effects are minimal, and cosmetic results are excellent. PMID:26035158

  15. Chronic stimulation of cultured neuronal networks boosts low-frequency oscillatory activity at theta and gamma with spikes phase-locked to gamma frequencies

    NASA Astrophysics Data System (ADS)

    Leondopulos, Stathis S.; Boehler, Michael D.; Wheeler, Bruce C.; Brewer, Gregory J.

    2012-04-01

    Slow wave oscillations in the brain are essential for coordinated network activity but have not been shown to self-organize in vitro. Here, the development of dissociated hippocampal neurons into an active network with oscillations on multi-electrode arrays was evaluated in the absence and presence of chronic external stimulation. Significant changes in signal power were observed in the range of 1-400 Hz with an increase in amplitude during bursts. Stimulation increased oscillatory activity primarily in the theta (4-11 Hz) and slow gamma (30-55 Hz) bands. Spikes were most prominently phase-locked to the slow gamma waves. Notably, the dissociated network self-organized to exhibit sustained delta, theta, beta and gamma oscillations without input from cortex, thalamus or organized pyramidal cell layers.

  16. Neuroplastic Effects of Transcranial Direct Current Stimulation on Painful Symptoms Reduction in Chronic Hepatitis C: A Phase II Randomized, Double Blind, Sham Controlled Trial

    PubMed Central

    Brietzke, Aline P.; Rozisky, Joanna R.; Dussan-Sarria, Jairo A.; Deitos, Alicia; Laste, Gabriela; Hoppe, Priscila F. T.; Muller, Suzana; Torres, Iraci L. S.; Alvares-da-Silva, Mário R.; de Amorim, Rivadavio F. B.; Fregni, Felipe; Caumo, Wolnei

    2016-01-01

    Introduction: Pegylated Interferon Alpha (Peg-IFN) in combination with other drugs is the standard treatment for chronic hepatitis C infection (HCV) and is related to severe painful symptoms. The aim of this study was access the efficacy of transcranial direct current stimulation (tDCS) in controlling the painful symptoms related to Peg-IFN side effects. Materials and Methods: In this phase II double-blind trial, twenty eight (n = 28) HCV subjects were randomized to receive either 5 consecutive days of active tDCS (n = 14) or sham (n = 14) during 5 consecutive days with anodal stimulation over the primary motor cortex region using 2 mA for 20 min. The primary outcomes were visual analogue scale (VAS) pain and brain-derived neurotrophic factor (BDNF) serum levels. Secondary outcomes were the pressure-pain threshold (PPT), the Brazilian Profile of Chronic Pain: Screen (B-PCP:S), and drug analgesics use. Results: tDCS reduced the VAS scores (P < 0.003), with a mean pain drop of 56% (p < 0.001). Furthermore, tDCS was able to enhance BDNF levels (p < 0.01). The mean increase was 37.48% in the active group. Finally, tDCS raised PPT (p < 0.001) and reduced the B-PCP:S scores and analgesic use (p < 0.05). Conclusions: Five sessions of tDCS were effective in reducing the painful symptoms in HCV patients undergoing Peg-IFN treatment. These findings support the efficacy of tDCS as a promising therapeutic tool to improve the tolerance of the side effects related to the use of Peg-IFN. Future larger studies (phase III and IV trials) are needed to confirm the clinical use of the therapeutic effects of tDCS in such condition. Trial registration: Brazilian Human Health Regulator for Research with the approval number CAAE 07802012.0.0000.5327. PMID:26793047

  17. Which method better evaluates the molecular response in newly diagnosed chronic phase chronic myeloid leukemia patients with imatinib treatment, BCR-ABL(IS) or log reduction from the baseline level?

    PubMed

    Qin, Ya-Zhen; Jiang, Qian; Jiang, Hao; Li, Jin-Lan; Li, Ling-Di; Zhu, Hong-Hu; Lai, Yue-Yun; Lu, Xi-Jing; Liu, Yan-Rong; Jiang, Bin; Huang, Xiao-Jun

    2013-09-01

    The molecular response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment can be evaluated either by BCR-ABL mRNA levels on international scale (IS) or by log reduction from the baseline level of the laboratory. Both methods were compared in 248 newly diagnosed chronic phase CML patients treated with imatinib. The major molecular responses (MMR) obtained by both methods predict progression-free survival (PFS, all P<0.0001). Thirty-six patients, who were identified as MMR patients by the IS method but as non-MMR patients by the log reduction method, had the same PFS as MMR patients identified by both methods. The molecular responses of patients at 3 and 6 months, as evaluated by the two methods, have similar predictive values on their cytogenetic responses at 12 months and on their molecular responses at 18 months. Both ≤ 10%(IS) and ≥ 1 log reduction at 3 months and ≤ 1%(IS) at 6 months were significantly associated with PFS (P=0.0011, 0.0090, and 0.0064). The percentages of patients with BCR-ABL(IS) of ≤ 1%, >1-10%, and of >10% at 3 months and 6 months in the German CML Study IV were similar with those with corresponding BCR-ABL(IS) in our center, but was significantly different with those evaluated by the log reduction method. Therefore, the molecular response evaluated by BCR-ABL(IS) has similar trends in PFS and in response prediction, but can better differentiate patients than that by the log reduction method. Furthermore, the IS method allows comparison among molecular response results from different laboratories.

  18. Comparison of the utility and applicability of the Sokal, Hasford, and EUTOS scores in a population of Chinese patients with chronic-phase chronic myeloid leukemia undergoing imatinib therapy

    PubMed Central

    Xia, Leiming; Qian, Wei; Yang, Mingzhen; Li, Qingsheng; Liu, Fei; Xie, Yanyan

    2015-01-01

    Background Tyrosine kinase inhibitors are increasingly used to treat chronic myeloid leukemia (CML), but loss of complete cytogenetic response (CCyR) indicates treatment failure. Aim To compare the efficacy of Sokal, European Treatment Outcome Study (EUTOS), and Hasford prognostic scores with 3-month and 12-month CCyR, event-free survival (EFS) and progression-free survival (PFS) in patients with chronic-phase CML (CP-CML) undergoing imatinib therapy. Methods We retrospectively analyzed the outcome of 210 patients with CP-CML treated at the First Affiliated Hospital of Anhui Medical University treated between January 2006 and December 2013. Sokal, EUTOS, and Hasford scores were compared with 3-month and 12-month CCyR, EFS, and PFS. Results Kaplan–Meier analyses revealed that 3-month and 12-month CCyR and PFS were lower in patients with high EUTOS scores, and intermediate or high Sokal and Hasford scores (all P<0.05). Furthermore, EFS was lower in patients with intermediate or high Sokal and Hasford scores (both P<0.05). Hasford score (hazard ratio =2.608, 95% confidence interval: 1.473–4.617, P=0.001) was independently associated with 3-month CCyR. Conclusion Although all three scoring systems were associated with EFS, PFS, and 3-month and 12-month CCyR in the Kaplan–Meier analyses (except EFS with EUTOS), only the Hasford score was independently associated with 3m-CCyR, while EUTOS score and Sokal score were not independently associated with any of these outcomes. PMID:26392775

  19. Wakefield accelerators

    SciTech Connect

    Simpson, J.D.

    1990-01-01

    The search for new methods to accelerate particle beams to high energy using high gradients has resulted in a number of candidate schemes. One of these, wakefield acceleration, has been the subject of considerable R D in recent years. This effort has resulted in successful proof of principle experiments and in increased understanding of many of the practical aspects of the technique. Some wakefield basics plus the status of existing and proposed experimental work is discussed, along with speculations on the future of wake field acceleration. 10 refs., 6 figs.

  20. LINEAR ACCELERATOR

    DOEpatents

    Colgate, S.A.

    1958-05-27

    An improvement is presented in linear accelerators for charged particles with respect to the stable focusing of the particle beam. The improvement consists of providing a radial electric field transverse to the accelerating electric fields and angularly introducing the beam of particles in the field. The results of the foregoing is to achieve a beam which spirals about the axis of the acceleration path. The combination of the electric fields and angular motion of the particles cooperate to provide a stable and focused particle beam.

  1. Decreased levels of the high molecular weight subunit of neurofilaments and accelerated neurofilament transport during the recovery phase of 2,5-hexanedione exposure.

    PubMed

    Pyle, S J; Amarnath, V; Graham, D G; Anthony, D C

    1993-01-01

    The neurotoxicant 2,5-hexanedione (HD) causes the accumulation of neurofilaments in the distal axon and an acceleration of neurofilament transport proximal to the site of their accumulation. It has been proposed that the acceleration of transport is due to the direct reaction of HD with neurofilament proteins and, conversely, that this acceleration is a secondary response to the axon to injury. The objective of this study was to determine whether the response of axons to HD intoxication includes acceleration of neurofilament transport. Pulse labelling was used to analyze neurofilament transport in age-matched rats exposed to HD or PBS. The animals receiving HD were exposed either throughout the period of radiolabel transport, or prior to the pulse labeling of neurofilament proteins. If acceleration of the rate of neurofilament transport was due to the direct reaction of HD with proteins, then neurofilaments synthesized after the exposure period should travel at control rates, since these proteins would not have been exposed to the toxicant. After 28 days of transport, optic nerve proteins were examined using SDS-PAGE, fluorography, and computerized densitometry. In both HD-treated groups, neurofilament transport was accelerated relative to age-matched control animals. In addition, the amount of NFH was decreased relative to other neurofilament subunits. The combination of accelerated transport and a diminished proportion of NFH is similar to the observations of neurofilament axonal transport during growth and development. These observations suggest that this persistent, secondary effect is a reparative response to injury that recapitulates axonal growth and development.

  2. A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia

    PubMed Central

    Lamanna, Nicole; Kipps, Thomas J.; Flinn, Ian; Zelenetz, Andrew D.; Burger, Jan A.; Keating, Michael; Mitra, Siddhartha; Holes, Leanne; Yu, Albert S.; Johnson, David M.; Miller, Langdon L.; Kim, Yeonhee; Dansey, Roger D.; Dubowy, Ronald L.; Coutre, Steven E.

    2015-01-01

    Idelalisib is a first-in-class oral inhibitor of PI3Kδ that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-naïve older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375 mg/m2 weekly ×8 and idelalisib 150 mg twice daily continuously for 48 weeks. Patients completing 48 weeks without progression could continue to receive idelalisib on an extension study. The median time on treatment was 22.4 months (range, 0.8-45.8+). The overall response rate (ORR) was 97%, including 19% complete responses. The ORR was 100% in patients with del(17p)/TP53 mutations and 97% in those with unmutated IGHV. Progression-free survival was 83% at 36 months. The most frequent (>30%) adverse events (any grade) were diarrhea (including colitis) (64%), rash (58%), pyrexia (42%), nausea (38%), chills (36%), cough (33%), and fatigue (31%). Elevated alanine transaminase/aspartate transaminase was seen in 67% of patients (23% grade ≥3). The combination of idelalisib and rituximab was highly active, resulting in durable disease control in treatment-naïve older patients with CLL. These results support the further development of idelalisib as initial treatment of CLL. This study is registered at ClinicalTrials.gov as #NCT01203930. PMID:26472751

  3. ION ACCELERATOR

    DOEpatents

    Bell, J.S.

    1959-09-15

    An arrangement for the drift tubes in a linear accelerator is described whereby each drift tube acts to shield the particles from the influence of the accelerating field and focuses the particles passing through the tube. In one embodiment the drift tube is splii longitudinally into quadrants supported along the axis of the accelerator by webs from a yoke, the quadrants. webs, and yoke being of magnetic material. A magnetic focusing action is produced by energizing a winding on each web to set up a magnetic field between adjacent quadrants. In the other embodiment the quadrants are electrically insulated from each other and have opposite polarity voltages on adjacent quadrants to provide an electric focusing fleld for the particles, with the quadrants spaced sufficienily close enough to shield the particles within the tube from the accelerating electric field.

  4. Acceleration switch

    DOEpatents

    Abbin, J.P. Jr.; Devaney, H.F.; Hake, L.W.

    1979-08-29

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  5. Acceleration switch

    DOEpatents

    Abbin, Jr., Joseph P.; Devaney, Howard F.; Hake, Lewis W.

    1982-08-17

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  6. LINEAR ACCELERATOR

    DOEpatents

    Christofilos, N.C.; Polk, I.J.

    1959-02-17

    Improvements in linear particle accelerators are described. A drift tube system for a linear ion accelerator reduces gap capacity between adjacent drift tube ends. This is accomplished by reducing the ratio of the diameter of the drift tube to the diameter of the resonant cavity. Concentration of magnetic field intensity at the longitudinal midpoint of the external sunface of each drift tube is reduced by increasing the external drift tube diameter at the longitudinal center region.

  7. Granulocytic sarcoma with compressive myelopathy: a rare presentation of chronic myelogenous leukemia.

    PubMed

    Ganapule, Abhijeet P; Viswabandya, Auro; Jasper, Anita; Patel, Palak; Kokil, Gautami

    2014-07-01

    Granulocytic sarcoma occurs most commonly in acute myelogenous leukemia. The appearance of granulocytic sarcoma in chronic myelogenous leukemia signals accelerated phase/ blast transformation. This is a rare case of undiagnosed chronic myelogenous leukemia with granulocytic sarcoma causing cord compression, which went into tumour lysis syndrome requiring dialysis after starting of steroids and radiotherapy. A 43-year-old male presented in emergency department with acute onset of flaccid paralysis. On clinical examination, there was hepatosplenomegaly and lower motor neuron paralysis in the lower limbs. The peripheral smear was consistent with chronic myelogenous leukemia in chronic phase. The MRI spine revealed para-spinal and epidural masses causing cord compression and the biopsy from the paraspinal mass was consistent with granulocytic sarcoma. PMID:25177619

  8. Muon Acceleration - RLA and FFAG

    SciTech Connect

    Bogacz, Alex

    2011-10-01

    Various acceleration schemes for muons are presented. The overall goal of the acceleration systems: large acceptance acceleration to 25 GeV and 'beam shaping' can be accomplished by various fixed field accelerators at different stages. They involve three superconducting linacs: a single pass linear Pre-accelerator followed by a pair of multi-pass Recirculating Linear Accelerators (RLA) and finally a non-scaling FFAG ring. The present baseline acceleration scenario has been optimized to take maximum advantage of appropriate acceleration scheme at a given stage. The solenoid based Pre-accelerator offers very large acceptance and facilitates correction of energy gain across the bunch and significant longitudinal compression trough induced synchrotron motion. However, far off-crest acceleration reduces the effective acceleration gradient and adds complexity through the requirement of individual RF phase control for each cavity. The RLAs offer very efficient usage of high gradient superconducting RF and ability to adjust path-length after each linac pass through individual return arcs with uniformly periodic FODO optics suitable for chromatic compensation of emittance dilution with sextupoles. However, they require spreaders/recombiners switchyards at both linac ends and significant total length of the arcs. The non-scaling Fixed Field Alternating Gradient (FFAG) ring combines compactness with very large chromatic acceptance (twice the injection energy) and it allows for large number of passes through the RF (at least eight, possibly as high as 15).

  9. A phase I trial of the aurora kinase inhibitor, ENMD-2076, in patients with relapsed or refractory acute myeloid leukemia or chronic myelomonocytic leukemia.

    PubMed

    Yee, Karen W L; Chen, Hsiao-Wei T; Hedley, David W; Chow, Sue; Brandwein, Joseph; Schuh, Andre C; Schimmer, Aaron D; Gupta, Vikas; Sanfelice, Deborah; Johnson, Tara; Le, Lisa W; Arnott, Jamie; Bray, Mark R; Sidor, Carolyn; Minden, Mark D

    2016-10-01

    ENMD-2076 is a novel, orally-active molecule that inhibits Aurora A kinase, as well as c-Kit, FLT3 and VEGFR2. A phase I study was conducted to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and toxicities of ENMD-2076 in patients with acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Patients received escalating doses of ENMD-2076 administered orally daily [225 mg (n = 7), 375 mg (n = 6), 325 mg (n = 9), or 275 mg (n = 5)]. Twenty-seven patients were treated (26 AML; 1 CMML-2). The most common non-hematological toxicities of any grade, regardless of association with drug, were fatigue, diarrhea, dysphonia, dyspnea, hypertension, constipation, and abdominal pain. Dose-limiting toxicities (DLTs) consisted of grade 3 fatigue, grade 3 typhilitis, grade 3 syncope and grade 3 QTc prolongation). Of the 16 evaluable patients, one patient achieved a complete remission with incomplete count recovery (CRi), three experienced a morphologic leukemia-free state (MLFS) with a major hematologic improvement in platelets (HI-P), and 5 other patients had a reduction in marrow blast percentage (i.e. 11-65 %). The RP2D in this patient population is 225 mg orally once daily. PMID:27406088

  10. Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones.

    PubMed

    Gur, Ali; Cevik, Remzi; Nas, Kemal; Colpan, Leyla; Sarac, Serdar

    2004-01-01

    We investigated abnormalities of the hypothalamic-pituitary-gonadal axis and cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome (CFS) who were in the follicular phase of their menstrual cycle, and whether their scores for depressive symptoms were related to levels of these hormones. A total of 176 subjects participated - 46 healthy volunteers, 68 patients with fibromyalgia, and 62 patients with CFS. We examined concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, prolactin, and cortisol. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Cortisol levels were significantly lower in patients with fibromyalgia or CFS than in healthy controls (P < 0.05); there were no significant differences in other hormone levels between the three groups. Fibromyalgia patients with high BDI scores had significantly lower cortisol levels than controls (P < 0.05), and so did CFS patients, regardless of their BDI scores (P < 0.05). Among patients without depressive symptoms, cortisol levels were lower in CFS than in fibromyalgia (P < 0.05). Our study suggests that in spite of low morning cortisol concentrations, the only abnormalities in hypothalamic-pituitary-gonadal axis hormones among follicular-phase women with fibromyalgia or CFS are those of LH levels in fibromyalgia patients with a low BDI score. Depression may lower cortisol and LH levels, or, alternatively, low morning cortisol may be a biological factor that contributes to depressive symptoms in fibromyalgia. These parameters therefore must be taken into account in future investigations.

  11. Inhibition of Acute-, Latent-, and Chronic-Phase Human Immunodeficiency Virus Type 1 (HIV-1) Replication by a Bistriazoloacridone Analog That Selectively Inhibits HIV-1 Transcription

    PubMed Central

    Turpin, Jim A.; Buckheit, Robert W.; Derse, David; Hollingshead, Melinda; Williamson, Karen; Palamone, Carla; Osterling, M. Clayton; Hill, Shawn A.; Graham, Lisa; Schaeffer, Catherine A.; Bu, Ming; Huang, Mingjun; Cholody, Wieslaw M.; Michejda, Christopher J.; Rice, William G.

    1998-01-01

    Nanomolar concentrations of temacrazine (1,4-bis[3-(6-oxo-6H-v-triazolo[4,5,1-de]acridin-5-yl)amino-propyl]piperazine) were discovered to inhibit acute human immunodeficiency virus type 1 (HIV-1) infections and suppress the production of virus from chronically and latently infected cells containing integrated proviral DNA. This bistriazoloacridone derivative exerted its mechanism of antiviral action through selective inhibition of HIV-1 transcription during the postintegrative phase of virus replication. Mechanistic studies revealed that temacrazine blocked HIV-1 RNA formation without interference with the transcription of cellular genes or with events associated with the HIV-1 Tat and Rev regulatory proteins. Although temacrazine inhibited the in vitro 3′ processing and strand transfer activities of HIV-1 integrase, with a 50% inhibitory concentration of approximately 50 nM, no evidence of an inhibitory effect on the intracellular integration of proviral DNA into the cellular genome during the early phase of infection could be detected. Furthermore, temacrazine did not interfere with virus attachment or fusion to host cells or the enzymatic activities of HIV-1 reverse transcriptase or protease, and the compound was not directly virucidal. Demonstration of in vivo anti-HIV-1 activity by temacrazine identifies bistriazoloacridones as a new class of pharmaceuticals that selectively blocks HIV-1 transcription. PMID:9517921

  12. Microwave inverse Cerenkov accelerator

    NASA Astrophysics Data System (ADS)

    Zhang, T. B.; Marshall, T. C.; LaPointe, M. A.; Hirshfield, J. L.

    1997-03-01

    A Microwave Inverse Cerenkov Accelerator (MICA) is currently under construction at the Yale Beam Physics Laboratory. The accelerating structure in MICA consists of an axisymmetric dielectrically lined waveguide. For the injection of 6 MeV microbunches from a 2.856 GHz RF gun, and subsequent acceleration by the TM01 fields, particle simulation studies predict that an acceleration gradient of 6.3 MV/m can be achieved with a traveling-wave power of 15 MW applied to the structure. Synchronous injection into a narrow phase window is shown to allow trapping of all injected particles. The RF fields of the accelerating structure are shown to provide radial focusing, so that longitudinal and transverse emittance growth during acceleration is small, and that no external magnetic fields are required for focusing. For 0.16 nC, 5 psec microbunches, the normalized emittance of the accelerated beam is predicted to be less than 5πmm-mrad. Experiments on sample alumina tubes have been conducted that verify the theoretical dispersion relation for the TM01 mode over a two-to-one range in frequency. No excitation of axisymmetric or non-axisymmetric competing waveguide modes was observed. High power tests showed that tangential electric fields at the inner surface of an uncoated sample of alumina pipe could be sustained up to at least 8.4 MV/m without breakdown. These considerations suggest that a MICA test accelerator can be built to examine these predictions using an available RF power source, 6 MeV RF gun and associated beam line.

  13. High field gradient particle accelerator

    DOEpatents

    Nation, J.A.; Greenwald, S.

    1989-05-30

    A high electric field gradient electron accelerator utilizing short duration, microwave radiation, and capable of operating at high field gradients for high energy physics applications or at reduced electric field gradients for high average current intermediate energy accelerator applications is disclosed. Particles are accelerated in a smooth bore, periodic undulating waveguide, wherein the period is so selected that the particles slip an integral number of cycles of the r.f. wave every period of the structure. This phase step of the particles produces substantially continuous acceleration in a traveling wave without transverse magnetic or other guide means for the particle. 10 figs.

  14. High field gradient particle accelerator

    DOEpatents

    Nation, John A.; Greenwald, Shlomo

    1989-01-01

    A high electric field gradient electron accelerator utilizing short duration, microwave radiation, and capable of operating at high field gradients for high energy physics applications or at reduced electric field gradients for high average current intermediate energy accelerator applications. Particles are accelerated in a smooth bore, periodic undulating waveguide, wherein the period is so selected that the particles slip an integral number of cycles of the r.f. wave every period of the structure. This phase step of the particles produces substantially continuous acceleration in a traveling wave without transverse magnetic or other guide means for the particle.

  15. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial

    PubMed Central

    Koh, Christopher; Canini, Laetitia; Dahari, Harel; Zhao, Xiongce; Uprichard, Susan L; Haynes-Williams, Vanessa; Winters, Mark A; Subramanya, Gitanjali; Cooper, Stewart L; Pinto, Peter; Wolff, Erin F; Bishop, Rachel; Han, Ma Ai Thanda; Cotler, Scott J; Kleiner, David E; Keskin, Onur; Idilman, Ramazan; Yurdaydin, Cihan; Glenn, Jeffrey S; Heller, Theo

    2015-01-01

    Summary Background Therapies for chronic hepatitis delta virus (HDV) infection are unsatisfactory. Prenylation is essential for HDV and inhibition abrogates HDV production in experimental models. In a proof-of-concept study, we aimed to assess the effect on HDV RNA levels, safety, and tolerability of the prenylation inhibitor lonafarnib in patients with chronic delta hepatitis. Methods In this phase 2A double-blind, randomised, placebo-controlled study, patients aged 18 years or older with chronic HDV infection were randomly assigned (3:1 in group 1 and 2:1 in group 2) to receive lonafarnib 100 mg (group 1) or lonafarnib 200 mg (group 2) twice daily for 28 days with 6 months’ follow-up. Participants were randomised by random-number tables blocked in groups of four without stratification. Both groups enrolled six treatment participants and two placebo participants. Group 1 placebo patients received open-label lonafarnib as group 2 participants. The primary therapeutic endpoint was a decrease in HDV RNA viral titre in serum and the primary safety endpoint was the ability to tolerate the drug at the prescribed dose for the full 4-week duration, defined as drug discontinuation due to intolerance or grade 3/4 adverse events. This trial is registered with ClinicalTrials.gov, number NCT01495585. Findings Between Jan 19, 2012, and April 28, 2014, 14 patients were enrolled, of whom eight were assigned to group 1 and six were assigned to group 2. At day 28, compared with placebo, mean log HDV RNA declines from baseline were −0.73 log IU/mL in group 1 (95% CI 0.17–1.31; p=0.03) and −1.54 log IU/mL in group 2 (1.21–1.93; p<0.0001). Lonafarnib serum concentrations correlated with HDV RNA change (r2=0.78, p<0.0001). Model fits show that hepatitis B surface antigen (HBsAg) remained stable after a short pharmacological delay (0.75 days [SE 0.24]), lonafarnib effectiveness in blocking HDV production was greater in group 2 than in group 1 (0.952 [SE 0.06] vs 0.739 [0

  16. Impact of BCR-ABL transcript type on outcome in patients with chronic-phase CML treated with tyrosine kinase inhibitors.

    PubMed

    Jain, Preetesh; Kantarjian, Hagop; Patel, Keyur P; Gonzalez, Graciela Nogueras; Luthra, Rajyalakshmi; Kanagal Shamanna, Rashmi; Sasaki, Koji; Jabbour, Elias; Romo, Carlos Guillermo; Kadia, Tapan M; Pemmaraju, Naveen; Daver, Naval; Borthakur, Gautam; Estrov, Zeev; Ravandi, Farhad; O'Brien, Susan; Cortes, Jorge

    2016-03-10

    The most common breakpoint cluster region gene-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) transcripts in chronic myeloid leukemia (CML) are e13a2 (b2a2) and e14a2 (b3a2). The impact of the type of transcript on response and survival after initial treatment with different tyrosine kinase inhibitors is unknown. This study involved 481 patients with chronic phase CML expressing various BCR-ABL transcripts. Two hundred patients expressed e13a2 (42%), 196 (41%) expressed e14a2, and 85 (18%) expressed both transcripts. The proportion of patients with e13a2, e14a2, and both achieving complete cytogenetic response at 3 and 6 months was 59%, 67%, and 63% and 73%, 81%, and 82%, respectively, whereas major molecular response rates were 27%, 49%, and 50% at 3 months, 42%, 67%, and 70% at 6 months, and 55%, 83%, and 76% at 12 months, respectively. Median (international scale) levels of transcripts e13a2, e14a2, and both at 3 months were 0.2004, 0.056, and 0.0612 and at 6 months were 0.091, 0.0109, and 0.0130, respectively. In multivariate analysis, e14a2 and both predicted for optimal responses at 3, 6, and 12 months. The type of transcript also predicted for improved probability of event-free (P = .043; e14a2) and transformation-free survival (P = .04 for both). Compared to e13a2 transcripts, patients with e14a2 (alone or with coexpressed e13a2) achieved earlier and deeper responses, predicted for optimal European Leukemia Net (ELN) responses (at 3, 6, and 12 months) and predicted for longer event-free and transformation-free survival. PMID:26729897

  17. A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient

    PubMed Central

    Ash, Stephen R; Singh, Bhupinder; Lavin, Philip T; Stavros, Fiona; Rasmussen, Henrik S

    2015-01-01

    Hyperkalemia contributes to significant mortality and limits the use of cardioprotective and renoprotective renin–angiotensin–aldosterone blockers. Current therapies are poorly tolerated and not always effective. Here we conducted a phase 2 randomized, double-blind, placebo-controlled dose-escalation study to assess safety and efficacy of ZS-9. This oral selective cation exchanger that preferentially entraps potassium in the gastrointestinal tract was given to patients with stable Stage 3 chronic kidney disease and hyperkalemia (5.0 to 6.0 mEq/l) during a 2-day period. Of 90 eligible patients with mean baseline serum potassium of 5.1 mEq/l, 30 were randomized to placebo, 12–0.3 g, 24–3 g, or 24 to 10 g of ZS-9 three times daily for 2 days with regular meals. None withdrew and ZS-9 dose-dependently reduced serum potassium. The primary efficacy end point (rate of serum potassium decline in the first 48 h) was met with significance in the 3- and 10-g cohorts. From baseline, mean serum potassium was significantly decreased by 0.92±0.52 mEq/l at 38 h. Urinary potassium excretion significantly decreased with 10-g ZS-9 as compared to placebo at day 2 (+15.8 +/− 21.8 vs. +8.9 +/− 22.9 mEq per 24h) from placebo at day 2. In this short-term study, no serious adverse events were reported; only mild constipation in the 3-g dose group was possibly related to treatment. Thus, ZS-9 was well-tolerated in patients with stable chronic kidney disease and hyperkalemia leading to a rapid, sustained reduction in serum potassium. PMID:25651363

  18. Accelerator simulation of astrophysical processes

    NASA Technical Reports Server (NTRS)

    Tombrello, T. A.

    1983-01-01

    Phenomena that involve accelerated ions in stellar processes that can be simulated with laboratory accelerators are described. Stellar evolutionary phases, such as the CNO cycle, have been partially explored with accelerators, up to the consumption of He by alpha particle radiative capture reactions. Further experimentation is indicated on reactions featuring N-13(p,gamma)O-14, O-15(alpha, gamma)Ne-19, and O-14(alpha,p)F-17. Accelerated beams interacting with thin foils produce reaction products that permit a determination of possible elemental abundances in stellar objects. Additionally, isotopic ratios observed in chondrites can be duplicated with accelerator beam interactions and thus constraints can be set on the conditions producing the meteorites. Data from isotopic fractionation from sputtering, i.e., blasting surface atoms from a material using a low energy ion beam, leads to possible models for processes occurring in supernova explosions. Finally, molecules can be synthesized with accelerators and compared with spectroscopic observations of stellar winds.

  19. A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics

    PubMed Central

    Sculier, J P; Paesmans, M; Lecomte, J; Van Cutsem, O; Lafitte, J J; Berghmans, T; Koumakis, G; Florin, M C; Thiriaux, J; Michel, J; Giner, V; Berchier, M C; Mommen, P; Ninane, V; Klastersky, J

    2001-01-01

    The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m−2, vindesine 3 mg m−2, ifosfamide 5 g m−2; all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.   http://www.bjcancer.com PMID:11720426

  20. High-Intensity Proton Accelerator

    SciTech Connect

    Jay L. Hirshfield

    2011-12-27

    Analysis is presented for an eight-cavity proton cyclotron accelerator that could have advantages as compared with other accelerators because of its potentially high acceleration gradient. The high gradient is possible since protons orbit in a sequence of TE111 rotating mode cavities of equally diminishing frequencies with path lengths during acceleration that greatly exceed the cavity lengths. As the cavities operate at sequential harmonics of a basic repetition frequency, phase synchronism can be maintained over a relatively wide injection phase window without undue beam emittance growth. It is shown that use of radial vanes can allow cavity designs with significantly smaller radii, as compared with simple cylindrical cavities. Preliminary beam transport studies show that acceptable extraction and focusing of a proton beam after cyclic motion in this accelerator should be possible. Progress is also reported on design and tests of a four-cavity electron counterpart accelerator for experiments to study effects on beam quality arising from variations injection phase window width. This device is powered by four 500-MW pulsed amplifiers at 1500, 1800, 2100, and 2400 MHz that provide phase synchronous outputs, since they are driven from a with harmonics derived from a phase-locked 300 MHz source.

  1. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  2. Combination of White Blood Cell Count at Presentation With Molecular Response at 3 Months Better Predicts Deep Molecular Responses to Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients

    PubMed Central

    Qin, Ya-Zhen; Jiang, Qian; Jiang, Hao; Lai, Yue-Yun; Zhu, Hong-Hu; Liu, Yan-Rong; Jiang, Bin; Huang, Xiao-Jun

    2016-01-01

    Abstract The aim of this study was to evaluate the impact of white blood cell (WBC) counts at presentation on the achievement of deep molecular response. A total of 362 newly diagnosed chronic-phase chronic myeloid leukemia patients (CML-CP) receiving 400 mg/day imatinib were serially monitored for a median of 36 months (range 6–115). Patients showing an optimal response at 3, 6, and 12 months as defined by the 2013 European LeukemiaNet recommendations had significantly lower WBC counts at presentation than those showing nonoptimal responses (all P < 0.0001). Among the cutoff values with a similar Youden index, 150 × 10E9/L (abbreviated WBC > 150) was selected to identify the greatest amount of patients with the potential to achieve a sustained molecular response of 4.5 (MR4.5). Regardless of whether the Sokal risk score was included, the BCR-ABLIS value at 3 months, WBC counts at presentation, hemoglobin levels, and sex were the common independent predictors for an MR4.5, with the former 2 presenting the highest hazard risk. Low Sokal risk scores did not independently predict the achievement of an MR4.5. Patients with concurrent WBC > 150 and BCR-ABLIS ≤ 10% had a similar incidence of 4-year MR4.5 compared with patients with concurrent WBC ≤ 150 and BCR-ABLIS > 10% and concurrent WBC > 150 and BCR-ABLIS > 10% (13.5% vs 13.2% vs 8.8%, P = 0.47), and all of these values were significantly lower than the values for patients with concurrent WBC ≤ 150 and BCR-ABLIS ≤ 10% (55.0%, all P < 0.0001). Patients with concurrent WBC ≤ 150 and BCR-ABLIS ≤ 10% had better 4-year event-free survival rates, progression-free survival rates, and overall survival rates compared with patients with WBC > 150 or BCR-ABLIS > 10%. The combination of WBC count at presentation and BCR-ABLIS at 3 months provides improved predictions of deep molecular response in imatinib-treated CML-CP patients. Therefore, the WBC count at presentation might be used to

  3. Effects of chronic acceleration on body composition

    NASA Technical Reports Server (NTRS)

    Pitts, G. C.

    1982-01-01

    Studies of the centrifugation of adult rats showed an unexpected decrease in the mass of fat-free muscle and bone, in spite of the added load induced by centrifugation. It is suggested that the lower but constant fat-free body mass was probably regulated during centrifugation. Rats placed in weightless conditions for 18.5 days gave indirect but strong evidence that the muscle had increased in mass. Other changes in the rats placed in weightless conditions included a smaller fraction of skeletal mineral, a smaller fraction of water in the total fat-free body, and a net shift of fluid from skin to viscera. Adult rats centrifuged throughout the post-weaning growth period exhibited smaller masses of bone and central nervous system (probably attributable to slower growth of the total body), and a larger mass of skin than controls at 1 G. Efforts at simulating the effects of weightlessness or centrifugation on the body composition of rats by regimens at terrestrial gravity were inconclusive.

  4. Increased chronic acceleration exposure enhances work capacity.

    PubMed

    Burton, R R; Smith, A H

    1997-10-01

    Adult male chickens adapted to 1.75 or 2.5 G from long term centrifugation, were maximally exercised on an animal treadmill at 1 g (Earth's gravity) and compared with the exercise capacities of control chickens raised at 1 g. The increased-G birds had statistically significantly greater exercise capacities than the controls during the first 3 weeks of the study after the initial exercise exposure. Thereafter however for the following two months of the study, there was no difference in either group's exercise capacities. This early increased work capacity was attributed to the increased-G birds improved ability to maximize their muscular strength with neurological adaptation. The increased-G birds lost body mass at a 31% greater rate during exercise than the controls although this difference was not statistically significant. This increased body mass loss was considered to have resulted from increased use of glycogen during exercise.

  5. Effect of solution and solid-phase conditions on the Fe(II)-accelerated transformation of ferrihydrite to lepidocrocite and goethite.

    PubMed

    Boland, Daniel D; Collins, Richard N; Miller, Christopher J; Glover, Chris J; Waite, T David

    2014-05-20

    Aqueous ferrous iron (Fe(II)) accelerates the transformation of ferrihydrite into secondary, more crystalline minerals however the factors controlling the rate and, indeed, the underlying mechanism of this transformation process remain unclear. Here, we present the first detailed study of the kinetics of the Fe(II)-accelerated transformation of ferrihydrite to goethite, via lepidocrocite, for a range of pH and Fe(II) concentrations and, from the results obtained, provide insight into the factors controlling the transformation rate and the processes responsible for transformation. A reaction scheme for the Fe(II)-accelerated secondary mineralization of ferrihydrite is developed in which an Fe(II) atom attaches to the ferrihydrite surface where it is immediately oxidized to Fe(III) with the resultant electron transferred, sequentially, to other iron oxyhydroxide Fe(III) atoms before release to solution as Fe(II). This freshly precipitated Fe(III) forms the nuclei for the formation of secondary minerals and also facilitates the ongoing uptake of Fe(II) from solution by creation of fresh surface sites. The concentration of solid-associated Fe(II) and the rate of transport of Fe(II) to the oxyhydroxide surface appear to determine which particular secondary minerals form and their rates of formation. Lepidocrocite growth is enhanced at lower solid-associated Fe(II) concentrations while conditions leading to more rapid uptake of Fe(II) from solution lead to higher goethite growth rates.

  6. Particle acceleration

    NASA Technical Reports Server (NTRS)

    Vlahos, L.; Machado, M. E.; Ramaty, R.; Murphy, R. J.; Alissandrakis, C.; Bai, T.; Batchelor, D.; Benz, A. O.; Chupp, E.; Ellison, D.

    1986-01-01

    Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV.

  7. Accelerated Achievement

    ERIC Educational Resources Information Center

    Ford, William J.

    2010-01-01

    This article focuses on the accelerated associate degree program at Ivy Tech Community College (Indiana) in which low-income students will receive an associate degree in one year. The three-year pilot program is funded by a $2.3 million grant from the Lumina Foundation for Education in Indianapolis and a $270,000 grant from the Indiana Commission…

  8. ACCELERATION INTEGRATOR

    DOEpatents

    Pope, K.E.

    1958-01-01

    This patent relates to an improved acceleration integrator and more particularly to apparatus of this nature which is gyrostabilized. The device may be used to sense the attainment by an airborne vehicle of a predetermined velocitv or distance along a given vector path. In its broad aspects, the acceleration integrator utilizes a magnetized element rotatable driven by a synchronous motor and having a cylin drical flux gap and a restrained eddy- current drag cap deposed to move into the gap. The angular velocity imparted to the rotatable cap shaft is transmitted in a positive manner to the magnetized element through a servo feedback loop. The resultant angular velocity of tae cap is proportional to the acceleration of the housing in this manner and means may be used to measure the velocity and operate switches at a pre-set magnitude. To make the above-described dcvice sensitive to acceleration in only one direction the magnetized element forms the spinning inertia element of a free gyroscope, and the outer housing functions as a gimbal of a gyroscope.

  9. Plasma accelerator

    DOEpatents

    Wang, Zhehui; Barnes, Cris W.

    2002-01-01

    There has been invented an apparatus for acceleration of a plasma having coaxially positioned, constant diameter, cylindrical electrodes which are modified to converge (for a positive polarity inner electrode and a negatively charged outer electrode) at the plasma output end of the annulus between the electrodes to achieve improved particle flux per unit of power.

  10. Modulational effects in accelerators

    SciTech Connect

    Satogata, T.

    1997-12-01

    We discuss effects of field modulations in accelerators, specifically those that can be used for operational beam diagnostics and beam halo control. In transverse beam dynamics, combined effects of nonlinear resonances and tune modulations influence diffusion rates with applied tune modulation has been demonstrated. In the longitudinal domain, applied RF phase and voltage modulations provide mechanisms for parasitic halo transport, useful in slow crystal extraction. Experimental experiences with transverse tune and RF modulations are also discussed.

  11. The role and importance of glycosylation of acute phase proteins with focus on alpha-1 antitrypsin in acute and chronic inflammatory conditions.

    PubMed

    McCarthy, Cormac; Saldova, Radka; Wormald, Mark R; Rudd, Pauline M; McElvaney, Noel G; Reeves, Emer P

    2014-07-01

    Acute phase proteins (APPs) are a group of circulating plasma proteins which undergo changes quantitatively or qualitatively at the time of inflammation. Many of these APPs are glycosylated, and it has been shown that alterations in glycosylation may occur in inflammatory and malignant conditions. Changes in glycosylation have been studied as potential biomarkers in cancer and also in chronic inflammatory conditions and have been shown to correlate with disease severity in certain conditions. Serine protease inhibitors (serpins), many of which are also APPs, are proteins involved in the control of proteases in numerous pathways. Alpha-1 Antitrypsin (AAT) is the most abundant serpin within the circulation and is an APP which has been shown to increase in response to inflammation. The primary role of AAT is maintaining the protease/antiprotease balance in the lung, but it also possesses important anti-inflammatory and immune-modulating properties. Several glycoforms of AAT exist, and they possess differing properties in regard to plasma half-life and stability. Glycosylation may also be important in determining the immune modulatory properties of AAT. The review will focus on the role and importance of glycosylation in acute phase proteins with particular attention to AAT and its use as a biomarker of disease. The review describes the processes involved in glycosylation, how glycosylation changes in differing disease states, and the alterations that occur to glycans of APPs with disease and inflammation. Finally, the review explores the importance of changes in glycosylation of AAT at times of inflammation and in malignant conditions and how this may impact upon the functions of AAT.

  12. A Phase I Dose Escalation Study Demonstrates Quercetin Safety and Explores Potential for Bioflavonoid Antivirals in Patients with Chronic Hepatitis C.

    PubMed

    Lu, Nu T; Crespi, Catherine M; Liu, Natalie M; Vu, James Q; Ahmadieh, Yasaman; Wu, Sheng; Lin, Sherry; McClune, Amy; Durazo, Francisco; Saab, Sammy; Han, Steven; Neiman, David C; Beaven, Simon; French, Samuel W

    2016-01-01

    The hepatitis C virus (HCV) infects more than 180 million people worldwide, with long-term consequences including liver failure and hepatocellular carcinoma. Quercetin bioflavonoids can decrease HCV production in tissue culture, in part through inhibition of heat shock proteins. If quercetin demonstrates safety and antiviral activity in patients, then it could be developed into an inexpensive HCV treatment for third world countries or other affected populations that lack financial means to cover the cost of mainstream antivirals. A phase 1 dose escalation study was performed to evaluate the safety of quercetin in 30 untreated patients with chronic HCV infection and to preliminarily characterize quercetin's potential in suppressing viral load and/or liver injury. Quercetin displayed safety in all trial participants. Additionally, 8 patients showed a "clinically meaningful" 0.41-log viral load decrease. There was a positive correlation (r = 0.41, p = 0.03) indicating a tendency for HCV decrease in patients with a lower ratio of plasma quercetin relative to dose. No significant changes in aspartate transaminase and alanine transaminase were detected. In conclusion, quercetin exhibited safety (up to 5 g daily) and there was a potential for antiviral activity in some hepatitis C patients.

  13. An open-label phase 2 trial of entospletinib (GS-9973), a selective spleen tyrosine kinase inhibitor, in chronic lymphocytic leukemia

    PubMed Central

    Hawkins, Michael; Kolibaba, Kathryn; Boxer, Michael; Klein, Leonard; Wu, Meihua; Hu, Jing; Abella, Steve; Yasenchak, Chris

    2015-01-01

    Small-molecule inhibitors of kinases involved in B-cell receptor signaling are an important advance in managing lymphoid malignancies. Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. This multicenter, phase 2 study enrolled subjects with relapsed or refractory chronic lymphocytic leukemia (CLL; n = 41) or non-Hodgkin lymphoma (n = 145). Participants received 800 mg entospletinib twice daily. We report efficacy outcomes in the CLL cohort (n = 41) and safety outcomes in all cohorts (N = 186). The primary end point was a progression-free survival (PFS) rate at 24 weeks in subjects with CLL. The PFS rate at 24 weeks was 70.1% (95% confidence interval [CI], 51.3%-82.7%); median PFS was 13.8 months (95% CI, 7.7 months to not reached). The objective response rate was 61.0% (95% CI, 44.5%-75.8%), including 3 subjects (7.3%) who achieved nodal response with persistent lymphocytosis. Fifty-four subjects (29.0%) had serious adverse events (SAEs). The most common treatment-emergent SAEs included dyspnea, pneumonia, febrile neutropenia, dehydration, and pyrexia. Common grade 3/4 laboratory abnormalities included neutropenia (14.5%) and reversible alanine aminotransferase/aspartate aminotransferase elevations (13.4%). Entospletinib demonstrates clinical activity in subjects with relapsed or refractory CLL with acceptable toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01799889. PMID:25696919

  14. Intensive care unit nurses' perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation: an interview study

    PubMed Central

    Kvangarsnes, Marit; Torheim, Henny; Hole, Torstein; Öhlund, Lennart S

    2013-01-01

    Aim To report a study conducted to explore intensive care unit nurses’ perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation. Background An acute exacerbation is a life-threatening situation, which patients often consider to be extremely frightening. Healthcare personnel exercise considerable power in this situation, which challenges general professional notions of patient participation. Design Critical discourse analysis. Methods In the autumn of 2009, three focus group interviews with experienced intensive care nurses were conducted at two hospitals in western Norway. Two groups had six participants each, and one group had five (N = 17). The transcribed interviews were analysed by means of critical discourse analysis. Findings The intensive care nurses said that an exacerbation is often an extreme situation in which healthcare personnel are exercising a high degree of control and power over patients. Patient participation during exacerbation often takes the form of non-involvement. The participating nurses attached great importance to taking a sensitive approach when meeting patients. The nurses experienced challenging ethical dilemmas. Conclusion This study shows that patient participation should not be understood in universal terms, but rather in relation to a specific setting and the interactions that occur in this setting. Healthcare personnel must develop skill, understanding, and competence to meet these challenging ethical dilemmas. A collaborative inter-professional approach between physicians and nurses is needed to meet the patients’ demand for involvement. PMID:22512673

  15. Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial

    PubMed Central

    Bühler, A; Wendtner, C-M; Kipps, T J; Rassenti, L; Fraser, G A M; Michallet, A-S; Hillmen, P; Dürig, J; Gregory, S A; Kalaycio, M; Aurran-Schleinitz, T; Trentin, L; Gribben, J G; Chanan-Khan, A; Purse, B; Zhang, J; De Bedout, S; Mei, J; Hallek, M; Stilgenbauer, S

    2016-01-01

    Efficacy of lenalidomide was investigated in 103 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) treated on the prospective, multicenter randomized phase-II CLL-009 trial. Interphase cytogenetic and mutational analyses identified TP53 mutations, unmutated IGHV, or del(17p) in 36/96 (37.5%), 68/88 (77.3%) or 22/92 (23.9%) patients. The overall response rate (ORR) was 40.4% (42/104). ORRs were similar irrespective of TP53 mutation (36.1% (13/36) vs 43.3% (26/60) for patients with vs without mutation) or IGHV mutation status (45.0% (9/20) vs 39.1% (27/68)); however, patients with del(17p) had lower ORRs than those without del(17p) (21.7% (5/22) vs 47.1% (33/70); P=0.049). No significant differences in progression-free survival and overall survival (OS) were observed when comparing subgroups defined by the presence or absence of high-risk genetic characteristics. In multivariate analyses, only multiple prior therapies (⩾3 lines) significantly impacted outcomes (median OS: 21.2 months vs not reached; P=0.019). This analysis indicates that lenalidomide is active in patients with relapsed/refractory CLL with unfavorable genetic profiles, including TP53 inactivation or unmutated IGHV. (ClinicalTrials.gov identifier: NCT00963105). PMID:26967821

  16. Kinematics of transition during human accelerated sprinting

    PubMed Central

    Nagahara, Ryu; Matsubayashi, Takeo; Matsuo, Akifumi; Zushi, Koji

    2014-01-01

    ABSTRACT This study investigated kinematics of human accelerated sprinting through 50 m and examined whether there is transition and changes in acceleration strategies during the entire acceleration phase. Twelve male sprinters performed a 60-m sprint, during which step-to-step kinematics were captured using 60 infrared cameras. To detect the transition during the acceleration phase, the mean height of the whole-body centre of gravity (CG) during the support phase was adopted as a measure. Detection methods found two transitions during the entire acceleration phase of maximal sprinting, and the acceleration phase could thus be divided into initial, middle, and final sections. Discriminable kinematic changes were found when the sprinters crossed the detected first transition—the foot contacting the ground in front of the CG, the knee-joint starting to flex during the support phase, terminating an increase in step frequency—and second transition—the termination of changes in body postures and the start of a slight decrease in the intensity of hip-joint movements, thus validating the employed methods. In each acceleration section, different contributions of lower-extremity segments to increase in the CG forward velocity—thigh and shank for the initial section, thigh, shank, and foot for the middle section, shank and foot for the final section—were verified, establishing different acceleration strategies during the entire acceleration phase. In conclusion, there are presumably two transitions during human maximal accelerated sprinting that divide the entire acceleration phase into three sections, and different acceleration strategies represented by the contributions of the segments for running speed are employed. PMID:24996923

  17. Systematic review of dasatinib in chronic myeloid leukemia.

    PubMed

    Breccia, Massimo; Salaroli, Adriano; Molica, Matteo; Alimena, Giuliana

    2013-01-01

    Dasatinib is a dual tyrosine kinase inhibitor active against ABL and Src family kinases, and is approved for the treatment of chronic myeloid leukemia (CML) patients in chronic, accelerated, or blast phase with resistance or intolerance to imatinib therapy, for newly diagnosed chronic phase patients, and for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia who have become resistant to or intolerant of other treatments. This review presents clinical data regarding different trials involving CML patients in different phases of the disease. Six-year follow-up of the Phase III dose-optimization study are described, showing overall survival of 71% with the current approved dose of 100 mg once daily. Three-year results of the randomized Phase III DASISION (DASatinib vs Imatinib Study In Treatment-Naïve CML patients) trial confirmed that dasatinib 100 mg once daily was superior to standard-dose imatinib in terms of achieving a faster and deeper molecular response, with similar activity regardless of baseline prognostic score.

  18. Compact accelerator

    DOEpatents

    Caporaso, George J.; Sampayan, Stephen E.; Kirbie, Hugh C.

    2007-02-06

    A compact linear accelerator having at least one strip-shaped Blumlein module which guides a propagating wavefront between first and second ends and controls the output pulse at the second end. Each Blumlein module has first, second, and third planar conductor strips, with a first dielectric strip between the first and second conductor strips, and a second dielectric strip between the second and third conductor strips. Additionally, the compact linear accelerator includes a high voltage power supply connected to charge the second conductor strip to a high potential, and a switch for switching the high potential in the second conductor strip to at least one of the first and third conductor strips so as to initiate a propagating reverse polarity wavefront(s) in the corresponding dielectric strip(s).

  19. BICEP's acceleration

    SciTech Connect

    Contaldi, Carlo R.

    2014-10-01

    The recent Bicep2 [1] detection of, what is claimed to be primordial B-modes, opens up the possibility of constraining not only the energy scale of inflation but also the detailed acceleration history that occurred during inflation. In turn this can be used to determine the shape of the inflaton potential V(φ) for the first time — if a single, scalar inflaton is assumed to be driving the acceleration. We carry out a Monte Carlo exploration of inflationary trajectories given the current data. Using this method we obtain a posterior distribution of possible acceleration profiles ε(N) as a function of e-fold N and derived posterior distributions of the primordial power spectrum P(k) and potential V(φ). We find that the Bicep2 result, in combination with Planck measurements of total intensity Cosmic Microwave Background (CMB) anisotropies, induces a significant feature in the scalar primordial spectrum at scales k∼ 10{sup -3} Mpc {sup -1}. This is in agreement with a previous detection of a suppression in the scalar power [2].

  20. Beam acceleration through proton radio frequency quadrupole accelerator in BARC

    NASA Astrophysics Data System (ADS)

    Bhagwat, P. V.; Krishnagopal, S.; Mathew, J. V.; Singh, S. K.; Jain, P.; Rao, S. V. L. S.; Pande, M.; Kumar, R.; Roychowdhury, P.; Kelwani, H.; Rama Rao, B. V.; Gupta, S. K.; Agarwal, A.; Kukreti, B. M.; Singh, P.

    2016-05-01

    A 3 MeV proton Radio Frequency Quadrupole (RFQ) accelerator has been designed at the Bhabha Atomic Research Centre, Mumbai, India, for the Low Energy High Intensity Proton Accelerator (LEHIPA) programme. The 352 MHz RFQ is built in 4 segments and in the first phase two segments of the LEHIPA RFQ were commissioned, accelerating a 50 keV, 1 mA pulsed proton beam from the ion source, to an energy of 1.24 MeV. The successful operation of the RFQ gave confidence in the physics understanding and technology development that have been achieved, and indicate that the road forward can now be traversed rather more quickly.

  1. Phase precession through acceleration of local theta rhythm: a biophysical model for the interaction between place cells and local inhibitory neurons.

    PubMed

    Castro, Luísa; Aguiar, Paulo

    2012-08-01

    Phase precession is one of the most well known examples within the temporal coding hypothesis. Here we present a biophysical spiking model for phase precession in hippocampal CA1 which focuses on the interaction between place cells and local inhibitory interneurons. The model's functional block is composed of a place cell (PC) connected with a local inhibitory cell (IC) which is modulated by the population theta rhythm. Both cells receive excitatory inputs from the entorhinal cortex (EC). These inputs are both theta modulated and space modulated. The dynamics of the two neuron types are described by integrate-and-fire models with conductance synapses, and the EC inputs are described using non-homogeneous Poisson processes. Phase precession in our model is caused by increased drive to specific PC/IC pairs when the animal is in their place field. The excitation increases the IC's firing rate, and this modulates the PC's firing rate such that both cells precess relative to theta. Our model implies that phase coding in place cells may not be independent from rate coding. The absence of restrictive connectivity constraints in this model predicts the generation of phase precession in any network with similar architecture and subject to a clocking rhythm, independently of the involvement in spatial tasks.

  2. Prospects for Accelerator Technology

    NASA Astrophysics Data System (ADS)

    Todd, Alan

    2011-02-01

    Accelerator technology today is a greater than US$5 billion per annum business. Development of higher-performance technology with improved reliability that delivers reduced system size and life cycle cost is expected to significantly increase the total accelerator technology market and open up new application sales. Potential future directions are identified and pitfalls in new market penetration are considered. Both of the present big market segments, medical radiation therapy units and semiconductor ion implanters, are approaching the "maturity" phase of their product cycles, where incremental development rather than paradigm shifts is the norm, but they should continue to dominate commercial sales for some time. It is anticipated that large discovery-science accelerators will continue to provide a specialty market beset by the unpredictable cycles resulting from the scale of the projects themselves, coupled with external political and economic drivers. Although fraught with differing market entry difficulties, the security and environmental markets, together with new, as yet unrealized, industrial material processing applications, are expected to provide the bulk of future commercial accelerator technology growth.

  3. Advanced concepts for acceleration

    SciTech Connect

    Keefe, D.

    1986-07-01

    Selected examples of advanced accelerator concepts are reviewed. Such plasma accelerators as plasma beat wave accelerator, plasma wake field accelerator, and plasma grating accelerator are discussed particularly as examples of concepts for accelerating relativistic electrons or positrons. Also covered are the pulsed electron-beam, pulsed laser accelerator, inverse Cherenkov accelerator, inverse free-electron laser, switched radial-line accelerators, and two-beam accelerator. Advanced concepts for ion acceleration discussed include the electron ring accelerator, excitation of waves on intense electron beams, and two-wave combinations. (LEW)

  4. Accelerators and the Accelerator Community

    SciTech Connect

    Malamud, Ernest; Sessler, Andrew

    2008-06-01

    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process.

  5. Accelerated test methods for predicting the life of motor materials exposed to refrigerant/lubricant mixtures. Phase 1, Conceptual design: Final report

    SciTech Connect

    Ellis, P.F. II; Ferguson, A.

    1993-08-18

    The federally mandated phase-out of chlorofluorocarbon refrigerants requires screening tests for motor materials compatibility with alternative refrigerant/lubricant mixtures. In the current phase of the program, ARTI is supporting tests of promising candidate refrigeration/lubricant systems in key refrigeration component systems such as bearings and hermetic motor insulation systems to screen for more subtle detrimental effects and allow estimates of motor-compressor life. This report covers: mechanisms of failure of hermetic motor insulation, current methods for estimation of life of hermetic motors, and conceptual design of improved stator simulator device for testing of alternative refrigerant/lubricant mixtures.

  6. Continuous accelerated 7-days-a-week radiotherapy for head-and-neck cancer: Long-term results of Phase III clinical trial

    SciTech Connect

    Skladowski, Krzysztof . E-mail: skladowski@io.gliwice.pl; Maciejewski, Boguslaw; Golen, Maria; Tarnawski, Rafal; Slosarek, Krzysztof; Suwinski, Rafal; Sygula, Mariusz; Wygoda, Andrzej

    2006-11-01

    Purpose: To update 5-year results of a previously published study on special 7-days-a-week fractionation continuous accelerated irradiation (CAIR) for head-and-neck cancer patients. Methods and Materials: One hundred patients with squamous cell carcinoma of head and neck in Stage T{sub 2-4}N{sub 0-1}M were randomized between two definitive radiation treatments: accelerated fractionation 7 days a week including weekends (CAIR) and conventional 5 days a week (control). Hence the overall treatment time was 2 weeks shorter in CAIR. Results: Five-year local tumor control was 75% in the CAIR group and 33% in the control arm (p < 0.00004). Tumor-cure benefit corresponded with significant improvement in disease-free survival and overall survival rates. Confluent mucositis was the main acute toxicity, with the incidence significantly higher in CAIR patients than in control (respectively, 94% vs. 53%). When 2.0-Gy fractions were used, radiation necrosis developed in 5 patients (22%) in the CAIR group as a consequential late effect (CLE), but when fraction size was reduced to 1.8 Gy no more CLE occurred. Actuarial 5-year morbidity-free survival rate was similar for both treatments. Conclusions: Selected head-and-neck cancer patients could be treated very effectively with 7-days-a-week radiation schedule with no compromise of total dose and with slight 10% reduction of fraction dose (2 Gy-1.8 Gy), which article gives 1 week reduction of overall treatment time compared with standard 70 Gy in 35 fractions over 47-49 days. Although this report is based on the relatively small group of patients, its results have encouraged us to use CAIR fractionation in a standard radiation treatment for moderately advanced head-and-neck cancer patients.

  7. SL-401 and SL-501, targeted therapeutics directed at the interleukin-3 receptor, inhibit the growth of leukaemic cells and stem cells in advanced phase chronic myeloid leukaemia.

    PubMed

    Frolova, Olga; Benito, Juliana; Brooks, Chris; Wang, Rui-Yu; Korchin, Borys; Rowinsky, Eric K; Cortes, Jorge; Kantarjian, Hagop; Andreeff, Michael; Frankel, Arthur E; Konopleva, Marina

    2014-09-01

    While imatinib and other tyrosine kinase inhibitors (TKIs) are highly efficacious in the treatment of chronic myeloid leukaemia (CML), some patients become refractory to these therapies. After confirming that interleukin-3 receptor (IL3R, CD123) is highly expressed on CD34(+) /CD38(-) BCR-ABL1(+) CML stem cells, we investigated whether targeting IL3R with diphtheria toxin (DT)-IL3 fusion proteins SL-401 (DT388 -IL3) and SL-501 (DT388 -IL3[K116W]) could eradicate these stem cells. SL-401 and SL-501 inhibited cell growth and induced apoptosis in the KBM5 cell line and its TKI-resistant KBM5-STI subline. Combinations of imatinib with these agents increased apoptosis in KBM5 and in primary CML cells. In six primary CML samples, including CML cells harbouring the ABL1 T315I mutation, SL-401 and SL-501 decreased the absolute numbers of viable CD34(+) /CD38(-) /CD123(+) CML progenitor cells by inducing apoptosis. IL3-targeting agents reduced clonogenic growth and diminished the fraction of primitive long-term culture-initiating cells in samples from patients with advanced phase CML that were resistant to TKIs or harboured an ABL1 mutation. Survival was also extended in a mouse model of primary TKI-resistant CML blast crisis. These data suggest that the DT-IL3 fusion proteins, SL-401 and SL-501, deplete CML stem cells and may increase the effectiveness of current CML treatment, which principally targets tumour bulk.

  8. Phase I, Open-Label, Single-Dose Study To Evaluate the Pharmacokinetics and Safety of Telbivudine in Children and Adolescents with Chronic Hepatitis B

    PubMed Central

    Ke, June; Uy, Grace; Bosheva, Miroslava; Qi, Yin; Praestgaard, Jens

    2013-01-01

    Telbivudine is a nucleoside analogue that has been approved for the treatment of chronic hepatitis B virus (HBV) infection in adults at 600 mg/day. We conducted a phase I, open-label, first-in-pediatrics study to investigate the safety and pharmacokinetics of a single dose of telbivudine in HBV-infected children and adolescents. Eligible patients were enrolled sequentially from older to younger groups, with evaluation of safety and available pharmacokinetic data after each stratum. Adolescent patients (>12 to 18 years) received a single dose of 600 mg telbivudine as an oral solution, while children aged 2 to 12 years received a single dose of 15 or 25 mg/kg of body weight up to a maximum of 600 mg. Telbivudine was well tolerated; all adverse events were mild, and none occurred in more than one patient. The plasma telbivudine concentration-versus-time profiles in adolescents given 600 mg were similar to the mean profile of healthy adults receiving the same oral dose. Children aged 2 to <6 and 6 to 12 years receiving a single 15-mg/kg dose showed similar plasma exposures. To predict the steady-state exposure, plasma concentration-versus-time profiles for patients aged 2 to 12 years (15 mg/kg) and >12 to 18 years (600 mg) were fitted to a two-compartment 1st-order, microconstant, lag time, 1st-order elimination pharmacokinetic (PK) model. This analysis predicted the following dosages to mimic exposures in healthy adults receiving 600 mg/day: 20 mg/kg/day for children 2 to 12 years and 600 mg/day for adolescents. Studies are ongoing to evaluate the efficacy of the recommended dose in pediatric patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00907894.) PMID:23774433

  9. Chronic Bronchitis

    MedlinePlus

    ... chronic. Chronic bronchitis is one type of COPD (chronic obstructive pulmonary disease). The inflamed bronchial tubes produce a lot of mucus. This leads to coughing and difficulty breathing. Cigarette smoking is the most ... diagnose chronic bronchitis, your doctor will look at your signs ...

  10. Accelerating PV Cost Effectiveness Through Systems Design, Engineering, and Quality Assurance: Phase I Annual Technical Report, 4 November 2004 - 3 November 2005

    SciTech Connect

    Botkin, J.

    2006-07-01

    During Phase I of this PV Manufacturing R&D subcontract, PowerLight Corporation has made significant progress toward the reduction of installed costs for commercial-scale, rooftop PV systems. PowerLight has worked to reduce operating costs by improving long-term reliability and performance through the development of more sophisticated tools used in system design and monitoring. Additionally, PowerLight has implemented design improvements with the goal of reducing cost while maintaining and/or improving product quality. As part of this effort, PowerLight also modified manufacturing and shipping processes to accommodate these design changes, streamline material flow, reduce cost, and decrease waste streams. During Phase II of this project, PowerLight plans to continue this work with the goal of reducing system cost and improving system performance.

  11. Hyperbaric oxygen for patients with chronic bowel dysfunction after pelvic radiotherapy (HOT2): a randomised, double-blind, sham-controlled phase 3 trial

    PubMed Central

    Glover, Mark; Smerdon, Gary R; Andreyev, H Jervoise; Benton, Barbara E; Bothma, Pieter; Firth, Oliver; Gothard, Lone; Harrison, John; Ignatescu, Mihaela; Laden, Gerard; Martin, Sue; Maynard, Lauren; McCann, Des; Penny, Christine E L; Phillips, Spencer; Sharp, Grace; Yarnold, John

    2016-01-01

    Summary Background Hyperbaric oxygen has been used as a therapy for patients experiencing chronic intestinal syndromes after pelvic radiotherapy for decades, yet the evidence to support the use of this therapy is based almost exclusively on non-randomised studies. We aimed to provide conclusive results for the clinical benefits of hyperbaric oxygen in patients with chronic bowel dysfunction after radiotherapy for pelvic malignancies. Methods HOT2 was a double-blind, sham-controlled, phase 3 randomised study of patients (≥18 years) with chronic gastrointestinal symptoms for 12 months or more after radiotherapy and which persisted despite at least 3 months of optimal medical therapy and no evidence of cancer recurrence. Participants were stratified by participating hyperbaric centre and randomly assigned (2:1) by a computer-generated list (block size nine or 12) to receive treatment with hyperbaric oxygen therapy or sham. Participants in the active treatment group breathed 100% oxygen at 2·4 atmospheres of absolute pressure (ATA) and the control group breathed 21% oxygen at 1·3 ATA; both treatment groups received 90-min air pressure exposures once daily for 5 days per week for a total of 8 weeks (total of 40 exposures). Staff at the participating hyperbaric medicine facilities knew the allocated treatment, but patients, clinicians, nurse practitioners, and other health-care professionals associated with patients' care were masked to treatment allocation. Primary endpoints were changes in the bowel component of the modified Inflammatory Bowel Disease Questionnaire (IBDQ) score and the IBDQ rectal bleeding score 12 months after start of treatment relative to baseline. The primary outcome was analysed in a modified intention-to-treat population, excluding patients who did not provide IBDQ scores within a predetermined time-frame. All patients have completed 12 months of follow-up and the final analysis is complete. The trial is registered with the ISRCTN registry

  12. Accelerated solvent extraction followed by on-line solid-phase extraction coupled to ion trap LC/MS/MS for analysis of benzalkonium chlorides in sediment samples

    USGS Publications Warehouse

    Ferrer, I.; Furlong, E.T.

    2002-01-01

    Benzalkonium chlorides (BACs) were successfully extracted from sediment samples using a new methodology based on accelerated solvent extraction (ASE) followed by an on-line cleanup step. The BACs were detected by liquid chromatography/ion trap mass spectrometry (LC/MS) or tandem mass spectrometry (MS/MS) using an electrospray interface operated in the positive ion mode. This methodology combines the high efficiency of extraction provided by a pressurized fluid and the high sensitivity offered by the ion trap MS/MS. The effects of solvent type and ASE operational variables, such as temperature and pressure, were evaluated. After optimization, a mixture of acetonitrile/water (6:4 or 7:3) was found to be most efficient for extracting BACs from the sediment samples. Extraction recoveries ranged from 95 to 105% for C12 and C14 homologues, respectively. Total method recoveries from fortified sediment samples, using a cleanup step followed by ASE, were 85% for C12BAC and 79% for C14-BAC. The methodology developed in this work provides detection limits in the subnanogram per gram range. Concentrations of BAC homologues ranged from 22 to 206 ??g/kg in sediment samples from different river sites downstream from wastewater treatment plants. The high affinity of BACs for soil suggests that BACs preferentially concentrate in sediment rather than in water.

  13. Topics in Cosmic Acceleration and Braneworlds

    NASA Astrophysics Data System (ADS)

    West, Eric J.

    Cosmic acceleration has come to be a standard, and perhaps required, ingredient in our current understanding of the universe. In the early universe, under the name of inflation, a phase of accelerated expansion is used to solve many problems with the standard Hot Big Bang cosmology. In the late universe, cosmic acceleration seems to best explain a wide variety of observations. In both cases, we lack a complete theory of what drives cosmic acceleration. In this thesis I discuss some open issues in our understanding of cosmic acceleration, both in the early and late universe.

  14. Accelerator system and method of accelerating particles

    NASA Technical Reports Server (NTRS)

    Wirz, Richard E. (Inventor)

    2010-01-01

    An accelerator system and method that utilize dust as the primary mass flux for generating thrust are provided. The accelerator system can include an accelerator capable of operating in a self-neutralizing mode and having a discharge chamber and at least one ionizer capable of charging dust particles. The system can also include a dust particle feeder that is capable of introducing the dust particles into the accelerator. By applying a pulsed positive and negative charge voltage to the accelerator, the charged dust particles can be accelerated thereby generating thrust and neutralizing the accelerator system.

  15. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study

    PubMed Central

    Brightling, Christopher E; Bleecker, Eugene R; Panettieri, Reynold A; Bafadhel, Mona; She, Dewei; Ward, Christine K; Xu, Xiao; Birrell, Claire; van der Merwe, René

    2016-01-01

    Summary Background Chronic obstructive pulmonary disease (COPD) is associated with eosinophilic airway inflammation in 10–20% of patients. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, depletes blood and sputum eosinophils. We aimed to establish whether benralizumab reduces acute exacerbations of COPD in patients with eosinophilia and COPD. Methods We did this randomised, double-blind, placebo-controlled, phase 2a study between Nov 18, 2010, and July 13, 2013, at 26 sites in the UK, Poland, Germany, Canada, the USA, Denmark, and Spain. Adults aged 40–85 years, with moderate-to-severe COPD, at least one acute exacerbation of COPD, and a sputum eosinophil count of 3·0% or more within the previous year, were randomly assigned (1:1) via computer-generated permuted block randomisation (block size of four), with an interactive voice or web-response system, to receive placebo or 100 mg benralizumab subcutaneously, every 4 weeks (three doses), then every 8 weeks (five doses) over 48 weeks. Study site personnel included in study assessments, participants, and data analysts, were masked to treatment allocation. The primary endpoint was the annualised rate of acute exacerbations of COPD at week 56, defined as the number of acute exacerbations divided by total duration of person-year follow-up. Secondary and exploratory endpoints included COPD-specific Saint George’s Respiratory Questionnaire (SGRQ-C), Chronic Respiratory Questionnaire self-administered standardised format (CRQ-SAS), pre-bronchodilator forced expiratory volume in 1 second (FEV1), and safety. We did a prespecified subgroup analysis by baseline blood eosinophil count. Analyses were by intention to treat and per-protocol. This trial is registered with ClinicalTrials.gov, number NCT01227278. Findings We randomly assigned 101 patients to receive placebo (n=50) or benralizumab (n=51), of whom 88 (87%) patients completed the study. Six patients who completed the study were excluded from

  16. Gymnastics in Phase Space

    SciTech Connect

    Chao, Alexander Wu; /SLAC

    2012-03-01

    As accelerator technology advances, the requirements on accelerator beam quality become increasingly demanding. Facing these new demands, the topic of phase space gymnastics is becoming a new focus of accelerator physics R&D. In a phase space gymnastics, the beam's phase space distribution is manipulated and precision tailored to meet the required beam qualities. On the other hand, all realization of such gymnastics will have to obey accelerator physics principles as well as technological limitations. Recent examples of phase space gymnastics include Emittance exchanges, Phase space exchanges, Emittance partitioning, Seeded FELs and Microbunched beams. The emittance related topics of this list are reviewed in this report. The accelerator physics basis, the optics design principles that provide these phase space manipulations, and the possible applications of these gymnastics, are discussed. This fascinating new field promises to be a powerful tool of the future.

  17. Long-term Cosmetic Outcomes and Toxicities of Proton Beam Therapy Compared With Photon-Based 3-Dimensional Conformal Accelerated Partial-Breast Irradiation: A Phase 1 Trial

    SciTech Connect

    Galland-Girodet, Sigolène; Pashtan, Itai; MacDonald, Shannon M.; Ancukiewicz, Marek; Hirsch, Ariel E.; Kachnic, Lisa A.; Specht, Michelle; Gadd, Michele; Smith, Barbara L.; Powell, Simon N.; Recht, Abram; Taghian, Alphonse G.

    2014-11-01

    Purpose: To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. Methods and Materials: From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. Results: At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). Conclusions: Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity.

  18. Carrier-envelope phase-tagged imaging of the controlled electron acceleration from SiO2 nanospheres in intense few-cycle laser fields

    NASA Astrophysics Data System (ADS)

    Zherebtsov, S.; Süßmann, F.; Peltz, C.; Plenge, J.; Betsch, K. J.; Znakovskaya, I.; Alnaser, A. S.; Johnson, N. G.; Kübel, M.; Horn, A.; Mondes, V.; Graf, C.; Trushin, S. A.; Azzeer, A.; Vrakking, M. J. J.; Paulus, G. G.; Krausz, F.; Rühl, E.; Fennel, T.; Kling, M. F.

    2012-07-01

    Waveform-controlled light fields offer the possibility of manipulating ultrafast electronic processes on sub-cycle timescales. The optical lightwave control of the collective electron motion in nanostructured materials is key to the design of electronic devices operating at up to petahertz frequencies. We have studied the directional control of the electron emission from 95 nm diameter SiO2 nanoparticles in few-cycle laser fields with a well-defined waveform. Projections of the three-dimensional (3D) electron momentum distributions were obtained via single-shot velocity-map imaging (VMI), where phase tagging allowed retrieving the laser waveform for each laser shot. The application of this technique allowed us to efficiently suppress background contributions in the data and to obtain very accurate information on the amplitude and phase of the waveform-dependent electron emission. The experimental data that are obtained for 4 fs pulses centered at 720 nm at different intensities in the range (1-4) × 1013 W cm-2 are compared to quasi-classical mean-field Monte-Carlo simulations. The model calculations identify electron backscattering from the nanoparticle surface in highly dynamical localized fields as the main process responsible for the energetic electron emission from the nanoparticles. The local field sensitivity of the electron emission observed in our studies can serve as a foundation for future research on propagation effects for larger particles and field-induced material changes at higher intensities.

  19. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial

    PubMed Central

    Farooqui, Mohammed Z H; Valdez, Janet; Martyr, Sabrina; Aue, Georg; Saba, Nakhle; Niemann, Carsten U; Herman, Sarah E M; Tian, Xin; Marti, Gerald; Soto, Susan; Hughes, Thomas E; Jones, Jade; Lipsky, Andrew; Pittaluga, Stefania; Stetler-Stevenson, Maryalice; Yuan, Constance; Lee, Yuh Shan; Pedersen, Lone B; Geisler, Christian H; Calvo, Katherine R; Arthur, Diane C; Maric, Irina; Childs, Richard; Young, Neal S; Wiestner, Adrian

    2015-01-01

    Summary Background Patients with chronic lymphocytic leukaemia (CLL) with TP53 aberrations respond poorly to first-line chemoimmunotherapy resulting in early relapse and short survival. We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53 aberrations. Methods In this investigator-initiated, single-arm phase 2 study we enrolled eligible adult patients with active CLL with TP53 aberrations at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Patients received 28-day cycles of ibrutinib 420 mg orally once daily until disease progression or the occurrence of limiting toxicities. The primary endpoint was overall response to treatment at 24 weeks in all evaluable patients. This study is registered with ClinicalTrials.gov number NCT01500733, and is fully enrolled. Findings Between Dec 22, 2011 and Jan 2, 2014 we enrolled 51 patients; 47 had CLL with deletion 17p13.1 and four carried a TP53 mutation in the absence of deletion 17p13.1. All patients had active disease requiring therapy. 35 enrolled patients had previously untreated CLL and 16 had relapsed or refractory disease. Median follow-up was 24 months (IQR 12·9-27·0). 33 previously untreated patients and 15 patients with relapsed or refractory CLL were evaluable for response at 24 weeks. 32 (97%; 95% CI 86-100) of 33 previously untreated patients achieved an objective response, including partial response in 18 patients (55%) and partial response with lymphocytosis in 14 (42%). One patient had progressive disease at 0·4 months. 12 (80%; 95% CI 52-96) of the 15 patients with relapsed or refractory CLL had an objective response: six (40%) achieved a partial response and six (40%) a partial response with lymphocytosis; the remaining three (20%) patients had stable disease. Grade 3 or worse treatment-related adverse events were neutropenia in 12 (24%) patients (grade 4 in one [2%] patient), anaemia in seven (14%) patients, and

  20. Early phase viral kinetics of chronic hepatitis C patients receiving telaprevir-based triple therapy: a comparison of two real-time PCR assays.

    PubMed

    Ogawa, Eiichi; Furusyo, Norihiro; Murata, Masayuki; Toyoda, Kazuhiro; Eiraku, Kunimitsu; Shimizu, Motohiro; Harada, Yuji; Mitsumoto, Fujiko; Takayama, Koji; Okada, Kyoko; Kainuma, Mosaburo; Hayashi, Jun

    2013-08-01

    Monitoring hepatitis C virus (HCV) kinetics during antiviral treatment is recommended for determining the best form of treatment management. We compared the measurement of HCV RNA by two Real-time PCR assays during the first 12weeks phase of telaprevir in combination with pegylated interferon α2b and ribavirin treatment for chronic hepatitis C patients. The viral kinetics of 65 patients with HCV genotype 1b was assessed. HCV RNA was tested at baseline, on day 3, and every week from 1 to 12 by both the first-generation Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV (CAP/CTM) assay and the Abbott RealTime HCV (ART) assay. A total of 910 serum samples were obtained from the 65 patients. Of these, 168 (28.5%) of the 590 samples HCV RNA negative by CAP/CTM were positive by ART. In contrast, 17 (3.9%) of the 439 samples HCV RNA negative by ART were positive by CAP/CTM. The rates of HCV RNA negativity by ART at weeks 3, 4, and 5 were significantly lower than those by CAP/CTM (21.5% vs. 50.8%, 36.9% vs. 70.8% and 44.6% vs. 81.5%; P<0.001, P<0.0001 and P<0.05, respectively). Although the ART is superior for the determination of HCV RNA negativity, the predictive value of detectable HCV RNA for non-sustained virological response (non-SVR) by CAP/CTM is higher than by ART at weeks 4, 6, and 8. We also found that 16 (24.6%) by CAP/CTM and 28 (43.1%) by ART had a reappearance of residual HCV RNA during the telaprevir treatment period. However, the reappearance of residual HCV RNA was not associated with non-SVR. In conclusion, a significant difference was found between the two real-time PCR assays for the assessment of virological response based on undetectable HCV RNA.

  1. Particle Acceleration in Solar Flares

    NASA Astrophysics Data System (ADS)

    Petrosian, V.

    Several new observations notably high spatial and spectral X-ray observations of impulsive phase of solar flares by YOHKOH and RHESSI, and Solar Energetic Particle (SEP) spectra by ACE have provided strong evidence in favor of stochastic acceleration of electrons, protons and other ions by plasma waves or turbulence. Theoretical arguments also favor such a model if the seed particles come from the background thermal plasma. I will describe these evidences and the theoretical framework for evaluation of the accelerated particle spectra, their transport and radiation. The predictions of the models will be compared with several features of the observations with specific emphasize on heating vs acceleration by turbulence, thermal vs nonthermal electron spectra, looptop vs footpoint emission fro flaring loops, electron vs proton acceleration rates and 3He vs 4He (and other ion) abundances in SEPs.

  2. Computer assisted accelerator tuning

    SciTech Connect

    Boyd, J.K.

    1993-04-14

    The challenge of tuning an induction accelerator in real time has been addressed with the new TUNE GUIDE code. The code initializes a beam at a particular position using a tracer particle representation of the phase space. The particles are transported, using a matrix formulation, element by element along the beamline assuming that the field of a solenoid, or steering element is constant over its length. The other allowed elements are gaps and drift sections. A great deal of effort has been spent programming TUNE GUIDE to operate under the IBMPC Windows 3.1 system. This system features an intuitive, menu driven interface, which provides an ability to rapidly change beamline component parameter values. Consequently various accelerator setups can be explored and new values determined in real time while the accelerator is operating. In addition the code has the capability of varying a capability value over a range and then plotting the resulting beam properties, such as radius or centroid position, at a down stream position. Element parameter editing is also included along with an on-line hyper text oriented help package.

  3. Phase 2 Study of Accelerated Hypofractionated Thoracic Radiation Therapy and Concurrent Chemotherapy in Patients With Limited-Stage Small-Cell Lung Cancer

    SciTech Connect

    Xia, Bing; Hong, Ling-Zhi; Cai, Xu-Wei; Zhu, Zheng-Fei; Liu, Qi; Zhao, Kuai-Le; Fan, Min; Mao, Jing-Fang; Yang, Huan-Jun; Wu, Kai-Liang; Fu, Xiao-Long

    2015-03-01

    Purpose: To prospectively investigate the efficacy and toxicity of accelerated hypofractionated thoracic radiation therapy (HypoTRT) combined with concurrent chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC), with the hypothesis that both high radiation dose and short radiation time are important in this setting. Methods and Materials: Patients with previously untreated LS-SCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. HypoTRT of 55 Gy at 2.5 Gy per fraction over 30 days was given on the first day of the second or third cycle of chemotherapy. An etoposide/cisplatin regimen was given to 4 to 6 cycles. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 2-year progression-free survival rate. Results: Fifty-nine patients were enrolled from July 2007 through February 2012 (median age, 58 years; 86% male). The 2-year progression-free survival rate was 49.0% (95% confidence interval [CI] 35.3%-62.7%). Median survival time was 28.5 months (95% CI 9.0-48.0 months); the 2-year overall survival rate was 58.2% (95% CI 44.5%-71.9%). The 2-year local control rate was 76.4% (95% CI 63.7%-89.1%). The severe hematologic toxicities (grade 3 or 4) were leukopenia (32%), neutropenia (25%), and thrombocytopenia (15%). Acute esophagitis and pneumonitis of grade ≥3 occurred in 25% and 10% of the patients, respectively. Thirty-eight patients (64%) received prophylactic cranial irradiation. Conclusion: Our study showed that HypoTRT of 55 Gy at 2.5 Gy per fraction daily concurrently with etoposide/cisplatin chemotherapy has favorable survival and acceptable toxicity. This radiation schedule deserves further investigation in LS-SCLC.

  4. Accelerated formation of 110 K high T sub c phase in the Ca- and Cu-rich Bi-Pb-Sr-Ca-Cu-O system

    SciTech Connect

    Huang, Y.T.; Liu, R.G.; Lu, S.W.; Wu, P.T. ); Wang, W.N. )

    1990-02-19

    The crystal structure and superconducting properties of the Bi-Pb-Sr-Ca-Cu-O system with Ca- and Cu-rich nominal composition were investigated. A nearly single-phased 110 K high {ital T}{sub {ital c}} superconductor can be obtained with 852 {degree}C/20 h sintering from the starting composition of Bi{sub 1.7}Pb{sub 0.4}Sr{sub 1.6}Ca{sub 2.4}Cu{sub 3.6}O{sub {ital y}}. X-ray diffraction patterns, resistivity measurement, diamagnetic susceptibility results, and scanning electron micrographs all indicate that the Ca- and Cu-rich nominal composition would result in better superconducting properties than those of Ca:Sr=1:1 Bi-Pb-Sr-Ca-Cu-O compounds in a much shorter sintering time.

  5. Algorithmic-Reducibility = Renormalization-Group Fixed-Points; ``Noise''-Induced Phase-Transitions (NITs) to Accelerate Algorithmics (``NIT-Picking'') Replacing CRUTCHES!!!: Gauss Modular/Clock-Arithmetic Congruences = Signal X Noise PRODUCTS..

    NASA Astrophysics Data System (ADS)

    Siegel, J.; Siegel, Edward Carl-Ludwig

    2011-03-01

    Cook-Levin computational-"complexity"(C-C) algorithmic-equivalence reduction-theorem reducibility equivalence to renormalization-(semi)-group phase-transitions critical-phenomena statistical-physics universality-classes fixed-points, is exploited with Gauss modular/clock-arithmetic/model congruences = signal X noise PRODUCT reinterpretation. Siegel-Baez FUZZYICS=CATEGORYICS(SON of ``TRIZ''): Category-Semantics(C-S) tabular list-format truth-table matrix analytics predicts and implements "noise"-induced phase-transitions (NITs) to accelerate versus to decelerate Harel [Algorithmics(1987)]-Sipser[Intro. Theory Computation(1997) algorithmic C-C: "NIT-picking" to optimize optimization-problems optimally(OOPO). Versus iso-"noise" power-spectrum quantitative-only amplitude/magnitude-only variation stochastic-resonance, this "NIT-picking" is "noise" power-spectrum QUALitative-type variation via quantitative critical-exponents variation. Computer-"science" algorithmic C-C models: Turing-machine, finite-state-models/automata, are identified as early-days once-workable but NOW ONLY LIMITING CRUTCHES IMPEDING latter-days new-insights!!!

  6. Multi-beam linear accelerator EVT

    NASA Astrophysics Data System (ADS)

    Teryaev, Vladimir E.; Kazakov, Sergey Yu.; Hirshfield, Jay L.

    2016-09-01

    A novel electron multi-beam accelerator is presented. The accelerator, short-named EVT (Electron Voltage Transformer) belongs to the class of two-beam accelerators. It combines an RF generator and essentially an accelerator within the same vacuum envelope. Drive beam-lets and an accelerated beam are modulated in RF modulators and then bunches pass into an accelerating structure, comprising uncoupled with each other and inductive tuned cavities, where the energy transfer from the drive beams to the accelerated beam occurs. A phasing of bunches is solved by choice correspond distances between gaps of the adjacent cavities. Preliminary results of numerical simulations and the initial specification of EVT operating in S-band, with a 60 kV gun and generating a 2.7 A, 1.1 MV beam at its output is presented. A relatively high efficiency of 67% and high design average power suggest that EVT can find its use in industrial applications.

  7. An Epigenetic Clock Measures Accelerated Aging in Treated HIV Infection.

    PubMed

    Boulias, Konstantinos; Lieberman, Judy; Greer, Eric Lieberman

    2016-04-21

    In this issue of Molecular Cell, Gross et al. (2016) find a CpG DNA methylation signature in blood cells of patients with chronic well-controlled HIV infection that correlates with accelerated aging. PMID:27105110

  8. Randomized Phase III Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Stage III to IV Head and Neck Carcinoma: RTOG 0522

    PubMed Central

    Ang, K. Kian; Zhang, Qiang; Rosenthal, David I.; Nguyen-Tan, Phuc Felix; Sherman, Eric J.; Weber, Randal S.; Galvin, James M.; Bonner, James A.; Harris, Jonathan; El-Naggar, Adel K.; Gillison, Maura L.; Jordan, Richard C.; Konski, Andre A.; Thorstad, Wade L.; Trotti, Andy; Beitler, Jonathan J.; Garden, Adam S.; Spanos, William J.; Yom, Sue S.; Axelrod, Rita S.

    2014-01-01

    Purpose Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS). Patients and Methods Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers. Results Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v 2.0%, respectively; P = .81), 3-year PFS (61.2% v 58.9%, respectively; P = .76), 3-year OS (72.9% v 75.8%, respectively; P = .32), locoregional failure (19.9% v 25.9%, respectively; P = .97), or distant metastasis (13.0% v 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v 49.2%, respectively; P < .001) and OS (85.6% v 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome. Conclusion Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS

  9. Accelerated glass reaction under PCT conditions

    SciTech Connect

    Ebert, W.L.; Bates, J.K.; Buck, E.C.; Bradley, C.R.

    1992-01-01

    Static leach tests similar to PCT (Product Consistency Test) were performed for up to 2 years to assess long-term reaction behavior of high-level nuclear waste glasses similar to those at Defense Waste Processing Facility. These tests show the reaction rate to decrease with the reaction time from an initially high rate to a low rate, but then to accelerate to a higher rate after reaction times of about 1 year, depending on glass surface area/leachant volume ratio used. Solution concentrations of soluble glass components increase as the reaction is accelerated, while release of other glass components into solution is controlled by secondary phases. Net result is that transformation of glass to stable phases is accelerated while the solution becomes enriched in soluble components not effectively contained in secondary phases. Rate becomes linear in time after the acceleration and may be similar to the initial forward rate. A current model of glass reaction predicts that the glass reaction will be accelerated upon the formation of secondary phases which lower the silicic acid solution concentration. These tests show total Si concentration to increase upon reaction acceleration, however, which may be due to the slightly higher pH attained with the acceleration. The sudden change in the reaction rate is likely due to secondary phase formation. 17 refs, 2 tabs, 3 figs.

  10. Accelerated glass reaction under PCT conditions

    SciTech Connect

    Ebert, W.L.; Bates, J.K.; Buck, E.C.; Bradley, C.R.

    1992-12-31

    Static leach tests similar to PCT (Product Consistency Test) were performed for up to 2 years to assess long-term reaction behavior of high-level nuclear waste glasses similar to those at Defense Waste Processing Facility. These tests show the reaction rate to decrease with the reaction time from an initially high rate to a low rate, but then to accelerate to a higher rate after reaction times of about 1 year, depending on glass surface area/leachant volume ratio used. Solution concentrations of soluble glass components increase as the reaction is accelerated, while release of other glass components into solution is controlled by secondary phases. Net result is that transformation of glass to stable phases is accelerated while the solution becomes enriched in soluble components not effectively contained in secondary phases. Rate becomes linear in time after the acceleration and may be similar to the initial forward rate. A current model of glass reaction predicts that the glass reaction will be accelerated upon the formation of secondary phases which lower the silicic acid solution concentration. These tests show total Si concentration to increase upon reaction acceleration, however, which may be due to the slightly higher pH attained with the acceleration. The sudden change in the reaction rate is likely due to secondary phase formation. 17 refs, 2 tabs, 3 figs.

  11. Analyses of critical target cell responses during preclinical phases of evolving chronic radiation-induced myeloproliferative disease-exploitation of a unique canine model

    SciTech Connect

    Seed, T.M.; Kaspar, L.V.; Tolle, D.V.; Fritz, T.E.; Frazier, M.E.

    1988-01-01

    This document briefly summarizes and highlights ongoing studies on the cellular and molecular processes involved in the induction and progression of myeloid leukemia in dogs chronically exposed to low daily doses of wholebody gamma irradiation. Under such conditions, select groups of dogs exhibit extremely high frequencies of myeloproliferative disease (MPD) (i.e., /congruent/50%) of which myeloid leukemia is most prominent. 2 figs.

  12. Laser Acceleration in Vacuum and Gases with Capillary Waveguide

    SciTech Connect

    Xie, Ming

    1999-02-01

    A unified framework is developed to overcome all three major limitations on acceleration and distance and hence on the feasibility of two classes of laser acceleration. The three limitations are due to laser diffraction, acceleration phase slippage, and structure damage by high power laser if solid-state optical waveguide is used. The two classes of laser acceleration are direct-field acceleration and ponderomotive-driven acceleration. Thus this letter and its companion [1] provide solutions that are crucial to all mainstream approaches for laser acceleration, either in vacuum, gases or plasmas.

  13. Thermodynamics of Accelerating Black Holes

    NASA Astrophysics Data System (ADS)

    Appels, Michael; Gregory, Ruth; KubizÅák, David

    2016-09-01

    We address a long-standing problem of describing the thermodynamics of an accelerating black hole. We derive a standard first law of black hole thermodynamics, with the usual identification of entropy proportional to the area of the event horizon—even though the event horizon contains a conical singularity. This result not only extends the applicability of black hole thermodynamics to realms previously not anticipated, it also opens a possibility for studying novel properties of an important class of exact radiative solutions of Einstein equations describing accelerated objects. We discuss the thermodynamic volume, stability, and phase structure of these black holes.

  14. Elementary principles of linear accelerators

    NASA Astrophysics Data System (ADS)

    Loew, G. A.; Talman, R.

    1983-09-01

    A short chronology of important milestones in the field of linear accelerators is presented. Proton linacs are first discussed and elementary concepts such as transit time, shunt impedance, and Q are introduced. Critical issues such as phase stability and transverse forces are addressed. An elementary discussion of waveguide acclerating structures is also provided. Finally, electron accelerators addressed. Taking SLAC as an exmple, various topics are discussed such as structure design, choice of parameters, frequency optmization, beam current, emittance, bunch length and beam loading. Recent developments and future challenges are mentioned briefly.

  15. Microcomputer-based Acceleration Sensor Device for Swimming Stroke Monitoring

    NASA Astrophysics Data System (ADS)

    Ohgi, Yuji; Ichikawa, Hiroshi; Miyaji, Chikara

    The purpose of this study was to develop a microcomputer-based acceleration logger device for the swimming stroke monitoring. The authors measured the swimmer's tri-axial wrist acceleration and applied this device for the fatigue evaluation of the swimmers. The experimental protocol led the swimmers exhausted after the crawl stroke interval training. Every single stroke was determined by the impact acceleration peak, which appeared on the x and z-axis acceleration. The change of the underwater stroke phases was identified by the characteristics of the acceleration peaks. In their exhaustion, the y-axis acceleration, which was longitudinal forearm acceleration decreased at the beginning of the upsweep phase. At that time, the swimmer could not extend his elbow joint. Since the developed acceleration data logger could provide us the information about the underwater stroke phases and it would be a helpful tool in the swimming training.

  16. Acceleration schedules for a recirculating heavy-ion accelerator

    SciTech Connect

    Sharp, W.M.; Grote, D.P.

    2002-05-01

    Recent advances in solid-state switches have made it feasible to design programmable, high-repetition-rate pulsers for induction accelerators. These switches could lower the cost of recirculating induction accelerators, such as the ''small recirculator'' at Lawrence Livermore National Laboratory (LLNL), by substantially reducing the number of induction modules. Numerical work is reported here to determine what effects the use of fewer pulsers at higher voltage would have on the beam quality of the LLNL small recirculator. Lattices with different numbers of pulsers are examined using the fluid/envelope code CIRCE, and several schedules for acceleration and compression are compared for each configuration. For selected schedules, the phase-space dynamics is also studied using the particle-in-cell code WARP3d.

  17. EDITORIAL: Laser and plasma accelerators Laser and plasma accelerators

    NASA Astrophysics Data System (ADS)

    Bingham, Robert

    2009-02-01

    as photon deceleration and acceleration and is the result of a modulational instability. Simulations reported by Trines et al using a photon-in-cell code or wave kinetic code agree extremely well with experimental observation. Ion acceleration is actively studied; for example the papers by Robinson, Macchi, Marita and Tripathi all discuss different types of acceleration mechanisms from direct laser acceleration, Coulombic explosion and double layers. Ion acceleration is an exciting development that may have great promise in oncology. The surprising application is in muon acceleration, demonstrated by Peano et al who show that counterpropagating laser beams with variable frequencies drive a beat structure with variable phase velocity, leading to particle trapping and acceleration with possible application to a future muon collider and neutrino factory. Laser and plasma accelerators remain one of the exciting areas of plasma physics with applications in many areas of science ranging from laser fusion, novel high-brightness radiation sources, particle physics and medicine. The guest editor would like to thank all authors and referees for their invaluable contributions to this special issue.

  18. Management of chronic immune thrombocytopenic purpura: targeting insufficient megakaryopoiesis as a novel therapeutic principle

    PubMed Central

    Rank, Andreas; Weigert, Oliver; Ostermann, Helmut

    2010-01-01

    Traditionally, anti-platelet autoantibodies accelerating platelet clearance from the peripheral circulation have been recognized as the primary pathopysiological mechanism in chronic immune thrombocytopenia (ITP). Recently, increasing evidence supports the co-existence of insufficient megakaryopoiesis. Inadequate low thrombopoietin (TPO) levels are associated with insufficient proliferation and differentiation of megakaryocytes, decreased proplatelet formation, and subsequent platelet release. Recently two novel activators of TPO receptors have been made available: romiplostim and eltrombopag. In several phase III studies, both agents demonstrated increase of platelet counts in about 80% of chronic ITP patients within 2 to 3 weeks. These agents substantially broaden the therapeutic options for patients with chronic ITP although long-term results are still pending. This review will provide an update on the current conception of underlying mechanisms in ITP and novel, pathophysiologically based treatment options. PMID:20531970

  19. Alterations of the renal function and oxidative stress in renal tissue from rats chronically treated with aluminium during the initial phase of hepatic regeneration.

    PubMed

    Mahieu, Stella; Millen, Néstor; González, Marcela; Contini, María del Carmen; Elías, María Mónica

    2005-09-01

    Various indices of renal functions during the early stage of hepatic injury were studied in rats chronically treated with aluminum (Al) lactate. Tubular and hemodynamic parameters were analyzed four days after producing a 65% partial hepatectomy (PH). Water and sodium balances were also studied. Oxidative stress and the activity of Na-K-ATPase were determined in renal tissue. The rats were distributed in four groups: control, Al, PH, Al+PH. Al did not modify the hemodynamic renal functions and the PH-group reduced the glomerular filtrate rate (GFR). The Al + PH group presented a decrease in the renal blood flow and accentuated the GFR fall as compared with PH. The fractional excretion (FE) of water and sodium increased in the PH group. The rats chronically treated with Al and then submitted to the PH protocol developed a further increase in FE of water but a reduction in FE of sodium. Both PH and Al promoted an increase in the aldosterone. PH and Al induced a similar increase of the lipoperoxidation status with reduction of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). The data indicated that Al is an inhibitor of catalase. The GSH and GSH-Px activity in the Al + PH group demonstrated a synergic effect of Al and PH. This work demonstrates that rats treated chronically with Al and submitted to another injury (such as hepatic damage) can aggravate renal functions, probably by increasing the oxidative state, at least in kidneys. PMID:16129492

  20. Alterations of the renal function and oxidative stress in renal tissue from rats chronically treated with aluminium during the initial phase of hepatic regeneration.

    PubMed

    Mahieu, Stella; Millen, Néstor; González, Marcela; Contini, María del Carmen; Elías, María Mónica

    2005-09-01

    Various indices of renal functions during the early stage of hepatic injury were studied in rats chronically treated with aluminum (Al) lactate. Tubular and hemodynamic parameters were analyzed four days after producing a 65% partial hepatectomy (PH). Water and sodium balances were also studied. Oxidative stress and the activity of Na-K-ATPase were determined in renal tissue. The rats were distributed in four groups: control, Al, PH, Al+PH. Al did not modify the hemodynamic renal functions and the PH-group reduced the glomerular filtrate rate (GFR). The Al + PH group presented a decrease in the renal blood flow and accentuated the GFR fall as compared with PH. The fractional excretion (FE) of water and sodium increased in the PH group. The rats chronically treated with Al and then submitted to the PH protocol developed a further increase in FE of water but a reduction in FE of sodium. Both PH and Al promoted an increase in the aldosterone. PH and Al induced a similar increase of the lipoperoxidation status with reduction of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). The data indicated that Al is an inhibitor of catalase. The GSH and GSH-Px activity in the Al + PH group demonstrated a synergic effect of Al and PH. This work demonstrates that rats treated chronically with Al and submitted to another injury (such as hepatic damage) can aggravate renal functions, probably by increasing the oxidative state, at least in kidneys.

  1. Laser driven ion accelerator

    DOEpatents

    Tajima, Toshiki

    2006-04-18

    A system and method of accelerating ions in an accelerator to optimize the energy produced by a light source. Several parameters may be controlled in constructing a target used in the accelerator system to adjust performance of the accelerator system. These parameters include the material, thickness, geometry and surface of the target.

  2. Accelerating Spectrum Sharing Technologies

    SciTech Connect

    Juan D. Deaton; Lynda L. Brighton; Rangam Subramanian; Hussein Moradi; Jose Loera

    2013-09-01

    Spectrum sharing potentially holds the promise of solving the emerging spectrum crisis. However, technology innovators face the conundrum of developing spectrum sharing technologies without the ability to experiment and test with real incumbent systems. Interference with operational incumbents can prevent critical services, and the cost of deploying and operating an incumbent system can be prohibitive. Thus, the lack of incumbent systems and frequency authorization for technology incubation and demonstration has stymied spectrum sharing research. To this end, industry, academia, and regulators all require a test facility for validating hypotheses and demonstrating functionality without affecting operational incumbent systems. This article proposes a four-phase program supported by our spectrum accountability architecture. We propose that our comprehensive experimentation and testing approach for technology incubation and demonstration will accelerate the development of spectrum sharing technologies.

  3. Visions for the future of particle accelerators

    NASA Astrophysics Data System (ADS)

    Romaniuk, Ryszard S.

    2013-10-01

    The ambitions of accelerator based science, technology and applications far exceed the present accelerator possibilities. Accelerator science and technology is one of a key enablers of the developments in the particle physic, photon physics and also applications in medicine and industry. The paper presents a digest of the research results and visions for the future in the domain of accelerator science and technology in Europe, shown during the final fourth annual meeting of the EuCARD - European Coordination of Accelerator Research and Development. The conference concerns building of the research infrastructure, including advanced photonic and electronic systems for servicing large high energy physics experiments. There are debated a few basic groups of such systems like: measurement - control networks of large geometrical extent, multichannel systems for large amounts of metrological data acquisition, precision photonic networks of reference time, frequency and phase distribution. The main subject is however the vision for the future of particle accelerators and next generation light sources.

  4. Chronic migraine.

    PubMed

    Schwedt, Todd J

    2014-03-24

    Chronic migraine is a disabling neurologic condition that affects 2% of the general population. Patients with chronic migraine have headaches on at least 15 days a month, with at least eight days a month on which their headaches and associated symptoms meet diagnostic criteria for migraine. Chronic migraine places an enormous burden on patients owing to frequent headaches; hypersensitivity to visual, auditory, and olfactory stimuli; nausea; and vomiting. It also affects society through direct and indirect medical costs. Chronic migraine typically develops after a slow increase in headache frequency over months to years. Several factors are associated with an increased risk of transforming to chronic migraine. The diagnosis requires a carefully performed patient interview and neurologic examination, sometimes combined with additional diagnostic tests, to differentiate chronic migraine from secondary headache disorders and other primary chronic headaches of long duration. Treatment takes a multifaceted approach that may include risk factor modification, avoidance of migraine triggers, drug and non-drug based prophylaxis, and abortive migraine treatment, the frequency of which is limited to avoid drug overuse. This article provides an overview of current knowledge regarding chronic migraine, including epidemiology, risk factors for its development, pathophysiology, diagnosis, management, and guidelines. The future of chronic migraine treatment and research is also discussed.

  5. Pros and Cons of the Acceleration Scheme (NF-IDS)

    SciTech Connect

    Bogacz, Alex; Bogacz, Slawomir

    2008-07-01

    The overall goal of the acceleration systems: large acceptance acceleration to 25 GeV and beam shaping can be accomplished by various fixed field accelerators at different stages. They involve three superconducting linacs: a single pass linear Pre-accelerator followed by a pair of multi-pass Recirculating Linear Accelerators (RLA) and finally a nonâ scaling FFAG ring. The present baseline acceleration scenario has been optimized to take maximum advantage of appropriate acceleration scheme at a given stage. Pros and cons of various stages are discussed here in detail. The solenoid based Pre-accelerator offers very large acceptance and facilitates correction of energy gain across the bunch and significant longitudinal compression trough induced synchrotron motion. However, far off-crest acceleration reduces the effective acceleration gradient and adds complexity through the requirement of individual RF phase control for each cavity. Close proximity of strong solenoids and superc

  6. Method and apparatus for varying accelerator beam output energy

    DOEpatents

    Young, Lloyd M.

    1998-01-01

    A coupled cavity accelerator (CCA) accelerates a charged particle beam with rf energy from a rf source. An input accelerating cavity receives the charged particle beam and an output accelerating cavity outputs the charged particle beam at an increased energy. Intermediate accelerating cavities connect the input and the output accelerating cavities to accelerate the charged particle beam. A plurality of tunable coupling cavities are arranged so that each one of the tunable coupling cavities respectively connect an adjacent pair of the input, output, and intermediate accelerating cavities to transfer the rf energy along the accelerating cavities. An output tunable coupling cavity can be detuned to variably change the phase of the rf energy reflected from the output coupling cavity so that regions of the accelerator can be selectively turned off when one of the intermediate tunable coupling cavities is also detuned.

  7. Chronic kidney disease

    MedlinePlus

    Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure ... Chronic kidney disease (CKD) slowly gets worse over months or years. You may not notice any symptoms for some ...

  8. Beam dynamics for induction accelerators

    NASA Astrophysics Data System (ADS)

    Lee, Edward P.

    2014-01-01

    An induction linac uses pulsed power that is applied directly, without any intervening resonant cavities, to accelerate a charged particle pulse. This approach can accommodate a large multiple-beam focusing lattice capable of transporting a large total beam current with a long pulse duration, which may be compressed while accelerating as well as afterward. The mean accelerating gradient is relatively low (less than about 1.5 MV/m), but the potential efficiency of energy transfer can be large up to about 50%. A multiple-beam induction linac is therefore a natural candidate accelerator for a heavy ion fusion (HIF) driver. However, the accelerated beams must meet stringent requirements on occupied phase space volume in order to be focused accurately and with small radius onto the fusion target. Dynamical considerations in the beam injector and linac, as well as in the final compression, final focus, and the fusion chamber, determine the quality of the driver beams as they approach the target. Requirements and tolerances derived from beam dynamics strongly influence the linac configuration and component design.

  9. HI-CHART: A Phase I/II Study on the Feasibility of High-Dose Continuous Hyperfractionated Accelerated Radiotherapy in Patients With Inoperable Non-Small-Cell Lung Cancer

    SciTech Connect

    Ruysscher, Dirk de Wanders, Rinus; Haren, Erik van; Hochstenbag, Monique; Geraedts, Wiel; Pitz, Cordula; Simons, Jean; Boersma, Liesbeth; Verschueren, Tom; Minken, Andre; Bentzen, Soren M.; Lambin, Philippe

    2008-05-01

    Purpose: To determine the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). Patients and Methods: In a prospective, Phase I/II study, according to the risk for radiation pneumonitis, three risk groups were defined: V{sub 20} <25%, V{sub 20} 25-37%, and V{sub 20} >37%. The dose was administered in three steps from 61.2 Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38 fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional conformal technique. Only the mediastinal lymph node areas that were positive on the pretreatment {sup 18}F-deoxy-D-glucose positron emission tomography scan were included in the target volume. The primary endpoint was toxicity. Results: A total of 48 Stage I-IIIB patients were included. In all risk groups, 68.40 Gy/38 fractions/25 days could be administered. Maximal toxicity according to the risk groups was as follows: V{sub 20} <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3 reversible esophageal toxicity; V{sub 20} 35-37% (n = 12): 1 G5 lung and 1 G3 reversible esophageal toxicity. For the whole group, local tumor recurrence occurred in 25% (95% confidence interval 14%-40%) of the patients, with 1 of 48 (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal recurrence. The median actuarial overall survival was 20 months, with a 2-year survival rate of 36%. Conclusions: High-dose continuous hyperfractionated accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a biologic equivalent of approximately 80 Gy when delivered in conventional fractionation) in patients with inoperable NSCLC and a V{sub 20} up to 37% is feasible.

  10. Circulating endothelial cells are increased in chronic myeloid leukemia blast crisis.

    PubMed

    Godoy, C R T; Levy, D; Giampaoli, V; Chamone, D A F; Bydlowski, S P; Pereira, J

    2015-06-01

    We measured circulating endothelial precursor cells (EPCs), activated circulating endothelial cells (aCECs), and mature circulating endothelial cells (mCECs) using four-color multiparametric flow cytometry in the peripheral blood of 84 chronic myeloid leukemia (CML) patients and 65 healthy controls; and vascular endothelial growth factor (VEGF) by quantitative real-time PCR in 50 CML patients and 32 healthy controls. Because of an increase in mCECs, the median percentage of CECs in CML blast crisis (0.0146%) was significantly higher than in healthy subjects (0.0059%, P<0.01) and in the accelerated phase (0.0059%, P=0.01). There were no significant differences in the percentages of CECs in chronic- or active-phase patients and healthy subjects (P>0.05). In addition, VEGF gene expression was significantly higher in all phases of CML: 0.245 in blast crisis, 0.320 in the active phase, and 0.330 in chronic phase patients than it was in healthy subjects (0.145). In conclusion, CML in blast crisis had increased levels of CECs and VEGF gene expression, which may serve as markers of disease progression and may become targets for the management of CML.

  11. [Chronicity, chronicization, systematization of delusions].

    PubMed

    Trapet, P; Fernandez, C; Galtier, M C; Gisselmann, A

    1984-05-01

    Chronicity in psychopathology is indicative of a term, a decay. Chronicization only leads the way to this term. Here, chronicization is taken literally as an inscription in the time course of delusions. The mechanism of systematization seems to be a central mark in the approach to chronic delusions. It is not an alienation or an irreversible closing but an attempted accommodation with reality in the life of psychotic subjects, irrespective of the delusional structure. The role of therapy and drug treatment as a follow-up may in that case assume another meaning.

  12. Diagnosing and managing advanced chronic myeloid leukemia.

    PubMed

    Deininger, Michael W

    2015-01-01

    Clinical staging of chronic myeloid leukemia (CML) distinguishes between chronic phase (CP-CML), accelerated phase (AP-CML), and blastic phase (BP-CML), reflecting its natural history in the absence of effective therapy. Morphologically, transformation from CP-CML to AP/BP-CML is characterized by a progressive or sudden loss of differentiation. Multiple different somatic mutations have been implicated in transformation from CP-CML to AP/BC-CML, but no characteristic mutation or combination of mutations have emerged. Gene expression profiles of AP-CML and BP-CML are similar, consistent with biphasic evolution at the molecular level. Gene expression of tyrosine kinase inhibitor (TKI)-resistant CP-CML and second CP-CML resemble AP/BP-CML, suggesting that morphology alone is a poor predictor of biologic behavior. At the clinical level, progression to AP/BP-CML or resistance to first-line TKI therapy distinguishes a good risk condition with survival close to the general population from a disease likely to reduce survival. Progression while receiving TKI therapy is frequently caused by mutations in the target kinase BCR-ABL1, but progression may occur in the absence of explanatory BCR-ABL1 mutations, suggesting involvement of alternative pathways. Identifying patients in whom milestones of TKI response fail to occur or whose disease progress while receiving therapy requires appropriate molecular monitoring. Selection of salvage TKI depends on prior TKI history, comorbidities, and BCR-ABL1 mutation status. Despite the introduction of novel TKIs, therapy of AP/BP-CML remains challenging and requires accepting modalities with substantial toxicity, such as hematopoietic stem cell transplantation (HSCT). PMID:25993200

  13. Chronic pancreatitis.

    PubMed

    Chari, S T; DiMagno, E P

    2001-09-01

    An increasing number of novel mutations are associated with chronic pancreatitis. Some cause a high-penetrance, autosomal dominant type of clinical picture (eg, mutations at codons 29 and 122 of the cationic trypsinogen gene), whereas others have a low penetrance or are frequent in the general population (eg, mutations in Kazal type 1 [SPINK1] and in codons 16, 22, and 23 of the cationic trypsinogen gene) and act as disease modifiers. The results of recent studies indicate that smoking adversely affects the course and complications of chronic pancreatitis (more frequent and faster rate of calcification and higher risk of development of pancreatic cancer). Thus, regardless of the cause of chronic pancreatis, patients with this condition should not smoke. Using current diagnostic criteria, the accuracy of endoscopic ultrasound for the diagnosis of chronic pancreatitis is not good. For example, 39% of dyspeptic persons without any other evidence of chronic pancreatitis fulfilled the endoscopic ultrasound criteria for chronic pancreatitis. Diabetes frequently occurs in chronic pancreatitis, but it is not prevented or increased by pancreatic surgery. Islet cell autotransplantation holds promise for the prevention of diabetes in patients requiring total pancreatectomy if the pancreas is not extensively fibrotic. Splenic vein occlusion is present in 7% of patients undergoing surgery for chronic pancreatitis, but fewer than one fifth of these patients have variceal bleeding before or after surgery.

  14. Chronic pancreatitis.

    PubMed

    Majumder, Shounak; Chari, Suresh T

    2016-05-01

    Chronic pancreatitis describes a wide spectrum of fibro-inflammatory disorders of the exocrine pancreas that includes calcifying, obstructive, and steroid-responsive forms. Use of the term chronic pancreatitis without qualification generally refers to calcifying chronic pancreatitis. Epidemiology is poorly defined, but incidence worldwide seems to be on the rise. Smoking, drinking alcohol, and genetic predisposition are the major risk factors for chronic calcifying pancreatitis. In this Seminar, we discuss the clinical features, diagnosis, and management of chronic calcifying pancreatitis, focusing on pain management, the role of endoscopic and surgical intervention, and the use of pancreatic enzyme-replacement therapy. Management of patients is often challenging and necessitates a multidisciplinary approach. PMID:26948434

  15. From Ideas to Efficacy: The ORBIT Model for Developing Behavioral Treatments for Chronic Diseases

    PubMed Central

    Czajkowski, Susan M.; Powell, Lynda H.; Adler, Nancy; Naar-King, Sylvie; Reynolds, Kim D.; Hunter, Christine M.; Laraia, Barbara; Olster, Deborah H.; Perna, Frank M.; Peterson, Janey C.; Epel, Elissa; Boyington, Josephine E.; Charlson, Mary E.

    2015-01-01

    Objective Given the critical role of behavior in preventing and treating chronic diseases, it is important to accelerate the development of behavioral treatments that can improve chronic disease prevention and outcomes. Findings from basic behavioral and social science research hold great promise for addressing behaviorally-based clinical health problems, yet there is currently no established pathway for translating fundamental behavioral science discoveries into health-related treatments ready for Phase III efficacy testing. This article provides a systematic framework for guiding efforts to translate basic behavioral science findings into behavioral treatments for preventing and treating chronic illness. Methods The ORBIT model for behavioral treatment development is described as involving a flexible and progressive process, pre-specified clinically significant milestones for forward movement, and return to earlier stages for refinement and optimization. Results This article presents the background and rationale for the ORBIT model, a summary of key questions for each phase, a selection of study designs and methodologies well-suited to answering these questions, and pre-specified milestones for forward or backward movement across phases. Conclusions The ORBIT model provides a progressive, clinically-relevant approach to increasing the number of evidence-based behavioral treatments available to prevent and treat chronic diseases. PMID:25642841

  16. Advanced Beamline Design for Fermilab's Advanced Superconducting Test Accelerator

    SciTech Connect

    Prokop, Christopher

    2014-01-01

    The Advanced Superconducting Test Accelerator (ASTA) at Fermilab is a new electron accelerator currently in the commissioning stage. In addition to testing superconducting accelerating cavities for future accelerators, it is foreseen to support a variety of Advanced Accelerator R&D (AARD) experiments. Producing the required electron bunches with the expected flexibility is challenging. The goal of this dissertation is to explore via numerical simulations new accelerator beamlines that can enable the advanced manipulation of electron bunches. The work especially includes the design of a low-energy bunch compressor and a study of transverse-to-longitudinal phase space exchangers.

  17. Advanced beamline design for Fermilab's Advanced Superconducting Test Accelerator

    NASA Astrophysics Data System (ADS)

    Prokop, Christopher R.

    The Advanced Superconducting Test Accelerator (ASTA) at Fermilab is a new electron accelerator currently in the commissioning stage. In addition to testing superconducting accelerating cavities for future accelerators, it is foreseen to support a variety of Advanced Accelerator R&D (AARD) experiments. Producing the required electron bunches with the expected flexibility is challenging. The goal of this dissertation is to explore via numerical simulations new accelerator beamlines that can enable the advanced manipulation of electron bunches. The work especially includes the design of a low-energy bunch compressor and a study of transverse-to-longitudinal phase space exchangers.

  18. TURBULENT SHEAR ACCELERATION

    SciTech Connect

    Ohira, Yutaka

    2013-04-10

    We consider particle acceleration by large-scale incompressible turbulence with a length scale larger than the particle mean free path. We derive an ensemble-averaged transport equation of energetic charged particles from an extended transport equation that contains the shear acceleration. The ensemble-averaged transport equation describes particle acceleration by incompressible turbulence (turbulent shear acceleration). We find that for Kolmogorov turbulence, the turbulent shear acceleration becomes important on small scales. Moreover, using Monte Carlo simulations, we confirm that the ensemble-averaged transport equation describes the turbulent shear acceleration.

  19. The direction of acceleration

    NASA Astrophysics Data System (ADS)

    Wilhelm, Thomas; Burde, Jan-Philipp; Lück, Stephan

    2015-11-01

    Acceleration is a physical quantity that is difficult to understand and hence its complexity is often erroneously simplified. Many students think of acceleration as equivalent to velocity, a ˜ v. For others, acceleration is a scalar quantity, which describes the change in speed Δ|v| or Δ|v|/Δt (as opposed to the change in velocity). The main difficulty with the concept of acceleration therefore lies in developing a correct understanding of its direction. The free iOS app AccelVisu supports students in acquiring a correct conception of acceleration by showing acceleration arrows directly at moving objects.

  20. Nonresected Non-Small-Cell Lung Cancer in Stages I Through IIIB: Accelerated, Twice-Daily, High-Dose Radiotherapy-A Prospective Phase I/II Trial With Long-Term Follow-Up

    SciTech Connect

    Wurstbauer, Karl; Deutschmann, Heinz; Kopp, Peter; Kranzinger, Manfred; Merz, Florian; Nairz, Olaf; Studnicka, Michael; Sedlmayer, Felix

    2010-08-01

    Purpose: Our purpose was to investigate the tolerability of accelerated, twice-daily, high-dose radiotherapy. The secondary endpoints were survival and locoregional tumor control. Methods and Materials: Thirty consecutive patients with histologically/cytologically proven non-small-cell lung cancer were enrolled. Tumor Stage I, II, IIIA, and IIIB was found in 7, 3, 12, and 8 patients, respectively. We applied a median of 84.6 Gy (range, 75.6-90.0 Gy) to the primary tumors, 63.0 Gy (range, 59.4-72.0 Gy) to lymph nodes, and 45 Gy to nodes electively (within a region of about 6 cm cranial to macroscopically involved sites). Fractional doses of 1.8 Gy twice daily, with an interval of 11 hours, were given, resulting in a median treatment time of 35 days. In the majority of patients the conformal target-splitting technique was used. In 19 patients (63%) two cycles of induction chemotherapy were given. The median follow-up time of survivors is 72 months (range, 62-74 months). Results: We found Grade 1, 2 and 3 acute esophageal toxicity in 11 patients (37%), 2 patients (7%), and 2 patients (7%), respectively. Grade 2 acute pneumonitis was seen in 2 patients (7%). No late toxicity greater than Grade 1 was observed. The actual overall survival rates at 2 and 5 years are 63% and 23%, respectively; the median overall survival, 27.7 months. In 9 patients a local failure occurred, 7 of them presenting initially with an atelectasis without availability of 18-fluorodeoxyglucose-positron emission tomography staging at that time. In 4 patients recurrence occurred regionally. Conclusions: This Phase I/II trial with long-term follow-up shows low toxicity with promising results for survival and locoregional tumor control.

  1. Prognostic importance of single-nucleotide polymorphisms in IL-6, IL-10, TGF-β1, IFN-γ, and TNF-α genes in chronic phase chronic myeloid leukemia.

    PubMed

    Pehlivan, Mustafa; Sahin, Handan Haydaroglu; Pehlivan, Sacide; Ozdilli, Kursat; Kaynar, Leylagul; Oguz, Fatma Savran; Sever, Tugce; Yilmaz, Mehmet; Eser, Bulent; Ogret, Yeliz Duvarci; Kis, Cem; Okan, Vahap; Cetin, Mustafa; Carin, Mahmut

    2014-06-01

    The aim of this study was to explore the association between polymorphisms of five cytokine genes and clinical parameters in patients with Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) treated with imatinib. We analyzed five cytokine genes (interleukin [IL]-6, IL-10, gamma interferon [IFN-γ], transforming growth factor beta-1 [TGF-β1], and tumor necrosis factor-alpha [TNF-α]) in 60 cases with Ph+ CML and 74 healthy controls. Cytokine genotyping was performed by the polymerase chain reaction-sequence-specific primer. All data were analyzed using the de Finetti program and SPSS version 14.0 for Windows. No significant differences were detected between the CML group and healthy controls with respect to the distributions and numbers of genotypes and alleles in TNF-α, TGF-β1, IL-10, and IFN-γ. However, the GG genotype associated with high expression in IL-6 was found to be significantly more frequent in CML as compared to controls (p=0.010). The median follow-up time was 49.3 months (range 6.1-168.4) and the median duration of imatinib treatment was 39.5 months (range 5.2-103.4) for these patients. On multivariateanalysis, only IL-10 GCC/GCC highly produced haplotypes were significantly associated with a shorter event-free survival. The relationship between cytokine genotypes/haplotypes and clinical parameters in CML has not been investigated before. Our results suggest that IL-10 may be a useful marker for CML prognosis and theGG genotype of the IL-6 gene may be associated with susceptibility.

  2. The prodromal phase of obesity-related chronic kidney disease: early alterations in cardiovascular and renal function in obese children and adolescents.

    PubMed

    Doyon, Anke; Schaefer, Franz

    2013-11-01

    Childhood overweight and obesity is a relevant health condition with multi-organ involvement. Obesity shows significant tracking into adult life and is associated with an increased risk of serious adverse health outcomes both during childhood and later adulthood. The classical sequelae of obesity such as hypertension, metabolic syndrome and inflammation do develop at a paediatric age. Cardiovascular consequences, such as increased carotid intima-media thickness, and left ventricular hypertrophy, as well as functional alterations of the heart and arteries, are commonly traceable at an early age. Renal involvement can occur at a young age and is associated with a high probability of progressive chronic kidney disease. There is solid evidence suggesting that consequent treatment including both lifestyle changes and pharmacological therapy can reduce cardiovascular, metabolic and renal risks in obese children and adolescents.

  3. Enhanced striatial /sup 3/H-spiroperidol binding induced by chronic haloperidol treatment inhibited by peptides administered during the withdrawal phase

    SciTech Connect

    Bhargava, H.N.

    1984-02-27

    Chronic intragastric administration of haloperidol (1.5 mg/kg/day) for 21 days followed by a 3-day withdrawal period resulted in the development of enhanced locomotor activity response to apomorphine, and an increase in the number of binding sites for /sup 3/H-spiroperidol in the striatal membranes of the rat brain. Subcutaneous administration of Pro-Leu-Gly-NH/sub 2/ or cyclo-(Leu-Gly) in doses of 2 mg/kg/day given for 3-days after termination of haloperidol treatment inhibited the enhanced response to apomorphine, as well as the increases in the number of /sup 3/H-spiroperidol binding sites in the striatum. If indeed, the supersensitivity of striatal dopamine receptors is one of the mechanisms in the development of tardive dyskinesia symptoms, the present results suggest that the above peptides may be helpful in ameliorating some of the symptoms of tardive dyskinesia induced by neuroleptic drugs. 31 references, 3 figures.

  4. The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study.

    PubMed

    Eisenberg, Elon; Ogintz, Miri; Almog, Shlomo

    2014-09-01

    Chronic neuropathic pain is often refractory to standard pharmacological treatments. Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a "main stream" pharmacological treatment for neuropathic pain. The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis. In a single-dose, open-label study, patients inhaled a single 15.1 ± 0.1 mg dose of cannabis using the Syqe Inhaler device. Blood samples for Δ(9)-tetrahydrocannabinol (THC) and 11-hydroxy-Δ(9)-THC were taken at baseline and up to 120 minutes. Pain intensity (0-10 VAS), adverse events, and satisfaction score were monitored following the inhalation. A uniform pharmacokinetic profile was exhibited across all participants (Δ(9)-THC plasma Cmax ± SD was 38 ± 10 ng/mL, Tmax ± SD was 3 ± 1 minutes, AUC₀→infinity ± SD was 607 ± 200 ng·min/mL). Higher plasma Cmax increase per mg Δ(9)-THC administered (12.3 ng/mL/mg THC) and lower interindividual variability of Cmax (25.3%), compared with reported alternative modes of THC delivery, were measured. A significant 45% reduction in pain intensity was noted 20 minutes post inhalation (P = .001), turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15-30 minutes and requiring no intervention, was the only reported adverse event. This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Δ(9)-THC pharmacokinetic profile with low interindividual variation of Cmax, achieving pharmaceutical standards for inhaled drugs. PMID:25118789

  5. The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study.

    PubMed

    Eisenberg, Elon; Ogintz, Miri; Almog, Shlomo

    2014-09-01

    Chronic neuropathic pain is often refractory to standard pharmacological treatments. Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a "main stream" pharmacological treatment for neuropathic pain. The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis. In a single-dose, open-label study, patients inhaled a single 15.1 ± 0.1 mg dose of cannabis using the Syqe Inhaler device. Blood samples for Δ(9)-tetrahydrocannabinol (THC) and 11-hydroxy-Δ(9)-THC were taken at baseline and up to 120 minutes. Pain intensity (0-10 VAS), adverse events, and satisfaction score were monitored following the inhalation. A uniform pharmacokinetic profile was exhibited across all participants (Δ(9)-THC plasma Cmax ± SD was 38 ± 10 ng/mL, Tmax ± SD was 3 ± 1 minutes, AUC₀→infinity ± SD was 607 ± 200 ng·min/mL). Higher plasma Cmax increase per mg Δ(9)-THC administered (12.3 ng/mL/mg THC) and lower interindividual variability of Cmax (25.3%), compared with reported alternative modes of THC delivery, were measured. A significant 45% reduction in pain intensity was noted 20 minutes post inhalation (P = .001), turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15-30 minutes and requiring no intervention, was the only reported adverse event. This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Δ(9)-THC pharmacokinetic profile with low interindividual variation of Cmax, achieving pharmaceutical standards for inhaled drugs.

  6. Accelerating Particles with Plasma

    SciTech Connect

    Litos, Michael; Hogan, Mark

    2014-11-05

    Researchers at SLAC explain how they use plasma wakefields to accelerate bunches of electrons to very high energies over only a short distance. Their experiments offer a possible path for the future of particle accelerators.

  7. Accelerator Technology Division

    NASA Astrophysics Data System (ADS)

    1992-04-01

    In fiscal year (FY) 1991, the Accelerator Technology (AT) division continued fulfilling its mission to pursue accelerator science and technology and to develop new accelerator concepts for application to research, defense, energy, industry, and other areas of national interest. This report discusses the following programs: The Ground Test Accelerator Program; APLE Free-Electron Laser Program; Accelerator Transmutation of Waste; JAERI, OMEGA Project, and Intense Neutron Source for Materials Testing; Advanced Free-Electron Laser Initiative; Superconducting Super Collider; The High-Power Microwave Program; (Phi) Factory Collaboration; Neutral Particle Beam Power System Highlights; Accelerator Physics and Special Projects; Magnetic Optics and Beam Diagnostics; Accelerator Design and Engineering; Radio-Frequency Technology; Free-Electron Laser Technology; Accelerator Controls and Automation; Very High-Power Microwave Sources and Effects; and GTA Installation, Commissioning, and Operations.

  8. Linear accelerator: A concept

    NASA Technical Reports Server (NTRS)

    Mutzberg, J.

    1972-01-01

    Design is proposed for inexpensive accelerometer which would work by applying pressure to fluid during acceleration. Pressure is used to move shuttle, and shuttle movement is sensed and calibrated to give acceleration readings.

  9. Improved plasma accelerator

    NASA Technical Reports Server (NTRS)

    Cheng, D. Y.

    1971-01-01

    Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

  10. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  11. Muon Collider Progress: Accelerators

    SciTech Connect

    Zisman, Michael S.

    2011-09-10

    A muon collider would be a powerful tool for exploring the energy-frontier with leptons, and would complement the studies now under way at the LHC. Such a device would offer several important benefits. Muons, like electrons, are point particles so the full center-of-mass energy is available for particle production. Moreover, on account of their higher mass, muons give rise to very little synchrotron radiation and produce very little beamstrahlung. The first feature permits the use of a circular collider that can make efficient use of the expensive rf system and whose footprint is compatible with an existing laboratory site. The second feature leads to a relatively narrow energy spread at the collision point. Designing an accelerator complex for a muon collider is a challenging task. Firstly, the muons are produced as a tertiary beam, so a high-power proton beam and a target that can withstand it are needed to provide the required luminosity of ~1 × 10{sup 34} cm{sup –2}s{sup –1}. Secondly, the beam is initially produced with a large 6D phase space, which necessitates a scheme for reducing the muon beam emittance (“cooling”). Finally, the muon has a short lifetime so all beam manipulations must be done very rapidly. The Muon Accelerator Program, led by Fermilab and including a number of U.S. national laboratories and universities, has undertaken design and R&D activities aimed toward the eventual construction of a muon collider. Design features of such a facility and the supporting R&D program are described.

  12. MEQALAC rf accelerating structure

    SciTech Connect<