Addition of High-Dose Cytarabine to Fludarabine-Based Conditioning for Hematopoietic Stem Cell Transplantation for Treating Fanconi Anemia Patients with Advanced Myeloid Malignancy: A Single-Center Experience and Literature Review.

PubMed

Aoki, Takahiro; Koh, Katsuyoshi; Ikeda, Yuhachi; Sekinaka, Yujin; Akiyama, Kosuke; Mori, Makiko; Arakawa, Yuki; Hanada, Ryoji

2016-09-01

The complication of Fanconi anemia (FA) with acute leukemia is rare and challenging to treat because of high relapse rates, despite the improved outcome of hematopoietic stem cell transplantation with fludarabine-based conditioning for treating FA patients with hematological abnormalities. We added high-dose cytarabine to fludarabine-based conditioning to promote an enhanced antitumor effect and successfully subjected 4 patients with FA, including 3 with acute leukemia, to hematopoietic stem cell transplantation. All patients remain alive without treatment-related mortality or evidence of disease. Adding high-dose cytarabine to fludarabine-based conditioning may be tolerable and effective for treating FA patients with acute leukemia. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Intesive fludarabine-high dose cytarabine-idarubicin combination as induction therapy with risk-adapted consolidation may improve treatment efficacy in younger Acute Myeloid Leukemia (AML) patients: Rationales, evidences and future perspectives.

PubMed

Guolo, Fabio; Minetto, Paola; Clavio, Marino; Miglino, Maurizio; Lemoli, Roberto Massimo; Gobbi, Marco

2017-03-22

Acute Myeloid Leukemia (AML) is the commonest form of leukemia in the adults, with an incidence of 3-4 cases per 100,000 people/year. After the first description of the effective cytarabine + antracycline (3+7) induction regimen, in the last 3 decades, no effective targeted drug has been included in the standard treatment of AML. Many efforts of modifying 3+7 adding a third drug or increasing the dose of anthracycline, cytarabine or both did not lead to substantial improvements, mainly due to increased toxicity. Many in vitro and in vivo evidences suggested that fludarabine may increase efficacy of cytarabine through a synergistic effect. Considering the continuous improvements in supportive care and management of infectious complications the feasibility of more intensive induction strategies have increased and a renewed interest in fludarabine-containing induction strategies arose. The recent MRC AML 15 trial has shown that a fludarabine-containing induction, FLAG-Ida, resulted superior to conventional 3+7 in terms of complete remission rates, relapse incidence and survival, although only a minority of patients could complete the whole planned consolidation program due to an excessive hematological toxicity. Our group recently published a 10-year experience with a fludarabine-containing induction that slightly differed from the MRC one and resulted in good efficacy and higher feasibility. In this commentary we review the major evidences supporting the employ of a fludarabine-containing induction in AML, and discuss the future perspectives.

Successful treatment of IgM paraproteinaemic neuropathy with fludarabine

PubMed Central

Wilson, H.; Lunn, M.; Schey, S.; Hughes, R

1999-01-01

OBJECTIVES—To evaluate the response of four patients with IgM paraproteinaemic neuropathy to a novel therapy—pulsed intravenous fludarabine.
BACKGROUND—The peripheral neuropathy associated with IgM paraproteinaemia usually runs a chronic, slowly progressive course which may eventually cause severe disability. Treatment with conventional immunosuppressive regimens has been unsatisfactory. Fludarabine is a novel purine analogue which has recently been shown to be effective in low grade lymphoid malignancies.
METHODS—Four patients were treated with IgM paraproteinaemic neuropathy with intravenous pulses of fludarabine. Two of the four patients had antibodies to MAG and characteristic widely spaced myelin on nerve biopsy and a third had characteristic widely spaced myelin only. The fourth had an endoneurial lymphocytic infiltrate on nerve biopsy and a diagnosis of Waldenström's macroglobulinaemia.
RESULTS—In all cases subjective and objective clinical improvement occurred associated with a significant fall in the IgM paraprotein concentration in three cases. Neurophysiological parameters improved in the three patients examined. The treatment was well tolerated. All patients developed mild, reversible lymphopenia and 50% mild generalised myelosuppression, but there were no febrile episodes.
CONCLUSION—Fludarabine should be considered as a possible treatment for patients with IgM MGUS paraproteinaemic neuropathy.

 PMID:10209166

A Phase 2 Study of Concurrent Fludarabine and Rituximab for the Treatment of Marginal Zone Lymphomas

PubMed Central

Brown, Jennifer R; Friedberg, Jonathan W.; Feng, Yang; Scofield, Sarah; Phillips, Kimberly; Cin, Paola Dal; Joyce, Robin; Takvorian, Ronald W; Fisher, David C; Fisher, Richard I; Liesveld, Jane; Marquis, Diana; Neuberg, Donna; Freedman, Arnold S

2009-01-01

SUMMARY The marginal zone lymphomas are a recently defined group of related diseases likely arising from a common cell of origin, the marginal zone B cell. Data on therapy for subtypes other than gastric MALT has been largely limited to retrospective case series. We therefore undertook this prospective phase 2 study of fludarabine and rituximab for the treatment of marginal zone lymphomas. 26 patients were enrolled, 14 with nodal MZL, 8 with MALT lymphomas and 4 with splenic MZL; 81% were receiving initial systemic therapy. Only 58% (95% CI 37–77%) of patients completed the planned six cycles, due to significant hematologic, infectious and allergic toxicity. Four late toxic deaths occurred due to infections (15% (95% CI 4.3–35%), two related to delayed bone marrow aplasia and two related to MDS. Nonetheless, the ORR was 85% (95% CI 65–96%), with 54% CRs. The progression-free survival at 3.1 years of follow-up is 79.5% (95% CI, 63–96%). We conclude that although concurrent fludarabine and rituximab given at this dose and schedule is a highly effective regimen in the treatment of marginal zone lymphomas, the significant hematologic and infectious toxicity observed both during and after therapy is prohibitive in this patient population, emphasizing the need to study marginal zone lymphomas as a separate entity. PMID:19344412

Outcomes of Cord Blood Transplantation Using Reduced-Intensity Conditioning for Chronic Lymphocytic Leukemia: A Study on Behalf of Eurocord and Cord Blood Committee of Cellular Therapy and Immunobiology Working Party, Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation, and the Societé Française de Greffe de Moelle et Therapie Cellulaire.

PubMed

Xavier, Erick; Cornillon, Jérôme; Ruggeri, Annalisa; Chevallier, Patrice; Cornelissen, Jan J; Andersen, Niels S; Maillard, Natacha; Nguyen, Stephanie; Blaise, Didier; Deconinck, Eric; Veelken, Hendrik; Milpied, Noel; Van Gelder, Michel; Peffault de Latour, Regis; Gluckman, Eliane; Kröger, Nicolaus; Schetelig, Johannes; Rocha, Vanderson

2015-08-01

Outcomes after umbilical cord blood transplantation (UCBT) for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are unknown. We analyzed outcomes of 68 patients with poor-risk CLL/SLL who underwent reduced-intensity (RIC) UCBT from 2004 to 2012. The median age was 57 years and median follow-up 36 months; 17 patients had del 17p/p53mutation, 19 patients had fludarabine-refractory disease, 11 relapsed after autologous stem cell transplantation, 8 had diagnosis of prolymphocytic leukemia, 4 had Richter syndrome, and 8 underwent transplantation with progressive or refractory disease. The most common RIC used was cyclophosphamide, fludarabine, and total body irradiation (TBI) in 82%; 15 patients received antithymocyte globulin. Most of the cord blood grafts were HLA mismatched and 76% received a double UCBT. Median total nucleated cells collected was 4.7 × 10(7)/kg. The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 72% at 60 and 180 days respectively; day 100 graft-versus-host disease (GVHD) (grade II to IV) was 43% and 3-year chronic GVHD was 32%. The CI of relapse, nonrelapse mortality, overall survival, and progression-free survival (PFS) at 3 years were 16%, 39%, 54%, and 45%, respectively. Fludarabine-sensitive disease at transplantation and use of low-dose TBI regimens were associated with acceptable PFS. In conclusion, use of RIC-UCBT seems to be feasible in patients with poor-risk CLL/SLL and improved outcomes were observed in patients with fludarabine-sensitive disease who received low-dose TBI regimens. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Outpatient-Based Therapy of Oral Fludarabine and Subcutaneous Alemtuzumab for Asian Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

PubMed Central

Hwang, William Y. K.; Dearden, Claire; Loh, Yvonne S. M.; Linn, Yeh C.; Tien, Sim L.; Teoh, Gerrard K. H.; How, Gee F.; Heng, Kee K.; Goh, Yeow T.; Lee, Lai H.

2009-01-01

Background. Intravenous alemtuzumab and fludarabine are effective in combination for the treatment of chronic lymphocytic leukemia (CLL), but require hospital visits for intravenous injection. We performed a pilot study to assess the safety and efficacy of outpatient-based oral fludarabine with subcutaneous alemtuzumab (OFSA) for the treatment of relapsed/refractory CLL. Results. Depending on their response, patients were given two to six 28-day cycles of subcutaneous alemtuzumab 30 mg on days 1,3, and 5 and oral fludarabine 40 mg/m2/day for 5 days. Median patient age was 74. The lymphocyte counts of all five patients fell after the 1st cycle of treatment and reached normal/low levels on completion of 2 to 6 cycles of therapy. Platelet counts and hemoglobin were unaffected. All five patients achieved complete hematological remission, while two attained minimal residual disease negativity on 4-color flow cytometry. Conclusions. Our OFSA regimen was effective in elderly Asian patients with relapsed/refractory CLL, and it should be investigated further. PMID:19960058

Determination of intracellular fludarabine triphosphate in human peripheral blood mononuclear cells by LC-MS/MS.

PubMed

Huang, Liusheng; Lizak, Patricia; Aweeka, Francesca; Long-Boyle, Janel

2013-12-01

Fludarabine is a nucleoside analog routinely used in conditioning regimens of pediatric allogeneic stem cell transplantation to promote stem cell engraftment. In children, it remains a challenge to accurately and precisely quantify the active intracellular triphosphate species of fludarabine in vivo, primarily due to limitations on blood volume and inadequate assay sensitivity. Here we report a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determination of fludarabine triphosphate in human peripheral blood mononuclear cells (PBMC). PBMC (∼5 million cells) were collected and lysed in 1mL 70% methanol containing 1.2mM tris buffer (pH 7.4). The lysate (80μL) was mixed with internal standard (2-chloro-adenosine triphosphate, 150ng/mL, 20μL) and injected onto an API5000 LC-MS/MS system. Separation was achieved on a hypercarb column (100mm×2.1mm, 3μm) eluted with 100mM ammonium acetate (pH 9.8) and acetonitrile in a gradient mode at a flow rate of 0.4mL/min. Multiple reactions monitoring (MRM) and electrospray ionization in negative mode (ESI(-)) were used for detection. The ion pairs 524.0/158.6 for the drug and 540.0/158.8 for the IS were selected for quantification and 524.0/425.7 used for confirmation. Retention time was 3.0 and 3.4min for fludarabine triphosphate and the IS, respectively. The concentration range for the calibration curve was 1.52-76nM. Our method is simple, fast, and has been successfully applied in a clinical dose-concentration study in children to quantify intracellular fludarabine in low volume clinical samples. The median concentration was 1.03 and 3.19pmole/million PBMC at trough and peak time points, respectively. Fludarabine triphosphate is degraded in water within hours but relatively stable in 70% methanol-tris (1.2mM, pH 7.4). One limitation is that the hypercarb column takes a longer time to equilibrate than conventional reverse phase columns, and peaks become broad and distorted if the column is not washed and stored properly. Copyright © 2013 Elsevier B.V. All rights reserved.

Gemcitabine, Fludarabine, and Melphalan for Reduced-Intensity Conditioning and Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma.

PubMed

Anderlini, Paolo; Saliba, Rima M; Ledesma, Celina; Plair, Tamera; Alousi, Amin M; Hosing, Chitra M; Khouri, Issa F; Nieto, Yago; Popat, Uday R; Shpall, Elizabeth J; Fanale, Michelle A; Hagemeister, Frederick B; Oki, Yasuhiro; Neelapu, Saatva; Romaguera, Jorge E; Younes, Anas; Champlin, Richard E

2016-07-01

Forty patients (median age, 31 years; range, 20 to 63) with Hodgkin lymphoma underwent an allogeneic stem cell transplant with the gemcitabine-fludarabine-melphalan reduced-intensity conditioning regimen. Thirty-one patients (77%) had undergone a prior autologous stem cell transplant, with a median time to progression after transplant of 6 months (range, 1 to 68). Disease status at transplant was complete remission/complete remission, undetermined (n = 23; 57%), partial remission (n = 14; 35%), and other (n = 3; 8%). Twenty-six patients (65%) received brentuximab vedotin before allotransplant. The overall complete response rate before allotransplant was 65% in brentuximab-treated patients versus 42% in brentuximab-naive patients (P = .15). At the latest follow-up (October 2015) 31 patients were alive. The median follow-up was 41 months (range, 5 to 87). Transplant-related mortality rate at 3 years was 17%. Pulmonary, skin toxicities, and nausea were seen in 13 (33%), 11 (28%), and 37 (93%) patients, respectively. At 3 years, estimates for overall and progression-free survival were 75% (95% CI, 57% to 86%) and 54% (95% CI, 36% to 70%). Overall incidence for disease progression was 28% (95% CI, 16% to 50%). We believe the gemcitabine-fludarabine-melphalan regimen allows moderate dose intensification with acceptable morbidity and mortality. The inclusion of gemcitabine affected nausea, pulmonary, and likely skin toxicity. Exposure to brentuximab vedotin allowed more patients to reach allogeneic stem cell transplantation in complete remission. With over 50% of patients progression-free at 3 years, allogeneic stem cell transplantation with reduced-intensity conditioning remains an effective and relevant treatment option for Hodgkin lymphoma in the brentuximab vedotin era. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Ajoene, a garlic-derived natural compound, enhances chemotherapy-induced apoptosis in human myeloid leukaemia CD34-positive resistant cells.

PubMed

Ahmed, N; Laverick, L; Sammons, J; Zhang, H; Maslin, D J; Hassan, H T

2001-01-01

The reputation of garlic as an effective remedy for tumours extends back to the Egyptian Codex Ebers of 1550 BC. Several garlic compounds, including allicin and its corresponding sulfide, inhibit the proliferation of several human malignant cells. Ajoene is a garlic-derived compound produced most efficiently from pure allicin and has the advantage of a greater chemical stability than allicin. Recently, ajoene was shown to inhibit proliferation and induce apoptosis of human leukaemia CD34-negative cells including HL-60, U937, HEL and OCIM-I. More significantly, ajoene was shown to induce 30% apoptosis in myeloblasts from a chronic myeloid leukaemia patient in blastic crisis. Acute myeloid leukaemia (AML) is a heterogeneous malignant disease in which disease progression at the level of CD34-positive cells has a major impact on resistance to chemotherapy and relapse. The aim of the present study was to investigate the effect of ajoene on changes in the expression of apoptosis-related proteins: bcl-2 and caspase-3, induced by two principal drugs used in treatment of AML, cytarabine and fludarabine, in KGI human myeloid leukaemia CD34-positive-resistant cells. Both quantitative ELISA measurement of bcl-2 and colourimetric measurement of active caspase-3 were used. Quantitative ELISA measurement of bcl-2 (units per million cells) showed treatment of KG1-resistant leukaemia cells with 40 microM ajoene alone to significantly reduce the bcl-2-expression from 239.5 +/- 1.5 in control cultures to only 22.0 +/- 4.0 in ajoene-treated cultures. Fludarabine had significantly more inhibitory effect on bcl-2-expression than cytarabine in KGI-resistant myeloid leukaemia cells. Ajoene significantly enhanced the inhibitory effect of the two chemotherapeutic drugs, cytarabine and fludarabine, on bcl-2-expression in KGI cells. Bcl-2-expression could not be detected in fludarabine + ajoene-treated cultures. The Western blot of bcl-2-expression in KGI control and treated cells confirmed the quantitative ELISA measurements. Quantitative measurement of activated caspase-3 (pg per million cells) showed the two drugs, cytarabine and fludarabine, significantly increased the activated caspase-3 level in KGI myeloid leukaemia cells. The addition of ajoene enhanced the activation of caspase-3 in both cytarabine- and fludarabine-treated KGI cells. In conclusion, the present results suggest a potential role for the combination of ajoene with fludarabine-based chemotherapy in the treatment of refractory and/or relapsed AML patients. Further studies are warranted to evaluate a similar enhancing effect for ajoene in blast cells from AML patients in primary cultures.

A Phase II Trial of Fludarabine/Melphalan 100 Conditioning Therapy Followed by Allogeneic Hematopoietic Cell Transplantation for Patients With Lymphoma.

PubMed

Lee, Jung-Hee; Lee, Je-Hwan; Kim, Dae-Young; Seol, Miee; Lee, Young-Shin; Kang, Young-Ah; Jeon, Mijin; Lee, Kyoo-Hyung

2015-11-01

Conditioning therapy with fludarabine and melphalan 140 mg/m(2) has been widely used before allogeneic hematopoietic cell transplantation (HCT) for lymphoma. A lower dose of melphalan might result in lower mortality and morbidity without compromising engraftment. In our phase II trial, we investigated a conditioning regimen of fludarabine (30 mg/m(2)/day for 5 days on days -6 to -2) and melphalan (100 mg/m(2) on day -2). Antithymocyte globulin was added to fludarabine and melphalan for unrelated or mismatched familial donor HCT. The present study included 26 patients with lymphoma (B-cell in 10, T-cell in 11, and natural killer/T-cell lymphoma in 2). An objective tumor response after HCT was observed in 18 patients (75.0%; complete in 14 and partial in 4). Acute and chronic graft-versus-host disease (GVHD) occurred in 23.1% and 55.0% of the assessable patients, respectively. The 5-year overall survival, nonrelapse mortality, progression-free survival, and event-free survival rate was 40.4%, 21.6%, 39.2%, and 30.8%, respectively. Donor lymphocyte infusions were given to 3 patients who had developed a relapse or progression after HCT, and 2 of whom had a showed partial response. Patients with severe chronic GVHD had greater overall survival than those with no, mild, or moderate chronic GVHD. Conditioning therapy with a lower dose of melphalan, combined with fludarabine, appears to be promising in allogeneic HCT for lymphoma. The Clinicaltrials.gov identification number for the present study is NCT00772811. Copyright © 2015 Elsevier Inc. All rights reserved.

Transplant results in adults with Fanconi anaemia.

PubMed

Bierings, Marc; Bonfim, Carmem; Peffault De Latour, Regis; Aljurf, Mahmoud; Mehta, Parinda A; Knol, Cora; Boulad, Farid; Tbakhi, Abdelghani; Esquirol, Albert; McQuaker, Grant; Sucak, Gulsan A; Othman, Tarek B; Halkes, Constantijn J M; Carpenter, Ben; Niederwieser, Dietger; Zecca, Marco; Kröger, Nicolaus; Michallet, Mauricette; Risitano, Antonio M; Ehninger, Gerhard; Porcher, Raphael; Dufour, Carlo

2018-01-01

The outcomes of adult patients transplanted for Fanconi anaemia (FA) have not been well described. We retrospectively analysed 199 adult patients with FA transplanted between 1991 and 2014. Patients were a median of 16 years of age when diagnosed with FA, and underwent transplantation at a median age of 23 years. Time between diagnosis and transplant was shortest (median 2 years) in those patients who had a human leucocyte antigen identical sibling donor. Fifty four percent of patients had bone marrow (BM) failure at transplantation and 46% had clonal disease (34% myelodysplasia, 12% acute leukaemia). BM was the main stem cell source, the conditioning regimen included cyclophosphamide in 96% of cases and fludarabine in 64%. Engraftment occurred in 82% (95% confidence interval [CI] 76-87%), acute graft-versus-host disease (GvHD) grade II-IV in 22% (95% CI 16-28%) and the incidence of chronic GvHD at 96 months was 26% (95% CI 20-33). Non-relapse mortality at 96 months was 56% with an overall survival of 34%, which improved with more recent transplants. Median follow-up was 58 months. Patients transplanted after 2000 had improved survival (84% at 36 months), using BM from an identical sibling and fludarabine in the conditioning regimen. Factors associated with improved outcome in multivariate analysis were use of fludarabine and an identical sibling or matched non-sibling donor. Main causes of death were infection (37%), GvHD (24%) and organ failure (12%). The presence of clonal disease at transplant did not significant impact on survival. Secondary malignancies were reported in 15 of 131 evaluable patients. © 2017 John Wiley & Sons Ltd.

Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage

PubMed Central

Ye, YongBin; Wang, Jing; Huang, YuXian; Weng, GuangYang; Zhang, MingWan

2016-01-01

Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a major cause of nonrelapse mortality after allo-HSCT. A conditioning regimen plays a pivotal role in the development of aGVHD. To provide a platform for studying aGVHD and evaluating the impact of different conditioning regimens, we established a murine aGVHD model that simulates the clinical situation and can be conditioned with Busulfan-Cyclophosphamide (Bu-Cy) and Fludarabine-Busulfan (Flu-Bu). In our study, BALB/c mice were conditioned with Bu-Cy or Flu-Bu and transplanted with 2 × 107 bone marrow cells and 2 × 107 splenocytes from either allogeneic (C57BL/6) or syngeneic (BALB/c) donors. The allogeneic recipients conditioned with Bu-Cy had shorter survivals (P < 0.05), more severe clinical manifestations, and higher hepatic and intestinal pathology scores, associated with increased INF-γ expression and diminished IL-4 expression in serum, compared to allogeneic recipients conditioned with Flu-Bu. Moreover, higher donor-derived T-cell infiltration and severely impaired B-cell development were seen in the bone marrow of mice, exhibiting aGVHD and conditioned with Flu-Bu. Our study showed that the conditioning regimen with Bu-Cy resulted in more severe aGVHD while the Flu-Bu regimen was associated with more extensive and long standing bone marrow damage. PMID:27843940

In silico simulations of STAT1 and STAT3 inhibitors predict SH2 domain cross-binding specificity.

PubMed

Szelag, Malgorzata; Sikorski, Krzysztof; Czerwoniec, Anna; Szatkowska, Katarzyna; Wesoly, Joanna; Bluyssen, Hans A R

2013-11-15

Signal transducers and activators of transcription (STATs) comprise a family of transcription factors that are structurally related and which participate in signaling pathways activated by cytokines, growth factors and pathogens. Activation of STAT proteins is mediated by the highly conserved Src homology 2 (SH2) domain, which interacts with phosphotyrosine motifs for specific contacts between STATs and receptors and for STAT dimerization. By generating new models for human (h)STAT1, hSTAT2 and hSTAT3 we applied comparative in silico docking to determine SH2-binding specificity of the STAT3 inhibitor stattic, and of fludarabine (STAT1 inhibitor). Thus, we provide evidence that by primarily targeting the highly conserved phosphotyrosine (pY+0) SH2 binding pocket stattic is not a specific hSTAT3 inhibitor, but is equally effective towards hSTAT1 and hSTAT2. This was confirmed in Human Micro-vascular Endothelial Cells (HMECs) in vitro, in which stattic inhibited interferon-α-induced phosphorylation of all three STATs. Likewise, fludarabine inhibits both hSTAT1 and hSTAT3 phosphorylation, but not hSTAT2, by competing with the highly conserved pY+0 and pY-X binding sites, which are less well-preserved in hSTAT2. Moreover we observed that in HMECs in vitro fludarabine inhibits cytokine and lipopolysaccharide-induced phosphorylation of hSTAT1 and hSTAT3 but does not affect hSTAT2. Finally, multiple sequence alignment of STAT-SH2 domain sequences confirmed high conservation between hSTAT1 and hSTAT3, but not hSTAT2, with respect to stattic and fludarabine binding sites. Together our data offer a molecular basis that explains STAT cross-binding specificity of stattic and fludarabine, thereby questioning the present selection strategies of SH2 domain-based competitive small inhibitors. © 2013 Elsevier B.V. All rights reserved.

Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia.

PubMed

Hopfinger, Georg; Busch, Raymonde; Pflug, Natali; Weit, Nicole; Westermann, Anne; Fink, Anna-Maria; Cramer, Paula; Reinart, Nina; Winkler, Dirk; Fingerle-Rowson, Günter; Stilgenbauer, Stephan; Döhner, Hartmut; Kandler, Gabriele; Eichhorst, Barbara; Hallek, Michael; Herling, Marco

2013-06-15

Scarce systematic trial data have prevented uniform therapeutic guidelines for T-cell prolymphocytic leukemia (T-PLL). A central need in this historically refractory tumor is the controlled evaluation of multiagent chemotherapy and its combination with the currently most active single agent, alemtuzumab. This prospective multicenter phase 2 trial assessed response, survival, and toxicity of a novel regimen in previously treated (n = 9) and treatment-naive (n = 16) patients with T-PLL. Induction by fludarabine, mitoxantrone, and cyclophosphamide (FMC), for up to 4 cycles, was followed by alemtuzumab (A) consolidation, up to 12 weeks. Of the 25 patients treated with FMC, 21 subsequently received alemtuzumab. Overall response rate to FMC was 68%, comprising 6 complete remissions (all bone-marrow confirmed) and 11 partial remissions. Alemtuzumab consolidation increased the intent-to-treat overall response rate to 92% (12 complete remissions; 11 partial remissions). Median overall survival after FMC-A was 17.1 months and median progression-free survival was 11.9 months. Progression-free survival tended to be shorter for patients with high-level T-cell leukemia 1 oncoprotein expression. Hematologic toxicities were the most frequent grade 3/4 side effects under FMC-A. Exclusively in the 21 alemtuzumab-consolidated patients, 13 cytomegalovirus reactivations were observed; 9 of these 13 represented a clinically relevant infection. FMC-A is a safe and efficient protocol in T-PLL, which compares favorably to published data. Copyright © 2013 American Cancer Society.

Viewpoint dependence in the recognition of non-elongated familiar objects: testing the effects of symmetry, front-back axis, and familiarity.

PubMed

Niimi, Ryosuke; Yokosawa, Kazuhiko

2009-01-01

Visual recognition of three-dimensional (3-D) objects is relatively impaired for some particular views, called accidental views. For most familiar objects, the front and top views are considered to be accidental views. Previous studies have shown that foreshortening of the axes of elongation of objects in these views impairs recognition, but the influence of other possible factors is largely unknown. Using familiar objects without a salient axis of elongation, we found that a foreshortened symmetry plane of the object and low familiarity of the viewpoint accounted for the relatively worse recognition for front views and top views, independently of the effect of a foreshortened axis of elongation. We found no evidence that foreshortened front-back axes impaired recognition in front views. These results suggest that the viewpoint dependence of familiar object recognition is not a unitary phenomenon. The possible role of symmetry (either 2-D or 3-D) in familiar object recognition is also discussed.

Impact of novel agents on patient-relevant outcomes in patients with previously untreated chronic lymphocytic leukemia who are not eligible for fludarabine-based therapy.

PubMed

Singh, Moushmi; Mealing, Stuart; Baculea, Simona; Cote, Sarah; Whelan, Jo

2017-10-01

Chronic lymphocytic leukemia (CLL) is an orphan disease that primarily affects the elderly. The majority of symptomatic patients eligible for frontline treatment are unfit for fludarabine based chemoimmunotherapy. Historical treatment includes chlorambucil (Chl), bendamustine/rituximab (BR), and chlorambucil/rituximab/ChlR combination. Clinical guidelines now recommend the use of novel agents, such as ibrutinib (Ibr), in both frontline and relapse settings and other novel agents, such as idelalisib (with rituximab), in relapse settings. Despite compelling clinical results for novel agents, follow-up in clinical trials is relatively short and, thus, the comparative long-term benefits are still unknown. The authors developed a simulation model to generate treatment specific lifetime estimates of Overall Survival (OS) and Quality Adjusted Life Years (QALYs) for treatment with BR, Chl, ChlR, and Ibr. Two potential clinical scenarios were modelled: with and without novel agents for treating CLL. The model was based on health states relating to first- and second-line progression-free survival (PFS), post-progression survival, and death. Where novel agents were assumed unavailable, mean OS ranged from 5.4-8.5 years and QALYs from 3.5-6.1. Where novel agents were available, the mean OS increased to 10.0 years, with a corresponding increase in QALYs to 7.6. Frontline Ibr use followed by Physician's Choice, including novel agents at relapse, resulted in projected increase in OS of between 18% (1.5 years) and 85% (4.6 years), corresponding to a 25-117% increase in QALYs, compared with currently available traditional therapies. The limitations of this analysis include immature OS data and the assumption of equivalent efficacy across all novel agents in terms of their impact on PFS and OS. The use of novel agents is predicted to yield substantive gains in predicted lifetime OS and QALY improvements compared to traditional therapies in CLL patients who are ineligible for fludarabine-based chemoimmunotherapy.

Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens.

PubMed

Lin, Katherine I; Tam, Constantine S; Keating, Michael J; Wierda, William G; O'Brien, Susan; Lerner, Susan; Coombes, Kevin R; Schlette, Ellen; Ferrajoli, Alessandra; Barron, Lynn L; Kipps, Thomas J; Rassenti, Laura; Faderl, Stefan; Kantarjian, Hagop; Abruzzo, Lynne V

2009-04-02

Although immunoglobulin V(H) mutation status (IgV(H) MS) is prognostic in patients with chronic lymphocytic leukemia (CLL) who are treated with alkylating agents or single-agent fludarabine, its significance in the era of chemoimmunotherapy is not known. We determined the IgV(H) somatic mutation status (MS) in 177 patients enrolled in a phase 2 study of fludarabine, cyclophosphamide, and rituximab (FCR) and in 127 patients treated with subsequent chemoimmunotherapy protocols. IgV(H) MS did not impact significantly on the complete remission (CR) rate of patients receiving FCR or related regimens. However, CR duration was significantly shorter in patients with CLL that used unmutated IgV(H) than those whose CLL used mutated IgV(H) (TTP 47% vs 82% at 6 years, P < .001). In a multivariate model considering all baseline characteristics, IgV(H) MS emerged as the only determinant of remission duration (hazard ratio 3.8, P < .001). Our results suggest that postremission interventions should be targeted toward patients with unmutated IgV(H) status.

Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab).

PubMed

Tam, Constantine S; O'Brien, Susan; Plunkett, William; Wierda, William; Ferrajoli, Alessandra; Wang, Xuemei; Do, Kim-Anh; Cortes, Jorge; Khouri, Issa; Kantarjian, Hagop; Lerner, Susan; Keating, Michael J

2014-11-13

Although fludarabine, cyclophosphamide, and rituximab (FCR) together are established as a standard first-line treatment of younger patients with chronic lymphocytic leukemia (CLL), there is little information to guide the management of patients with CLL refractory to, or who have relapsed after, receiving frontline FCR treatment. To define optimal salvage strategy and identify patients unsuitable for retreatment with FCR, we examined the survival and treatment outcome of 300 patients enrolled in a phase 2 study of FCR. After a median 142 months of follow-up, 156 patients developed progressive CLL, with a median survival of 51 months after disease progression. The duration of first remission (REM1) was a key determinant of survival after disease progression and first salvage. Patients with a short REM1 (<3 years) had a short survival period, irrespective of salvage therapy received; these patients have high unmet medical needs and are good candidates for investigation of novel therapies. In patients with a long REM1 (≥3 years), salvage treatment with either repeat FCR or lenalidomide-based therapy results in subsequent median survival exceeding 5 years; for these patients, FCR rechallenge represents a reasonable standard of care. © 2014 by The American Society of Hematology.

Fludarabine Melphalan reduced-intensity conditioning allotransplanation provides similar disease control in lymphoid and myeloid malignancies: analysis of 344 patients.

PubMed

Bryant, A; Nivison-Smith, I; Pillai, E S; Kennedy, G; Kalff, A; Ritchie, D; George, B; Hertzberg, M; Patil, S; Spencer, A; Fay, K; Cannell, P; Berkahn, L; Doocey, R; Spearing, R; Moore, J

2014-01-01

This was an Australasian Bone Marrow Transplant Recipient Registry (ABMTRR)-based retrospective study assessing the outcome of Fludarabine Melphalan (FluMel) reduced-intensity conditioning between 1998 and 2008. Median follow-up was 3.4 years. There were 344 patients with a median age of 54 years (18-68). In all, 234 patients had myeloid malignancies, with AML (n=166) being the commonest indication. There were 110 lymphoid patients with non-hodgkins lymphoma (NHL) (n=64) the main indication. TRM at day 100 was 14% with no significant difference between the groups. OS and disease-free survival (DFS) were similar between myeloid and lymphoid patients (57 and 50% at 3 years, respectively). There was no difference in cumulative incidence of relapse or GVHD between groups. Multivariate analysis revealed four significant adverse risk factors for DFS: donor other than HLA-identical sibling donor, not in remission at transplant, previous autologous transplant and recipient CMV positive. Chronic GVHD was associated with improved DFS in multivariate analysis predominantly due to a marked reduction in relapse (HR:0.44, P=0.003). This study confirms that FluMel provides durable and equivalent remissions in both myeloid and lymphoid malignancies. Disease stage and chronic GVHD remain important determinants of outcome for FluMel allografting.

Channel Analysis for a 6.4 Gb s-1 DDR5 Data Buffer Receiver Front-End

NASA Astrophysics Data System (ADS)

Lehmann, Stefanie; Gerfers, Friedel

2017-09-01

In this contribution, the channel characteristic of the next generation DDR5-SDRAM architecture and possible approaches to overcome channel impairments are analysed. Because modern enterprise server applications and networks demand higher memory bandwidth, throughput and capacity, the DDR5-SDRAM specification is currently under development as a follow-up of DDR4-SDRAM technology. In this specification, the data rate is doubled to DDR5-6400 per IO as compared to the former DDR4-3200 architecture, resulting in a total per DIMM data rate of up to 409.6 Gb s-1. The single-ended multi-point-to-point CPU channel architecture in DDRX technology remains the same for DDR5 systems. At the specified target data rate, insertion loss, reflections, cross-talk as well as power supply noise become more severe and have to be considered. Using the data buffer receiver front-end of a load-reduced memory module, sophisticated equalisation techniques can be applied to ensure target BER at the increased data rate. In this work, the worst case CPU back-plane channel is analysed to derive requirements for receiver-side equalisation from the channel response characteristics. First, channel impairments such as inter-symbol-interference, reflections from the multi-point channel structure, and crosstalk from neighboring lines are analysed in detail. Based on these results, different correction methods for DDR5 data buffer front-ends are discussed. An architecture with 1-tap FFE in combination with a multi-tap DFE is proposed. Simulation of the architecture using a random input data stream is used to reveal the required DFE tap filter depth to effectively eliminate the dominant ISI and reflection based error components.

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

PubMed Central

Barrientos, Jacqueline C.; Barr, Paul M.; Flinn, Ian W.; Burger, Jan A.; Tran, Anh; Clow, Fong; James, Danelle F.; Graef, Thorsten; Friedberg, Jonathan W.; Rai, Kanti; O’Brien, Susan

2015-01-01

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135. PMID:25755291

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia.

PubMed

Brown, Jennifer R; Barrientos, Jacqueline C; Barr, Paul M; Flinn, Ian W; Burger, Jan A; Tran, Anh; Clow, Fong; James, Danelle F; Graef, Thorsten; Friedberg, Jonathan W; Rai, Kanti; O'Brien, Susan

2015-05-07

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135. © 2015 by The American Society of Hematology.

Flai (fludarabine, cytarabine, idarubicin) plus low-dose Gemtuzumab Ozogamicin as induction therapy in CD33-positive AML: Final results and long term outcome of a phase II multicenter clinical trial.

PubMed

Candoni, Anna; Papayannidis, Cristina; Martinelli, Giovanni; Simeone, Erica; Gottardi, Michele; Iacobucci, Ilaria; Gherlinzoni, Filippo; Visani, Giuseppe; Baccarani, Michele; Fanin, Renato

2018-05-01

The aim of this prospective clinical trial was to evaluate the efficacy and safety of a combination of Gemtuzumab-Ozogamicin (GO) and FLAI scheme (fludarabine, cytarabine, idarubicin) as a first-line therapy in CD33 positive AML. We treated 130 patients, aged <65, with a median age of 52 years. FLAI-GO induction regimen included fludarabine (30 mg/sqm) and cytarabine (2 g/sqm) on days 1-5; idarubicin (10 mg/sqm) on days 1, 3, and 5; and GO (3 mg/sqm) on day 6. SCT was planned for all high-risk AML patients, after consolidation with intermediate doses of cytarabine and idarubicin and a high dose of cytarabine. CD33 expression exceeded 20% in all cases. Primary endpoints of the study included feasibility, overall response rate (ORR) and toxicity. Secondary endpoints included the evaluation of MRD by WT1 expression, feasibility and outcome of consolidation with SCT, overall survival (OS) and disease-free survival (DFS). After induction with FLAI-GO, complete remission (CR) rate was 82%. Four patients achieved partial remission (PR) and 12% were resistant (ORR 85%); death during induction (DDI) was 3%. The hematological and extra hematological toxicity of FLAI-GO was manageable; 45% of patients experienced transient and reversible GO infusion related adverse events. In the setting of patients who achieved a cytological CR after FLAI-GO, the mean of WT1 copies dropped from 8337±9936 copies/10 4 ABL (diagnosis) to 182 ± 436 copies after induction therapy (p = 0.0001) showing a very good disease debulking. After a median follow-up of 54 months, 67/130 (52%) patients were alive. The probability of 1, 2, and 5-year OS was 80%, 63%, and 52%, respectively. The probability of 1, 2, and 5-year DFS was 77%, 58%, and 52%, respectively. Allogeneic and autologous SCT was performed in 60 (46%) and 23 (18%) patients, respectively. In summary, the final results of this trial confirm that FLAI-GO is an active and safe treatment strategy for CD33-positive AML patients aged ≤ 65 years, allowing a high ORR, a good disease debulking, favorable safety profile, low DDI, and subsequent high SCT rate. The encouraging results of this trial, consolidated by a long follow-up, support the reintroduction of GO in clinical practice. © 2018 Wiley Periodicals, Inc.

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

PubMed Central

van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

2016-01-01

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II–IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID:26869630

Real-time dangling objects sensing: A preliminary design of mobile headset ancillary device for visual impaired.

PubMed

Lin, C H; Cheng, P H; Shen, S T

2014-01-01

Blinds and severe visual impairments can utilize tactile sticks to assist their walking. However, they cannot fully understand the dangling objects in front of their walking routes. This research proposed a mobile real-time dangling objects sensing (RDOS) prototype, which is located on the cap to sense any front barrier. This device utilized cheap ultrasonic sensor to act as another complement eye for blinds to understand the front dangling objects. Meanwhile, the RDOS device can dynamically adjust the sensor's front angle that is depended on the user's body height and promote the sensing accuracy. Meanwhile, two major required algorithms, height-angle measurement and ultrasonic sensor alignment, are proposed with this prototype. The research team also integrated the RDOS device prototype with mobile Android devices by communicating with Bluetooth to record the walking route.

Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

ClinicalTrials.gov

2017-10-25

Acute Myeloid Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Malignant Lymphoma; Hodgkin's Disease; Multiple Myeloma; Lymphocytic Leukemia; Myeloproliferative Disorder; Polycythemia Vera; Myelofibrosis; Aplastic Anemia

Concurrent classical Hodgkin lymphoma and plasmablastic lymphoma in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with fludarabine: a dimorphic presentation of iatrogenic immunodeficiency-associated lymphoproliferative disorder with evidence suggestive of multiclonal transformability of B cells by Epstein-Barr virus.

PubMed

Foo, Wen-Chi; Huang, Qin; Sebastian, Siby; Hutchinson, Charles B; Burchette, Jim; Wang, Endi

2010-12-01

A small fraction of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma develop Epstein-Barr virus-positive B-cell lymphoproliferative disorders. These Epstein-Barr virus-B-cell lymphoproliferative disorders are thought to be related to immune suppression induced by fludarabine/other chemotherapeutic regimens. As in other immunodeficiency-associated lymphoproliferative disorders, these disorders demonstrate a heterogeneous histological spectrum that ranges from polymorphic to monomorphic to classical Hodgkin lymphoma-like lesions. We report a case of concurrent classical Hodgkin lymphoma and plasmablastic lymphoma in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with fludarabine. Both classical Hodgkin lymphoma and plasmablastic lymphoma were positive for Epstein-Barr virus-encoded RNA, whereas classical Hodgkin lymphoma was also positive for Epstein-Barr virus- latent membrane protein 1, suggesting a different viral latency. Immunoglobulin gene rearrangement studies demonstrated distinct clones in the plasmablastic lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. These findings suggest biclonal secondary lymphomas associated with iatrogenic immunodeficiency. Epstein-Barr virus-B-cell lymphoproliferative disorders in the setting of chronic lymphocytic leukemia/small lymphocytic lymphoma, in particular those arising after chemotherapy, should be separated from true Richter's transformation, and be categorized as (iatrogenic) immunodeficiency-associated lymphoproliferative disorder. Copyright © 2010 Elsevier Inc. All rights reserved.

Matrix metalloproteinase-9 is involved in chronic lymphocytic leukemia cell response to fludarabine and arsenic trioxide.

PubMed

Amigo-Jiménez, Irene; Bailón, Elvira; Ugarte-Berzal, Estefanía; Aguilera-Montilla, Noemí; García-Marco, José A; García-Pardo, Angeles

2014-01-01

Matrix metalloproteinase-9 (MMP-9) contributes to chronic lymphocytic leukemia (CLL) pathology by regulating cell migration and preventing spontaneous apoptosis. It is not known if MMP-9 is involved in CLL cell response to chemotherapy and we address this in the present study, using arsenic trioxide (ATO) and fludarabine as examples of cytotoxic drugs. We used primary cells from the peripheral blood of CLL patients and MEC-1 cells stably transfected with an empty vector or a vector containing MMP-9. The effect of ATO and fludarabine was determined by flow cytometry and by the MTT assay. Expression of mRNA was measured by RT-PCR and qPCR. Secreted and cell-bound MMP-9 was analyzed by gelatin zymography and flow cytometry, respectively. Protein expression was analyzed by Western blotting and immunoprecipitation. Statistical analyses were performed using the two-tailed Student's t-test. In response to ATO or fludarabine, CLL cells transcriptionally upregulated MMP-9, preceding the onset of apoptosis. Upregulated MMP-9 primarily localized to the membrane of early apoptotic cells and blocking apoptosis with Z-VAD prevented MMP-9 upregulation, thus linking MMP-9 to the apoptotic process. Culturing CLL cells on MMP-9 or stromal cells induced drug resistance, which was overcome by anti-MMP-9 antibodies. Accordingly, MMP-9-MEC-1 transfectants showed higher viability upon drug treatment than Mock-MEC-1 cells, and this effect was blocked by silencing MMP-9 with specific siRNAs. Following drug exposure, expression of anti-apoptotic proteins (Mcl-1, Bcl-xL, Bcl-2) and the Mcl-1/Bim, Mcl-1/Noxa, Bcl-2/Bax ratios were higher in MMP-9-cells than in Mock-cells. Similar results were obtained upon culturing primary CLL cells on MMP-9. Our study describes for the first time that MMP-9 induces drug resistance by modulating proteins of the Bcl-2 family and upregulating the corresponding anti-apoptotic/pro-apoptotic ratios. This is a novel role for MMP-9 contributing to CLL progression. Targeting MMP-9 in combined therapies may thus improve CLL response to treatment.

Matrix Metalloproteinase-9 Is Involved in Chronic Lymphocytic Leukemia Cell Response to Fludarabine and Arsenic Trioxide

PubMed Central

Amigo-Jiménez, Irene; Bailón, Elvira; Ugarte-Berzal, Estefanía; Aguilera-Montilla, Noemí; García-Marco, José A.; García-Pardo, Angeles

2014-01-01

Background Matrix metalloproteinase-9 (MMP-9) contributes to chronic lymphocytic leukemia (CLL) pathology by regulating cell migration and preventing spontaneous apoptosis. It is not known if MMP-9 is involved in CLL cell response to chemotherapy and we address this in the present study, using arsenic trioxide (ATO) and fludarabine as examples of cytotoxic drugs. Methods We used primary cells from the peripheral blood of CLL patients and MEC-1 cells stably transfected with an empty vector or a vector containing MMP-9. The effect of ATO and fludarabine was determined by flow cytometry and by the MTT assay. Expression of mRNA was measured by RT-PCR and qPCR. Secreted and cell-bound MMP-9 was analyzed by gelatin zymography and flow cytometry, respectively. Protein expression was analyzed by Western blotting and immunoprecipitation. Statistical analyses were performed using the two-tailed Student's t-test. Results In response to ATO or fludarabine, CLL cells transcriptionally upregulated MMP-9, preceding the onset of apoptosis. Upregulated MMP-9 primarily localized to the membrane of early apoptotic cells and blocking apoptosis with Z-VAD prevented MMP-9 upregulation, thus linking MMP-9 to the apoptotic process. Culturing CLL cells on MMP-9 or stromal cells induced drug resistance, which was overcome by anti-MMP-9 antibodies. Accordingly, MMP-9-MEC-1 transfectants showed higher viability upon drug treatment than Mock-MEC-1 cells, and this effect was blocked by silencing MMP-9 with specific siRNAs. Following drug exposure, expression of anti-apoptotic proteins (Mcl-1, Bcl-xL, Bcl-2) and the Mcl-1/Bim, Mcl-1/Noxa, Bcl-2/Bax ratios were higher in MMP-9-cells than in Mock-cells. Similar results were obtained upon culturing primary CLL cells on MMP-9. Conclusions Our study describes for the first time that MMP-9 induces drug resistance by modulating proteins of the Bcl-2 family and upregulating the corresponding anti-apoptotic/pro-apoptotic ratios. This is a novel role for MMP-9 contributing to CLL progression. Targeting MMP-9 in combined therapies may thus improve CLL response to treatment. PMID:24956101

Intracyclic velocity variation and arm coordination assessment in swimmers with Down syndrome.

PubMed

Marques-Aleixo, Inês; Querido, Ana; Figueiredo, Pedro; Vilas-Boas, João Paulo; Corredeira, Rui; Daly, Daniel; Fernandes, Ricardo J

2013-01-01

This study examined the differences in intracycle velocity variation and arm coordination in front crawl in swimmers with Down syndrome in three breathing conditions. International swimmers with Down syndrome (N = 16) performed 3 × 20 m front crawl at 50 m race speed: without breathing, breathing to the preferred side, and breathing to the nonpreferred side. A two dimensional video movement analysis was performed using the APASystem. Breathing conditions were compared using Repeated Measures ANOVA. Swimming velocity was higher without breathing and intracyclic velocity variation was higher while breathing. Swimmers tended to a catch up arm coordination mode for both breathing conditions and a superposition mode when not breathing. These data reflect arm coordination compromising swimming performance, particularly when comparing with non disabled swimmers in literature. The physical and perhaps cognitive impairment associated with Down syndrome may result in a disadvantage in both propulsion and drag, more evident when breathing.

Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT

ClinicalTrials.gov

2009-01-22

Chronic Myeloid Leukemia; Acute Myelogenous Leukemia; Myelodysplasia; Acute Lymphocytic Leukemia; Severe Aplastic Anemia; Non-Hodgkin's Lymphoma; Lymphoproliferative Disease; Multiple Myeloma; Advanced Myeloproliferative Disease

Fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) combination therapy for elderly acute myeloid leukemia patients.

PubMed

Kim, Inho; Koh, Youngil; Yoon, Sung-Soo; Park, Seonyang; Kim, Byoung Kook; Kim, Dae-Young; Lee, Jung-Hee; Lee, Kyoo-Hyung; Cheong, June-Won; Lee, Hong-Kee; Kim, Sung-Hyun; Kim, Hyuk; Joo, Young Don; Lee, Sang-Min; Won, Jong-Ho; Park, Sung-Kyu; Hong, Dae-Sik; Kim, Se-Hyung; Sohn, Sang Kyun; Kim, Chul-Soo; Park, Eunkyung; Kim, Min Kyoung; Park, Moo Rim; Lee, Je-Hwan; Min, Yoo Hong

2013-01-01

We performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in elderly acute myeloid leukemia (AML) patients. Elderly (≥60 years) AML patients who had not previously received chemotherapy were enrolled in the study. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen comprised fludarabine (25 mg/m(2) , days 1-4), cytarabine (1,000 mg/m(2) , days 1-4), and attenuated-dose idarubicin (5 mg/m(2) , days 1-3). The primary end point was complete remission (CR) rate. Secondary end points were overall survival (OS), event-free survival (EFS), and treatment-related mortality (TRM). There were 108 patients (median age 68.4 years, M:F = 64:44) enrolled in the study. CR was achieved in 56.5% of patients, and the TRM rate was 21.3%. Median OS and median EFS were 10.2 and 6.6 months, respectively. The mortality at 30 and 60 days was 15 and 21%, respectively. Performance status and comorbidity did not have prognostic value in this patient cohort. Bone marrow expression of CD117 was associated with increased EFS and OS. m-FLAI is an effective induction regimen for previously untreated AML in elderly patients. In addition, bone-marrow CD117 expression is an independent favorable prognostic factor in elderly AML patients. (ClinicalTrials.gov number, NCT01247493). Copyright © 2012 Wiley Periodicals, Inc.

Fludarabine and rituximab with escalating doses of lenalidomide followed by lenalidomide/rituximab maintenance in previously untreated chronic lymphocytic leukaemia (CLL): the REVLIRIT CLL-5 AGMT phase I/II study.

PubMed

Egle, Alexander; Steurer, Michael; Melchardt, Thomas; Weiss, Lukas; Gassner, Franz Josef; Zaborsky, Nadja; Geisberger, Roland; Catakovic, Kemal; Hartmann, Tanja Nicole; Pleyer, Lisa; Voskova, Daniela; Thaler, Josef; Lang, Alois; Girschikofsky, Michael; Petzer, Andreas; Greil, Richard

2018-06-04

Despite recent advances, chemoimmunotherapy remains a standard for fit previously untreated chronic lymphocytic leukaemia patients. Lenalidomide had activity in early monotherapy trials, but tumour lysis and flare proved major obstacles in its development. We combined lenalidomide in increasing doses with six cycles of fludarabine and rituximab (FR), followed by lenalidomide/rituximab maintenance. In 45 chemo-naive patients, included in this trial, individual tolerability of the combination was highly divergent and no systematic toxicity determining a maximum tolerated dose was found. Grade 3/4 neutropenia (71%) was high, but only 7% experienced grade 3 infections. No tumour lysis or flare > grade 2 was observed, but skin toxicity proved dose-limiting in nine patients (20%). Overall and complete response rates after induction were 89 and 44% by intention-to-treat, respectively. At a median follow-up of 78.7 months, median progression-free survival (PFS) was 60.3 months. Minimal residual disease and immunoglobulin variable region heavy chain mutation state predicted PFS and TP53 mutation most strongly predicted OS. Baseline clinical factors did not predict tolerance to the immunomodulatory drug lenalidomide, but pretreatment immunophenotypes of T cells showed exhausted memory CD4 cells to predict early dose-limiting non-haematologic events. Overall, combining lenalidomide with FR was feasible and effective, but individual changes in the immune system seemed associated with limiting side effects. clinicaltrials.gov (NCT00738829) and EU Clinical Trials Register ( www.clinicaltrialsregister.eu , 2008-001430-27).

Late-onset Pneumocystis jirovecii pneumonia post-fludarabine, cyclophosphamide and rituximab: implications for prophylaxis.

PubMed

Haeusler, Gabrielle M; Slavin, Monica A; Seymour, John F; Lingaratnam, Senthil; Teh, Benjamin W; Tam, Constantine S; Thursky, Karin A; Worth, Leon J

2013-08-01

Fludarabine, cyclophosphamide and rituximab (FCR) therapy for lymphoid malignancies has historically been associated with a low reported incidence of Pneumocystis jirovecii pneumonia (PJP). However, prophylaxis was routinely used in early studies, and molecular diagnostic tools were not employed. The objective of this study was to review the incidence of PJP during and post-FCR in the era of highly sensitive molecular diagnostics and (18) F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computerised tomography (CT). All patients treated with standard FCR at the Peter MacCallum Cancer Centre (March 2009 to June 2012) were identified from a medications management database. Laboratory-confirmed PJP cases during this time were identified from an electronic database. Overall, 66 patients were treated with a median of 5.5 FCR cycles. Eight PJP cases were identified, 6 of whom had received chemotherapy prior to FCR. In 5 cases, (18) F-FDG PET demonstrated bilateral ground-glass infiltrates. Median CD4(+) lymphocyte counts at time of PJP diagnosis and 9-12 months following FCR were 123 and 400 cells/μL, respectively. In patients receiving no prophylaxis, 9.1% developed PJP during FCR. The rate following FCR was 18.4%, with median onset at 6 months (2.4-24 months). Given the high rate of late-onset PJP, consideration should be given for extended PJP prophylaxis for up to 12 months post-FCR, particularly in pretreated patients. Further evaluation of the role of CD4(+) monitoring is warranted to quantify risk of disease development and to guide duration of prophylaxis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Busulfan, Fludarabine, Donor Stem Cell Transplant, and Cyclophosphamide in Treating Patients With Multiple Myeloma or Myelofibrosis

ClinicalTrials.gov

2018-01-31

Anemia; ASXL1 Gene Mutation; EZH2 Gene Mutation; IDH1 Gene Mutation; IDH2 Gene Mutation; Plasma Cell Myeloma; Primary Myelofibrosis; Recurrent Plasma Cell Myeloma; Secondary Myelofibrosis; Thrombocytopenia

Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2013-09-27

B-cell Chronic Lymphocytic Leukemia; Leukemia; Prolymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

PubMed

Abuelgasim, Khadega A; Rehan, Hinna; Alsubaie, Maha; Al Atwi, Nasser; Al Balwi, Mohammed; Alshieban, Saeed; Almughairi, Areej

2018-03-11

Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases. Here, we describe the first reported case of concurrent chronic myeloid leukemia and diffuse large B-cell lymphoma in a background of chronic lymphocytic leukemia. A 60-year-old Saudi man known to have diabetes, hypertension, and chronic active hepatitis B was diagnosed as having Rai stage II chronic lymphocytic leukemia, with trisomy 12 and rearrangement of the CCND1 gene in December 2012. He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission. One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. Fluorescence in situ hybridization from bone marrow aspirate was positive for translocation (9;22) and reverse transcription polymerase chain reaction detected BCR-ABL fusion gene consistent with chronic myeloid leukemia. He had no morphologic or immunophenotypic evidence of chronic lymphocytic leukemia at the time. Imatinib, a first-line tyrosine kinase inhibitor, was started. Eight months later, a screening imaging revealed new liver lesions, which were confirmed to be diffuse large B-cell lymphoma. In chronic lymphocytic leukemia, progressive leukocytosis and splenomegaly caused by emerging chronic myeloid leukemia can be easily overlooked. It is unlikely that chronic myeloid leukemia arose as a result of clonal evolution secondary to fludarabine treatment given the very short interval after receiving fludarabine. It is also unlikely that imatinib contributed to the development of diffuse large B-cell lymphoma; rather, diffuse large B-cell lymphoma arose as a result of Richter's transformation. Fludarabine, trisomy 12, and CCND1 gene rearrangement might have increased the risk of Richter's transformation in this patient.

The changing paradigm of chronic lymphocytic leukemia management.

PubMed

Lobetti-Bodoni, Chiara; Bertoni, Francesco; Stussi, Georg; Cavalli, Franco; Zucca, Emanuele

2013-07-01

B cell-chronic lymphocytic leukemia (CLL), the commonest adult leukemia in western world, is today most often diagnosed at early-stage, following the accidental detection of lymphocytosis during a routine blood analysis. Moreover, the expectations of CLL patients have dramatically changed in the past decade and for the first time a significant overall survival improvement has been demonstrated in the disease--at least in the younger and fit patients--with the use of the FCR regimen, which combines rituximab fludarabine and cyclophosphamide. New drugs and new regimens are currently being developed for the relapsed patients and for those too old or too frail to receive aggressive treatments. Some of these promising compounds will likely be part of the future front-line treatments. Additionally, the increasing knowledge on the molecular features that predict the clinical outcome may soon result in a molecular classification of the disease. These acquisitions are producing a migration from palliative care to a curative and individually-tailored approach. In this review we tried to summarize the advances achieved in the past decade and help the specialists in internal medicine and the general practitioners to understand the completely changed scenario in which the disease should nowadays be managed. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Waldenstrom macroglobulinemia: prognosis and management

PubMed Central

Oza, A; Rajkumar, S V

2015-01-01

Waldenstrom macroglobulinemia (WM) is a B-cell lymphoplasmacytic lymphoma characterized by monoclonal immunoglobulin M protein in the serum and infiltration of bone marrow with lymphoplasmacytic cells. Asymptomatic patients can be observed without therapy. First-line therapy should consist of the monoclonal anti-CD20 antibody, rituximab, given typically in combination with other agents. We prefer dexamethasone, rituximab, cyclophosphamide (DRC) as initial therapy for most patients with symptomatic WM. Other reasonable options are bortezomib, rituximab, dexamethasone (BoRD) or bendamustine plus rituximab (BR). All of these regimens are associated with excellent response and tolerability. Initial therapy is usually administered for 6 months, followed by observation. Response to therapy is assessed using the standard response criteria developed by the International Working Group on Waldenstrom macroglobulinemia. Relapse is almost inevitable in WM but may occur years after initial therapy. In symptomatic patients relapsing more than 1–2 years after initial therapy, the original treatment can be repeated. For relapse occurring sooner, an alternative regimen is used. In select patients, high-dose chemotherapy followed by autologous hematopoietic cell transplantation may be an option at relapse. Options for therapy of relapsed WM besides regimens used in the front-line setting include ibrutinib, purine nucleoside analogs (cladribine, fludarabine), carfilzomib and immunomodulatory agents (thalidomide, lenalidomide). PMID:25815903

Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

ClinicalTrials.gov

2017-12-05

B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

Downregulation of deoxycytidine kinase in cytarabine-resistant mantle cell lymphoma cells confers cross-resistance to nucleoside analogs gemcitabine, fludarabine and cladribine, but not to other classes of anti-lymphoma agents

PubMed Central

2014-01-01

Background Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin lymphoma associated with poor prognosis. Implementation of high-dose cytarabine (araC) into induction therapy became standard-of-care for all newly diagnosed younger MCL patients. However, many patients relapse even after araC-based regimen. Molecular mechanisms responsible for araC resistance in MCL are unknown and optimal treatment strategy for relapsed/refractory MCL patients remains elusive. Methods Five araC-resistant (R) clones were derived by long-term culture of five MCL cell lines (CTRL) with increasing doses of araC up to 50 microM. Illumina BeadChip and 2-DE proteomic analysis were used to identify gene and protein expression changes associated with araC resistance in MCL. In vitro cytotoxicity assays and experimental therapy of MCL xenografts in immunodeficient mice were used to analyze their relative responsiveness to a set of clinically used anti-MCL drugs. Primary MCL samples were obtained from patients at diagnosis and after failure of araC-based therapies. Results Marked downregulation of deoxycytidine-kinase (DCK) mRNA and protein expression was identified as the single most important molecular event associated with araC-resistance in all tested MCL cell lines and in 50% primary MCL samples. All R clones were highly (20-1000x) cross-resistant to all tested nucleoside analogs including gemcitabine, fludarabine and cladribine. In vitro sensitivity of R clones to other classes of clinically used anti-MCL agents including genotoxic drugs (cisplatin, doxorubicin, bendamustine) and targeted agents (bortezomib, temsirolimus, rituximab) remained unaffected, or was even increased (ibrutinib). Experimental therapy of immunodeficient mice confirmed the anticipated loss of anti-tumor activity (as determined by overall survival) of the nucleoside analogs gemcitabine and fludarabine in mice transplanted with R clone compared to mice transplanted with CTRL cells, while the anti-tumor activity of cisplatin, temsirolimus, bortezomib, bendamustine, cyclophosphamide and rituximab remained comparable between the two cohorts. Conclusions Acquired resistance of MCL cells to araC is associated with downregulation of DCK, enzyme of the nucleotide salvage pathway responsible for the first phosphorylation (=activation) of most nucleoside analogs used in anti-cancer therapy. The data suggest that nucleoside analogs should not be used in the therapy of MCL patients, who relapse after failure of araC-based therapies. PMID:24972933

Tacrolimus and mycophenolate mofetil after nonmyeloablative matched-sibling donor allogeneic stem-cell transplantations conditioned with fludarabine and low-dose total body irradiation.

PubMed

Nieto, Yago; Patton, Nigel; Hawkins, Timothy; Spearing, Ruth; Bearman, Scott I; Jones, Roy B; Shpall, Elizabeth J; Rabinovitch, Rachel; Zeng, Chan; Barón, Anna; McSweeney, Peter A

2006-02-01

We evaluated tacrolimus/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after a nonmyeloablative stem cell transplantation (NST) from a matched sibling donor (MSD). Thirty-two patients (median age, 57 years) with advanced hematologic malignancies, who were poor candidates for a conventional myeloablative transplantation, received fludarabine (30 mg/m(2), day -4 to day -2), total-body irradiation (TBI) (200 cGy, day 0), infusion of donor peripheral blood progenitor cells (day 0), oral tacrolimus 0.06 mg/kg twice daily (from day 3), and oral MMF at 15 mg/kg twice daily (days 0-+27). Tacrolimus was tapered from day +100 to day +180 in those patients with indolent malignancies (n = 25), and from day +35 to day +56 in those with aggressive tumors (n = 7). Regimen toxicities and myelosuppression were mild, allowing 75% of patients to have entirely outpatient transplantations. One patient (3%) experienced a nonfatal graft rejection. Rates of grades II-IV and III-IV acute GVHD were 15.6% and 3%, respectively. Acute GVHD was diagnosed at median day +78 (range, days +31-+84). Extensive chronic GVHD was observed in 10 of 24 evaluable patients (41.6%) at a median onset of day +198 (range, days +128-+277), either spontaneously (n = 5) or elicited after tumor progression (n = 5). Five patients experienced transplantation-related mortality (TRM) (15.6%) from either acute GVHD-related multiorgan failure (MOF) (n = 3) or infectious complications (n = 2). At median follow-up of 19 months (range, 2-41 months), the overall survival, progression-free survival, and disease-free survival rates are 62.5%, 50%, and 40%, respectively. In conclusion, the use of tacrolimus/MMF after MSD NST is associated with encouraging rates of GVHD control.

National Institutes of Health classification for chronic graft-versus-host disease predicts outcome of allo-hematopoietic stem cell transplant after fludarabine-busulfan-antithymocyte globulin conditioning regimen.

PubMed

Saillard, Colombe; Crocchiolo, Roberto; Furst, Sabine; El-Cheikh, Jean; Castagna, Luca; Signori, Alessio; Oudin, Claire; Faucher, Catherine; Lemarie, Claude; Chabannon, Christian; Granata, Angela; Blaise, Didier

2014-05-01

Abstract In 2005, the National Institutes of Health (NIH) proposed standard criteria for diagnosis, organ scoring and global assessment of chronic graft-versus-host disease (cGvHD) severity. We retrospectively reclassified cGvHD with NIH criteria in a monocentric cohort of 130 consecutive adult patients with hematological malignancies presenting cGvHD after receiving allo-hematopoietic stem cell transplant (HSCT) with a fludarabine-busulfan-antithymocyte globulin (ATG) conditioning regimen, among 313 consecutive HSCT recipients. We compared NIH and Seattle classifications to correlate severity and outcome. The follow up range was effectively 2-120 months. Forty-four percent developed Seattle-defined cGvHD (22% limited, 78% extensive forms). Using NIH criteria, there were 23%, 40% and 37% mild, moderate and severe forms, respectively, and 58%, 32% and 8% classic cGvHD, late acute GvHD and overlap syndrome. Five-year overall survival was 55% (49-61), and cumulative incidences of non-relapse mortality (NRM) and relapse/progression at 2 years were 19% (14-23) and 19% (14-24). NIH mild and moderate forms were associated with better survival compared to severe cGvHD (hazard ratio [HR] = 3.28, 95% confidence interval [CI]: 1.38-7.82, p = 0.007), due to higher NRM among patients with severe cGvHD (HR = 3.04, 95% CI: 1.05-8.78, p = 0.04) but comparable relapse risk (p = NS). In conclusion, the NIH classification appears to be more accurate in predicting outcome mostly by the reclassification of old-defined extensive forms into NIH-defined moderate or severe.

Radiosensitization by inhibiting STAT1 in renal cell carcinoma.

PubMed

Hui, Zhouguang; Tretiakova, Maria; Zhang, Zhongfa; Li, Yan; Wang, Xiaozhen; Zhu, Julie Xiaohong; Gao, Yuanhong; Mai, Weiyuan; Furge, Kyle; Qian, Chao-Nan; Amato, Robert; Butler, E Brian; Teh, Bin Tean; Teh, Bin S

2009-01-01

Renal cell carcinoma (RCC) has been historically regarded as a radioresistant malignancy, but the molecular mechanism underlying its radioresistance is not understood. This study investigated the role of signal transducer and activator of transcription 1 (STAT1), a transcription factor downstream of the interferon-signaling pathway, in radioresistant RCC. The expressions of STAT1 and STAT3 in 164 human clear cell RCC samples, 47 papillary RCC samples, and 15 normal kidney tissue samples were examined by microarray expression profiling and immunohistochemistry. Western blotting was performed to evaluate the total and phosphorylated STAT1 expression in CRL-1932 (786-O) (human clear cell RCC), SKRC-39 (human papillary RCC), CCL-116 (human fibroblast), and CRL-1441 (G-401) (human Wilms tumor). STAT1 was reduced or inhibited by fludarabine and siRNA, respectively, and the effects on radiation-induced cell death were investigated using clonogenic assays. STAT1 expression, but not STAT3 expression, was significantly greater in human RCC samples (p = 1.5 x 10(-8) for clear cell; and p = 3.6 x 10(-4) for papillary). Similarly, the expression of STAT1 was relatively greater in the two RCC cell lines. STAT1 expression was reduced by both fludarabine and siRNA, significantly increasing the radiosensitivity in both RCC cell lines. This is the first study reporting the overexpression of STAT1 in human clear cell and papillary RCC tissues. Radiosensitization in RCC cell lines was observed by a reduction or inhibition of STAT1 signaling, using fludarabine or siRNA. Our data suggest that STAT1 may play a key role in RCC radioresistance and manipulation of this pathway may enhance the efficacy of radiotherapy.

Quantitative real-time polymerase chain reaction for monitoring minimal residual disease in patients with advanced indolent lymphomas treated with rituximab, fludarabine, mitoxantrone, and dexamethasone.

PubMed

Sarris, Andreas H; Jiang, Yunfang; Tsimberidou, Apostolia M; Thomaides, Athanasios; Rassidakis, George Z; Ford, Richard J; Medeiros, L Jeffrey; Cabanillas, Fernando; McLaughlin, Peter

2002-02-01

Fludarabine and rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) are active against indolent lymphomas. We have previously shown the safety and efficacy of the combination of FND (fludarabine/mitoxantrone/dexamethasone) in relapsed and subsequently untreated patients with stage IV indolent lymphomas. Currently, we treat patients with stage IV indolent lymphomas who are previously untreated, younger than 60 years, human immunodeficiency virus-negative, and have adequate organ and marrow function with FND and random assignment to concurrent or delayed administration of rituximab. We have developed a quantitative real-time polymerase chain reaction assay for t(14;18). With 1 μg of DNA, this assay detects 0.6 copies in 55% of reactions, as expected for the Poisson distribution. When 1μg of DNA was analyzed in duplicate, cells with the t(14;18) were detected in peripheral blood of 22% of 152 volunteer blood donors. Quantitation showed that numbers of t(14;18) cells were higher than the statistical upper normal limit (mean of all volunteer values plus standard deviations) in 2% of volunteer blood donors. By contrast, 36% of blood or marrow specimens from follicular lymphoma patients were positive, and the number of cells with t(14;18) was higher than the normal upper limit in 26%. The presence of cells with t(14;18) and their numbers are prospectively quantitated in blood and marrow of patients treated with FND plus rituximab to determine their clinical significance both at presentation and during therapy. Semin Oncol 29 (suppl 2):48-55. Copyright © 2002 by W.B. Saunders Company. Copyright © 2002 W.B. Saunders Company. All rights reserved.

Gain-of-function STAT1 mutations impair STAT3 activity in patients with chronic mucocutaneous candidiasis (CMC).

PubMed

Zheng, Jie; van de Veerdonk, Frank L; Crossland, Katherine L; Smeekens, Sanne P; Chan, Chun M; Al Shehri, Tariq; Abinun, Mario; Gennery, Andrew R; Mann, Jelena; Lendrem, Dennis W; Netea, Mihai G; Rowan, Andrew D; Lilic, Desa

2015-10-01

Signal transducer and activator of transcription 3 (STAT3) triggered production of Th-17 cytokines mediates protective immunity against fungi. Mutations affecting the STAT3/interleukin 17 (IL-17) pathway cause selective susceptibility to fungal (Candida) infections, a hallmark of chronic mucocutaneous candidiasis (CMC). In patients with autosomal dominant CMC, we and others previously reported defective Th17 responses and underlying gain-of-function (GOF) STAT1 mutations, but how this affects STAT3 function leading to decreased IL-17 is unclear. We also assessed how GOF-STAT1 mutations affect STAT3 activation, DNA binding, gene expression, cytokine production, and epigenetic modifications. We excluded impaired STAT3 phosphorylation, nuclear translocation, and sequestration of STAT3 into STAT1/STAT3 heterodimers and confirm significantly reduced transcription of STAT3-inducible genes (RORC/IL-17/IL-22/IL-10/c-Fos/SOCS3/c-Myc) as likely underlying mechanism. STAT binding to the high affinity sis-inducible element was intact but binding to an endogenous STAT3 DNA target was impaired. Reduced STAT3-dependent gene transcription was reversed by inhibiting STAT1 activation with fludarabine or enhancing histone, but not STAT1 or STAT3 acetylation with histone deacetylase (HDAC) inhibitors trichostatin A or ITF2357. Silencing HDAC1, HDAC2, and HDAC3 indicated a role for HDAC1 and 2. Reduced STAT3-dependent gene transcription underlies low Th-17 responses in GOF-STAT1 CMC, which can be reversed by inhibiting acetylation, offering novel targets for future therapies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Total Marrow and Lymphoid Irradiation, Fludarabine, and Melphalan Before Donor Stem Cell Transplant in Treating Participants With High-Risk Acute Leukemia or Myelodysplastic Syndrome

ClinicalTrials.gov

2018-06-01

Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia; Acute Myeloid Leukemia in Remission; Hematopoietic Cell Transplantation Recipient; Minimal Residual Disease; Myelodysplastic Syndrome; Secondary Acute Myeloid Leukemia

Busulfan, Fludarabine, and Thiotepa Conditioning Regimen for Non Malignant Disease

ClinicalTrials.gov

2018-06-20

Bone Marrow Failure Syndrome; Thalassemia; Sickle Cell Disease; Diamond Blackfan Anemia; Acquired Neutropenia in Newborn; Acquired Anemia Hemolytic; Acquired Thrombocytopenia; Hemophagocytic Lymphohistiocytoses; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Common Variable Immunodeficiency; X-linked Lymphoproliferative Disease; Severe Combined Immunodeficiency; Hurler Syndrome; Mannosidosis; Adrenoleukodystrophy

Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

PubMed

Aisa, Yoshinobu; Mori, Takehiko; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Yokoyama, Akihiro; Ikeda, Yasuo; Okamoto, Shinichiro

2005-04-01

The purpose of this study was to evaluate the efficacy of oral cryotherapy to prevent high-dose melphalan-induced stomatitis. Eighteen consecutive recipients of allogeneic hematopoietic stem cell transplant conditioned with high-dose melphalan (140 mg/m2) in combination with fludarabine alone or with fludarabine and additional chemotherapy or radiation were enrolled. The severity of stomatitis was graded according to the National Cancer Institute Common Toxicity Criteria. Patients were kept on oral cryotherapy using ice chips and ice-cold water shortly before, during, and for additional 90 min after completion of melphalan administration. Only two of 18 patients (11.1%) developed grade 2 or 3 stomatitis while six of seven patients in the historical control developed it (85.7%; P=0.001). These results suggested that oral cryotherapy could effectively prevent stomatitis caused by high-dose melphalan, and we recommend that it should be incorporated into the conditioning regimen with high-dose melphalan.

Simple Smartphone-Based Guiding System for Visually Impaired People

PubMed Central

Lin, Bor-Shing; Lee, Cheng-Che; Chiang, Pei-Ying

2017-01-01

Visually impaired people are often unaware of dangers in front of them, even in familiar environments. Furthermore, in unfamiliar environments, such people require guidance to reduce the risk of colliding with obstacles. This study proposes a simple smartphone-based guiding system for solving the navigation problems for visually impaired people and achieving obstacle avoidance to enable visually impaired people to travel smoothly from a beginning point to a destination with greater awareness of their surroundings. In this study, a computer image recognition system and smartphone application were integrated to form a simple assisted guiding system. Two operating modes, online mode and offline mode, can be chosen depending on network availability. When the system begins to operate, the smartphone captures the scene in front of the user and sends the captured images to the backend server to be processed. The backend server uses the faster region convolutional neural network algorithm or the you only look once algorithm to recognize multiple obstacles in every image, and it subsequently sends the results back to the smartphone. The results of obstacle recognition in this study reached 60%, which is sufficient for assisting visually impaired people in realizing the types and locations of obstacles around them. PMID:28608811

Simple Smartphone-Based Guiding System for Visually Impaired People.

PubMed

Lin, Bor-Shing; Lee, Cheng-Che; Chiang, Pei-Ying

2017-06-13

Visually impaired people are often unaware of dangers in front of them, even in familiar environments. Furthermore, in unfamiliar environments, such people require guidance to reduce the risk of colliding with obstacles. This study proposes a simple smartphone-based guiding system for solving the navigation problems for visually impaired people and achieving obstacle avoidance to enable visually impaired people to travel smoothly from a beginning point to a destination with greater awareness of their surroundings. In this study, a computer image recognition system and smartphone application were integrated to form a simple assisted guiding system. Two operating modes, online mode and offline mode, can be chosen depending on network availability. When the system begins to operate, the smartphone captures the scene in front of the user and sends the captured images to the backend server to be processed. The backend server uses the faster region convolutional neural network algorithm or the you only look once algorithm to recognize multiple obstacles in every image, and it subsequently sends the results back to the smartphone. The results of obstacle recognition in this study reached 60%, which is sufficient for assisting visually impaired people in realizing the types and locations of obstacles around them.

Reduced-intensity versus reduced-toxicity myeloablative fludarabine/busulfan-based conditioning regimens for allografted non-Hodgkin lymphoma adult patients: a retrospective study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Le Bourgeois, A; Labopin, M; Blaise, D; Ceballos, P; Vigouroux, S; Peffault de Latour, R; Marçais, A; Bulabois, C E; Bay, J O; Chantepie, S; Deconinck, E; Daguindau, E; Contentin, N; Yakoub-Agha, I; Cornillon, J; Mercier, M; Turlure, P; Charbonnier, A; Rorhlich, P S; N'Guyen, S; Maillard, N; Marchand, T; Mohty, M; Chevallier, P

2017-09-01

Fludarabine/busulfan-based conditioning regimens are widely used to perform allogeneic stem-cell transplantation (allo-SCT) in high-risk non-Hodgkin lymphoma (NHL) patients. The impact of the dose intensity of busulfan on outcomes has not been reported yet. This was a retrospective with the aim to compare the outcomes of NHL patients who received before allo-SCT a fludarabine/busulfan conditioning regimen, either of reduced intensity (FB2, 2 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 277) or at a myeloablative reduced-toxicity dose (FB3/FB4, 3 or 4 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 101). In univariate analysis, the 2-year overall survival (FB2 66.5% versus 60.3%, P = 0.33), lymphoma-free survival (FB2 57.9% versus 49.8%, P = 0.26), and non-relapse mortality (FB2 19% versus 21.1%, P = 0.91) were similar between both groups. Cumulative incidence of grade III-IV acute graft versus host disease (GVHD) (FB2 11.2% versus 18%, P = 0.08), extensive chronic GVHD (FB2: 17.3% versus 10.7%, P = 0.18) and 2-year GVHD free-relapse free survival (FB2: 44.4% versus 42.8%, P = 0.38) were also comparable. In multivariate analysis there was a trend for a worse outcome using FB3/FB4 regimens (overall survival: HR 1.47, 95% CI: 0.96-2.24, P = 0.08; lymphoma-free survival: HR: 1.43, 95% CI: 0.99-2.06, P = 0.05; relapse incidence: HR 1.54; 95% CI: 0.96-2.48, P = 0.07). These results were confirmed using a propensity score-matching strategy. We conclude that reduced toxicity myeloablative conditioning with fludarabine/busulfan does not improve the outcomes compared with reduced-intensity conditioning in adults receiving allo-SCT for NHL. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia.

PubMed

Dretzke, J; Barton, P; Kaambwa, B; Connock, M; Uthman, O; Bayliss, S; Meads, C

2010-10-01

This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of rituximab with chemotherapy compared to chemotherapy only for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one open-label, ongoing, unpublished randomised controlled trial (RCT), REACH (Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia), conducted by the manufacturer, which compared rituximab with a fludarabine and cyclophosphamide combination (R-FC) to fludarabine and cyclophosphamide (FC) only. REACH was scheduled to run for 8 years; however, the data provided were immature, with a median observation time at the time of data analysis of 2.1 years. REACH provided evidence of prolonged progression free survival with R-FC compared to FC (10 months, investigators' data), but no evidence of an overall survival benefit with R-FC. Patients refractory to fludarabine and with prior rituximab exposure were excluded from REACH and no controlled studies were identified by the ERG for these patient groups. The ERG had concerns about the structure of the economic model submitted by the manufacturer, which did not allow improvement in quality of life from treatment while in a progressed state. The manufacturer's model further assumed a divergence in cumulative deaths between the R-FC and FC treatment arms from the outset, which did not accord with observed data from REACH. When the survival advantage was removed, the manufacturer's base-case incremental cost-effectiveness ratio (ICER) changed from 15,593 pounds to between 40,000 pounds and 42,000 pounds per quality-adjusted life-year (QALY). With no survival advantage, the ICER became sensitive to changes in utility. There was no good empirical evidence on the utility of CLL patients in different states. Allowing for the possibility of a survival advantage with rituximab (although not supported by current evidence), the ERG performed further modelling, which found that rituximab would be cost-effective at 20,000 pounds/QALY (30,000 pounds/QALY) if a reduction in survival advantage relative to the manufacturer's base case of 40% (80%) was assumed. The guidance issued by NICE in July 2010 as a result of the STA recommends rituximab with FC for people with relapsed or refractory chronic lymphocytic leukaemia, except when the condition is refractory to fludarabine or where there has been previous treatment with rituximab.

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

Vorinostat, Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2018-01-12

Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Alkylating agents for Waldenstrom's macroglobulinaemia.

PubMed

Yang, Kun; Tan, Jianlong; Wu, Taixiang

2009-01-21

Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal immunoglobulin. Uncertainty remains if alkylating agents, such as chlorambucil, melphalan or cyclophosphamide, are an effective form of management. To assess the effects and safety of the alkylating agents on Waldenstrom's macroglobulinaemia (WM). We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008), the Chinese Biomedical Base (1982 to 2008) and reference lists of articles.We also handsearched relevant conference proceedings from 1990 to 2008. Randomised controlled trials (RCTs) comparing alkylating agents given concomitantly with radiotherapy, splenectomy, plasmapheresis, stem-cell transplantation in patients with a confirmed diagnosis of WM. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. One trial involving 92 participants with pretreated/relapsed WM compared the effect of fludarabine versus the combination of cyclophosphamide (the alkylating agent), doxorubicin and prednisone (CAP). Compared to CAP, the Hazard ratio (HR) for deaths of treatment with fludarabine was estimated to be 1.04, with a standard error of 0.30 (95% CI 0.58 to 1.48) and it indicated that the mean difference of median survival time was -4.00 months, and 16.00 months for response duration. The relative risks (RR) of response rate was 2.80 (95% CI 1.10 to 7.12). There were no statistically difference in overall survival rate and median survival months, while on the basis of response rate and response duration, fludarabine seemed to be superior to CAP for pretreated/relapsed patients with macroglobulinaemia. Although alkylating agents have been used for decades they have never actually been tested in a proper randomised trial. This review demonstrated that there is currently no evidence to suggest that alkylating agents are effective in treating Waldenstrom's macroglobulinaemia.

Juan Ruiz De Alarcón: Impairment as Empowerment in Early Modern Spain

ERIC Educational Resources Information Center

Clark, Gloria Bodtorf

2016-01-01

Juan Ruiz de Alarcón, a seventeenth-century writer and native of New Spain, so excelled at the craft of writing "comedias" that he is recognized as one of the great writers of early modern Spain. In his personal life Ruiz de Alarcón struggled with a significant bodily impairment, a large hump on both his back and front, which made him…

Improvement of Head-Up Display Standards. Volume 5. Head Up Display ILS (Instrument Landing System) Accuracy Flight Tests.

DTIC Science & Technology

1987-09-01

amber system. The front canopy of the NT-33A is cov- ered with an amber plastic sheet; when the front seat pilot low- ers his blue visor, the...tigation of the effect of head-up display symbol dynamic response caracteristics on flying qualities; Task B was an investigation of symbol accuracy...An amber vinyl plastic sheet covered the in- side front half of the NT-33 canopy. Blue snap-on visors were pi ovided to the evaluation pilots. The

Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2018-03-26

Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; T-Cell Large Granular Lymphocyte Leukemia

Retrospective Comparison of Fludarabine in Combination With Intermediate-Dose Cytarabine Versus High-Dose Cytarabine As Consolidation Therapies for Acute Myeloid Leukemia

PubMed Central

Zhang, Wenjun; Ding, Yi; Wu, Hao; Chen, Yuhua; Lu, Huina; Chen, Chunying; Fu, Jianfei; Wang, Weiguang; Liang, Aibin; Zou, Shanhua

2014-01-01

Abstract This retrospective study compared efficacy and safety of fludarabine combined with intermediate-dose cytarabine (FA regimen) versus high-dose cytarabine (HiDAC regimen) as consolidation therapy in acute myeloid leukemia (AML) patients who achieved complete remission. Disease-free survival (DFS) and overall survival (OS) based on age (≥60, <60 years) and cytogenetics were evaluated from data between January 2005 and March 2013. Total 82 patients (FA, n = 45; HiDAC, n = 37; 14–65 years) were evaluated. Five-year DFS was 32.0% and 36.2% for FA and HiDAC groups, respectively (P = 0.729), and 5-year OS was 39.5% and 47.8% (P = 0.568), respectively. Among older patients (≥60 years), 3-year DFS was 26.0% for FA group and 12.5% for HiDAC group (P = 0.032), and 3-year OS was 34.6% and 12.5%, respectively (P = 0.026). In FA group, hematological toxicities were significantly lower. FA regimen was as effective as HiDAC regimen in patients with good/intermediate cytogenetics and significantly improved DFS and OS in older patients. PMID:25501050

Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

ClinicalTrials.gov

2017-04-07

Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Aggressive Non-Hodgkin Lymphoma; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Waldenstrom Macroglobulinemia

Genetics Home Reference: DNMT3A overgrowth syndrome

MedlinePlus

... eyes (narrowed palpebral fissures). Additionally, the upper front teeth are often larger than normal. Intellectual disability in DNMT3A overgrowth syndrome ranges from mild to severe. Individuals may have features of autism spectrum disorder , which are characterized by impaired communication ...

Radiation Is an Important Component of Multimodality Therapy for Pediatric Non-Pineal Supratentorial Primitive Neuroectodermal Tumors

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

McBride, Sean M.; Daganzo, Sally M.; Banerjee, Anuradha

Purpose: To review a historical cohort of pediatric patients with supratentorial primitive neuroectodermal tumors (sPNET), to clarify the role of radiation in the treatment of these tumors. Patients and Methods: Fifteen children aged <18 years with non-pineal sPNETs diagnosed between 1992 and 2006 were identified. Initial therapy consisted of surgical resection and chemotherapy in all patients and up-front radiotherapy (RT) in 5 patients. Five patients had RT at the time of progression, and 5 received no RT whatever. Kaplan-Meier estimates of overall survival were then calculated. Results: The median follow-up from diagnosis for all patients was 31 months (range, 0.5-165more » months) and for surviving patients was 49 months (range, 10-165). Of the 5 patients who received up-front RT, all were alive without evidence of disease at a median follow-up of 50 months (range, 25-165 months). Only 5 of the 10 patients who did not receive up-front RT were alive at last follow-up. There was a statistically significant difference in overall survival between the patient group that received up-front RT and the group that did not (p = 0.048). In addition, we found a trend toward a statistically significant improvement in overall survival for those patients who received gross total resections (p = 0.10). Conclusions: Up-front RT and gross total resection may confer a survival benefit in patients with sPNET. Local failure was the dominant pattern of recurrence. Efforts should be made to determine patients most likely to have local failure exclusively or as a first recurrence, in order to delay or eliminate craniospinal irradiation.« less

24 CFR 290.27 - Up-front grants and loans.

Code of Federal Regulations, 2010 CFR

2010-04-01

... URBAN DEVELOPMENT HUD-OWNED PROPERTIES DISPOSITION OF MULTIFAMILY PROJECTS AND SALE OF HUD-HELD...) Eligible projects. An up-front grant or loan can be made available in the sale of a HUD-owned multifamily... income in a competitive market to cover all operating expenses, meet after sale debt service requirements...

24 CFR 290.27 - Up-front grants and loans.

Code of Federal Regulations, 2011 CFR

2011-04-01

... may provide up-front grants and loans for rehabilitation, demolition, rebuilding and other related... determination that such a grant or loan, plus any additional project-based assistance made available, would be more cost-effective than the use of the maximum permissible project-based rental assistance alone. (b...

24 CFR 290.27 - Up-front grants and loans.

Code of Federal Regulations, 2014 CFR

2014-04-01

... URBAN DEVELOPMENT HUD-OWNED PROPERTIES DISPOSITION OF MULTIFAMILY PROJECTS AND SALE OF HUD-HELD MULTIFAMILY MORTGAGES Disposition of Multifamily Projects § 290.27 Up-front grants and loans. (a) General. HUD... development costs as part of the disposition of a multifamily housing project that is HUD-owned, upon making a...

24 CFR 290.27 - Up-front grants and loans.

Code of Federal Regulations, 2012 CFR

2012-04-01

... URBAN DEVELOPMENT HUD-OWNED PROPERTIES DISPOSITION OF MULTIFAMILY PROJECTS AND SALE OF HUD-HELD MULTIFAMILY MORTGAGES Disposition of Multifamily Projects § 290.27 Up-front grants and loans. (a) General. HUD... development costs as part of the disposition of a multifamily housing project that is HUD-owned, upon making a...

Traveling waves in a spatially-distributed Wilson-Cowan model of cortex: From fronts to pulses

NASA Astrophysics Data System (ADS)

Harris, Jeremy D.; Ermentrout, Bard

2018-04-01

Wave propagation in excitable media has been studied in various biological, chemical, and physical systems. Waves are among the most common evoked and spontaneous organized activity seen in cortical networks. In this paper, we study traveling fronts and pulses in a spatially-extended version of the Wilson-Cowan equations, a neural firing rate model of sensory cortex having two population types: Excitatory and inhibitory. We are primarily interested in the case when the local or space-clamped dynamics has three fixed points: (1) a stable down state; (2) a saddle point with stable manifold that acts as a threshold for firing; (3) an up state having stability that depends on the time scale of the inhibition. In the case when the up state is stable, we look for wave fronts, which transition the media from a down to up state, and when the up state is unstable, we are interested in pulses, a transient increase in firing that returns to the down state. We explore the behavior of these waves as the time and space scales of the inhibitory population vary. Some interesting findings include bistability between a traveling front and pulse, fronts that join the down state to an oscillation or spatiotemporal pattern, and pulses which go through an oscillatory instability.

Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

PubMed

Khouri, I F; Sui, D; Jabbour, E J; Samuels, B I; Turturro, F; Alatrash, G; Anderlini, P; Ahmed, S; Oran, B; Ciurea, S O; Marin, D; Olson, A; Patel, K K; Popat, U R; Ledesma, C; Kadia, T M; Ferrajoli, A; Burger, J A; Jorgensen, J L; Medeiros, L J; Bassett, R L; Gulbis, A M

2017-01-01

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance

PubMed Central

Kurtova, Antonina V.; Balakrishnan, Kumudha; Chen, Rong; Ding, Wei; Schnabl, Susanne; Quiroga, Maite P.; Sivina, Mariela; Wierda, William G.; Estrov, Zeev; Keating, Michael J.; Shehata, Medhat; Jäger, Ulrich; Gandhi, Varsha; Kay, Neil E.; Plunkett, William

2009-01-01

Marrow stromal cells (MSCs) provide important survival and drug resistance signals to chronic lymphocytic leukemia (CLL) cells, but current models to analyze CLL–MSC interactions are heterogeneous. Therefore, we tested different human and murine MSC lines and primary human MSCs for their ability to protect CLL cells from spontaneous and drug-induced apoptosis. Our results show that both human and murine MSCs are equally effective in protecting CLL cells from fludarabine-induced apoptosis. This protective effect was sustained over a wide range of CLL–MSC ratios (5:1 to 100:1), and the levels of protection were reproducible in 4 different laboratories. Human and murine MSCs also protected CLL cells from dexamethasone- and cyclophosphamide-induced apoptosis. This protection required cell–cell contact and was virtually absent when CLL cells were separated from the MSCs by micropore filters. Furthermore, MSCs maintained Mcl-1 and protected CLL cells from spontaneous and fludarabine-induced Mcl-1 and PARP cleavage. Collectively, these studies define common denominators for CLL cocultures with MSCs. They also provide a reliable, validated tool for future investigations into the mechanism of MSC–CLL cross talk and for drug testing in a more relevant fashion than the commonly used suspension cultures. PMID:19762485

Hematopoietic Stem Cell Transplantation for Progressive Combined Immunodeficiency and Lymphoproliferation in Activated PI3K Syndrome Type 1.

PubMed

Okano, Tsubasa; Imai, Kohsuke; Tsujita, Yuki; Mitsuiki, Noriko; Yoshida, Kenichi; Kamae, Chikako; Honma, Kenichi; Mitsui-Sekinaka, Kanako; Sekinaka, Yujin; Kato, Tamaki; Hanabusa, Katsuyuki; Endo, Eri; Takashima, Takehiro; Hiroki, Haruka; Yeh, Tzu-Wen; Tanaka, Keisuke; Nagahori, Masakazu; Tsuge, Ikuya; Bando, Yuki; Iwasaki, Fuminori; Shikama, Yoshiaki; Inoue, Masami; Kimoto, Tomiko; Moriguchi, Naohiko; Yuza, Yuki; Kaneko, Takashi; Suzuki, Kyoko; Matsubara, Tomoyo; Maruo, Yoshihiro; Kunitsu, Tomoaki; Waragai, Tomoko; Sano, Hideki; Hashimoto, Yuko; Tasaki, Kazuhiro; Suzuki, Osamu; Shirakawa, Toshihiko; Kato, Motohiro; Uchiyama, Toru; Ishimura, Masataka; Tauchi, Tetsuzo; Yagasaki, Hiroshi; Jou, Shiann-Tarng; Yu, Hsin-Hui; Kanegane, Hirokazu; Kracker, Sven; Durandy, Anne; Kojima, Daiei; Muramatsu, Hideki; Wada, Taizo; Inoue, Yuzaburo; Takada, Hidetoshi; Kojima, Seiji; Ogawa, Seishi; Ohara, Osamu; Nonoyama, Shigeaki; Morio, Tomohiro

2018-05-17

Activated phosphatidylinositol-3-OH kinase-delta (PI3Kδ) syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory infections, lymphoid hyperplasia, and herpesviridae infections due to germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) may be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, method, and outcomes of HSCT for APDS1 remain undefined. Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. We retrospectively reviewed the medical records of cohorts undergoing HSCT at collaborating facilities. Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence, and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced intensity conditioning (RIC). Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based RIC-HSCT ameliorated clinical symptoms, but transplant-related complications were frequent, including graft failure. Copyright © 2018. Published by Elsevier Inc.

Risk adjusted therapy in chronic lymphocytic leukemia: a phase II cancer trials Ireland (CTRIAL-IE [ICORG 07-01]) study of fludarabine, cyclophosphamide, and rituximab therapy evaluating response adapted, abbreviated frontline therapy with FCR in non-del(17p) CLL.

PubMed

Appleby, Niamh; O'Brien, David; Quinn, Fiona M; Smyth, Liam; Kelly, Johanna; Parker, Imelda; Scott, Kathleen; Cahill, Mary R; Crotty, Gerard; Enright, Helen; Hennessy, Brian; Hodgson, Andrew; Leahy, Maeve; O'Leary, Hilary; O'Dwyer, Michael; Hayat, Amjad; Vandenberghe, Elisabeth A

2018-06-01

Minimal residual disease negative complete response (MRD-negative CR) provides an early marker for time to treatment failure (TTF) in CLL treated with fludarabine, cyclophosphamide, and rituximab (FCR). MRD was assessed after four FCR cycles (FCR4); MRD-negative CR patients discontinued treatment. Fifty-two patients (35M; 17F) were enrolled. Eighteen (18/52; 34.6%) patients reached MRD-negative CR after FCR4 and 29/52 (55.8%) were MRD-negative CR at end of treatment (EOT). Median TTF was 71.1 months (95% CI 61.3-84.1 months), with median overall survival not reached. Mutated immunoglobulin heavy chain gene rearrangements (IGHV) were associated with early MRD-negative remissions, translating into prolonged TTF. Unmutated-IGHV, mutated-SF3B1 and mutated-NOTCH1 were associated with shortened TTF. No TTF difference was observed between patients in MRD-negative CR after four versus six cycles (82.2 versus 85.3 months, p = .6306). Abbreviated FCR therapy is effective for patients achieving early MRD-negative remissions. Interim MRD assessment assists in personalizing therapy and reducing chemotherapy-associated toxicity.

Inhibition of maternal embryonic leucine zipper kinase with OTSSP167 displays potent anti-leukemic effects in chronic lymphocytic leukemia.

PubMed

Zhang, Ya; Zhou, Xiangxiang; Li, Ying; Xu, Yangyang; Lu, Kang; Li, Peipei; Wang, Xin

2018-06-12

TP53 pathway defects contributed to therapy resistance and adverse clinical outcome in chronic lymphocytic leukemia (CLL), which represents an unmet clinical need with few therapeutic options. Maternal embryonic leucine zipper kinase (MELK) is a novel oncogene, which plays crucial roles in mitotic progression and stem cell maintenance. OTSSP167, an orally administrated inhibitor targeting MELK, is currently in a phase I/II clinical trial in patients with advanced breast cancer and acute myeloid leukemia. Yet, no investigation has been elucidated to date regarding the oncogenic role of MELK and effects of OTSSP167 in chronic lymphocytic leukemia (CLL). Previous studies confirmed MELK inhibition abrogated cancer cell survival via p53 signaling pathway. Thus, we aimed to determine the biological function of MELK and therapeutic potential of OTSSP167 in CLL. Herein, MELK over-expression was observed in CLL cells, and correlated with higher WBC count, advanced stage, elevated LDH, increased β2-MG level, unmutated IGHV, positive ZAP-70, deletion of 17p13 and inferior prognosis of CLL patients. In accordance with functional enrichment analyses in gene expression profiling, CLL cells with depletion or inhibition of MELK exhibited impaired cell proliferation, enhanced fast-onset apoptosis, induced G2/M arrest, attenuated cell chemotaxis and promoted sensitivity to fludarabine and ibrutinib. However, gain-of-function assay showed increased cell proliferation and cell chemotaxis. In addition, OTSSP167 treatment reduced phosphorylation of AKT and ERK1/2. It decreased FoxM1 phosphorylation, expression of FoxM1, cyclin B1 and CDK1, while up-regulating p53 and p21 expression. Taken together, MELK served as a candidate of therapeutic target in CLL. OTSSP167 exhibits potent anti-tumor activities in CLL cells, highlighting a novel molecule-based strategy for leukemic interventions.

A wearable multipoint ultrasonic travel aids for visually impaired

NASA Astrophysics Data System (ADS)

Ercoli, Ilaria; Marchionni, Paolo; Scalise, Lorenzo

2013-09-01

In 2010, the World Health Organization estimates that there were about 285 million people in the world with disabling eyesight loss (246 millions are visually impaired (VI) and 39 millions are totally blind). For such users, hits during mobility tasks are the reason of major concerns and can reduce the quality of their life. The white cane is the primary device used by the majority of blind or VI users to explore and possibly avoid obstacles; it can monitor only the ground (< 1m) and it does not provide protection for the legs, the trunk and the head. In this paper, authors propose a novel stand-alone Electronic Travel Aid (ETA) device for obstacle detection based on multi- sensing (by 4 ultrasonic transducers) and a microcontroller. Portability, simplicity, reduced dimensions and cost are among the major pros of the reported system, which can detect and localize (angular position and distance from the user) obstacles eventually present in the volume in front of him and on the ground in front of him.

How patients understand physicians' solicitations of additional concerns: implications for up-front agenda setting in primary care.

PubMed

Robinson, Jeffrey D; Heritage, John

2016-01-01

In the more than 1 billion primary-care visits each year in the United States, the majority of patients bring more than one distinct concern, yet many leave with "unmet" concerns (i.e., ones not addressed during visits). Unmet concerns have potentially negative consequences for patients' health, and may pose utilization-based financial burdens to health care systems if patients return to deal with such concerns. One solution to the problem of unmet concerns is the communication skill known as up-front agenda setting, where physicians (after soliciting patients' chief concerns) continue to solicit patients' concerns to "exhaustion" with questions such as "Are there some other issues you'd like to address?" Although this skill is trainable and efficacious, it is not yet a panacea. This article uses conversation analysis to demonstrate that patients understand up-front agenda-setting questions in ways that hamper their effectiveness. Specifically, we demonstrate that up-front agenda-setting questions are understood as making relevant "new problems" (i.e., concerns that are either totally new or "new since last visit," and in need of diagnosis), and consequently bias answers away from "non-new problems" (i.e., issues related to previously diagnosed concerns, including much of chronic care). Suggestions are made for why this might be so, and for improving up-front agenda setting. Data are 144 videotapes of community-based, acute, primary-care, outpatient visits collected in the United States between adult patients and 20 family-practice physicians.

Changes in entrance surface dose in relation to the location of shielding material in chest computed tomography

NASA Astrophysics Data System (ADS)

Kang, Y. M.; Cho, J. H.; Kim, S. C.

2015-07-01

This study examined the effects of entrance surface dose (ESD) on the abdomen and pelvis of the patient when undergoing chest computed tomography (CT) procedure, and evaluated the effects of ESD reduction depending on the location of radiation shield. For CT scanner, the 64-slice multi-detector computed tomography was used. The alderson radiation therapy phantom and optically stimulated luminescence dosimeter (OSLD), which enabled measurement from low to high dose, were also used. For measurement of radiation dose, the slice number from 9 to 21 of the phantom was set as the test range, which included apex up to both costophrenic angles. A total of 10 OSLD nanoDots were attached for measurement of the front and rear ESD. Cyclic tests were performed using the low-dose chest CT and high-resolution CT (HRCT) protocol on the following set-ups: without shielding; shielding only on the front side; shielding only on the rear side; and shielding for both front and rear sides. According to the test results, ESD for both front and rear sides was higher in HRCT than low-dose CT when radiation shielding was not used. It was also determined that, compared to the set-up that did not use the radiation shield, locating the radiation shield on the front side was effective in reducing front ESD, while locating the radiation shield on the rear side reduced rear ESD level. Shielding both the front and rear sides resulted in ESD reduction. In conclusion, it was confirmed that shielding the front and rear sides was the most effective method to reduce the ESD effect caused by scatter ray during radiography.

The effect of frequency-dependent microphone directionality on horizontal localization performance in hearing-aid users.

PubMed

Keidser, Gitte; O'Brien, Anna; Hain, Jens-Uwe; McLelland, Margot; Yeend, Ingrid

2009-11-01

Frequency-dependent microphone directionality alters the spectral shape of sound as a function of arrival azimuth. The influence of this on horizontal-plane localization performance was investigated. Using a 360 degrees loudspeaker array and five stimuli with different spectral characteristics, localization performance was measured on 21 hearing-impaired listeners when wearing no hearing aids and aided with no directionality, partial (from 1 and 2 kHz) directionality, and full directionality. The test schemes were also evaluated in everyday life. Without hearing aids, localization accuracy was significantly poorer than normative data. Due to inaudibility of high-frequency energy, front/back reversals were prominent. Front/back reversals remained prominent when aided with omnidirectional microphones. For stimuli with low-frequency emphasis, directionality had no further effect on localization. For stimuli with sufficient mid- and high-frequency information, full directionality had a small positive effect on front/back localization but a negative effect on left/right localization. Partial directionality further improved front/back localization and had no significant effect on left/right localization. The field test revealed no significant effects. The alternative spectral cues provided by frequency-dependent directionality improve front/back localization in hearing-aid users.

AUTOMOTIVE DIESEL MAINTENANCE 1. UNIT XIX, I--ENGINE TUNE-UP--CUMMINS DIESEL ENGINE, II--FRONT END SUSPENSION AND AXLES.

ERIC Educational Resources Information Center

Minnesota State Dept. of Education, St. Paul. Div. of Vocational and Technical Education.

THIS MODULE OF A 30-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF DIESEL ENGINE TUNE-UP PROCEDURES AND THE DESIGN OF FRONT END SUSPENSION AND AXLES USED ON DIESEL ENGINE EQUIPMENT. TOPICS ARE (1) PRE-TUNE-UP CHECKS, (2) TIMING THE ENGINE, (3) INJECTOR PLUNGER AND VALVE ADJUSTMENTS, (4) FUEL PUMP ADJUSTMENTS ON THE ENGINE (PTR AND PTG),…

Bortezomib and Fludarabine With or Without Rituximab in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2013-09-27

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hematopoietic/Lymphoid Cancer; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders

ClinicalTrials.gov

2018-03-28

Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Polycythemia Vera; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Primary Myelofibrosis; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

Null geodesics and wave front singularities in the Gödel space-time

NASA Astrophysics Data System (ADS)

Kling, Thomas P.; Roebuck, Kevin; Grotzke, Eric

2018-01-01

We explore wave fronts of null geodesics in the Gödel metric emitted from point sources both at, and away from, the origin. For constant time wave fronts emitted by sources away from the origin, we find cusp ridges as well as blue sky metamorphoses where spatially disconnected portions of the wave front appear, connect to the main wave front, and then later break free and vanish. These blue sky metamorphoses in the constant time wave fronts highlight the non-causal features of the Gödel metric. We introduce a concept of physical distance along the null geodesics, and show that for wave fronts of constant physical distance, the reorganization of the points making up the wave front leads to the removal of cusp ridges.

Utility of up-front transoral robotic surgery in tailoring adjuvant therapy.

PubMed

Gildener-Leapman, Neil; Kim, Jeehong; Abberbock, Shira; Choby, Garret W; Mandal, Rajarsi; Duvvuri, Umamaheswar; Ferris, Robert L; Kim, Seungwon

2016-08-01

The purpose of this study was to describe how the up-front transoral robotic surgery (TORS) approach could be used to individually tailor adjuvant therapy based on surgical pathology. Between January 2009 and December 2013, 76 patients received TORS for oropharyngeal squamous cell carcinoma (OPSCC). Clinical predictors of adjuvant therapy were analyzed and comparisons were made between recommended treatment guidelines for up-front surgery versus definitive nonsurgical approaches. Advanced N classification, human papillomavirus (HPV)-positive tumor, extracapsular spread (ECS; 26 of 76), perineural invasion (PNI; 14 of 76), and positive margins (7 of 76) were significant predictors of adjuvant chemoradiotherapy (CRT) (p < .05). Up-front TORS deintensified adjuvant therapy; 76% of stage I/II and 46% of stage III/IV patients avoided CRT. Conversely, pathologic staging resulted in 33% of patients who would have received radiotherapy (RT) alone based on clinical staging, to be intensified to receive adjuvant CRT. The TORS approach deintensifies adjuvant therapy and provides valuable pathologic information to intensify treatment in select patients. TORS may be less effective in deintensification of adjuvant therapy in patients with clinically advanced N classification disease. © 2016 Wiley Periodicals, Inc. Head Neck 38:1201-1207, 2016. © 2016 Wiley Periodicals, Inc.

Growth and gravitational collapse of a mountain front of the Eastern Cordillera of Colombia

NASA Astrophysics Data System (ADS)

Kammer, Andreas; Montana, Jorge; Piraquive, Alejandro

2016-04-01

The Eastern Cordillera of Colombia is bracketed between the moderately east-dipping flank of the Central Cordillera on its western and the gently bent Guayana shield on its eastern side. It evolved as a response to a considerable displacement transfer from the Nazca to the Southamerican plate since the Oligocene break-up of the Farallon plate. One of its distinctive traits refers to its significant shortening by penetrative strain at lower and folding at higher structural levels, approximating a wholesale pure-shear in analogy to a vice model or a crustal welt sandwiched between rigid buttresses. This contrasting behavior may be explained by the spatial coincidence between Neogene mountain belt and a forebulge that shaped the foreland trough during a Cretaceous subduction cycle and was very effective in localizing a weakening of the backarc region comprised between two basin margin faults. In this paper we examine a two-phase evolution of the Eastern mountain front. Up to the late Miocene deformation was restrained by the inherited eastern basin margin fault and as the cordilleran crust extruded, a deformation front with an amplitude similar the present structural relief of up to 10.000 m may have built up. In the Pliocene convergence changed from a roughly strike-perpendicular to an oblique E-W direction and caused N-S trending faults to branch off from the deformation front. This shortening was partly driven by a gravitational collapse of the Miocene deformation front, that became fragmented by normal faults and extruded E on newly formed Pliocene thrust faults. Normal faults display displacements of up to 3000 m and channelized hydrothermal fluids, leading to the formation of widely distributed fault breccias and giving rise to a prolific Emerald mineralization. In terms of wedge dynamics, the Pliocene breaching of the early formed deformation front helped to establish a critical taper.

Department of Clinical Investigation Annual Research Progress Report, Fiscal Year 1985. Volume 2,

DTIC Science & Technology

1985-10-01

Objective(s): To study the feasibility of cytosine arabinoside (ara-C), used in high dosage in conjunction with fractionated total body irradiation... Using High Dose Ara-C 335 in Adult Acute Leukemia and Chronic Granulocytic Leukemia in Blastic Crisis, Phase III. (0) SWOG 8328 Evaluation of...Fludarabine Phosphate in Cervical Cancer, 336 Phase II. (0) SWOG 8360 Use of the Surgically Implanted "Infusaid" Pump for Ambula- 337 tory Ottpatient Hepatic

Reduced dose cyclophosphamide, fludarabine and antithymocyte globulin for sibling and unrelated transplant of children with severe and very severe aplastic anemia.

PubMed

Chung, Nack-Gyun; Lee, Jae Wook; Jang, Pil-Sang; Jeong, Dae-Chul; Cho, Bin; Kim, Hack-Ki

2013-06-01

We evaluated the results of a novel conditioning regimen of reduced dose cyclophosphamide (Cy, 25 mg/kg for four days), fludarabine (Flu, 30 mg/m(2) for four days), and rabbit ATG (2.5 mg/kg for three days) for allogeneic transplant of children with SAA, implemented since January 2009. Overall, 23 patients were treated with this regimen (16 male, seven female), including 10 diagnosed with VSAA. Donors included eight-MSD and 15 UD (five-matched UD, and 10 mismatched UD). All patients showed neutrophil and platelet engraftment. Cumulative incidence of acute (grade 2 or above) and chronic GVHD was 26.1% and 8.7%, respectively. Estimated two-yr FFS and OS for the entire cohort was 90.3 ± 6.5%. Rates of TRM and graft failure were 5.3% and 4.3%, respectively. No difference in OS was found according to disease severity (SAA vs. VSAA, p = 0.184), or according to donor type (MSD vs. UD, p = 0.699). Excellent outcomes of patients with VSAA underscore the efficacy of allogeneic transplant as a means of expediting hematopoietic recovery. Improved survival of UD transplant reaffirms its role as a valid therapeutic alternative in the absence of MSD. © 2013 John Wiley & Sons A/S.

Adoptive Cell Transfer Therapy Following Non-Myeloablative but Lymphodepleting Chemotherapy for the Treatment of Patients With Refractory Metastatic Melanoma

PubMed Central

Dudley, Mark E.; Wunderlich, John R.; Yang, James C.; Sherry, Richard M.; Topalian, Suzanne L.; Restifo, Nicholas P.; Royal, Richard E.; Kammula, Udai; White, Don E.; Mavroukakis, Sharon A.; Rogers, Linda J.; Gracia, Gerald J.; Jones, Stephanie A.; Mangiameli, David P.; Pelletier, Michelle M.; Gea-Banacloche, Juan; Robinson, Michael R.; Berman, David M.; Filie, Armando C.; Abati, Andrea; Rosenberg, Steven A.

2006-01-01

Purpose We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma. Patients and Methods Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL)-2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m2). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy. Results Eighteen (51%) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 ± 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus-related lymphoproliferation. Conclusion Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma. PMID:15800326

Front-form spinors in the Weinberg-Soper formalism and generalized Melosh transformations for any spin

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

Ahluwalia, D.V.; Sawicki, M.

Using the Weinberg-Soper formalism we construct the front-form ([ital j],0)[direct sum](0,[ital j]) spinors. Explicit expressions for the generalized Melosh transformations up to spin two are obtained. The formalism, without explicitly invoking any wave equations, reproduces the spin-1/2 front-form results of Melosh, Lepage and Brodsky, and Dziembowski.

Allogeneic hematopoietic cell transplantation for consolidation of VGPR or CR for newly diagnosed multiple myeloma

PubMed Central

Nishihori, T; Ochoa-Bayona, JL; Kim, J; Pidala, J; Shain, K; Baz, R; Sullivan, D; Jim, HS; Anasetti, C; Alsina, M

2015-01-01

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative approach in patients with multiple myeloma, but its use for consolidation of first remission has not yet been fully explored. Twenty-two myeloma patients with very good partial response (VGPR) or CR received allogeneic peripheral blood grafts as consolidation from HLA-matched donors between 2007 and 2012. Conditioning regimens were fludarabine (30 mg/m2 i.v. if with bortezomib and 40 mg/m2 i.v. when without bortezomib, ×4 days) plus melphalan (70 mg/m2 intravenously ×2 days) with (n = 13) or without (n = 9) bortezomib (1.3 mg/m2). The cumulative incidence of grades 2–4 acute GVHD at day 100 was 45% (95% CI: 24–65%) and moderate-to-severe chronic GVHD at 2 years was 46% (95% CI: 19–69%). With a median follow-up of 18 (range, 2–61) months, the 2-year PFS estimate is 74.8% (95% CI: 45–90%), which compares favorably with the 52% (95% CI: 35–66%) after autologous HCT for similar patients (a median follow-up of 30 (range, 9–55) months). We are conducting a phase 2 study to assess the efficacy of allogeneic HCT as post-remission therapy. PMID:23542223

An Overview of the Major Phenomena of the Localization of Sound Sources by Normal-Hearing, Hearing-Impaired, and Aided Listeners

PubMed Central

2014-01-01

Localizing a sound source requires the auditory system to determine its direction and its distance. In general, hearing-impaired listeners do less well in experiments measuring localization performance than normal-hearing listeners, and hearing aids often exacerbate matters. This article summarizes the major experimental effects in direction (and its underlying cues of interaural time differences and interaural level differences) and distance for normal-hearing, hearing-impaired, and aided listeners. Front/back errors and the importance of self-motion are noted. The influence of vision on the localization of real-world sounds is emphasized, such as through the ventriloquist effect or the intriguing link between spatial hearing and visual attention. PMID:25492094

Factors influencing load-haul-dump operator line of sight in underground mining.

PubMed

Eger, Tammy; Salmoni, Alan; Whissell, Robert

2004-03-01

The inability of load-haul-dump (LHD) equipment operators to see people, objects or hazards around the LHD machine they drive is a causal factor in a number of serious accidents. Line of sight evaluations were conducted on 11 different LHD models. Results indicated blind spots were caused by cab posts, and vehicles lights and light brackets. Line of sight impairments were caused by wheel well covers, buckets, fire extinguisher, light posts, radiator covers, booms, radio remote boxes, elevated engine profiles and air intake cylinders. These results were supported by questionnaires completed by 130 LHD operators. The operators indicated the bucket, lights and light brackets, boom and cab impaired line of sight. Line of sight testing and LHD operator feedback indicated line of sight to the right front corner and back right corner were typically worse than line of sight to the front left side of the vehicle. Results of this study have been used to conduct awareness campaigns within the Ontario mining industry and to suggest vehicle design modifications to LHD manufacturers.

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

Huang Meijuan; Jiang Yu; State Key Laboratory of Biotherapy, West China Hospital, Medical School, Sichuan University, Chengdu

Purpose: To investigate the role of early or up-front radiotherapy (RT), the optimal RT dose required to achieve appropriate treatment outcome and prognostic factors for patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. Methods and Materials: Eighty-two patients were reviewed. Eight patients were treated with chemotherapy (CT) alone, 9 patients received RT alone, and 65 patients were given combined modality treatment of CT and RT (CMT). Of those 74 patients receiving RT, 31 patients were given up-front RT, whereas CT was the initial therapy for 43 patients and 41 of those 43 patients received early RT.more » Results: Five-year overall survival (OS) and disease-free survival (DFS) were 52.3% and 39.2%, respectively. RT was the only independent prognostic factor for both OS and DFS at both the univariate and multivariate level. The 5-year OS and DFS were better in patients receiving {>=}54 Gy of RT as compared with that of <54 Gy (5-year OS 75.5% vs. 46.1%, p = 0.019; 5-year DFS 60.3% vs. 33.4%, p = 0.004). Up-front RT presented better survival in Stage I patients when compared with that of initial CT followed by early RT (5-year OS 90.0% vs. 48.9%, p = 0.012; 5-year DFS 78.7% vs. 39.9%, p = 0.021). Conclusion: Early or up-front RT had an essential role in improved OS and DFS in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. The recommended tumor dose was at least 54 Gy. Up-front RT may yield more benefits on survival in patients with Stage I disease.« less

Can computerized tomography accurately stage childhood renal tumors?

PubMed

Abdelhalim, Ahmed; Helmy, Tamer E; Harraz, Ahmed M; Abou-El-Ghar, Mohamed E; Dawaba, Mohamed E; Hafez, Ashraf T

2014-07-01

Staging of childhood renal tumors is crucial for treatment planning and outcome prediction. We sought to identify whether computerized tomography could accurately predict the local stage of childhood renal tumors. We retrospectively reviewed our database for patients diagnosed with childhood renal tumors and treated surgically between 1990 and 2013. Inability to retrieve preoperative computerized tomography, intraoperative tumor spillage and nonWilms childhood renal tumors were exclusion criteria. Local computerized tomography stage was assigned by a single experienced pediatric radiologist blinded to the pathological stage, using a consensus similar to the Children's Oncology Group Wilms tumor staging system. Tumors were stratified into up-front surgery and preoperative chemotherapy groups. The radiological stage of each tumor was compared to the pathological stage. A total of 189 tumors in 179 patients met inclusion criteria. Computerized tomography staging matched pathological staging in 68% of up-front surgery (70 of 103), 31.8% of pre-chemotherapy (21 of 66) and 48.8% of post-chemotherapy scans (42 of 86). Computerized tomography over staged 21.4%, 65.2% and 46.5% of tumors in the up-front surgery, pre-chemotherapy and post-chemotherapy scans, respectively, and under staged 10.7%, 3% and 4.7%. Computerized tomography staging was more accurate in tumors managed by up-front surgery (p <0.001) and those without extracapsular extension (p <0.001). The validity of computerized tomography staging of childhood renal tumors remains doubtful. This staging is more accurate for tumors treated with up-front surgery and those without extracapsular extension. Preoperative computerized tomography can help to exclude capsular breach. Treatment strategy should be based on surgical and pathological staging to avoid the hazards of inaccurate staging. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Smart walking stick for blind people: an application of 3D printer

NASA Astrophysics Data System (ADS)

Ikbal, Md. Allama; Rahman, Faidur; Ali, Md. Ripon; Kabir, M. Hasnat; Furukawa, Hidemitsu

2017-04-01

A prototype of the smart walking stick has been designed and characterized for the people who are visually impaired. In this study, it was considered that the proposed system will alert visuallyimpaired people over the obstacles which are in front of blind people as well as the obstacles of the street such as a manhole, when the blind people are walking in the street. The proposed system was designed in two stages, i.e. hardware and software which makes the system as a complete prototype. Three ultrasonic sonar sensors were used to detect in front obstacle and street surface obstacle such as manhole. Basically the sensor transmits an electromagnetic wave which travels toward the obstacle and back to the sensor receiver. The distance between the sensor and the obstacle is calculated from the received signal. The calculated distance value is compared with the pre-defined value and determines whether the obstacle is present or not. The 3D CAD software was used to design the sensor holder. An Up-Mini 3D printer was used to print the sensor holders which were mounted on the walking stick. Therefore, the sensors were fixed in the right position. Another sensor was used for the detecting the water on the walking street. The performance for detecting the obstacles and water indicate the merit of smart walking stick.

Aerial Observations of Symmetric Instability at the North Wall of the Gulf Stream

NASA Astrophysics Data System (ADS)

Savelyev, I.; Thomas, L. N.; Smith, G. B.; Wang, Q.; Shearman, R. K.; Haack, T.; Christman, A. J.; Blomquist, B.; Sletten, M.; Miller, W. D.; Fernando, H. J. S.

2018-01-01

An unusual spatial pattern on the ocean surface was captured by thermal airborne swaths taken across a strong sea surface temperature front at the North Wall of the Gulf Stream. The thermal pattern on the cold side of the front resembles a staircase consisting of tens of steps, each up to ˜200 m wide and up to ˜0.3°C warm. The steps are well organized, clearly separated by sharp temperature gradients, mostly parallel and aligned with the primary front. The interpretation of the airborne imagery is aided by oceanographic measurements from two research vessels. Analysis of the in situ observations indicates that the front was unstable to symmetric instability, a type of overturning instability that can generate coherent structures with similar dimensions to the temperature steps seen in the airborne imagery. It is concluded that the images capture, for the first time, the surface temperature field of symmetric instability turbulence.

Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

ClinicalTrials.gov

2018-05-14

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer

ClinicalTrials.gov

2017-11-08

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma; Previously Treated Myelodysplastic Syndrome; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

Social Security and Disability Due to Mental Impairment in Adults.

PubMed

Goldman, Howard H; Frey, William D; Riley, Jarnee K

2018-05-07

The Social Security Administration (SSA) oversees two disability programs, Social Security Disability Insurance (SSDI) and Supplemental Security Income (SSI). Adults with mental impairments represent a very large component of the programs. Policy makers and SSA are concerned about the accuracy of disability determination and also about low levels of labor force participation among individuals with disabilities. Adults with mental impairments are challenging to assess for work-related functional limitations. They are also a challenge to return to labor force participation. SSA has sponsored several demonstration research programs focusing on improving the accuracy of disability determination and on interventions in supported employment to return individuals with mental impairments to competitive employment. This article reviews the demonstration research focused on both entry into the disability system (at the "front door") and potential exit from it (through the "back door"). All of the research holds promise to "right-size" the SSA disability program.

Vibrotactile Feedbacks System for Assisting the Physically Impaired Persons for Easy Navigation

NASA Astrophysics Data System (ADS)

Safa, M.; Geetha, G.; Elakkiya, U.; Saranya, D.

2018-04-01

NAYAN architecture is for a visually impaired person to help for navigation. As well known, all visually impaired people desperately requires special requirements even to access services like the public transportation. This prototype system is a portable device; it is so easy to carry in any conduction to travel through a familiar and unfamiliar environment. The system consists of GPS receiver and it can get NEMA data through the satellite and it is provided to user's Smartphone through Arduino board. This application uses two vibrotactile feedbacks that will be placed in the left and right shoulder for vibration feedback, which gives information about the current location. The ultrasonic sensor is used for obstacle detection which is found in front of the visually impaired person. The Bluetooth modules connected with Arduino board is to send information to the user's mobile phone which it receives from GPS.

Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study.

PubMed

Anderlini, Paolo; Wu, Juan; Gersten, Iris; Ewell, Marian; Tolar, Jakob; Antin, Joseph H; Adams, Roberta; Arai, Sally; Eames, Gretchen; Horwitz, Mitchell E; McCarty, John; Nakamura, Ryotaro; Pulsipher, Michael A; Rowley, Scott; Leifer, Eric; Carter, Shelly L; DiFronzo, Nancy L; Horowitz, Mary M; Confer, Dennis; Deeg, H Joachim; Eapen, Mary

2015-09-01

The optimum preparative regimen for unrelated donor marrow transplantation in patients with severe aplastic anaemia remains to be established. We investigated whether the combination of fludarabine, anti-thymocyte globulin, and total body irradiation (TBI) would enable reduction of the cyclophosphamide dose to less than 200 mg/kg while maintaining engraftment and having a survival similar to or better than that with standard regimens using a cyclophosphamide dose of 200 mg/kg (known to be associated with significant organ toxicity) for unrelated donor transplantation for severe aplastic anaemia. We have previously shown that cyclophosphamide at 150 mg/kg resulted in excess toxicity and its omission (0 mg/kg) resulted in unacceptable graft failure (three of three patients had secondary graft failure). Here we report results for the 50 mg/kg and 100 mg/kg cohorts. In a multicentre phase 1-2 study, patients (aged ≤65 years) with severe aplastic anaemia, adequate organ function, and an unrelated adult marrow donor HLA matched at the allele level for HLA A, B, C, and DRB1 or mismatched at a single HLA locus received bone marrow grafts from unrelated donors. All patients received anti-thymocyte globulin (rabbit derived 3 mg/kg per day, intravenously, on days -4 to -2, or equine derived 30 mg/kg per day, intravenously, on days -4 to -2), fludarabine (30 mg/m(2) per day, intravenously, on days -5 to -2), and TBI (2 Gy). Cyclophosphamide dosing started at 150 mg/kg and was de-escalated in steps of 50 mg/kg (to 100 mg/kg, 50 mg/kg, and 0 mg/kg). The primary endpoint was the selection of the optimum cyclophosphamide dose based on assessments of graft failure (primary or secondary), toxicity, and early death during 100 days of follow-up after the transplant; this is the planned final analysis for the primary endpoint. This trial is registered with ClinicalTrials.gov, number NCT00326417. 96 patients had bone marrow transplant. At day 100, 35 (92%) of 38 patients were engrafted and alive in the cyclophosphamide 50 mg/kg cohort and 35 (85%) of 41 in the 100 mg/kg cohort. Cyclophosphamide 50 mg/kg and 100 mg/kg resulted in posterior means for fatality without graft failure of 0·7% (credible interval 0-3·3) and 1·4% (0-4·9), respectively. Three patients (8%) had graft failure with cyclophosphamide 50 mg/kg and six (15%) with cyclophosphamide 100 mg/kg. Four (11%) patients had major regimen-related toxicity with cyclophosphamide 50 mg/kg and nine (22%) with cyclophosphamide 100 mg/kg. The most common organ toxicity was pulmonary (grade 3 or 4 dyspnoea or hypoxia including mechanical ventilation), and occurred in three (8%) and four (10%) patients given cyclophosphamide 50 mg/kg and 100 mg/kg, respectively. Cyclophosphamide at 50 mg/kg and 100 mg/kg with TBI 2 Gy, fludarabine, and anti-thymocyte globulin results in effective conditioning and few early deaths after unrelated donor transplantation for severe aplastic anaemia. These doses of cyclophosphamide provide a framework for further regimen optimisation strategies. US National Heart, Lung, and Blood Institute and National Cancer Institute. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterising a holographic modal phase mask for the detection of ocular aberrations

NASA Astrophysics Data System (ADS)

Corbett, A. D.; Leyva, D. Gil; Diaz-Santana, L.; Wilkinson, T. D.; Zhong, J. J.

2005-12-01

The accurate measurement of the double-pass ocular wave front has been shown to have a broad range of applications from LASIK surgery to adaptively corrected retinal imaging. The ocular wave front can be accurately described by a small number of Zernike circle polynomials. The modal wave front sensor was first proposed by Neil et al. and allows the coefficients of the individual Zernike modes to be measured directly. Typically the aberrations measured with the modal sensor are smaller than those seen in the ocular wave front. In this work, we investigated a technique for adapting a modal phase mask for the sensing of the ocular wave front. This involved extending the dynamic range of the sensor by increasing the pinhole size to 2.4mm and optimising the mask bias to 0.75λ. This was found to decrease the RMS error by up to a factor of three for eye-like aberrations with amplitudes up to 0.2μm. For aberrations taken from a sample of real-eye measurements a 20% decrease in the RMS error was observed.

Front-end electronics development for TPC detector in the MPD/NICA project

NASA Astrophysics Data System (ADS)

Cheremukhina, G.; Movchan, S.; Vereschagin, S.; Zaporozhets, S.

2017-06-01

The article is aimed at describing the development status, measuring results and design changes of the TPC front-end electronics. The TPC is placed in the middle of Multi-Purpose Detector (MPD) and provides tracing and identifying of charged particles in the pseudorapidity range |η| < 1.2. The readout system is one of the most complex parts of the TPC. The electronics of each readout chamber is an independent system. The whole system contains 95232 channels, 1488 64-channel—front-end cards (FEC), 24 readout control units (RCU). The front-end electronics (FEE) is based on ASICs, FPGAs and high-speed serial links. The concept of the TPC front-end electronics has been motivated from one side—by the requirements concerning the NICA accelerator complex which will operate at the luminosity up to 1027 cm-2 s-1 for Au79+ ions over the energy range of 4 < √SNN < 11 GeV with the trigger rate up to 7 kHz and from the other side—by the requirements of the 4-π geometry to minimize the substance on the end-caps of the TPC.

The cutting edge of aplastic anemia treatment.

PubMed

Obara, Naoshi

2017-01-01

Aplastic anemia is a syndrome in which hematopoietic stem cells are decreased and bone marrow hypoplasia and pancytopenia are observed; it is considered as a T cell-mediated autoimmune disease. Recently, it has been reported that gene mutations suggestive of clonal hematopoiesis are detected in approximately one third of the patients with aplastic anemia. Among treatment approaches other than hematopoietic stem cell transplantation, immunosuppressive therapy with antithymocyte globulin (ATG) plus cyclosporin is a basic approach, although it has been shown that eltrombopag, a thrombopoietin receptor agonist, is effective and that the recovery of hematopoiesis in three blood lineage is observed in some patients. Studies on the optimum dose of ATG are in progress. Regarding hematopoietic stem cell transplantation for aplastic anemia, regimens are being designed in which cyclophosphamide as a pretreatment is reduced and fludarabine is instead used in combination for the reduction of cardiotoxicity. Because HLA haploidentical transplantation has been developed and its reports are increasing for patients who cannot find appropriate donors, transplantation may be possible in patients who had previously given up on it.

40 CFR 35.4080 - Does my group get a lump sum up front, or does EPA reimburse us for costs we incur?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Does my group get a lump sum up front, or does EPA reimburse us for costs we incur? 35.4080 Section 35.4080 Protection of Environment... reimburse us for costs we incur? (a) EPA pays your group by reimbursing you for “allowable” costs, which are...

40 CFR 35.4080 - Does my group get a lump sum up front, or does EPA reimburse us for costs we incur?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Does my group get a lump sum up front, or does EPA reimburse us for costs we incur? 35.4080 Section 35.4080 Protection of Environment... reimburse us for costs we incur? (a) EPA pays your group by reimbursing you for “allowable” costs, which are...

Lean-driven improvements slash wait times, drive up patient satisfaction scores.

PubMed

2012-07-01

Administrators at LifePoint Hospitals, based in Brentwood, TN, used lean manufacturing techniques to slash wait times by as much as 30 minutes and achieve double-digit increases in patient satisfaction scores in the EDs at three hospitals. In each case, front-line workers took the lead on identifying opportunities for improvement and redesigning the patient-flow process. As a result of the new efficiencies, patient volume is up by about 25% at all three hospitals. At each hospital, the improvement process began with Kaizen, a lean process that involves bringing personnel together to flow-chart the current system, identify problem areas, and redesign the process. Improvement teams found big opportunities for improvement at the front end of the flow process. Key to the approach was having a plan up front to deal with non-compliance. To sustain improvements, administrators gather and disseminate key metrics on a daily basis.

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis

PubMed Central

Ladomenou, Fani; Carpenter, Ben; Chandra, Sharat; Sedlacek, Petr; Formankova, Renata; Grandage, Vicky; Friswell, Mark; Cant, Andrew J.; Nademi, Zohreh; Slatter, Mary A.; Gennery, Andrew R.; Hambleton, Sophie; Flood, Terence J.; Lucchini, Giovanna; Chiesa, Robert; Rao, Kanchan; Amrolia, Persis J.; Brogan, Paul; Wedderburn, Lucy R.; Glanville, Julie M.; Hough, Rachael; Marsh, Rebecca; Abinun, Mario; Veys, Paul

2018-01-01

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor–negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely. PMID:29618462

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

PubMed

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

2017-06-22

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

Cladribine and Fludarabine Nucleotides Induce Distinct Hexamers Defining a Common Mode of Reversible RNR Inhibition.

PubMed

Wisitpitthaya, Somsinee; Zhao, Yi; Long, Marcus J C; Li, Minxing; Fletcher, Elaine A; Blessing, William A; Weiss, Robert S; Aye, Yimon

2016-07-15

The enzyme ribonucleotide reductase (RNR) is a major target of anticancer drugs. Until recently, suicide inactivation in which synthetic substrate analogs (nucleoside diphosphates) irreversibly inactivate the RNR-α2β2 heterodimeric complex was the only clinically proven inhibition pathway. For instance, this mechanism is deployed by the multifactorial anticancer agent gemcitabine diphosphate. Recently reversible targeting of RNR-α-alone coupled with ligand-induced RNR-α-persistent hexamerization has emerged to be of clinical significance. To date, clofarabine nucleotides are the only known example of this mechanism. Herein, chemoenzymatic syntheses of the active forms of two other drugs, phosphorylated cladribine (ClA) and fludarabine (FlU), allow us to establish that reversible inhibition is common to numerous drugs in clinical use. Enzyme inhibition and fluorescence anisotropy assays show that the di- and triphosphates of the two nucleosides function as reversible (i.e., nonmechanism-based) inhibitors of RNR and interact with the catalytic (C site) and the allosteric activity (A site) sites of RNR-α, respectively. Gel filtration, protease digestion, and FRET assays demonstrate that inhibition is coupled with formation of conformationally diverse hexamers. Studies in 293T cells capable of selectively inducing either wild-type or oligomerization-defective mutant RNR-α overexpression delineate the central role of RNR-α oligomerization in drug activity, and highlight a potential resistance mechanism to these drugs. These data set the stage for new interventions targeting RNR oligomeric regulation.

Allogeneic hematopoietic cell transplantation after conditioning with I-131-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

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

Pagel, John M.; Gooley, T. A.; Rajendran, Joseph G.

2009-12-24

We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the bloodmore » by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.« less

Inhibitory effect of leptin on rosiglitazone-induced differentiation of primary adipocytes prepared from TallyHO/Jng mice

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

Kim, Ki Young; Kim, Joo Young; Sung, Yoon-Young

2011-03-25

Research highlights: {yields} In this study, we investigated the effects of leptin on adipocyte differentiation prepared from subcutaneous fat of TallyHo mice. {yields} Leptin inhibited the adipocytes differentiation at physiological concentration via inhibition of PPAR{gamma} expression. {yields} Inhibitors of ERK and STAT1 restored the leptin's inhibitory activity both in vitro and in vivo. -- Abstract: The effects of leptin on rosiglitazone-induced adipocyte differentiation were investigated in the primary adipocytes prepared from subcutaneous fat of TallyHO/Jng (TallyHO) mouse, a recently developed model animal for type 2 diabetes mellitus (T2DM). The treatment of leptin inhibited the rosiglitazone-induced adipocyte differentiation with a decreasedmore » expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) a key adipogenic transcription factor, both in mRNA and protein levels. Leptin (10 nM) was sufficient to inhibit the adipocyte differentiation, which seemed to come from increased expression of leptin receptor genes in the fat of TallyHO mice. The inhibition of adipogenesis by leptin was restored by the treatment of inhibitors for extracellular-signal-regulated kinase (ERK) (PD98059) and signal transducer and activator of transcription-1 (STAT1) (fludarabine). Furthermore, in vivo intraperitoneal administration of PD98059 and fludarabine increased the PPAR{gamma} expression in the subcutaneous fat of TallyHO mice. These data suggest that leptin could inhibit the PPAR{gamma} expression and adipocyte differentiation in its physiological concentration in TallyHO mice.« less

Targeting cholesterol synthesis increases chemoimmuno-sensitivity in chronic lymphocytic leukemia cells

PubMed Central

2014-01-01

Background Cholesterol plays an important role in cancer development, drug resistance and chemoimmuno-sensitivity. Statins, cholesterol lowering drugs, can induce apoptosis, but also negatively interfere with CD-20 and rituximab-mediated activity. Our goal is to identify the alternative targets that could reduce cholesterol levels but do not interfere with CD-20 in chemo immunotherapy of chronic lymphocytic leukemia (CLL). Methods MEC-2 cells, a CLL cell line, and the peripheral blood mononuclear cells (PBMCs) from CLL patients were treated with cholesterol lowering agents, and analyzed the effect of these agents on cholesterol levels, CD-20 expression and distribution, and cell viability in the presence or absence of fludarabine, rituximab or their combinations. Results We found that MEC-2 cells treated with cholesterol lowering agents (BIBB-515, YM-53601 or TAK-475) reduced 20% of total cellular cholesterol levels, but also significantly promoted CD-20 surface expression. Furthermore, treatment of cells with fludarabine, rituximab or their combinations in the presence of BIBB-515, YM-53601 or TAK-475 enhanced MEC-2 cell chemoimmuno-sensitivity measured by cell viability. More importantly, these cholesterol lowering agents also significantly enhanced chemoimmuno-sensitivity of the PBMCs from CLL patients. Conclusion Our data demonstrate that BIBB-515, YM53601 and TAK-475 render chemoimmuno-therapy resistant MEC-2 cells sensitive to chemoimmuno-therapy and enhance CLL cell chemoimmuno-sensitivity without CD-20 epitope presentation or its downstream signaling. These results provide a novel strategy which could be applied to CLL treatment. PMID:25401046

Targeting cholesterol synthesis increases chemoimmuno-sensitivity in chronic lymphocytic leukemia cells.

PubMed

Benakanakere, Indira; Johnson, Tyler; Sleightholm, Richard; Villeda, Virgilio; Arya, Monika; Bobba, Ravi; Freter, Carl; Huang, Chunfa

2014-01-01

Cholesterol plays an important role in cancer development, drug resistance and chemoimmuno-sensitivity. Statins, cholesterol lowering drugs, can induce apoptosis, but also negatively interfere with CD-20 and rituximab-mediated activity. Our goal is to identify the alternative targets that could reduce cholesterol levels but do not interfere with CD-20 in chemo immunotherapy of chronic lymphocytic leukemia (CLL). MEC-2 cells, a CLL cell line, and the peripheral blood mononuclear cells (PBMCs) from CLL patients were treated with cholesterol lowering agents, and analyzed the effect of these agents on cholesterol levels, CD-20 expression and distribution, and cell viability in the presence or absence of fludarabine, rituximab or their combinations. We found that MEC-2 cells treated with cholesterol lowering agents (BIBB-515, YM-53601 or TAK-475) reduced 20% of total cellular cholesterol levels, but also significantly promoted CD-20 surface expression. Furthermore, treatment of cells with fludarabine, rituximab or their combinations in the presence of BIBB-515, YM-53601 or TAK-475 enhanced MEC-2 cell chemoimmuno-sensitivity measured by cell viability. More importantly, these cholesterol lowering agents also significantly enhanced chemoimmuno-sensitivity of the PBMCs from CLL patients. Our data demonstrate that BIBB-515, YM53601 and TAK-475 render chemoimmuno-therapy resistant MEC-2 cells sensitive to chemoimmuno-therapy and enhance CLL cell chemoimmuno-sensitivity without CD-20 epitope presentation or its downstream signaling. These results provide a novel strategy which could be applied to CLL treatment.

Numerical analysis of wavefront measurement characteristics by using plenoptic camera

NASA Astrophysics Data System (ADS)

Lv, Yang; Ma, Haotong; Zhang, Xuanzhe; Ning, Yu; Xu, Xiaojun

2016-01-01

To take advantage of the large-diameter telescope for high-resolution imaging of extended targets, it is necessary to detect and compensate the wave-front aberrations induced by atmospheric turbulence. Data recorded by Plenoptic cameras can be used to extract the wave-front phases associated to the atmospheric turbulence in an astronomical observation. In order to recover the wave-front phase tomographically, a method of completing the large Field Of View (FOV), multi-perspective wave-front detection simultaneously is urgently demanded, and it is plenoptic camera that possesses this unique advantage. Our paper focuses more on the capability of plenoptic camera to extract the wave-front from different perspectives simultaneously. In this paper, we built up the corresponding theoretical model and simulation system to discuss wave-front measurement characteristics utilizing plenoptic camera as wave-front sensor. And we evaluated the performance of plenoptic camera with different types of wave-front aberration corresponding to the occasions of applications. In the last, we performed the multi-perspective wave-front sensing employing plenoptic camera as wave-front sensor in the simulation. Our research of wave-front measurement characteristics employing plenoptic camera is helpful to select and design the parameters of a plenoptic camera, when utilizing which as multi-perspective and large FOV wave-front sensor, which is expected to solve the problem of large FOV wave-front detection, and can be used for AO in giant telescopes.

[A comparison of toxicity and efficacy between busulfan plus fludarabine and busulfan plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia].

PubMed

Liu, Hui; Fan, Zhi-ping; Jiang, Qian-li; Huang, Fen; Zhou, Hong-sheng; Zhang, Xian; Yu, Guo-pan; Wu, Mei-qing; Sun, Jing; Liu, Qi-fa

2012-11-01

To compare the transplant-related toxicity and the efficacy of busulfan/fludarabine (Bu/Flu) and busulfan/cyclophosphamide (Bu/Cy) as conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia(AML) in the first complete remission (CR1). Totally 32 AML-CR1 patients underwent allo-HSCT were divided into Bu/Cy (Bu 3.2 mg×kg(-1)×d(-1), 7 - 4 days before transplantation; Cy 60 mg×kg(-1)×d(-1), 3 - 2 days before transplantation) and Bu/Flu (Bu 3.2 mg×kg(-1)×d(-1), 5 - 2 days before transplantation; Flu 30 mg×m(-2)×d(-1), 6 - 2 days before transplantation) groups. The regimen-related toxicity (RRT), incidence and severity of graft-versus-host disease (GVHD), 3-year cumulative relapse rate, non-relapse mortality (NRM), 3-year event-free survival (EFS) rate and overall survival (OS) rate were compared between the two groups. The median follow-up duration was 617.5 (6 - 1261) days. All patients achieved successful engraftment on 30 day after transplantation. There were no significant differences in the median time to neutrophil engraftment (P = 0.121) and platelet engraftment (P = 0.171) between the two groups. The median duration of neutrophil count under 0.1×10(9)/L and platelet count under 20×10(9)/L in the Bu/Cy group were significantly longer than those in the Bu/Flu group (P = 0.000 and P = 0.047). The incidence of grades II-IV RRT were 68.8% and 25.0% (P = 0.032) in the Bu/Cy and the Bu/Flu groups, respectively. There were no significant differences in the incidence of acute GVHD (P = 0.149), chronic GVHD (P = 0.149), incidence of NRM (P = 0.333), 3-year cumulative relapse rates (P = 0.834), 3-year EFS rate (P = 0.362) and OS rate (P = 0.111) between the two groups. Compared with Bu/Cy, Bu/Flu is a myeloablative condition regimen with milder bone marrow suppression and lower RRT incidence rate in allogeneic HSCT for AML-CR1 patients without compromising the efficacy.

Effects of two doses of anti-T lymphocyte globulin-Fresenius given after full-match sibling stem cell transplantation in acute myeloblastic leukemia patients who underwent myeloablative fludarabine/busulfan conditioning.

PubMed

Boga, Can; Yeral, Mahmut; Gereklioglu, Ciğdem; Asma, Suheyl; Maytalman, Erkan; Aytan, Pelin; Kozanoglu, Ilknur; Sariturk, Cagla; Ozdogu, Hakan

2018-02-20

Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III-IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667-199.255; p = <.02). No patients developed rATG-F-related severe adverse events (Common Terminology Criteria grade 4 or 5). Dose difference of rATG-F did not influence survival parameters; however, increasing the dose to 30 mg/kg seems to be effective for reducing cGVHD with an increase in infection rate requiring close monitoring of infections in AML patients who received myeloablative fludarabine/busulfan conditioning. Copyright © 2018 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Travelling Fronts and Entire Solutionsof the Fisher-KPP Equation in N

NASA Astrophysics Data System (ADS)

Hamel, François; Nadirashvili, Nikolaï

This paper is devoted to time-global solutions of the Fisher-KPP equation in N: where f is a C2 concave function on [0,1] such that f(0)=f(1)=0 and f>0 on (0,1). It is well known that this equation admits a finite-dimensional manifold of planar travelling-fronts solutions. By considering the mixing of any density of travelling fronts, we prove the existence of an infinite-dimensional manifold of solutions. In particular, there are infinite-dimensional manifolds of (nonplanar) travelling fronts and radial solutions. Furthermore, up to an additional assumption, a given solution u can be represented in terms of such a mixing of travelling fronts.

Spectrally tunable, temporally shaped parametric front end to seed high-energy Nd:glass laser systems

DOE PAGES

Dorrer, C.; Consentino, A.; Cuffney, R.; ...

2017-10-18

Here, we describe a parametric-amplification–based front end for seeding high-energy Nd:glass laser systems. The front end delivers up to 200 mJ by parametric amplification in 2.5-ns flat-in-time pulses tunable over more than 15 nm. Spectral tunability over a range larger than what is typically achieved by laser media at similar energy levels is implemented to investigate cross-beam energy transfer in multibeam target experiments. The front-end operation is simulated to explain the amplified signal’s sensitivity to the input pump and signal. A large variety of amplified waveforms are generated by closed-loop pulse shaping. Various properties and limitations of this front endmore » are discussed.« less

Spectrally tunable, temporally shaped parametric front end to seed high-energy Nd:glass laser systems

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

Dorrer, C.; Consentino, A.; Cuffney, R.

Here, we describe a parametric-amplification–based front end for seeding high-energy Nd:glass laser systems. The front end delivers up to 200 mJ by parametric amplification in 2.5-ns flat-in-time pulses tunable over more than 15 nm. Spectral tunability over a range larger than what is typically achieved by laser media at similar energy levels is implemented to investigate cross-beam energy transfer in multibeam target experiments. The front-end operation is simulated to explain the amplified signal’s sensitivity to the input pump and signal. A large variety of amplified waveforms are generated by closed-loop pulse shaping. Various properties and limitations of this front endmore » are discussed.« less

SU-G-IeP4-09: Method of Human Eye Aberration Measurement Using Plenoptic Camera Over Large Field of View

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

Lv, Yang; Wang, Ruixing; Ma, Haotong

Purpose: The measurement based on Shack-Hartmann wave-front sensor(WFS), obtaining both the high and low order wave-front aberrations simultaneously and accurately, has been applied in the detection of human eyes aberration in recent years. However, Its application is limited by the small field of view (FOV), slight eye movement leads the optical bacon image exceeds the lenslet array which result in uncertain detection error. To overcome difficulties of precise eye location, the capacity of detecting eye wave-front aberration over FOV much larger than simply a single conjugate Hartmann WFS accurately and simultaneously is demanded. Methods: Plenoptic camera’s lenslet array subdivides themore » aperture light-field in spatial frequency domain, capture the 4-D light-field information. Data recorded by plenoptic cameras can be used to extract the wave-front phases associated to the eyes aberration. The corresponding theoretical model and simulation system is built up in this article to discuss wave-front measurement performance when utilizing plenoptic camera as wave-front sensor. Results: The simulation results indicate that the plenoptic wave-front method can obtain both the high and low order eyes wave-front aberration with the same accuracy as conventional system in single visual angle detectionand over FOV much larger than simply a single conjugate Hartmann systems. Meanwhile, simulation results show that detection of eye aberrations wave-front in different visual angle can be achieved effectively and simultaneously by plenoptic method, by both point and extended optical beacon from the eye. Conclusion: Plenoptic wave-front method possesses the feasibility in eye aberrations wave-front detection. With larger FOV, the method can effectively reduce the detection error brought by imprecise eye location and simplify the eye aberrations wave-front detection system comparing with which based on Shack-Hartmann WFS. Unique advantage of the plenoptic method lies in obtaining wave-front in different visual angle simultaneously, which provides an approach in building up 3-D model of eye refractor tomographically. Funded by the key Laboratory of High Power Laser and Physics, CAS Research Project of National University of Defense Technology No. JC13-07-01; National Natural Science Foundation of China No. 61205144.« less

Rethinking the laryngopharyngeal reflux treatment algorithm: Evaluating an alternate empiric dosing regimen and considering up-front, pH-impedance, and manometry testing to minimize cost in treating suspect laryngopharyngeal reflux disease.

PubMed

Carroll, Thomas L; Werner, Astrid; Nahikian, Kael; Dezube, Aaron; Roth, Douglas F

2017-10-01

Empiric proton pump inhibitor (PPI) trials for laryngopharyngeal reflux (LPR) are common. A majority of the patients respond to acid suppression. This work intends to evaluate once-daily, 40 mg omeprazole and once-nightly, 300 mg ranitidine (QD/QHS) dosing as an alternative regimen, and use this study's cohort to evaluate empiric regimens prescribed for LPR as compared to up-front testing with pH impedance multichannel intraluminal impedance (MII) with dual pH probes and high-resolution manometry (HRM) for potential cost minimization. Retrospective cohort review and cost minimization study. A chart review identified patients diagnosed with LPR. All subjects were treated sequentially and outcomes recorded. Initial QD/QHS dosing increased after 3 months to BID if no improvement and ultimately prescribed MII and HRM if they failed BID dosing. Decision tree diagrams were constructed to determine costs of two empiric regimens and up-front MII and HRM. Ninety-seven subjects met the criteria. Responders and nonresponders to empiric therapy were identified. Seventy-two subjects (74%) responded. Forty-eight (67% of responders and 49% of all) improved with QD/QHS dosing. Forty-nine (51%) subjects escalated to BID dosing. Twenty-four subjects (33% of responders and 25% of all) improved on BID therapy. Twenty-five subjects (26%) did not respond to acid suppression. Average weighted cost was $1,897.00 per patient for up-front testing, $3,033.00 for initial BID, and $3,366.00 for initial QD/QHS. An alternate QD/QHS regimen improved the majority who presented with presumed LPR. Cost estimates demonstrate that the QD/QHS regimen was more expensive than the initial BID high-dose PPI for 6 months. Overall per-patient cost appears less with up-front MII and HRM. 4. Laryngoscope, 127:S1-S13, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Observations and Simulations of Electron Dynamics Near an Active Neutral Line

NASA Technical Reports Server (NTRS)

Goldstein, M. L.; Hwang, Kyoung-Joo; Ashour-Abdalla, Maha; El-Aloui, Mostafa; Schriver, David; Richard, Robert; Zhou, Meng; Walker, Ray

2010-01-01

Recent observations in the Earth's magnetotail have shown rapid increases in the fluxes of energetic electrons with energies up to 100's of keV associated with dipolarization fronts that propagate into the inner magnetosphere. On August 15, 2001 the four Cluster spacecraft located slightly dawnward of midnight (yGSM approx. -5.4RE) at xGSM approx. -18RE observed a series of earthward propagating dipolarization fronts [Hwang et al., 2010]. At least 6 dipolarization fronts were observed in a 20m interval. Unlike previously reported cases the fluxes of electrons up to 95keV decreased during the passage of the first three fronts over the spacecraft. The energetic electron fluxes increased during the passage of the last three fronts. We have performed a global magnetohydrodynamic simulation of this event using solar wind observations from the ACE satellite to drive the simulation. In the simulation a very complex reconnection system in the near-Earth tail at XGSM approx. -20RE launched a series of earthward propagating dipolarization fronts that are similar to those observed on Cluster. The simulation results indicate that the Cluster spacecraft were just earthward of the reconnection site. In this paper we will present a study of the dynamics of electrons associated with these events by using the large-scale kinetic simulation approach in which we launch a large number of electrons into the electric and magnetic fields from this simulation.

Standing up against the Giant

ERIC Educational Resources Information Center

Benson, Diane E.

2003-01-01

On December 12, 2000, one of the top three headlines on the front page of the "Anchorage Daily News" ("ADN") read, "Student Attacks Professor's Poem." The subtitle read, ""Indian Girls" described as racist, insulting." One of the two primary photos on the front page that garnered attention was the…

Structure of the detonation wave front in a mixture of nitromethane with acetone

NASA Astrophysics Data System (ADS)

Buravova, S. N.

2012-09-01

It is shown that the leading front of an inhomogeneous detonation wave is a shock wave in which wave structures of the type of triple shock configurations are moving. It was experimentally found that the reaction in these inhomogeneities occurs in oblique shock waves. The reaction sites at the wave front are ring-shaped. In a 75: 25 mixture of nitromethane with acetone, up to 70% of the front surface is occupied by the reaction at the sites in the wave front. Measurements of the mass velocity profile indicate that afterburning takes place in the unloading area behind the Jouguet plane. Calculations of the heat release in the reaction mixture with a decrease in the mass velocity indicate that the material that have not reacted in the inhomogeneities can be ignited in the induction zone. It is suggested that the adiabatic flashes are a mechanism that generates inhomogeneities in the detonation wave front.

Case study of mesospheric front dissipation observed over the northeast of Brazil

NASA Astrophysics Data System (ADS)

Fragoso Medeiros, Amauri; Paulino, Igo; Wrasse, Cristiano Max; Fechine, Joaquim; Takahashi, Hisao; Valentin Bageston, José; Paulino, Ana Roberta; Arlen Buriti, Ricardo

2018-03-01

On 3 October 2005 a mesospheric front was observed over São João do Cariri (7.4° S, 36.5° W). This front propagated to the northeast and appeared in the airglow images on the west side of the observatory. By about 1.5 h later, it dissipated completely when the front crossed the local zenith. Ahead of the front, several ripple structures appeared during the dissipative process of the front. Using coincident temperature profile from the TIMED/SABER satellite and wind profiles from a meteor radar at São João do Cariri, the background of the atmosphere was investigated in detail. On the one hand, it was noted that a strong vertical wind shear in the propagation direction of the front produced by a semidiunal thermal tide was mainly responsible for the formation of duct (Doppler duct), in which the front propagated up to the zenith of the images. On the other hand, the evolution of the Richardson number as well as the appearance of ripples ahead of the main front suggested that a presence of instability in the airglow layer that did not allow the propagation of the front to the other side of the local zenith.

Pulsed discharges produced by high-power surface waves

NASA Astrophysics Data System (ADS)

Böhle, A.; Ivanov, O.; Kolisko, A.; Kortshagen, U.; Schlüter, H.; Vikharev, A.

1996-02-01

The mechanisms of the ionization front advance in surface-wave-produced discharges are investigated using two experimental set-ups. The high-power surface waves are excited in a 3 cm wavelength band by a surfaguide and a novel type of launcher (an E-plane junction). The ionization front velocity of the surface wave is measured for a wide range of gas pressures, incident microwave power and initial pre-ionization. The experimental results are compared with theoretical ones based on three different models. The comparison between theory and experiment allows one to suggest a new interpretation of the ionization front's advance. The ionization front velocity is determined by a breakdown wave or an ionization wave in the electric field of a high-power surface wave in the zone near the ionization front.

Cognitive function during and six months following chemotherapy for front-line treatment of ovarian, primary peritoneal or fallopian tube cancer: An NRG oncology/gynecologic oncology group study.

PubMed

Hess, Lisa M; Huang, Helen Q; Hanlon, Alexandra L; Robinson, William R; Johnson, Rhonda; Chambers, Setsuko K; Mannel, Robert S; Puls, Larry; Davidson, Susan A; Method, Michael; Lele, Shashikant; Havrilesky, Laura; Nelson, Tina; Alberts, David S

2015-12-01

Changes in cognitive function have been identified in and reported by many cancer survivors. These changes have the potential to impact patient quality of life and functional ability. This prospective longitudinal study was designed to quantify the incidence of change in cognitive function in newly diagnosed ovarian cancer patients throughout and following primary chemotherapy. Eligible patients had newly diagnosed, untreated ovarian cancer and had planned to receive chemotherapy. Web-based and patient reported cognitive assessments and quality of life questionnaires were conducted prior to chemotherapy, prior to cycle four, after cycle six, and six months after completion of primary therapy. Two-hundred-thirty-one evaluable patients entered this study between May 2010 and October 2011. At the cycle 4 time point, 25.2% (55/218) of patients exhibited cognitive impairment in at least one domain. At the post-cycle 6 and 6-month follow up time points, 21.1% (44/208) and 17.8% (30/169) of patients, respectively, demonstrated impairment in at least one domain of cognitive function. There were statistically significant, but clinically small, improvements in processing speed (p<0.001) and attention (p<0.001) but not in motor response time (p=0.066), from baseline through the six-month follow up time period. This was a large, prospective study designed to measure cognitive function in ovarian cancer. A subset of patients had evidence of cognitive decline from baseline during chemotherapy treatment in this study as measured by the web-based assessment; however, changes were generally limited to no more than one domain. Copyright © 2015 Elsevier Inc. All rights reserved.

Front to back ocular injury from a vaping-related explosion.

PubMed

Khairudin, Muhammad Najmi; Mohd Zahidin, Aida Zairani; Bastion, Mae-Lynn Catherine

2016-04-05

We describe a case of extensive ocular injury secondary to an electronic cigarette (e-cigarette)-related explosion. The explosion was the result of modifications made to a heating element of the e-cigarette device by a non-professional. Extensive ocular injuries that result from an explosion of an e-cigarette device can potentially cause significant and permanent visual impairment. 2016 BMJ Publishing Group Ltd.

[Case of callosal disconnection syndrome with a chief complaint of right-hand disability, despite presence of left-hand diagonistic dyspraxia].

PubMed

Okamoto, Yoko; Saida, Hisako; Yamamoto, Toru

2009-04-01

e report the case of 48-year-old right-handed male patient with an infarction affecting most part of the body and the splenium of the left half of the corpus callosum. Neuropsychological examination revealed typical signs of callosal disconnection including left-sided apraxia, diagonistic dyspraxia, left-sided agraphia, left-hand tactile anomia, left hemialexia, and right-sided constructional disability. Moreover, he complained of impairment in activities involving the right hand disability and agraphia. He could not stop behaving with his right hand when he had a vague idea. For example, he involuntarily picked up a tea bottle with his right hand when he had a desire to drink, although the action was not appropriate to that occasion. The imitation and utilization behavior did not imply this case, because his right hand behaviors were not exaggerated in response to external stimuli, such as the gestures of the examiner or the subjects in front of the patient. Unexpectedly, he complained about impairment of the activity of his right hand and was unaware of left hand apraxia or diagonistic dyspraxia; this trend continued for 6 months, at the time of this writing. We argue that the patient may have been subconsciouly aware of the symptoms of his left hand but had not verbalized them.

Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study

PubMed Central

Michallet, Anne-Sophie; Aktan, Melih; Hiddemann, Wolfgang; Ilhan, Osman; Johansson, Peter; Laribi, Kamel; Meddeb, Balkis; Moreno, Carol; Raposo, João; Schuh, Anna; Ünal, Ali; Widenius, Tom; Bernhardt, Alf; Kellershohn, Kerstin; Messeri, Dimitri; Osborne, Stuart; Leblond, Véronique

2018-01-01

MABLE investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabine-ineligible patients with chronic lymphocytic leukemia. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every four weeks for six cycles. Rituximab plus chlorambucil-treated patients without a complete response after Cycle 6 received chlorambucil monotherapy for at least six additional cycles or until complete response. The primary endpoint was complete response rate (confirmed by bone marrow biopsy) after Cycle 6 in first-line patients. Secondary endpoints included progression-free survival, overall survival, minimal residual disease, and safety. Overall, 357 patients were randomized (rituximab plus bendamustine, n=178; rituximab plus chlorambucil, n=179; intent-to-treat population), including 241 first-line patients (n=121 and n=120, respectively); 355 patients received treatment (n=177 and n=178, respectively; safety population). In first-line patients, complete response rate after Cycle 6 (rituximab plus bendamustine, 24%; rituximab plus chlorambucil, 9%; P=0.002) and median progression-free survival (rituximab plus bendamustine, 40 months; rituximab plus chlorambucil, 30 months; P=0.003) were higher with rituximab plus bendamustine than rituximab plus chlorambucil. Overall response rate and overall survival were not different. In first-line patients with a complete response, minimal residual disease-negativity was higher with rituximab plus bendamustine than rituximab plus chlorambucil (66% vs. 36%). Overall adverse event incidence was similar (rituximab plus bendamustine, 98%; rituximab plus chlorambucil, 97%). Rituximab plus bendamustine may be a valuable first-line option for fludarabine-ineligible patients with chronic lymphocytic leukemia. PMID:29419437

Modulation of the human equilibrative nucleoside transporter1 (hENT1) activity by IL-4 and PMA in B cells from chronic lymphocytic leukemia.

PubMed

Fernández Calotti, Paula; Galmarini, Carlos María; Cañones, Cristian; Gamberale, Romina; Saénz, Daniel; Avalos, Julio Sánchez; Chianelli, Mónica; Rosenstein, Ruth; Giordano, Mirta

2008-02-15

Nucleoside transporters (NTs) are essential for the uptake of therapeutic nucleoside analogs, broadly used in cancer treatment. The mechanisms responsible for NT regulation are largely unknown. IL-4 is a pro-survival signal for chronic lymphocytic leukemia (CLL) cells and has been shown to confer resistance to nucleoside analogs. The aim of this study was to investigate whether IL-4 is able to modulate the expression and function of the human equilibrative NT1 (hENT1) in primary cultures of CLL cells and, consequently, to affect cytotoxicity induced by therapeutic nucleosides analogs. We found that treatment with IL-4 (20 ng/ml for 24 h) increased mRNA hENT1 expression in CLL cells without affecting that of normal B cells. Given that the enhanced mRNA levels of hENT1 in CLL cells did not result in increased transport activity, we examined the possibility that hENT1 induced by IL-4 may require post-translational modifications to become active. We found that the acute stimulation of PKC in IL-4-treated CLL cells by short-term incubation with PMA significantly increased hENT1 transport activity and favoured fludarabine-induced apoptosis. By contrast, and in line with previous reports, IL-4 plus PMA protected CLL cells from a variety of cytotoxic agents. Our findings indicate that the combined treatment with IL-4 and PMA enhances hENT1 activity and specifically sensitizes CLL cells to undergo apoptosis induced by fludarabine.

Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

PubMed

Mori, Takehiko; Yamazaki, Rie; Aisa, Yoshinobu; Nakazato, Tomonori; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Ikeda, Yasuo; Okamoto, Shinichiro

2006-04-01

We previously reported the efficacy of oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis. The purpose of this study was to evaluate whether the further shortening of the duration of oral cryotherapy could minimize its side effects while sparing its efficacy. Seventeen consecutive recipients of allogeneic hematopoieic stem cell transplant conditioned with high-dose melphalan in combination with fludarabine alone or with fludarabine and additional radiation were enrolled in the study. The severity of stomatitis was graded according to the National Cancer Institute-Common Toxicity Criteria. Patients were kept on oral cryotherapy shortly before, during, and for additional 30 min after the completion of melphalan administration (60-min oral cryotherapy). Patients who were also enrolled in our previous study received the same type of oral cryotherapy but for additional 90 min after the completion of melphalan administration (120-min oral cryotherapy), and they served as controls. Only 2 (11.8%) of 17 patients receiving 60-min oral cryotherapy and 2 (11.1%) of 18 patients receiving 120-min oral cryotherapy developed grade 2 or 3 stomatitis, respectively. The difference between groups was not statistically significant (P = 0.677). The incidence of unpleasant symptoms such as chills and nausea during oral cryotherapy decreased significantly with 60-min oral cryotherapy, as compared with that associated with 120-min oral cryotherapy (P < 0.01). These results suggest that 60-min oral cryotherapy is as effective as 120-min oral cryotherapy at preventing high-dose melphalan-induced stomatitis, and shorter treatment might have contributed to relieve patient discomfort during oral cryotherapy.

"All Quiet on the Western Front."

ERIC Educational Resources Information Center

Soderquist, Alisa

Based on Erich Maria Remarque's novel "All Quiet on the Western Front" and other war literature, this lesson plan presents activities designed to help students understand that works of art about war can call up strong emotions in readers; and that the writing process can be applied to writing poems. The main activity of the lesson involves…

24 CFR 203.18c - One-time or up-front mortgage insurance premium excluded from limitations on maximum mortgage...

Code of Federal Regulations, 2010 CFR

2010-04-01

... insurance premium excluded from limitations on maximum mortgage amounts. 203.18c Section 203.18c Housing and...-front mortgage insurance premium excluded from limitations on maximum mortgage amounts. After... LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES SINGLE FAMILY MORTGAGE...

24 CFR 203.18c - One-time or up-front mortgage insurance premium excluded from limitations on maximum mortgage...

Code of Federal Regulations, 2011 CFR

2011-04-01

... insurance premium excluded from limitations on maximum mortgage amounts. 203.18c Section 203.18c Housing and...-front mortgage insurance premium excluded from limitations on maximum mortgage amounts. After... LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES SINGLE FAMILY MORTGAGE...

Helmet Electronics & Display System-Upgradeable Protection (HEaDS-UP) Phase III Assessment: Headgear Effects on Auditory Perception

DTIC Science & Technology

2013-11-01

difference between front and rear was less pronounced. Localization errors near 0° and 180° are dominated by front-back confusions because binaural ...used to disambiguate binaural information; therefore, it can be argued that most differences in auditory localization ability resulting from

Interior. Looking from balance room to the front entrance. Chemicals ...

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

Interior. Looking from balance room to the front entrance. Chemicals related to Edison's experiments on the extraction of latex for rubber from the goldenrod plant. Room is set up based on reconstruction research done in 1972. - Thomas A. Edison Laboratories, Building No. 2, Main Street & Lakeside Avenue, West Orange, Essex County, NJ

Sarcocystis sp. from white-fronted goose (Anser albifrons): cyst morphology and life cycle studies.

PubMed

Kutkiene, L; Sruoga, A; Butkauskas, D

2006-10-01

An experiment was carried out using three cubs of the arctic fox (Alopex lagopus). Twenty-five-day-old cubs were infected by feeding them with the leg muscles of the white-fronted goose (Anser albifrons) containing Sarcocystis sp. (cyst type III) cysts. Under the light microscope, the cysts were ribbon-shaped up to 4 mm long and up to 750 microm wide. On the surface of the wall (up to 2.4 microm), they had teat- or finger-like villar protrusions. Ultrastructurally, the cyst wall was a type-9 with villar protrusions (up to 2.3 microm long) different in size. The 11.4x1.7 (10.0-13.5x1.5-2.5)microm cystozoites were almost straight and shuttle-shaped. The fox cubs started shedding typical 12.0x8.0 (10.0-12.8x6.8-8.6)microm Sarcocystis sp. sporocysts on the 13th-14th days post-infection. The patent period lasted 19 days. The conclusion drawn was that the arctic fox (A. lagopus) can be one of the definitive hosts of Sarcocystis sp. (cyst type III) from the white-fronted goose.

Internal quantum efficiency mapping analysis for a >20%-efficiency n-type bifacial solar cell with front-side emitter formed by BBr3 thermal diffusion

NASA Astrophysics Data System (ADS)

Simayi, Shalamujiang; Mochizuki, Toshimitsu; Kida, Yasuhiro; Shirasawa, Katsuhiko; Takato, Hidetaka

2017-10-01

This paper presents a large-area (239-cm2) high-efficiency n-type bifacial solar cell that is processed using tube-furnace thermal diffusion employing liquid sources BBr3 for the front-side boron emitter and POCl3 for the rear-side phosphorus back surface field (BSF). The SiN x /Al2O3 stack was applied to the front-side boron emitter as a passivation layer. Both the front and rear-side electrodes are obtained using screen-printed contacts with H-patterns. The resulting highest-efficiency solar cell has front- and rear-side efficiencies of 20.3 and 18.7%, respectively, while the corresponding bifaciality is up to 92%. Finally, the passivation quality of the SiN x /Al2O3 stack on the front-side boron emitter and rear-side phosphorus BSF is investigated and visualized by measuring the internal quantum efficiency mapping of the bifacial solar cell.

Clinical Practice Guidelines for Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL) in The Netherlands.

PubMed

Kersting, Sabina; Neppelenbroek, Suzanne I M; Visser, Hein P J; van Gelder, Michel; Levin, Mark-David; Mous, Rogier; Posthuma, Ward; van der Straaten, Hanneke M; Kater, Arnon P

2018-01-01

In recent years, considerable progress has been made in the treatment of patients with chronic lymphocytic leukemia (CLL), and new potent drugs have become available. Therefore, the CLL working party revised the Dutch guidelines. Not only efficacy but also quality of life and socio-economic impact were taken into account in the formulation of treatment recommendations. The working party discussed a set of questions regarding diagnostic tests and treatment and wrote the draft guideline. This was evidence-based whenever possible, but in cases of low evidence, an expert-based recommendation was formulated with input of the entire working party. The draft guideline was sent to all hematologists in the Netherlands for comment and was subsequently approved. Recommendations were formulated on diagnostic tests and work-up before treatment. Also, recommendations were made for treatment with fludarabine-cyclophosphamide-rituximab, bendamustine-rituximab, chlorambucil with anti-CD20 antibody, ibrutinib, idelalisib-rituximab, venetoclax, and allogeneic stem cell transplantation. In the revised Dutch CLL guidelines, chemo-immunotherapy is still the cornerstone of CLL treatment with novel targeted drugs for specific risk groups. Copyright © 2017 Elsevier Inc. All rights reserved.

A Reduced-Intensity Conditioning Regimen for Patients with Dyskeratosis Congenita Undergoing Hematopoietic Stem Cell Transplantation.

PubMed

Nelson, Adam S; Marsh, Rebecca A; Myers, Kasiani C; Davies, Stella M; Jodele, Sonata; O'Brien, Tracey A; Mehta, Parinda A

2016-05-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for progressive marrow failure, myelodysplastic syndrome, or leukemia associated with dyskeratosis congenita (DC). HSCT for DC is limited by a high incidence of treatment-related mortality, thought to be related to underlying chromosomal instability and sensitivity to chemotherapy and radiation. We report our experience in 7 patients with DC who underwent allogeneic transplantation using a reduced-intensity conditioning (RIC) preparative regimen that contained chemotherapy only (no radiation). This RIC regimen, designed specifically for patients with DC, contained alemtuzumab, fludarabine, and melphalan (with melphalan at 50% reduced dosing), with the goal of decreasing toxicity and improving outcome. All 7 patients engrafted, with none developing mixed chimerism or rejection. Two patients experienced acute graft-versus-host disease (GVHD) and 1 went on to develop limited chronic GVHD of the skin. Five patients remain alive and well at a median follow-up of 44 months (range, 14 to 57 months). We conclude that a radiation-free RIC regimen results in durable engraftment, acceptable toxicity, and improved overall survival in patients with DC undergoing allogeneic HSCT. Published by Elsevier Inc.

The Influence of Resistance Training Experience on the Between-Day Reliability of Commonly Used Strength Measures in Male Youth Athletes.

PubMed

Weakley, Jonathon J S; Till, Kevin; Darrall-Jones, Joshua; Roe, Gregory A B; Phibbs, Padraic J; Read, Dale B; Jones, Ben L

2017-07-01

Weakley, JJS, Till, K, Darrall-Jones, J, Roe, GAB, Phibbs, PJ, Read, DB, and Jones, BL. The influence of resistance training experience on the between-day reliability of commonly used strength measures in male youth athletes. J Strength Cond Res 31(7): 2005-2010, 2017-The purpose of this study was to determine the between-day reliability of commonly used strength measures in male youth athletes while considering resistance training experience. Data were collected on 25 male athletes over 2 testing sessions, with 72 hours rest between, for the 3 repetition maximum (3RM) front squat, chin-up, and bench press. Subjects were initially categorized by resistance training experience (inexperienced; 6-12 months, experienced; >2 years). The assessment of the between-day reliability (coefficient of variation [CV%]) showed that the front squat (experienced: 2.90%; inexperienced: 1.90%), chin-up (experienced: 1.70%; inexperienced: 1.90%), and bench press (experienced: 4.50%; inexperienced: 2.40%) were all reliable measures of strength in both groups. Comparison between groups for the error of measurement for each exercise showed trivial differences. When both groups were combined, the CV% for the front squat, bench press, and chin-up were 2.50, 1.80, and 3.70%, respectively. This study provides scientists and practitioners with the between-day reliability reference data to determine real and practical changes for strength in male youth athletes with different resistance training experience. Furthermore, this study demonstrates that 3RM front squat, chin-up, and bench press are reliable exercises to quantify strength in male youth athletes.

Heat and mass transfer scale-up issues during freeze-drying, III: control and characterization of dryer differences via operational qualification tests.

PubMed

Rambhatla, S; Tchessalov, S; Pikal, Michael J

2006-04-21

The objective of this research was to estimate differences in heat and mass transfer between freeze dryers due to inherent design characteristics using data obtained from sublimation tests. This study also aimed to provide guidelines for convenient scale-up of the freeze-drying process. Data obtained from sublimation tests performed on laboratory-scale, pilot, and production freeze dryers were used to evaluate various heat and mass transfer parameters: nonuniformity in shelf surface temperatures, resistance of pipe, refrigeration system, and condenser. Emissivity measurements of relevant surfaces such as the chamber wall and the freeze dryer door were taken to evaluate the impact of atypical radiation heat transfer during scale-up. "Hot" and "cold" spots were identified on the shelf surface of different freeze dryers, and the impact of variation in shelf surface temperatures on the primary drying time and the product temperature during primary drying was studied. Calculations performed using emissivity measurements on different freeze dryers suggest that a front vial in the laboratory lyophilizer received 1.8 times more heat than a front vial in a manufacturing freeze dryer operating at a shelf temperature of -25 degrees C and a chamber pressure of 150 mTorr during primary drying. Therefore, front vials in the laboratory are much more atypical than front vials in manufacturing. Steady-state heat and mass transfer equations were used to study a combination of different scale-up issues pertinent during lyophilization cycles commonly used for the freeze-drying of pharmaceuticals.

Iodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2014-08-04

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia

ClinicalTrials.gov

2017-02-16

Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; Fanconi Anemia; Previously Treated Myelodysplastic Syndromes

Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2017-04-17

B-cell Chronic Lymphocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

The thermodynamic and dynamical features of double front structures during 21 31 July 1998 in China

NASA Astrophysics Data System (ADS)

Zhou, Yushu; Deng, Guo; Lei, Ting; Ju, Jianhua

2005-11-01

The daily 1° × 1° data of the Aviation (AVN) model, the black body temperature (TBB) data of cloud top, and cloud images by geostationary meteorological satellite (GMS) are used to identify a dew-point front near the periphery of the western Pacific subtropical high (WPSH). The results clearly demonstrate the existence of the dew-point front, and its thermodynamic and dynamic structural characteristics are analyzed in detail. The dew-point front is a transitional belt between the moist southwest monsoon flow and the dry adiabatic sinking flow near the WPSH, manifested by a large horizontal moisture gradient in the mid-lower troposphere and conjugated with the mei-yu front to form a predominant double-front structure associated with intense rainfall in the mei-yu period. The mei-yu front is located between 30° and 35°N, vertically extends from the ground level to the upper level and shifts northward. The dew-point front is to the south of the mei-yu front and lies up against the periphery of the WPSH. Generally, it is located between 850 hPa and 500 hPa. On the dew-point front side, the southwesterly prevails at the lower level and the northeasterly at the upper level; this wind distribution is different from that on the mei-yu front side. Vertical ascending motion exists between the two fronts, and there are descending motions on the north side of the mei-yu front and on the south side of the dew-point front, which form a secondary circulation. The dynamics of the double fronts also have some interesting features. At the lower level, positive vertical vorticity and obvious convergence between the two fronts are clearly identified. At the mid-lower level, negative local change of the divergence (corresponding to increasing convergence) is often embedded in the two fronts or against the mei-yu front. Most cloud clusters occur between the two fronts and propagate down stream in a wave-like manner.

Modelling the average velocity of propagation of the flame front in a gasoline engine with hydrogen additives

NASA Astrophysics Data System (ADS)

Smolenskaya, N. M.; Smolenskii, V. V.

2018-01-01

The paper presents models for calculating the average velocity of propagation of the flame front, obtained from the results of experimental studies. Experimental studies were carried out on a single-cylinder gasoline engine UIT-85 with hydrogen additives up to 6% of the mass of fuel. The article shows the influence of hydrogen addition on the average velocity propagation of the flame front in the main combustion phase. The dependences of the turbulent propagation velocity of the flame front in the second combustion phase on the composition of the mixture and operating modes. The article shows the influence of the normal combustion rate on the average flame propagation velocity in the third combustion phase.

The Front-End System For MARE In Milano

NASA Astrophysics Data System (ADS)

Arnaboldi, Claudio; Pessina, Gianluigi

2009-12-01

The first phase of MARE consists of 72 μ-bolometers composed each of a crystal of AgReO4 readout by Si thermistors. The spread in the thermistor characteristics and bolometer thermal coupling leads to different energy conversion gains and optimum operating points of the detectors. Detector biasing levels and voltage gains are completely remote-adjustable by the front end system developed, the subject of this paper, achieving the same signal range at the input of the DAQ system. The front end consists of a cold buffer stage, a second pseudo differential stage followed by a gain stage, an antialiasing filter, and a battery powered detector biasing set up. The DAQ system can be used to set all necessary parameters of the electronics remotely, by writing to a μ-controller located on each board. Fiber optics are used for the serial communication between the DAQ and the front end. To suppress interference noise during normal operation, the clocked devices of the front end are maintained in sleep-mode, except during the set-up phase of the experiment. An automatic DC detector characterization procedure is used to establish the optimum operating point of every detector of the array. A very low noise level has been achieved: about 3nV/□Hz at 1 Hz and 1 nV/□Hz for the white component, high frequencies.

Tidal variations of flow convergence, shear, and stratification at the Rio de la Plata estuary turbidity front

NASA Astrophysics Data System (ADS)

FramiñAn, Mariana B.; Valle-Levinson, Arnoldo; Sepúlveda, HéCtor H.; Brown, Otis B.

2008-08-01

Intratidal variability of density and velocity fields is investigated at the turbidity front of the Río de la Plata Estuary, South America. Current velocity and temperature-salinity profiles collected in August 1999 along a repeated transect crossing the front are analyzed. Horizontal and vertical gradients, stability of the front, convergence zones, and transverse flow associated to the frontal boundary are described. Strong horizontal convergence of the across-front velocity and build up of along-front velocity shear were observed at the front. In the proximity of the front, enhanced transverse (or along-front) flow created jet-like structures at the surface and near the bottom flowing in opposite directions. These structures persisted throughout the tidal cycle and were advected upstream (downstream) by the flood (ebb) current through a distance of ˜10 km. During peak flood, the upper layer flow reversed from its predominant downstream direction and upstreamflow occupied the entire water column; outside the peak flood, two-layer estuarine circulation dominated. Changes in density field were observed in response to tidal straining, tidal advection, and wind-induced mixing, but stratification remained throughout the tidal cycle. This work demonstrates the large spatial variability of the velocity field at the turbidity front; it provides evidence of enhanced transverse circulation along the frontal boundary; and reveals the importance of advective and frictional intratidal processes in the dynamics of the central part of the estuary.

The influence of cricket fast bowlers' front leg technique on peak ground reaction forces.

PubMed

Worthington, Peter; King, Mark; Ranson, Craig

2013-01-01

High ground reaction forces during the front foot contact phase of the bowling action are believed to be a major contributor to the high prevalence of lumbar stress fractures in fast bowlers. This study aimed to investigate the influence of front leg technique on peak ground reaction forces during the delivery stride. Three-dimensional kinematic data and ground reaction forces during the front foot contact phase were captured for 20 elite male fast bowlers. Eight kinematic parameters were determined for each performance, describing run-up speed and front leg technique, in addition to peak force and time to peak force in the vertical and horizontal directions. There were substantial variations between bowlers in both peak forces (vertical 6.7 ± 1.4 body weights; horizontal (braking) 4.5 ± 0.8 body weights) and times to peak force (vertical 0.03 ± 0.01 s; horizontal 0.03 ± 0.01 s). These differences were found to be linked to the orientation of the front leg at the instant of front foot contact. In particular, a larger plant angle and a heel strike technique were associated with lower peak forces and longer times to peak force during the front foot contact phase, which may help reduce the likelihood of lower back injuries.

West elevation of shed. Metal siding covers up the original ...

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

West elevation of shed. Metal siding covers up the original front of what was once the Middlekauf shoe shop. - Kreider-Reisner Aircraft Company, Shed, 851 Pennsylvania Avenue, Hagerstown, Washington County, MD

Consciousness as a useful concept in epilepsy classification

PubMed Central

Blumenfeld, Hal; Meador, Kimford J.

2014-01-01

Summary Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms “dyscognitive” or “dialeptic” should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic–clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired consciousness in epilepsy, but the first step is to keep this crucial practical and physiologic aspect of seizures front-and-center in our discussions. PMID:24981294

Consciousness as a useful concept in epilepsy classification.

PubMed

Blumenfeld, Hal; Meador, Kimford J

2014-08-01

Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms "dyscognitive" or "dialeptic" should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic-clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired consciousness in epilepsy, but the first step is to keep this crucial practical and physiologic aspect of seizures front-and-center in our discussions. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

The Pressure Available for Ground Cooling in Front of the Cowling of Air-cooled Airplane Engines

NASA Technical Reports Server (NTRS)

Stickle, George W; Joyner, Upshur T

1938-01-01

A study was made of the factors affecting the pressure available for ground cooling in front of a cowling. Most of the results presented were obtained with a set-up that was about one-third full scale. A number of isolated tests on four full-scale airplanes were made to determine the general applicability of the model results. The full-scale tests indicated that the model results may be applied qualitatively to full-scale design and quantitatively as a first approximation of the front pressure available for ground cooling.

The Giga Bit Transceiver based Expandable Front-End (GEFE)—a new radiation tolerant acquisition system for beam instrumentation

NASA Astrophysics Data System (ADS)

Barros Marin, M.; Boccardi, A.; Donat Godichal, C.; Gonzalez, J. L.; Lefevre, T.; Levens, T.; Szuk, B.

2016-02-01

The Giga Bit Transceiver based Expandable Front-End (GEFE) is a multi-purpose FPGA-based radiation tolerant card. It is foreseen to be the new standard FMC carrier for digital front-end applications in the CERN BE-BI group. Its intended use ranges from fast data acquisition systems to slow control installed close to the beamlines, in a radioactive environment exposed to total ionizing doses of up to 750 Gy. This paper introduces the architecture of the GEFE, its features as well as examples of its application in different setups.

Long-term outcomes of fludarabine, melphalan and antithymocyte globulin as reduced-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiency disorders: a prospective single center study.

PubMed

Hamidieh, A A; Behfar, M; Pourpak, Z; Faghihi-Kashani, S; Fazlollahi, M R; Hosseini, A S; Movahedi, M; Mozafari, M; Moin, M; Ghavamzadeh, A

2016-02-01

Reduced-intensity conditioning (RIC) has offered many primary immunodeficiency disorder (PID) patients who are ineligible for myeloablative regimens a chance of cure. However, the beneficial role of RIC was questioned following reports suggesting higher chance of rejection and lower symptom resolution rate in mixed chimerism settings. Forty-five children affected by PIDs with a median age of 21 months underwent allogeneic hematopoietic stem cell transplantation in our institute from 2007 to 2013. All patients received an identical RIC regimen. Forty-one patients had successful primary engraftment (91%). Of the successful engraftments, 80% (n=33) had stable full donor chimerism at last contact. Overall, eleven transplant-related mortalities were reported including five patients due to sepsis, three children due to grade IV acute GvHD, two due to chronic GvHD and one patient due to sepsis after primary graft failure. The median post-transplantation follow-up of deceased patients was 55 days. Five-year overall survival and disease-free survival was 75.6% and 68.89%, respectively. All surviving patients with successful engraftment became disease free, regardless of having full or mixed chimerism. Our study suggests that RIC regimen provides satisfactory rates of successful engraftment and full chimerism. Furthermore, patients with mixed chimerism were stable in long-term follow-up and this chimerism status offered the potential to resolve symptoms of immunodeficiency.

Estimation of Survival Probabilities for Use in Cost-effectiveness Analyses: A Comparison of a Multi-state Modeling Survival Analysis Approach with Partitioned Survival and Markov Decision-Analytic Modeling

PubMed Central

Williams, Claire; Lewsey, James D.; Mackay, Daniel F.; Briggs, Andrew H.

2016-01-01

Modeling of clinical-effectiveness in a cost-effectiveness analysis typically involves some form of partitioned survival or Markov decision-analytic modeling. The health states progression-free, progression and death and the transitions between them are frequently of interest. With partitioned survival, progression is not modeled directly as a state; instead, time in that state is derived from the difference in area between the overall survival and the progression-free survival curves. With Markov decision-analytic modeling, a priori assumptions are often made with regard to the transitions rather than using the individual patient data directly to model them. This article compares a multi-state modeling survival regression approach to these two common methods. As a case study, we use a trial comparing rituximab in combination with fludarabine and cyclophosphamide v. fludarabine and cyclophosphamide alone for the first-line treatment of chronic lymphocytic leukemia. We calculated mean Life Years and QALYs that involved extrapolation of survival outcomes in the trial. We adapted an existing multi-state modeling approach to incorporate parametric distributions for transition hazards, to allow extrapolation. The comparison showed that, due to the different assumptions used in the different approaches, a discrepancy in results was evident. The partitioned survival and Markov decision-analytic modeling deemed the treatment cost-effective with ICERs of just over £16,000 and £13,000, respectively. However, the results with the multi-state modeling were less conclusive, with an ICER of just over £29,000. This work has illustrated that it is imperative to check whether assumptions are realistic, as different model choices can influence clinical and cost-effectiveness results. PMID:27698003

Estimation of Survival Probabilities for Use in Cost-effectiveness Analyses: A Comparison of a Multi-state Modeling Survival Analysis Approach with Partitioned Survival and Markov Decision-Analytic Modeling.

PubMed

Williams, Claire; Lewsey, James D; Mackay, Daniel F; Briggs, Andrew H

2017-05-01

Modeling of clinical-effectiveness in a cost-effectiveness analysis typically involves some form of partitioned survival or Markov decision-analytic modeling. The health states progression-free, progression and death and the transitions between them are frequently of interest. With partitioned survival, progression is not modeled directly as a state; instead, time in that state is derived from the difference in area between the overall survival and the progression-free survival curves. With Markov decision-analytic modeling, a priori assumptions are often made with regard to the transitions rather than using the individual patient data directly to model them. This article compares a multi-state modeling survival regression approach to these two common methods. As a case study, we use a trial comparing rituximab in combination with fludarabine and cyclophosphamide v. fludarabine and cyclophosphamide alone for the first-line treatment of chronic lymphocytic leukemia. We calculated mean Life Years and QALYs that involved extrapolation of survival outcomes in the trial. We adapted an existing multi-state modeling approach to incorporate parametric distributions for transition hazards, to allow extrapolation. The comparison showed that, due to the different assumptions used in the different approaches, a discrepancy in results was evident. The partitioned survival and Markov decision-analytic modeling deemed the treatment cost-effective with ICERs of just over £16,000 and £13,000, respectively. However, the results with the multi-state modeling were less conclusive, with an ICER of just over £29,000. This work has illustrated that it is imperative to check whether assumptions are realistic, as different model choices can influence clinical and cost-effectiveness results.

Platinum and high-dose cytarabine-based regimens are efficient in ultra high/high-risk chronic lymphocytic leukemia and Richter's syndrome: results of a French retrospective multicenter study.

PubMed

Durot, Eric; Michallet, Anne-Sophie; Leprêtre, Stéphane; Le, Quoc-Hung; Leblond, Véronique; Delmer, Alain

2015-08-01

Ultra high-risk chronic lymphocytic leukemia (CLL) and Richter's syndrome (RS) usually display a poor prognosis. Platinum and cytarabine-based regimens have not been evaluated in large cohorts of patients with CLL or RS. This retrospective study was aimed to assess the efficacy of these regimens in 75 patients with relapsed/refractory (R/R) CLL or RS. Forty-seven patients had R/R CLL (including 36 ultra high-risk CLL) and 28 had RS. Median age was 62 years (range, 18-79 years). Median number of previous therapies was 3 (range, 1-7), including fludarabine-based regimens (75%) and alemtuzumab (32%), and 61% of patients were refractory to their last treatment. Deletions of chromosomes 17p and 11q were found in 40% and 39% of cases, respectively. The overall response rates were 60% with 24% complete response (CR) in CLL, and 43% with 25% CR in RS. The median progression-free survival and overall survival were 11 and 14.6 months, respectively. Fludarabine refractoriness and 17p deletion were not associated with a poorer outcome. The only factors predicting shorter survival were performance status ≥ 2 (P = 0.04) and albumin level <3.5 g/dL (P = 0.0004). Toxicities were mainly myelosuppression and infectious complications. Platinum and high-dose cytarabine-based regimens provide high response rates in high-risk CLL and in RS. However, these results will be challenged by the new arriving agents at least in non-transformed CLL. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome.

PubMed

Ferrara, Felicetto; Palmieri, Salvatore; Izzo, Tiziana; Criscuolo, Clelia; Riccardi, Cira

2010-12-01

Acute myeloid leukaemia (AML) secondary to myelodysplastic syndrome (MDS) is characterized by poor prognosis, namely in older patients. The combination of fludarabine (F) with cytarabine (ARA-C) ± G-CSF was proven as effective in patients with poor risk AML. The efficacy and toxicity of a regimen including F + ARA-C as sequential continuous infusion (CI-FLA) in 64 untreated patients aged >60 years, in which AML arose after a previous MDS, was investigated. Median age was 67 years (61-81). In patients achieving CR, an additional course, followed by G-CSF to mobilize CD34+ cells and subsequent autologous stem cell transplantation (ASCT) were programmed. Overall, 43 patients (67%) achieved complete remission (CR). There were 10 induction deaths (16%), while 11 patients (17%) were refractory to induction treatment. Thirty-four patients (79% of remitters) were eligible for the consolidation and 30 were monitorized for the mobilization of CD34+ cells, collection being successful in 20 of them (67%). Median number of CD34+ cells/kg collected was 6.8 × 10E6. Thirteen patients (20% of the whole population) received ASCT. Median disease free survival (DFS) and overall survival (OS) were 10 and 9 months, respectively. Survival at 5 years is projected to 15%. The only parameter significantly related to either DFS duration or OS duration was unfavourable cytogenetics, which did significantly influence also CR achievement. CI-FLA is effective in elderly patients with AML secondary to previously diagnosed MDS. Best results are achievable in the subgroup of patients with diploid karyotype. Copyright © 2010 John Wiley & Sons, Ltd.

Cost-Effectiveness Model for Chemoimmunotherapy Options in Patients with Previously Untreated Chronic Lymphocytic Leukemia Unsuitable for Full-Dose Fludarabine-Based Therapy.

PubMed

Becker, Ursula; Briggs, Andrew H; Moreno, Santiago G; Ray, Joshua A; Ngo, Phuong; Samanta, Kunal

2016-06-01

To evaluate the cost-effectiveness of treatment with anti-CD20 monoclonal antibody obinutuzumab plus chlorambucil (GClb) in untreated patients with chronic lymphocytic leukemia unsuitable for full-dose fludarabine-based therapy. A Markov model was used to assess the cost-effectiveness of GClb versus other chemoimmunotherapy options. The model comprised three mutually exclusive health states: "progression-free survival (with/without therapy)", "progression (refractory/relapsed lines)", and "death". Each state was assigned a health utility value representing patients' quality of life and a specific cost value. Comparisons between GClb and rituximab plus chlorambucil or only chlorambucil were performed using patient-level clinical trial data; other comparisons were performed via a network meta-analysis using information gathered in a systematic literature review. To support the model, a utility elicitation study was conducted from the perspective of the UK National Health Service. There was good agreement between the model-predicted progression-free and overall survival and that from the CLL11 trial. On incorporating data from the indirect treatment comparisons, it was found that GClb was cost-effective with a range of incremental cost-effectiveness ratios below a threshold of £30,000 per quality-adjusted life-year gained, and remained so during deterministic and probabilistic sensitivity analyses under various scenarios. GClb was estimated to increase both quality-adjusted life expectancy and treatment costs compared with several commonly used therapies, with incremental cost-effectiveness ratios below commonly referenced UK thresholds. This article offers a real example of how to combine direct and indirect evidence in a cost-effectiveness analysis of oncology drugs. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Impact of cyclophosphamide dose of conditioning on the outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia from human leukocyte antigen-identical sibling.

PubMed

Mori, Takehiko; Koh, Hideo; Onishi, Yasushi; Kako, Shinichi; Onizuka, Makoto; Kanamori, Heiwa; Ozawa, Yukiyasu; Kato, Chiaki; Iida, Hiroatsu; Suzuki, Ritsuro; Ichinohe, Tatsuo; Kanda, Yoshinobu; Maeda, Tetsuo; Nakao, Shinji; Yamazaki, Hirohito

2016-04-01

The standard conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia from a human leukocyte antigen (HLA)-identical sibling has been high-dose cyclophosphamide (CY 200 mg/kg). In the present study, results for 203 patients with aplastic anemia aged 16 years or older who underwent allogeneic HSCT from HLA-identical siblings were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. Conditioning regimens were defined as a (1) high-dose CY (200 mg/kg or greater)-based (n = 117); (2) reduced-dose CY (100 mg/kg or greater, but less than 200 mg/kg)-based (n = 38); and (3) low-dose CY (less than 100 mg/kg)-based (n = 48) regimen. Patient age and the proportion of patients receiving fludarabine were significantly higher in the reduced- and low-dose CY groups than the high-dose CY group. Engraftment was comparable among the groups. Five-year overall survival (OS) tended to be higher in the low-dose CY group [93.0 % (95 % CI 85.1-100.0 %)] than the high-dose CY [84.2 % (95 % CI 77.1-91.3 %)] or reduced-dose CY groups [83.8 % (95 % CI 71.8-95.8 %); P = 0.214]. Age-adjusted OS was higher in the low-dose CY group than the high- and reduced-dose CY groups with borderline significance (P = 0.067). These results suggest that CY dose can safely be reduced without increasing graft rejection by adding fludarabine in allogeneic HSCT for aplastic anemia from an HLA-identical sibling.

Comparison of pediatric allogeneic transplant outcomes using myeloablative busulfan with cyclophosphamide or fludarabine

PubMed Central

Artz, Andrew; Frangoul, Haydar; Loren, Alison; Mineishi, Shin

2018-01-01

Busulfan combined with cyclophosphamide (BuCy) has long been considered a standard myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (HCT), including both nonmalignant conditions and myeloid diseases. Substituting fludarabine for cyclophosphamide (BuFlu) to reduce toxicity without an increase in relapse has been increasingly performed in children, but without comparison with BuCy. We retrospectively analyzed 1781 children transplanted from 2008 to 2014 to compare the effectiveness of BuCy with BuFlu. Nonmalignant and malignant disease populations were analyzed separately. Overall mortality was comparable for children with nonmalignant conditions who received BuFlu or BuCy (relative risk [RR], 1.14, P = .52). Lower incidences of sinusoidal obstruction syndrome (P = .04), hemorrhagic cystitis (P = .04), and chronic graft-versus-host disease (P = .02) were observed after BuFlu, but the influence of the conditioning regimen could not be assessed by multivariate analysis because of the low frequency of these complications. Children transplanted for malignancies were more likely to receive BuFlu if they had higher hematopoietic cell transplantation-comorbidity index scores (P < .001) or their donor was unrelated and HLA-mismatched (P = .004). Nevertheless, there were no differences in transplant toxicities and comparable transplant-related mortality (RR, 1.2; P = .46), relapse (RR, 1.2; P = .15), and treatment failure (RR, 1.2; P = .12). BuFlu was associated with higher overall mortality (RR, 1.4; P = .008) related to inferior postrelapse survival (P = .001). Our findings demonstrated that outcomes after BuFlu are similar to those for BuCy for children, but for unclear reasons, those receiving BuFlu for malignancy may be at risk for shorter postrelapse survival. PMID:29844205

Contrasting in vitro effects for the combination of fludarabine, cytosine arabinoside (Ara-C) and granulocyte colony-stimulating factor (FLAG) compared with daunorubicin and Ara-C in P-glycoprotein-positive and P-glycoprotein-negative acute myeloblastic leukaemia.

PubMed

Higashi, Y; Turzanski, J; Pallis, M; Russell, N H

2000-11-01

It has been suggested that the FLAG remission induction regimen comprising fludarabine (F-ara), cytosine arabinoside (Ara-C) and granulocyte colony-stimulating factor (G-CSF) may be capable of overcoming P-glycoprotein (P-gp)-related multidrug resistance (MDR) in patients with acute myeloblastic leukaemia (AML). We have investigated the in vitro response of P-gp-positive and -negative AML clones to FLAG and compared this with their response to treatment with Ara-C and daunorubicin (DNR). Twenty-four cryopreserved samples from patients with AML were studied using a flow cytometric technique for the enumeration of viable (7-amino actinomycin D negative) cells. Samples consisted of 12 P-gp-positive and 12 P-gp-negative cases, as measured by the MRK16 antibody. The results were analysed by calculating the comparative drug resistance (CDR), i.e. the percentage cell death caused by Ara-C + DNR subtracted from the percentage cell death, caused by FLAG after 48 h incubation in suspension culture. P-gp-positive clones were shown to have a significantly higher CDR than P-gp-negative clones (P = 0. 001). Furthermore, a significant positive correlation (r2 = 0.40, P < 0.01) was found between P-gp protein expression and CDR. However, P-gp function, measured using cyclosporin modulation of rhodamine 123 (R123) uptake, was not associated with the CDR, demonstrating that there are other properties of P-gp, besides its role in drug efflux, that modulate the responsiveness of AML blasts to chemotherapy. These results are consistent with a potential benefit for FLAG in P-gp-positive AML, but not P-gp-negative AML, compared with standard anthracycline and Ara-C therapy.

Using Data From the Microsoft Kinect 2 to Quantify Upper Limb Behavior: A Feasibility Study.

PubMed

Dehbandi, Behdad; Barachant, Alexandre; Harary, David; Long, John Davis; Tsagaris, K Zoe; Bumanlag, Silverio Joseph; He, Victor; Putrino, David

2017-09-01

The objective of this study was to assess whether the novel application of a machine learning approach to data collected from the Microsoft Kinect 2 (MK2) could be used to classify differing levels of upper limb impairment. Twenty-four healthy subjects completed items of the Wolf Motor Function Test (WMFT), which is a clinically validated metric of upper limb function for stroke survivors. Subjects completed the WMFT three times: 1) as a healthy individual; 2) emulating mild impairment; and 3) emulating moderate impairment. A MK2 was positioned in front of participants, and collected kinematic data as they completed the WMFT. A classification framework, based on Riemannian geometry and the use of covariance matrices as feature representation of the MK2 data, was developed for these data, and its ability to successfully classify subjects as either "healthy," "mildly impaired," or "moderately impaired" was assessed. Mean accuracy for our classifier was 91.7%, with a specific accuracy breakdown of 100%, 83.3%, and 91.7% for the "healthy," "mildly impaired," and "moderately impaired" conditions, respectively. We conclude that data from the MK2 is of sufficient quality to perform objective motor behavior classification in individuals with upper limb impairment. The data collection and analysis framework that we have developed has the potential to disrupt the field of clinical assessment. Future studies will focus on validating this protocol on large populations of individuals with actual upper limb impairments in order to create a toolkit that is clinically validated and available to the clinical community.

Passive microwave detection of river-plume fronts in the German Bight

NASA Technical Reports Server (NTRS)

Blume, H.-J. C.

1982-01-01

The NASA P-3 aircraft with the L- and S-band radiometer system on board participated in the MARSEN experiments carried out between August 30 and September 23, 1979. Measurements of surface temperature and salinity were concentrated on freshwater outflows of the Rivers Weser and Elbe in the German Bight. Three missions were carried out, on September 19, 22, and 23. The values of salinity are plotted as a function of geographic position, and contour maps of the salinity distribution are generated from the value plots. It is noted that on September 22, during a noon flood-tide, two river-plume salinity fronts were detected when a body of water with higher salinity existed in front of the Weser delta near Bremerhaven generating with the river outflow of lower saline waters a front of delta-S equals 5 per thousand. Another pocket of lower saline waters was found in front of the Elbe delta at Cuxhaven, which in turn set up a strong front of delta-S equals 6 per thousand. The morning low tide of September 23 did not exhibit this extreme condition.

Chondrule-forming Shock Fronts in the Solar Nebula: A Possible Unified Scenario for Planet and Chondrite Formation

NASA Astrophysics Data System (ADS)

Boss, A. P.; Durisen, R. H.

2005-03-01

Chondrules are millimeter-sized spherules found throughout primitive chondritic meteorites. Flash heating by a shock front is the leading explanation of their formation. However, identifying a mechanism for creating shock fronts inside the solar nebula has been difficult. In a gaseous disk capable of forming Jupiter, the disk must have been marginally gravitationally unstable at and beyond Jupiter's orbit. We show that this instability can drive inward spiral shock fronts with shock speeds of up to ~10 km s-1 at asteroidal orbits, sufficient to account for chondrule formation. The mixing and transport of solids in such a disk, combined with the planet-forming tendencies of gravitational instabilities, results in a unified scenario linking chondrite production with gas giant planet formation.

Seasonal variability in ice-front position, glacier speed, and surface elevation at Helheim Glacier, SE Greenland, from 2010-2016

NASA Astrophysics Data System (ADS)

Kehrl, L. M.; Joughin, I. R.; Shean, D. E.

2016-12-01

Marine-terminating glaciers can be very sensitive to changes in ice-front position, depending on their geometry. If a nearly grounded glacier retreats into deeper water, the glacier typically must speed up to produce the additional longitudinal and lateral stress gradients necessary to restore force balance. This speedup often causes thinning, which can increase the glacier's susceptibility to further retreat. In this study, we combine satellite observations and numerical modeling (Elmer/Ice) to investigate how seasonal changes in ice-front position affect glacier speed and surface elevation at Helheim Glacier, SE Greenland, from 2010-2016. Helheim's calving front position fluctuated about a mean position from 2010-2016. During 2010/11, 2013/14, and 2015/16, Helheim seasonally retreated and advanced along a reverse bed slope by > 3 km. During these years, the glacier retreated from winter/spring to late summer and then readvanced until winter/spring. During the retreat, Helheim sped up by 20-30% and thinned by 20 m near its calving front. This thinning caused the calving front to unground, and a floating ice tongue was then able to readvance over the following winter with limited iceberg calving. The advance, which continued until the glacier reached the top of the bathymetric high, caused the glacier to slow and thicken. During years when Helheim likely did not form a floating ice tongue, iceberg calving continued throughout the winter. Consequently, the formation of this floating ice tongue may have helped stabilize Helheim after periods of rapid retreat and dynamic thinning. Helheim's rapid retreat from 2001-2005 also ended when a floating ice tongue formed and readvanced over the 2005/06 winter. These seasonal retreat/advance cycles may therefore be important for understanding Helheim's long-term behavior.

The risk of newly developed visual impairment in treated normal-tension glaucoma: 10-year follow-up.

PubMed

Choi, Yun Jeong; Kim, Martha; Park, Ki Ho; Kim, Dong Myung; Kim, Seok Hwan

2014-12-01

To investigate the risk and risk factors for newly developed visual impairment in treated patients with normal-tension glaucoma (NTG) followed up on for 10 years. Patients with NTG, who did not have visual impairment at the initial diagnosis and had undergone intraocular pressure (IOP)-lowering treatment for more than 7 years, were included on the basis of a retrospective chart review. Visual impairment was defined as either low vision (0.05 [20/400] ≤ visual acuity (VA) <0.3 [20/60] and/or 10 degrees ≤ central visual field (VF) <20 degrees) or blindness (VA <0.05 [20/400] and/or central VF <10 degrees) by World Health Organization (WHO) criteria. To investigate the risk and risk factors for newly developed visual impairment, Kaplan-Meier survival analysis and generalized linear mixed effects models were utilized. During the 10.8 years mean follow-up period, 20 eyes of 16 patients were diagnosed as visual impairment (12 eyes as low vision, 8 as blindness) among 623 eyes of 411 patients. The cumulative risk of visual impairment in at least one eye was 2.8% at 10 years and 8.7% at 15 years. The risk factors for visual impairment from treated NTG were worse VF mean deviation (MD) at diagnosis and longer follow-up period. The risk of newly developed visual impairment in the treated patients with NTG was relatively low. Worse VF MD at diagnosis and longer follow-up period were associated with development of visual impairment. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[Apolipoprotein e polymorphism and cognitive function change of the elderly in a rural area, Korea].

PubMed

Kim, Sang Kyu; Hwang, Tae Yoon; Lee, Kyeong Soo; Kang, Pock Soo; Cho, Hee Soon; Bae, Young Kyung

2009-07-01

The aim of this study is to examine the cognitive function change related to aging, the incidence of cognitive impairment, and the association between apolipoprotein E polymorphism and cognitive impairment through a follow-up of the elderly with normal cognitive ability at baseline. Two hundred and fifteen subjects aged 65 and over were surveyed in February, 1998 (baseline survey), and their cognitive function was assessed again in 2003 (1st follow-up) and the once again in 2006 (2nd follow-up). Ninety one subjects completed all surveys up through the 2nd follow-up and their cognitive function scores using MMSE-K (Korean Version of the Mini-Mental State Examination) and the distribution of apolipoprotein E allele were analyzed. The cognitive function scores decreased with aging and the difference between baseline and the 2nd follow-up scores of the study increased with the age group. The incidence rate of cognitive impairment through an 8-year follow-up was 38.5% and higher in older age groups. Age was the only significant factor for incidence of cognitive impairment, but there was no significant association between apolipoprotein E genotype and incidence of cognitive impairment. The cognition of the elderly decreased with aging and the association of apolipoprotein E genotype with incidence of cognitive impairment was not significant in this study. To confirm the association between apolipoprotein E polymorphism and incidence of cognitive impairment further studies will be needed.

Biophysical Processes at the Boundary between the Arctic and Subarctic in the Barents Sea

NASA Astrophysics Data System (ADS)

Drinkwater, K.

2016-02-01

The boundary between the Arctic and Subarctic is often in the form of a strong front. Results from field studies on the Polar Front in the Barents Sea separating Arctic and Atlantic waters are presented. The focus is on the physical dynamics of the front and their influence on the structure and function of the associated marine biology from biogeochemistry and nutrient dynamics through plankton ecology up to fish. Data were collected using CTDs, autonomous gliders, microstructure profilers, a Fast Repetition Rate Flourometer (FRRF) and conventional nets for capturing plankton and fish. The Polar Front exhibits strong horizontal gradients in temperature and salinity but weak density gradients owing to density compensation of the water mass characteristics. Intense interleaving of the water masses occurs at the front along isopycnals resulting in large variability in the vertical profiles of the temperature-salinity characteristics. Although there are elevated turbulence levels in the vicinity of the front owing to both current shear and double diffusion, turbulence levels are still relatively weak and not strong enough to create strong vertical mixing. As a result nutrient levels in the near surface layers remain low through the summer following the spring bloom and there is no evidence of greatly enhanced primary production or high phytoplankton biomass in the front. Small zooplankton appear to be more prominent at the front and large zooplankton away from the front. Capelin show a similar distribution with small individuals in the front and larger capelin away from the front, mainly in the Arctic waters. Hypotheses on the relationship between the frontal dynamics and fish distributions are presented. Changes in the frontal position and intensity under climate change will also be discussed.

Low-cost SI-POF analogue TIA and equaliser

NASA Astrophysics Data System (ADS)

Lope, Ignacio; García del Pozo, Jose Maria; Mateo, Javier; Urdangarín, Julen; Celma, Santiago

2012-11-01

This article proposes the two first blocks of an analogue front-end suitable for plastic optical fibre systems suitable for the standard IEEE 1394. These blocks consist of a preamplifier followed by an equaliser which employs low-cost commercial components and are designed with two different bipolar technologies. With a supply voltage of 3.3 V, the front-end consumes 396 mW. The total gain is 70 dBΩ and it operates at up to 800 Mb/s. At this bit rate, with fibre lengths of up to 30 m, the circuit has a BER ≤ 10-12 and a maximum jitter of 170 psrms.

Advanced RF Front End Technology

NASA Technical Reports Server (NTRS)

Herman, M. I.; Valas, S.; Katehi, L. P. B.

2001-01-01

The ability to achieve low-mass low-cost micro/nanospacecraft for Deep Space exploration requires extensive miniaturization of all subsystems. The front end of the Telecommunication subsystem is an area in which major mass (factor of 10) and volume (factor of 100) reduction can be achieved via the development of new silicon based micromachined technology and devices. Major components that make up the front end include single-pole and double-throw switches, diplexer, and solid state power amplifier. JPL's Center For Space Microsystems - System On A Chip (SOAC) Program has addressed the challenges of front end miniaturization (switches and diplexers). Our objectives were to develop the main components that comprise a communication front end and enable integration in a single module that we refer to as a 'cube'. In this paper we will provide the latest status of our Microelectromechanical System (MEMS) switches and surface micromachined filter development. Based on the significant progress achieved we can begin to provide guidelines of the proper system insertion for these emerging technologies. Additional information is contained in the original extended abstract.

Experimental studies of one-way reaction front barriers in three-dimensional vortex flows

NASA Astrophysics Data System (ADS)

Gannon, Joanie; Doan, Minh; Simons, Jj; Mitchell, Kevin; Solomon, Tom

2017-11-01

We present results of experimental studies of the evolution of the excitable, Ruthenium (Ru)-catalyzed, Belousov-Zhabotinsky (BZ) reaction in a three-dimensional (3D) flow composed of the superposition of horizontal and vertical vortex chains. The reaction fronts are imaged in 3D with a scanning, laser-induced fluorescence technique that takes advantage of the differential fluoresence of the Ruthenium indicated at the front. When the horizontal and vertical vortex chains are lined up, a dominant scroll structure is observed that acts as a one-way barrier blocking fronts propagating across vortex boundaries and into vortex centers. A second, quarter-tube barrier is observed along the edges of the unit cell. When the vortices are shifted relative to each other, tube-like barriers are observed in the interior. All of these barriers are compared with burning invariant manifolds predicted from a 6D set of differential equations describing the evolution of front elements in the flow. Supported by NSF Grants DMR-1361881 and DUE-1317446.

Color multiplexing method to capture front and side images with a capsule endoscope.

PubMed

Tseng, Yung-Chieh; Hsu, Hsun-Ching; Han, Pin; Tsai, Cheng-Mu

2015-10-01

This paper proposes a capsule endoscope (CE), based on color multiplexing, to simultaneously record front and side images. Only one lens associated with an X-cube prism is employed to catch the front and side view profiles in the CE. Three color filters and polarizers are placed on three sides of an X-cube prism. When objects locate at one of the X-cube's three sides, front and side view profiles of different colors will be caught through the proposed lens and recorded at the color image sensor. The proposed color multiplexing CE (CMCE) is designed with a field of view of up to 210 deg and a 180 lp/mm resolution under f-number 2.8 and overall length 13.323 mm. A ray-tracing simulation in the CMCE with the color multiplexing mechanism verifies that the CMCE not only records the front and side view profiles at the same time, but also has great image quality at a small size.

Front-office staff can improve clinical tobacco intervention: health coordinator pilot project.

PubMed

Bass, Frederic; Naish, Brigham; Buwembo, Isaac

2013-11-01

To learn whether front-line personnel in primary care practices can increase delivery of clinical tobacco interventions and also help smokers address physical inactivity, at-risk alcohol use, and depression. Uncontrolled before-and-after design. Vancouver, BC, area (4 practices); northern British Columbia (2 practices). Six practices, with 1 staff person per practice serving as a "health coordinator" who tracked and, after the baseline period, delivered preventive interventions to all patients who smoked. To assess delivery of preventive interventions, each practice was to sample 300 consecutive patient records, both at baseline and at follow-up 15 months later. Front-office staff were recruited, trained, paid, and given ongoing support to provide preventive care. Clinicians supplemented this care with advice and guided the use of medication. Effectiveness of the intervention was based on comparison, at baseline and at follow-up, of the proportion of patients with any of the following 6 proven intervention components documented in their medical records: chart reminder, advice received, self-management plan, target quit date, referral, and follow-up date (as they applied to tobacco, physical inactivity, at-risk alcohol use, and depression). A Tobacco Intervention Flow Sheet cued preventive care, and its data were entered into a spreadsheet (which served as a smokers' registry). Qualitative appraisal data were noted. For tobacco, substantial increases occurred after the intervention period in the proportion of patients with each of the intervention components noted in their charts: chart reminder (20% vs 94%); provision of advice (34% vs 79%); self-management plan (14% vs 57%); target quit date (5% vs 11%); referral (6% vs 11%); and follow-up date (7% vs 42%). Interventions for physical inactivity and depression showed some gains, but there were no gains for at-risk alcohol use. Front-line staff, patients, and clinicians were enthusiastic about the services offered. Selected front-office personnel can substantially increase the delivery of evidence-based clinical tobacco intervention and increase patient and staff satisfaction in doing so. How far these findings can be generalized and their population effects require further study.

Front-end electronics and DAQ for the EURITRACK tagged neutron inspection system

NASA Astrophysics Data System (ADS)

Lunardon, M.; Bottosso, C.; Fabris, D.; Moretto, S.; Nebbia, G.; Pesente, S.; Viesti, G.; Bigongiari, A.; Colonna, A.; Tintori, C.; Valkovic, V.; Sudac, D.; Peerani, P.; Sequeira, V.; Salvato, M.

2007-08-01

The EURopean Illicit TRAfficing Countermeasures Kit (EURITRACK) Front-End and Data Acquisition System is a compact set of VME boards interfaced with a standard PC. The system is part of a cargo container inspection portal based on the tagged neutrons technique. The front-end processes all detector signals and checks coincidences between any of the 64 pixels of the alpha particle detector and any gamma-ray signals in 22 NaI(Tl) scintillators. The system is capable of handling the data flow at neutron flux up to the portal limiting value of 108 neutrons/second. Some typical applications are presented.

Automatic low-order aberrations compensator for a conduction-cooled end-pumped solid-state zigzag slab laser

NASA Astrophysics Data System (ADS)

Yu, Xin; Dong, Lizhi; Lai, Boheng; Yang, Ping; Wang, Shuai; Wang, Xun; Liu, Yong; Tang, Guomao; Xu, Bing

2017-11-01

In order to solve the problem of large low-order aberrations with solid-state zigzag slab lasers, an automatic compensator has been developed in this paper. In this compensator, three lenses are mounted on a motorized rail, whose positions can be obtained using ray tracing method based on the beam parameters detected by a wave-front sensor. The initial peak to valley (PV) values of the wave-front range up to several tens of microns. Both simulated and experimental results show that the PV values of the wave-front can be reduced to around 1 . 6 μm with the proposed automatic compensator.

Hearing in Noise Test Brazil: standardization for young adults with normal hearing.

PubMed

Sbompato, Andressa Forlevise; Corteletti, Lilian Cassia Bornia Jacob; Moret, Adriane de Lima Mortari; Jacob, Regina Tangerino de Souza

2015-01-01

Individuals with the same ability of speech recognition in quiet can have extremely different results in noisy environments. To standardize speech perception in adults with normal hearing in the free field using the Brazilian Hearing in Noise Test. Contemporary, cross-sectional cohort study. 79 adults with normal hearing and without cognitive impairment participated in the study. Lists of Hearing in Noise Test sentences were randomly in quiet, noise front, noise right, and noise left. There were no significant differences between right and left ears at all frequencies tested (paired t-1 test). Nor were significant differences observed when comparing gender and interaction between these conditions. A difference was observed among the free field positions tested, except in the situations of noise right and noise left. Results of speech perception in adults with normal hearing in the free field during different listening situations in noise indicated poorer performance during the condition with noise and speech in front, i.e., 0°/0°. The values found in the standardization of the Hearing in Noise Test free field can be used as a reference in the development of protocols for tests of speech perception in noise, and for monitoring individuals with hearing impairment. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Prospective environmental restoration/ restoration up front: a concept for an incentive-based program to increase restoration planning and implementation in the United States.

PubMed

Stahl, Ralph G; Gouguet, Ron; DeSantis, Amanda; Liu, Jenny; Ammann, Michael

2008-01-01

This article describes a concept variously termed prospective environmental restoration, restoration up front, or restoration banking. Briefly, the concept centers on the ability of an entity, public or private, to gain durable credits for undertaking proactive restoration activities. Once obtained, these credits can be applied to an existing liability, held in the event of a future liability, or traded or sold to others that might have need for the credits. In the case of a natural resource damage claim or response action, possessing or applying the credits does not negate the need for responsible entities to clean up spills or releases of hazardous substances or oil or to address their clean-up requirements under applicable federal and state statutes. Concepts similar to prospective environmental restoration/restoration up front include wetlands mitigation banking, conservation habitat banking, and emissions trading. Much of the concept and details provided herein stem from the practice of natural resource damage assessment, although that is not the sole driver for the concept. The concept could also apply where the credits could be used to offset other environmental liabilities, for example, to provide habitat mitigation where development is being planned. The authors believe that the concept, if widely applied, could reduce the time and costs associated with restoration and perhaps lead to an increase in voluntary restoration and conservation nationally. Currently, there are no state or federal regulations or policies that directly provide for this approach.

Resent Status of ITER Equatorial Launcher Development

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

Takahashi, K.; Kajiwara, K.; Kasugai, A.

2009-11-26

The ITER equatorial launcher is divided into a front shield and a port plug. The front shield is composed of fourteen blanket shield modules so as to form three openings for the injection of mm-wave beams into plasma. Twenty-four waveguide transmission lines, internal shields, cooling pipes and so on are installed in the port plug. The transmission lines consist of the corrugated waveguides, miter bends and the free space propagation region utilizing two mirrors in front of the waveguide outlet. The analysis of mm-wave beam propagation in the region shows that the transmission efficiency more than 99.5% is attained. Themore » high power experiments of the launcher mock-up have been carried out and the measured field patterns at each mirror and the outlet of the launcher are agreed with the calculations. It is concluded that the transmission line components in the launcher mock-up are fabricated as designed and the present mm-wave design in the launcher is feasible.« less

Oblique Wing Research Aircraft on ramp

NASA Image and Video Library

1976-08-02

This 1976 photograph of the Oblique Wing Research Aircraft was taken in front of the NASA Flight Research Center hangar, located at Edwards Air Force Base, California. In the photograph the noseboom, pitot-static probe, and angles-of-attack and sideslip flow vanes(covered-up) are attached to the front of the vehicle. The clear nose dome for the television camera, and the shrouded propellor for the 90 horsepower engine are clearly seen.

Large-area triple-junction a-Si alloy production scaleup. Annual subcontract report, 17 March 1993--18 March 1994

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

Oswald, R.; Morris, J.

1994-11-01

The objective of this subcontract over its three-year duration is to advance Solarex`s photovoltaic manufacturing technologies, reduce its a-Si:H module production costs, increase module performance and expand the Solarex commercial production capacity. Solarex shall meet these objectives by improving the deposition and quality of the transparent front contact, by optimizing the laser patterning process, scaling-up the semiconductor deposition process, improving the back contact deposition, scaling-up and improving the encapsulation and testing of its a-Si:H modules. In the Phase 2 portion of this subcontract, Solarex focused on improving deposition of the front contact, investigating alternate feed stocks for the front contact,more » maximizing throughput and area utilization for all laser scribes, optimizing a-Si:H deposition equipment to achieve uniform deposition over large-areas, optimizing the triple-junction module fabrication process, evaluating the materials to deposit the rear contact, and optimizing the combination of isolation scribe and encapsulant to pass the wet high potential test. Progress is reported on the following: Front contact development; Laser scribe process development; Amorphous silicon based semiconductor deposition; Rear contact deposition process; Frit/bus/wire/frame; Materials handling; and Environmental test, yield and performance analysis.« less

Attitude and Behavior Factors Associated with Front-of-Package Label Use with Label Users Making Accurate Product Nutrition Assessments.

PubMed

Roseman, Mary G; Joung, Hyun-Woo; Littlejohn, Emily I

2018-05-01

Front-of-package (FOP) labels are increasing in popularity on retail products. Reductive FOP labels provide nutrient-specific information, whereas evaluative FOP labels summarize nutrient information through icons. Better understanding of consumer behavior regarding FOP labels is beneficial to increasing consumer use of nutrition labeling when making grocery purchasing decisions. We aimed to determine FOP label format effectiveness in aiding consumers at assessing nutrient density of food products. In addition, we sought to determine relationships between FOP label use and attitude toward healthy eating, diet self-assessment, self-reported health and nutrition knowledge, and label and shopping behaviors. A between-subjects experimental design was employed. Participants were randomly assigned to one of four label conditions: Facts Up Front, Facts Up Front Extended, a binary symbol, and no-label control. One hundred sixty-one US primary grocery shoppers, aged 18 to 69 years. Participants were randomly invited to the online study. Participants in one of four label condition groups viewed three product categories (cereal, dairy, and snacks) with corresponding questions. Adults' nutrition assessment of food products based on different FOP label formats, along with label use and attitude toward healthy eating, diet self-assessment, self-reported health and nutrition knowledge, and label and shopping behaviors. Data analyses included descriptive statistics, χ 2 tests, and logistical regression. Significant outcomes were set to α=.05. Participants selected the more nutrient-dense product in the snack food category when it contained an FOP label. Subjective health and nutrition knowledge and frequency of selecting food for healthful reasons were associated with FOP label use (P<0.01 and P<0.05, respectively). Both Facts Up Front (reductive) and binary (evaluative) FOP labels appear effective for nutrition assessment of snack products compared with no label. Specific attitude and behavior factors were associated with label use. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Can we observe the fronts of the Antarctic Circumpolar Current using GRACE OBP?

NASA Astrophysics Data System (ADS)

Makowski, J.; Chambers, D. P.; Bonin, J. A.

2014-12-01

The Antarctic Circumpolar Current (ACC) and the Southern Ocean remains one of the most undersampled regions of the world's oceans. The ACC is comprised of four major fronts: the Sub-Tropical Front (STF), the Polar Front (PF), the Sub-Antarctic Front (SAF), and the Southern ACC Front (SACCF). These were initially observed individually from repeat hydrographic sections and their approximate locations globally have been quantified using all available temperature data from the World Ocean and Climate Experiment (WOCE). More recent studies based on satellite altimetry have found that the front positions are more dynamic and have shifted south by up to 1° on average since 1993. Using ocean bottom pressure (OBP) data from the current Gravity Recovery and Climate Experiment (GRACE) we have measured integrated transport variability of the ACC south of Australia. However, differentiation of variability of specific fronts has been impossible due to the necessary smoothing required to reduce noise and correlated errors in the measurements. The future GRACE Follow-on (GFO) mission and the post 2020 GRACE-II mission are expected to produce higher resolution gravity fields with a monthly temporal resolution. Here, we study the resolution and error characteristics of GRACE gravity data that would be required to resolve variations in the front locations and transport. To do this, we utilize output from a high-resolution model of the Southern Ocean, hydrology models, and ice sheet surface mass balance models; add various amounts of random and correlated errors that may be expected from GFO and GRACE-II; and quantify requirements needed for future satellite gravity missions to resolve variations along the ACC fronts.

Language-learning impairments: a 30-year follow-up of language-impaired children with and without psychiatric, neurological and cognitive difficulties.

PubMed

Elbro, Carsten; Dalby, Mogens; Maarbjerg, Stine

2011-01-01

This study investigated the long-term consequences of language impairments for academic, educational and socio-economic outcomes. It also assessed the unique contributions of childhood measures of speech and language, non-verbal IQ, and of psychiatric and neurological problems. The study was a 30-year follow-up of 198 participants originally diagnosed with language impairments at 3-9 years. Childhood diagnoses were based on language and cognitive abilities, social maturity, motor development, and psychiatric and neurological signs. At follow-up the participants responded to a questionnaire about literacy, education, employment, economic independence and family status. The response rate was 42% (198/470). At follow-up a majority of the participants reported literacy difficulties, unemployment and low socio-economic status-at rates significantly higher than in the general population. Participants diagnosed as children with specific language impairments had significantly better outcomes than those with additional diagnoses, even when non-verbal IQ was normal or statistically controlled. Childhood measures accounted for up to 52% of the variance in adult outcomes. Psychiatric and neurological comorbidity is relevant for adult outcomes of language impairments even when non-verbal IQ is normal. © 2011 Royal College of Speech & Language Therapists.

System-level considerations for the front-end readout ASIC in the CBM experiment from the power supply perspective

NASA Astrophysics Data System (ADS)

Kasinski, K.; Koczon, P.; Ayet, S.; Löchner, S.; Schmidt, C. J.

2017-03-01

New fixed target experiments using high intensity beams with energy up to 10 AGeV from the SIS100 synchrotron presently being constructed at FAIR/GSI are under preparation. Most of the readout electronics and power supplies are expected to be exposed to a very high flux of nuclear reaction products and have to be radiation tolerant up to 3 MRad (TID) and sustain up to 1014/cm2 of 1 MeV neutron equivalent in their life time. Moreover, the mostly minimum ionising particles under investigation leave very little signal in the sensors. Therefore very low noise level amplitude measurements are required by the front-end electronics for effective tracking. Sensor and interconnecting micro-cable capacitance and series resistance in conjunction with intrinsic noise of the charge sensitive amplifier are dominant noise sources in the system. However, the single-ended architecture of the amplifiers employed for the charge processing channels implies a potential problem with noise contributions from power supply sources. Strict system-level constraints leave very little freedom in selecting a power supply structure optimal with respect to: power efficiency, cooling capabilities and power density on modules, but also noise injection to the front-end via the power supply lines. Design of the power supply and distribution system of the Silicon Tracking System in the CBM experiment together with details on the front-end ASICs (STS -XYTER2) and measurement results of power supply and conditioning electronics (selected DC/DC converter and LDO regulators) are presented.

Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and R-FC in CLL at diagnosis.

PubMed

Magni, M; Di Nicola, M; Patti, C; Scimè, R; Mulè, A; Rambaldi, A; Intermesoli, T; Viero, P; Tarella, C; Gueli, A; Bergui, L; Trentin, L; Barzan, A; Benedetti, F; Ambrosetti, A; Di Raimondo, F; Chiarenza, A; Parvis, G; Billio, A; Attolico, I; Olivieri, A; Montanari, M; Carlo-Stella, C; Matteucci, P; Devizzi, L; Guidetti, A; Viviani, S; Valagussa, P; Gianni, A M

2014-04-01

The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.

Tensile forces drive a reversible fibroblast-to-myofibroblast transition during tissue growth in engineered clefts

PubMed Central

Kollmannsberger, Philip; Bidan, Cécile M.; Dunlop, John W. C.; Fratzl, Peter; Vogel, Viola

2018-01-01

Myofibroblasts orchestrate wound healing processes, and if they remain activated, they drive disease progression such as fibrosis and cancer. Besides growth factor signaling, the local extracellular matrix (ECM) and its mechanical properties are central regulators of these processes. It remains unknown whether transforming growth factor–β (TGF-β) and tensile forces work synergistically in up-regulating the transition of fibroblasts into myofibroblasts and whether myofibroblasts undergo apoptosis or become deactivated by other means once tissue homeostasis is reached. We used three-dimensional microtissues grown in vitro from fibroblasts in macroscopically engineered clefts for several weeks and found that fibroblasts transitioned into myofibroblasts at the highly tensed growth front as the microtissue progressively closed the cleft, in analogy to closing a wound site. Proliferation was up-regulated at the growth front, and new highly stretched fibronectin fibers were deposited, as revealed by fibronectin fluorescence resonance energy transfer probes. As the tissue was growing, the ECM underneath matured into a collagen-rich tissue containing mostly fibroblasts instead of myofibroblasts, and the fibronectin fibers were under reduced tension. This correlated with a progressive rounding of cells from the growth front inward, with decreased α–smooth muscle actin expression, YAP nuclear translocation, and cell proliferation. Together, this suggests that the myofibroblast phenotype is stabilized at the growth front by tensile forces, even in the absence of endogenously supplemented TGF-β, and reverts into a quiescent fibroblast phenotype already 10 μm behind the growth front, thus giving rise to a myofibroblast-to-fibroblast transition. This is the hallmark of reaching prohealing homeostasis. PMID:29349300

STS-41 crew poses in front of OV-103 on concrete runway 22 at EAFB, Calif

NASA Technical Reports Server (NTRS)

1990-01-01

STS-41 crewmembers give 'thumbs up' signal while standing in front of Discovery, Orbiter Vehicle (OV) 103, parked on concrete runway 22 at Edwards Air Force Base (EAFB), California. Having just completed their mission, the crewmembers are still wearing their launch and entry suits (LESs). From left to right are Mission Specialist (MS) Thomas D. Akers, Pilot Robert D. Cabana, Commander Richard N. Richards, MS Bruce E. Melnick, and MS William M. Shepherd. Set up at OV-103's side hatch is a mobile stairway which the crew uses to egress the vehicle and which technicians use when safing the vehicle during postflight operations.

System for the design, manufacture, and testing of custom lenses with known amounts of high-order aberrations.

PubMed

Chernyak, Dimitri A; Campbell, Charles E

2003-11-01

Now that excimer laser systems can be programmed to correct complex aberrations of the eye on the basis of wave-front measurements, a method is needed to test the accuracy of the system from measurement through treatment. A closed-loop test method was developed to ensure that treatment plans generated by a wavefront measuring system were accurately transferred to and executed by the excimer laser. A surface was analytically defined, and a Shack-Hartmann-based wave-front system was used to formulate a treatment plan, which was downloaded to an excimer laser system. A plastic lens was ablated by the laser and then returned to the wave-front device, where it was measured and compared with the analytically defined wave-front surface. The two surfaces agreed up to 6th-order Zernike terms, validating the accuracy of the system.

The DIRC front-end electronics chain for BaBar

NASA Astrophysics Data System (ADS)

Bailly, P.; Beigbeder, C.; Bernier, R.; Breton, D.; Bonneaud, G.; Caceres, T.; Chase, R.; Chauveau, J.; Del Buono, L.; Dohou, F.; Ducorps, A.; Gastaldi, F.; Genat, J. F.; Hrisoho, A.; Imbert, P.; Lebbolo, H.; Matricon, P.; Oxoby, G.; Renard, C.; Roos, L.; Sen, S.; Thiebaux, C.; Truong, K.; Tocut, V.; Vasileiadis, G.; Va'Vra, J.; Verderi, M.; Warner, D.; Wilson, R. J.; Wormser, G.; Zhang, B.; Zomer, F.

2000-12-01

Recent results from the Front-End electronics of the Detector of Internally Reflected Cerenkov light (DIRC) for the BaBar experiment at SLAC (Stanford, USA) are presented. It measures to better than 1 ns the arrival time of Cerenkov photoelectrons detected in a 11000 phototubes array and their amplitude spectra. It mainly comprises 64-channel DIRC Front-End Boards (DFB) equipped with eight full-custom analog chips performing zero-cross discrimination with 2 mV threshold and pulse shaping, four full-custom digital time to digital chips (TDC) for timing measurements with 500 ps binning and a readout logic selecting hits in the trigger window, and DIRC Crate Controller cards (DCC) serializing the data collected front up to 16 DFBs onto a 1.2 Gb/s optical link. Extensive test results of the pre-production chips are presented, as well as system tests.

Observational evidence for thermal wave fronts in solar flares

NASA Technical Reports Server (NTRS)

Rust, D. M.; Simnett, G. M.; Smith, D. F.

1985-01-01

Images in 3.5-30 keV X-rays obtained during the first few minutes of seven solar flares show rapid motions. In each case X-ray emission first appeared at one end of a magnetic field structure, and then propagated along the field at a velocity between 800 and 1700 km/s. The observed X-ray structures were 45,000-230,000 km long. Simultaneous H-alpha images were available in three cases; they showed brightenings when the fast-moving fronts arrived at the chromosphere. The fast-moving fronts are interpreted as electron thermal conduction fronts since their velocities are consistent with conduction at the observed temperatures of 1-3 x 10 to the 7th K. The inferred conductive heat flux of up to 10-billion ergs/s sq cm accounts for most of the energy released in the flares, implying that the flares were primarily thermal phenomena.

Disease-Associated Mutant Ubiquitin Causes Proteasomal Impairment and Enhances the Toxicity of Protein Aggregates

PubMed Central

Tank, Elizabeth M. H.; True, Heather L.

2009-01-01

Protein homeostasis is critical for cellular survival and its dysregulation has been implicated in Alzheimer's disease (AD) and other neurodegenerative disorders. Despite the growing appreciation of the pathogenic mechanisms involved in familial forms of AD, much less is known about the sporadic cases. Aggregates found in both familial and sporadic AD often include proteins other than those typically associated with the disease. One such protein is a mutant form of ubiquitin, UBB+1, a frameshift product generated by molecular misreading of a wild-type ubiquitin gene. UBB+1 has been associated with multiple disorders. UBB+1 cannot function as a ubiquitin molecule, and it is itself a substrate for degradation by the ubiquitin/proteasome system (UPS). Accumulation of UBB+1 impairs the proteasome system and enhances toxic protein aggregation, ultimately resulting in cell death. Here, we describe a novel model system to investigate how UBB+1 impairs UPS function and whether it plays a causal role in protein aggregation. We expressed a protein analogous to UBB+1 in yeast (Ubext) and demonstrated that it caused UPS impairment. Blocking ubiquitination of Ubext or weakening its interactions with other ubiquitin-processing proteins reduced the UPS impairment. Expression of Ubext altered the conjugation of wild-type ubiquitin to a UPS substrate. The expression of Ubext markedly enhanced cellular susceptibility to toxic protein aggregates but, surprisingly, did not induce or alter nontoxic protein aggregates in yeast. Taken together, these results suggest that Ubext interacts with more than one protein to elicit impairment of the UPS and affect protein aggregate toxicity. Furthermore, we suggest a model whereby chronic UPS impairment could inflict deleterious consequences on proper protein aggregate sequestration. PMID:19214209

Slow Progress in Dune (Left Front Wheel)

NASA Technical Reports Server (NTRS)

2005-01-01

The left front wheel of NASA's Mars Exploration Rover Opportunity makes slow but steady progress through soft dune material in this movie clip of frames taken by the rover's front hazard identification camera over a period of several days. The sequence starts on Opportunity's 460th martian day, or sol (May 10, 2005) and ends 11 days later. In eight drives during that period, Opportunity advanced a total of 26 centimeters (10 inches) while spinning its wheels enough to have driven 46 meters (151 feet) if there were no slippage. The motion appears to speed up near the end of the clip, but that is an artifact of individual frames being taken less frequently.

Design of an optical lens combined with a total internal reflection (TIR) freeform surface for a LED front fog lamp

NASA Astrophysics Data System (ADS)

Wang, Hong; Li, Xiufeng; Ge, Peng

2017-02-01

We propose a design method of an optical lens combined with a total internal reflection (TIR) freeform surface for a LED front fog lamp. The TIR freeform surface controls the edge rays of the LED source. It totally reflects the edge rays and makes them emit from the top surface of the lens. And the middle rays of the LED source go through the refractive surface and reach the measured plane. We simulate the model by Monte Carlo method. Simulation results show that the front fog lamp system can satisfy the requirement of ECE R19 Rev7. The light control efficiency can reach up to 76%.

Age-Related Sensory Impairments and Risk of Cognitive Impairment

PubMed Central

Fischer, Mary E; Cruickshanks, Karen J.; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara EK; Klein, Ronald; Tweed, Ted S.

2016-01-01

Background/Objectives To evaluate the associations of sensory impairments with the 10-year risk of cognitive impairment. Previous work has primarily focused on the relationship between a single sensory system and cognition. Design The Epidemiology of Hearing Loss Study (EHLS) is a longitudinal, population-based study of aging in the Beaver Dam, WI community. Baseline examinations were conducted in 1993 and follow-up exams have been conducted every 5 years. Setting General community Participants EHLS members without cognitive impairment at EHLS-2 (1998–2000). There were 1,884 participants (mean age = 66.7 years) with complete EHLS-2 sensory data and follow-up information. Measurements Cognitive impairment was a Mini-Mental State Examination score of < 24 or history of dementia or Alzheimer’s disease. Hearing impairment was a pure-tone average of hearing thresholds (0.5, 1, 2 and 4 kHz) of > 25 decibel Hearing Level in either ear. Visual impairment was Pelli-Robson contrast sensitivity of < 1.55 log units in the better eye and olfactory impairment was a San Diego Odor Identification Test score of < 6. Results Hearing, visual, and olfactory impairment were independently associated with cognitive impairment risk [Hearing: Hazard Ratio (HR) = 1.90, 95% Confidence Interval (C.I.) = 1.11, 3.26; Vision: HR = 2.05, 95% C.I. = 1.24, 3.38; Olfaction: HR = 3.92, 95% C.I. = 2.45, 6.26]. However, 85% with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. Conclusion The relationship between sensory impairment and cognitive impairment was not unique to one sensory system suggesting sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. PMID:27611845

Age-Related Sensory Impairments and Risk of Cognitive Impairment.

PubMed

Fischer, Mary E; Cruickshanks, Karen J; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara E K; Klein, Ronald; Tweed, Ted S

2016-10-01

To evaluate the associations between sensory impairments and 10-year risk of cognitive impairment. The Epidemiology of Hearing Loss Study (EHLS), a longitudinal, population-based study of aging in the Beaver Dam, Wisconsin community. Baseline examinations were conducted in 1993 and follow-up examinations have been conducted every 5 years. General community. EHLS members without cognitive impairment at EHLS-2 (1998-2000). There were 1,884 participants (mean age 66.7) with complete EHLS-2 sensory data and follow-up information. Cognitive impairment was defined as a Mini-Mental State Examination score of <24 or history of dementia or Alzheimer's disease. Hearing impairment was a pure-tone average of hearing thresholds (0.5, 1, 2, 4 kHz) of >25 dB hearing level in either ear, visual impairment was a Pelli-Robson contrast sensitivity of <1.55 log units in the better eye, and olfactory impairment was a San Diego Odor Identification Test score of <6. Hearing, visual, and olfactory impairment were independently associated with cognitive impairment risk (hearing: hazard ratio (HR) = 1.90, 95% confidence interval (CI) = 1.11-3.26; vision: HR = 2.05, 95% CI = 1.24-3.38; olfaction: HR = 3.92, 95% CI = 2.45-6.26)). Nevertheless, 85% of participants with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. The relationship between sensory impairment and cognitive impairment was not unique to one sensory system, suggesting that sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Self-reported vision impairment and incident prefrailty and frailty in English community-dwelling older adults: findings from a 4-year follow-up study.

PubMed

Liljas, Ann E M; Carvalho, Livia A; Papachristou, Efstathios; De Oliveira, Cesar; Wannamethee, S Goya; Ramsay, Sheena E; Walters, Kate R

2017-11-01

Little is known about vision impairment and frailty in older age. We investigated the relationship of poor vision and incident prefrailty and frailty. Cross-sectional and longitudinal analyses with 4-year follow-up of 2836 English community-dwellers aged ≥60 years. Vision impairment was defined as poor self-reported vision. A score of 0 out of the 5 Fried phenotype components was defined as non-frail, 1-2 prefrail and ≥3 as frail. Participants non-frail at baseline were followed-up for incident prefrailty and frailty. Participants prefrail at baseline were followed-up for incident frailty. 49% of participants (n=1396) were non-frail, 42% (n=1178) prefrail and 9% (n=262) frail. At follow-up, there were 367 new cases of prefrailty and frailty among those non-frail at baseline, and 133 new cases of frailty among those prefrail at baseline. In cross-sectional analysis, vision impairment was associated with frailty (age-adjustedandsex-adjusted OR 2.53, 95% CI 1.95 to 3.30). The association remained after further adjustment for wealth, education, cardiovascular disease, diabetes, falls, cognition and depression. In longitudinal analysis, compared with non-frail participants with no vision impairment, non-frail participants with vision impairment had twofold increased risks of prefrailty or frailty at follow-up (OR 2.07, 95% CI 1.32 to 3.24). The association remained after further adjustment. Prefrail participants with vision impairment did not have greater risks of becoming frail at follow-up. Non-frail older adults who experience poor vision have increased risks of becoming prefrail and frail over 4 years. This is of public health importance as both vision impairment and frailty affect a large number of older adults. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Acceptance and Commitment Therapy for the Treatment of Music Performance Anxiety: A Pilot Study with Student Vocalists

PubMed Central

Juncos, David G.; Heinrichs, Glenn A.; Towle, Philip; Duffy, Kiera; Grand, Sebastian M.; Morgan, Matthew C.; Smith, Jonathan D.; Kalkus, Evan

2017-01-01

This study investigated the use of Acceptance and Commitment Therapy (ACT) as a treatment for music performance anxiety (MPA) in an uncontrolled pilot design. ACT is a newer, “third-wave” therapy that differs from previous MPA treatments, because its goal is not to reduce symptoms of MPA. Rather, ACT aims to enhance psychological flexibility in the presence of unwanted symptoms through the promotion of six core processes collectively known as the ACT “Hexaflex.” A small group of student vocalists (N = 7) from an elite choral college were recruited using objective criteria for evaluating MPA. Participants received 12 ACT sessions, and their baseline functioning served as a pre-treatment control. Treatment consisted of an orientation to ACT, identifying experientially avoidant behaviors, facilitation of Hexaflex processes, group performances in which valued behaviors were practiced in front of one another, meditations, homework, and completion of self-report measures before, during, and after treatment (at a 1- and 3-month follow-up). Improvements were observed in participants' cognitive defusion, acceptance of MPA symptoms, and psychological flexibility at post-treatment and follow-ups. Students also appeared to improve their performance quality and reduce their shame over having MPA. These results add to existing research suggesting ACT is a promising intervention for MPA, while also highlighting how vocal students may be less impaired by physical MPA symptoms. PMID:28674509

Acceptance and Commitment Therapy for the Treatment of Music Performance Anxiety: A Pilot Study with Student Vocalists.

PubMed

Juncos, David G; Heinrichs, Glenn A; Towle, Philip; Duffy, Kiera; Grand, Sebastian M; Morgan, Matthew C; Smith, Jonathan D; Kalkus, Evan

2017-01-01

This study investigated the use of Acceptance and Commitment Therapy (ACT) as a treatment for music performance anxiety (MPA) in an uncontrolled pilot design. ACT is a newer, "third-wave" therapy that differs from previous MPA treatments, because its goal is not to reduce symptoms of MPA. Rather, ACT aims to enhance psychological flexibility in the presence of unwanted symptoms through the promotion of six core processes collectively known as the ACT "Hexaflex." A small group of student vocalists ( N = 7) from an elite choral college were recruited using objective criteria for evaluating MPA. Participants received 12 ACT sessions, and their baseline functioning served as a pre-treatment control. Treatment consisted of an orientation to ACT, identifying experientially avoidant behaviors, facilitation of Hexaflex processes, group performances in which valued behaviors were practiced in front of one another, meditations, homework, and completion of self-report measures before, during, and after treatment (at a 1- and 3-month follow-up). Improvements were observed in participants' cognitive defusion, acceptance of MPA symptoms, and psychological flexibility at post-treatment and follow-ups. Students also appeared to improve their performance quality and reduce their shame over having MPA. These results add to existing research suggesting ACT is a promising intervention for MPA, while also highlighting how vocal students may be less impaired by physical MPA symptoms.

Effect of high up front charges on access to surgery for poor patients at a public hospital in New Mexico.

PubMed

Kaufman, Will; Chavez, Augustine S; Skipper, Betty; Kaufman, Arthur

2006-06-23

A public hospital in New Mexico required collection of 50% of estimated costs prior to elective surgeries for self-pay patients. This study assesses the impact of this policy on access to elective surgical procedures. Chi-square tests determined if there was a statistically significant difference between the number of self-pay and insured patient cancellations for financial reasons. A multivariate binomial regression model was used to calculate risk ratios and confidence limits for effects of race/ethnicity, and insurance status, controlling for gender, on these cancellations. Of the 667 cancellations, there were 99 self-pay and 568 insured patients. Cancellations for financial reasons occurred in 55.6% of self-pay and 9.3% of insured patients (p < 0.0001). Inability to pay 50% up front accounted for 76.4% of self-pay patient cancellations for financial reasons. Self-pay, non-Hispanic whites and minority race/ethnicities were 8.76 and 8.61 times more likely to cancel for financial reasons, respectively, than insured non-Hispanic whites. Self-pay patients, regardless of race/ethnicity, have elective surgical procedures cancelled for financial reasons significantly more often than insured patients. The hospital's 50% up-front payment policy represents a significant financial barrier to accessing elective surgical procedures for self-pay patients.

Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial.

PubMed

Dreger, Peter; Döhner, Hartmut; Ritgen, Matthias; Böttcher, Sebastian; Busch, Raymonde; Dietrich, Sascha; Bunjes, Donald; Cohen, Sandra; Schubert, Jörg; Hegenbart, Ute; Beelen, Dietrich; Zeis, Matthias; Stadler, Michael; Hasenkamp, Justin; Uharek, Lutz; Scheid, Christof; Humpe, Andreas; Zenz, Thorsten; Winkler, Dirk; Hallek, Michael; Kneba, Michael; Schmitz, Norbert; Stilgenbauer, Stephan

2010-10-07

The purpose of this prospective multicenter phase 2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (17p-). In multivariate analyses, uncontrolled disease at alloSCT and in vivo T-cell depletion with alemtuzumab, but not 17p-, previous purine analogue refractoriness, or donor source (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at http://clinicaltrials.gov as NCT00281983.

Experimental injury study of children seated behind collapsing front seats in rear impacts.

PubMed

Saczalski, Kenneth J; Sances, Anthony; Kumaresan, Srirangam; Burton, Joseph L; Lewis, Paul R

2003-01-01

In the mid 1990's the U.S. Department of Transportation made recommendations to place children and infants into the rear seating areas of motor vehicles to avoid front seat airbag induced injuries and fatalities. In most rear-impacts, however, the adult occupied front seats will collapse into the rear occupant area and pose another potentially serious injury hazard to the rear-seated children. Since rear-impacts involve a wide range of speeds, impact severity, and various sizes of adults in collapsing front seats, a multi-variable experimental method was employed in conjunction with a multi-level "factorial analysis" technique to study injury potential of rear-seated children. Various sizes of Hybrid III adult surrogates, seated in a "typical" average strength collapsing type of front seat, and a three-year-old Hybrid III child surrogate, seated on a built-in booster seat located directly behind the front adult occupant, were tested at various impact severity levels in a popular "minivan" sled-buck test set up. A total of five test configurations were utilized in this study. Three levels of velocity changes ranging from 22.5 to 42.5 kph were used. The average of peak accelerations on the sled-buck tests ranged from approximately 8.2 G's up to about 11.1 G's, with absolute peak values of just over 14 G's at the higher velocity change. The parameters of the test configuration enabled the experimental data to be combined into a polynomial "injury" function of the two primary independent variables (i.e. front seat adult occupant weight and velocity change) so that the "likelihood" of rear child "injury potential" could be determined over a wide range of the key parameters. The experimentally derived head injury data was used to obtain a preliminary HIC (Head Injury Criteria) polynomial fit at the 900 level for the rear-seated child. Several actual accident cases were compared with the preliminary polynomial fit. This study provides a test efficient, multi-variable, method to compare the injury biomechanical data with actual accident cases.

Follow-up of permanent hearing impairment in childhood.

PubMed

Della Volpe, A; De Lucia, A; Pastore, V; Bracci Laudiero, L; Buonissimo, I; Ricci, G

2016-02-01

Programmes for early childhood childhood hearing impairment identification allows to quickly start the appropriate hearing aid fitting and rehabilitation process; nevertheless, a large number of patients do not join the treatment program. The goal of this article is to present the results of a strategic review of the strengths, weaknesses, opportunities and threats connected with the audiologic/prosthetic/language follow-up process of children with bilateral permanent hearing impairment. Involving small children, the follow-up includes the involvement of specialised professionals of a multidisciplinary team and a complex and prolonged multi-faced management. Within the framework of the Italian Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for Early Identification, Intervention and Care of Hearing Impaired Children", the purpose of this analysis was to propose recommendations that can harmonise criteria for outcome evaluation and provide guidance on the most appropriate assessment methods to be used in the follow-up course of children with permanent hearing impairment. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale.

Investigating the response of Crane Glacier, Antarctic Peninsula to the disintegration of the Larsen B ice shelf using a 2-D flowline model

NASA Astrophysics Data System (ADS)

Campbell, A. J.; Hulbe, C. L.; Sergienko, O.

2009-12-01

Many of the glaciers flowing into the Larsen B ice shelf sped up and experienced front retreat following its March 2002 disintegration. Crane Glacier stands out among the fast responding glaciers for its dramatic increase in speed, from ~500 m/a to ~1500 m/a in its downstream reach, large surface lowering, and front retreat. Between march 2002 and early 2005, the glacier's calving front retreated by about 11.5 km to a location at which it has remained since that time. In order to investigate the physical processes that control the reaction of Crane Glacier to ice shelf disintegration, a flowline model has been developed. The model solves for the full momentum balance along the flowline using the finite element method and allows for basal sliding using a Budd type sliding relation. Model parameters are tuned to reproduce observation of surface velocity prior to ice shelf disintegration. Model can be applied diagnostically to examine instantaneous changes in boundary conditions or prognostically to evolve surface elevation over time. The instantaneous model response of the glacier to ice shelf removal produces surface velocities and thinning rates that agree well with observations. When the front position is modified to represent the steady position reached in 2005, the model again produces velocities similar to those observed on the glacier. A typical tidewater calving criterion can be used to predict the steady position toward which the front retreated. We conclude that the post-collapse speed up is facilitated by rapid basal sliding, which allows a small perturbation in vertical shearing to be amplified into a large velocity response. The pattern of glacier front retreat can be explained by a tidewater calving instability. These conclusions underscore the importance of basal sliding parametrizations in understanding observed changes in ice sheet outlet glaciers and modeling their future behavior. Correct representation of iceberg calving is also important.

Financial capacity in older adults: a growing concern for clinicians.

PubMed

Gardiner, Paul A; Byrne, Gerard J; Mitchell, Leander K; Pachana, Nancy A

2015-02-02

Older people with cognitive impairment and/or dementia may be particularly vulnerable to diminished financial decision-making capacity. Financial capacity refers to the ability to satisfactorily manage one's financial affairs in a manner consistent with personal self-interest and values. Impairment of financial capacity makes the older individual vulnerable to financial exploitation, may negatively affect their family's financial situation and places strain on relationships within the family. Clinicians are often on the front line of responding to queries regarding decision-making capacity, and clinical evaluation options are often not well understood. Assessment of financial capacity should include formal objective assessment in addition to a clinical interview and gathering contextual data. Development of a flexible, empirically supported and clinically relevant assessment approach that spans all dimensions of financial capacity yet is simple enough to be used by non-specialist clinicians is needed.

Strength Enhancement of Car Front Bumper for Slow Speed Impact by FEA Method as per IIHS Regulation

NASA Astrophysics Data System (ADS)

Sonawane, Chandrakant Rameshchandra; Shelar, Ajit Lavaji

2017-05-01

Low speed collisions happen significantly due to on road slow moving heavy traffic as well as during parking of vehicles. The bumpers are provided in front and back side of a vehicle has two main purposes: first is to absorb the energy generated during these kinds of slow speed impacts and secondly to protect the expensive parts like main engine parts, radiators and connected engine cooling mechanism, headlights, taillights, etc, by slowing down the vehicles. The problem often in various cars bumper is that they doesn't line-up vertically during low speed impact and leads to damage of various parts which are costly to repair. Many a times bumper design does not have sufficient capacity to absorb the energy generated during these impact. Guideline by International Institute Highway Safety (IIHS) regulation provides useful insight for such low speed impact study. In this paper, slow speed impact test were conducted as per IIHS regulation in three positions namely central impact, left hand corner impact and right hand corner impact. Parameters including bumper material, shape, thickness and impact condition are analyzed using fine element analysis (FEA) to enhance crashworthiness design in low speed impact. Then the vehicle front structure has been modified suitably. It has been observed that lining up the front metal bumper with suitable stiffness provides the best result which ultimately reduces the damage to the vehicle parts.

On the ability of human listeners to distinguish between front and back.

PubMed

Zhang, Peter Xinya; Hartmann, William M

2010-02-01

In order to determine whether a sound source is in front or in back, listeners can use location-dependent spectral cues caused by diffraction from their anatomy. This capability was studied using a precise virtual reality technique (VRX) based on a transaural technology. Presented with a virtual baseline simulation accurate up to 16 kHz, listeners could not distinguish between the simulation and a real source. Experiments requiring listeners to discriminate between front and back locations were performed using controlled modifications of the baseline simulation to test hypotheses about the important spectral cues. The experiments concluded: (1) Front/back cues were not confined to any particular 1/3rd or 2/3rd octave frequency region. Often adequate cues were available in any of several disjoint frequency regions. (2) Spectral dips were more important than spectral peaks. (3) Neither monaural cues nor interaural spectral level difference cues were adequate. (4) Replacing baseline spectra by sharpened spectra had minimal effect on discrimination performance. (5) When presented with an interaural time difference less than 200 micros, which pulled the image to the side, listeners still successfully discriminated between front and back, suggesting that front/back discrimination is independent of azimuthal localization within certain limits. Copyright 2009 Elsevier B.V. All rights reserved.

On the ability of human listeners to distinguish between front and back

PubMed Central

Zhang, Peter Xinya; Hartmann, William M.

2009-01-01

In order to determine whether a sound source is in front or in back, listeners can use location-dependent spectral cues caused by diffraction from their anatomy. This capability was studied using a precise virtual-reality technique (VRX) based on a transaural technology. Presented with a virtual baseline simulation accurate up to 16 kHz, listeners could not distinguish between the simulation and a real source. Experiments requiring listeners to discriminate between front and back locations were performed using controlled modifications of the baseline simulation to test hypotheses about the important spectral cues. The experiments concluded: (1) Front/back cues were not confined to any particular 1/3rd or 2/3rd octave frequency region. Often adequate cues were available in any of several disjoint frequency regions. (2) Spectral dips were more important than spectral peaks. (3) Neither monaural cues nor interaural spectral level difference cues were adequate. (4) Replacing baseline spectra by sharpened spectra had minimal effect on discrimination performance. (5) When presented with an interaural time difference less than 200 μs, which pulled the image to the side, listeners still successfully discriminated between front and back, suggesting that front/back discrimination is independent of azimuthal localization within certain limits. PMID:19900525

Frontal dynamics at the edge of the Columbia River plume

NASA Astrophysics Data System (ADS)

Akan, Çiğdem; McWilliams, James C.; Moghimi, Saeed; Özkan-Haller, H. Tuba

2018-02-01

In the tidal ebb-cycle at the Mouth of the Columbia River, strong density and velocity fronts sometimes form perpendicular to the coast at the edges of the freshwater plume. They are distinct from previously analyzed fronts at the offshore western edge of the plume that evolve as a gravity-wave bore. We present simulation results to demonstrate their occurrence and investigate the mechanisms behind their frontogenesis and evolution. Tidal velocities on average ranged between 1.5 m s-1 in flood and 2.5 m s-1 in ebb during the brief hindcast period. The tidal fronts exhibit strong horizontal velocity and buoyancy gradients on a scale ∼ 100 m in width with normalized relative vorticity (ζz/f) values reaching up to 50. We specifically focus on the front on the northern edge of the plume and examine the evolution in plume characteristics such as its water mass gradients, horizontal and vertical velocity structure, vertical velocity, turbulent vertical mixing, horizontal propagation, cross-front momentum balance, and Lagrangian frontogenetic tendencies in both buoyancy and velocity gradients. Advective frontogenesis leads to a very sharp front where lateral mixing near the grid-resolution limit arrests its further contraction. The negative vorticity within the front is initiated by the positive bottom drag curl on the north side of the Columbia estuary and against the north jetty. Because of the large negative vorticity and horizontal vorticity gradient, centrifugal and lateral shear instability begins to develop along the front, but frontal fragmentation and decay set in only after the turn of the tide because of the briefness of the ebb interval.

In-Situ Observations of a Subglacial Outflow Plume in a Greenland Fjord

NASA Astrophysics Data System (ADS)

Mankoff, K. D.; Straneo, F.; Singh, H.; Das, S. B.

2014-12-01

We present oceanographic observations collected in and immediately outside of a buoyant, fresh, sediment-laden subglacial outflow plume rising up the marine-terminating front of Sarqardleq Glacier, Greenland (68.9 N, 50.4 W). Subglacial outflow plumes, associated with the discharge at depth of upstream glacial surface melt, entrain the relatively warm fjord waters and are correlated with enhanced submarine melt and increased calving. Few in-situ observations exist due to the challenges of making measurements at the calving front of glaciers. Our data were collected using a small boat, a helicopter, and a JetYak (a remote-controlled jet-ski-powered kayak). Temperature and salinity profiles in, around, and far from the plume are used to described its oceanographic properties, spatial extent, and temporal variability. This plume rises vertically up the ice front expanding laterally and away from the ice, over-shoots its stable isopycnal and reaches the surface. Its surface expression is identified by colder, saltier, sediment-laden water flowing at ~5 m/s away from the ice face. Within ~300 m from the ice it submerges as it seeks buoyant stability.

Priorities of pedestrian protection--a real-life study of severe injuries and car sources.

PubMed

Fredriksson, Rikard; Rosén, Erik; Kullgren, Anders

2010-11-01

The aim of this study was to aid the optimisation of future, vehicle based, pedestrian injury countermeasures. The German In-Depth Accident Study (GIDAS) database was queried for pedestrians impacted by the front of a passenger car or van. A total of 1030 cases from 1998 to 2008 were studied including 161 severely (AIS3+) injured pedestrians. Considering the severe injuries, the most frequent injury mechanisms were "leg-to-front end", "head-to-windscreen area", "chest-to-bonnet area", and "chest-to-windscreen area". For children, a "head-to-bonnet area" impact was the second most common source of injury. With safety systems targeting these five injury mechanisms, 73% (95% confidence interval [CI], 65-81%) of the severely injured pedestrians would be provided protection from all of their vehicle-induced severe injuries. Omitting the windscreen area, this figure is decreased to 44% (CI, 36-53%). Furthermore, 31% of the surviving pedestrians were estimated to sustain a permanent medical impairment at any level. For more severe impairment, head was the dominating body region. The study shows that when developing countermeasures for the windscreen area to mitigate head injuries, attention should be paid to the structural parts of the windscreen area with a special focus on brain injuries. Finally, the incidence and risk of severe injury were derived as functions of impact speed for different body regions and injury sources. 2010 Elsevier Ltd. All rights reserved.

Up-Close Look at 'Bread-Basket'

NASA Technical Reports Server (NTRS)

2004-01-01

NASA's Mars Exploration Rover Spirit took this image with its front hazard-avoidance camera on sol 175 (June 30, 2004). It captures the instrument deployment device in perfect position as the rover uses its microscopic imager to get an up-close look at the rock target 'Bread-Basket.'

6. Workers laying up the graphite core of the 105B ...

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

6. Workers laying up the graphite core of the 105-B file. In the lower-left can be seen a portion of the rear face of the pile, the top of its shielding wall, and the gun barrels protruding through it. The inside of the front face of the pile and its gun barrels can be seen toward the upper-right side. The angled top of the front shielding wall can be seen in the picture. All four walls were "stepped" in this manner where they joined with another wall or the ceiling to form a "labyrinth" joint, so that radiation would not have a straight route through any gaps in the joints. D-3045 - B Reactor, Richland, Benton County, WA

Comparing five front-of-pack nutrition labels' influence on consumers' perceptions and purchase intentions.

PubMed

Gorski Findling, Mary T; Werth, Paul M; Musicus, Aviva A; Bragg, Marie A; Graham, Dan J; Elbel, Brian; Roberto, Christina A

2018-01-01

In 2011, a National Academy of Medicine report recommended that packaged food in the U.S. display a uniform front-of-package nutrition label, using a system such as a 0-3 star ranking. Few studies have directly compared this to other labels to determine which best informs consumers and encourages healthier purchases. In 2013, we randomized adult participants (N=1247) in an Internet-based survey to one of six conditions: no label control; single traffic light; multiple traffic light; Facts Up Front; NuVal; or 0-3 star ranking. We compared groups on purchase intentions and accuracy of participants' interpretation of food labels. There were no differences in the nutritional quality of hypothetical shopping baskets across conditions (p=0.845). All labels improved consumers' abilities to judge the nutritional quality of foods relative to no label, but the best designs varied by outcomes. NuVal and multiple traffic light labels led to the greatest accuracy identifying the healthier of two products (p<0.001), while the multiple traffic light also led to the most accurate estimates of saturated fat, sugar, and sodium (p<0.001). The single traffic light outperformed other labels when participants compared nutrient levels between similar products (p<0.03). Single/multiple traffic light and Facts Up Front labels led to the most accurate calories per serving estimations (p<0.001). Although front-of-package labels helped participants more accurately assess products' nutrition information relative to no label, no conditions shifted adults' purchase intentions. Results did not point to a clearly superior label design, but they suggest that a 3-star label might not be best for educating consumers. Copyright © 2017 Elsevier Inc. All rights reserved.

Test of ATLAS RPCs Front-End electronics

NASA Astrophysics Data System (ADS)

Aielli, G.; Camarri, P.; Cardarelli, R.; Di Ciaccio, A.; Di Stante, L.; Liberti, B.; Paoloni, A.; Pastori, E.; Santonico, R.

2003-08-01

The Front-End Electronics performing the ATLAS RPCs readout is a full custom 8 channels GaAs circuit, which integrates in a single die both the analog and digital signal processing. The die is bonded on the Front-End board which is completely closed inside the detector Faraday cage. About 50 000 FE boards are foreseen for the experiment. The complete functionality of the FE boards will be certificated before the detector assembly. We describe here the systematic test devoted to check the dynamic functionality of each single channel and the selection criteria applied. It measures and registers all relevant electronics parameters to build up a complete database for the experiment. The statistical results from more than 1100 channels are presented.

FELIX: a PCIe based high-throughput approach for interfacing front-end and trigger electronics in the ATLAS Upgrade framework

NASA Astrophysics Data System (ADS)

Anderson, J.; Bauer, K.; Borga, A.; Boterenbrood, H.; Chen, H.; Chen, K.; Drake, G.; Dönszelmann, M.; Francis, D.; Guest, D.; Gorini, B.; Joos, M.; Lanni, F.; Lehmann Miotto, G.; Levinson, L.; Narevicius, J.; Panduro Vazquez, W.; Roich, A.; Ryu, S.; Schreuder, F.; Schumacher, J.; Vandelli, W.; Vermeulen, J.; Whiteson, D.; Wu, W.; Zhang, J.

2016-12-01

The ATLAS Phase-I upgrade (2019) requires a Trigger and Data Acquisition (TDAQ) system able to trigger and record data from up to three times the nominal LHC instantaneous luminosity. The Front-End LInk eXchange (FELIX) system provides an infrastructure to achieve this in a scalable, detector agnostic and easily upgradeable way. It is a PC-based gateway, interfacing custom radiation tolerant optical links from front-end electronics, via PCIe Gen3 cards, to a commodity switched Ethernet or InfiniBand network. FELIX enables reducing custom electronics in favour of software running on commercial servers. The FELIX system, the design of the PCIe prototype card and the integration test results are presented in this paper.

Extendable pipe crawler

DOEpatents

Hapstack, Mark

1991-01-01

A pipe crawler having a front leg assembly and a back leg assembly connected together by two air cylinders, each leg assembly having four extendable legs and a pair of actuators for sliding the extendable legs radially outward to increase the range of the legs when the pipe crawler enters a section of a pipe having a larger diameter. The crawler crawls by "inchworm"-like motion, the front leg assembly and back leg assembly alternately engaging and disengaging the wall of the pipe to hold the pipe crawler as the air cylinders alternately advance the front leg assembly and bring up the rear leg assembly. The pair of actuators of each leg assembly are parallel, adjacent and opposing acting so that each slides two adjacent extendable legs radially outward.

Get up, Stand up

ERIC Educational Resources Information Center

Melia, Ed

2009-01-01

Ignorance about dyslexia meant a miserable school experience for Barrie Hughes. He was in his 50s when he found the courage to stand up in front of a classroom of learners and admit he couldn't read. Barrie, who is now 59 and works for the parks department of Brighton and Hove Council, only began to learn how to read words in the last three years…

Location of the ischemic focus in rehabilitated stroke patients with impairment of executive functions.

PubMed

Jankowska, Agnieszka M; Klimkiewicz, Robert; Kubsik, Anna; Klimkiewicz, Paulina; Śmigielski, Janusz; Woldańska-Okońska, Marta

2017-08-01

Executive dysfunctions are part of the clinical symptoms of a stroke and can inhibit the process of rehabilitation. Patients with impaired executive functions may manifest aggression, impulsiveness, impaired thinking and planning. The aim of this study was to assess the effect of the ischemic focus location on the effectiveness of physiotherapy in improving the executive functions in patients after stroke. Ninety patients after unilateral ischemic cerebral stroke were studied. We studied 45 patients treated at the Department of Rehabilitation and Physical Medicine of the WAM University Hospital of Lodz for 5 weeks. The rehabilitation program included: kinesitherapy, physiotherapy, speech therapy, psychological consultations and psychotherapy. The control group consisted of patients who were waiting for admission to the Department of Rehabilitation. The patients in both groups were divided into three subgroups with different locations of stroke: front, back and subcortical. Executive functions were measured by the Wisconsin Card Sorting Test (WCST), the trail making test (TMT - A, TMT - B), the verbal fluency test (VFT). Patients rehabilitated in the hospital with the front and subcortical lesion location reported improvement in executive functions in terms of a greater number of the analyzed indicators of the Wisconsin Card Sorting Test (WCST) than those with the back lesion location. Patients rehabilitated at home with the subcortical lesion location did not experience a significant improvement in executive functions in any of the analyzed indicators of the Wisconsin Card Sorting Test (WCST). Most of the indicators, with the exception of the total errors of Wisconsin Card Sorting Test (WCST) and TMT B, have not been modified by the location of stroke. Executive dysfunction occurs not only in patients with an anterior location of the stroke, but also in the posterior and subcortical locations. Patients with a subcortical location of the stroke require more treatment to mitigate the dysfunction.

Towards Useful and Dangerous Theories

ERIC Educational Resources Information Center

Sikes, Pat

2006-01-01

Like Norman Denzin and Yvonna Lincoln, and many others, the author "wants a social science that is committed up front to issues of social justice, equity, non-violence, peace, and universal human rights" (Denzin & Lincoln, 2005). Educational research, as she and the three authors whose papers make up this symposium of…

Taxonomy of Greater White-fronted Geese (Aves: Anatidae)

USGS Publications Warehouse

Banks, Richard C.

2011-01-01

Five subspecies of the Greater White-fronted Goose, Anser albifrons (Scopoli, 1769), have been named, all on the basis of wintering birds, and up to six subspecies have been recognized. There has been confusion over the application of some names, particularly in North America, because of lack of knowledge of the breeding ranges and type localities, and incorrect taxonomic decisions. There is one clinally varying subspecies in Eurasia, one that breeds in Greenland, and three in North America, one newly named herein.

ASSESSING THE KNOWLEDGE, ATTITUDES AND PRACTICES OF SCHOOL TEACHERS REGARDING DYSLEXIA, ATTENTION-DEFICIT/ HYPERACTIVITY AND AUTISTIC SPECTRUM DISORDERS IN KARACHI, PAKISTAN.

PubMed

Lodhi, Shaia Kan; Thaver, Danyal; Akhtar, Irfan Nake; Javaid, Hina; Masoor, Maman; Bano, Shah; Malik, Fatima Noor; Iqbal, Mehreen Rizwana; Hashmi, Hassan Raza; Siddiqullah, Syed; Saleem, Sarah

2016-01-01

Learning impairments in children consist of a spectrum of disorders that are under diagnosed in Pakistan. Most learning disorders have long term consequences for a child and early detection is thus imperative. Teachers may be able to play a key role in such identification. The objective of our study was to survey knowledge, attitudes and practices of school teachers regarding dyslexia, Attention-deficit/hyperactivity disorder (ADHD) and autistic spectrum disorder, and assess their ability to identify learning disabilities. A cross-sectional study was conducted with 233 primary school teachers from Karachi using a self-administered questionnaire. Mean scores for the knowledge test and the ability to identify learning- impaired children were 58.8% and 53.3%, respectively. Better qualified teachers scored significantly more on the knowledge and ability to identify learning impairments sections. Most teachers believed that these students should study in mainstream schools with special educators. Majority of the teachers belonged to schools where children with learning disabilities were detected using teachers' judgment. Most teachers manage these children by involving them in discussions, seating them at the front of the class, and giving them extra time. Knowledge about learning disabilities is very low amongst school teachers, which may limit their ability to identify learning impairments.

The effect of timing of incentive payments on response rates for cohort study telephone interviews in primary care setting with cost-minimization analysis, a randomized controlled trial.

PubMed

Chin, Weng-Yee; Choi, Edmond P H; Lam, Cindy L K

2015-10-06

The effect of timing of incentive payments on the response rate of telephone surveys is unknown. This study examined whether up-front or delayed incentive payments were associated with higher response rates for participation in a telephone interview administered longitudinal cohort study amongst primary care patients with lower urinary tract symptoms, and to compare the costs between the two timing methods. This study was conducted as part of a naturalistic observation study on the health-related quality of life and health outcomes of Chinese primary care patients with lower urinary tract symptoms. The incentive payment was in the form of a supermarket gift voucher to the value of HD$50 (US$6.50) and could be used in lieu of cash at a major supermarket chain.720 subjects with lower urinary tract symptoms were randomly assigned into two groups. One group was offered an incentive of supermarket cash voucher at time of recruitment ('up-front' payment). The other group was told that the voucher would be sent to them after the complete of their 1-year follow-up telephone interview ('delayed' payment). Primary outcomes were the baseline and 1-year follow-up telephone survey response rates. There was no statistical difference in response rates at baseline (p-value = 0.938) or at the 1-year follow-up (p-value = 0.751) between groups. Cost per completed subject interviews for the up-front payment method was USD16.64, whilst cost for the delayed payment was USD 13.85. It appears the timing of incentive payments does not affect response rates for telephone interview surveys conducted on primary care patients in Hong Kong at baseline or at 1-year follow-up. Delayed incentive payments can reduce the overall cost per successful case. ClinicalTrials.gov Identifier: NCT02307929 Registered 28 August 2013.

Fludarabine and cytarabine versus high-dose cytarabine in consolidation treatment of t(8; 21) acute myeloid leukemia: A prospective, randomized study.

PubMed

Li, Ruiqi; Hu, Xiaoxia; Wang, Libing; Cheng, Hui; Lv, Shuqing; Zhang, Weiping; Wang, Jianmin; Yang, Jianmin; Song, Xianmin

2017-01-01

Acute myeloid leukemia (AML) patients with t(8;21) aberration often have favorable outcomes, however, relapse still occurs in 30-40% patients, with only 50-60% of patients with t(8;21) AML cured with regimens containing high-dose cytarabine (HD-Ara-C). To evaluate the effects of fludarabine and cytarabine (FA) consolidation therapy for t(8;21) AML patients, a prospective randomized study was performed. A total of 45 patients with t(8;21) AML after achieving complete remission (CR) were randomly assigned to receive four course consolidation with FA (n = 23) or HD-Ara-C (n = 22). Our study showed that at 36-months, relapse-free survival (RFS) was 81.73% in the FA arm and 50.73% in the HD-Ara-C arm (P = 0.04), overall survival (OS) was 91.1% and 48.4% (P = 0.01) in the FA arm and in the HD-Ara-C arm respectively; whereas cumulative incidence of relapse (CIR) was 18.27% and 47.39%, in the FA arm and in the HD-Ara-C arm respectively (P = 0.05). In our study, treatment with FA, MRD2 status (reduction ≥ 3-log) and absence of c-kit mutations were identified as independent prognostic factors for lower risk of relapse, improved RFS and OS. We also found RFS for patients without c-kit mutations was 100% in FA arm, and 57.8% in HD-Ara-C arm at 36 months (P = 0.005); OS of both groups at 36 months was 100% and 51.4%, respectively (P = 0.004), suggesting a benefit of consolidation therapy with FA for t(8;21) AML patients, especially, those without c-kit mutations (Clinicaltrials.org ID NCT# 02024308). Am. J. Hematol. 92:12-17, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Economic burden of follicular non-Hodgkin's lymphoma.

PubMed

Foster, Talia; Miller, Jeffrey D; Boye, Mark E; Russell, Mason W

2009-01-01

Follicular non-Hodgkin's lymphoma (FNHL), a slow-growing cancer of the immune system, constitutes about 15-30% of all incident non-Hodgkin's lymphoma in developed countries. Its incidence is rising worldwide. Patients can live many years, but FNHL is considered incurable. We systematically reviewed the English-language MEDLINE-indexed and non-indexed economic literature published in the past 10 years on FNHL, identifying 23 primary economic studies. The economic burden of FNHL is significant, but available data are generally limited to retrospective considerations of hospital-based direct treatment costs, with little information available regarding societal cost of illness. Most direct cost information originates from the US, with one estimate of $US36 000 for the per-patient incremental cost of FNHL care during the first year following diagnosis. The most studied treatment is rituximab, which may offer similar overall costs to fludarabine considering higher resource use with fludarabine complications. Nearly all cost-effectiveness models identified by this review evaluated rituximab for relapsed/refractory FNHL responding to chemotherapy induction. Rituximab is supported as a cost-effective addition to standard chemotherapy by two models in the UK and one in the US, as maintenance therapy instead of stem-cell transplant by one UK model, and as maintenance therapy instead of observation alone by one model each in France, Spain and Canada. The UK National Institute for Health and Clinical Excellence updated guidance on rituximab in February 2008, concluding that it is cost effective when added to induction chemotherapy, and when used as maintenance therapy. No studies of per-patient or national indirect costs of illness were identified, with the only study of indirect costs a Canadian survey documenting lost work productivity. Across all study types identified by our review, the most common focus was on the direct costs of rituximab. As new treatments for FNHL come to market, more real-life cost data are imperative to calculate their relative cost effectiveness.

Thrombotic microangiopathy after allogeneic stem cell transplantation in the era of reduced-intensity conditioning: The incidence is not reduced.

PubMed

Shimoni, Avichai; Yeshurun, Moshe; Hardan, Izhar; Avigdor, Abraham; Ben-Bassat, Isaac; Nagler, Arnon

2004-07-01

Thrombotic microangiopathy (TMA) is one of the most severe complications of stem cell transplantation (SCT). Endothelial cell injury caused by the toxic effects of high-dose chemoradiotherapy is likely the primary event in pathogenesis. The incidence, clinical settings, and risk factors for TMA in the era of nonmyeloablative conditioning have not been well defined. The data on 147 consecutive SCTs in a single center were collected, and patients with TMA were identified. Patient characteristics, response to therapy, and outcome were recorded, and risk factors were determined. TMA occurred in 22 of 147 transplantations, with a projected incidence of 20% +/- 4%. TMA occurred in 3 clinical settings: classic multifactorial TMA, TMA associated with severe hepatic graft-versus-host disease (GVHD), and TMA associated with second SCT, with a projected incidence of 8% +/- 3%, 73% +/- 14%, and 70% +/- 16% of patients at risk, respectively. TMA occurred after 23% +/- 6% of nonmyeloablative and 16% +/- 5% of myeloablative conditioning regimens (not significant). Univariate analysis determined SCT from unrelated donors, SCT during advanced or active disease, second SCT within 6 months of a prior SCT, and acute GVHD as risk factors for TMA. The last 2 factors remained significant in a multivariate model. Thirty-two percent of patients responded to therapy. The peri-TMA mortality rate was 68% +/- 10%. Six patients had diffuse alveolar hemorrhage complicating TMA. SCT-associated TMA is a relatively common complication with unsatisfactory therapy and grim prognosis. Fludarabine-based nonmyeloablative conditioning does not confer a lesser risk for TMA. This observation may relate to the selective use of these regimens in elderly and heavily pretreated patients or to the lack of reduction of GVHD with these regimens, and fludarabine itself may be involved in causing endothelial damage. Further exploration of novel preventive and therapeutic measurements is required in high-risk settings.

β2 -microglobulin normalization within 6 months of ibrutinib-based treatment is associated with superior progression-free survival in patients with chronic lymphocytic leukemia.

PubMed

Thompson, Philip A; O'Brien, Susan M; Xiao, Lianchun; Wang, Xuemei; Burger, Jan A; Jain, Nitin; Ferrajoli, Alessandra; Estrov, Zeev; Keating, Michael J; Wierda, William G

2016-02-15

A high pretreatment β2 -microglobulin (B2M) level is associated with inferior survival outcomes in patients with chronic lymphocytic leukemia. However, to the authors' knowledge, the prognostic and predictive significance of changes in B2M during treatment have not been reported to date. The authors analyzed 83 patients treated with ibrutinib-based regimens (66 with recurrent/refractory disease) and 198 treatment-naive patients who were treated with combined fludarabine, cyclophosphamide, and rituximab (FCR) to characterize changes in B2M and their relationship with clinical outcomes. B2M rapidly decreased during treatment with ibrutinib; on multivariable analysis, patients who received FCR (odds ratio, 0.40; 95% confidence interval [95% CI], 0.18-0.90 [P = .027]) were less likely to have normalized B2M at 6 months than patients treated with ibrutinib. On univariable analysis, normalization of B2M was associated with superior progression-free survival (PFS) from the 6-month landmark in patients treated with ibrutinib-based regimens and FCR. On multivariable analysis, failure to achieve normalized B2M at 6 months of treatment was associated with inferior PFS (hazard ratio, 16.9; 95% CI, 1.3-220.0 [P = .031]) for patients treated with ibrutinib, after adjusting for the effects of baseline B2M, stage of disease, fludarabine-refractory disease, and del(17p). In contrast, in patients treated with FCR, negative minimal residual disease status in the bone marrow was the only variable found to be significantly associated with superior PFS (hazard ratio, 0.28; 95% CI, 0.12-0.67 [P = .004]). Normalization of B2M at 6 months in patients treated with ibrutinib was found to be a useful predictor of subsequent PFS and may assist in clinical decision-making. © 2015 American Cancer Society.

Solar tomography adaptive optics.

PubMed

Ren, Deqing; Zhu, Yongtian; Zhang, Xi; Dou, Jiangpei; Zhao, Gang

2014-03-10

Conventional solar adaptive optics uses one deformable mirror (DM) and one guide star for wave-front sensing, which seriously limits high-resolution imaging over a large field of view (FOV). Recent progress toward multiconjugate adaptive optics indicates that atmosphere turbulence induced wave-front distortion at different altitudes can be reconstructed by using multiple guide stars. To maximize the performance over a large FOV, we propose a solar tomography adaptive optics (TAO) system that uses tomographic wave-front information and uses one DM. We show that by fully taking advantage of the knowledge of three-dimensional wave-front distribution, a classical solar adaptive optics with one DM can provide an extra performance gain for high-resolution imaging over a large FOV in the near infrared. The TAO will allow existing one-deformable-mirror solar adaptive optics to deliver better performance over a large FOV for high-resolution magnetic field investigation, where solar activities occur in a two-dimensional field up to 60'', and where the near infrared is superior to the visible in terms of magnetic field sensitivity.

Ultraviolet Properties of Halo Coronal Mass Ejections: Doppler Shifts, Angles, Shocks, and Bulk Morphology

NASA Astrophysics Data System (ADS)

Ciaravella, A.; Raymond, J. C.; Kahler, S. W.

2006-11-01

We present UV spectral information for 22 halo or partial halo CMEs observed by UVCS. The CME fronts show broad line profiles, while the line intensities are comparable to the background corona. The Doppler shifts of the front material are generally small, showing that the motion of gas in the fronts is mostly transverse to the line of sight. This indicates that, at least in halo CMEs, the fronts generally correspond to coronal plasma swept up by a shock or compression wave, rather than plasma carried outward by magnetic loops. This favors an ice cream cone (or a spherical shell) model, as opposed to an expanding arcade of loops. We use the line widths to discriminate between shock heating and bulk expansion. Of 14 cases where we detected the CME front, the line broadening in 7 cases can be attributed to shock heating, while in 3 cases it is the line-of-sight component of the CME expansion. For the CME cores we determine the angles between the motion and the plane of the sky, along with the actual heliocentric distances, in order to provide quantitative estimates of projection effects.

Pipe crawler with stabilizing midsection

DOEpatents

Zollinger, W.T.; Treanor, R.C.

1994-12-27

A pipe crawler is described having a midsection that provides the stability and flexibility to allow the pipe crawler to negotiate curved and uneven segments of piping while traveling through piping systems. The pipe crawler comprises a front leg assembly, a rear leg assembly, a midsection with a gimbal at each end for connecting the midsection to the front and rear leg assemblies in a flexible manner, and an air cylinder for changing the distance between the front and rear leg assemblies. The pipe crawler moves in ''inch worm'' fashion with the front and rear leg assemblies alternating between an extended and a retracted position as the air cylinder moves the retracted leg assembly forward. The midsection has a plurality of legs extending radially for holding the midsection within a maximum displacement from the piping axis so that the gimbals are not pivoted to extreme angles where they might lock up or seize. When the midsection is displaced sufficiently, its legs with wheels on each end engage the interior surface of the piping and prevent further displacement. Using two gimbals divides the angle between the planes defined by the front and rear leg assemblies which also helps to prevent excessive gimbal pivoting. 5 figures.

Age Appropriate Restraints for the Right Front Passenger

PubMed Central

Augenstein, J; Perdeck, E.; Digges, K.; Bahouth, G.

2007-01-01

This study applies NASS/CDS, GES and FARS data to examine occupant exposure plus injury and fatality rates for belted occupants in frontal crashes by seating position, age and gender. The NASS data was used to examine the distributions by crash severity. The GES data showed that when two elderly occupants (age 65+) were present, the female occupied the right front passenger position 73% of the time. A paired comparison analysis using FARS data showed that, for elderly occupants (age 65+), the fatality risk for elderly right front passengers is 42% higher than for elderly drivers. The NASS/CDS analysis found 74% of the seriously injured vulnerable passengers with MAIS 3+ injuries were in crashes less severe than 26 mph. This group of injured occupants was made up of 43% aged 50 and older and 42% younger females. The injury rates for the older (age 50+) right front passengers were 1.8 times the rates for the elderly drivers. These results suggest the need for more benign safety systems for the right front passenger that are appropriate for the lower injury tolerance of the predominant occupants of that seating position. PMID:18184503

Pipe crawler with stabilizing midsection

DOEpatents

Zollinger, William T.; Treanor, Richard C.

1994-01-01

A pipe crawler having a midsection that provides the stability and flexibty to allow the pipe crawler to negotiate curved and uneven segments of piping while traveling through piping systems. The pipe crawler comprises a front leg assembly, a rear leg assembly, a midsection with a gimbal at each end for connecting the midsection to the front and rear leg assemblies in a flexible manner, and an air cylinder for changing the distance between the front and rear leg assemblies. The pipe crawler moves in "inch worm" fashion with the front and rear leg assemblies alternating between an extended and a retracted position as the air cylinder moves the retracted leg assembly forward. The midsection has a plurality of legs extending radially for holding the midsection within a maximum displacement from the piping axis so that the gimbals are not pivoted to extreme angles where they might lock up or seize. When the midsection is displaced sufficiently, its legs with wheels on each end engage the interior surface of the piping and prevent further displacement. Using two gimbals divides the angle between the planes defined by the front and rear leg assemblies which also helps to prevent excessive gimbal pivoting.

Pipe crawler with stabilizing midsection

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

Zollinger, W.T.; Treanor, R.C.

1993-09-20

This invention is comprised of a pipe crawler having a midsection that provides the stability and flexibility to allow the pipe crawler to negotiate curved and uneven segments of piping while traveling through piping systems. The pipe crawler comprises a front leg assembly, a rear leg assembly, a midsection with a gimbal at each end for connecting the midsection to the front and rear leg assemblies in a flexible manner, and an air cylinder for changing the distance between the front and rear leg assemblies. The pipe crawler moves in ``inch worm`` fashion with the front and rear leg assembliesmore » alternating between an extended and a retracted position as the air cylinder moves the retracted leg assembly forward. The midsection has a plurality of legs extending radially for holding the midsection within a maximum displacement from the piping axis so that the gimbals are not pivoted to extreme angles where they might lock up or seize. When the midsection is displaced sufficiently, its legs with wheels on each end engage the interior surface of the piping and prevent further displacement. Using two gimbals divides the angle between the planes defined by the front and rear leg assemblies which also helps to prevent excessive gimbal pivoting.« less

Pipe crawler with stabilizing midsection

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

Zollinger, W.T.; Treanor, R.C.

1994-12-27

A pipe crawler is described having a midsection that provides the stability and flexibility to allow the pipe crawler to negotiate curved and uneven segments of piping while traveling through piping systems. The pipe crawler comprises a front leg assembly, a rear leg assembly, a midsection with a gimbal at each end for connecting the midsection to the front and rear leg assemblies in a flexible manner, and an air cylinder for changing the distance between the front and rear leg assemblies. The pipe crawler moves in ''inch worm'' fashion with the front and rear leg assemblies alternating between anmore » extended and a retracted position as the air cylinder moves the retracted leg assembly forward. The midsection has a plurality of legs extending radially for holding the midsection within a maximum displacement from the piping axis so that the gimbals are not pivoted to extreme angles where they might lock up or seize. When the midsection is displaced sufficiently, its legs with wheels on each end engage the interior surface of the piping and prevent further displacement. Using two gimbals divides the angle between the planes defined by the front and rear leg assemblies which also helps to prevent excessive gimbal pivoting. 5 figures.« less

Planar microlens with front-face angle: design, fabrication, and characterization

NASA Astrophysics Data System (ADS)

Al Hafiz, Md. Abdullah; Michael, Aron; Kwok, Chee-Yee

2016-07-01

This paper studies the effect of microlens front-face angle on the performance of an optical system consisting of a planar-graded refractive index (GRIN) lens pair facing each other separated by a free-space region. The planar silica microlens pairs are designed to facilitate low-loss optical signal propagation in the free-space region between the opposing optical waveguides. The planar lens is fabricated from a 38-μm-thick fluorine-doped silica layer on a silicon substrate. It has a parabolic refractive index profile in the vertical direction, which is achieved by controlled fluorine incorporation in the silica film to collimate the optical beam in the vertical direction. Horizontal beam collimation is achieved by incorporating a horizontal curvature at the front face of the lens defined by deep oxide etch. A generalized 3×3 ABCDGH transformation matrix method has been derived to compute the coupling efficiency of such microlens pairs to take front-face angles that may be present due to fabrication variations or limitations and possible input/output optical fiber offset/tilt into considerations. Pairs of such planar GRIN lens with various free-space propagation distances between them ranging from 75 to 2500 μm and with front-face angles of 1.5 deg, 2 deg, and 4 deg have been fabricated and characterized. Beam propagation method simulations have been carried out to substantiate the theoretical and experimental results. The results indicate that the optical loss is reasonably low up to 1.5 deg of front-face angles and increases significantly with further increase in the front-face angle. Analysis shows that for a given system with specific microlens front-face angle, the optical loss can be significantly reduced by properly compensating the vertical position of the input and output fibers.

Sidewall crystallization and saturation front formation in silicic magma chambers

NASA Astrophysics Data System (ADS)

Lake, E. T.

2012-12-01

The cooling and crystallization style of silicic magma bodies in the upper crust falls on a continuum between whole-chamber processes of convection, crystal settling, and cumulate formation and interface driven processes of conduction and crystallization front migration. In the former case, volatile saturation occurs uniformly chamber wide, in the latter volatile saturation occurs along an inward propagating front. Ambient thermal gradient primarily controls the propagation rate; warm (> 30 °C / km) geothermal gradients promote 1000m+ thick crystal mush zones but slow crystallization front propagation. Cold geothermal gradients support the opposite. Magma chamber geometry plays a second order role in controlling propagation rates; bodies with high surface to magma ratio and large Earth's surface parallel faces exhibit more rapid propagation and smaller mush zones. Crystallization front propagation occurs at speeds of up to 6 cm/year (rhyolitic magma, thin sill geometry, 10 °C / km geotherm), far faster than diffusion of volatiles in magma and faster than bubbles can nucleate and ascend under certain conditions. Saturation front propagation is fixed by pressure and magma crystal content; above certain modest initial water contents (4.4 wt% in a dacite) mobile magma above 10 km depth always contains a saturation front. Saturation fronts propagate down from the magma chamber roof at lower water contents (3.3 wt% in a dacite at 5 km depth), creating an upper saturated interface for most common (4 - 6 wt%) magma water contents. This upper interface promotes the production of a fluid pocket underneath the apex of the magma chamber. Magma de-densification by bubble nucleation promotes convection and homogenization in dacitic systems. If the fluid pocket grew rapidly without draining, hydro-fracturing and eruption would result. The combination of fluid escape pathways and metal scavenging would generate economic vein or porphyry deposits.

Preservation of the endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound ablation of submucosal uterine fibroids.

PubMed

Kim, Young-Sun; Kim, Tae-Joong; Lim, Hyo Keun; Rhim, Hyunchul; Jung, Sin-Ho; Ahn, Joong Hyun; Lee, Jeong-Won; Kim, Byoung-Gie

2017-09-01

To evaluate the integrity of endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) ablation of submucosal uterine fibroids based on contrast-enhanced MRI findings, and to identify the risk factors for endometrial impairment. In total, 117 submucosal fibroids (diameter: 5.9 ± 3.0 cm) in 101 women (age: 43.6 ± 4.4 years) treated with MR-HIFU ablation were retrospectively analysed. Endometrial integrity was assessed with contrast-enhanced T1-weighted images at immediate (n = 101), 3-month (n = 62) and 12-month (n = 15) follow-ups. Endometrial impairment was classified into grades 0 (continuous endometrium), 1 (pin-point, full-thickness discontinuity), 2 (between grade 1 and 3), or 3 (full-thickness discontinuity >1 cm). Risk factors were assessed with generalized estimating equation (GEE) analysis. Among 117 fibroids, grades 0, 1, 2 and 3 endometrial impairments were observed at initial examination in 56.4%, 24.8%, 13.7% and 4.3%, respectively. Among 37 fibroid cases of endometrial impairment for which follow-ups were conducted, 30 showed improvements at 3- and/or 12-month follow-up. GEE analysis revealed the degree of endometrial protrusion was significantly associated with severity of endometrial injury (P < 0.0001). After MR-HIFU ablation of submucosal fibroids, endometrial enhancement was preserved intact or minimally impaired in most cases. Impaired endometrium, which is more common after treating endometrially-protruded fibroids, may recover spontaneously. • After MR-HIFU ablation for submucosal fibroid, endometrium is mostly preserved/minimally impaired. • Endometrial-protruded submucosal fibroid is susceptible to more severe endometrial impairment. • The impaired endometrium may recover spontaneously at follow-up MR exams.

Interaction of lateral baroclinic forcing and turbulence in an estuary

USGS Publications Warehouse

Lacy, J.R.; Stacey, M.T.; Burau, J.R.; Monismith, Stephen G.

2003-01-01

Observations of density and velocity in a channel in northern San Francisco Bay show that the onset of vertical density stratification during flood tides is controlled by the balance between the cross-channel baroclinic pressure gradient and vertical mixing due to turbulence. Profiles of velocity, salinity, temperature, and suspended sediment concentration were measured in transects across Suisun Cutoff, in northern San Francisco Bay, on two days over the 12.5-hour tidal cycle. During flood tides an axial density front developed between fresher water flowing from the shallows of Grizzly Bay into the northern side of Suisun Cutoff and saltier water flowing up the channel. North of the front, transverse currents were driven by the lateral salinity gradient, with a top-to-bottom velocity difference greater than 30 cm/s. South of the front, the secondary circulation was weak, and along-channel velocities were greater than to the north. The gradient Richardson number shows that stratification was stable north of the front, while the water column was turbulently mixed south of the front. Time-series measurements of velocity and salinity demonstrate that the front develops during each tidal cycle. In estuaries, longitudinal dynamics predict less stratification during flood than ebb tides. These data show that stratification can develop during flood tides due to a lateral baroclinic pressure gradient in estuaries with complex bathymetry.

Submesoscale CO2 variability across an upwelling front off Peru

NASA Astrophysics Data System (ADS)

Köhn, Eike E.; Thomsen, Sören; Arévalo-Martínez, Damian L.; Kanzow, Torsten

2017-12-01

As a major source for atmospheric CO2, the Peruvian upwelling region exhibits strong variability in surface fCO2 on short spatial and temporal scales. Understanding the physical processes driving the strong variability is of fundamental importance for constraining the effect of marine emissions from upwelling regions on the global CO2 budget. In this study, a frontal decay on length scales of 𝒪(10 km) was observed off the Peruvian coast following a pronounced decrease in down-frontal (equatorward) wind speed with a time lag of 9 h. Simultaneously, the sea-to-air flux of CO2 on the inshore (cold) side of the front dropped from up to 80 to 10 mmol m-2 day-1, while the offshore (warm) side of the front was constantly outgassing at a rate of 10-20 mmol m-2 day-1. Based on repeated ship transects the decay of the front was observed to occur in two phases. The first phase was characterized by a development of coherent surface temperature anomalies which gained in amplitude over 6-9 h. The second phase was characterized by a disappearance of the surface temperature front within 6 h. Submesoscale mixed-layer instabilities were present but seem too slow to completely remove the temperature gradient in this short time period. Dynamics such as a pressure-driven gravity current appear to be a likely mechanism behind the evolution of the front.

Why Does Attention to Web Articles Fall With Time?

PubMed

Simkin, Mikhail V; Roychowdhury, Vwani P

2015-09-01

We analyze access statistics of 150 blog entries and news articles for periods of up to 3 years. Access rate falls as an inverse power of time passed since publication. The power law holds for periods of up to 1,000 days. The exponents are different for different blogs and are distributed between 0.6 and 3.2. We argue that the decay of attention to a web article is caused by the link to it first dropping down the list of links on the website's front page and then disappearing from the front page and its subsequent movement further into background. The other proposed explanations that use a decaying with time novelty factor, or some intricate theory of human dynamics, cannot explain all of the experimental observations.

FELIX: a PCIe based high-throughput approach for interfacing front-end and trigger electronics in the ATLAS Upgrade framework

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

Anderson, J.; Bauer, K.; Borga, A.

The ATLAS Phase-I upgrade (2019) requires a Trigger and Data Acquisition (TDAQ) system able to trigger and record data from up to three times the nominal LHC instantaneous luminosity. Furthermore, the Front-End LInk eXchange (FELIX) system provides an infrastructure to achieve this in a scalable, detector agnostic and easily upgradeable way. It is a PC-based gateway, interfacing custom radiation tolerant optical links from front-end electronics, via PCIe Gen3 cards, to a commodity switched Ethernet or InfiniBand network. FELIX enables reducing custom electronics in favour of software running on commercial servers. Here, the FELIX system, the design of the PCIe prototypemore » card and the integration test results are presented.« less

The Ring of Fire: The Effects of Slope upon Pattern Formation in Simulated Forest Fire Systems

NASA Astrophysics Data System (ADS)

Morillo, Robin; Manz, Niklas

We report about spreading fire fronts under sloped conditions using the general cellular automaton model and data from physical scaled-down experiments. Punckt et al. published experimental and computational results for planar systems and our preliminary results confirmed the expected speed-slope dependence of fire fronts propagating up or down the hill with a cut-off slope value above which no fire front can exist. Here we focus on two fascinating structures in reaction-diffusion systems: circular expanding target pattern and rotating spirals. We investigated the behaviors of both structures with varied values for the slope of the forest and the homogeneity of the trees. For both variables, a range of values was found for which target pattern or spiral formation was possible.

FELIX: a PCIe based high-throughput approach for interfacing front-end and trigger electronics in the ATLAS Upgrade framework

DOE PAGES

Anderson, J.; Bauer, K.; Borga, A.; ...

2016-12-13

The ATLAS Phase-I upgrade (2019) requires a Trigger and Data Acquisition (TDAQ) system able to trigger and record data from up to three times the nominal LHC instantaneous luminosity. Furthermore, the Front-End LInk eXchange (FELIX) system provides an infrastructure to achieve this in a scalable, detector agnostic and easily upgradeable way. It is a PC-based gateway, interfacing custom radiation tolerant optical links from front-end electronics, via PCIe Gen3 cards, to a commodity switched Ethernet or InfiniBand network. FELIX enables reducing custom electronics in favour of software running on commercial servers. Here, the FELIX system, the design of the PCIe prototypemore » card and the integration test results are presented.« less

Comparing a Coevolutionary Genetic Algorithm for Multiobjective Optimization

NASA Technical Reports Server (NTRS)

Lohn, Jason D.; Kraus, William F.; Haith, Gary L.; Clancy, Daniel (Technical Monitor)

2002-01-01

We present results from a study comparing a recently developed coevolutionary genetic algorithm (CGA) against a set of evolutionary algorithms using a suite of multiobjective optimization benchmarks. The CGA embodies competitive coevolution and employs a simple, straightforward target population representation and fitness calculation based on developmental theory of learning. Because of these properties, setting up the additional population is trivial making implementation no more difficult than using a standard GA. Empirical results using a suite of two-objective test functions indicate that this CGA performs well at finding solutions on convex, nonconvex, discrete, and deceptive Pareto-optimal fronts, while giving respectable results on a nonuniform optimization. On a multimodal Pareto front, the CGA finds a solution that dominates solutions produced by eight other algorithms, yet the CGA has poor coverage across the Pareto front.

Extendable pipe crawler

DOEpatents

Hapstack, M.

1991-05-28

A pipe crawler is described having a front leg assembly and a back leg assembly connected together by two air cylinders, each leg assembly having four extendable legs and a pair of actuators for sliding the extendable legs radially outward to increase the range of the legs when the pipe crawler enters a section of a pipe having a larger diameter. The crawler crawls by inchworm'-like motion, the front leg assembly and back leg assembly alternately engaging and disengaging the wall of the pipe to hold the pipe crawler as the air cylinders alternately advance the front leg assembly and bring up the rear leg assembly. The pair of actuators of each leg assembly are parallel, adjacent and opposing acting so that each slides two adjacent extendable legs radially outward. 5 figures.

[Demands for death (suicide assistance and euthanasia) in palliative medicine].

PubMed

Moynier-Vantieghem, Karine; Weber, Catherine; Espolio, Desbaillet Yolanda; Pautex, Sophie; Zulian, Gilbert

2010-02-03

During a prospective open survey over 12 months of hospitalized patients, 44 death demands were registered for 39 patients (25 cancer, 6 cardiovascular disorder, 2 Parkinson's disease, 3 arthritis, 1 COPD, 1 dementia and 1 severe depression). 14 patients were also depressed. 28 requested euthanasia, 16 suicide assistance. At 1 month, 3 persisted, 16 had abandoned, 16 had died and 4 were not questioned. At 6 months, 7 were alive but had abandoned and 2 had committed suicide at their home. The majority of death demands correspond to euthanasia which is a murder according to the penal code. In front of such demand, realistic short-term objectives must be established. Many patients give up their project. This indicates great uncertainty in front of care and greatest ambivalence in front of life.

Extendable pipe crawler

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

Hapstack, M.

1991-05-28

A pipe crawler is described having a front leg assembly and a back leg assembly connected together by two air cylinders, each leg assembly having four extendable legs and a pair of actuators for sliding the extendable legs radially outward to increase the range of the legs when the pipe crawler enters a section of a pipe having a larger diameter. The crawler crawls by inchworm'-like motion, the front leg assembly and back leg assembly alternately engaging and disengaging the wall of the pipe to hold the pipe crawler as the air cylinders alternately advance the front leg assembly andmore » bring up the rear leg assembly. The pair of actuators of each leg assembly are parallel, adjacent and opposing acting so that each slides two adjacent extendable legs radially outward. 5 figures.« less

Extendable pipe crawler

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

Hapstack, M.

1990-05-01

A pipe crawler having a front leg assembly and a back leg assembly connected together by two air cylinders, each leg assembly having four extendable legs and a pair of actuators for sliding the extendable legs radically outward to increase the range of the legs when the pipe crawler enters a section of pipe having a larger diameter. The crawler crawls by inchworm''-like motion, the front leg assembly and back leg assembly alternately engaging and disengaging the wall of the pipe to hold the pipe crawler as the air cylinders alternately advance the front leg assembly and bring up themore » rear leg assembly. The pair of actuators of each leg assembly are parallel, adjacent and opposing acting so that each slides two adjacent extendable legs radially outward. 5 figs.« less

Starting up the upstarts.

PubMed

Greene, J

1997-12-20

Venture capitalists pour $1 billion a year into health care--and that investment may be the most overlooked indicator of new business opportunities. Signs show that companies focused on consolidation and cost-cutting are off the A list for risk capital. Instead, venture capitalists are targeting start-ups that save money on the front lines by truly managing care.

Addressing water scarcity through limited irrigation cropping: Field experiments and modeling

USDA-ARS?s Scientific Manuscript database

Population growth in urbanizing areas such as the Front Range of Colorado has led to increased pressure to transfer water from agriculture to municipalities. In many cases this has led to complete dry up of productive irrigated lands. An option to complete dry-up is the practice of limited or defi...

Impediments to Increasing Diversity in Post-Secondary Education

ERIC Educational Resources Information Center

Johnson, Carol Siri

2007-01-01

Due to the increasing complexity in the financial aid process and the movement of available financial aid up the economic scale, poor people and minorities have less access to college, including engineering programs. Some impediments are lack of access to knowledge about college, increasing complexity and up-front costs in the application process…

New dosing strategies for an old antibiotic: pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease.

PubMed

Rao, Gauri G; Ly, Neang S; Haas, Curtis E; Garonzik, Samira; Forrest, Alan; Bulitta, Jurgen B; Kelchlin, Pamela A; Holden, Patricia N; Nation, Roger L; Li, Jian; Tsuji, Brian T

2014-01-01

Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an in vitro pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10(8) CFU/ml) of Pseudomonas aeruginosa. The pharmacokinetics were simulated for patients with hepatic (half-life [t1/2] of 3.2 h) or renal (t1/2 of 14.8 h) disease. Front-loaded regimens (n=5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (fAUC) compared to those with traditional dosing regimens (n=14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log10 within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of P. aeruginosa. The current study, which utilizes an in vitro pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.

Umbilical Cord Blood Transplant, Cyclophosphamide, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematologic Disease

ClinicalTrials.gov

2018-03-23

Acute Biphenotypic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Adult Acute Lymphoblastic Leukemia in Complete Remission; Aggressive Non-Hodgkin Lymphoma; Beta-2-Microglobulin Greater Than 3 g/mL; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Complete Remission; Chromosome 13 Abnormality; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Lymphoblastic Lymphoma; Mantle Cell Lymphoma; Myelodysplastic Syndrome With Excess Blasts; Myelofibrosis; Pancytopenia; Plasma Cell Myeloma; Prolymphocytic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma

Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children.

PubMed

Goto, Hiroaki; Naruto, Takuya; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Fujii, Hisaki; Yokota, Shumpei; Komine, Hiromi

2009-10-01

Sensitivity to 10 anticancer drugs was evaluated in 6 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. Authenticity of newly established cell lines was confirmed by genomic fingerprinting. The line YCUB-5R established at relapse was more resistant to 4-hydroperoxy-cyclophosphamide, cytarabine, L-asparaginase, topotecan, fludarabine, and etoposide than YCUB-5 from the same patient at diagnosis. Of the drugs tested, etoposide and SN-38 (irinotecan) showed highest efficacy in the panel, with 50% growth inhibition at 0.22-1.8 microg/ml and 0.57-3.6 ng/ml, respectively. This cell line panel offers an in vitro model for the development of new therapies for childhood BCP-ALL.

A new data acquisition system for the CMS Phase 1 pixel detector

NASA Astrophysics Data System (ADS)

Kornmayer, A.

2016-12-01

A new pixel detector will be installed in the CMS experiment during the extended technical stop of the LHC at the beginning of 2017. The new pixel detector, built from four layers in the barrel region and three layers on each end of the forward region, is equipped with upgraded front-end readout electronics, specifically designed to handle the high particle hit rates created in the LHC environment. The DAQ back-end was entirely redesigned to handle the increased number of readout channels, the higher data rates per channel and the new digital data format. Based entirely on the microTCA standard, new front-end controller (FEC) and front-end driver (FED) cards have been developed, prototyped and produced with custom optical link mezzanines mounted on the FC7 AMC and custom firmware. At the same time as the new detector is being assembled, the DAQ system is set up and its integration into the CMS central DAQ system tested by running the pilot blade detector already installed in CMS. This work describes the DAQ system, integration tests and gives an outline for the activities up to commissioning the final system at CMS in 2017.

The South African isotope facility project

NASA Astrophysics Data System (ADS)

Bark, R. A.; Barnard, A. H.; Conradie, J. L.; de Villiers, J. G.; van Schalkwyk, P. A.

2018-05-01

The South African Isotope Facility (SAIF) is a project in which iThemba LABS plans to build a radioactive-ion beam (RIB) facility. The project is divided into the Accelerator Centre of Exotic Isotopes (ACE Isotopes) and the Accelerator Centre for Exotic Beams (ACE Beams). For ACE Isotopes, a high-current, 70 MeV cyclotron will be acquired to take radionuclide production off the existing Separated Sector Cyclotron (SSC). A freed up SSC will then be available for an increased tempo of nuclear physics research and to serve as a driver accelerator for the ACE Beams project, in which protons will be used for the direct fission of Uranium, producing beams of fission fragments. The ACE Beams project has begun with "LeRIB" - a Low Energy RIB facility, now under construction. In a collaboration with INFN Legnaro, the target/ion-source "front-end" will be a copy of the front-end developed for the SPES project. A variety of targets may be inserted into the SPES front-end; a uranium-carbide target has been designed to produce up to 2 × 1013 fission/s using a 70 MeV proton beam of 150 µA intensity.

Frontline treatment of acute myeloid leukemia in adults

PubMed Central

Tamamyan, Gevorg; Kadia, Tapan; Ravandi, Farhad; Borthakur, Gautam; Cortes, Jorge; Jabbour, Elias; Daver, Naval; Ohanian, Maro; Kantarjian, Hagop; Konopleva, Marina

2017-01-01

Recent years have highlighted significant progress in understanding the underlying genetic and epigenetic signatures of acute myeloid leukemia(AML). Most importantly, novel chemotherapy and targeted strategies have led to improved outcomes in selected genetic subsets. AML is a remarkably heterogeneous disease, and individualized therapies for disease-specific characteristics (considering patients’ age, cytogenetics, and mutations) could yield better outcomes. Compared with the historical 5-to 10-year survival rate of 10%, the survival of patients who undergo modern treatment approaches reaches up to 40–50%, and for specific subsets, the improvements are even more dramatic; for example, in acute promyelocytic leukemia, the use of all-trans retinoic acid and arsenic trioxide improved survival from 30–40% up to 80–90%. Similar progress has been documented in core-binding-factor-AML, with an increase in survival from 30% to 80% upon the use of high-dose cytarabine/fludarabine/granulocyte colony-stimulating factor combination regimens. AML treatment was also recently influenced by the discovery of the superiority of regimens with higher dose Ara-C and nucleoside analogues compared with the “7+3” regimen, with about a 20% improvement in overall survival. Despite these significant differences, most centers continue to use the “7+3” regimen, and greater awareness will improve the outcome. The discovery of targetable molecular abnormalities and recent studies of targeted therapies (gemtuzumab ozagomycin, FLT3 inhibitors, isocitrate dehydrogenase inhibitors, and epigenetic therapies), future use of checkpoint inhibitors and other immune therapies such as chimeric antigen receptor T-cells, and maintenance strategies based on the minimal residual disease evaluation represent novel, exciting clinical leads aimed to improve AML outcomes in the near future. PMID:28109402

Up Front for Business Ed

ERIC Educational Resources Information Center

American School and University, 1978

1978-01-01

A new addition to the high school in Parma, a large suburban district near Cleveland, Ohio, contains space for business education courses and expansion of the library with an audiovisual center. (Author/MLF)

4. James L. Dillon and Company, Inc., photographer January, 1967 ...

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

4. James L. Dillon and Company, Inc., photographer January, 1967 INTERESTING OVAL STAIRWELL, LOOKING STRAIGHT UP FROM SECOND FLOOR - 626 South Front Street (House), Philadelphia, Philadelphia County, PA

Adapting for Impaired Patrons.

ERIC Educational Resources Information Center

Schuyler, Michael

1999-01-01

Describes how a library, with an MCI Corporation grant, approached the process of setting up computers for the visually impaired. Discusses preparations, which included hiring a visually-impaired user as a consultant and contacting the VIP (Visually Impaired Persons) group; equipment; problems with the graphical user interface; and training.…

Ocean wave generation by collapsing ice shelves

NASA Astrophysics Data System (ADS)

Macayeal, D. R.; Bassis, J. N.; Okal, E. A.; Aster, R. C.; Cathles, L. M.

2008-12-01

The 28-29 February, 2008, break-up of the Wilkins Ice Shelf, Antarctica, exemplifies the now-familiar, yet largely unexplained pattern of explosive ice-shelf break-up. While environmental warming is a likely ultimate cause of explosive break-up, several key aspects of their short-term behavior need to be explained: (1) The abrupt, near-simultaneous onset of iceberg calving across long spans of the ice front margin; (2) High outward drift velocity (about 0.3 m/s) of a leading phalanx of tabular icebergs that originate from the seaward edge of the intact ice shelf prior to break-up; (3) Rapid coverage of the ocean surface in the wake of this leading phalanx by small, capsized and dismembered tabular icebergs; (4) Extremely large gravitational potential energy release rates, e.g., up to 3 × 1010 W; (5) Lack of proximal iceberg-calving triggers that control the timing of break-up onset and that maintain the high break-up calving rates through to the conclusion of the event. Motivated by seismic records obtained from icebergs and the Ross Ice Shelf that show hundreds of micro- tsunamis emanating from near the ice shelf front, we re-examine the basic dynamic features of ice- shelf/ocean-wave interaction and, in particular, examine the possibility that collapsing ice shelves themselves are a source of waves that stimulate the disintegration process. We propose that ice-shelf generated surface-gravity waves associated with initial calving at an arbitrary seed location produce stress perturbations capable of triggering the onset of calving on the entire ice front. Waves generated by parting detachment rifts, iceberg capsize and break-up act next to stimulate an inverted submarine landslide (ice- slide) process, where gravitational potential energy released by upward movement of buoyant ice is radiated as surface gravity waves in the wake of the advancing phalanx of tabular icebergs. We conclude by describing how field research and remote sensing can be used to test the various conjectures about ice- shelf/wave interaction that appear to be at play during ice-shelf disintegration.

Peculiarity of convergence of shock wave generated by underwater electrical explosion of ring-shaped wire

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

Shafer, D.; Toker, G. R.; Gurovich, V. Tz.

2013-05-15

Nanosecond timescale underwater electrical wire explosions of ring-shaped Cu wires were investigated using a pulsed generator with a current amplitude up to 50 kA. It was shown that this type of wire explosion results in the generation of a toroidal shock wave (SW). Time- and space-resolved optical diagnostics were used to determine azimuthal uniformity of the shock wave front and its velocity. It was found that the shock wave preserves its circular front shape in the range of radii 50μm

Sandia technology & entrepreneurs improve Lasik

ScienceCinema

Neal, Dan; Turner, Tim

2018-05-11

Former Sandian Dan Neal started his company, WaveFront Sciences, based on wavefront sensing metrology technologies licensed from Sandia National Laboratories and by taking advantage of its Entrepreneurial Separation to Transfer Technology (ESTT) program. Abbott Medical Optics since acquired WaveFront and estimates that one million patients have improved the quality of their vision thanks to its products. ESTT is a valuable tool which allows Sandia to transfer technology to the private sector and Sandia employees to leave the Labs in order to start up new technology companies or help expand existing companies.

Sandia technology & entrepreneurs improve Lasik

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

Neal, Dan; Turner, Tim

2013-11-21

Former Sandian Dan Neal started his company, WaveFront Sciences, based on wavefront sensing metrology technologies licensed from Sandia National Laboratories and by taking advantage of its Entrepreneurial Separation to Transfer Technology (ESTT) program. Abbott Medical Optics since acquired WaveFront and estimates that one million patients have improved the quality of their vision thanks to its products. ESTT is a valuable tool which allows Sandia to transfer technology to the private sector and Sandia employees to leave the Labs in order to start up new technology companies or help expand existing companies.

Parent-reported symptoms, impairment, helpfulness of treatment, and unmet service needs in a follow-up of outpatient children with attention-deficit/hyperactivity disorder.

PubMed

Sollie, Henrik; Larsson, Bo

2016-11-01

Limited information exists regarding the associations between impairment, symptoms, helpfulness of treatments, and service needs after initial treatment of children with attention-deficit/hyperactivity disorder (ADHD). The aims of this study were to examine persistence rates and associations between parent-reported symptoms, impairment, helpfulness of treatments, and service needs in a retrospective follow-up study of children with ADHD. Parents of 214 children with a mean age of 12.6 years (SD = 2.1) who were diagnosed with ADHD at five child and adolescent mental health clinics (CAMHS) completed questionnaires 1-10 years (mean = 3.7 years, SD = 2.2) after baseline assessment. The response rate was 43.4%. A community comparison group (n = 110) was recruited from the same area. Approximately two-thirds (60.3%) of the sample fulfilled the DSM-IV symptom criteria of ADHD at follow-up, 84.3% were functionally impaired, and most children (84.7%) were on medication. Inattentive and emotional symptoms were the strongest predictors of impairment across impairment areas. Perceived helpfulness of different treatments varied from 71.8-88.7%, and no significant difference was found between the ADHD sub-groups regarding reported helpfulness. 'Adjustment of the school situation' was the most frequent service need, and approximately half of the parents reported needs for care co-ordination. Children fulfilling the symptom criteria of the ADHD Combined sub-group were most impaired and had most service needs. At follow-up, children were highly symptomatic and impaired, despite a high rate of persistent medication treatment. The findings underline the need for more tailored treatment and co-ordinated care over time.

78 FR 21218 - Disclosure of Consumer Complaint Data

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-10

... customer service and alleviate problems up front by helping consumers avoid ``bad actors.'' They further... Wire Jan. 31, 2013, available at http://www.businesswire.com/news/home/20130131006068/en/Arc-Analyzes...

Tendinitis (image)

MedlinePlus

... fibrous structure that joins muscle to bone. Tendinitis pain in the knee is located in the front of the knee. ... going up and down stairs or inclines. Tendinitis knee pain can happen in runners, skiers, and cyclists.

5. Historic American Buildings Survey E. W. Russell, Photographer, August ...

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

5. Historic American Buildings Survey E. W. Russell, Photographer, August 4, 1936 CLOSE-UP OF MAIN ENTRANCE (FRONT) - Government Street Presbyterian Church, Government & Jackson Streets, Mobile, Mobile County, AL

Radar observation of an along-front jet and transverse flow convergence associated with a North Sea front

NASA Astrophysics Data System (ADS)

Matthews, J. P.; Fox, A. D.; Prandle, D.

1993-01-01

This paper describes the first synoptic mapping of surface currents across a strong and stable tidal mixing front by HF radar. The radar deployment took place along the coast of northeast England during August and early September 1988 in parallel with extensive ship based CTD density and ADCP (Acoustic Doppler Current Profiler) measurements which provided data in the vertical plane to complement those of the HF radar. We describe two main results. Firstly, during a spring-tide period of strengthening inshore density gradients, an along-front jet with speeds of up to 14 cm s -1 was detected in the long term IIF radar residual field. The location and spatial form of this jet correspond with estimates of geostrophic currents derived from the measured density field. Secondly, a transverse "double-sided" surface flow convergence centred close to the frontal boundary and of net magnitude 4 cm s -1 accompanied the large along-front jet. Such a weaker cross-frontal component has been anticipated on theoretical grounds but never previously observed in this detailed fashion. The experiment underlines the power of a synergistic approach, based on HF remote sensing radar and ADCP, for the study of frontal circulation in coastal zones.

Radiation hydrodynamical instabilities in cosmological and galactic ionization fronts

NASA Astrophysics Data System (ADS)

Whalen, Daniel J.; Norman, Michael L.

2011-11-01

Ionization fronts, the sharp radiation fronts behind which H/He ionizing photons from massive stars and galaxies propagate through space, were ubiquitous in the universe from its earliest times. The cosmic dark ages ended with the formation of the first primeval stars and galaxies a few hundred Myr after the Big Bang. Numerical simulations suggest that stars in this era were very massive, 25-500 solar masses, with H(II) regions of up to 30,000 light-years in diameter. We present three-dimensional radiation hydrodynamical calculations that reveal that the I-fronts of the first stars and galaxies were prone to violent instabilities, enhancing the escape of UV photons into the early intergalactic medium (IGM) and forming clumpy media in which supernovae later exploded. The enrichment of such clumps with metals by the first supernovae may have led to the prompt formation of a second generation of low-mass stars, profoundly transforming the nature of the first protogalaxies. Cosmological radiation hydrodynamics is unique because ionizing photons coupled strongly to both gas flows and primordial chemistry at early epochs, introducing a hierarchy of disparate characteristic timescales whose relative magnitudes can vary greatly throughout a given calculation. We describe the adaptive multistep integration scheme we have developed for the self-consistent transport of both cosmological and galactic ionization fronts.

Shock Heating of the Merging Galaxy Cluster A521

NASA Technical Reports Server (NTRS)

Bourdin, H.; Mazzotta, P.; Markevitch, M.; Giacintucci, S.; Brunetti, G.

2013-01-01

A521 is an interacting galaxy cluster located at z = 0.247, hosting a low-frequency radio halo connected to an eastern radio relic. Previous Chandra observations hinted at the presence of an X-ray brightness edge at the position of the relic, which may be a shock front. We analyze a deep observation of A521 recently performed with XMM-Newton in order to probe the cluster structure up to the outermost regions covered by the radio emission. The cluster atmosphere exhibits various brightness and temperature anisotropies. In particular, two cluster cores appear to be separated by two cold fronts. We find two shock fronts, one that was suggested by Chandra and that is propagating to the east, and another to the southwestern cluster outskirt. The two main interacting clusters appear to be separated by a shock-heated region, which exhibits a spatial correlation with the radio halo. The outer edge of the radio relic coincides spatially with a shock front, suggesting that this shock is responsible for the generation of cosmic-ray electrons in the relic. The propagation direction and Mach number of the shock front derived from the gas density jump, M = 2.4 +/- 0.2, are consistent with expectations from the radio spectral index, under the assumption of Fermi I acceleration mechanism.

Use of glacial fronts by narwhals (Monodon monoceros) in West Greenland

PubMed Central

Moon, Twila; Hauser, Donna D. W.; McGovern, Richard; Heide-Jørgensen, Mads Peter; Dietz, Rune; Hudson, Ben

2016-01-01

Glacial fronts are important summer habitat for narwhals (Monodon monoceros); however, no studies have quantified which glacial properties attract whales. We investigated the importance of glacial habitats using telemetry data from n = 15 whales tagged in September of 1993, 1994, 2006 and 2007 in Melville Bay, West Greenland. For 41 marine-terminating glaciers, we estimated (i) narwhal presence/absence, (ii) number of 24 h periods spent at glaciers and (iii) the fraction of narwhals that visited each glacier (at 5, 7 and 10 km) in autumn. We also compiled data on glacier width, ice thickness, ice velocity, front advance/retreat, area and extent of iceberg discharge, bathymetry, subglacial freshwater run-off and sediment flux. Narwhal use of glacial habitats expanded in the 2000s probably due to reduced summer fast ice and later autumn freeze-up. Using a generalized multivariate framework, glacier ice front thickness (vertical height in the water column) was a significant covariate in all models. A negative relationship with glacier velocity was included in several models and glacier front width was a significant predictor in the 2000s. Results suggest narwhals prefer glaciers with potential for higher ambient freshwater melt over glaciers with silt-laden discharge. This may represent a preference for summer freshwater habitat, similar to other Arctic monodontids. PMID:27784729

Use of glacial fronts by narwhals (Monodon monoceros) in West Greenland.

PubMed

Laidre, Kristin L; Moon, Twila; Hauser, Donna D W; McGovern, Richard; Heide-Jørgensen, Mads Peter; Dietz, Rune; Hudson, Ben

2016-10-01

Glacial fronts are important summer habitat for narwhals (Monodon monoceros); however, no studies have quantified which glacial properties attract whales. We investigated the importance of glacial habitats using telemetry data from n = 15 whales tagged in September of 1993, 1994, 2006 and 2007 in Melville Bay, West Greenland. For 41 marine-terminating glaciers, we estimated (i) narwhal presence/absence, (ii) number of 24 h periods spent at glaciers and (iii) the fraction of narwhals that visited each glacier (at 5, 7 and 10 km) in autumn. We also compiled data on glacier width, ice thickness, ice velocity, front advance/retreat, area and extent of iceberg discharge, bathymetry, subglacial freshwater run-off and sediment flux. Narwhal use of glacial habitats expanded in the 2000s probably due to reduced summer fast ice and later autumn freeze-up. Using a generalized multivariate framework, glacier ice front thickness (vertical height in the water column) was a significant covariate in all models. A negative relationship with glacier velocity was included in several models and glacier front width was a significant predictor in the 2000s. Results suggest narwhals prefer glaciers with potential for higher ambient freshwater melt over glaciers with silt-laden discharge. This may represent a preference for summer freshwater habitat, similar to other Arctic monodontids. © 2016 The Author(s).

24 CFR 203.284 - Calculation of up-front and annual MIP on or after July 1, 1991.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Obligations Calculation of Mortgage Insurance Premium on Or After July 1, 1991 § 203.284 Calculation of up... refund all of the unearned premium charges paid on a mortgage upon termination of insurance by voluntary... HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS...

24 CFR 203.284 - Calculation of up-front and annual MIP on or after July 1, 1991.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Obligations Calculation of Mortgage Insurance Premium on Or After July 1, 1991 § 203.284 Calculation of up... refund all of the unearned premium charges paid on a mortgage upon termination of insurance by voluntary... HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS...

Additional testing of the inlets designed for a tandem fan V/STOL nacelle

NASA Technical Reports Server (NTRS)

Ybarra, A. H.

1981-01-01

The wind tunnel testing of a scale model of a tandem fan nacelle designed for a type (subsonic cruise) V/STOL aircraft configuration is discussed. The performance for the isolated front inlet and for the combined front and aft inlets is reported. Model variables include front and aft inlets with aft inlet variations of short and long aft inlet cowls, with a shaft simulator and diffuser vortex generators, cowl lip fillets, and nacelle strakes. Inlet pressure recovery, distortion, and inlet angle-to-attack separation limits were evaluated at tunnel velocity from 0 to 240 knots, angles-of-attack from -10 to +40 degrees and inlet flow rates corresponding to throat Mach number from 0.0 to 0.6. Combined nacelle pitch and yaw runs up to 30 deg. were also made.

The influence of coastal fronts on the movement and dispersion of oil slicks. [Delaware Bay

NASA Technical Reports Server (NTRS)

Klemas, V. (Principal Investigator); Davis, G.; Kupferman, S.

1976-01-01

The author has identified the following significant results. LANDSAT, aircraft, and boats were used successfully to study estuarine and coastal fronts or boundaries. Horizontal salinity gradients of 4% in one meter and convergence velocities of the order of 0.1 m/sec were observed. Visibility improved from one meter to two meters as certain boundaries were crossed. Fronts near the mouth of the bay are associated with the tidal exchange with shelf water. By capturing and holding oil slicks, these frontal systems also significantly influence the movement and dispersion of oil slicks in Delaware Bay. Recent oil slick tracking experiments conducted to verify a predictive oil dispersion and movement model have shown that during certain parts of the tidal cycle the oil slicks tend to line up along boundaries.

Indoor fitness routine

MedlinePlus

... keep your back straight. Using your front leg, push back into the starting position. Repeat on the other ... your back sag. Press into your arms to push yourself back up. If it is too hard to do ...

24 CFR 4001.122 - Fees and closing costs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... originating the Program mortgage; (3) Premium pricing by the mortgagee providing the Program mortgage; (4... loan-to-value ratio does not exceed 90 percent (including the up-front premium required under § 4001...

3. Historic American Buildings Survey E. W. Russell, Photographer, June ...

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

3. Historic American Buildings Survey E. W. Russell, Photographer, June 19, 1937 CLOSE-UP OF FRONT ENTRANCE FROM SOUTH SIDE. - Jenkins-Carlton-Autry House, County Road 52, Alpine, Talladega County, AL

Lensless microscopy technique for static and dynamic colloidal systems.

PubMed

Alvarez-Palacio, D C; Garcia-Sucerquia, J

2010-09-15

We present the application of a lensless microscopy technique known as digital in-line holographic microscopy (DIHM) to image dynamic and static colloidal systems of microspheres. DIHM has been perfected up to the point that submicrometer lateral resolution with several hundreds of micrometers depth of field is achieved with visible light; it is shown that the lateral resolution of DIHM is enough to resolve self-assembled colloidal monolayers built up from polystyrene spheres with submicrometer diameters. The time resolution of DIHM is of the order of 4 frames/s at 2048 x 2048 pixels, which represents an overall improvement of 16 times the time resolution of confocal scanning microscopy. This feature is applied to the visualization of the migration of dewetting fronts in dynamic colloidal systems and the formation of front-like arrangements of particles. Copyright 2010 Elsevier Inc. All rights reserved.

The influence of isolated thoracoplasty on the evolution of pulmonary function after treatment of severe thoracic scoliosis.

PubMed

Koller, Heiko; Schulte, Tobias L; Meier, Oliver; Koller, Juliane; Bullmann, Viola; Hitzl, Wolfgang; Mayer, Michael; Lange, Tobias; Schmücker, Jens

2017-06-01

Isolated thoracoplasty (iTP) on the convex side is performed long time after scoliosis surgery has been performed. ITP is thought to cause a further decline in pulmonary function (PF); however, the amount of decline is ill defined. The objectives of this study were to examine the influence of iTP on the postoperative evolution of PF and rib hump reduction in patients that previously undergone scoliosis surgery. Over an 11-year period, 75 patients underwent iTP. The authors performed a retrospective case series review. Patients with data from PF tests performed preoperatively and at the last follow-up were included. Minimum follow-up was 12 months. The PF value reported was predicted FVC (FVC%). According to the American Thoracic Society, pulmonary impairment was classified as no impairment (FVC: >80-100%), mild (FVC: >65 ≤80%), moderate (FVC: >50 ≤65), and severe (FVC ≤50%). The outcome was studied using validated measures (SRS-24 score, COMI, and the COPD Assessment Test (CAT)). The CAT is stratified into mild impairment (<10 pts), moderate impairment (10-20 pts), severe impairment (>20-30 pts), and disabled (>30 pts). Twenty-six patients fulfilled the inclusion criteria. The patients' average age was 28 years at surgery with iTP, and 22 were females; the average BMI was 23, and the average follow-up was 76 months. Twenty of the patients had AIS, and six had congenital scoliosis. The time between scoliosis correction and iTP averaged 39 months. The mean number of resected rib segments was 7, and the mean blood loss was 834 ml. FVC% was 66% preoperatively and 57% at follow-up, with a significant change of 9% (p < .02). Fourteen patients had a FVC% change between preoperation and follow-up that was ≥5%; this change was not dependent on the preoperative FVC%. PF showed a slight but non-significant improvement with longer follow-up. At the time of iTP, the thoracic curve averaged 67°, and thoracic kyphosis averaged 46°. Rib hump height was 34 mm before iTP and 15 mm at follow-up (p < .03). At follow-up, the SRS-24 score was 81, the COMI score was 4 points, and the CAT score was 8 points. Eight patients had a CAT >10. Two patients had a major complication. A comparison of patients with pulmonary impairment preoperation vs. follow-up found 4 vs. 1 patients had no PF impairment, 8 vs. 4 patients had mild impairment, 10 vs. 13 patients had moderate impairment, and 4 vs. 8 patients had severe impairment. Isolated TP was shown an effective technique for rib hump resection. Six years after iTP, the FVC% declined by an average of 9%. Several patients had long-lasting effects in terms of %FVC decline. iTP should be reserved for patients with significant rib hump deformity.

[Comparison of efficacy on functional constipation treated with electroacupuncture of different acupoint prescriptions: a randomized controlled pilot trial].

PubMed

Wu, Jia-Ni; Zhang, Bi-Ying; Zhu, Wen-Zeng; Du, Ruo-Sang; Liu, Zhi-Shun

2014-06-01

To evaluate preliminarily the efficacy on functional constipation treated with electroacupuncture of different acupoint prescriptions. One hundred and four patients were randomized into a front-mu and back-shu points group (19 cases), a he-sea points group (34 cases), a he-sea, front-mu and back-shu points group (26 cases) and a western medication control group (25 cases). In the front-mu and back-shu points group, electroacupuncture was applied at bilateral Tianshu (ST 25) and Dachangshu (BL 25). In the he-sea points group, electroacupuncture was applied at bilateral Quchi (LI 11) and Shangjuxu (ST 37). In the he-sea, front-mu and back-shu points group, electroacupuncture was applied at unilateral Tianshu (ST 25), Dachangshu (BL 25), Quchi (LI 11) and Shangjuxu (ST 37). In the three groups above, the treatment was given 5 times a week in the first two weeks and 3 times a week in the next two weeks. In the western medication control group, mosapride citrate tablets were prescribed for oral administration, 1 table (5 mg) each time, 3 times a day, continuously for 4 weeks. The period of research was 9 weeks, including 1 week for baseline evaluation, 4 weeks for treatment and 4 weeks for follow-up. The weekly defecation frequency was taken as primary index, while the defecation difficulty and life quality score were taken as the secondary indices for the efficacy evaluation after treatment and in follow-up. According to the intention-to-treat (ITT) analytic principle, 104 cases were all enrolled in the final analysis. (1) After treatment, the weekly frequency of defecation was all increased significantly in the four groups (P < 0.05, P < 0.01). The efficacy of the three electroacupuncture groups was similar to that of western medication control group (P > 0.05). In follow-up, the increasing effect on the weekly frequency of defecation was maintained in the he-sea points group (P < 0.01), superior to the front-mu and back-shu points group and the western medication control group (P < 0.05, P < 0.01); the weekly frequency of defecation was not improved in the rest three groups (P > 0.05). (2) After treatment, defecation difficulty was relieved in the he-sea points group, the he-sea, front-mu and back-shu points group and the western medication control group (P < 0.05, P < 0.01). In follow-up, the improvements were still significant in the he-sea points group and the he-sea, front-mu and back-shu points group (both P < 0.01). (3) After treatment, the life quality score was significantly improved in the patients of the he-sea points group (P < 0.05). The difference was not significant in the rest three groups as compared with that before treatment (all P > 0.05). The weekly frequency of defecation is increased effectively after treatment in the three electroacupuncture groups and the efficacy is similar to mosapride citrate tablets. The bilateral Quchi (LI 11) and Shangjuxu (ST 37) in he-sea acupoints increase significantly the weekly frequency of defecation, relieve defecation difficulty and improve life quality. Acupuncture efficacy is sustained for 4 weeks. This acupoints prescription is the best in the treatment of functional constipation.

Effectively Transparent Front Contacts for Optoelectronic Devices

DOE PAGES

Saive, Rebecca; Borsuk, Aleca M.; Emmer, Hal S.; ...

2016-06-10

Effectively transparent front contacts for optoelectronic devices achieve a measured transparency of up to 99.9% and a measured sheet resistance of 4.8 Ω sq-1. These 3D microscale triangular cross-section grid fingers redirect incoming photons efficiently to the active semiconductor area and can replace standard grid fingers as well as transparent conductive oxide layers in optoelectronic devices. Optoelectronic devices such as light emitting diodes, photodiodes, and solar cells play an important and expanding role in modern technology. Photovoltaics is one of the largest optoelectronic industry sectors and an ever-increasing component of the world's rapidly growing renewable carbon-free electricity generation infrastructure. Inmore » recent years, the photovoltaics field has dramatically expanded owing to the large-scale manufacture of inexpensive crystalline Si and thin film cells and modules. The current record efficiency (η = 25.6%) Si solar cell utilizes a heterostructure intrinsic thin layer (HIT) design[1] to enable increased open circuit voltage, while more mass-manufacturable solar cell architectures feature front contacts.[2, 3] Thus improved solar cell front contact designs are important for future large-scale photovoltaics with even higher efficiency.« less

A 4 μW/Ch analog front-end module with moderate inversion and power-scalable sampling operation for 3-D neural microsystems.

PubMed

Al-Ashmouny, Khaled M; Chang, Sun-Il; Yoon, Euisik

2012-10-01

We report an analog front-end prototype designed in 0.25 μm CMOS process for hybrid integration into 3-D neural recording microsystems. For scaling towards massive parallel neural recording, the prototype has investigated some critical circuit challenges in power, area, interface, and modularity. We achieved extremely low power consumption of 4 μW/channel, optimized energy efficiency using moderate inversion in low-noise amplifiers (K of 5.98 × 10⁸ or NEF of 2.9), and minimized asynchronous interface (only 2 per 16 channels) for command and data capturing. We also implemented adaptable operations including programmable-gain amplification, power-scalable sampling (up to 50 kS/s/channel), wide configuration range (9-bit) for programmable gain and bandwidth, and 5-bit site selection capability (selecting 16 out of 128 sites). The implemented front-end module has achieved a reduction in noise-energy-area product by a factor of 5-25 times as compared to the state-of-the-art analog front-end approaches reported to date.

Life Course Pathways to Racial Disparities in Cognitive Impairment among Older Americans*

PubMed Central

Zhang, Zhenmei; Hayward, Mark D.; Yu, Yan-Liang

2016-01-01

Blacks are especially hard hit by cognitive impairment at older ages compared to whites. Here, we take advantage of the Health and Retirement Study (1998–2010) to assess how this racial divide in cognitive impairment is associated with the racial stratification of life course exposures and resources over a 12-year period among 8,946 non-Hispanic whites and blacks aged 65 and older in 1998. We find that blacks suffer from a higher risk of moderate/severe cognitive impairment at baseline and during the follow-up. Blacks are also more likely to report childhood adversity and to have grown up in the segregated South, and these early-life adversities put blacks at a significantly higher risk of cognitive impairment. Adulthood socioeconomic status is strongly associated with the risk of cognitive impairment, net of childhood conditions. However, racial disparities in cognitive impairment, though substantially reduced, are not eliminated when controlling for these life course factors. PMID:27247126

Systematic analysis of diffuse rear reflectors for enhanced light trapping in silicon solar cells

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

Pfeffer, Florian; Eisenlohr, Johannes; Basch, Angelika

Simple diffuse rear reflectors can enhance the light path length of weakly absorbed near infrared light in silicon solar cells and set a benchmark for more complex and expensive light trapping structures like dielectric gratings or plasmonic particles. We analyzed such simple diffuse rear reflectors systematically by optical and electrical measurements. We applied white paint, TiO 2 nanoparticles, white backsheets and a silver mirror to bifacial silicon solar cells and measured the enhancement of the external quantum efficiency for three different solar cell geometries: planar front and rear side, textured front and planar rear side, and textured front and rearmore » side. We showed that an air-gap between the solar cell and the reflector decreases the absorption enhancement significantly, thus white paint and TiO 2 nanoparticles directly applied to the rear cell surface lead to the highest short circuit current density enhancements. Here, the short circuit current density gains for a 200 um thick planar solar cell reached up to 1.8 mA/cm 2, compared to a non-reflecting black rear side and up to 0.8 mA/cm 2 compared to a high-quality silver mirror rear side. For solar cells with textured front side the short circuit current density gains are in the range between 0.5 and 1.0 mA/cm 2 compared to a non-reflecting black rear side and do not significantly depend on the angular characteristic of the rear side reflector but mainly on its absolute reflectance.« less

Systematic analysis of diffuse rear reflectors for enhanced light trapping in silicon solar cells

DOE PAGES

Pfeffer, Florian; Eisenlohr, Johannes; Basch, Angelika; ...

2016-04-08

Simple diffuse rear reflectors can enhance the light path length of weakly absorbed near infrared light in silicon solar cells and set a benchmark for more complex and expensive light trapping structures like dielectric gratings or plasmonic particles. We analyzed such simple diffuse rear reflectors systematically by optical and electrical measurements. We applied white paint, TiO 2 nanoparticles, white backsheets and a silver mirror to bifacial silicon solar cells and measured the enhancement of the external quantum efficiency for three different solar cell geometries: planar front and rear side, textured front and planar rear side, and textured front and rearmore » side. We showed that an air-gap between the solar cell and the reflector decreases the absorption enhancement significantly, thus white paint and TiO 2 nanoparticles directly applied to the rear cell surface lead to the highest short circuit current density enhancements. Here, the short circuit current density gains for a 200 um thick planar solar cell reached up to 1.8 mA/cm 2, compared to a non-reflecting black rear side and up to 0.8 mA/cm 2 compared to a high-quality silver mirror rear side. For solar cells with textured front side the short circuit current density gains are in the range between 0.5 and 1.0 mA/cm 2 compared to a non-reflecting black rear side and do not significantly depend on the angular characteristic of the rear side reflector but mainly on its absolute reflectance.« less

Driving with pets and motor vehicle collision involvement among older drivers: a prospective population-based study

PubMed Central

Huisingh, Carrie; Levitan, Emily B.; Irvin, Marguerite R.; Owsley, Cynthia; McGwin, Gerald

2016-01-01

Objective Distracted driving is a major cause of motor vehicle collision (MVC) involvement. Pets have been identified as potential distraction to drivers, particularly in the front. This type of distraction could be worse for those with impairment in the cognitive aspects of visual processing. The purpose of this study is to evaluate the association between driving with pets and rates of motor vehicle collision involvementin a cohort of older drivers. Methods A three-year prospective was conducted in a population-based sample of 2000 licensed drivers aged 70 years and older. At the baseline visit, a trained interviewer asked participants about pet ownership, whether they drive with pets, how frequently, and where the pet sits in the vehicle. Motor vehicle collision (MVC) involvement during the three-year study period was obtained from the Alabama Department of Public Safety. At-fault status was determined by the police officer who arrived on the scene. Participants were followed until the earliest of death, driving cessation, or end of the study period. Poisson regression was used to calculate crude and adjusted rate ratios (RR) examining the association between pet ownership, presence of a pet in a vehicle, frequency of driving with a pet, and location of the pet inside with vehicle with any and at-fault MVC involvement. We examined whether the associations differed by higher order visual processing impairment status, as measured by Useful Field Of View, Trails B, and Motor-free Visual Perception Test. Results Rates of crash involvement were similar for older adults who have ever driven with a pet compared to those who never drove with their pet (RR=1.15, 95% CI 0.76-1.75). Drivers who reported always or sometimes driving with their pet had higherMVC rates compared topet owners who never drive with a pet, but this association was not statistically significant (RR=1.39, 95% CI 0.86-2.24). In terms of location, those reporting having a pet frequently ride in the front of the vehicle had similar rates of MVC involvement compared to those who did not drive with a pet in the front. A similar pattern of results was observed for at-fault MVCs. This association was not modified by visual processing impairment status. Conclusion The current study demonstrates a positive but non-significant association between frequently driving with pets and MVC involvement. More research is needed, particularly on restraint use and whether the pet was in the car at the time of the crash, to help characterize the public safety benefit of regulations on driving with pets. PMID:26774042

Driving with pets and motor vehicle collision involvement among older drivers: A prospective population-based study.

PubMed

Huisingh, Carrie; Levitan, Emily B; Irvin, Marguerite R; Owsley, Cynthia; McGwin, Gerald

2016-03-01

Distracted driving is a major cause of motor vehicle collision (MVC) involvement. Pets have been identified as potential distraction to drivers, particularly in the front. This type of distraction could be worse for those with impairment in the cognitive aspects of visual processing. The purpose of this study is to evaluate the association between driving with pets and rates of motor vehicle collision involvement in a cohort of older drivers. A three-year prospective study was conducted in a population-based sample of 2000 licensed drivers aged 70 years and older. At the baseline visit, a trained interviewer asked participants about pet ownership, whether they drive with pets, how frequently, and where the pet sits in the vehicle. Motor vehicle collision (MVC) involvement during the three-year study period was obtained from the Alabama Department of Public Safety. At-fault status was determined by the police officer who arrived on the scene. Participants were followed until the earliest of death, driving cessation, or end of the study period. Poisson regression was used to calculate crude and adjusted rate ratios (RR) examining the association between pet ownership, presence of a pet in a vehicle, frequency of driving with a pet, and location of the pet inside with vehicle with any and at-fault MVC involvement. We examined whether the associations differed by higher order visual processing impairment status, as measured by Useful Field of View, Trails B, and Motor-free Visual Perception Test. Rates of crash involvement were similar for older adults who have ever driven with a pet compared to those who never drove with their pet (RR=1.15, 95% CI 0.76-1.75). Drivers who reported always or sometimes driving with their pet had higher MVC rates compared to pet owners who never drive with a pet, but this association was not statistically significant (RR=1.39, 95% CI 0.86-2.24). In terms of location, those reporting having a pet frequently ride in the front of the vehicle had similar rates of MVC involvement compared to those who did not drive with a pet in the front. A similar pattern of results was observed for at-fault MVCs. This association was not modified by visual processing impairment status. The current study demonstrates a positive but non-significant association between frequently driving with pets and MVC involvement. More research is needed, particularly on restraint use and whether the pet was in the car at the time of the crash, to help characterize the public safety benefit of regulations on driving with pets. Copyright © 2015 Elsevier Ltd. All rights reserved.

Plant nutrient acquisition strategies in tundra species: at which soil depth do species take up their nitrogen?

NASA Astrophysics Data System (ADS)

Limpens, Juul; Heijmans, Monique; Nauta, Ake; van Huissteden, Corine; van Rijssel, Sophie

2016-04-01

The Arctic is warming at unprecedented rates. Increased thawing of permafrost releases nutrients locked up in the previously frozen soils layers, which may initiate shifts in vegetation composition. The direction in which the vegetation shifts will co-determine whether Arctic warming is mitigated or accelerated, making understanding successional trajectories urgent. One of the key factors influencing the competitive relationships between plant species is their access to nutrients, in particularly nitrogen (N). We assessed the depth at which plant species took up N by performing a 15N tracer study, injecting 15(NH4)2SO4 at three depths (5, 15, 20 cm) into the soil in arctic tundra in north-eastern Siberia in July. In addition we explored plant nutrient acquisition strategy by analyzing natural abundances of 15N in leaves. We found that vascular plants took up 15N at all injection depths, irrespective of species, but also that species showed a clear preference for specific soil layers that coincided with their functional group (graminoids, dwarf shrubs, cryptogams). Graminoids took up most 15N at 20 cm depth nearest to the thaw front, with grasses showing a more pronounced preference than sedges. Dwarf shrubs took up most 15N at 5 cm depth, with deciduous shrubs displaying more preference than evergreens. Cryptogams did not take up any of the supplied 15N . The natural 15N abundances confirmed the pattern of nutrient acquisition from deeper soil layers in graminoids and from shallow soil layers in both deciduous and evergreen dwarf shrubs. Our results prove that graminoids and shrubs differ in their N uptake strategies, with graminoids profiting from nutrients released at the thaw front, whereas shrubs forage in the upper soil layers. The above implies that graminoids, grasses in particular, will have a competitive advantage over shrubs as the thaw front proceeds and/or superficial soil layers dry out. Our results suggest that the vertical distribution of nutrients over the soil will play an important role in vegetation succession as permafrost thaw progresses.

PubMed Central

DE LUCIA, A.; PASTORE, V.; BRACCI LAUDIERO, L.; BUONISSIMO, I.; RICCI, G.

2016-01-01

SUMMARY Programmes for early childhood childhood hearing impairment identification allows to quickly start the appropriate hearing aid fitting and rehabilitation process; nevertheless, a large number of patients do not join the treatment program. The goal of this article is to present the results of a strategic review of the strengths, weaknesses, opportunities and threats connected with the audiologic/prosthetic/language follow-up process of children with bilateral permanent hearing impairment. Involving small children, the follow-up includes the involvement of specialised professionals of a multidisciplinary team and a complex and prolonged multi-faced management. Within the framework of the Italian Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for Early Identification, Intervention and Care of Hearing Impaired Children", the purpose of this analysis was to propose recommendations that can harmonise criteria for outcome evaluation and provide guidance on the most appropriate assessment methods to be used in the follow-up course of children with permanent hearing impairment. PMID:27054392

Long-Term Cognitive Impairment after Hospitalization for Community-Acquired Pneumonia: a Prospective Cohort Study.

PubMed

Girard, Timothy D; Self, Wesley H; Edwards, Kathryn M; Grijalva, Carlos G; Zhu, Yuwei; Williams, Derek J; Jain, Seema; Jackson, James C

2018-06-01

Recent studies suggest older patients hospitalized for community-acquired pneumonia are at risk for new-onset cognitive impairment. The characteristics of long-term cognitive impairment after pneumonia, however, have not been elucidated. To characterize long-term cognitive impairment among adults of all ages hospitalized for community-acquired pneumonia. Prospective cohort study. Adults without severe preexisting cognitive impairment who were hospitalized with community-acquired pneumonia. At enrollment, we estimated baseline cognitive function with the Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). At 2- and 12-month follow-up, we assessed cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and tests of executive function, diagnosing cognitive impairment when results were ≥ 1.5 standard deviations below published age-adjusted means for the general population. We also identified subtypes of mild cognitive impairment using standard definitions. We assessed 58 (73%) of 80 patients who survived to 2-month follow-up and 57 (77%) of 74 who survived to 12-month follow-up. The median [range] age of survivors tested was 57 [19-97] years. Only 8 (12%) had evidence of mild cognitive impairment at baseline according to the Short IQCODE, but 21 (38%) at 2 months and 17 (30%) at 12 months had mild cognitive impairment per the RBANS. Moderate-to-severe cognitive impairment was common among adults ≥ 65 years [4/13 (31%) and 5/13 (38%) at 2 and 12 months, respectively] but also affected many of those < 65 years [10/43 (23%) and 8/43 (19%) at 2 and 12 months, respectively]. Deficits were most often noted in visuospatial function, attention, and memory. A year after hospitalization for community-acquired pneumonia, moderate-to-severe impairment in multiple cognitive domains affected one-third of patients ≥ 65 years old and 20% of younger patients, and another third of survivors had mild cognitive impairment.

24 CFR 234.1 - Cross-reference.

Code of Federal Regulations, 2011 CFR

2011-04-01

... new construction. 203.14Builders' warranty. 203.18aSolar energy system. 203.18cOne-time or up-front.... 1709) apply to mortgages on individually owned units insured under section 234 of the National Housing...

24 CFR 234.1 - Cross-reference.

Code of Federal Regulations, 2010 CFR

2010-04-01

... new construction. 203.14Builders' warranty. 203.18aSolar energy system. 203.18cOne-time or up-front.... 1709) apply to mortgages on individually owned units insured under section 234 of the National Housing...

5. Historic American Buildings Survey W. N. Manning, Photographer, September ...

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

5. Historic American Buildings Survey W. N. Manning, Photographer, September 10, 1935 CLOSE-UP OF COLUMN BASE ON FRONT PORCH - James Ellington House, Oak Bowery Road vicinity, Gold Hill, Lee County, AL

Turning in the Testbed

NASA Image and Video Library

2004-01-13

This image, taken in the JPL In-Situ Instruments Laboratory or Testbed, shows the view from the front hazard avoidance cameras on the Mars Exploration Rover Spirit after the rover has backed up and turned 45 degrees counterclockwise.

The Impact of Exercise, Cognitive Activities, and Socialization on Cognitive Function: Results From the National Long-Term Care Survey

PubMed Central

Jedrziewski, M. Kathryn; Ewbank, Douglas C.; Wang, Haidong; Trojanowski, John Q.

2014-01-01

Currently, there are no effective treatments for Alzheimer’s disease and related disorders and age continues to be a robust risk factor. Thus, population aging in the United States may have catastrophic results if interventions are not found and implemented. This study examines possible associations between cognitive impairment and exercise, cognitive activities, and socialization. Cognitive activities, socialization, and exercise were assessed at baseline, and cognitive function was measured at baseline, 5-year, and 10-year follow-up. Controlling for baseline cognitive function, age, sex, education, diabetes, and hypertension, linear regression was performed. Engagement in cognitive activities was inversely associated with the onset of cognitive impairment at 5-year follow-up but was no longer significant at 10-year follow-up. Exercise was associated with a lower risk of cognitive impairment at 10-year follow-up but was not significant at 5-year follow-up. Associations with socialization were not statistically significant at either follow-up. PMID:24408752

Nineteenth Century English Homosexual Teachers: The Up Front and Back Stage Performance.

ERIC Educational Resources Information Center

Bullough, Vern; Bullough, Bonnie

Although homosexuality was considered to be a crime in nineteenth-century England, the subculture of the school system promoted it. For example, in the early nineteenth century schoolboys of all ages were locked up in dormitories at 8:00 p.m. and no master entered the building until the next morning. No-one supervised the boys' activities during…

First steps in designing an all-in-one ICT-based device for persons with cognitive impairment: evaluation of the first mock-up.

PubMed

Boman, Inga-Lill; Persson, Ann-Christine; Bartfai, Aniko

2016-03-07

This project Smart Assisted Living involving Informal careGivers++ (SALIG) intends to develop an ICT-based device for persons with cognitive impairment combined with remote support possibilities for significant others and formal caregivers. This paper presents the identification of the target groups' needs and requirements of such device and the evaluation of the first mock-up, demonstrated in a tablet. The inclusive design method that includes end-users in the design process was chosen. First, a scoping review was conducted in order to examine the target group's need of an ICT-based device, and to gather recommendations regarding its design and functionalities. In order to capture the users' requirements of the design and functionalities of the device three targeted focus groups were conducted. Based on the findings from the publications and the focus groups a user requirement specification was developed. After that a design concept and a first mock-up was developed in an iterative process. The mock-up was evaluated through interviews with persons with cognitive impairment, health care professionals and significant others. Data were analysed using content analysis. Several useful recommendations of the design and functionalities of the SALIG device for persons with cognitive impairment were identified. The main benefit of the mock-up was that it was a single device with a set of functionalities installed on a tablet and designed for persons with cognitive impairment. An additional benefit was that it could be used remotely by significant others and formal caregivers. The SALIG device has the potentials to facilitate everyday life for persons with cognitive impairment, their significant others and the work situation for formal caregivers. The results may provide guidance in the development of different types of technologies for the target population and for people with diverse disabilities. Further work will focus on developing a prototype to be empirically tested by persons with cognitive impairment, their significant others and formal caregivers.

Predictors of work status and quality of life 9-13 years after aneurysmal subarachnoid hemorrahage.

PubMed

Vilkki, Juhani; Juvela, Seppo; Malmivaara, Kirsi; Siironen, Jari; Hernesniemi, Juha

2012-08-01

Aneurysmal subarachnoid hemorrhage (SAH) causes long-term psychosocial impairments even in patients who regain functional independence. Little is known about predictors of these impairments. We studied how early clinical data and neuropsychological results predict work status and health-related quality of life (HRQoL) 9-13 years after SAH. One hundred one patients performed a neuropsychological test battery and returned their self-rating and partner's rating of a psychosocial impairment questionnaire approximately 1 year after SAH. These data were analyzed for association to the patients' work status and self-rated HRQoL approximately 10 years later. Age inversely, lower levels of self-rated impairments, employment and higher levels of education at the first follow-up independently predicted employment at the long-term follow-up. Although most cognitive test results were significantly associated with employment status at the long-term follow-up, they were of limited additional value as predictors of work status. The best predictor combination for long-term high HRQoL was good performance in a face recognition test and lower levels of self-rated impairments at the first follow-up as well as male sex. Problems in usual activities at the long-term follow-up were predicted by poor results in the face recognition and in a word list-learning task. Questionnaire ratings of patients' psychosocial impairments 1 year after SAH give important information for the long-term prediction of their work status and HRQoL. In the long run, patients' unemployment becomes strongly associated with higher age, while their performance of usual activities can be predicted with learning and memory results.

[Advances in the treatment of chronic lymphocytic leukaemia].

PubMed

Mozas, Pablo; Delgado, Julio

2016-11-18

Chronic lymphocytic leukemia (CLL), a proliferation of mature B cells, is one of the most prevalent haematological malignancies. Progress has been made in its treatment during the last few decades, and chemoimmunotherapy based on fludarabine, cyclophosphamide and rituximab is considered the treatment of choice for patients with standard-risk CLL and good performance status. However, due to the characterization of high-risk biological subgroups and its presentation in elderly patients and/or with comorbidities, targeted therapies, such as B-cell receptor inhibitors, have been developed and approved during the last few years. The current review examines traditional therapeutic strategies and focuses on new small molecules that already represent promising elements of the CLL treatment landscape. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Language-Impaired Preschoolers: A Follow-Up into Adolescence.

ERIC Educational Resources Information Center

Stothard, Susan E.; Snowling, Margaret J.; Bishop, D. V. M.; Chipchase, Barry B.; Kaplan, Carole A.

1998-01-01

A follow-up study of 71 adolescents with preschool histories of speech-language impairments found children whose language problems had been resolved by ages 5 to 6 did not differ from controls on tests of vocabulary and language-comprehension skills, however, they performed significantly less well on tests of phonological processing and literacy…

Universality of Generalized Parton Distributions in Light-Front Holographic QCD

NASA Astrophysics Data System (ADS)

de Téramond, Guy F.; Liu, Tianbo; Sufian, Raza Sabbir; Dosch, Hans Günter; Brodsky, Stanley J.; Deur, Alexandre; Hlfhs Collaboration

2018-05-01

The structure of generalized parton distributions is determined from light-front holographic QCD up to a universal reparametrization function w (x ) which incorporates Regge behavior at small x and inclusive counting rules at x →1 . A simple ansatz for w (x ) that fulfills these physics constraints with a single-parameter results in precise descriptions of both the nucleon and the pion quark distribution functions in comparison with global fits. The analytic structure of the amplitudes leads to a connection with the Veneziano model and hence to a nontrivial connection with Regge theory and the hadron spectrum.

Universality of Generalized Parton Distributions in Light-Front Holographic QCD.

PubMed

de Téramond, Guy F; Liu, Tianbo; Sufian, Raza Sabbir; Dosch, Hans Günter; Brodsky, Stanley J; Deur, Alexandre

2018-05-04

The structure of generalized parton distributions is determined from light-front holographic QCD up to a universal reparametrization function w(x) which incorporates Regge behavior at small x and inclusive counting rules at x→1. A simple ansatz for w(x) that fulfills these physics constraints with a single-parameter results in precise descriptions of both the nucleon and the pion quark distribution functions in comparison with global fits. The analytic structure of the amplitudes leads to a connection with the Veneziano model and hence to a nontrivial connection with Regge theory and the hadron spectrum.

Constraining calving front processes on W Greenland outlet glaciers using inertial-corrected laser scanning & swath-bathymetry

NASA Astrophysics Data System (ADS)

Bates, R.; Hubbard, A.; Neale, M.; Woodward, J.; Box, J. E.; Nick, F.

2010-12-01

Calving and submarine melt account for the majority of loss from the Antarctic and over 50% of that from the Greenland Ice Sheet. These ice-ocean processes are highly efficient mass-loss mechanisms, providing a rapid link between terrestrial ice (storage) and the oceanic sink (sea level/freshwater flux) which renders the ocean-outlet-ice sheet system potentially highly non-linear. Despite this, the controls on tidewater processes are poorly understood and a process based description of them is lacking from the present generation of coupled ice sheet models. We present details from an innovative study where two survey techniques are integrated to enable the construction of accurate, ~m resolution 3d digital terrain models (DTMs) of the aerial and submarine ice front of calving outlet glaciers. A 2km range terrestrial laser scanner was combined with a 416KHz swath-interferometric system and corrected via an inertial motion unit stabilized by RTK GPS and gyro-compass data. The system was mounted aboard a heavy displacement (20,000kg) yacht in addition to a light displacement (100kg) semi-autonomous boat and used to image the aerial and submarine calving fronts of two large outlet glaciers in W Greenland. Six daily surveys, each 2.5km long were repeated across Lille Glacier during which significant ice flow, melt and calving events were observed and captured from on-ice GPS stations and time-lapse sequences. A curtain of CTD and velocity casts were also conducted to constrain the fresh and oceanic mass and energy fluxes within the fjord. The residual of successive DTMs yield the spatial pattern of frontal change enabling the processes of aerial and submarine calving and melt to be quantified and constrained in unprecedented detail. These observed frontal changes are tentatively related to local dynamic, atmospheric and oceanographic processes that drive them. A partial survey of Store Glacier (~7km calving front & W Greenland 2nd largest outlet after Jakobshavn Isbrae) was conducted, indicating that the technique is successful up to ~500m from the ice front and to a similar water depth. These data sets show that it is possible to integrate and build 3d DTMs at the metre-scale both above and below the water surface. The successful acquisition from our semi-autonomous vessel supervised up to 2km away greatly eases repeat surveys and reduces the exposure of equipment and personnel to the risks posed by large, active calving glaciers. Lille Glacier and s/v Gambo surveyed & photographed from the semi-autonomous vessel. Mock-up of Lille Glacier calving front and fore-bay submarine topography imaged by interferometric swath-bathymetry.

Dynamics of vapor emissions at wire explosion thresholda)

NASA Astrophysics Data System (ADS)

Belony, Paul A.; Kim, Yong W.

2010-10-01

X-pinch plasmas have been actively studied in the recent years. Numerical simulation of the ramp-up of metallic vapor emissions from wire specimens shows that under impulsive Ohmic heating the wire core invariably reaches a supercritical state before explosion. The heating rate depends sensitively on the local wire resistance, leading to highly variable vapor emission flux along the wire. To examine the vapor emission process, we have visualized nickel wire explosions by means of shock formation in air. In a single explosion as captured by shadowgraphy, there usually appear several shocks with spherical or cylindrical wave front originating from different parts of the wire. Growth of various shock fronts in time is well characterized by a power-law scaling in one form or another. Continuum emission spectra are obtained and calibrated to measure temperature near the explosion threshold. Shock front structures and vapor plume temperature are examined.

Langevin approach to a chemical wave front: Selection of the propagation velocity in the presence of internal noise

NASA Astrophysics Data System (ADS)

Lemarchand, A.; Lesne, A.; Mareschal, M.

1995-05-01

The reaction-diffusion equation associated with the Fisher chemical model A+B-->2A admits wave-front solutions by replacing an unstable stationary state with a stable one. The deterministic analysis concludes that their propagation velocity is not prescribed by the dynamics. For a large class of initial conditions the velocity which is spontaneously selected is equal to the minimum allowed velocity vmin, as predicted by the marginal stability criterion. In order to test the relevance of this deterministic description we investigate the macroscopic consequences, on the velocity and the width of the front, of the intrinsic stochasticity due to the underlying microscopic dynamics. We solve numerically the Langevin equations, deduced analytically from the master equation within a system size expansion procedure. We show that the mean profile associated with the stochastic solution propagates faster than the deterministic solution at a velocity up to 25% greater than vmin.

Reduction of front-metallization grid shading in concentrator cells through laser micro-grooved cover glass

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

García-Linares, Pablo, E-mail: pablo.garcia-linares@cea.fr; Voarino, Philippe; Besson, Pierre

2015-09-28

Concentrator solar cell front-grid metallizations are designed so that the trade-off between series resistance and shading factor (SF) is optimized for a particular irradiance. High concentrator photovoltaics (CPV) typically requires a metallic electrode pattern that covers up to 10% of the cell surface. The shading effect produced by this front electrode results in a significant reduction in short-circuit current (I{sub SC}) and hence, in a significant efficiency loss. In this work we present a cover glass (originally meant to protect the cell surface) that is laser-grooved with a micrometric pattern that redirects the incident solar light towards interfinger regions andmore » away from the metallic electrodes, where they would be wasted in terms of photovoltaic generation. Quantum efficiency (QE) and current (I)-voltage (V) characterization under concentration validate the proof-of-concept, showing great potential for CPV applications.« less

Mirrors for High Resolution X-Ray Optics---Figure Preserving IR/PT Coating

NASA Technical Reports Server (NTRS)

Chan, Kai-Wing; Olsen, Lawrence; Sharpe, Marton; Numata, Ai; McClelland, Ryan; Saha, Timo; Zhang, Will

2016-01-01

Coating stress of 10 - 20 nm of Ir is sufficiently high to distort the figure of arc-second thin lightweight mirrors. For iridium: --Stress sigma 4 GPa for 15 nm film implies 60 Nm integrated stress-- Need less than 3 N/m (or stress less than 200 MPa) for sub-arcsecond optics. Basic Approaches for Mitigation. A. Annealing the film-- Glass can be heat up to 400 C without distortion. Silicon is even more resistant.-- It was found that recovery is limited by residual thermal stress from taking the mirror down from high T. B. Coating bi-layer films with compressive stress with tensile stress. C. Front-and-back coating with magnetron sputtering or atomic layer deposition-- Sputtering involve spanning of substrates. Geometric difference in setup (convexness/concaveness of curved mirrors) does not permit precise front-and-back matching-- Atomic layer deposition can provide a uniform deposition front and back simultaneously.

Density profiles around A+B→C reaction-diffusion fronts in partially miscible systems: A general classification.

PubMed

Loodts, V; Trevelyan, P M J; Rongy, L; De Wit, A

2016-10-01

Various spatial density profiles can develop in partially miscible stratifications when a phase A dissolves with a finite solubility into a host phase containing a dissolved reactant B. We investigate theoretically the impact of an A+B→C reaction on such density profiles in the host phase and classify them in a parameter space spanned by the ratios of relative contributions to density and diffusion coefficients of the chemical species. While the density profile is either monotonically increasing or decreasing in the nonreactive case, reactions combined with differential diffusivity can create eight different types of density profiles featuring up to two extrema in density, at the reaction front or below it. We use this framework to predict various possible hydrodynamic instability scenarios inducing buoyancy-driven convection around such reaction fronts when they propagate parallel to the gravity field.

Study of Super- and Subsonic Ionization Fronts in Low-Density, Soft X-Ray-Irradiated Foam Targets

NASA Astrophysics Data System (ADS)

Willi, O.; Barringer, L.; Vickers, C.; Hoarty, D.

2000-04-01

The transition from super- to subsonic propagation of an ionization front has been studied in X-ray irradiated, low-density foam targets using soft X-ray imaging and point projection absorption spectroscopy. The foams were doped with chlorine and irradiated with an intense pulse of soft X-ray radiation with a temperature up to 120 eV produced by laser heating a burnthrough converter foil. The cylindrical foam targets were radiographed side-on allowing the change in the chlorine ionization and hence the front to be observed. From the absolute target transmission the density profile was obtained. Comparison of experimental absorption spectra with simulated ones allowed the temperature of the heated material to be inferred for the first time without reliance on detailed hydrodynamic simulations to interpret the data. The experimental observations were compared to radiation hydrodynamic simulations.

Ultrafast semi-metallic layer formation in detonating nitromethane

NASA Astrophysics Data System (ADS)

Reed, Evan; Manaa, M. Riad; Fried, Laurence; Glaesemann, Kurt; Joannopoulos, John

2008-03-01

We present the first quantum molecular dynamics simulations behind a detonation front (up to 0.2 ns) of the explosive nitromethane (CH3NO2) represented by the density-functional-based tight-binding method (DFTB). This simulation is enabled by our recently developed multi-scale shock wave molecular dynamics technique (MSST) that opens the door to longer duration simulations by several orders of magnitude. The electronic density of states around the Fermi energy initially increases as metastable material states are produced but then later decreases, perhaps unexpectedly. These changes indicate that the shock front is characterized by an increase in optical thickness and conductivity followed by a reduction around 100 picoseconds behind the front. We find that a significant population of intermediate metastable molecules are charged and charged species play an important role in the density of states evolution. The transient transformation to a semi-metallic state can be understood within the Anderson picture of metallization.

A semi-metallic layer in detonating nitromethane

NASA Astrophysics Data System (ADS)

Reed, Evan; Manaa, Riad; Fried, Laurence; Glaesemann, Kurt; Joannopoulos, John

2007-06-01

We present the first ever glimpse behind a detonation front in a chemically reactive quantum molecular dynamics simulation (up to 0.2 ns) of the explosive nitromethane (CH3NO2) represented by the density-functional-based tight-binding method (DFTB). This simulation is enabled by our recently developed multi-scale shock wave molecular dynamics technique (MSST) that opens the door to longer duration simulations by several orders of magnitude. The electronic DOS around the Fermi energy initially increases as metastable material states are produced but then later decreases, perhaps unexpectedly. These changes indicate that the shock front is characterized by an increase in optical thickness followed by a reduction in optical thickness hundreds of picoseconds behind the front, explaining recent experimental observations. We find that a significant population of intermediate metastable molecules are charged and charged species play an important role in the density of states evolution and a possible Mott metal-insulator transition.

LH Power Losses In Front of the JET Launcher

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

Jacquet, P.; Arnoux, G.; Kirov, K.

2009-11-26

In recent JET experiments, Lower Hybrid (LH) power losses in the Scrape-Off Layer (SOL) were characterized using infra-red (IR) thermography. Hot spots were observed on objects intercepting the field lines passing in front of the LH launcher, i.e. on poloidal limiters and on dumplates located at the top of the tokamak; their locations being in good agreement with magnetic field line tracing using the EFIT equilibrium code. The dumplate temperature was monitored while scanning the launcher position so that the radial distance between field lines intercepting the hot spots and the launcher was increased up to 3.5 cm. The dissipationmore » layer in front of the launcher was estimated to be at least 3.5 cm wide, in agreement with recent measurements on Tore-Supra, but not with simple models that predict a dissipation layer in the mm range.« less

Plasma ignition for laser propulsion

NASA Technical Reports Server (NTRS)

Askew, R. F.

1982-01-01

For a specific optical system a pulsed carbon dioxide laser having an energy output of up to 15 joules was used to initiate a plasma in air at one atmosphere pressure. The spatial and temporal development of the plasma were measured using a multiframe image converter camera. In addition the time dependent velocity of the laser supported plasma front which moves opposite to the direction of the laser pulse was measured in order to characterize the type of wavefront developed. Reliable and reproducible spark initiation was achieved. The lifetime of the highly dense plasma at the initial focal spot was determined to be less than 100 nanoseconds. The plasma front propagates toward the laser at a variable speed ranging from zero to 1.6 x 1,000,000 m/sec. The plasma front propagates for a total distance of approximately five centimeters for the energy and laser pulse shape employed.

Shock waves in molecular solids: ultrafast vibrational spectroscopy of the first nanosecond

NASA Astrophysics Data System (ADS)

Franken, J.; Hambir, S. A.; Hare, D. E.; Dlott, D. D.

A novel technique which uses a microfabricated shock target array assembly is described, where the passage of a shock front through a thin (0.5μm) polycrystalline layer and the subsequent unloading process is monitored in real time with ultrafast coherent Raman spectroscopy. Using a high repetition rate laser shock generation technique, high resolution, coherent Raman spectra are obtained in shocked anthracene and in a high explosive material, NTO, with time resolution of 50 ps. Spectroscopic measurements are presented which yield the shock pressure (up to 5 GPa), the shock velocity ( 4 km/s), the shock front risetime (tr < 25 ps), and the temperature ( 400°C). A brief discussion is presented, how this new technique can be used to determine the Hugoniot, the equation of state, the entropy increase across the shock front, and monitor shock induced chemical reactions in real time.

Engineering data exchange.

PubMed

Moore, M

2001-11-01

Mount Clemens General Hospsital, Mount Clemens, Mich. performance anomalies due to multiple interfaces with separate systems. implementation of an interface engine. improved management of data exchange among disparate systems. up-front studies of vendor offerings, potential problems, and long-term needs.

22. Photocopy of photograph (from 'The Grizzly Bear', September 1909) ...

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

22. Photocopy of photograph (from 'The Grizzly Bear', September 1909) EXTERIOR, CLOSE-UP OF SOUTH FRONT & WEST SIDE RUINOUS STATE, 1909 - Mission San Francisco Solano de Sonoma, First & Spain Streets, Sonoma, Sonoma County, CA

25. Photocopy of photograph (Source unknown, c. 19231925) EXTERIOR, CLOSEUP ...

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

25. Photocopy of photograph (Source unknown, c. 1923-1925) EXTERIOR, CLOSE-UP OF SOUTH FRONT OF MISSION AFTER RESTORATION, C. 1923-1925 - Mission San Francisco Solano de Sonoma, First & Spain Streets, Sonoma, Sonoma County, CA

3. Historic American Buildings Survey Alex Bush, Photographer, March 24, ...

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

3. Historic American Buildings Survey Alex Bush, Photographer, March 24, 1937 CLOSE-UP OF FRONT ELEVATION FROM SOUTH SIDE - Colonel Joseph R. Hawthorne House, Broad Street (County Road 59), Pine Apple, Wilcox County, AL

47 CFR 1.8003 - Providing the FRN in Commission filings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... subpart G of this part, anyone participating in a spectrum auction, making up-front payments or deposits in a spectrum auction, anyone making a payment on an auction loan, anyone making a contribution to...

47 CFR 1.8003 - Providing the FRN in Commission filings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... subpart G of this part, anyone participating in a spectrum auction, making up-front payments or deposits in a spectrum auction, anyone making a payment on an auction loan, anyone making a contribution to...

47 CFR 1.8003 - Providing the FRN in Commission filings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... from paying statutory charges under subpart G of this part, anyone participating in a spectrum auction, making up-front payments or deposits in a spectrum auction, anyone making a payment on an auction loan...

47 CFR 1.8003 - Providing the FRN in Commission filings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... from paying statutory charges under subpart G of this part, anyone participating in a spectrum auction, making up-front payments or deposits in a spectrum auction, anyone making a payment on an auction loan...

Chemoselection: A Paradigm for Optimization of Organ Preservation in Locally Advanced Larynx Cancer

PubMed Central

Vainshtein, Jeffrey M.; Wu, Vivian F.; Spector, Matthew E.; Bradford, Carol R.; Wolf, Gregory T.; Worden, Francis P.

2014-01-01

Summary Definitive chemoradiation (CRT) and laryngectomy followed by postoperative radiotherapy (RT) are both considered standard of care options for the management of advanced laryngeal cancer. While organ preservation with chemoradiotherapy is often the preferred up-front approach for appropriately selected candidates, the functional benefits of organ preservation must be carefully balanced against the considerable morbidity of salvage laryngectomy in patients who fail primary chemoradiation. Up-front identification of patients who are likely to require surgical salvage, therefore, is an important aim of any organ preserving approach in order to minimize morbidity while maximizing organ preservation. To this end, a strategy of “chemoselection”, using the primary tumor's response after one cycle of induction chemotherapy as an in vivo method of selecting responders for definitive chemoradiation while reserving primary surgical management for non-responders, has been employed extensively at our institution. The rationale, treatment results, and future directions of this approach are discussed. PMID:24053204

STS117-S-006

NASA Image and Video Library

2007-06-08

STS117-S-006 (8 June 2007) --- After suiting up, the STS-117 crewmembers exit the Operations and Checkout Building to board the Astrovan, which will take them to launch pad 39A at Kennedy Space Center. On the right (front to back) are astronauts Rick Sturckow, commander; Steven Swanson, Clayton Anderson and Jim Reilly (center back), all mission specialists. On the left (front to back) are astronauts Lee Archambault, pilot; Patrick Forrester and John "Danny" Olivas, both mission specialists. Anderson will join Expedition 15 in progress to serve as a flight engineer aboard the International Space Station. Atlantis will link up with the International Space Station on Sunday, June 10, to begin a joint mission that will increase the complex's power generation capability. Using the shuttle and station robotic arms and conducting three scheduled spacewalks, the astronauts will install another set of giant solar array wings on the station and retract another array, preparing it for a future move.

STS117-S-007

NASA Image and Video Library

2007-06-08

STS117-S-007 (8 June 2007) --- After suiting up, the STS-117 crewmembers exit the Operations and Checkout Building to board the Astrovan, which will take them to launch pad 39A at Kennedy Space Center. On the right (front to back) are astronauts Rick Sturckow, commander; Steven Swanson, Clayton Anderson and Jim Reilly, all mission specialists. On the left (front to back) are astronauts Lee Archambault, pilot; Patrick Forrester and John "Danny" Olivas, both mission specialists. Anderson will join Expedition 15 in progress to serve as a flight engineer aboard the International Space Station. Atlantis will link up with the International Space Station on Sunday, June 10, to begin a joint mission that will increase the complex's power generation capability. Using the shuttle and station robotic arms and conducting three scheduled spacewalks, the astronauts will install another set of giant solar array wings on the station and retract another array, preparing it for a future move.

Design of a wideband CMOS impedance spectroscopy ASIC analog front-end for multichannel biosensor interfaces.

PubMed

Valente, Virgilio; Dai Jiang; Demosthenous, Andreas

2015-08-01

This paper presents the preliminary design and simulation of a flexible and programmable analog front-end (AFE) circuit with current and voltage readout capabilities for electric impedance spectroscopy (EIS). The AFE is part of a fully integrated multifrequency EIS platform. The current readout comprises of a transimpedance stage and an automatic gain control (AGC) unit designed to accommodate impedance changes larger than 3 order of magnitude. The AGC is based on a dynamic peak detector that tracks changes in the input current over time and regulates the gain of a programmable gain amplifier in order to optimise the signal-to-noise ratio. The system works up to 1 MHz. The voltage readout consists of a 2 stages of fully differential current-feedback instrumentation amplifier which provide 100 dB of CMRR and a programmable gain up to 20 V/V per stage with a bandwidth in excess of 10MHz.

Delayed recovery of cognitive function following hypoglycemia in adults with type 1 diabetes: effect of impaired awareness of hypoglycemia.

PubMed

Zammitt, Nicola N; Warren, Roderick E; Deary, Ian J; Frier, Brian M

2008-03-01

Recovery times of cognitive functions were examined after exposure to hypoglycemia in people with diabetes with and without impaired hypoglycemia awareness. A total of 36 subjects with type 1 diabetes were studied (20 with normal hypoglycemia awareness [NHA] and 16 with impaired hypoglycemia awareness [IHA]). A hyperinsulinemic glucose clamp was used to lower blood glucose to 2.5 mmol/l (45 mg/dl) (hypoglycemia) for 1 h or to maintain blood glucose at 4.5 mmol/l (81 mg/dl) (euglycemia) on separate occasions. Cognitive tests were applied during each experimental condition and were repeated at 10- to 15-min intervals for 90 min after euglycemia had been restored. In the NHA group, performance was impaired on all cognitive tasks during hypoglycemia and remained impaired for up to 75 min on the choice reaction time (CRT) task (P = 0.03, eta(2) = 0.237). In the IHA group, performance did not deteriorate significantly during hypoglycemia. When all subjects were analyzed within the same general linear model, performance was impaired during hypoglycemia on all tasks. Significant impairment during recovery persisted for up to 40 min on the CRT task (P = 0.04, eta(2) = 0.125) with a significant glycemia-awareness interaction for CRT after one hour of hypoglycemia (P = 0.045, eta(2) = 0.124). Performance on the trail-making B task was impaired for up to 10 min after euglycemia was restored (P = 0.024, eta(2) = 0.158). Following hypoglycemia, the recovery time for different cognitive tasks varied considerably. In the IHA group, performance was not significantly impaired during hypoglycemia. The state of awareness of hypoglycemia may influence cognitive function during and after hypoglycemia.

The lisse effect revisited

USGS Publications Warehouse

Weeks, E.P.

2002-01-01

The Lisse effect is a rarely noted phenomenon occurring when infiltration caused by intense rain seals the surface soil layer to airflow, trapping air in the unsaturated zone. Compression of air by the advancing front results in a pressure increase that produces a water-level rise in an observation well screened below the water table that is several times as large as the distance penetrated by the wetting front. The effect is triggered by intense rains and results in a very rapid water-level rise, followed by a recession lasting a few days. The Lisse effect was first noted and explained by Thal Larsen in 1932 from water-level observations obtained in a shallow well in the village of Lisse, Holland. The original explanation does not account for the increased air pressure pushing up on the bottom of the wetting front. Analysis of the effect of this upward pressure indicates that a negative pressure head at the base of the wetting front, ??f, analogous to that postulated by Green and Ampt (1911) to explain initially rapid infiltration rates into unsaturated soils, is involved in producing the Lisse effect. Analysis of recorded observations of the Lisse effect by Larsen and others indicates that the water-level rise, which typically ranges from 0.10 to 0.55 m, should be only slightly larger than |??f| and that the depth of penetration of the wetting front is no more than several millimeters.

Dynamic estuarine plumes and fronts: importance to small fish and plankton in coastal waters of NSW, Australia

NASA Astrophysics Data System (ADS)

Kingsford, M. J.; Suthers, I. M.

1994-05-01

In 1990, low density estuarine plumes in the vicinity of Botany Bay, Australia, extended up to 11 km across a narrow continental shelf ( ca 25 km) on ebb tides. The shape and seaward extent of plumes varied according to a combination of state of the tide, freshwater input and the direction and intensity of coastal currents. Offshore plumes dissipated on the flood tide and fronts reformed at the entrance of Botany Bay. Major differences in the abundance and composition of ichthyoplankton and other zooplankton were found over a 400-800 m stretch of water encompassing waters of the plume, front and ocean on seven occasions. For example, highest abundances of the fishes Gobiidae, Sillaginidae, Gerreidae and Sparidae as well as barnacle larvae and fish eggs were found in plumes. Cross-shelf distribution patterns of zooplankton, therefore, are influenced by plumes. Distinct assemblages of plankters accumulated in fronts, e.g. fishes of the Mugilidae and Gonorynchidae and other zooplankters (e.g. Jaxea sp.). Accumulation in fronts was variable and may relate to variable convergence according to the tide. We argue that plumes provide a significant cue to larvae in coastal waters that an estuary is nearby. Moreover, although many larvae may be retained in the turbid waters of plumes associated with riverine input, larvae are potentially exported in surface waters on ebb tides.

Gauss-Seidel Iterative Method as a Real-Time Pile-Up Solver of Scintillation Pulses

NASA Astrophysics Data System (ADS)

Novak, Roman; Vencelj, Matja¿

2009-12-01

The pile-up rejection in nuclear spectroscopy has been confronted recently by several pile-up correction schemes that compensate for distortions of the signal and subsequent energy spectra artifacts as the counting rate increases. We study here a real-time capability of the event-by-event correction method, which at the core translates to solving many sets of linear equations. Tight time limits and constrained front-end electronics resources make well-known direct solvers inappropriate. We propose a novel approach based on the Gauss-Seidel iterative method, which turns out to be a stable and cost-efficient solution to improve spectroscopic resolution in the front-end electronics. We show the method convergence properties for a class of matrices that emerge in calorimetric processing of scintillation detector signals and demonstrate the ability of the method to support the relevant resolutions. The sole iteration-based error component can be brought below the sliding window induced errors in a reasonable number of iteration steps, thus allowing real-time operation. An area-efficient hardware implementation is proposed that fully utilizes the method's inherent parallelism.

Changes in Social Impairment for People with Intellectual Disabilities: A Follow-up of the Camberwell Cohort.

ERIC Educational Resources Information Center

Beadle-Brown, Julie; Murphy, Glynis; Wing, Lorna; Gould, Judy; Shah, Amitta; Holmes, Nan

2002-01-01

The skills and social impairments of 146 adolescents and young adults in London who had been found to have severe intellectual disabilities and/or autism as children in the 1970s were assessed. Classification as socially impaired or not remained relatively stable over time. Within the socially impaired group, there was a significant increase in…

Depressive Symptoms and Impaired Physical Function after Acute Lung Injury

PubMed Central

Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Dinglas, Victor D.; Shanholtz, Carl; Husain, Nadia; Dennison, Cheryl R.; Herridge, Margaret S.; Pronovost, Peter J.; Needham, Dale M.

2012-01-01

Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (“depressive symptoms”) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (“impaired physical function”) in patients without baseline impairment. Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors’ long-term outcomes. PMID:22161158

Precursory, Nucleation and Propagation of Ruptures Along Heterogeneously Loaded, Circular Experimental Faults

NASA Astrophysics Data System (ADS)

Reches, Z.; Zu, X.; Jeffers, J.

2017-12-01

We explored the evolution of dynamic rupture along a circular experimental fault composed of clear acrylic blocks. The ring-shaped fault surface has inner and outer diameters of 7.72 and 10.16 cm, respectively. An array of ten rossette strain-gauges is attached to the outer rim of one block that provide the 2D strain tensor in a plane normal to the fault. The 30 components of the gauges are monitored at 10^6 samples/second. One 3D miniature accelerometer is attached to the fault block. The initial asperities of the fault surface generated a non-uniform strain (=stress) distribution that was recorded, and indicated local deviations of ±30% from the mean stress. The mean normal stress was up to 3.5 MPa, the remotely applied velocity was up to .002 m/s, and the slip velocities during rupture were not measured. The rupture characteristics, namely propagation velocity and rupture front strain-field, were determined from strain-gauge outputs. The analysis of tens of stick-slip events revealed the following preliminary results: (1) The ruptures consistently nucleated at sites of high local strains (=stresses) that were formed by the pre-shear, normal stress loading. (2) The pre-rupture nucleation process was recognized a by temporal (< 0.1 s), local (<20 mm) reduction of the shear strain. (3) Commonly, the initiation of nucleation was associated with micro acoustic emissions, whereas the initiation of rupture was associated with intense acoustic activity. (4) Nucleation could occur quasi-simultaneously at two, highly stressed sites. (5) From the nucleation site, the ruptures propagated in two directions along the ring-shaped fault, and the collision between the two fronts led to rupture `shut-off'. (5) The strain-field of rupture fronts was well-recognized for ruptures propagating faster than 50 m/s, and the fastest fronts propagated at 1000 m/s. (7) It appears that the rupture front strain-field close to the nucleation site differs from the front strain-field far from nucleation site. (8) Post-shear examination of the fault surfaces revealed evidence of brittle wear of the acrylic including gouge formation, ploughing, and powder smearing. (9) Work in progress includes attempts to achieve faster dynamic ruptures, and the utilization of the existing monitoring system to rupture granite faults.

Normality and Impairment following Profound Early Institutional Deprivation: A Longitudinal follow-up into Early Adolescence

ERIC Educational Resources Information Center

Kreppner, Jana M.; Rutter, Michael; Beckett, Celia; Castle, Jenny; Colvert, Emma; Groothues, Christine; Hawkins, Amanda; O'Connor, Thomas G.; Stevens, Suzanne; Sonuga-Barke, Edmund J. S.

2007-01-01

Longitudinal analyses on normal versus impaired functioning across 7 domains were conducted in children who had experienced profound institutional deprivation up to the age of 42 months and were adopted from Romania into U.K. families. Comparisons were made with noninstitutionalized children adopted from Romania and with nondeprived within-U.K.…

Perceptions of Teachers of Students with Visual Impairments regarding Assistive Technology: A Follow-Up Study to a University Course

ERIC Educational Resources Information Center

Kamei-Hannan, Cheryl; Howe, Jon; Herrera, Robyn Rene; Erin, Jane N.

2012-01-01

Introduction: The study presented here examined the learning outcomes of graduate students in visual impairment who were enrolled in an assistive technology course in three university programs. Methods: The students' perceptions of learning were evaluated using pre- and posttests administered during the course. A follow-up questionnaire was…

Transport and retention of vertically migrating adult mysid and decapod shrimp in the tidal front on Georges Bank

USGS Publications Warehouse

Lough, R. Gregory; Aretxabaleta, Alfredo L.

2014-01-01

Vertical profiles of the adult epibenthic shrimp Neomysis americana and Crangon septemspinosus obtained during June 1985 were used to simulate possible rates of ascent from bottom (40 to 50 m) to near surface at night and return by day, and the consequence of these rates on their horizontal distribution. Numerical particles were released at the sampling site using archived model current fields with specified vertical rates (from no swim behavior to 20 mm s(-1)) and tracked for up to 30 d. The best match between observed and modeled vertical profiles was with a vertical swimming speed of 10 mm s(-1) for N. americana and 2 mm s(-1) for C. septemspinosus. Whereas N. americana rapidly swims towards the surface at dusk and descends to bottom by dawn, C. septemspinosus tends to only swim up to the middle of the water column at night. After 16 d, the simulation with 10 mm s(-1) swim speed showed most particles were concentrated in an area centered around the 60 m isobath, where the tidal front was located. At 2 mm s(-1) swim speed particles were concentrated more shoalward onto the western end of Georges Bank. N. americana are expected to be more closely associated with the tidal front, since they spend more time near the front surface convergence, but are more likely to be transported off the bank due to the south-westward-flowing surface tidal jet, whereas C. septemspinosus would be retained primarily on the bank, since they are found deeper in the water column during both day and night.

STS-106 Orbit 2 Flight Team

NASA Image and Video Library

2000-09-14

JSC2000-06244 (September 2000)--- Flight director Jeff Hanley, front center, and the fifty-odd flight controllers making up the ISS Orbit 2 Team pose for their group portrait in the ISS Flight Control Room of Houston's Mission Control Center.

The role of whole brain radiation therapy in the management of melanoma brain metastases

PubMed Central

2014-01-01

Background Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as “radioresistant,” the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). Methods We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). Conclusions Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials. PMID:24954062

Musical Chairs: An Innovative Teaching and Learning Method

ERIC Educational Resources Information Center

Kuo, Ya-Hui

2010-01-01

How teaching and learning takes place in classrooms can be easily seen by the way classrooms are set up: Students' desks and chairs are arranged in rolls while teachers' desks are up front. Yet, why must teachers be the ones who lecture, why can't it be students? Would it be better or worse when teachers are the receivers and the students are the…

Colorado Pulls out Stops in Bid for "Race to Top" Aid

ERIC Educational Resources Information Center

Klein, Alyson

2009-01-01

If the competition for a slice of $4 billion in federal Race to the Top Fund money were a school class, Colorado would be one of the kids sitting up front, furiously taking notes, and leaping up to answer every one of the teacher's questions. Officials here began plotting their strategy for receiving one of the coveted grants nearly as soon as the…

Prediction of dementia by subjective memory impairment: effects of severity and temporal association with cognitive impairment.

PubMed

Jessen, Frank; Wiese, Birgitt; Bachmann, Cadja; Eifflaender-Gorfer, Sandra; Haller, Franziska; Kölsch, Heike; Luck, Tobias; Mösch, Edelgard; van den Bussche, Hendrik; Wagner, Michael; Wollny, Anja; Zimmermann, Thomas; Pentzek, Michael; Riedel-Heller, Steffi G; Romberg, Heinz-Peter; Weyerer, Siegfried; Kaduszkiewicz, Hanna; Maier, Wolfgang; Bickel, Horst

2010-04-01

Subjective memory impairment (SMI) is receiving increasing attention as a pre-mild cognitive impairment (MCI) condition in the course of the clinical manifestation of Alzheimer disease (AD). To determine the risk for conversion to any dementia, dementia in AD, or vascular dementia by SMI, graded by the level of SMI-related worry and by the temporal association of SMI and subsequent MCI. Longitudinal cohort study with follow-up examinations at 1(1/2) and 3 years after baseline. Primary care medical record registry sample. A total of 2415 subjects without cognitive impairment 75 years or older in the German Study on Aging, Cognition and Dementia in Primary Care Patients. Conversion to any dementia, dementia in AD, or vascular dementia at follow-up 1 or follow-up 2 predicted by SMI with or without worry at baseline and at follow-up 2 predicted by different courses of SMI at baseline and MCI at follow-up 1. In the first analysis, SMI with worry at baseline was associated with greatest risk for conversion to any dementia (hazard ratio [HR], 3.53; 95% confidence interval [CI], 2.07-6.03) or dementia in AD (6.54; 2.82-15.20) at follow-up 1 or follow-up 2. The sensitivity was 69.0% and the specificity was 74.3% conversion to dementia in AD. In the second analysis, SMI at baseline and MCI at follow-up 1 were associated with greatest risk for conversion to any dementia (odds ratio [OR], 8.92; 95% CI, 3.69-21.60) or dementia in AD (19.33; 5.29-70.81) at follow-up 2. Furthermore, SMI at baseline and amnestic MCI at follow-up 1 increased the risk for conversion to any dementia (OR, 29.24; 95% CI, 8.75-97.78) or dementia in AD (60.28; 12.23-297.10), with a sensitivity of 66.7% and a specificity of 98.3% for conversion to dementia in AD. The prediction of dementia in AD by SMI with subsequent amnestic MCI supports the model of a consecutive 3-stage clinical manifestation of AD from SMI via MCI to dementia.

Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia in Ukraine.

PubMed

Mandrik, Olena; Corro Ramos, Isaac; Knies, Saskia; Al, Maiwenn; Severens, Johan L

2015-01-01

The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC) for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER) for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars) of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER. Furthermore, probabilistic sensitivity analyses have shown that for refractory/relapsed patients the probability of FCR being cost-effective is higher than for treatment-naïve patients and is close to one if the threshold is higher than US$15,000. State coverage of rituximab treatment may be considered a cost-effective treatment for the Ukrainian population under conditions of economic stability, cost-effectiveness threshold growth, or rituximab price negotiations.

Dietary Habits and Cognitive Impairment Risk Among Oldest-Old Chinese.

PubMed

An, Ruopeng; Liu, Gordon; Khan, Naiman; Yan, Hai; Wang, Youfa

2017-02-10

This study examined the longitudinal relationship between dietary habits and cognitive impairment among the oldest-old Chinese. Cognitively intact adults aged 80 or older (N = 4,749) came from the Chinese Longitudinal Healthy Longevity Survey. Cognitive impairment was assessed by Mini-mental State Examination. Cox regressions were performed to examine the relationship between dietary habits and cognitive impairment onset during follow-up period of 1998-2012, adjusting for various time-variant and time-invariant individual characteristics. Compared with those who rarely/never consumed fruit, vegetables, meat, and soybean-derived products, participants consuming such products almost every day were 21%, 25%, 17%, and 20% less likely to develop cognitive impairment during follow-up, respectively. Compared with those who rarely/never consumed sugar, participants consuming sugar almost every day were 17% more likely to develop cognitive impairment during follow-up. Consumption of fish, egg, salt-preserved vegetable, tea, and garlic was not found to be associated with cognitive impairment. Dietary habits might profoundly impact cognitive functioning among the oldest-old Chinese. This work has limitations pertaining to study design and measure. Future work adopting experimental design and refined dietary measures is warranted to confirm these findings and inform public nutrition practices aiming at preventing cognitive decline among the oldest-old Chinese population. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Osteogenesis imperfecta in childhood: impairment and disability--a follow-up study.

PubMed

Engelbert, R H; Beemer, F A; van der Graaf, Y; Helders, P J

1999-08-01

To evaluate differences over time (mean follow-up, 14 months) on impairment parameters (range of joint motion and muscle strength), functional limitation parameters (functional ability), and disability parameters (caregiver assistance in achieving functional skills) in osteogenesis imperfecta (OI), related to the different types of the disease. A prospective, descriptive study. Fifty-four children with OI and their parents participated at the start of the study. At the end, 44 children participated in the assessment of functional skills and 42 of them participated in clinical assessment (OI type I, n = 19; OI type III, n = 13; OI type IV, n = 10). Range of joint motion was measured by means of goniometry. Generalized hypermobility was scored according to Bulbena. Manual muscle strength was scored by means of the MRC grading system. The level of ambulation was scored according to Bleck, and functional skills and caregiver assistance were scored with the Pediatric Evaluation of Disability Inventory. The different types of OI have impact on impairment, functional limitation, and disability. Almost all impairment parameters did not change significantly over time, whereas some disability parameters seemed to improve significantly. Impairment parameters in OI are presumably not always preconditions for functional limitation and disability. A 1-year follow-up revealed no significant changes in impairment parameters, whereas some disability parameters improved. Treatment strategies in OI should, therefore, focus primarily on improving functional ability, with respect to the natural course of the disease, and not only on impairment parameters.

Desktop Application Program to Simulate Cargo-Air-Drop Tests

NASA Technical Reports Server (NTRS)

Cuthbert, Peter

2009-01-01

The DSS Application is a computer program comprising a Windows version of the UNIX-based Decelerator System Simulation (DSS) coupled with an Excel front end. The DSS is an executable code that simulates the dynamics of airdropped cargo from first motion in an aircraft through landing. The bare DSS is difficult to use; the front end makes it easy to use. All inputs to the DSS, control of execution of the DSS, and postprocessing and plotting of outputs are handled in the front end. The front end is graphics-intensive. The Excel software provides the graphical elements without need for additional programming. Categories of input parameters are divided into separate tabbed windows. Pop-up comments describe each parameter. An error-checking software component evaluates combinations of parameters and alerts the user if an error results. Case files can be created from inputs, making it possible to build cases from previous ones. Simulation output is plotted in 16 charts displayed on a separate worksheet, enabling plotting of multiple DSS cases with flight-test data. Variables assigned to each plot can be changed. Selected input parameters can be edited from the plot sheet for quick sensitivity studies.

Cruise noise of counterrotation propeller at angle of attack in wind tunnel

NASA Technical Reports Server (NTRS)

Dittmar, J. H.

1986-01-01

The noise of a counterrotation propeller at angle of attack was measured in the NASA Lewis 8- by 6-Foot Supersonic Wind Tunnel at cruise conditions. Noise increases of as much as 4 dB were measured at positive angles of attack on the tunnel side wall, which represented an airplane fuselage. These noise increases could be minimized or eliminated by operating the counterrotation propeller with the front propeller turning up-inboard. This would require oppositely rotating propellers on opposite sides of the airplane. Noise analyses at different bandwidths enabled the separate front- and rear-propeller tones, as well as the total noise, at each harmonic to be determined. A simplified noise model was explored to show how the observed circumferential noise patterns of the separate propeller tones might have occurred. The total noise pattern, which represented the sum of the front- and rear-propeller tones at a particular harmonic, showed trends that would be hard to interpret without the separate-tone results. Therefore it is important that counterrotation angle-of-attack noise data be taken in such a manner that the front- and rear-propeller tones can be separated.

Ageostrophic Frontal Processes Controlling Phytoplankton Production in the Catalano-Balearic Sea (Western Mediterranean)

PubMed Central

Oguz, Temel; Macias, Diego; Tintore, Joaquin

2015-01-01

Buoyancy-induced unstable boundary currents and the accompanying retrograde density fronts are often the sites of pronounced mesoscale activity, ageostrophic frontal processes, and associated high biological production in marginal seas. Biophysical model simulations of the Catalano-Balearic Sea (Western Mediterranean) illustrated that the unstable and nonlinear southward frontal boundary current along the Spanish coast resulted in a strain-driven frontogenesis mechanism. High upwelling velocities of up to 80 m d-1 injected nutrients into the photic layer and promoted enhanced production on the less dense, onshore side of the front characterized by negative relative vorticity. Additional down-front wind stress and heat flux (cooling) intensified boundary current instabilities and thus ageostrophic cross-frontal circulation and augmented production. Specifically, entrainment of nutrients by relatively strong buoyancy-induced vertical mixing gave rise to a more widespread phytoplankton biomass distribution within the onshore side of the front. Mesoscale cyclonic eddies contributed to production through an eddy pumping mechanism, but it was less effective and more limited regionally than the frontal processes. The model was configured for the Catalano-Balearic Sea, but the mechanisms and model findings apply to other marginal seas with similar unstable frontal boundary current systems. PMID:26065688

Progression of impairment in adolescents with ADHD through the transition out of high school: Contributions of parent involvement and college attendance

PubMed Central

Howard, Andrea L.; Strickland, Noelle; Murray, Desiree W.; Tamm, Leanne; Swanson, James M.; Hinshaw, Stephen P.; Arnold, L. Eugene; Molina, Brooke S. G.

2016-01-01

Long-term, prospective follow-up studies of children diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD) show that symptoms tend to decline with age, but impairments in daily life functioning often persist into adulthood. We examined the developmental progression of impairments before and after the transition out of high school in relation to parent involvement during adolescence, parent support during adulthood, and college attendance, using 8 waves of data from the prospective 16-year follow-up of the Multimodal Treatment of ADHD (MTA) Study. Participants were 548 proband children diagnosed with DSM-IV ADHD Combined Type and 258 age- and sex-matched comparison children (Local Normative Comparison Group; LNCG) randomly sampled from probands' schools. Impairment was assessed consistently by parent report from childhood through adulthood. Results showed that impairment worsens over time both before and after the transition to adulthood for those with ADHD histories, in contrast to non-ADHD peers, whose impairments remained stably low over time. However, impairment stabilized after leaving high school for young adults with ADHD histories who attended college. Involved parenting in adolescence was associated with less impairment overall. Attending college was associated with a stable post-high school trajectory of impairment regardless of parents' involvement during adolescence, but young adults with histories of involved parenting and who attended college were the least impaired overall. PMID:26854508

Haploidentical HCT using an αβ T-cell-depleted graft with targeted αβ(+) cells by add-back after a reduced intensity preparative regimen containing low-dose TBI.

PubMed

Im, H J; Koh, K N; Suh, J K; Lee, S W; Choi, E S; Jang, S; Kwon, S W; Park, C-J; Seo, J J

2016-09-01

Between 2012 and 2015, 42 pediatric patients underwent haploidentical hematopoietic cell transplantation using an αβ(+) T-cell-depleted graft with targeted αβ cells at 1-5 × 10(5)/kg by add-back; 31 had hematologic malignancy (HM), 8 had non-malignant disease (NM) and 3 had solid tumors. All patients received uniform reduced-intensity conditioning with fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin and low-dose TBI. All 42 patients achieved neutrophil engraftment at a median of 10 days. The cumulative incidences (CIs) of ⩾grade II and ⩾grade III acute GvHD were 31±7.1% (SE) and 12±5.0%, respectively, and 1-year CI of chronic GvHD was 15±5.8%. One patient died of CMV pneumonia, leading to transplant-related mortality (TRM) of 2.6±2.5%. Sixteen patients relapsed and 11 died of disease. At a median follow-up of 19 months (range, 5-43 months), the estimated 2-year event-free survival for NM and HM were 88±11.7 and 50±10.1%, respectively. Our study demonstrated that haploidentical hematopoietic cell transplantation after ex vivo depletion of αβ(+) T cells with targeted dose noticeably reduced the graft failure rate and TRM in pediatric patients and could be applied to patients lacking a suitable related or unrelated donor.

c-Abl kinase inhibitors overcome CD40-mediated drug resistance in CLL: implications for therapeutic targeting of chemoresistant niches.

PubMed

Hallaert, Delfine Y H; Jaspers, Annelieke; van Noesel, Carel J; van Oers, Marinus H J; Kater, Arnon P; Eldering, Eric

2008-12-15

In lymph node (LN) proliferation centers in chronic lymphocytic leukemia (CLL), the environment protects from apoptotic and cytotoxic triggers. Here, we aimed to define the molecular basis for the increased drug resistance and searched for novel strategies to circumvent it. The situation in CLL LN could be mimicked by prolonged in vitro CD40 stimulation, which resulted in up-regulation of antiapoptotic Bcl-xL, A1/Bfl-1, and Mcl-1 proteins, and afforded resistance to various classes of drugs (fludarabine, bortezomib, roscovitine). CD40 stimulation also caused ERK-dependent reduction of Bim-EL protein, but ERK inhibition did not prevent drug resistance. Drugs combined with sublethal doses of the BH3-mimetic ABT-737 displayed partial and variable effects per individual CD40-stimulated CLL. The antiapoptotic profile of CD40-triggered CLL resembled BCR-Abl-dependent changes seen in chronic myeloid leukemia (CML), which prompted application of c-Abl inhibitors imatinib or dasatinib. Both compounds, but especially dasatinib, prevented the entire antiapoptotic CD40 program in CLL cells, and restored drug sensitivity. These effects also occurred in CLL samples with dysfunctional p53. Importantly, ex vivo CLL LN samples also displayed strong ERK activation together with high Bcl-xL and Mcl-1 but low Bim levels. These data indicate that CLL cells in chemoresistant niches may be sensitive to therapeutic strategies that include c-Abl inhibitors.

A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders.

PubMed

Shenoy, S; Grossman, W J; DiPersio, J; Yu, L C; Wilson, D; Barnes, Y J; Mohanakumar, T; Rao, A; Hayashi, R J

2005-02-01

Bone marrow transplantation (BMT) benefits nonmalignant diseases but is limited by regimen-related toxicity, graft-versus-host disease (GVHD), donor availability, and graft rejection (GR). To overcome some of these barriers, we developed a new conditioning strategy for these patients. In total, 16 patients received Campath-1H (33/48 mg; days -21 to -19), fludarabine (150 mg/m(2); days -8 to -4), melphalan (140/70 mg/m(2); day -3), and transplant using related/unrelated stem cells. GVHD prophylaxis included cyclosporine/methylprednisolone for cord cells. Other recipients also received methotrexate. Risk factors for GR included multiple transfusions (6), low stem cell numbers (1), and immunologic/metabolic disorders (3). Donor engraftment was present in 14/16 recipients. Neutrophils (ANC>0.5 x 10(9)/l) and platelets (>50 x 10(9)/l) engrafted at a median of 13 and 24 days. Two patients died of Pseudomonas sepsis prior to engraftment, one of CMV disease, and another of intracranial hemorrhage. With median follow-up of 281 days (78-907), 12/16 are stable/improved, or cured. Acute GVHD was absent (n=10) or mild and transient (grade1-2 skin) (n=4). There was no chronic GVHD. Toxicities were predominantly early infections within 100 days, and correlated with lymphopenia (CD4+ T and B cells). Stable engraftment and low incidence of significant GVHD, irrespective of age or stem cell source, make this reduced-intensity regimen attractive for nonmalignant disorders.

Richter transformation driven by Epstein-Barr virus reactivation during therapy-related immunosuppression in chronic lymphocytic leukaemia.

PubMed

García-Barchino, Maria J; Sarasquete, Maria E; Panizo, Carlos; Morscio, Julie; Martinez, Antonio; Alcoceba, Miguel; Fresquet, Vicente; Gonzalez-Farre, Blanca; Paiva, Bruno; Young, Ken H; Robles, Eloy F; Roa, Sergio; Celay, Jon; Larrayoz, Marta; Rossi, Davide; Gaidano, Gianluca; Montes-Moreno, Santiago; Piris, Miguel A; Balanzategui, Ana; Jimenez, Cristina; Rodriguez, Idoia; Calasanz, Maria J; Larrayoz, Maria J; Segura, Victor; Garcia-Muñoz, Ricardo; Rabasa, Maria P; Yi, Shuhua; Li, Jianyong; Zhang, Mingzhi; Xu-Monette, Zijun Y; Puig-Moron, Noemi; Orfao, Alberto; Böttcher, Sebastian; Hernandez-Rivas, Jesus M; Miguel, Jesus San; Prosper, Felipe; Tousseyn, Thomas; Sagaert, Xavier; Gonzalez, Marcos; Martinez-Climent, Jose A

2018-05-01

The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV - tumours, EBV + DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV + DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy-related immunosuppression can transform either CLL cells or non-tumoural B lymphocytes into EBV + DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2 -/- IL2γc -/- mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV + B-cell clones from 95% of CLL and 64% of MBL patients samples, but not from healthy donors. Eventually, these cells generated monoclonal tumours (mostly CLL-unrelated but also CLL-related), recapitulating the principal features of EBV + DLBCL in patients. Accordingly, clonally related and unrelated EBV + DLBCL xenografts showed indistinguishable cellular, virological and molecular features, and synergistically responded to combined inhibition of EBV replication with ganciclovir and B-cell receptor signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by EBV in CLL patients receiving immunosuppressive therapies, and provides the scientific rationale for testing ganciclovir and ibrutinib in EBV + DLBCL. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A kinematic analysis of the rapid step test in balance-impaired and unimpaired older women.

PubMed

Schulz, Brian W; Ashton-Miller, James A; Alexander, Neil B

2007-04-01

Little is known about the kinematic and kinetic determinants that might explain age and balance-impairment alterations in the results of volitional stepping performance tests. Maximal unipedal stance time (UST) was used to distinguish "balance-impaired" old (BI, UST<10s, N=15, mean age=76 years) from unimpaired old (O, UST>30s, N=12, mean age=71 years) before they and healthy young females (Y, UST>30s, N=13, mean age=23 years) performed the rapid step test (RST). The RST evaluates the time required to take volitional front, side, and back steps of at least 80% maximum step length in response to verbal commands. Kinematic and kinetic data were recorded during the RST. The results indicate that the initiation phase of the step was the major source of age- and balance impairment-related delays. The delays in BI were primarily caused by increased postural adjustments prior to step initiation, as measured by center-of-pressure (COP) path length (p<0.003). The Step landing phase showed similar, but non-significant, temporal trends. Step length and peak center-of-mass (COM) deceleration during the Step-Out landing decreased in O by 18% (p=0.0002) and 24% (p=0.001), respectively, and a further 12% (p=0.04) and 18% (p=0.08) in BI. We conclude that the delay in BI step initiation was due to the increase in their postural adjustments prior to step initiation.

2. Historic American Buildings Survey E. W. Russell, Photographer, September ...

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

2. Historic American Buildings Survey E. W. Russell, Photographer, September 1, 1936 CLOSE- UP OF SECTION ON FRONT OF PORCH, WILLIAM H. KETCHUM - 400 GOVERNMENT STREET - William H. Ketchum House & Gates (Ironwork), 400 Government Street, Mobile, Mobile County, AL

Practice Makes Learning.

ERIC Educational Resources Information Center

Neill, Judy

This paper focuses on how people learn to help educators design curriculum that will enable students to successfully complete a distance learning class. Up-front organization, clear communication about performance expectations, outcome driven assessment, and imaginative learning strategies are critical to successful distance learning.…

Computer/gaming station use in youth: Correlations among use, addiction and functional impairment

PubMed Central

Baer, Susan; Saran, Kelly; Green, David A

2012-01-01

OBJECTIVE: Computer/gaming station use is ubiquitous in the lives of youth today. Overuse is a concern, but it remains unclear whether problems arise from addictive patterns of use or simply excessive time spent on use. The goal of the present study was to evaluate computer/gaming station use in youth and to examine the relationship between amounts of use, addictive features of use and functional impairment. METHOD: A total of 110 subjects (11 to 17 years of age) from local schools participated. Time spent on television, video gaming and non-gaming recreational computer activities was measured. Addictive features of computer/gaming station use were ascertained, along with emotional/behavioural functioning. Multiple linear regressions were used to understand how youth functioning varied with time of use and addictive features of use. RESULTS: Mean (± SD) total screen time was 4.5±2.4 h/day. Addictive features of use were consistently correlated with functional impairment across multiple measures and informants, whereas time of use, after controlling for addiction, was not. CONCLUSIONS: Youth are spending many hours each day in front of screens. In the absence of addictive features of computer/gaming station use, time spent is not correlated with problems; however, youth with addictive features of use show evidence of poor emotional/ behavioural functioning. PMID:24082802

Apparatus and method for harvesting woody plantations

DOEpatents

Eggen, David L.

1988-11-15

A tree harvester for harvesting felled trees includes a wheel mounted wood chipper which moves toward the butt ends of the tree stems to be processed. The harvester includes a plurality of rotating alignment discs in front of the chipper. These discs align the tree stems to be processed with the mouth of the chipper. A chipper infeed cylinder is rotatably mounted between the discs and the front end of the chipper, and lifts the tree stem butts up from the ground into alignment with the chipper inlet port. The chips discharge from the chipper and go into a chip hopper which moves with the tree harvester.

Apparatus and method for harvesting woody plantations

DOEpatents

Eggen, D.L.

1988-11-15

A tree harvester for harvesting felled trees includes a wheel mounted wood chipper which moves toward the butt ends of the tree stems to be processed. The harvester includes a plurality of rotating alignment discs in front of the chipper. These discs align the tree stems to be processed with the mouth of the chipper. A chipper infeed cylinder is rotatably mounted between the discs and the front end of the chipper, and lifts the tree stem butts up from the ground into alignment with the chipper inlet port. The chips discharge from the chipper and go into a chip hopper which moves with the tree harvester. 8 figs.

Retired NASA F-18 being hoisted up by crane to pedestal mount at Lancaster California Municipal Base

NASA Technical Reports Server (NTRS)

1997-01-01

Workers adjust a sling holding an F/A-18 Hornet aircraft formerly flown by NASA's Dryden Flight Research Center, Edwards, California, during operations to mount the airframe for display in front of the municipal baseball stadium on Lancaster, California. The F/A-18 was used as a safety chase and support aircraft prior to its recent retirement. The aircraft is now mounted nose skyward on a 28-foot-tall pedestal in front of the stadium. The stadium, known as 'The Hangar,' is the home field of the Lancaster Jethawks, a Class-A farm team of the Seattle Mariners.

Analog Signal Correlating Using an Analog-Based Signal Conditioning Front End

NASA Technical Reports Server (NTRS)

Prokop, Norman; Krasowski, Michael

2013-01-01

This innovation is capable of correlating two analog signals by using an analog-based signal conditioning front end to hard-limit the analog signals through adaptive thresholding into a binary bit stream, then performing the correlation using a Hamming "similarity" calculator function embedded in a one-bit digital correlator (OBDC). By converting the analog signal into a bit stream, the calculation of the correlation function is simplified, and less hardware resources are needed. This binary representation allows the hardware to move from a DSP where instructions are performed serially, into digital logic where calculations can be performed in parallel, greatly speeding up calculations.

Fragmentation Speed at Magmatic Temperatures: an Experimental Determination

NASA Astrophysics Data System (ADS)

Alatorre-Ibarguengoitia, M. A.; Scheu, B.; Dingwell, D. B.

2011-12-01

The propagation speed of the fragmentation front (fragmentation speed) is a controlling factor in the dynamics of explosive volcanic eruptions and can affect the eruptive regime. It is impossible to measure the fragmentation speed directly in natural systems. Thus, laboratory experiments using natural samples represent a unique source of information revealing the dynamics of fragmentation processes. Rapid decompression experiments of natural samples from several volcanoes allowed us to quantify the influence of sample porosity and pressure differential on the fragmentation speed. These previous experiments have been performed almost exclusively at temperatures up to 300 °C. Due to experimental constraints it is not possible to measure directly the fragmentation speed at magmatic temperatures using the same procedure as in the experiments up to moderate temperature. The magmatic temperature for the analyzed rock types varies typically between 700 - 900 °C, reflecting their moderate to high silica content. For this reason, the influence of the temperature on the fragmentation speed had not been investigated systematically. In order to determine the fragmentation speed at magmatic temperatures (700 - 900 °C), we performed rapid decompression experiments of volcanic rocks and measured with a high-speed camera the ejection speed at the front of the gas-particle mixture produced by fragmentation. Then we used a theoretical model based on a 1-D shock-tube theory considering the conservation laws across the fragmentation front that provides a relationship between the fragmentation speed and the ejection speed at the front of the gas-particle mixture. This model has been validated in fragmentation experiments at room temperature where the fragmentation and ejection speed were measured simultaneously. We investigated natural volcanic samples covering a broad range of connected porosity (16 - 65 vol. %) and applied pressures (4-20 MPa) at room temperature and up to 850 °C. To our knowledge, this is the first systematic investigation of the fragmentation speed of volcanic samples at magmatic temperatures. These results enhance our understanding of explosive volcanic eruptions. As has been shown by recent studies, a quantitative knowledge of the dynamics of magma fragmentation is critical for determining the eruptive regime.

Somatosensory impairment and its association with balance limitation in people with multiple sclerosis.

PubMed

Jamali, Akram; Sadeghi-Demneh, Ebrahim; Fereshtenajad, Niloufar; Hillier, Susan

2017-09-01

Somatosensory impairments are common in multiple sclerosis. However, little data are available to characterize the nature and frequency of these problems in people with multiple sclerosis. To investigate the frequency of somatosensory impairments and identify any association with balance limitations in people with multiple sclerosis. The design was a prospective cross-sectional study, involving 82 people with multiple sclerosis and 30 healthy controls. Tactile and proprioceptive sensory acuity were measured using the Rivermead Assessment of Somatosensory Performance. Vibration duration was assessed using a tuning fork. Duration for the Timed Up and Go Test and reaching distance of the Functional Reach Test were measured to assess balance limitations. The normative range of sensory modalities was defined using cut-off points in the healthy participants. The multivariate linear regression was used to identify the significant predictors of balance in people with multiple sclerosis. Proprioceptive impairments (66.7%) were more common than tactile (60.8%) and vibration impairments (44.9%). Somatosensory impairments were more frequent in the lower limb (78.2%) than the upper limb (64.1%). All sensory modalities were significantly associated with the Timed Up and Go and Functional Reach tests (p<0.05). The Timed Up and Go test was independently predicted by the severity of the neurological lesion, Body Mass Index, ataxia, and tactile sensation (R2=0.58), whereas the Functional Reach test was predicted by the severity of the neurological lesion, lower limb strength, and vibration sense (R2=0.49). Somatosensory impairments are very common in people with multiple sclerosis. These impairments are independent predictors of balance limitation. Copyright © 2017 Elsevier B.V. All rights reserved.

Light-front holographic QCD and emerging confinement

DOE PAGES

Brodsky, Stanley J.; de Téramond, Guy F.; Dosch, Hans Günter; ...

2015-05-21

In this study we explore the remarkable connections between light-front dynamics, its holographic mapping to gravity in a higher-dimensional anti-de Sitter (AdS) space, and conformal quantum mechanics. This approach provides new insights into the origin of a fundamental mass scale and the physics underlying confinement dynamics in QCD in the limit of massless quarks. The result is a relativistic light-front wave equation for arbitrary spin with an effective confinement potential derived from a conformal action and its embedding in AdS space. This equation allows for the computation of essential features of hadron spectra in terms of a single scale. Themore » light-front holographic methods described here give a precise interpretation of holographic variables and quantities in AdS space in terms of light-front variables and quantum numbers. This leads to a relation between the AdS wave functions and the boost-invariant light-front wave functions describing the internal structure of hadronic bound-states in physical spacetime. The pion is massless in the chiral limit and the excitation spectra of relativistic light-quark meson and baryon bound states lie on linear Regge trajectories with identical slopes in the radial and orbital quantum numbers. In the light-front holographic approach described here currents are expressed as an infinite sum of poles, and form factors as a product of poles. At large q 2 the form factor incorporates the correct power-law fall-off for hard scattering independent of the specific dynamics and is dictated by the twist. At low q 2 the form factor leads to vector dominance. The approach is also extended to include small quark masses. We briefly review in this report other holographic approaches to QCD, in particular top-down and bottom-up models based on chiral symmetry breaking. We also include a discussion of open problems and future applications.« less

Wave front sensing for next generation earth observation telescope

NASA Astrophysics Data System (ADS)

Delvit, J.-M.; Thiebaut, C.; Latry, C.; Blanchet, G.

2017-09-01

High resolution observations systems are highly dependent on optics quality and are usually designed to be nearly diffraction limited. Such a performance allows to set a Nyquist frequency closer to the cut off frequency, or equivalently to minimize the pupil diameter for a given ground sampling distance target. Up to now, defocus is the only aberration that is allowed to evolve slowly and that may be inflight corrected, using an open loop correction based upon ground estimation and refocusing command upload. For instance, Pleiades satellites defocus is assessed from star acquisitions and refocusing is done with a thermal actuation of the M2 mirror. Next generation systems under study at CNES should include active optics in order to allow evolving aberrations not only limited to defocus, due for instance to in orbit thermal variable conditions. Active optics relies on aberration estimations through an onboard Wave Front Sensor (WFS). One option is using a Shack Hartmann. The Shack-Hartmann wave-front sensor could be used on extended scenes (unknown landscapes). A wave-front computation algorithm should then be implemented on-board the satellite to provide the control loop wave-front error measure. In the worst case scenario, this measure should be computed before each image acquisition. A robust and fast shift estimation algorithm between Shack-Hartmann images is then needed to fulfill this last requirement. A fast gradient-based algorithm using optical flows with a Lucas-Kanade method has been studied and implemented on an electronic device developed by CNES. Measurement accuracy depends on the Wave Front Error (WFE), the landscape frequency content, the number of searched aberrations, the a priori knowledge of high order aberrations and the characteristics of the sensor. CNES has realized a full scale sensitivity analysis on the whole parameter set with our internally developed algorithm.

Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

ClinicalTrials.gov

2018-06-22

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

A 24-GHz Front-End Integrated on a Multilayer Cellulose-Based Substrate for Doppler Radar Sensors.

PubMed

Alimenti, Federico; Palazzi, Valentina; Mariotti, Chiara; Virili, Marco; Orecchini, Giulia; Bonafoni, Stefania; Roselli, Luca; Mezzanotte, Paolo

2017-09-12

This paper presents a miniaturized Doppler radar that can be used as a motion sensor for low-cost Internet of things (IoT) applications. For the first time, a radar front-end and its antenna are integrated on a multilayer cellulose-based substrate, built-up by alternating paper, glue and metal layers. The circuit exploits a distributed microstrip structure that is realized using a copper adhesive laminate, so as to obtain a low-loss conductor. The radar operates at 24 GHz and transmits 5 mW of power. The antenna has a gain of 7.4 dBi and features a half power beam-width of 48 degrees. The sensor, that is just the size of a stamp, is able to detect the movement of a walking person up to 10 m in distance, while a minimum speed of 50 mm/s up to 3 m is clearly measured. Beyond this specific result, the present paper demonstrates that the attractive features of cellulose, including ultra-low cost and eco-friendliness (i.e., recyclability and biodegradability), can even be exploited for the realization of future high-frequency hardware. This opens opens the door to the implementation on cellulose of devices and systems which make up the "sensing layer" at the base of the IoT ecosystem.

Study of self-generated electric field at shock front by broadband proton probing and soft X-ray emission

NASA Astrophysics Data System (ADS)

Hua, Rui; Sio, Hong; Wilks, Scott; McGuffey, Christopher; Bailly-Grandvaux, Mathieu; Heeter, Bob; Beg, Farhat; Collins, Gilbert; Ping, Yuan; MIT Collaboration; LLNL Collaboration; UCSD Collaboration

2017-10-01

Self-generated electric fields arise from gradients in the electron pressure at shock fronts. We report observations of such E-fields from experiments conducted on OMEGA EP. In the experiments, strong shock waves were generated in low density gas under a quasi-planar geometry and diagnosed by broadband proton radiography. The broad proton spectrum allows energy-dependent measurements of deflection from which one can quantitatively constrain the electrical potential and field thickness. Three UV beams delivering up to 6.4 kJ energy in 2ns were used for shock generation and a short laser pulse of energy up to 850 J, 10 ps duration, was used to accelerate the broadband proton beam for point-projection radiography. Observations show the existence of electric fields with potential 300 V at the front of a Mach 9 shock in helium gas. A Mach 16 shock is also studied, from which both the field thickness and electric potential are reproduced. Simultaneous spatially resolved soft-x-ray spectroscopy provided additional measurements of shock velocity, particle velocity and thermal emission. This work was performed under DOE contract DE-AC52-07NA27 344 with support from OFES Early Career program and LLNL LDRD program. This work has been partially supported by the University of California Office of the President Lab Fee Grant Number LFR-17-449059.

Magnetohydrodynamical Effects on Nuclear Deflagration Fronts in Type Ia Supernovae

NASA Astrophysics Data System (ADS)

Hristov, Boyan; Collins, David C.; Hoeflich, Peter; Weatherford, Charles A.; Diamond, Tiara R.

2018-05-01

This article presents a study of the effects of magnetic fields on non-distributed nuclear burning fronts as a possible solution to a fundamental problem for the thermonuclear explosion of a Chandrasekhar mass ({M}Ch}) white dwarf (WD), the currently favored scenario for the majority of Type Ia SNe. All existing 3D hydrodynamical simulations predict strong global mixing of the burning products due to Rayleigh–Taylor (RT) instabilities, which contradicts observations. As a first step toward studying the flame physics, we present a set of computational magnet-hydrodynamic models in rectangular flux tubes, resembling a small inner region of a WD. We consider initial magnetic fields up to {10}12 {{G}} of various orientations. We find an increasing suppression of RT instabilities starting at about {10}9 {{G}}. The front speed tends to decrease with increasing magnitude up to about {10}11 {{G}}. For even higher fields new small-scale, finger-like structures develop, which increase the burning speed by a factor of 3 to 4 above the field-free RT-dominated regime. We suggest that the new instability may provide sufficiently accelerated energy production during the distributed burning regime to go over the Chapman–Jougey limit and trigger a detonation. Finally, we discuss the possible origins of high magnetic fields during the final stage of the progenitor evolution or the explosion.

Cognitive impairment and mortality among the oldest-old Chinese.

PubMed

An, Ruopeng; Liu, Gordon G

2016-12-01

This study examined the relationship between cognitive impairment status and all-cause mortality among the oldest-old Chinese. A total of 7474 survey participants 80 years of age and above came from the Chinese Longitudinal Healthy Longevity Survey 1998-2012 waves. Baseline cognitive impairment status was assessed using the Chinese version of the mini-mental state examination (MMSE), with total score ranging from 0 to 30. Cox proportional hazards regressions were performed to examine the relationship between baseline cognitive impairment status in 1998 and subsequent all-cause mortality during 1998-2012, adjusting for various individual characteristics at baseline. Compared with those with no or mild cognitive impairment (18 ≤ MMSE score ≤ 30) at baseline, participants with moderate-to-severe cognitive impairment (0 ≤ MMSE score ≤ 17) were 28% (95% confidence interval = 20%, 37%) more likely to die during the follow-up period from 1998 to 2012. A dose-response relationship between baseline severity level of cognitive impairment and mortality was evident. Compared with those without cognitive impairment (25 ≤ MMSE score ≤ 30) at baseline, those having mild cognitive impairment (18 ≤ MMSE score ≤ 24), moderate cognitive impairment (10 ≤ MMSE score ≤ 17), and severe cognitive impairment (0 ≤ MMSE score ≤ 9), were 20% (13%, 28%), 38% (27%, 51%), and 47% (33%, 62%) more likely to die during the follow-up period. No statistically significant gender differences in the relationship between cognitive impairment status and mortality were found. Baseline cognitive impairment was inversely associated with longevity among the oldest-old Chinese. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Adaptive changes in autophagy after UPS impairment in Parkinson's disease.

PubMed

Shen, Yu-fei; Tang, Yu; Zhang, Xiao-jie; Huang, Kai-xing; Le, Wei-dong

2013-05-01

Ubiquitin-proteasome system (UPS) and autophagosome-lysosome pathway (ALP) are the most important machineries responsible for protein degradation in Parkinson's disease (PD). The aim of this study is to investigate the adaptive alterations in autophagy upon proteasome inhibition in dopaminergic neurons in vitro and in vivo. Human dopaminergic neuroblastoma SH-SY5Y cells were treated with the proteasome inhibitor lactacystin (5 μmol/L) for 5, 12, or 24 h. The expression of autophagy-related proteins in the cells was detected with immunoblotting. UPS-impaired mouse model of PD was established by microinjection of lactacystin (2 μg) into the left hemisphere of C57BL/6 mice that were sacrificed 2 or 4 weeks later. The midbrain tissues were dissected to assess alterations in autophagy using immunofluorescence, immunoblotting and electron microscopy assays. Both in SH-SY5Y cells and in the midbrain of UPS-impaired mouse model of PD, treatment with lactacystin significantly increased the expression levels of LC3-I/II and Beclin 1, and reduced the levels of p-mTOR, mTOR and p62/SQSTM1. Furthermore, lactacystin treatment in UPS-impaired mouse model of PD caused significant loss of TH-positive neurons in the substantia nigra, and dramatically increased the number of autophagosomes in the left TH-positive neurons. Inhibition of UPS by lactacystin in dopaminergic neurons activates another protein degradation system, the ALP, which includes both the mTOR signaling pathway and Beclin 1-associated pathway.

Safer passenger car front shapes for pedestrians: A computational approach to reduce overall pedestrian injury risk in realistic impact scenarios.

PubMed

Li, Guibing; Yang, Jikuang; Simms, Ciaran

2017-03-01

Vehicle front shape has a significant influence on pedestrian injuries and the optimal design for overall pedestrian protection remains an elusive goal, especially considering the variability of vehicle-to-pedestrian accident scenarios. Therefore this study aims to develop and evaluate an efficient framework for vehicle front shape optimization for pedestrian protection accounting for the broad range of real world impact scenarios and their distributions in recent accident data. Firstly, a framework for vehicle front shape optimization for pedestrian protection was developed based on coupling of multi-body simulations and a genetic algorithm. This framework was then applied for optimizing passenger car front shape for pedestrian protection, and its predictions were evaluated using accident data and kinematic analyses. The results indicate that the optimization shows a good convergence and predictions of the optimization framework are corroborated when compared to the available accident data, and the optimization framework can distinguish 'good' and 'poor' vehicle front shapes for pedestrian safety. Thus, it is feasible and reliable to use the optimization framework for vehicle front shape optimization for reducing overall pedestrian injury risk. The results also show the importance of considering the broad range of impact scenarios in vehicle front shape optimization. A safe passenger car for overall pedestrian protection should have a wide and flat bumper (covering pedestrians' legs from the lower leg up to the shaft of the upper leg with generally even contacts), a bonnet leading edge height around 750mm, a short bonnet (<800mm) with a shallow or steep angle (either >17° or <12°) and a shallow windscreen (≤30°). Sensitivity studies based on simulations at the population level indicate that the demands for a safe passenger car front shape for head and leg protection are generally consistent, but partially conflict with pelvis protection. In particular, both head and leg injury risk increase with increasing bumper lower height and depth, and decrease with increasing bonnet leading edge height, while pelvis injury risk increases with increasing bonnet leading edge height. However, the effects of bonnet leading edge height and windscreen design on head injury risk are complex and require further analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

SDO AIA Observations of Large-Scale Coronal Disturbances in the Form of Propagating Fronts

NASA Astrophysics Data System (ADS)

Nitta, Nariaki V.; Schrijver, Carolus J.; Title, Alan M.; Liu, Wei

2013-03-01

One of the most spectacular phenomena detected by SOHO EIT was the large-scale propagating fronts associated with solar eruptions. Initially these 'EIT' waves were thought to be coronal counterparts of chromospheric Moreton waves. However, different spatial and kinematic properties of the fronts seen in H-alpha and EUV images, and far more frequent occurrences of the latter have led to various interpretations that are still actively debated by a number of researchers. A major factor for the lack of closure was the various limitation in EIT data, including the cadence that was typically every 12 minutes. Now we have significantly improved data from SDO AIA, which have revealed some very interesting phenomena associated with EIT waves. However, the studies so far conducted using AIA data have primarily dealt with single or a small number of events, where selection bias and particular observational conditions may prevent us from discovering the general and true nature of EIT waves. Although automated detection of EIT waves was promised for AIA images some time ago, it is still not actually implemented in the data pipeline. Therefore we have manually found nearly 200 examples of large-scale propagating fronts, going through movies of difference images from the AIA 193 A channel up to January 2013. We present our study of the kinematic properties of the fronts in a subset of about 150 well-observed events in relation with other phenomena that can accompany EIT waves. Our emphasis is on the relation of the fronts with the associated coronal eruptions often but not always taking the form of full-blown CMEs, utilizing STEREO data for a subset of more than 80 events that have occurred near the limb as viewed from one of the STEREO spacecraft. In these events, the availability of data from the STEREO inner coronagraph (COR1) as well as from the EUVI allows us to trace eruptions off the solar disk during the times of our propagating fronts. The representative relations between the fronts and CMEs will be discussed in terms of the evolution of EIT waves observed in different channels of AIA, which provide information of the thermal properties of the fronts. Our study will further clarify the variety of solar eruptions and their associated manifestations in the corona.

Firing up the front line.

PubMed

Katzenbach, J R; Santamaria, J A

1999-01-01

For many organizations, achieving competitive advantage means eliciting superior performance from employees on the front line--the burger flippers, hotel room cleaners, and baggage handlers whose work has an enormous effect on customers. That's no easy task. Front line workers are paid low wages, have scant hope of advancement, and--not surprisingly--often care little about the company's performance. But then how do some companies succeed in engaging the emotional energy of rank-and-file workers? A team of researchers at McKinsey & Company and the Conference Board recently explored that question and discovered that one highly effective route is demonstrated by the U.S. Marine Corps. The Marines' approach to motivation follows the "mission, values, and pride" path, which researchers say is practical and relevant for the business world. More specifically, the authors say the Marines follow five practices: they over-invest in cultivating core value; prepare every person to lead, including front line supervisors; learn when to create teams and when to create single-leader work groups; attend to all employees, not just the top half; and encourage self-discipline as a way of building pride. The authors admit there are critical differences between the Marines and most businesses. But using vivid examples from companies such as KFC and Marriott International, the authors illustrate how the Marines' approach can be translated for corporate use. Sometimes, the authors maintain, minor changes in a company's standard operating procedure can have a powerful effect on front line pride and can result in substantial payoffs in company performance.

Energy Optimal Path Planning: Integrating Coastal Ocean Modelling with Optimal Control

NASA Astrophysics Data System (ADS)

Subramani, D. N.; Haley, P. J., Jr.; Lermusiaux, P. F. J.

2016-02-01

A stochastic optimization methodology is formulated for computing energy-optimal paths from among time-optimal paths of autonomous vehicles navigating in a dynamic flow field. To set up the energy optimization, the relative vehicle speed and headings are considered to be stochastic, and new stochastic Dynamically Orthogonal (DO) level-set equations that govern their stochastic time-optimal reachability fronts are derived. Their solution provides the distribution of time-optimal reachability fronts and corresponding distribution of time-optimal paths. An optimization is then performed on the vehicle's energy-time joint distribution to select the energy-optimal paths for each arrival time, among all stochastic time-optimal paths for that arrival time. The accuracy and efficiency of the DO level-set equations for solving the governing stochastic level-set reachability fronts are quantitatively assessed, including comparisons with independent semi-analytical solutions. Energy-optimal missions are studied in wind-driven barotropic quasi-geostrophic double-gyre circulations, and in realistic data-assimilative re-analyses of multiscale coastal ocean flows. The latter re-analyses are obtained from multi-resolution 2-way nested primitive-equation simulations of tidal-to-mesoscale dynamics in the Middle Atlantic Bight and Shelbreak Front region. The effects of tidal currents, strong wind events, coastal jets, and shelfbreak fronts on the energy-optimal paths are illustrated and quantified. Results showcase the opportunities for longer-duration missions that intelligently utilize the ocean environment to save energy, rigorously integrating ocean forecasting with optimal control of autonomous vehicles.

Microgrid-Ready Solar PV - Planning for Resiliency

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

Booth, Samuel S

2017-10-17

This fact sheet provides background information on microgrids with suggested language for several up-front considerations that can be added to a solar project procurement or request for proposal (RFP) that will help ensure that PV systems are built for future microgrid connection.

Preventative Maintenance.

ERIC Educational Resources Information Center

Migliorino, James

Boards of education must be convinced that spending money up front for preventive maintenance will, in the long run, save districts' tax dollars. A good program of preventive maintenance can minimize disruption of service; reduce repair costs, energy consumption, and overtime; improve labor productivity and system equipment reliability; handle…

People, Planet and Profit: Unintended Consequences of Legacy Building Materials

EPA Science Inventory

Although an explosion of new building materials are being introduced into today's market, adequate up-front research into their chemical and physical properties as well as their potential health and environmental consequences is lacking. History has provided us with several exam...

The geological and microbiological controls on the enrichment of Se and Te in sedimentary rocks

NASA Astrophysics Data System (ADS)

Bullock, Liam; Parnell, John; Armstrong, Joseph; Boyce, Adrian; Perez, Magali

2017-04-01

Selenium (Se) and tellurium (Te) have become elements of high interest, mainly due to their photovoltaic and photoconductive properties, and can contaminate local soils and groundwater systems during mobilisation. Due to their economic and environmental significance, it is important to understand the processes that lead to Se- and Te-enrichment in sediments. The distribution of Se and Te in sedimentary environments is primarily a function of redox conditions, and may be transported and concentrated by the movement of reduced fluids through oxidised strata. Se and Te concentrations have been measured in a suite of late Neoproterozoic Gwna Group black shales (UK) and uranium red bed (roll-front) samples (USA). Due to the chemical affinity of Se and sulphur (S), variations in the S isotopic composition of pyrite have also been measured in order to provide insights into their origin. Scanning electron microscopy of pyrite in the black shales shows abundant inclusions of the lead selenide mineral clausthalite. The data for the black shale samples show marked enrichment in Te and Se relative to crustal mean and several hundreds of other samples processed through our laboratory. While Se levels in sulphidic black shales are typically below 5 ppm, the measured values of up to 116 ppm are remarkable. The Se enrichment in roll-fronts (up to 168 ppm) is restricted to a narrow band of alteration at the interface between the barren oxidised core, and the highly mineralised reduced nose of the front. Te is depleted in roll-fronts with respect to the continental crust and other geological settings and deposits. S isotope compositions for pyrite in both the black shales and roll-fronts are very light and indicate precipitation by microbial sulphate reduction, suggesting that Se was microbially sequestered. Results show that Gwna Group black shales and U.S roll-front deposits contain marked elemental enrichments (particularly Se content). In Gwna Group black shales, Se and Te were sequestered out of seawater into pyritic shales at a higher rate than into crusts. Se enrichment in roll-fronts relates to the initial mobilisation of trace elements in oxidised conditions, and later precipitation downgradient in reduced conditions. Results highlight the potential for sedimentary types of Se- and Te-bearing deposits. The enrichment of elements of high value for future technologies in sedimentary rocks deserve careful assessment for potential future resources, and should be monitored during exploration and mobilisation due to the potential contamination effects. This work forms part of the NERC-funded 'Security of Supply of Mineral Resources' project, which aims to detail the science needed to sustain the security of supply of strategic minerals in a changing environment.

Technology to promote safe mobility in the elderly.

PubMed

Nelson, Audrey; Powell-Cope, Gail; Gavin-Dreschnack, Deborah; Quigley, Pat; Bulat, Tatjana; Baptiste, Andrea S; Applegarth, Shawn; Friedman, Yvonne

2004-09-01

New technologies designed to help prevent adverse events related to the mobility of geriatric patients (ie, patient falls, bed-rail entrapment, patient handling, and wandering) are described. Technology offers the potential to eliminate or mitigate preventable adverse events that interfere with treatment, delay rehabilitation, potentiate impairment, and compromise patient safety. Unchecked, these adverse events can have a negative impact on patient health, functional status, and quality of life. It is not surprising that the elderly constitute the population at highest risk for adverse events, based on poor health, chronic conditions, long hospitalizations, and institutional care. Patient falls are a high-risk, high-volume, and high-cost adverse event. Key technologies to prevent falls and fall-related injuries include hip protectors, wheelchair/scooter safety features, intelligent walkers, fall alarms, and environmental aids. Bed-rail entrapment is a serious adverse event, which includes patients being trapped, entangled, or strangled in beds. New technologies to prevent bed-rail entrapment include new hospital bed designs, height-adjustable low beds, devices to close gaps in legacy beds, and bedside floor mats. Patients with mobility impairments necessitate physical assistance in transfers and other patient-handling tasks, which increases risk for the caregiver and the patient. Featured technologies to prevent patient handling injuries include innovations in floor-based lifts, new ceiling-mounted patient lifts, and improvements in powered standing lifts, new friction-reducing devices, and new patient transport technology. Wandering affects 39% of cognitively impaired nursing home residents and up to 70% of community-residing elderly persons with cognitive impairments. New technologies to prevent adverse events associated with wandering include door alarms and signal-transmitting devices. Nurses in geriatric settings would benefit from exposure to technologies that could improve patient and caregiver safety. To maximize the benefits of technology, it is critical that front-line nursing staff be involved in the testing and selection of devices that will be used in their practice. Further, to reap the full benefits of technology, a careful plan for implementation needs to be developed that would include integrating the new technology with existing infrastructure. Training needs to be provided for all staff who will be using the technology, and efforts to ensure competency over time is needed. A major barrier to widespread use of new technology is cost. Further research is needed to demonstrate the cost effectiveness of these devices. Results from these studies will help to build a business case, demonstrating that initial capital investments will result in cost savings, improved quality of care, and other benefits.

Predictors of presenteeism and activity impairment outside work in patients with spondyloarthritis.

PubMed

Haglund, Emma; Petersson, Ingemar F; Bremander, Ann; Bergman, Stefan

2015-06-01

To assess predictors of presenteeism (reduced productivity at work) and activity impairment outside work in patients with spondyloarthritis (SpA). Multivariate logistic regression analysis was used to study predictors of presenteeism and activity impairment in 1,253 patients with SpA based on a 2.5 year follow-up questionnaire. The Work Productivity and Activity Impairment (WPAI) questionnaire was used as main outcome. Age, gender, lifestyle factors, subgroups, disease duration, and different patient reported outcome measures (PROMs) were studied as possible predictors. The association between presenteeism and WPAI activity impairment outside work was assessed. Out of 1,253 patients, 757 reported being in work and of these 720 responded to the WPAI questionnaire. The mean (confidence interval, CI) reported presenteeism was 25% (23-27%) and mean activity impairment 33% (31-35%) (0-100%, 0 = no reduction). Significant predictors of presenteeism and activity impairment at follow-up (controlled for gender, age, spondyloarthritis subgroups and presenteeism at baseline) were presenteeism at baseline, poor quality of life, worse disease activity, decreased physical function, lower self-efficacy pain and symptom, higher scores of anxiety, depression, smoking and low education level, and for activity impairment also female sex. There was a strong association between presenteeism and activity impairment outside work (OR 16.7; 95% CI 11.6-24.3; p < 0.001). Presenteeism and activity impairment were not only predicted by presenteeism at baseline, but also by several PROMs commonly used in clinical rheumatology practice. Impaired activity outside work could indicate problems also at work suggesting why both areas need to be addressed in the clinical situation.

Dust Storm, Sahara Desert, Algeria/Niger Border, Africa

NASA Image and Video Library

1992-05-16

STS049-92-071 (13 May 1992) --- The STS-49 crew aboard the Earth-orbiting Space Shuttle Endeavour captured this Saharan dust storm on the Algeria-Niger border. The south-looking, late-afternoon view shows one of the best examples in the Shuttle photo data base of a dust storm. A series of gust fronts, caused by dissipating thunderstorms have picked up dust along the outflow boundaries. Small cumulus clouds have formed over the most vigorously ascending parts of the dust front, enhancing the visual effect of the front. The storm is moving roughly north-northwest, at right angles to the most typical path for dust storms in this part of the Sahara (shown by lines of sand on the desert surface in the foreground). Storms such as this can move out into the Atlantic, bringing dust even as far as the Americas on some occasions. A crewmember used a 70mm handheld Hasselblad camera with a 100mm lens to record the frame.

Frontal Polymerization in Microgravity: Bubble Behavior and Convection on the KC-135 Aircraft

NASA Technical Reports Server (NTRS)

Pojman, John A.; Ainsworth, William; Chekanov, Yuri; Masere, Jonathan; Volpert, Vitaly; Dumont, Thierry; Wilke, Hermann

2001-01-01

Frontal polymerization is a mode of converting monomer into polymer via a localized exothermic reaction zone that propagates through the coupling of thermal diffusion and Arrhenius reaction kinetics. Frontal polymerization was discovered in Russia by Chechilo and Enikolopyan in 1972. The macrokinetics and dynamics of frontal polymerization have been examined in detail and applications for materials synthesis considered. Large temperature and concentration gradients that occur in the front lead to large density gradients. A schematic is presented for a liquid monomer, usually a monoacrylate, being converted to a liquid (thermoplastic) polymer. The velocity can be controlled by the initiator concentration but is on the order of a cm/min. If the liquid monomer is multifunctional, then a solid (thermoset) polymer is formed. Convection can occur with all types of monomers if the front propagates up a tube. Bowden et al. studied liquid/solid systems. McCaughey et al. studied liquid polymer systems. Descending fronts in thermoplastic systems are also susceptible to the Rayleigh-Taylor instability.

Regimental Medical Officer Charles McKerrow: saving lives on the Western Front.

PubMed

Mayhew, E

2014-01-01

Ayrshire general practitioner Charles McKerrow was appointed regimental medical officer (RMO) to the 10th Battalion Northumberland Fusiliers in 1915. At this time, fundamental restructuring of the military medical service on the Western Front had two main effects: surgical capability was moved forward as close to the front as possible and specialist stretcher bearers were trained to apply emergency first aid at the place of injury and to triage casualties appropriately. The specialist stretcher bearers were the equivalent of today's combat medical technicians. The reorganisation was undertaken in a rapid, improvised 'bottom-up' manner and there are very few official records to detail the process. McKerrow and RMOs of his calibre were integral to the successful implementation and operation of this reorganisation so their personal archives are the primary sources for its history. McKerrow's record is particularly detailed and insightful on the process; he was not only an extraordinarily fine medical officer but also provided expert testimony on a period of military medical change that was enduringly successful.

Training giraffe (Giraffa camelopardalis reticulata) for front foot radiographs and hoof care.

PubMed

Dadone, Liza I; Schilz, Amy; Friedman, Susan G; Bredahl, Jason; Foxworth, Steve; Chastain, Bob

2016-05-01

For a large herd of reticulated giraffes, a mainly operant-based training program was created for front foot radiographs and hoof trims in an effort to diagnose and better manage lameness. Behaviors were shaped in a restricted contact set-up, using a positive reinforcement procedure to teach a series of mastered cued behaviors. This training was used to obtain lateral and lateral oblique front foot radiographs for the entire herd. Radiographs were diagnostic for multiple possible causes of lameness including fractures and osteitis of the distal phalangeal bone, hoof overgrowth, osteoarthritis of the distal interphalangeal joint, rotation of the distal phalangeal bone, sesamoid bone cysts, and sole foreign bodies. By training giraffe for foot radiographs and hoof trims, potential causes of lameness could be identified and better managed. Long-term, the results may help zoos identify best practices for managing and preventing lameness in giraffe. Zoo Biol. 35:228-236, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Application of dynamic displacement current for diagnostics of subnanosecond breakdowns in an inhomogeneous electric field

NASA Astrophysics Data System (ADS)

Shao, Tao; Tarasenko, Victor F.; Zhang, Cheng; Burachenko, Alexandr G.; Rybka, Dmitry V.; Kostyrya, Igor'D.; Lomaev, Mikhail I.; Baksht, Evgeni Kh.; Yan, Ping

2013-05-01

The breakdown of different air gaps at high overvoltages in an inhomogeneous electric field was investigated with a time resolution of up to 100 ps. Dynamic displacement current was used for diagnostics of ionization processes between the ionization wave front and a plane anode. It is demonstrated that during the generation of a supershort avalanche electron beam (SAEB) with amplitudes of ˜10 A and more, conductivity in the air gaps at the breakdown stage is ensured by the ionization wave, whose front propagates from the electrode of small curvature radius, and by the dynamic displacement current between the ionization wave front and the plane electrode. The amplitude of the dynamic displacement current measured by a current shunt is 100 times greater than the SAEB. It is shown that with small gaps and with a large cathode diameter, the amplitude of the dynamic displacement current during a subnanosecond rise time of applied pulse voltage can be higher than 4 kA.

Prospective Validation of the Ottawa 3DY Scale by Geriatric Emergency Management Nurses to Identify Impaired Cognition in Older Emergency Department Patients.

PubMed

Wilding, Laura; Eagles, Debra; Molnar, Frank; O'Brien, Jo-Anne; Dalziel, William B; Moors, Joy; Stiell, Ian

2016-02-01

Assessment of older emergency department (ED) patients with cognitive impairment is challenging because few tools exist that can be quickly administered by front-line practitioners. Our objective is to validate the Ottawa 3DY Scale, a 4-question screening tool for cognitive impairment, in older ED patients and compare its performance with that of the Animal Fluency Test. We conducted a prospective cohort study in 2 EDs and enrolled a convenience sample of patients aged 75 years or older with no history of cognitive impairment. Eligible patients were assessed by geriatric emergency management nurses who administered the Mini-Mental State Examination, ordered with the Ottawa 3DY Scale questions first, followed by the Animal Fluency Test. Mini-Mental State Examination score less than 25 was our criterion standard for cognitive impairment. Study patients (N=238) had a mean age of 81.9 years and were 60.1% women, and 26.5% were admitted to the hospital. The Ottawa 3DY Scale and Mini-Mental State Examination were in agreement for 75.6% of cases, with a sensitivity of 93.8% (95% confidence interval [CI] 77.8% to 98.9%) and specificity of 72.8% (95% CI 66.1% to 78.7%). The Animal Fluency Test score less than 15 and Mini-Mental State Examination score were in agreement for 46.2% of cases, with sensitivity 90.6% (95% CI 73.8% to 97.5%) and specificity 39.3% (95% CI 32.7% to 46.4%). Both the Ottawa 3DY Scale and the Animal Fluency Test demonstrated excellent sensitivity versus the Mini-Mental State Examination; however, the Animal Fluency Test exhibited poor specificity. The Ottawa 3DY Scale is an effective tool to screen for cognitive impairment in older ED patients, and its use may facilitate improved care in this vulnerable population. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Risk of long term renal impairment and duration of follow up recommended for Henoch-Schönlein purpura with normal or minimal urinary findings: a systematic review

PubMed Central

Narchi, H

2005-01-01

Background: The duration of follow up to assess the risk of long term renal impairment in Henoch-Schönlein purpura (HSP) without nephritic or nephrotic syndrome or renal failure on diagnosis remains undetermined. Aims: To undertake a systematic review of the literature to assess whether the risk of long term renal impairment without renal involvement on diagnosis could be estimated and to determine the time period when renal involvement is very unlikely after the diagnosis of HSP. Methods: Search of studies of unselected children with HSP, and available information on urinary findings, renal involvement, and long term renal function follow up. Studies of selected children with HSP nephropathy at diagnosis were excluded. Results: Twelve studies of 1133 children were reviewed. The follow up period ranged from 6 weeks to 36 years. Proteinuria and/or haematuria, which occurred in 34.2%, of which only one fifth were in association with nephritic or nephrotic syndrome, developed in 85% of cases within 4 weeks of the diagnosis of HSP, in 91% within 6 weeks, and in 97% within 6 months. Permanent renal impairment never developed after normal urinalysis; it occurred in 1.6% of those with isolated urinary abnormalities, and in 19.5% of those who developed nephritic or nephrotic syndrome. Conclusion: No long term renal impairment occurred after normal urinalysis. Even if urinalysis is normal at presentation, the testing should be continued for six months. There is no need to follow up after the first six months those whose urinalysis remains normal. PMID:15871983

Characteristics of pellet injuries to the orbit.

PubMed

Kükner, A Sahap; Yilmaz, Turgut; Celebi, Serdal; Karslioğlu, Safak; Alagöz, Gürsoy; Serin, Didem; Acar, M Akif; Ozveren, M Faik

2009-01-01

To investigate the features of orbital injuries by pellets fired from the front. Retrospective, 4 cases of pellet injuries. Five orbits of 4 patients who sustained pellet injuries received from the front were reviewed retrospectively. The course of injury and results were assessed. Radiological examinations were reviewed. The patients were evaluated between December 1996 and June 2004. Five orbits of 4 patients sustained injuries caused by pellets fired from an anterior direction. The globe in the injured orbit was intact in 2 cases. Severe loss of vision was also present in these 2 globes due to optic nerve involvement. Final visual acuity was down to no light perception in 4 eyes and limited to light perception in 1 eye. The prognosis of orbital pellet injuries is, unfortunately, poor. A pellet passing through the floor of the orbit often causes double perforation of the globe and, once in the orbital aperture, it travels towards the apex as a result of the conical shape of the orbit and lodges in the optic canal or its entrance, severely damaging the optic nerve. Surgery or other treatments are usually unsuccessful. Even if the globe is intact, vision is usually severely impaired. Copyright 2009 S. Karger AG, Basel.

Association of disease-specific causes of visual impairment and 10-year mortality amongst Indigenous Australians: the Central Australian Ocular Health Study.

PubMed

Estevez, José; Kaidonis, Georgia; Henderson, Tim; Craig, Jamie E; Landers, John

2018-01-01

Visual impairment significantly impairs the length and quality of life, but little is known of its impact in Indigenous Australians. To investigate the association of disease-specific causes of visual impairment with all-cause mortality. A retrospective cohort analysis. A total of 1347 Indigenous Australians aged over 40 years. Participants visiting remote medical clinics underwent clinical examinations including visual acuity, subjective refraction and slit-lamp examination of the anterior and posterior segments. The major ocular cause of visual impairment was determined. Patients were assessed periodically in these remote clinics for the succeeding 10 years after recruitment. Mortality rates were obtained from relevant departments. All-cause 10-year mortality and its association with disease-specific causes of visual impairment. The all-cause mortality rate for the entire cohort was 29.3% at the 10-year completion of follow-up. Of those with visual impairment, the overall mortality rate was 44.9%. The mortality rates differed for those with visual impairment due to cataract (59.8%), diabetic retinopathy (48.4%), trachoma (46.6%), 'other' (36.2%) and refractive error (33.4%) (P < 0.0001). Only those with visual impairment from diabetic retinopathy were any more likely to die during the 10 years of follow-up when compared with those without visual impairment (HR 1.70; 95% CI, 1.00-2.87; P = 0.049). Visual impairment was associated with all-cause mortality in a cohort of Indigenous Australians. However, diabetic retinopathy was the only ocular disease that significantly increased the risk of mortality. Visual impairment secondary to diabetic retinopathy may be an important predictor of mortality. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

STS-106 Orbit 1 Flight Team with Phil Engelhauf in WFCR

NASA Image and Video Library

2000-09-15

JSC2000-06253 (15 Sept. 2000) --- Flight director Phil Engelauf, front center, and the other fifty-odd flight controllers making up the STS-106 Orbit 1 team, pose for their group portrait in the Flight Control Room of Houston's Mission Control Center.

Absence of splash singularities for surface quasi-geostrophic sharp fronts and the Muskat problem.

PubMed

Gancedo, Francisco; Strain, Robert M

2014-01-14

In this paper, for both the sharp front surface quasi-geostrophic equation and the Muskat problem, we rule out the "splash singularity" blow-up scenario; in other words, we prove that the contours evolving from either of these systems cannot intersect at a single point while the free boundary remains smooth. Splash singularities have been shown to hold for the free boundary incompressible Euler equation in the form of the water waves contour evolution problem. Our result confirms the numerical simulations in earlier work, in which it was shown that the curvature blows up because the contours collapse at a point. Here, we prove that maintaining control of the curvature will remove the possibility of pointwise interphase collapse. Another conclusion that we provide is a better understanding of earlier work in which squirt singularities are ruled out; in this case, a positive volume of fluid between the contours cannot be ejected in finite time.

Absence of splash singularities for surface quasi-geostrophic sharp fronts and the Muskat problem

PubMed Central

Gancedo, Francisco; Strain, Robert M.

2014-01-01

In this paper, for both the sharp front surface quasi-geostrophic equation and the Muskat problem, we rule out the “splash singularity” blow-up scenario; in other words, we prove that the contours evolving from either of these systems cannot intersect at a single point while the free boundary remains smooth. Splash singularities have been shown to hold for the free boundary incompressible Euler equation in the form of the water waves contour evolution problem. Our result confirms the numerical simulations in earlier work, in which it was shown that the curvature blows up because the contours collapse at a point. Here, we prove that maintaining control of the curvature will remove the possibility of pointwise interphase collapse. Another conclusion that we provide is a better understanding of earlier work in which squirt singularities are ruled out; in this case, a positive volume of fluid between the contours cannot be ejected in finite time. PMID:24347645

Experimental evidence of a bubble-merger regime for the Rayleigh-Taylor Instability at the ablation front

NASA Astrophysics Data System (ADS)

Casner, A.; Liberatore, S.; Masse, L.; Martinez, D.; Haan, S. W.; Kane, J.; Moore, A. S.; Seugling, R.; Farrell, M.; Giraldez, E.; Nikroo, A.; Smalyuk, V. A.; Remington, B. A.

2016-05-01

Under the Discovery Science program, the longer pulses and higher laser energies provided by the National Ignition Facility (NIF) have been harnessed to study, first time in indirect-drive, the highly nonlinear stage of the Rayleigh-Taylor Instability (RTI) at the ablation front. A planar plastic package with pre-imposed two-dimensional broadband modulations is accelerated for up to 12 ns by the x-ray drive of a gas-filled gold radiation cavity with a radiative temperature plateau at 175 eV. This extended tailored drive allows a distance traveled in excess of 1 mm for a 130 μm thick foil, a factor 3x larger than previously achieved on other laser facilities. As a consequence, we have measured the ablative RTI in transition from the weakly nonlinear stage up to the deep nonlinear stage for various initial conditions. A bubble merger regime has been observed and the ablative stabilization strength varied by changing the plastic dopant from iodine to germanium.

The Canonical Robot Command Language (CRCL).

PubMed

Proctor, Frederick M; Balakirsky, Stephen B; Kootbally, Zeid; Kramer, Thomas R; Schlenoff, Craig I; Shackleford, William P

2016-01-01

Industrial robots can perform motion with sub-millimeter repeatability when programmed using the teach-and-playback method. While effective, this method requires significant up-front time, tying up the robot and a person during the teaching phase. Off-line programming can be used to generate robot programs, but the accuracy of this method is poor unless supplemented with good calibration to remove systematic errors, feed-forward models to anticipate robot response to loads, and sensing to compensate for unmodeled errors. These increase the complexity and up-front cost of the system, but the payback in the reduction of recurring teach programming time can be worth the effort. This payback especially benefits small-batch, short-turnaround applications typical of small-to-medium enterprises, who need the agility afforded by off-line application development to be competitive against low-cost manual labor. To fully benefit from this agile application tasking model, a common representation of tasks should be used that is understood by all of the resources required for the job: robots, tooling, sensors, and people. This paper describes an information model, the Canonical Robot Command Language (CRCL), which provides a high-level description of robot tasks and associated control and status information.

The Canonical Robot Command Language (CRCL)

PubMed Central

Proctor, Frederick M.; Balakirsky, Stephen B.; Kootbally, Zeid; Kramer, Thomas R.; Schlenoff, Craig I.; Shackleford, William P.

2017-01-01

Industrial robots can perform motion with sub-millimeter repeatability when programmed using the teach-and-playback method. While effective, this method requires significant up-front time, tying up the robot and a person during the teaching phase. Off-line programming can be used to generate robot programs, but the accuracy of this method is poor unless supplemented with good calibration to remove systematic errors, feed-forward models to anticipate robot response to loads, and sensing to compensate for unmodeled errors. These increase the complexity and up-front cost of the system, but the payback in the reduction of recurring teach programming time can be worth the effort. This payback especially benefits small-batch, short-turnaround applications typical of small-to-medium enterprises, who need the agility afforded by off-line application development to be competitive against low-cost manual labor. To fully benefit from this agile application tasking model, a common representation of tasks should be used that is understood by all of the resources required for the job: robots, tooling, sensors, and people. This paper describes an information model, the Canonical Robot Command Language (CRCL), which provides a high-level description of robot tasks and associated control and status information. PMID:28529393

Astronaut Gene Cernan poses in front of Gemini Mission Simulator

NASA Image and Video Library

1966-08-09

S66-32698 (17 June 1966) --- Astronaut Eugene A. Cernan discusses his Gemini-9A extravehicular activity before a gathering of news media representatives in the MSC auditorium. In the background is an Astronaut Maneuvering Unit (AMU) mock-up mounted in a mock-up of a Gemini spacecraft adapter equipment section. Astronauts Cernan and Thomas P. Stafford completed their three-day mission in space on June 6, 1966. Photo credit: NASA

An RFID tag system-on-chip with wireless ECG monitoring for intelligent healthcare systems.

PubMed

Wang, Cheng-Pin; Lee, Shuenn-Yuh; Lai, Wei-Chih

2013-01-01

This paper presents a low-power wireless ECG acquisition system-on-chip (SoC), including an RF front-end circuit, a power unit, an analog front-end circuit, and a digital circuitry. The proposed RF front-end circuit can provide the amplitude shift keying demodulation and distance to digital conversion to accurately receive the data from the reader. The received data will wake up the power unit to provide the required supply voltages of analog front-end (AFE) and digital circuitry. The AFE, including a pre-amplifier, an analog filter, a post-amplifier, and an analog-to-digital converter, is used for the ECG acquisition. Moreover, the EPC Class I Gen 2 UHF standard is employed in the digital circuitry for the handshaking of communication and the control of the system. The proposed SoC has been implemented in 0.18-µm standard CMOS process and the measured results reveal the communication is compatible to the RFID protocol. The average power consumption for the operating chip is 12 µW. Using a Sony PR44 battery to the supply power (605mAh@1.4V), the RFID tag SoC operates continuously for about 50,000 hours (>5 years), which is appropriate for wireless wearable ECG monitoring systems.

Effect of saline waste solution infiltration rates on uranium retention and spatial distribution in Hanford sediments.

PubMed

Wan, Jiamin; Tokunaga, Tetsu K; Kim, Yongman; Wang, Zheming; Lanzirotti, Antonio; Saiz, Eduardo; Serne, R Jeffrey

2008-03-15

The accidental overfilling of waste liquid from tank BX-102 at the Hanford Site in 1951 put about 10 t of U(VI) into the vadose zone. In order to understand the dominant geochemical reactions and transport processes that occurred during the initial infiltration and to help understand current spatial distribution, we simulated the waste liquid spilling event in laboratory sediment columns using synthesized metal waste solution. We found that, as the plume propagated through sediments, pH decreased greatly (as much as 4 units) at the moving plume front. Infiltration flow rates strongly affect U behavior. Slower flow rates resulted in higher sediment-associated U concentrations, and higher flow rates (> or =5 cm/day) permitted practically unretarded U transport. Therefore, given the very high Ksat of most of Hanford formation, the low permeability zones within the sediment could have been most important in retaining high concentrations of U during initial release into the vadose zone. Massive amount of colloids, including U-colloids, formed at the plume fronts. Total U concentrations (aqueous and colloid) within plume fronts exceeded the source concentration by up to 5-fold. Uranium colloid formation and accumulation at the neutralized plume front could be one mechanism responsible for highly heterogeneous U distribution observed in the contaminated Hanford vadose zone.

HUBBLE SPACE TELESCOPE AND HI IMAGING OF STRONG RAM PRESSURE STRIPPING IN THE COMA SPIRAL NGC 4921: DENSE CLOUD DECOUPLING AND EVIDENCE FOR MAGNETIC BINDING IN THE ISM

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

Kenney, Jeffrey D. P.; Abramson, Anne; Bravo-Alfaro, Hector, E-mail: jeff.kenney@yale.edu

Remarkable dust extinction features in the deep Hubble Space Telescope (HST) V and I images of the face-on Coma cluster spiral galaxy NGC 4921 show in unprecedented ways how ram pressure strips the ISM from the disk of a spiral galaxy. New VLA HI maps show a truncated and highly asymmetric HI disk with a compressed HI distribution in the NW, providing evidence for ram pressure acting from the NW. Where the HI distribution is truncated in the NW region, HST images show a well-defined, continuous front of dust that extends over 90° and 20 kpc. This dust front separatesmore » the dusty from dust-free regions of the galaxy, and we interpret it as galaxy ISM swept up near the leading side of the ICM–ISM interaction. We identify and characterize 100 pc–1 kpc scale substructure within this dust front caused by ram pressure, including head–tail filaments, C-shaped filaments, and long smooth dust fronts. The morphology of these features strongly suggests that dense gas clouds partially decouple from surrounding lower density gas during stripping, but decoupling is inhibited, possibly by magnetic fields that link and bind distant parts of the ISM.« less

Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later

PubMed Central

Fagan, Anne M.; Grant, Elizabeth A.; Hassenstab, Jason; Moulder, Krista L.; Maue Dreyfus, Denise; Sutphen, Courtney L.; Benzinger, Tammie L.S.; Mintun, Mark A.; Holtzman, David M.; Morris, John C.

2013-01-01

Objectives: We compared the ability of molecular biomarkers for Alzheimer disease (AD), including amyloid imaging and CSF biomarkers (Aβ42, tau, ptau181, tau/Aβ42, ptau181/Aβ42), to predict time to incident cognitive impairment among cognitively normal adults aged 45 to 88 years and followed for up to 7.5 years. Methods: Longitudinal data from Knight Alzheimer's Disease Research Center participants (N = 201) followed for a mean of 3.70 years (SD = 1.46 years) were used. Participants with amyloid imaging and CSF collection within 1 year of a clinical assessment indicating normal cognition were eligible. Cox proportional hazards models tested whether the individual biomarkers were related to time to incident cognitive impairment. “Expanded” models were developed using the biomarkers and participant demographic variables. The predictive values of the models were compared. Results: Abnormal levels of all biomarkers were associated with faster time to cognitive impairment, and some participants with abnormal biomarker levels remained cognitively normal for up to 6.6 years. No differences in predictive value were found between the individual biomarkers (p > 0.074), nor did we find differences between the expanded biomarker models (p > 0.312). Each expanded model better predicted incident cognitive impairment than the model containing the biomarker alone (p < 0.005). Conclusions: Our results indicate that all AD biomarkers studied here predicted incident cognitive impairment, and support the hypothesis that biomarkers signal underlying AD pathology at least several years before the appearance of dementia symptoms. PMID:23576620

Nephrogenic Systemic Fibrosis Risk After Liver Magnetic Resonance Imaging With Gadoxetate Disodium in Patients With Moderate to Severe Renal Impairment

PubMed Central

Lauenstein, Thomas; Ramirez-Garrido, Francisco; Kim, Young Hoon; Rha, Sung Eun; Ricke, Jens; Phongkitkarun, Sith; Boettcher, Joachim; Gupta, Rajan T.; Korpraphong, Pornpim; Tanomkiat, Wiwatana; Furtner, Julia; Liu, Peter S.; Henry, Maren; Endrikat, Jan

2015-01-01

Objective The objective of this study was to assess the risk of gadoxetate disodium in liver imaging for the development of nephrogenic systemic fibrosis (NSF) in patients with moderate to severe renal impairment. Materials and Methods We performed a prospective, multicenter, nonrandomized, open-label phase 4 study in 35 centers from May 2009 to July 2013. The study population consisted of patients with moderate to severe renal impairment scheduled for liver imaging with gadoxetate disodium. All patients received a single intravenous bolus injection of 0.025-mmol/kg body weight of liver-specific gadoxetate disodium. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. Results A total of 357 patients were included, with 85 patients with severe and 193 patients with moderate renal impairment, which were the clinically most relevant groups. The mean time period from diagnosis of renal disease to liver magnetic resonance imaging (MRI) was 1.53 and 5.46 years in the moderate and severe renal impairment cohort, respectively. Overall, 101 patients (28%) underwent additional contrast-enhanced MRI with other gadolinium-based MRI contrast agents within 12 months before the start of the study or in the follow-up. No patient developed symptoms conclusive of NSF within the 2-year follow-up. Conclusions Gadoxetate disodium in patients with moderate to severe renal impairment did not raise any clinically significant safety concern. No NSF cases were observed. PMID:25756684

Spatial Coding of Individuals with Visual Impairments

ERIC Educational Resources Information Center

Papadopoulos, Konstantinos; Koustriava, Eleni; Kartasidou, Lefkothea

2012-01-01

The aim of this study is to examine the ability of children and adolescents with visual impairments to code and represent near space. Moreover, it examines the impact of the strategies they use and individual differences in their performance. A total of 30 individuals with visual impairments up to the age of 18 were given eight different object…

A Review of Research on the Literacy of Students with Visual Impairments and Additional Disabilities

ERIC Educational Resources Information Center

Parker, Amy T.; Pogrund, Rona L.

2009-01-01

Research on the development of literacy in children with visual impairments and additional disabilities is minimal even though these children make up approximately 65% of the population of children with visual impairments. This article reports on emerging themes that were explored after a review of the literature revealed nine literacy studies…

The Transantarctic Mountains of southern Victoria Land: The application of Apatite fission track analysis to a rift shoulder uplift

NASA Astrophysics Data System (ADS)

Fitzgerald, Paul G.

1992-06-01

A fission track study of the Transantarctic Mountains (TAM) in the Granite Harbour and Wilson Piedmont Glacier areas of southern Victoria Land reveals information on the timing of uplift, the amount of uplift and erosion, and the structure of the mountains, especially the onshore Transantarctic Mountain Front (TAM Front), which represents the boundary between East and West Antarctica. Apatite ages are < 175 Ma and represent a thermal regime established after heating accompanying Jurassic magmatism. An apatite age profile from Mount England records a break in slope indicating uplift began at ˜55 Ma. Horizontal sampling traverses, plus fieldwork, delineate the structure of the TAM Front as a zone of north-south striking, steeply dipping normal faults, with displacements, dominantly down to the east, of 40-1000 m. The overall structure of the mountains in the area studied can be envisaged as a large tilt block or flexure. Its westerly limb dips gently under the ice cap, compared to its faulted eastern edge, the TAM Front. The bounding structure to the south is the Ferrar fault and to the north is a graben through which the Mackay Glacier drains the polar plateau. The edge of the flexure, or axis of maximum uplift, lies at Mount Termination, ˜30 km west of the McMurdo Sound coast. There has been ˜6 km of uplift since the early Cenozoic and 4.5-5 km of erosion along this axis. The amount of uplift decreases to the west at the same rate as the decrease in dip of the Kukri Peneplain, but the amount of erosion decreases more quickly as indicated by the increasing height of the mountains to the west. The axis of maximum uplift is traced north to Granite Harbour. The axis does not parallel the coast but has a more northerly trend. North-south striking longitudinal faults that delineate the structure of the TAM Front lie at an acute angle to the axis, indicating a dextral component to the dominantly east-west extension in the Ross Embayment. Architecture of the TAM typifies the features of an upper plate passive mountain range, whereas the Ross Embayment has the characteristics of a lower plate. The TAM Front represents an upper plate breakaway zone. Transfer faults may exist up major outlet glaciers that cut the TAM. The inflection point in the coastline at the southern end of McMurdo Sound may be due to the presence of a major transfer fault up or near the Skelton Glacier.

Forging Ahead

NASA Technical Reports Server (NTRS)

2004-01-01

This animation shows the front view from the Mars Exploration Rover Opportunity as it drives north towards the eastern edge of the rock outcropping near its landing site at Meridiani Planum, Mars. The movie strings together images taken over the past six martian days, or sols, of its journey, beginning with a 1 meter (3 feet) stroll away from the lander on sol 7. On the 12th sol, Opportunity drove another 3 1/2 meters (11 feet), and then, one sol later, another 1 1/2 meters (5 feet). On its way, the rover twisted and turned in a test of its driving capabilities. This movie is made up of fish-eye images taken by the rover's front hazard-identification camera.

Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders.

PubMed

Slack, James; Albert, Michael H; Balashov, Dmitry; Belohradsky, Bernd H; Bertaina, Alice; Bleesing, Jack; Booth, Claire; Buechner, Jochen; Buckley, Rebecca H; Ouachée-Chardin, Marie; Deripapa, Elena; Drabko, Katarzyna; Eapen, Mary; Feuchtinger, Tobias; Finocchi, Andrea; Gaspar, H Bobby; Ghosh, Sujal; Gillio, Alfred; Gonzalez-Granado, Luis I; Grunebaum, Eyal; Güngör, Tayfun; Heilmann, Carsten; Helminen, Merja; Higuchi, Kohei; Imai, Kohsuke; Kalwak, Krzysztof; Kanazawa, Nubuo; Karasu, Gülsün; Kucuk, Zeynep Y; Laberko, Alexandra; Lange, Andrzej; Mahlaoui, Nizar; Meisel, Roland; Moshous, D; Muramatsu, Hideki; Parikh, Suhag; Pasic, Srdjan; Schmid, Irene; Schuetz, Catharina; Schulz, Ansgar; Schultz, Kirk R; Shaw, Peter J; Slatter, Mary A; Sykora, Karl-Walter; Tamura, Shinobu; Taskinen, Mervi; Wawer, Angela; Wolska-Kuśnierz, Beata; Cowan, Morton J; Fischer, Alain; Gennery, Andrew R

2018-01-01

Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT). Data from 38 centers worldwide, including indication, donor, conditioning regimen, graft-versus-host disease, and outcome, were analyzed. Conditioning was classified as myeloablative conditioning (MAC) if it contained radiotherapy or alkylators and reduced-intensity conditioning (RIC) if no alkylators and/or 150 mg/m 2 fludarabine or less and 40 mg/kg cyclophosphamide or less were used. Fifty-five new, 14 updated, and 18 previously published patients were analyzed. Median age at HCT was 48 months (range, 1.5-552 months). Twenty-nine patients underwent transplantation for infection, 21 had malignancy, 13 had bone marrow failure, 13 received pre-emptive transplantation, 5 had multiple indications, and 6 had no information. Twenty-two received MAC, 59 received RIC, and 4 were infused; information was unavailable for 2 patients. Seventy-three of 77 patients with DNA ligase IV deficiency, Cernunnos-XLF deficiency, or Nijmegen breakage syndrome received conditioning. Survival was 53 (69%) of 77 and was worse for those receiving MAC than for those receiving RIC (P = .006). Most deaths occurred early after transplantation, suggesting poor tolerance of conditioning. Survival in patients with AT was 25%. Forty-one (49%) of 83 patients experienced acute GvHD, which was less frequent in those receiving RIC compared with those receiving MAC (26/56 [46%] vs 12/21 [57%], P = .45). Median follow-up was 35 months (range, 2-168 months). No secondary malignancies were reported during 15 years of follow-up. Growth and developmental delay remained after HCT; immune-mediated complications resolved. RIC HCT resolves DNA repair disorder-associated immunodeficiency. Long-term follow-up is required for secondary malignancy surveillance. Routine HCT for AT is not recommended. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Hearing Impairment, Mild Cognitive Impairment, and Dementia: A Meta-Analysis of Cohort Studies.

PubMed

Wei, Jingkai; Hu, Yirui; Zhang, Li; Hao, Qiang; Yang, Ruowei; Lu, Haidong; Zhang, Xuan; Chandrasekar, Eeshwar K

2017-01-01

To estimate a pooled association between hearing impairment and risk of mild cognitive impairment and dementia. PubMed, Embase, and Web of Science were searched for prospective cohort studies that examined the association between hearing impairment and risk of mild cognitive impairment and/or dementia. Random-effects models were fitted to estimate the summary risk ratios (RRs) and 95% confidence interval (CIs), which represents the pooled association between hearing impairment with risk of mild cognitive impairment and dementia, compared to subjects free of hearing impairment. Four studies on hearing impairment with mild cognitive impairment and 7 studies on hearing impairment with dementia were included in the meta-analysis. A total of 15,521 subjects were studied with follow-up periods between 2 and 16.8 years. Hearing impairment was associated with a greater risk of mild cognitive impairment (RR = 1.30, 95% CI: 1.12, 1.51) and dementia (RR = 2.39, 95% CI: 1.58, 3.61). The meta-analysis showed that hearing impairment is associated with a higher risk of mild cognitive impairment and dementia among older adults.

A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study.

PubMed

Sonoda, Nao; Morimoto, Akiko; Tatsumi, Yukako; Asayama, Kei; Ohkubo, Takayoshi; Izawa, Satoshi; Ohno, Yuko

2018-05-01

To assess the impact of diabetes on restrictive and obstructive lung function impairment. This 5-year prospective study included 7524 participants aged 40-69years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥7.0mmol/l (126mg/dl), HbA1c≥6.5% (48mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) <80% predicted and forced expiratory volume in 1s (FEV 1 ) to FVC ratio (FEV 1 /FVC) <0.70, respectively. Participants were screened until they developed restrictive or obstructive lung function impairment or until March 2014. During the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04-2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72-1.21)]. Diabetes was associated with restrictive lung function impairment but not obstructive lung function impairment. Copyright © 2017. Published by Elsevier Inc.

Progression of impairment in adolescents with attention-deficit/hyperactivity disorder through the transition out of high school: Contributions of parent involvement and college attendance.

PubMed

Howard, Andrea L; Strickland, Noelle J; Murray, Desiree W; Tamm, Leanne; Swanson, James M; Hinshaw, Stephen P; Arnold, L Eugene; Molina, Brooke S G

2016-02-01

Long-term, prospective follow-up studies of children diagnosed with attention-deficit/hyperactivity disorder (ADHD) show that symptoms tend to decline with age, but impairments in daily life functioning often persist into adulthood. We examined the developmental progression of impairments before and after the transition out of high school in relation to parent involvement during adolescence, parent support during adulthood, and college attendance, using 8 waves of data from the prospective 16-year follow-up of the Multimodal Treatment of ADHD (MTA) study. Participants were 548 proband children diagnosed with Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV; American Psychiatric Association, 2000) ADHD Combined Type and 258 age- and sex-matched comparison children (Local Normative Comparison Group; LNCG) randomly sampled from probands' schools. Impairment was assessed consistently by parent report from childhood through adulthood. Results showed that impairment worsens over time both before and after the transition to adulthood for those with ADHD histories, in contrast to non-ADHD peers, whose impairments remained stably low over time. However, impairment stabilized after leaving high school for young adults with ADHD histories who attended college. Involved parenting in adolescence was associated with less impairment overall. Attending college was associated with a stable post-high school trajectory of impairment regardless of parents' involvement during adolescence, but young adults with histories of involved parenting and who attended college were the least impaired overall. (c) 2016 APA, all rights reserved).

Assessment of a directional microphone array for hearing-impaired listeners.

PubMed

Soede, W; Bilsen, F A; Berkhout, A J

1993-08-01

Hearing-impaired listeners often have great difficulty understanding speech in surroundings with background noise or reverberation. Based on array techniques, two microphone prototypes (broadside and endfire) have been developed with strongly directional characteristics [Soede et al., "Development of a new directional hearing instrument based on array technology," J. Acoust. Soc. Am. 94, 785-798 (1993)]. Physical measurements show that the arrays attenuate reverberant sound by 6 dB (free-field) and can improve the signal-to-noise ratio by 7 dB in a diffuse noise field (measured with a KEMAR manikin). For the clinical assessment of these microphones an experimental setup was made in a sound-insulated listening room with one loudspeaker in front of the listener simulating the partner in a discussion and eight loudspeakers placed on the edges of a cube producing a diffuse background noise. The hearing-impaired subject wearing his own (familiar) hearing aid is placed in the center of the cube. The speech-reception threshold in noise for simple Dutch sentences was determined with a normal single omnidirectional microphone and with one of the microphone arrays. The results of monaural listening tests with hearing impaired subjects show that in comparison with an omnidirectional hearing-aid microphone the broadside and endfire microphone array gives a mean improvement of the speech reception threshold in noise of 7.0 dB (26 subjects) and 6.8 dB (27 subjects), respectively. Binaural listening with two endfire microphone arrays gives a binaural improvement which is comparable to the binaural improvement obtained by listening with two normal ears or two conventional hearing aids.

48 CFR 970.5215-4 - Cost reduction.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Cost reduction. 970.5215-4 Section 970.5215-4 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY SUPPLEMENTARY.... Development cost is the Contractor cost of up-front planning, engineering, prototyping, and testing of a...

24 CFR 203.280 - One-time or Up-front MIP.

Code of Federal Regulations, 2010 CFR

2010-04-01

... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES SINGLE FAMILY MORTGAGE INSURANCE Contract Rights and Obligations Mortgage Insurance Premiums-One-Time... endorsement of the mortgage for insurance, pay to the Commissioner for the account of the mortgagor, in a...

24 CFR 203.280 - One-time or Up-front MIP.

Code of Federal Regulations, 2011 CFR

2011-04-01

... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES SINGLE FAMILY MORTGAGE INSURANCE Contract Rights and Obligations Mortgage Insurance Premiums-One-Time... endorsement of the mortgage for insurance, pay to the Commissioner for the account of the mortgagor, in a...

Adjuvant therapeutic vaccination in patients with non-small cell lung cancer made lymphopenic and reconstituted with autologous PBMC: first clinical experience and evidence of an immune response

PubMed Central

Rüttinger, Dominik; van den Engel, Natasja K; Winter, Hauke; Schlemmer, Marcus; Pohla, Heike; Grützner, Stefanie; Wagner, Beate; Schendel, Dolores J; Fox, Bernard A; Jauch, K-W; Hatz, Rudolf A

2007-01-01

Background Given the considerable toxicity and modest benefit of adjuvant chemotherapy for non-small cell lung cancer (NSCLC), there is clearly a need for new treatment modalities in the adjuvant setting. Active specific immunotherapy may represent such an option. However, clinical responses have been rare so far. Manipulating the host by inducing lymphopenia before vaccination resulted in a magnification of the immune response in the preclinical setting. To evaluate feasibility and safety of an irradiated, autologous tumor cell vaccine given following induction of lymphopenia by chemotherapy and reinfusion of autologous peripheral blood mononuclear cells (PBMC), we are currently conducting a pilot-phase I clinical trial in patients with NSCLC following surgical resection. This paper reports on the first clinical experience and evidence of an immune response in patients suffering from NSCLC. Methods NSCLC patients stages I-IIIA are recruited. Vaccines are generated from their resected lung specimens. Patients undergo leukapheresis to harvest their PBMC prior to or following the surgical procedure. Furthermore, patients receive preparative chemotherapy (cyclophosphamide 350 mg/m2 and fludarabine 20 mg/m2 on 3 consecutive days) for induction of lymphopenia followed by reconstitution with their autologous PBMC. Vaccines are administered intradermally on day 1 following reconstitution and every two weeks for a total of up to five vaccinations. Granulocyte-macrophage-colony-stimulating-factor (GM-CSF) is given continuously (at a rate of 50 μg/24 h) at the site of vaccination via minipump for six consecutive days after each vaccination. Results To date, vaccines were successfully manufactured for 4 of 4 patients. The most common toxicities were local injection-site reactions and mild constitutional symptoms. Immune responses to chemotherapy, reconstitution and vaccination are measured by vaccine site and delayed type hypersensitivity (DTH) skin reactions. One patient developed positive DTH skin tests so far. Immunohistochemical assessment of punch biopsies taken at the local vaccine site reaction revealed a dense lymphocyte infiltrate. Further immunohistochemical differentiation showed that CD1a+ cells had been attracted to the vaccine site as well as predominantly CD4+ lymphocytes. The 3-day combination chemotherapy consisting of cyclophosphamide and fludarabine induced a profound lymphopenia in all patients. Sequential FACS analysis revealed that different T cell subsets (CD4, CD8, CD4CD25) as well as granulocytes, B cells and NK cells were significantly reduced. Here, we report on clinical safety and feasibility of this vaccination approach during lymphoid recovery and demonstrate a patient example. Conclusion Thus far, all vaccines were well tolerated. The overall trial design seems safe and feasible. Vaccine site reactions associated with infusion of GM-CSF via mini-pump are consistent with the postulated mechanism of action. More detailed immune-monitoring is required to evaluate a potential systemic immune response. Further studies to exploit homeostasis-driven T cell proliferation for the induction of a specific anti-tumor immune response in this clinical setting are warranted. PMID:17868452

Reductions in employee productivity impairment observed after implementation of web-based worksite health promotion programs.

PubMed

Silberman, Jordan; Schwartz, Steven; Giuseffi, Danielle L; Wang, Chun; Nevedal, Dana; Bedrosian, Richard

2011-12-01

To assess changes in employee productivity impairment observed after the implementation of several Web-based health promotion programs. Health risk assessments and self-report measures of productivity impairment were administered on-line to more than 43,000 participants of Web-based health promotion programs. Reductions in productivity impairment were observed after 1 month of program utilization. Productivity impairment at 90- and 180-day follow-ups also decreased relative to baseline. Improvements in employee health were associated with reductions in employee productivity impairment. The use of Web-based health promotion programs was associated with reductions in productivity impairment and improvements in employee health. After the implementation of Web-based health promotion programs, reductions in productivity impairment may be observed before reductions in direct health care costs.

Shocking features in the merging galaxy cluster RXJ0334.2-0111

NASA Astrophysics Data System (ADS)

Dasadia, Sarthak; Sun, Ming; Morandi, Andrea; Sarazin, Craig; Clarke, Tracy; Nulsen, Paul; Massaro, Francesco; Roediger, Elke; Harris, Dan; Forman, Bill

2016-05-01

We present a 66 ks Chandra X-ray observation of the galaxy cluster RXJ0334.2-0111. This deep observation revealed a unique bow shock system associated with a wide angle tail (WAT) radio galaxy and several intriguing substructures. The temperature across the bow shock jumps by a factor of ˜1.5 (from 4.1 to 6.2 keV), and is consistent with the Mach number M = 1.6_{-0.3}^{+0.5}. A second inner surface brightness edge is a cold front that marks the border between infalling subcluster cool core and the intracluster medium of the main cluster. The temperature across the cold front increases from 1.3_{-0.8}^{+0.3} to 6.2_{-0.6}^{+0.6} keV. We find an overpressurized region ˜250 kpc east of the cold front that is named `the eastern extension (EE)'. The EE may be a part of the third subcluster in the ongoing merger. We also find a tail shaped feature that originates near the bow shock and may extend up to a distance of ˜1 Mpc. This feature is also likely overpressurized. The luminous FR-I radio galaxy, 3C89, appears to be the cD galaxy of the infalling subcluster. We estimated 3C89's jet power from jet bending and the possible interaction between the X-ray gas and the radio lobes. A comparison between the shock stand-off distance and the Mach number for all known shock front/cold front combinations suggests that the core is continuously shrinking in size by stripping.

Biological Effects of Short, High-Level Exposure to Gases: Nitrogen Oxides.

DTIC Science & Technology

1980-07-01

damage. Proven effects are mainly on the respiratory tract. Intense exposures result in death, hospitalization with recovery, or severe responses not...and up, for single exposures of a few minutes up to 1 hour. At the other extreme the threshold of measurable respiratory impairment in volunteers is...reversible or irreversible respiratory impairment by NOx on oxygen sufficiency and,hence, physical and mental capacity has not been measured in man, but

Barking up the Wrong Tree? Lexical Ambiguity Resolution in Children with Language Impairments and Autistic Spectrum Disorders

ERIC Educational Resources Information Center

Norbury, C.F.

2005-01-01

Lexical ambiguity resolution was investigated in 9- to 17-year-olds with language impairment (LI, n=20), autistic spectrum disorder (ASD) plus language impairment (ALI, n=28), ASD and verbal abilities within the normal range (ASO, n=20), and typically developing children (TD, n=28). Experiment 1 investigated knowledge of dominant and subordinate…

The Alabama VIP older driver study rationale and design: examining the relationship between vision impairment and driving using naturalistic driving techniques.

PubMed

Owsley, Cynthia; McGwin, Gerald; Antin, Jonathan F; Wood, Joanne M; Elgin, Jennifer

2018-02-07

Older drivers aged ≥70 years old have among the highest rates of motor vehicle collisions (MVC) compared to other age groups. Driving is a highly visual task, and older adults have a high prevalence of vision impairment compared to other ages. Most studies addressing visual risk factors for MVCs by older drivers utilize vehicle accident reports as the primary outcome, an approach with several methodological limitations. Naturalistic driving research methods overcome these challenges and involve installing a high-tech, unobtrusive data acquisition system (DAS) in an older driver's own vehicle. The DAS continuously records multi-channel video of driver and roadway, sensor-based kinematics, GPS location, and presence of nearby objects in front of the vehicle, providing an objective measure of driving exposure. In this naturalistic driving study, the purpose is to examine the relationship between vision and crashes and near-crashes, lane-keeping, turning at intersections, driving performance during secondary tasks demands, and the role of front-seat passengers. An additional aim is to compare results of the on-road driving evaluation by a certified driving rehabilitation specialist to objective indicators of driving performance derived from the naturalistic data. Drivers ≥70 years old are recruited from ophthalmology clinics and a previous population-based study of older drivers, with the goal of recruiting persons with wide ranging visual function. Target samples size is 195 drivers. At a baseline visit, the DAS is installed in the participant's vehicle and a battery of health and functional assessments are administered to the driver including visual-sensory and visual-cognitive tests. The DAS remains installed in the vehicle for six months while the participant goes about his/her normal driving with no imposed study restrictions. After six months, the driver returns for DAS de-installation, repeat vision testing, and an on-road driving evaluation by a certified driving rehabilitation specialist (CDRS). The data streams recorded by the DAS are uploaded to the data coordinating center for analysis. The Alabama VIP Older Driver Study is the first naturalistic older driver study specifically focused on the enrollment of drivers with vision impairment in order to study the relationship between visual dysfunction and driver safety and performance.

The x-ray source application test cassette for radiation exposures at the OMEGA laser

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

Fournier, K. B.; Rekow, V.; Emig, J.

2012-10-15

We have designed a sample cassette that can be used to position up to six samples in the OMEGA laser chamber. The cassette accommodates round samples up to 38.1 mm (1.5{sup Double-Prime }) in diameter and square samples up to 27 mm on a side, any of which can be up to 12.7 mm thick. Smaller specimens are centered with spacers. The test cassette allows each sample to have a unique filter scheme, with multiple filter regions in front of each sample. This paper will present mechanical design considerations and operational aspects of the x-ray source application cassette.

Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

ClinicalTrials.gov

2017-12-11

Adult Acute Myeloid Leukemia in Remission; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndrome; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndrome; Metastatic Renal Cell Cancer; Previously Treated Myelodysplastic Syndrome; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Renal Medullary Carcinoma; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Complete molecular remission in relapsed and refractory acute myeloid leukaemia with MLL-AF9 treated with chidamide-based chemotherapy.

PubMed

Lun, Y; Yang, J-J; Wu, Y

2017-12-01

The mixed lineage leukaemia (MLL) gene translocations are found in approximately 10% of adults with acute myeloid leukaemia (AML) and are markers of poor prognosis. As the best reported response in relapsed and refractory MLL-rearranged AML is around 40%, reinduction treatment is very challenging for those patients. We report a case of relapsed and refractory AML with MLL-AF9, who did not respond to FLAG (fludarabine, cytarabine, granulocyte colony stimulating factor) regimen reinduction treatment, but achieved complete response and molecular remission after chidamide-based chemotherapy. Chidamide (CS055/HBI-8000) is a new histone deacetylase (HDAC) inhibitor that is clinically active in relapsed and refractory peripheral T-cell lymphomas. To the best of our knowledge, successful reinduction treatment on relapsed MLL-AF9 by chidamide-based regimen has not been previously reported. © 2017 John Wiley & Sons Ltd.

The HOVON68 CLL trial revisited: performance status and comorbidity affect survival in elderly patients with chronic lymphocytic leukemia.

PubMed

Vojdeman, Fie Juhl; Van't Veer, Mars B; Tjønnfjord, Geir E; Itälä-Remes, Maija; Kimby, Eva; Polliack, Aaron; Wu, Ka L; Doorduijn, Jeanette K; Alemayehu, Wendimagegn G; Wittebol, Shulamiet; Kozak, Tomas; Walewski, Jan; Abrahamse-Testroote, Martine C J; van Oers, Marinus H J; Geisler, Christian Hartmann

2017-03-01

In the HOVON68 CLL trial, patients 65 to 75 years of age had no survival benefit from the addition of low-dose alemtuzumab to fludarabine and cyclophosphamide (FC) in contrast to younger patients. The reasons are explored in this 5-year trial update using both survival analysis and competing risk analysis on non-CLL-related mortality. Elderly FCA patients died more frequently from causes not related to CLL, and more often related to comorbidity (mostly cardiovascular) than to infection. In a Cox multivariate analysis, del(17p), performance status >0, and comorbidity were associated with a higher non-CLL-related mortality in the elderly independent of the treatment modality. Thus, while the 'fit' elderly with no comorbidity or performance status of 0 might potentially benefit from chemo-immunotherapy with FC, caution is warranted, when considering alemtuzumab treatment in elderly patients with cardiovascular comorbidity.

Radiolabeled Monoclonal Antibody Therapy, Fludarabine Phosphate, and Low-Dose Total-Body Irradiation Followed by Donor Stem Cell Transplant and Immunosuppression Therapy in Treating Older Patients With Advanced Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

ClinicalTrials.gov

2017-11-06

Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies

ClinicalTrials.gov

2016-05-04

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Hematopoietic/Lymphoid Cancer; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

Leukaemia cutis after starting bendamustine: cause or coincidence?

PubMed

Mawri, Sagger; Nabi, Shahzaib; Jallad, Bassel; Won, Joseph

2015-09-21

A 55-year-old man with a history of chronic lymphocytic leukaemia presented with diffuse skin lesions that began 1 week after starting a new chemotherapy regimen with bendamustine and rituximab. The lesions appeared as erythematous papules that were neither itchy nor tender, and did not blanch with pressure. Initially, they began on his scalp and flanks and, over the next few days, spread diffusely throughout his body, becoming darker in colour. Skin biopsy showed atypical clonal B-cell proliferation in a perivascular, periadnexal and dermal band-like distribution, which was further characterised by immunohistochemical evaluation. These findings were suggestive of leukaemia cutis and consistent with the patient's chronic lymphocytic leukaemia, which was previously confirmed by bone marrow biopsy. The bendamustine was stopped and the patient's chemotherapy regimen was switched to fludarabine, cyclophosphamide and rituximab. Shortly thereafter, the leukaemia cutis regressed significantly. 2015 BMJ Publishing Group Ltd.

Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer

ClinicalTrials.gov

2018-06-13

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Leukemia in Remission; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; Aplastic Anemia; B-Cell Non-Hodgkin Lymphoma; CD40 Ligand Deficiency; Chronic Granulomatous Disease; Chronic Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Congenital Amegakaryocytic Thrombocytopenia; Congenital Neutropenia; Congenital Pure Red Cell Aplasia; Glanzmann Thrombasthenia; Immunodeficiency Syndrome; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Plasma Cell Myeloma; Polycythemia Vera; Recurrent Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Severe Aplastic Anemia; Shwachman-Diamond Syndrome; Sickle Cell Disease; T-Cell Non-Hodgkin Lymphoma; Thalassemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

Toward a fully integrated neurostimulator with inductive power recovery front-end.

PubMed

Mounaïm, Fayçal; Sawan, Mohamad

2012-08-01

In order to investigate new neurostimulation strategies for micturition recovery in spinal cord injured patients, custom implantable stimulators are required to carry-on chronic animal experiments. However, higher integration of the neurostimulator becomes increasingly necessary for miniaturization purposes, power consumption reduction, and for increasing the number of stimulation channels. As a first step towards total integration, we present in this paper the design of a highly-integrated neurostimulator that can be assembled on a 21-mm diameter printed circuit board. The prototype is based on three custom integrated circuits fabricated in High-Voltage (HV) CMOS technology, and a low-power small-scale commercially available FPGA. Using a step-down approach where the inductive voltage is left free up to 20 V, the inductive power and data recovery front-end is fully integrated. In particular, the front-end includes a bridge rectifier, a 20-V voltage limiter, an adjustable series regulator (5 to 12 V), a switched-capacitor step-down DC/DC converter (1:3, 1:2, or 2:3 ratio), as well as data recovery. Measurements show that the DC/DC converter achieves more than 86% power efficiency while providing around 3.9-V from a 12-V input at 1-mA load, 1:3 conversion ratio, and 50-kHz switching frequency. With such efficiency, the proposed step-down inductive power recovery topology is more advantageous than its conventional step-up counterpart. Experimental results confirm good overall functionality of the system.

Adiabatic burst evaporation from bicontinuous nanoporous membranes

PubMed Central

Ichilmann, Sachar; Rücker, Kerstin; Haase, Markus; Enke, Dirk

2015-01-01

Evaporation of volatile liquids from nanoporous media with bicontinuous morphology and pore diameters of a few 10 nm is an ubiquitous process. For example, such drying processes occur during syntheses of nanoporous materials by sol–gel chemistry or by spinodal decomposition in the presence of solvents as well as during solution impregnation of nanoporous hosts with functional guests. It is commonly assumed that drying is endothermic and driven by non-equilibrium partial pressures of the evaporating species in the gas phase. We show that nearly half of the liquid evaporates in an adiabatic mode involving burst-like liquid-to-gas conversions. During single adiabatic burst evaporation events liquid volumes of up to 107 μm3 are converted to gas. The adiabatic liquid-to-gas conversions occur if air invasion fronts get unstable because of the built-up of high capillary pressures. Adiabatic evaporation bursts propagate avalanche-like through the nanopore systems until the air invasion fronts have reached new stable configurations. Adiabatic cavitation bursts thus compete with Haines jumps involving air invasion front relaxation by local liquid flow without enhanced mass transport out of the nanoporous medium and prevail if the mean pore diameter is in the range of a few 10 nm. The results reported here may help optimize membrane preparation via solvent-based approaches, solution-loading of nanopore systems with guest materials as well as routine use of nanoporous membranes with bicontinuous morphology and may contribute to better understanding of adsorption/desorption processes in nanoporous media. PMID:25926406

Neutron energy spectra from the laser-induced Dd,n3He reaction.

PubMed

Hilscher, D; Berndt, O; Enke, M; Jahnke, U; Nickles, P V; Ruhl, H; Sandner, W

2001-07-01

Detailed neutron energy spectra were measured for the D(d,n)3He reaction induced in solid (CD2)(n) targets by irradiation with 50-fs 2 x 10(18) W/cm(2) light pulses from a 10-TW Ti:Sapphire laser. The neutrons were observed at two angles 5 degrees and 112 degrees relative to the incident laser beam. The neutron spectra at the two angles are characterized by peaks with large widths of about 700 keV full width at half maximum and a shift of 300 keV between them. Neutron energies of up to about 4 MeV were observed indicating that deuterons are accelerated up to an energy of 1 MeV in the laser produced plasma. Simulation calculations can describe qualitatively the neutron spectra by assuming isotropic deuteron acceleration and a reduction of the reaction probability by a factor of 1/3 for deuterons emitted from the front of the target. These calculations indicate in particular that it is necessary to assume deuterons moving both into and out of the front of the target in order to describe the neutron energy spectra at the two angles. The highest recorded mean neutron yield was about 10(4) neutrons per pulse. The neutron yield increases with the number of electrons emitted from the front of the target and with the intensity of the prompt gamma flash induced by the bremsstrahlung of energetic electrons.

75 FR 32190 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-07

... Cognitive Impairment on Co-Occurring Chronic Conditions SIP 10-037 and Epidemiologic Follow- Up Study of... received in response to ``Examining the Impact of Cognitive Impairment on Co- Occurring Chronic Conditions...

Designing, installing and operating low NOx combustion systems in power plants

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

Lazzeri, L.; Santis, R. de

1997-09-01

Ansaldo Energia, in strict cooperation with the Italian Electricity Board (ENEL), has developed and implemented innovative technologies for in furnace NOx control which have been applied, both in italy and abroad, on over 20,000 MWe boilers of every kind (Tangentially Fired, Front Fired, Opposite Fired) and for different fuels like oil, gas, coal and ORIMULSION{reg_sign}. Taking advantage of innovative low NOx burners and of optimized air and fuel staging techniques NOx reductions up to 85% have been obtained with no significant impact on boiler efficiency. The paper describes: characteristics and industrial application of TEA{reg_sign} oil/gas LNB which is now capablemore » of attaining NOx reductions up to 60% in respect to original circular burners; development and industrial applications of the TEA C{reg_sign} (oil/coal) LNB, capable of attaining NOx reductions up to 50% with contemporary control of unburned carbon levels (typical values less than 300 ppm NOx corrected to 6% O{sub 2} and less than 7% UBC); application of reburning oil over oil and gas over oil for both tangential and front-opposite fired boilers rated up 660 MWe; and information on the CEE THERMIE projects of gas over coal reburning in a 600 MWe Scottish Power boiler and oil over coal and coal over coal reburning in the ENEL plant of Vado Ligure unit 4, rated 320 MWe.« less

A 24-GHz Front-End Integrated on a Multilayer Cellulose-Based Substrate for Doppler Radar Sensors †

PubMed Central

Mariotti, Chiara; Virili, Marco; Orecchini, Giulia; Roselli, Luca; Mezzanotte, Paolo

2017-01-01

This paper presents a miniaturized Doppler radar that can be used as a motion sensor for low-cost Internet of things (IoT) applications. For the first time, a radar front-end and its antenna are integrated on a multilayer cellulose-based substrate, built-up by alternating paper, glue and metal layers. The circuit exploits a distributed microstrip structure that is realized using a copper adhesive laminate, so as to obtain a low-loss conductor. The radar operates at 24 GHz and transmits 5 mW of power. The antenna has a gain of 7.4 dBi and features a half power beam-width of 48 degrees. The sensor, that is just the size of a stamp, is able to detect the movement of a walking person up to 10 m in distance, while a minimum speed of 50 mm/s up to 3 m is clearly measured. Beyond this specific result, the present paper demonstrates that the attractive features of cellulose, including ultra-low cost and eco-friendliness (i.e., recyclability and biodegradability), can even be exploited for the realization of future high-frequency hardware. This opens opens the door to the implementation on cellulose of devices and systems which make up the “sensing layer” at the base of the IoT ecosystem. PMID:28895914

Pyroclastic flows generated by gravitational instability of the 1996-97 lava dome of Soufriere Hills Volcano, Montserrat

USGS Publications Warehouse

Cole, P.D.; Calder, E.S.; Druitt, T.H.; Hoblitt, R.; Robertson, R.; Sparks, R.S.J.; Young, S.R.

1998-01-01

Numerous pyroclastic flows were produced during 1996-97 by collapse of the growing andesitic lava dome at Soufriere Hills Volcano, Montserrat. Measured deposit volumes from these flows range from 0.2 to 9 ?? 106 m3. Flows range from discrete, single pulse events to sustained large scale dome collapse events. Flows entered the sea on the eastern and southern coasts, depositing large fans of material at the coast. Small runout distance (<1 km) flows had average flow front velocities in the order of 3-10 m/s while flow fronts of the larger runout distance flows (up to 6.5 km) advanced in the order of 15-30 m/s. Many flows were locally highly erosive. Field relations show that development of the fine grained ash cloud surge component was enhanced during the larger sustained events. Periods of elevated pyroclastic flow productivity and sustained dome collapse events are linked to pulses of high magma extrusion rates.Numerous pyroclastic flows were produced during 1996-97 by collapse of the growing andesitic lava dome at Soufriere Hills Volcano, Montserrat. Measured deposit volumes from these flows range from 0.2 to 9??106 m3. Flows range from discrete, single pulse events to sustained large scale dome collapse events. Flows entered the sea on the eastern and southern coasts, depositing large fans of material at the coast. Small runout distance (<1 km) flows had average flow front velocities in the order of 3-10 m/s while flow fronts of the larger runout distance flows (up to 6.5 km) advanced in the order of 15-30 m/s. Many flows were locally highly erosive. Field relations show that development of the fine grained ash cloud surge component was enhanced during the larger sustained events. Periods of elevated dome pyroclastic flow productivity and sustained collapse events are linked to pulses of high magma extrusion rates.

Up Front: Students Are Chafing under "Test Stress."

ERIC Educational Resources Information Center

American School Board Journal, 2001

2001-01-01

Although President Bush favors continuous testing, headlines reflect an intense, growing antitesting sentiment. One standard does not fit all, current systems are malfunctioning, and kids are short-changed. A recent report says abstinence-only sex education is ineffective; high teen birth rates underline the need for comprehensive approaches. (MLH)

78 FR 24736 - Energy Savings Performance Contracts: Extension of Comment Period

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... legislated and executive-ordered energy, greenhouse gas, and water goals. These are delivered through project..., obtaining, and implementing project funding for energy projects through the use of ESPCs. ESPCs allow Federal agencies to accomplish energy savings projects without up-front capital costs. In an ESPC, a...

Magnetic bearings for a high-performance optical disk buffer, volume 2

NASA Technical Reports Server (NTRS)

1990-01-01

The operating instructions for the magnetic bearings of a high-performance optical disk buffer are provided. Among the topics that are discussed are the following: front panel layout, turn-on procedure, shut-down procedure, and latch-up protection. Additionally, comprehensive engineering drawings are presented for the design.

Housing for Moderate Income Households.

ERIC Educational Resources Information Center

Brannigan, Vincent M.; Meeks, Carol B.

1991-01-01

Describes equity leasing, a program that enables people to acquire housing without an up-front investment but with an incentive to maintain and improve the property. Under this proposal, lessees would acquire a leasehold interest in a house and own the right to use the property for a continuously extended lease term. (JOW)

76 FR 8721 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

...'' grants that are awarded funds for their entire multi-year project up-front in a single grant award to... the ED 524B to submit their final performance reports to demonstrate project success, impact and..., mechanical, or other technological collection techniques or other forms of information technology. Dated...

76 FR 12945 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

... awarded funds for their entire multi-year project up- front in a single grant award to submit the RPPR on... their final performance reports to demonstrate project success, impact and outcomes. In both the annual..., mechanical, or other technological collection techniques or other forms of information technology. [[Page...

50 CFR 640.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC General Provisions... usually held up by means of a cord which is released when the net is dropped over a lobster. Carapace length means the measurement of the carapace (head, body, or front section) of a spiny lobster from the...

50 CFR 640.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC General Provisions... usually held up by means of a cord which is released when the net is dropped over a lobster. Carapace length means the measurement of the carapace (head, body, or front section) of a spiny lobster from the...

Identity Theft - The National Guard

Science.gov Websites

Legislative Liaison Small Business Programs Social Media State Websites Videos Featured Videos On Every Front name. Social Security Numbers - If after doing everything in your power to clear up the effects of identity theft you discover someone is still fraudulently using your Social Security Number, you can

Profit U

ERIC Educational Resources Information Center

Weinstein, Margery

2012-01-01

Preparing employees for the immediate work in front of them is a challenge. While most companies are still mastering effectively training their own workforce, some, such as "Training" magazine Top 10 Hall of Famer The Ritz-Carlton Hotel Company, have set up for-profit academies open to the public. When Ritz-Carlton won the national Malcolm…

Systems Librarian and Automation Review.

ERIC Educational Resources Information Center

Schuyler, Michael

1992-01-01

Discusses software sharing on computer networks and the need for proper bandwidth; and describes the technology behind FidoNet, a computer network made up of electronic bulletin boards. Network features highlighted include front-end mailers, Zone Mail Hour, Nodelist, NetMail, EchoMail, computer conferences, tosser and scanner programs, and host…

Developing a Successful Asynchronous Online Extension Program for Forest Landowners

ERIC Educational Resources Information Center

Zobrist, Kevin W.

2014-01-01

Asynchronous online Extension classes can reach a wide audience, is convenient for the learner, and minimizes ongoing demands on instructor time. However, producing such classes takes significant effort up front. Advance planning and good communication with contributors are essential to success. Considerations include delivery platforms, content…

Passive Infrared Detection of Microburst Induced Low Level Wind Shear

DTIC Science & Technology

1990-05-17

ring vortex breaks up as the microburst matures. Some rotor microbursts develops from larger scale macrobursts and gust fronts. From Fujita (1985) 2.2...Canada, Amer. Meteor. Soc., 638-645. , 1985:" The Downburst; Microburst and Macroburst ", University of Chicago, SRMP, University of Chicago. , 1986

Up the Front Staircase: A Proposal for Women to Achieve Parity with Men in the Field of Educational Administration

ERIC Educational Resources Information Center

Palmieri, Patricia; Shakeshaft, Charol Smith

1976-01-01

The various sexist attitudes and prejudices responsible for the decline of women's roles in educational institutions are discussed. Several suggestions are made to help women assert their rights and aspire as well as try to assume administrative positions. (SE)

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

none,

This Building America Top Innovations profile describes Building America research showing how some energy-efficiency measure cost increases can balance against measures that reduce up-front costs: Advanced framing cuts lumber costs, right sizing can mean downsizing the HVAC, moving HVAC into conditioned space cuts installation costs, designing on a 2-foot grid reduces materials waste, etc.

SETTING DATA QUALITY OBJECTIVES FOR THERMALLY ENHANCED, IN SITU REMEDIATION PROJECTS

EPA Science Inventory

The design and implementation of an in-situ technology requires an up-front and clear understanding of the remedial objectives of the technology application and the data that will be collected to track the progress of remediation and to assess the ultimate success of in-sit...

Feeling Older and the Development of Cognitive Impairment and Dementia.

PubMed

Stephan, Yannick; Sutin, Angelina R; Luchetti, Martina; Terracciano, Antonio

2017-10-01

Subjective age is a biopsychosocial marker of aging associated with a range of outcomes in old age. In the domain of cognition, feeling older than one's chronological age is related to lower cognitive performance and steeper cognitive decline among older adults. The present study examines whether an older subjective age is associated with the risk of incident cognitive impairment and dementia. Participants were 5,748 individuals aged 65 years and older drawn from the Health and Retirement Study. Measures of subjective age, cognition, and covariates were obtained at baseline, and follow-up cognition was assessed over a 2- to 4-year period. Only participants without cognitive impairment were included at baseline. At follow-up, participants were classified into one of the three categories: normal functioning, cognitive impairment without dementia (CIND), and dementia. An older subjective age at baseline was associated with higher likelihood of CIND (odds ratio [OR] = 1.18; 1.09-1.28) and dementia (OR = 1.29; 1.02-1.63) at follow-up, controlling for chronological age, other demographic factors, and baseline cognition. Physical inactivity and depressive symptoms partly accounted for these associations. An older subjective age is a marker of individuals' risk of subsequent cognitive impairment and dementia. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Midlife Hypertensive Status and Cognitive Function 20 Years Later: The Southall and Brent Revisited Study

PubMed Central

Taylor, Clare; Tillin, Therese; Chaturvedi, Nish; Dewey, Michael; Ferri, Cleusa P; Hughes, Alun; Prince, Martin; Richards, Marcus; Shah, Ajit; Stewart, Robert

2013-01-01

Objectives: To investigate long-term prospective associations between a range of measurements of hypertensive status in midlife and cognitive impairment 20 years later. Design: Cohort study. Setting: Two areas (Southall and Brent) of northwest London. Participants: Survey samples of a multiethnic population (European, African Caribbean, South Asian) aged 40 to 67 were followed up 20 years later. Measurements: Comprehensive cardiovascular assessments were performed at baseline, including measurements of resting blood pressure (BP) and, in a subsample, ambulatory BP. At follow-up, a battery of cognitive assessments was administered, and a composite outcome was derived, with impairment defined as the lowest 10% within each ethnic group. Logistic regression models were used to investigate associations with prior measures of hypertensive status. Results: In 1,484 participants at follow-up, cognitive impairment showed significant U-shaped associations with baseline diastolic BP (DBP) and mean arterial pressure (MAP; strongest for those aged ≥50 at baseline), independent of a range of covariates, but no associations were found with systolic BP or pulse pressure. Cognitive impairment was also associated with antihypertensive medication use and higher evening ambulatory DBP at baseline. No substantial differences in strengths of association were found between ethnic groups. Conclusion: Low and high DBP and MAP were associated with cognitive impairment 20 years later. Higher evening DBP on ambulatory monitoring was also associated with greater risk. PMID:24028355

Implementation of a level 1 trigger system using high speed serial (VXS) techniques for the 12GeV high luminosity experimental programs at Thomas Jefferson National Accelerator Facility

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

C. Cuevas, B. Raydo, H. Dong, A. Gupta, F.J. Barbosa, J. Wilson, W.M. Taylor, E. Jastrzembski, D. Abbott

We will demonstrate a hardware and firmware solution for a complete fully pipelined multi-crate trigger system that takes advantage of the elegant high speed VXS serial extensions for VME. This trigger system includes three sections starting with the front end crate trigger processor (CTP), a global Sub-System Processor (SSP) and a Trigger Supervisor that manages the timing, synchronization and front end event readout. Within a front end crate, trigger information is gathered from each 16 Channel, 12 bit Flash ADC module at 4 nS intervals via the VXS backplane, to a Crate Trigger Processor (CTP). Each Crate Trigger Processor receivesmore » these 500 MB/S VXS links from the 16 FADC-250 modules, aligns skewed data inherent of Aurora protocol, and performs real time crate level trigger algorithms. The algorithm results are encoded using a Reed-Solomon technique and transmission of this Level 1 trigger data is sent to the SSP using a multi-fiber link. The multi-fiber link achieves an aggregate trigger data transfer rate to the global trigger at 8 Gb/s. The SSP receives and decodes Reed-Solomon error correcting transmission from each crate, aligns the data, and performs the global level trigger algorithms. The entire trigger system is synchronous and operates at 250 MHz with the Trigger Supervisor managing not only the front end event readout, but also the distribution of the critical timing clocks, synchronization signals, and the global trigger signals to each front end readout crate. These signals are distributed to the front end crates on a separate fiber link and each crate is synchronized using a unique encoding scheme to guarantee that each front end crate is synchronous with a fixed latency, independent of the distance between each crate. The overall trigger signal latency is <3 uS, and the proposed 12GeV experiments at Jefferson Lab require up to 200KHz Level 1 trigger rate.« less

DESIGN OF MEDICAL RADIOMETER FRONT-END FOR IMPROVED PERFORMANCE

PubMed Central

Klemetsen, Ø.; Birkelund, Y.; Jacobsen, S. K.; Maccarini, P. F.; Stauffer, P. R.

2011-01-01

We have investigated the possibility of building a singleband Dicke radiometer that is inexpensive, small-sized, stable, highly sensitive, and which consists of readily available microwave components. The selected frequency band is at 3.25–3.75 GHz which provides a reasonable compromise between spatial resolution (antenna size) and sensing depth for radiometry applications in lossy tissue. Foreseen applications of the instrument are non-invasive temperature monitoring for breast cancer detection and temperature monitoring during heating. We have found off-the-shelf microwave components that are sufficiently small (< 5 mm × 5 mm) and which offer satisfactory overall sensitivity. Two different Dicke radiometers have been realized: one is a conventional design with the Dicke switch at the front-end to select either the antenna or noise reference channels for amplification. The second design places a matched pair of low noise amplifiers in front of the Dicke switch to reduce system noise figure. Numerical simulations were performed to test the design concepts before building prototype PCB front-end layouts of the radiometer. Both designs provide an overall power gain of approximately 50 dB over a 500 MHz bandwidth centered at 3.5 GHz. No stability problems were observed despite using triple-cascaded amplifier configurations to boost the thermal signals. The prototypes were tested for sensitivity after calibration in two different water baths. Experiments showed superior sensitivity (36% higher) when implementing the low noise amplifier before the Dicke switch (close to the antenna) compared to the other design with the Dicke switch in front. Radiometer performance was also tested in a multilayered phantom during alternating heating and radiometric reading. Empirical tests showed that for the configuration with Dicke switch first, the switch had to be locked in the reference position during application of microwave heating to avoid damage to the active components (amplifiers and power meter). For the configuration with a low noise amplifier up front, damage would occur to the active components of the radiometer if used in presence of the microwave heating antenna. Nevertheless, this design showed significantly improved sensitivity of measured temperatures and merits further investigation to determine methods of protecting the radiometer for amplifier first front ends. PMID:21779411

Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial.

PubMed

Dreger, Peter; Döhner, Hartmut; McClanahan, Fabienne; Busch, Raymonde; Ritgen, Matthias; Greinix, Hildegard; Fink, Anna-Maria; Knauf, Wolfgang; Stadler, Michael; Pfreundschuh, Michael; Dührsen, Ulrich; Brittinger, Günter; Hensel, Manfred; Schetelig, Johannes; Winkler, Dirk; Bühler, Andreas; Kneba, Michael; Schmitz, Norbert; Hallek, Michael; Stilgenbauer, Stephan

2012-05-24

The CLL3 trial was designed to study intensive treatment including autologous stem cell transplantation (autoSCT) as part of first-line therapy in patients with chronic lymphocytic leukemia (CLL). Here, we present the long-term outcome of the trial with particular focus on the impact of genomic risk factors, and we provide a retrospective comparison with patients from the fludarabine-cyclophosphamide-rituximab (FCR) arm of the German CLL Study Group (GCLLSG) CLL8 trial. After a median observation time of 8.7 years (0.3-12.3 years), median progression-free survival (PFS), time to retreatment, and overall survival (OS) of 169 evaluable patients, including 38 patients who did not proceed to autoSCT, was 5.7, 7.3, and 11.3 years, respectively. PFS and OS were significantly reduced in the presence of 17p- and of an unfavorable immunoglobulin heavy variable chain mutational status, but not of 11q-. Five-year nonrelapse mortality was 6.5%. When 110 CLL3 patients were compared with 126 matched patients from the FCR arm of the CLL8 trial, 4-year time to retreatment (75% vs 77%) and OS (86% vs 90%) was similar despite a significant benefit for autoSCT in terms of PFS. In summary, early treatment intensification including autoSCT can provide very effective disease control in poor-risk CLL, although its clinical benefit in the FCR era remains uncertain. The trial has been registered with www.clinicaltrials.gov as NCT00275015.

Four decades of stem cell transplantation for Fanconi anaemia in the Netherlands.

PubMed

Smetsers, Stephanie E; Smiers, Frans J; Bresters, Dorine; Sonnevelt, Martine C; Bierings, Marc B

2016-09-01

This article presents the haematopoietic stem cell transplantation (SCT) results of the complete Dutch Fanconi anaemia (FA) patient cohort. Sixty-eight Dutch FA patients have been transplanted since 1972. In total, 63 (93%) patients engrafted, 54 after first SCT and 9 after second SCT. Fludarabine (FLU)-based conditioning was associated with decreased graft failure (odds ratio 0·21, P = 0·01), decreased early mortality (hazard ratio 0·25, P = 0·01) and improved 5-year overall survival (FLU 87·8% [standard error (SE) 5·1%] versus non-FLU 59·3% [SE 9·5%], P = 0·01). Late mortality was mainly caused by squamous cell carcinoma. Twenty-two patients were treated with the current Dutch FA conditioning regimen (FLU 150 mg/m(2) and cyclophosphamide 30 mg/kg ± anti-thymocyte globulin - no irradiation). Stem cell donors were matched related (n = 8) or alternative donors (n = 14). Stable engraftment after first SCT was achieved in 19 (86%) patients. At a median follow-up of 3·9 years 20 (91%) patients are alive. Our study provides a unique overview of a nation-wide SCT cohort illustrating the major improvements in treatment regimen and patient outcome in recent years. It shows that a non-irradiation and busulfan-free conditioning regimen can be used successfully, also in alternative donor SCT. Furthermore, it underlines the importance of late cancer screening and comprehensive care for this complex disorder. © 2016 John Wiley & Sons Ltd.

Hematopoietic Cell Transplantation Using Reduced-Intensity Conditioning Is Successful in Children with Hematologic Cytopenias of Genetic Origin.

PubMed

Kothari, Alok; Ngwube, Alexander; Hayashi, Robert; Murray, Lisa; Davis, Jeffrey; Haut, Paul; Loechelt, Brett J; Shenoy, Shalini

2015-07-01

Genetically derived hematologic cytopenias are a rare heterogeneous group of disorders. Allogeneic hematopoietic cell transplantation (HCT) is curative but offset by organ toxicities from the preparative regimen, graft rejection, graft-versus-host disease (GVHD), or mortality. Because of these possibilities, consideration of HCT can be delayed, especially in the unrelated donor setting. We report a prospective multicenter trial of reduced-intensity conditioning (RIC) with alemtuzumab, fludarabine, and melphalan and HCT in 11 children with marrow failure of genetic origin (excluding Fanconi anemia) using the best available donor source (82% from unrelated donors). The median age at transplantation was 23 months (range, 2 months to 14 years). The median times to neutrophil (>500 × 10(6)/L) and platelet (>50 × 10(9)/L) engraftment were 13 (range, 12 to 24) and 30 (range, 7 to 55) days, respectively. The day +100 probability of grade II to IV acute GVHD and the 1-year probability of limited and extensive GVHD were 9% and 27%, respectively. The probability of 5-year overall and event-free survival was 82%; 9 patients were alive with normal blood counts at last follow-up and all were successfully off systemic immunosuppression. In patients with genetically derived severe hematologic cytopenias, allogeneic HCT with this RIC regimen was successful in achieving a cure. This experience supports consideration of HCT early in such patients even in the absence of suitable related donors. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The perfect ash-storm: large-scale Pyroclastic Density Current experiments reveal highly mobile, self-fluidising and air-cushioned flow transport regime

NASA Astrophysics Data System (ADS)

Lube, G.; Cronin, S. J.; Breard, E.; Valentine, G.; Bursik, M. I.; Hort, M. K.; Freundt, A.

2013-12-01

We report on the first systematic series of large-scale Pyroclastic Density Current (PDC) experiments using the New Zealand PDC Generator, a novel international research facility in Physical Volcanology recently commissioned at Massey University. Repeatable highly energetic and hot PDCs are synthesized by the controlled ';eruption column-collapse' of up to 3500 kg of homogenously aerated Taupo ignimbrite material from a 15 m-elevated hopper onto an instrumented inclined flume. At discharge rates between 250-1300 kg/s and low- to moderate gas injection rates (yielding initial solids concentration of 15-70 vol%) channelized gas-particle mixture flows life-scaled to dense PDCs can be generated. The flow fronts of the currents reach velocities of up to 9.5 m/s over their first 12 m of travel and rapidly develop strong vertical density stratification. The PDCs typically form a highly mobile, <60 cm-thick dense and channel-confined underflow, with an overriding dilute and turbulent ash cloud surge that also laterally escapes the flume boundaries. Depending on the PDC starting conditions underflows with 1-45 vol% solids concentration are formed, while the upper surge contains <<1 vol.% solids. A characteristic feature of the underflow is the occurrence of 'ignitive' front breakouts, producing jetted lobes that accelerate outward from the flow front, initially forming a lobe-cleft structure, followed by segregation downslope into multiple flow pulses. Depending on initial solids concentration and discharge rate, stratified, dune-bedded and inversely graded bedforms are created whose thicknesses are remarkably uniform along the medial to distal runout path characterising highly mobile flow runout. Along with high-speed video footage we present time-series data of basal arrays of load- and gas-pore pressure transducers to characterise the mobile dense underflows. Data shows that the PDCs are comprised of a turbulent coarse-grained and air-ingesting front with particle-solids concentrations of 1-5 vol%. The front shows a brief phase of negative pore pressure due to the entrainment and upward elutriation of ambient air inside this front. It is immediately followed by the fine-ash rich and highly impermeable main flow body. Passage of the flow body is accompanied by strongly increasing pore-pressures of 1-3 kPa that almost fully supports the weight of the entire underflow - depicting flow-induced fluidisation of the main flow part. The remainder of the flow body shows further increases in pore-pressure aside with strong reductions in flow mass. This suggests the occurrence of zones of air-cushions forming at the base of the underflow that largely aid its inviscid runout. This sequence is repeated during arrival and passage of up to three more flow pulses. The low-permeability deposits maintain high internal gas pore pressures for several minutes after emplacement, before sudden deaeration, settling and gas loss is caused by fracturing. Flow-induced fluidisation and basal air-cushioning provide key processes behind the enigmatic long runout behaviour of dense PDCs.

Impaired glucose metabolism in subjects with the Williams-Beuren syndrome: A five-year follow-up cohort study

PubMed Central

Lunati, Maria Elena; Bedeschi, Maria Francesca; Resi, Veronica; Grancini, Valeria; Palmieri, Eva; Salera, Simona; Lalatta, Faustina; Pugliese, Giuseppe

2017-01-01

Objective The Williams-Beuren syndrome (WS) is associated with impaired glucose metabolism (IGM) early in adulthood. However, the pathophysiology of IGM remains poorly defined, due to the lack of longitudinal studies investigating the contribution of β-cell dysfunction and impaired insulin sensitivity. This study aimed at assessing incidence of IGM and the underlying mechanisms in WS adults. Methods This observational, longitudinal (5-year), cohort study enrolled thirty-one consecutive WS subjects attending a tertiary referral center. An oral glucose tolerance test (OGTT) was performed yearly and used to classify patients as normal or IGM, including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and diabetes mellitus (DM), and to calculate surrogate measures of insulin secretion and/or sensitivity. Results IGM patients were 18 (58.1%, three DM) at baseline and 19 (61.3%, five DM) at end-of-follow-up. However, 13 individuals changed category of glucose homeostasis in both directions during follow-up (8 progressors, 5 regressors) and 18 did not (8 non-progressors, 10 non-regressors). New cases of IGM and DM were 11.1 and 2.53 per 100 persons-year, respectively, and were treated non-pharmacologically. In the whole cohort and, to a higher extent, in progressors, indices of early-phase insulin secretion and insulin sensitivity decreased significantly from baseline to end-of-follow-up, with concurrent reduction of the oral disposition index and insulin secretion-sensitivity index-2 (ISSI-2), compensating insulin secretion for the level of insulin resistance. No baseline measure independently predicted progression, which correlated with change from baseline in ISSI-2. Compared with patients with normal glucose homeostasis, IGT subjects had impaired insulin sensitivity, whereas insulin secretion was reduced only in those with IFG+IGT or DM. Conclusions IGM incidence is high in young adults with WS, suggesting the need of early screening and timed intervention. As in classical type 2 diabetes, impaired insulin sensitivity and β-cell dysfunction contribute, in this sequence, to progression to IGM and DM. PMID:29053727

The Uniform Data System for Medical Rehabilitation

PubMed Central

Graham, James E.; Granger, Carl V.; Karmarkar, Amol M.; Deutsch, Anne; Niewczyk, Paulette; DiVita, Margaret A.; Ottenbacher, Kenneth J.

2013-01-01

Objective Present yearly aggregated summaries of rehabilitation outcomes at admission, discharge, and follow-up from a national sample of patients receiving inpatient medical rehabilitation for stroke, traumatic brain injury, lower extremity fracture, lower extremity joint replacement, traumatic spinal cord injury, or debility. Design Analysis of secondary data from more than 300 inpatient rehabilitation facilities in the United States that contributed inpatient and follow-up data to the Uniform Data System for Medical Rehabilitation during the period January 2002 through December 2010. Aggregate variables reported include demographic information, social situation, and functional status (FIM® instrument ratings at admission, discharge, and follow-up). Follow-up data were obtained 80–180 days post-discharge through telephone interviews by trained clinical staff. Results The final sample included 287,104 patients with follow-up information. Median time to follow-up was 95 days. Overall, more than 90% of patients within each impairment group were living in the community at follow-up. Follow-up FIM total ratings were stable to slightly increased over time. Change scores (discharge to follow-up) increased in all six groups. Mean FIM gains from discharge to follow-up, as a percentage of mean gains from admission to discharge, varied by impairment category: 46% for spinal cord injury to 71% for lower extremity fracture. Locomotion yielded the lowest ratings at all three assessments within each of the six impairment groups. Conclusions Follow-up data from a national sample of patients discharged from inpatient rehabilitation indicate that gains in mean functional independence scores from both admission to discharge and discharge to follow-up gradually increased from 2002 to 2010. At follow-up, more than 9 out of 10 patients in all 6 groups are living in the community. PMID:24088780

Visual impairment at baseline is associated with future poor physical functioning among middle-aged women: The Study of Women's Health Across the Nation, Michigan Site.

PubMed

Chandrasekaran, Navasuja; Harlow, Sioban; Moroi, Sayoko; Musch, David; Peng, Qing; Karvonen-Gutierrez, Carrie

2017-02-01

Emerging evidence suggests that the prevalence rates of poor functioning and of disability are increasing among middle-aged individuals. Visual impairment is associated with poor functioning among older adults but little is known about the impact of vision on functioning during midlife. The objective of this study was to assess the impact of visual impairment on future physical functioning among middle-aged women. In this longitudinal study, the sample consisted of 483 women aged 42 to 56 years, from the Michigan site of the Study of Women's Health Across the Nation. At baseline, distance and near vision were measured using a Titmus vision screener. Visual impairment was defined as visual acuity worse than 20/40. Physical functioning was measured up to 10 years later using performance-based measures, including a 40-foot timed walk, timed stair climb and forward reach. Women with impaired distance vision at baseline had 2.81 centimeters less forward reach distance (95% confidence interval (CI): -4.19, -1.42) and 4.26s longer stair climb time (95% CI: 2.73, 5.79) at follow-up than women without impaired distance vision. Women with impaired near vision also had less forward reach distance (2.26 centimeters, 95% CI: -3.30, -1.21) than those without impaired near vision. Among middle-aged women, visual impairment is a marker of poor physical functioning. Routine eye testing and vision correction may help improve physical functioning among midlife individuals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Visual Impairment at Baseline is Associated with Future Poor Physical Functioning Among Middle-Aged Women: The Study of Women's Health Across the Nation, Michigan site

PubMed Central

Chandrasekaran, Navasuja; Harlow, Sioban; Moroi, Sayoko; Musch, David; Peng, Qing; Karvonen-Gutierrez, Carrie

2016-01-01

Objectives Emerging evidence suggests that the prevalence rates of poor functioning and of disability are increasing among middle-aged individuals. Visual impairment is associated with poor functioning among older adults but little is known about the impact of vision on functioning during midlife. The objective of this study was to assess the impact of visual impairment on future physical functioning among middle-aged women. Study design In this longitudinal study, the sample consisted of 483 women aged 42 to 56 years, from the Michigan site of the Study of Women's Health Across the Nation. Main Outcome Measures At baseline, distance and near vision were measured using a Titmus vision screener. Visual impairment was defined as visual acuity worse than 20/40. Physical functioning was measured up to 10 years later using performance-based measures, including a 40-foot timed walk, timed stair climb and forward reach. Results Women with impaired distance vision at baseline had 2.81 centimeters less forward reach distance (95% confidence interval (CI): −4.19,−1.42) and 4.26 seconds longer stair climb time (95% CI: 2.73, 5.79) at follow-up than women without impaired distance vision. Women with impaired near vision also had less forward reach distance (2.26 centimeters, 95% CI: −3.30,−1.21) than those without impaired near vision. Conclusion Among middle-aged women, visual impairment is a marker of poor physical functioning. Routine eye testing and vision correction may help improve physical functioning among midlife individuals. PMID:28041592

Quantifying the Clinical Significance of Cannabis Withdrawal

PubMed Central

Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

2012-01-01

Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

Cognitive impairments in former patients with work-related stress complaints - one year later.

PubMed

Eskildsen, Anita; Andersen, Lars Peter; Pedersen, Anders Degn; Andersen, Johan Hviid

2016-11-01

Patients on sick leave due to work-related stress often present with cognitive impairments. The aim of this prospective cohort study was to examine the long-term consequences of prolonged work-related stress in terms of cognitive functioning one year after initial professional care seeking. We tested a group of patients with work-related stress with a comprehensive neuropsychological test battery at two occasions, one year apart. At both time points, we compared the performance of patients with healthy controls matched pairwise on sex, age and length of education. This paper presents the results from the one-year follow-up. When adjusting for practice effects, patients improved on measures of prospective memory and processing speed. However, patients continued to perform worse than controls on all tests, though only half of the comparisons reached statistical significance. The effect sizes of the differences between the two groups at one-year follow-up were small to medium. In conclusion, former patients with prolonged work-related stress improved, but they continued to perform worse than controls after one year. In the acute phase, the largest impairments were related to executive function and mental speed but at follow-up memory impairments also became apparent.

Progressive Cortical Neuronal Damage and Chronic Hemodynamic Impairment in Atherosclerotic Major Cerebral Artery Disease.

PubMed

Yamauchi, Hiroshi; Kagawa, Shinya; Kishibe, Yoshihiko; Takahashi, Masaaki; Higashi, Tatsuya

2016-06-01

Cross-sectional studies suggest that chronic hemodynamic impairment may cause selective cortical neuronal damage in patients with atherosclerotic internal carotid artery or middle cerebral artery occlusive disease. The purpose of this longitudinal study was to determine whether the progression of cortical neuronal damage, evaluated as a decrease in central benzodiazepine receptors (BZRs), is associated with hemodynamic impairment at baseline or hemodynamic deterioration during follow-up. We evaluated the distribution of BZRs twice using positron emission tomography and (11)C-flumazenil over time in 80 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery occlusive disease that had no ischemic episodes during follow-up. Using 3D stereotactic surface projections, we quantified abnormal decreases in the BZRs in the cerebral cortex within the middle cerebral artery distribution and correlated changes in the BZR index with the mean hemispheric values of hemodynamic parameters obtained from (15)O gas positron emission tomography. In the hemisphere affected by arterial disease, the BZR index in 40 patients (50%) was increased during follow-up (mean 26±20 months). In multivariable logistic regression analyses, increases in the BZR index were associated with the decreased cerebral blood flow at baseline and an increased oxygen extraction fraction during follow-up. Increases in the oxygen extraction fraction during follow-up were associated with a lack of statin use. In patients with atherosclerotic internal carotid artery or middle cerebral artery disease, the progression of cortical neuronal damage was associated with hemodynamic impairment at baseline and hemodynamic deterioration during follow-up. Statin use may be beneficial against hemodynamic deterioration and therefore neuroprotective. © 2016 American Heart Association, Inc.

Relationship between attrition and neurodevelopmental impairment rates in extremely preterm infants at 18 to 24 months: a systematic review.

PubMed

Guillén, Ursula; DeMauro, Sara; Ma, Li; Zupancic, John; Roberts, Robin; Schmidt, Barbara; Kirpalani, Haresh

2012-02-01

To assess the effect of loss to follow-up rates at 18 to 24 months on neurodevelopmental outcome statistics for infants of less than 1000 g birth weight or less than 28 weeks' gestational age. MEDLINE, EMBASE, PubMed, and Cochrane Library databases (January 1, 2000, to June 30, 2010). We searched for studies reporting outcomes of infants of less than 1000 g birth weight or less than 28 weeks' gestational age who were born after 1990. Eligible articles had to report the primary outcome and follow-up rates at 18 to 24 months. Our primary composite outcome of neurodevelopmental impairment (NDI) was any of a mental developmental quotient 2 SDs below the mean, using the Bayley Scales of Infant Development II; cerebral palsy; visual impairment; or significant hearing impairment. Of 43 publications describing outcomes at 18 to 24 months, 20 provided rates of follow-up, describing a total of 34,185 infants. The NDI rates ranged between 12.4% and 57.5%. Follow-up rates ranged between 71.6% and 100%. Higher rates of NDI were significantly correlated with greater loss to follow-up (r(2) = 0.38, P = .007). Higher rates of both NDI and loss to follow-up were seen in the United States compared with Canada, the United Kingdom, Finland, Denmark, Austria, Germany, and Australia (r(2) = 0.70, P = .001). Ascertainment bias may overestimate NDI in extremely low-birth-weight or extremely low-gestational-age survivors at 18 to 24 months. Alternatively, the characteristics of different populations and health systems may contribute to higher rates of attrition and higher rates of NDI.

Oscillating-grid experiments in water and superfluid helium

NASA Astrophysics Data System (ADS)

Honey, Rose E.; Hershberger, Robert; Donnelly, Russell J.; Bolster, Diogo

2014-05-01

Passing a fluid through a grid is a well-known mechanism used to study the properties of turbulence. Oscillating a horizontal grid vertically in a tank has also been used extensively and is considered to be a source of almost homogenous isotropic turbulence. When the oscillating grid is turned on a turbulent flow is induced. A front translates into the experimental tank, behind which the flow is highly turbulent. Long predicted that the growth of such a front would grow diffusively as the square root of time (i.e., d ˜√t ) and Dickinson and Long presented experimental evidence for the diffusive result at a low mesh Reynolds number of 555. This paper revisits these experiments and attempts a set of two models for the advancing front in both square and round tanks. We do not observe significant differences between runs in square and round tanks. The experiments in water reach mesh Reynolds numbers of order 30000. Using some data from superfluid helium experiments we are able to explore mesh Reynolds numbers to about 43000. We find the power law for the advancing front decreases weakly with the mesh Reynolds number. Using a very long tank we find that the turbulent front stops completely at a certain depth and attempt a simple explanation for that behavior. We study the propagation of the turbulent front into tubes of different diameters inserted into the main tank. We show that these tubes exclude wavelengths much larger than the tube diameter. We explore the variation of the position of the steady-state boundary H on tube diameter D and find that H =cD with c ˜2. We suggest this may be explained by saturation of the energy-containing length scale ℓe. We also report on the effect of plugging up just one hole of the grid. Finally, we recall some earlier oscillating grid experiments in superfluid 4He in the light of the present results.

Hydrologically-induced slow-down as a mechanism for tidewater glacier retreat

NASA Astrophysics Data System (ADS)

Hewitt, Ian

2017-04-01

Outlet glaciers flowing into the ocean often terminate at a calving front, whose position is sensitively determined by the balance between ice discharge and calving/terminus-melting. Rapid retreat of tidewater glaciers can be initiated when the front is perturbed from a preferred pinning point, particularly when the glacier sits in an overdeepened trough. This is believed to make certain areas of ice sheets particularly vulnerable to ice loss. A number of factors may cause a previously stable front position to become unstable, including changes in buttressing provided by an ice shelf, and changes in ocean temperature. Another possibility is that initial retreat is induced by a reduction in the supply of ice from the interior of the ice sheet. Such a reduction can naturally arise from an increase in surface melting and runoff (in the absence of accumulation changes), and this may be amplified if more efficient meltwater routing reduces basal lubrication, as has been observed in some areas of the Greenland ice sheet. Since the initiation of rapid retreat often results in an increase of ice discharge at the front (due to increased ice thickness), such a process may not be easy to detect. In this study, I employ a simplified model of an outlet glacier and its frontal behaviour to examine the extent to which hydrologically induced slow-down of the feeding ice sheet may induce (or help to induce) calving front retreat. The model builds on earlier parameterisations of grounding line fluxes, and assumes that calving occurs according to a criterion that keeps the front close to the flotation thickness. The glacier bed is assumed to be plastic. This allows for a transparent identification of the different forcing terms affecting margin position. We conclude that hydrologically-induced slow-down of ice sheets is likely to have a more significant effect on mass loss than hydrologically-induced speed-up.

Factors Associated with Routine Dental Attendance among Aboriginal Australians.

PubMed

Amarasena, Najith; Kapellas, Kostas; Skilton, Michael R; Maple-Brown, Louise J; Brown, Alex; Bartold, Mark; O'Dea, Kerin; Celermajer, David; Jamieson, Lisa M

2016-01-01

To determine factors associated with routine dental attendance in Aboriginal Australians. Data of 271 Aboriginal adults residing in Australia's Northern Territory were used. Routine dental attendance was defined as last visiting a dentist less than one year ago or visiting a dentist for a check-up. Both bivariate and multivariable analytical techniques were used. While 27% visited a dentist in the past year, 29% of these visited for a check-up. In bivariate analysis, being female, low psychological distress, and low clinical attachment loss (CAL) were associated with visiting a dentist within last year. Being aged younger than 39 years, male, no oral health impairment, being caries-free, low CAL, and low apolipoprotein B were associated with visiting for a check-up. Clinical attachment loss remained associated with visiting a dentist less than one year ago while being younger than 39 years and having no oral health impairment remained associated with usually visiting for a check-up in multivariable analysis. Younger age, no oral health impairment, and low CAL were associated with routine dental attendance among Indigenous Australians.

Factors Associated with Routine Dental Attendance among Aboriginal Australians.

PubMed

Amarasena, Najith; Kapellas, Kostas; Skilton, Michael R; Maple-Brown, Louise J; Brown, Alex; Bartold, Mark; O'Dea, Kerin; Celermajer, David; Jamieson, Lisa M

2016-02-01

To determine factors associated with routine dental attendance in Aboriginal Australians. Data of 271 Aboriginal adults residing in Australia's Northern Territory were used. Routine dental attendance was defined as last visiting a dentist less than one year ago or visiting a dentist for a check-up. Both bivariate and multivariable analytical techniques were used. While 27% visited a dentist in the past year, 29% of these visited for a check-up. In bivariate analysis, being female, low psychological distress, and low clinical attachment loss (CAL) were associated with visiting a dentist within last year. Being aged younger than 39 years, male, no oral health impairment, being caries-free, low CAL, and low apolipoprotein B were associated with visiting for a check-up. Clinical attachment loss remained associated with visiting a dentist less than one year ago while being younger than 39 years and having no oral health impairment remained associated with usually visiting for a check-up in multivariable analysis. Younger age, no oral health impairment, and low CAL were associated with routine dental attendance among Indigenous Australians.

Chemokine-Dependent pH Elevation at the Cell Front Sustains Polarity in Directionally Migrating Zebrafish Germ Cells.

PubMed

Tarbashevich, Katsiaryna; Reichman-Fried, Michal; Grimaldi, Cecilia; Raz, Erez

2015-04-20

Directional cell migration requires cell polarization with respect to the distribution of the guidance cue. Cell polarization often includes asymmetric distribution of response components as well as elements of the motility machinery. Importantly, the function and regulation of most of these molecules are known to be pH dependent. Intracellular pH gradients were shown to occur in certain cells migrating in vitro, but the functional relevance of such gradients for cell migration and for the response to directional cues, particularly in the intact organism, is currently unknown. In this study, we find that primordial germ cells migrating in the context of the developing embryo respond to the graded distribution of the chemokine Cxcl12 by establishing elevated intracellular pH at the cell front. We provide insight into the mechanisms by which a polar pH distribution contributes to efficient cell migration. Specifically, we show that Carbonic Anhydrase 15b, an enzyme controlling the pH in many cell types, including metastatic cancer cells, is expressed in migrating germ cells and is crucial for establishing and maintaining an asymmetric pH distribution within them. Reducing the level of the protein and thereby erasing the pH elevation at the cell front resulted in abnormal cell migration and impaired arrival at the target. The basis for the disrupted migration is found in the stringent requirement for pH conditions in the cell for regulating contractility, for the polarization of Rac1 activity, and hence for the formation of actin-rich structures at the leading edge of the migrating cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improvement of Janus Using Pegasus 1-Meter Resolution Database With a Transputer Network

DTIC Science & Technology

1994-03-01

Figure 4.9 shows the six jacks on the end of the HSI-card. Facing the back of the SPARC Station LINKO LINKI LINK2 LINK3 DOWN UP Figure 4.9: HSI-Card Link...shown in Figure 4.22. Facing the back of the Sun SPARC Station LINK0 LINKI LINK2 LINK3 DOWN UP "b Telephone Cable Facing the front of the Remote Tram...Holder LINKO LINKI LINK2 LINK3 DOWN UPI Figure 4.20: The Connection Between Sun SPARC Station and Remote Tram Holder 58 (3) Se.inu Up t• Link Speed

Sleep Impairment and Prognosis of Acute Myocardial Infarction: A Prospective Cohort Study

PubMed Central

Clark, Alice; Lange, Theis; Hallqvist, Johan; Jennum, Poul; Rod, Naja Hulvej

2014-01-01

Study Objectives: Impaired sleep is an established risk factor for the development of cardiovascular disease, whereas less is known about how impaired sleep affects cardiovascular prognosis. The aim of this study is to determine how different aspects of impaired sleep affect the risk of case fatality and subsequent cardiovascular events following first-time acute myocardial infarction (AMI). Design: Prospective cohort study. Setting: The Stockholm Heart Epidemiology Program, Sweden. Participants: There were 2,246 first-time AMI cases. Measurements and Results: Sleep impairment was assessed by the Karolina Sleep Questionnaire, which covers various indices of impaired sleep: disturbed sleep, impaired awakening, daytime sleepiness, and nightmares. Case fatality, defined as death within 28 days of initial AMI, and new cardiovascular events within up to 10 y of follow-up were identified through national registries. In women, disturbed sleep showed a consistently higher risk of long-term cardiovascular events: AMI (hazard ratio [HR] = 1.69; 95% confidence interval [CI] 0.95–3.00), stroke (HR = 2.61; 95% CI: 1.19–5.76), and heart failure (HR = 2.43; 95% CI: 1.18–4.97), whereas no clear effect of impaired sleep on case fatality was found in women. In men, a strong effect on case fatality (odds ratio = 3.27; 95% CI: 1.76–6.06) was observed in regard to impaired awakening; however, no consistent effect of impaired sleep was seen on long-term cardiovascular prognosis. Conclusion: Results suggest sex-specific effects of impaired sleep that differ by short- and long-term prognosis. Sleep complaints are frequent, easily recognizable, and potentially manageable. Evaluation of sleep complaints may, even if they represent prognostic markers rather than risk factors, provide additional information in clinical risk assessment that could benefit secondary cardiovascular prevention. Citation: Clark A, Lange T, Hallqvist J, Jennum P, Rod NH. Sleep impairment and prognosis of acute myocardial infarction: a prospective cohort study. SLEEP 2014;37(5):851-858. PMID:24790263

Exercise Is Associated with Lower Long-Term Risk of Olfactory Impairment in Older Adults

PubMed Central

Schubert, Carla R.; Cruickshanks, Karen J.; Nondahl, David M.; Klein, Barbara EK; Klein, Ronald; Fischer, Mary E.

2013-01-01

Importance The prevalence of olfactory impairment is high in older adults and this decline in olfactory ability may pose health and safety risks, affect nutrition and decrease quality of life. It is important to identify modifiable risk factors to reduce the burden of olfactory impairment in aging populations. Objectives To determine if exercise is associated with the 10-year cumulative incidence of olfactory impairment. Design, Setting and Participants Observational longitudinal population-based Epidemiology of Hearing Loss Study. Participants without olfactory impairment (n=1611) were ages 53-97 years at baseline and were followed for up to ten years (1998-2010). Interventions None Main Outcome and Measures Olfaction was measured with the San Diego Odor Identification Test at three examinations (1998-2000, 2003-2005, 2009-2010) of the Epidemiology of Hearing Loss Study. The main outcome was the incidence of olfactory impairment five (2003-2005) or ten (2009-2010) years later and the association of baseline exercise with the long-term risk of developing olfactory impairment. Results The 10-year cumulative incidence of olfactory impairment was 27.6% (95% confidence interval =25.3, 29.9) and rates varied by age and sex; those who were older (Hazard Ratio =1.88, 95% Confidence Interval=1.74, 2.03, for every 5 years) or male (Hazard Ratio=1.27, 95% Confidence Interval=1.00, 1.61) had an increased risk of olfactory impairment. Participants who reported exercising at least once a week long enough to work up a sweat had a decreased risk of olfactory impairment (age and sex adjusted Hazard Ratio= 0.76, 95% CI= 0.60, 0.97). Increasing frequency of exercise was associated with decreasing risk of developing olfactory impairment (p for trend = 0.02). Conclusion and Relevance Regular exercise was associated with lower 10-year cumulative incidence of olfactory impairment. Older adults who exercise may be able to retain olfactory function with age. PMID:24135745

Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer's disease.

PubMed

Portelius, Erik; Zetterberg, Henrik; Skillbäck, Tobias; Törnqvist, Ulrika; Andreasson, Ulf; Trojanowski, John Q; Weiner, Michael W; Shaw, Leslie M; Mattsson, Niklas; Blennow, Kaj

2015-11-01

Synaptic dysfunction is linked to cognitive symptoms in Alzheimer's disease. Thus, measurement of synapse proteins in cerebrospinal fluid may be useful biomarkers to monitor synaptic degeneration. Cerebrospinal fluid levels of the postsynaptic protein neurogranin are increased in Alzheimer's disease, including in the predementia stage of the disease. Here, we tested the performance of cerebrospinal fluid neurogranin to predict cognitive decline and brain injury in the Alzheimer's Disease Neuroimaging Initiative study. An in-house immunoassay was used to analyse neurogranin in cerebrospinal fluid samples from a cohort of patients who at recruitment were diagnosed as having Alzheimer's disease with dementia (n = 95) or mild cognitive impairment (n = 173), as well as in cognitively normal subjects (n = 110). Patients with mild cognitive impairment were grouped into those that remained cognitively stable for at least 2 years (stable mild cognitive impairment) and those who progressed to Alzheimer's disease dementia during follow-up (progressive mild cognitive impairment). Correlations were tested between baseline cerebrospinal fluid neurogranin levels and baseline and longitudinal cognitive impairment, brain atrophy and glucose metabolism within each diagnostic group. Cerebrospinal fluid neurogranin was increased in patients with Alzheimer's disease dementia (P < 0.001), progressive mild cognitive impairment (P < 0.001) and stable mild cognitive impairment (P < 0.05) compared with controls, and in Alzheimer's disease dementia (P < 0.01) and progressive mild cognitive impairment (P < 0.05) compared with stable mild cognitive impairment. In the mild cognitive impairment group, high baseline cerebrospinal fluid neurogranin levels predicted cognitive decline as reflected by decreased Mini-Mental State Examination (P < 0.001) and increased Alzheimer's Disease Assessment Scale-cognitive subscale (P < 0.001) scores at clinical follow-up. In addition, high baseline cerebrospinal fluid neurogranin levels in the mild cognitive impairment group correlated with longitudinal reductions in cortical glucose metabolism (P < 0.001) and hippocampal volume (P < 0.001) at clinical follow-up. Furthermore, within the progressive mild cognitive impairment group, elevated cerebrospinal fluid neurogranin levels were associated with accelerated deterioration in Alzheimer's Disease Assessment Scale-cognitive subscale (β = 0.0017, P = 0.01). These data demonstrate that cerebrospinal fluid neurogranin is increased already at the early clinical stage of Alzheimer's disease and predicts cognitive deterioration and disease-associated changes in metabolic and structural biomarkers over time. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.